36a edizione Scivac Rimini by E.V. Soc. Cons. a r.l.

scivac

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THE FEDERATION OF EUROPEAN COMPANION ANIMAL VETERINARY ASSOCIATIONS

SOCIETÀ CULTURALE ITALIANA VETERINARI PER ANIMALI DA COMPAGNIA

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4° CONGRESSO

FECAVA SCIVAC EUROPEO

BOLOGNA

18-21

GIUGNO

PROGRAMMA DEFINITIVO a ne lta u o : sim ian tta do ne -ital i o r i e z du les ota 98 Tra ing er quio 19 p gg ine ma m r 5 1 Te

1998

Con il patrocinio di

Facoltà di Veterinaria dell’Università di Bologna FNOVI, Federazione Nazionale Ordini Veterinari Italiani Provincia di Bologna Comune di Bologna Ambiente, Sviluppo Sostenibile, Politiche Giovanili, Protezione Civile Comune di Bologna Politiche Sociali, Sanità e Sicurezza In collaborazione con A.I.V.P.A Associazione Italiana Veterinari Piccoli Animali

Circolo Veterinario Bolognese

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THE FEDERATION OF EUROPEAN COMPANION ANIMAL VETERINARY ASSOCIATIONS

SCIVAC

SOCIETÀ CULTURALE ITALIANA VETERINARI PER ANIMALI DA COMPAGNIA

PALAZZO

TRECCHI

26100

CREMONA

TEL. 0372 460440 FAX 0372 457091 - email: info.scivac@softeam.it

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FEDERATION OF EUROPEAN COMPANION ANIMAL VETERINARY ASSOCIATIONS

Caro Collega, sono veramente onorato di presentare il 4° Congresso Europeo della FECAVA che si terrà a Bologna dal 18 al 21 Giugno 1998. L’importanza di questo evento assume molteplici significati. Innanzitutto viene riconosciuta alla Medicina Veterinaria Italiana la crescita compiuta in questi anni che l’ha portata a qualificarsi a livello europeo in una posizione di tutto rispetto. Contemporaneamente, l’aver affidato a SCIVAC l’organizzazione congressuale testimonia il ruolo che la nostra Associazione ha assunto nell’ambito FECAVA, e questo ci rende giustamente orgogliosi. Queste le cifre del 4° Congresso FECAVA che dimostrano di quale portata sarà questo congresso: un pre-congress day con otto gruppi specialistici, dodici ore di discussione interattiva di casi clinici, tre giorni interi con un programma scientifico eccellente, sei sale con relazioni in contemporanea, relazioni dal livello base a quello avanzato, undici relazioni sullo stato dell’arte dei vari settori della clinica e della chirurgia, oltre quaranta relatori invitati, tredici argomenti trattati. In quattro giorni verranno trattati argomenti che spazieranno dalla clinica alla chirurgia, dalla medicina felina a quella degli animali esotici, dalla cardiologia all’oftalmologia senza tralasciare alcun argomento che possa interessare la clinica degli animali da compagnia. I relatori invitati sono stati selezionati tra i migliori d’Europa e degli Stati Uniti, con la presenza di un buon gruppo di Colleghi italiani. A questo congresso si sono completamente dedicati una Commissione Scientifica di altissimo livello, che ha lavoratto per oltre due anni al programma, e uno staff tecnico che renderà l’evento unico per la sua organizzazione. Ritengo quindi di poter dire che per molto tempo sarà difficile avere un’altra occasione di questa portata per fare il punto sui traguardi e sulle nuove indicazioni terapeutiche nella clinica degli animali da compagnia. La sede congressuale sarà la meravigliosa città di Bologna, ricca di storia e di tradizione. Sita in una delle più belle regioni d’Italia la città farà certamente da degna cornice ad un evento così importante. Mi preme ringraziare fin d’ora il Consiglio Direttivo della FECAVA che ha voluto accordarci la sua fiducia, dando mandato a SCIVAC di organizzare questo congresso. Devo inoltre un doveroso ringraziamento al Consiglio Direttivo e alla Commissione Scientifica della SCIVAC per il lavoro svolto ed infine a tutti gli Sponsor che hanno voluto sostenere questa importante iniziativa. In attesa di incontrarTi a Bologna Ti porgo i più cordiali saluti. Carlo Scotti Presidente SCIVAC

scivac

Presidente CARLO SCOTTI

Presidente Senior GIORGIO ROMANELLI

SOCIETÀ CULTURALE ITALIANA VETERINARI Vice Presidente PIERMARIO PIGA

Segretario UGO LOTTI

PER

Tesoriere GILDO BARONI

ANIMALI

Consigliere MARCO CALDIN

COMPAGNIA Consigliere MATTEO SPALLAROSSA

Uffici: Palazzo Trecchi - 26100 Cremona - Tel. O (0372) 460440 - Telefax (0372) 457091 - E MAIL: info.scivac@softeam.it - Partita I.V.A. 00861330199

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ANIMAL VETERINARY ASSOCIATIONS

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THE FEDERATION OF EUROPEAN COMPANION

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________ FECAVA _______

Cari Colleghi, a nome dei componenti del Direttivo della Federazione Europea delle Associazioni Veterinarie per Animali da Compagnia, ho il piacere di invitarvi al 4° Congresso Europeo FECAVA SCIVAC che si terrà in una delle più belle città d’Europa: Bologna. L’Associazione organizzatrice, la SCIVAC - Società Culturale Italiana Veterinari per Animali da Compagnia - il cui numero di iscritti è il più alto fra tutte le Società aderenti alla FECAVA - vi offre l’opportunità di prendere parte ad un evento unico per la vostra crescita professionale che unisce l’aggiornamento scientifico all’esperienza di una delle aree storico-geografiche che più hanno concorso alla formazione della civiltà moderna occidentale. La decisione del Direttivo FECAVA di aderire unanimemente e con entusiasmo alla proposta della SCIVAC di organizzare il 4 Congresso Europeo e di eleggere Bologna a sede congressuale ha un particolare significato. Abbiamo così voluto onorare la SCIVAC, Associazione fondatrice della Federazione attivamente impegnata a sostenerne i progetti e le iniziative, e rendere omaggio alla straordinaria bellezza della città di Bologna, alla sua felice collocazione geografica e al contributo che ha saputo dare allo sviluppo della vita artistica, culturale e spirituale d’Europa. Nessun altro Continente può paragonare il proprio passato a quello lunghissimo e affascinante che l’Europa ha conosciuto, sia per gli aspetti culturali e scientifici che per il sentimento d’amicizia maturato fra le sue popolazioni. L’Europa è da sempre la pietra di paragone di ogni progresso dell’umanità. È sulla base di questa concezione e di quest’orgoglio europeisti che qualche anno fa è nata la nostra Federazione. Allora, nessuno avrebbe potuto immaginare l’impatto e l’influenza che la FECAVA avrebbe ottenuto sulla professione veterinaria per animali da compagnia. La nascita della FECAVA è stata ufficialmente sancita il 12 maggio 1990, alla presenza di tredici Associazioni fondatrici; adesso, la FECAVA conta ventisei società aderenti, per un totale di circa venticinquemila soci effettivi e dieci Società Specialistiche veterinarie europee, in qualità di membri associati. I congressi europei fino ad ora realizzati si sono rivelati tra i principali eventi scientifici d’Europa. Anche in questa occasione, è stata rispettata la consuetudine di mantenere il programma scientifico ad alti livelli di qualità e successo come nei precedenti congressi europei e quindi offrire ai partecipanti conoscenze consolidate, aggiornamenti ed elementi di valutazione critica degli stessi, nell’intento di promuovere lo scambio e il confronto culturale. L’ottimo programma scientifico, l’invitante programma sociale e la città di Bologna, con la sua storia e i suoi paesaggi mirabili, sono elementi ideali combinati con la tradizionale ospitalità italiana, i vini e la cucina d’Italia. Sarò felice di vedervi numerosi, da tutti i Paesi d’Europa, e sono certo che ricorderete questa occasione come degna e importante. Dr. Ben Albalas Presidente FECAVA

RELATORIALCONG DAVID AUCOIN DVM, Dip ACVCP Vet’s Choice Santa Monica, California USA

MARCO CALDIN Med Vet Libero Professionista, Padova

ELLEN BJERKAS DVM, PhD, Dipl ECVO Dept of SA Clin Sciences Norwegian College of Vet Med NORVEGIA

MARIO CANIATTI DVM Università di Milano Istituto di Anatomia Patologica Veterinaria

CLAUDIO BROVIDA Med Vet Libero Professionista, Torino

DIDIER CARLOTTI DVM, Dipl ECVD Les Places Sainte Eulalie FRANCIA

LEONARDO BRUNETTI Med Vet Libero Professionista, Pistoia

DANIELE COTTO Med Vet Libero Professionista, Torino

PAOLO BURACCO Med Vet Università di Torino Dipartimento di Patologia Animale

GUILLERMO COUTO DVM, Dipl ACVIM The Ohio State University Columbus, Ohio USA

CLAUDIO BUSSADORI Med Vet, Dipl ECVIM Libero Professionista, Milano 6

GRESSO

LORENZO CROSTA Med Vet Libero Professionista, Milano

STEPHEN DIVERS Bsc, C Biol, M.I. Biol, B.Vet. Med, MRCVS Exotic Animal Center, Essex GRAN BRETAGNA

BERNARD F. FELDMAN DVM, PhD, Dipl ACVIM College of Vet Medicine Blacksburg, Virginia - USA LUIS FERRER DVM, Dipl ECVD Universitat Autonoma de Barcelona - Barcelona SPAGNA ANTONIO FERRETTI Med Vet, Dipl ECVS Libero Professionista, Milano

CORINNE FOURNEL-FLEURY DVM, PhD Ecole Nat Vet de Lyon Marcy l’Etoile - FRANCIA TOMMASO FURLANELLO Med Vet

Libero Professionista, Padova

ADOLFO GUANDALINI Med Vet Libero Professionista, Roma

HERMAN A. W. HAZEWINKEL DVM, PhD, Dipl ECVS State University of Utrecht OLANDA DOMINIQUE HERIPRET DVM, Dipl ECVD Clinique Veterinaire Fregis Arcueil - Paris - FRANCIA

RICHARD LeCOUTEUR VMD, PhD, Dipl ACVIM University of California Davis, California - USA

CHRISTOPHE LOMBARD DVM, Dipl ACVIM, Dipl ECVIM Universitat Bern SVIZZERA GEORGE LUBAS Med Vet 7 Università di Pisa, Istituto di Pat

RELATORIALCONG GIUSEPPE MOSCONI Med Vet, Libero Professionista, Ozzano Emilia

Speciale e Clin Med Veterinaria LUCA MECHELLI Med Vet Università di Perugia Istituto di Anatomia Patologica

GERT NIEBAUER Med Vet, PhD, MS, Dipl ECVS Libero Professionista, Orbetello

DENNY MEYER DVM, Dipl ACVP, Dipl ACVIM Boulder, Colorado - USA

CLAUDIO PERUCCIO Med Vet, Dipl ECVO Università di Torino Dipartimento di Patologia Animale

AR MICHELL Dsc, MRCVS Animal Health Trust Newmarket Suffolk GRAN BRETAGNA

S.M. PETERSEN-JONES DVO, Dipl ECVO, MRCVS University of Cambridge Cambridge GRAN BRETAGNA

MASSIMO MILLEFANTI Med Vet Libero Professionista, Milano

STEFANO PIZZIRANI Med Vet, Dipl ECVS Libero Professionista, Firenze

PIERRE M. MONTAVON DVM Veterinar-Chirurgische Klinik der Universitat Zurich SVIZZERA

AD RIJNBERK DVM PhD University of Utrecht OLANDA

GRESSO

GIORGIO ROMANELLI Med Vet, Dipl ECVS Libero Professionista, Milano

MATTEO TOMMASINI Med Vet, Dipl ECVS Libero Professionista, Roma

GIANLUCA ROVESTI Med Vet, Dipl ECVS Libero Professionista, Reggio Emilia

ALDO VEZZONI Med Vet, Dipl ECVS Libero Professionista, Cremona

ROBERTO SANTILLI Med Vet Libero Professionista, Milano

FRANK VERSTRAETE DVM, Dipl AVDC, Dipl ECVS University of California Davis, California, USA

KARSTEN SCHOBER DVM University of Leipzig GERMANIA

C. VON WERTHERN DVM, Dipl ECVS Veterinar-Chirurgische Klinik der Universitat Zurich SVIZZERA

PETER W. SCOTT Msc, BVSc, FRCVS Zoo & Aquatic Vet Group Winchester GRAN BRETAGNA

SIMON WHEELER BVSc, PhD, Dipl ECVN The Royal Veterinary College University of London GRAN BRETAGNA

DANIEL D. SMEAK DVM, Dipl ACVS The Ohio State University Columbus, Ohio USA

RICHARD A.S. WHITE PhD, DVR, FRCVS, Dipl ACVS, Dipl ECVS University of Cambridge GRAN BRETAGNA 9

SEMINARI PRE-C S

8,30

A G

D S

’ I T R

SALA ITALIA 350

SALA TOPAZIO 300

HOLIDAY INN 250

ESFM MEDICINA FELINA

SIDEV DERMATOLOGIA

ESVO - ECVO - SOVI OFTALMOLOGIA

ESCG GASTROENTEROLOGIA

Approccio diagnostico alle malattie cutanee su base autoimmune nel cane e nel gatto (30’) Dominique Heripret (F)

PALPEBRE E TERZA PALPEBRA Tecnica di cantoplastica laterale per la correzione della macro fessura palpebrale nel cane - P. Bedford (UK)

Tecniche per il trattamento dei tumori colorettali nel cane: valutazione critica (30’) R.A.S. White (UK)

10,00

Giovedì Mattina 18 Giugno 1998

L E

SALA EUROPA 900

9,30 Alterazioni ematiche (1a parte) Neutropenia e piressia nel gatto (60’)

Pemfigo e pemfigoide nel cane e nel gatto (1a parte) (30’)

Guillermo Couto (USA) e Bernard Feldman (USA) 10,30

A R

Luis Ferrer (E)

11,00 Alterazioni ematiche (2a parte) Il gatto anemico: modalità pratiche di valutazione (60’)

Pemfigo e pemfigoide nel cane e nel gatto (2a parte) (30’)

Luis Ferrer (E) 11,30

Guillermo Couto (USA) e Bernard Feldman (USA)

Lupus discoideo e lupus sistemico (60’)

Aspetto ultrasonografico e con Risonanza Magnetica dell'adenite eosinofilica della ghiandola della nittitante in un cane - S.M. Turner (UK)

Prolasso ed iperplasia della ghiandola della membrana nel coniglio P. Boydell (UK)

ORBITA Un caso di miosite eosinofilica unilaterale in un cane - M. Bandini (I)

Fisiopatologia della ritenzione degli acidi biliari (30’)

D. Meyer (USA)

CORNEA Un caso di ulcera bilaterale simmetrica e stagionale cortico-responsiva in un coniglio nano - P. Anfray, C. Bonetti (I) Individuazione con microscopio elettronico a trasmissione di particelle citoplasmatiche simil-virali nelle cornee e congiuntive di cani con panno (cheratite superficiale cronica - Uberreiter) F. Rapp (A) Cheratoplastica lamellare per la cura del sequestro corneale nel gatto M.T. Pena Gimenez (E) Uso di collanti tissutali per la cura dell'erosione corneale cronica nel gatto A.C. Leber (D) Applicazioni cliniche di lembi tarso-congiuntivali isolati nel cane e nel gatto: risultati in 40 casi - N. D'Anna (I)

L’ Helicobacter gastrico nel cane e nel gatto (30’)

G.Cattoli (I) Telediagnostica, telechirurgia e teleinsegnamento (30’) J. Uson (E) R

12,00 Discussione (30’)

12,30

Alterazioni ematiche (3a parte) Il gatto anemico: approccio terapeutico pratico (60’)

Luis Ferrer (E)

TERAPIA Penetrazione corneale, congiuntivale e intraoculare dell'acido fusidico per uso topico nel cane - G. J. McLellan (UK)

Dominique Heripret (F)

Guillermo Couto (USA) e Bernard Feldman (USA) 13,00

Altre malattie cutanee immunomediate (1a parte) (30’)

GLAUCOMA La crioterapia per la cura del glaucoma. Risultati con l'azoto liquido - B. Clerc (F) Glaucoma secondario a difetti oculari multipli in un Gatto Inglese a pelo corto R. Elks (UK) Displasia del legamento pettinato nel Siberian Husky. Studio clinico, biometrico e istopatologico G. Chaudieu (F)

CONGRESSUALI E S S O O N E

8,30

SALA AZZURRA 150

SALA BIANCA 200

IEWG ORTOPEDIA

SIMESC ESVC MEDICINA SPORTIVA CARDIOLOGIA

INTRODUCTION Fisiopatologia Who is IEWG? What are the aims of the dell’allenamento (15’) IEWG? Dominique Grandjean (F) Flückiger (Zurich - CH)

Diagnostic accurracy of high resolution radiography and arthroscopy of elbows in growing dogs Kramers (Zurich - CH)

Tecniche di allenamento (1a parte) (25’) Dominique Grandjean (F)

PATHOPHYSIOLOGY OF ED Pathophysiology of bony changes in the dysplastic elbow joint Poulos (Davis - USA) Role of nutrition on the skeletal development Hazewinkel/Nap (Utrecht/Eindhoven - NL) EPIDEMIOLOGY/PREVENTION CONCEPTS Incidence of developmental articular malformation in the Labrador Retriever Wind (Davis - USA) Effect of breed animal selection on the incidence of ED in German Shepherd dogs Lavelle (Melbourne - AUS) Prevalence and incidence of ED in a colony of Labrador Retrievers Lang/Ohlert (Bern - Switzerland) open Swenson (Uppsala - Sweden) Predictability of FCPM in Dutch Labrador Retrievers and Bernese Mountain dogs Ubbink (Utrecht - The Netherlands) Breed value estimation in the dog. Impact on the incidence of heritable diseases Beuing (Giessen - Germany) PREVENTION CONCEPTS (continued) The German ED prevention protocol; preliminary results in selected breeds Tellhelm (Giessen - Germany) The British ED protocol Pead (London - England) Incidence of canine ED in Italy and clinical approach by veterinary profession Mortellaro (Milano - Italy) The WSAVA Hereditary Defects Committee: Current activities and goals Hedhammar/Bedford (Sweden/London)

Anestesia degli uccelli da gabbia e da voliera (60’)

L.P. Tilley (USA)

Tecniche di allenamento (2a parte) (20’) Dominique Grandjean (F)

Peter Scott (UK)

Fisioterapia e riabilitazione nel cane sportivo (20’)

Recenti acquisizioni nei risultati clinici dell’impiego degli ACE inibitori in medicina per piccoli animali (40’) J.L. Pouchelon (F)

Problemi ortopedici di metacarpo, metatarso e falangi nel cane sportivo (20’) Alessandro Piras (I) e Brian Jones (IRL)

Aggiornamenti in tema di patologie valvolari acquisite nel cane (40’) J. Haggstrom (S)

Trattamento delle fratture delle ossa lunghe nel cane atleta (20’)

Problemi riproduttivi nei cani sportivi (20’) Giovanni Majolino (I)

Le più frequenti malattie virali dei pappagalli (50’) Claudio Peccati (I)

10,30 11,00

11,30

Tecniche diagnostiche impiegabili in medicina aviare (50’) Peter Scott (UK)

11,50 12,00

Difetti del setto interventricolare nel cane (40’) G. D’Agnolo (I) 12,30 Indagine sulla flora residen- 12,40 te nelle prime vie respiratorie degli psittacidi (20’)

L’inseminazione artificiale con seme fresco e congelato: che cosa c’è di nuovo (20’) Stefano Romagnoli (I)

9,30

10,00

Incongruenze articolari del gomito: un problema emergente nelle razze sportive (15’)

Hill’s*

Gruppo di Studio ANIMALI ESOTICI

Il prontuario farmaceutico cardiologico Tilley per il veterinario pratico (60’)

DIAGNOSIS OF ELBOW DYSPLASIA (ED) Radiographic technique and film interpretation for ED screening Lang (Bern - CH)

SALA SMERALDO 100

SALA BLU 150

Sandra De Oliveira (UK)

E 13,00

4 ° C O N G R E S S O F E C AVA S C I VA C

N G R A Z I

Giovedì Mattina 18 Giugno 1998

SEMINARI PRE-C SALA EUROPA 900

SALA ITALIA 350

SALA TOPAZIO 300

HOLIDAY INN 250

ESFM MEDICINA FELINA

SIDEV DERMATOLOGIA

ESVO - ECVO - SOVI OFTALMOLOGIA

ESCG GASTROENTEROLOGIA

14,00 Biochimica clinica felina: i gatti non sono cani piccoli da un punto di vista biochimico !!! (60’)

Altre malattie cutanee immunomediate (2a parte) (30’)

LENTE Controllo del diabete del cane e cataratta diabetica D. Salgado ( CH)

Luis Ferrer (E)

UVEA Uveite pigmentaria nel Golden Retriever: 43 casi J.S. Sapienza (USA)

Il trattamento endoscopico nella palliazione dei tumori gastrointestinali nell’uomo (30’) E. Meroni (I)

14,30

Diagnosi clinica differenziale delle patologie cutanee autoimmuni (45’)

Denny Meyer (USA)

Sindrome uveodermatologica in un cane V.J. Babo (BRA) L'uveite felina: riscontri sierologici e clinici in 44 casi M. Roze (F)

Il linfoma gastrointestinale del cane e del gatto (30’)

G.Couto (USA)

Giovedì Pomeriggio 18 Giugno 1998

15,00

Alterazioni vestibolari nel gatto (60’)

15,15

Dominique Heripret (F)

Valutazione immunoistochimica della risposta immune in un caso di uveite ricorrente nel cavallo L. Mertel (I)

Diagnosi istologica differenziale delle patologie cutanee autoimmuni (45’)

RETINA La retina normale nella Phoca vitulina, riscontri elettroretinografici e morfologici E. Bjerkas (N)

Approccio nutrizionale al paziente gastrectomizzato e\o enterectomizzato (30’) B. Stanley (USA) Discussione (30’)

Aspetti elettroretinografici dell'onda d nel gatto normale e distrofico B. Ekesten (S)

Rick LeCouteur (USA) Luis Ferrer (E) 16,00

16,30 Patologie spinali nel gatto (60’)

OTTICA E TECNICHE DIAGNOSTICHE Risultati della cheratometria e della schiascopia pre e post operatoria in 1000 cani di razze diverse - W. Neumann (D)

Protocolli terapeutici (e nuove terapie) delle malattie cutanee autoimmuni (60’)

Studio biometrico dell'occhio del cane mediante ultrasonografia - S. Schoofs (B) Indagine ultrasonografica dei nervi ottici in cani colpiti da cecità improvvisa P. Boydell (UK)

Rick LeCouteur (USA)

Fabbisogno dietetico nel cane con patologia epatica (30’)

H. Meyer (NL) Discussione (30’)

ANIMALI ESOTICI Anomalie dello sviluppo oculare in una tigre del Bengala - T. Grimes (UK)

Dominique Heripret (F)

Tonometria negli erbivori selvatici R. Ofri (ISR)

17,30 Disordini neuromuscolari nel gatto (60’)

Discussione (60’)

OCULOPATIE EREDITARIE Oculopatie ereditarie: il punto di vista Italiano - C. Peruccio (I) Oculopatie ereditarie: risultati preliminari in alcune razze in Italia E. Barbasso (I) Per le presunte malattie oculari ereditarie: note sulle procedure adottate dall'ECVO (relazione del Comitato Malattie Genetiche dell'ECVO) F.C. Stades (NL)

18,30 Rick LeCouteur (USA)

CONGRESSUALI

SALA AZZURRA 150

SALA BIANCA 200

IEWG ORTOPEDIA

SIMESC ESVC MEDICINA SPORTIVA CARDIOLOGIA

TREATMENT Arthroscopic approach in dogs with ED Meyer-Lindenberg, Hannover (D) Results of ulna ostectomy as a treatment for UAP Vezzoni (Cremona - I)

Doping nel cane sportivo: vecchi e nuovi concetti (20’) Dominique Grandjean (F)

SALA SMERALDO 100

SALA BLU 150

Rottura LCA: diagnosi, ricostruzione e follow-up (30’) Immunoprofilassi d’allevamento: organizzazione di un programma vaccinale (20’) Swanneke D. Hendriks (NL)

Gruppo di Studio ANIMALI ESOTICI

Ipertensione: diagnosi e Tecniche trattamento (40’) anestesiologiche e L.P. Tilley (USA) patologie chirurgiche nei rettili (60’)

14,00

14,30 Aggiornamenti in tema di cardiomiopatia dilatativa nel cane (40’) M. Borgarelli (I)

Distocie dei rettili (60’)

Rottura del gastrocnemio nei cani da caccia e da corsa (20’) Gianluca Rovesti (I)

15,15

Stress ossidativo indotto dall’esercizio nel cane sportivo e conseguenze sui fabbisogni nutrizionali di sostanze anti-ossidanti (30’)

Nuovi concetti nel trattamento della cardiomiopatia dilatativa del cane e terapie alternative (40’) C. Amberger (CH)

Comunicazioni libere

Discussion of the seminar films

Integrazione nutrizionale ergogenica nel cane atleta (15’) D. Grandjean (F)

Workshop di ecocardiografia (90’) C. Bussadori (I) e C. Lombard (CH)

Hill’s* La zoppia di spalla nel cane atleta: diagnosi e trattamento (15’) M. Olivieri (I)

Miopatia dei muscoli gracile e semitendinoso (15’) A. Piras (I)

Tecniche diagnostiche impiegabili nei rettili (50’) Stephen Divers (UK)

16,00 16,30

17,00

17,20 Utilizzo della miscela anestetica “ZKX” in pic17,30 coli animali esotici e selvatici (20’) Amerio Croce (I) Le più comuni patologie dei ricci: un problema veramente spinoso (50’) Rosanna Trossarello (I)

Patologie articolari degenerative: un aggiornamento (15’)

Impiego del Benazepril nel gatto: farmacocinetica ed efficacia nel trattamento della cardiomiopatia dilatativa (30’) C. Amberger (CH) e J.N. King (UK)

Alterazioni muscolo-tendinee nel cane atleta (15’) A. Piras (I) e B. Jones (IRL)

Annual General Meeting of the IEWG

Giuseppe Visigalli (I)

18,30

4 ° C O N G R E S S O F E C AVA S C I VA C

15,00 Film Reading Seminar Participants are encouraged to interpret some 2 dozens elbow cases, which then will be discussed with Dr. Alida Wind, former Small Animal staff surgeon at the University of California Veterinary Medical Teaching Hospital. Participant may also bring their own ED cases along for discussion (if time permits)

Giovedì Pomeriggio 18 Giugno 1998

Stephen Divers (UK)

PROGRAMMASCI S

8,30

A G

D S

’ I T R

SALA ITALIA 350

SALA TOPAZIO 300

EMATOLOGIA Chairman: Marco Caldin

ORTOPEDIA Chairman: Gildo Baroni

OFTALMOLOGIA Chairman: Claudio Peruccio

Formazioni ossee patologiche (60’) Segni clinici e radiologici, eziologia, trattamento e prognosi delle patologie caratterizzate da formazioni ossee: panosteite, osteodistrofia ipertrofia, ecc.

RELAZIONE SULLO STATO DELL’ARTE Recenti acquisizioni nell’interpretazione della GPRA Atrofia retinica generalizzata progressiva (60’)

Venerdì Mattina 19 Giugno 1998

L E

SALA EUROPA 900

9,30 Interpretazione della conta cellulare ematica: Prima parte L’emogramma completo (60’)

Bernard Feldman (USA) 10,30

A R

H.A.W. Hazewinkel (NL)

EMATOLOGIA Chairman: Marco Caldin 11,00 Interpretazione della conta cellulare ematica: Seconda parte RELAZIONE SULLO STATO DELL’ARTE Procedure diagnostiche speciali in ematologia (40’)

Bernard Feldman (USA)

Simon Petersen-Jones (UK)

ORTOPEDIA Chairman: Antonio Ferretti

OFTALMOLOGIA Chairman: Stefano Pizzirani

Il ruolo della nutrizione nelle patologie ortopediche (60’) L’influenza del contenuto energetico, proteico, minerale e vitaminico nella dieta sullo sviluppo scheletrico e sull’accrescimento

RELAZIONE SULLO STATO DELL’ARTE La cataratta nel cane: eziologia, evoluzione e riscontri clinici (60’)

H.A.W. Hazewinkel (NL)

Ellen Bjerkas (N)

Approccio clinico all’anemia (50’)

12,00

Bernard Feldman (USA) Anemia nel cane giovane (30’)

George Lubas (I) 13,00

Diagnosi precoce di displasia dell’anca (60’) Elementi clinici e radiografici che permettono una diagnosi precoce di displasia dell’anca in funzione della selezione cinofila e delle scelte terapeutiche più opportune

Interpretazione clinica delle emorragie oculari (60’)

Aldo Vezzoni (I)

Claudio Peruccio (I)

Livello di Aggiornamento

Livello Avanzato

Relazione sullo Stato de

IENTIFICO

N G R A Z I

E S S O O N E

SALA BIANCA 200

8,30

SALA BLU 120

SALA AZZURRA 100

MEDICINA PER ANIMALI ESOTICI Chairman: Lorenzo Crosta

MEDICINA PER ANIMALI ESOTICI Chairman: Massimo Millefanti

DERMATOLOGIA Sessione specialistica Chairman: Chiara Tieghi (I)

RIPRODUZIONE Chairmen: Matteo Spallarossa (I) e Patrizia Ponzio (I)

Medicina d’urgenza degli uccelli (60’)

Patologie infiammatorie dei follicoli piliferi (60’)

Efficacia luteolitica ed effetti collaterali dell’alfaprostol, un analogo sintetico della prostaglandina F2alfa, nella cagna: risultati preliminari Sandra Annarella (I)

10,30

11,00

Induzione dell’estro nella cagna con un analogo del GnRH Stefano Belluzzi (I)

Lorenzo Crosta (I)

Interruzione di gravidanza nella cagna mediante somministrazione endovaginale di PGF2 alfa Mario Cinone (I)

Luca Mechelli (I) O2@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@6K? ?O2@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@6K ?O2@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@6K O2@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@6K? 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W2@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@6X?hg ?W&@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@)Xhg W&@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ 7@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@)X?hf @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@1?hf ?J@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ W&@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@Lhf @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@)X?he ?W&@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@)Xhe W&@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ 7@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@)X?h @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@1?h ?J@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@Lh W&@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@)X?g 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I4@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ I4@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@0M? @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@0M? ?I4@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@0M ?I4@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@0M I4@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@0M?

Patologie cutanee degli uccelli: un incubo per il veterinario pratico (60’)

Safety trial in bitches with tablets containing oestriol (Incurin®) S. Hendriks (NL)

Displasia follicolare (60’)

12,00

Treatment of urinary incontinence in the bitch: clinical trail with tablets containing oestrol (Incurin®) S. Hendriks (NL) Trattamento con finasteride in cani affetti da patologie prostatiche Daniele Zambelli (I)

Peter Scott (UK)

ell’Arte

Induzione dell’estro nella gatta con cabergolina: studi preliminari Daniele Zambelli (I)

Luis Ferrer (E)

Sessione Specialistica

Sessione Interattiva

13,00

4 ° C O N G R E S S O F E C AVA S C I VA C

Peter Scott (UK)

Venerdì Mattina 19 Giugno 1998

9,30

Alimentazione e patologie nutrizionali degli uccelli (60’)

PROGRAMMASCI SALA EUROPA 900

SALA ITALIA 350

SALA TOPAZIO 300

EMATOLOGIA Chairman: George Lubas

ORTOPEDIA Chairman: Carlo Maria Mortellaro

OFTALMOLOGIA Chairman: Claudio Peruccio

Displasia del gomito: eziologia, epidemiologia, genetica, segni clinici, segni radiologici, diagnosi e approccio terapeutico (120’)

Approccio alla cecità improvvisa (60’)

14,30 RELAZIONE SULLO STATO DELL’ARTE Coagulopatie nel cane e nel gatto (60’)

Venerdì Pomeriggio 19 Giugno 1998

Marco Caldin (I)

Simon Petersen-Jones (UK)

15,30 D’accordo: è una coagulopatia! Ma non potrebbe essere Ehrilichiosi? (60’)

Guillermo Couto (USA) 16,30

Mancata unione del processo anconeo e frammentazione del processo coronoideo mediale, osteocondrosi e incongruità articolari del gomito: fattori eziologici e metodi di controllo. Una procedura guidata per il veterinario pratico per arrivare alla diagnosi. Indicazioni terapeutiche, vantaggi e svantaggi dei trattamenti chirurgici più comunemente impiegati.

H.A.W. Hazewinkel (NL)

ENDOCRINOLOGIA Chairman: Alessandra Fondati 17,00 RELAZIONE SULLO STATO DELL’ARTE Approccio diagnostico e terapeutico all’ipotiroidismo (60’) A.D. Rijnberk (NL)

Segni oculari di patologie sistemiche nel cane (60’)

Ellen Bjerkas (N)

ORTOPEDIA Chairman: Aldo Vezzoni

OFTALMOLOGIA Chairman: Antonella Vercelli

Nuove tecniche e nuovi materiali in ortopedia (120’)

Masse oculari pigmentate e non pigmentate (60’)

Fissatore esterno tubolare, PC-FIX, mini-placca maxillofacciale • Trattamento chirurgico alternativo nell’artrosi dell’anca del cane (15’) • Tenotomia dell’ileopsoas, neurectomia della capsula articolare, miectomia del pettineo • Protesi totale d’anca non cementata (20’) • Dagli studi sperimentali all’impiego clinico

Adolfo Guandalini (I)

Hill’s*

18,00 RELAZIONE SULLO STATO DELL’ARTE Approccio diagnostico e terapeutico all’iperadrenocorticismo (60’) A.D. Rijnberk (NL)

• Descrizione di una modifica della tecnica di Slocum per il trattamento non convenzionale della rottura del legamento crociato anteriore nel cane (25’) • Trattamento della lussazione rotulea nel cane e nel gatto (30’) • Cranializzazione della tuberosità tibiale per il ripristino della biomeccanica articolare

Pierre Montavon (CH) e Cornelius Von Werthern (CH)

Manifestazioni oculari del complesso eosinofilico del gatto (60’)

Stefano Pizzirani (I)

19,00 Interruzione 19,30

C E R I M O N I A 20,30

Livello di Aggiornamento

Livello Avanzato

S A L A E D ’ A P E R T U R Q U A F E T

R D

Relazione sullo Stato de

IENTIFICO SALA BIANCA 200

SALA BLU 120

SALA AZZURRA 100

MEDICINA PER ANIMALI ESOTICI Chairman: Peter Scott

NEUROLOGIA Sessione interattiva Chairmen: Massimo Baroni e Tommaso Furlanello

MALATTIE INFETTIVE Chairman: Alessandra Fondati (I)

Trattamento chirurgico delle più comuni patologie delle tartarughe (60’)

Il grande dibattito: vantaggi e svantaggi nell’uso dei corticosteroidi nelle patologie spinali del cane (60’)

Mielopatia degenerativa del Pastore Tedesco: una patologia controversa difficile da diagnosticare e da trattare (60’)

Rick LeCouteur (USA) e Simon Wheeler (UK)

15,30

Efficacy of a high titre MLV against CDV in puppies with maternal antibodies J.G.H.E Bergman (NL) Canine leptospirosis, do we use proper vaccination programmes? - D. Salgado (E) Un caso clinico di Febbre delle Montagne Rocciose in un cane del nord est dell’Italia Tommaso Furlanello (I)

16,30

MEDICINA PER ANIMALI ESOTICI Chairman: Leonardo Brunetti

TECNICHE DIAGNOSTICHE MINI-INVASIVE Sessione interattiva Chairman: Stefano Romussi

MEDICINA FELINA Chairmen: Stefano Bo (I) e Hans Lutz (CH)

Anestesia e chirurgia dei pesci ornamentali (50’)

Metodiche mini-invasive per l’approccio diagnostico alle principali patologie addominali Una discussione interattiva basata su casi clinici con l’ausilio della valutazione citologica (120’)

Attempts to cure feline leukemia virus infection with biologic response modifier treatment Karin Hartmann (D)

17,00

Peter Scott (UK)

Efficacia della marbofloxacina iniettabile nel trattamento delle infezioni delle vie urinarie distali nel cane - Claudio Brovida (I)

Più comuni malattie virali, batteriche e parassitarie dei pesci ornamentali (50’)

Mario Caniatti (I) e Roberto Santilli (I)

ell’Arte

Effect of recombinant human granulocyte colony-stimulating factor on hematopoiesis in neutropenic cats caused by different diseases Manuela Kuffer-Frank (D)

18,00

19,00

E U R O P A A E C O N C E R T O

P O B E

Comparative studies of the efficacy of two leukemia virus vaccines Hans Lutz (CH) Serum bile acids and feline trypsin-like immunoreactivity after exogenous pancreatic stimulation with ceruletid in normal cats Thomas Spillmann (D) Adenocarcinoma of a labial minor salivary gland in a cats Dimitrios Tontis (GR) Monitoraggio ecografico di morte fetale nel gatto: caso clinico Iacopo Vannozzi (I)

Massimo Millefanti (I) Recenti acquisizioni nell’impiego dei glucani come integrazione nutrizionale nei pesci ornamentali (20’) Giuseppe Mosconi (I)

R T I C O N V E N U

19,30

L I R I C O 20,30

Sessione Specialistica

Sessione Interattiva

4 ° C O N G R E S S O F E C AVA S C I VA C

Treatment of canine leishmaniosis with Amphtotericin B (Fungizone®): four years later - Jacques Lamothe (F)

Venerdì Pomeriggio 19 Giugno 1998

Rick LeCouteur (USA) e Simon Wheeler (UK)

Stephen Divers (UK)

14,30

A new drug for the teatment of canine leishmaniosis: Amphotericin B lipid complex (Abelcet®) - Jacques Lamothe (F)

Leonardo Brunetti (I)

RELAZIONE SULLO STATO DELL’ARTE Trattamento d’emergenza e stabilizzazione medica dei rettili (60’)

Protective effect of an insecticidal spray against Phlebotomus perniciosus , a vector of leishmaniasis - Frederic Ascher (F)

PROGRAMMASCI SALA EUROPA 900

SALA ITALIA 350

SALA TOPAZIO 300

ONCOLOGIA Chairman: Claudio Capurro

EPATOLOGIA Chairman: Marco Caldin

OFTALMOLOGIA Chairman: Alberto Crotti

Recenti applicazioni e interpretazioni degli esami epatici (60’)

Segni oculari di patologie sistemiche nel gatto (60’)

Denny Meyer (USA)

Ellen Bjerkas (N)

8,30 RELAZIONE SULLO STATO DELL’ARTE La chemioterapia da un punto di vista pratico (60’) Guillermo Couto (USA)

Sabato Mattina 20 Giugno 1998

9,30

Complicazioni della chemioterapia ed emergenze oncologiche (60’)

Guillermo Couto (USA) 10,30

DERMATOLOGIA Chairman: Antonella Vercelli 11,00 Manifestazioni dermatologiche di patologie sistemiche (60’)

Dominique Heripret (F)

Gli effetti delle patologie extra-epatiche sul fegato (60’)

Trattamento delle ulcere corneali nei piccoli animali (60’)

Denny Meyer (USA)

Simon Petersen-Jones (UK)

EPATOLOGIA Chairman: Ugo Lotti

OFTALMOLOGIA Chairman: Adolfo Guandalini

La biopsia epatica: quando e come eseguirla alla luce di una corretta interpretazione del referto clinico (60’) Quando il clinico e il patologo hanno bisogno l’uno dell’altro

Modificazioni oculari nell’animale anziano (60’)

Denny Meyer (USA)

Claudio Peruccio (I)

12,00 Patologie cutanee da micobatteri (60’)

Luis Ferrer (E) 13,00

Novità nell’approccio terapeutico alle patologie del fegato (60’)

Lussazioni della lente (60’)

Denny Meyer (USA)

Stefano Pizzirani (I)

Livello di Aggiornamento

Livello Avanzato

Relazione sullo Stato de

IENTIFICO SALA BIANCA 200

SALA BLU 120

SALA AZZURRA 100

DERMATOLOGIA Chairman: Alessandra Fondati

ORTOPEDIA Sessione specialistica Chairman: Piermario Piga

NEUROLOGIA Chairman: Stefano Pizzirani (I)

Discussione clinico-patologica di casi dermatologici (120’)

Progressi nel trattamento delle più frequenti patologie ortopediche Il metodo di Ilizarov in ortopedia dei piccoli animali: dall’analisi retrospettiva alle possibilità per il futuro (60’) Antonio Ferretti (I) e Matteo Tommasini (I)

Atypical behaviour of a nasopharyngeal polyp causing a vestibular syndrome in a cat - Marco Bernardini (I)

CITOLOGIA Chairman: Davide De Lorenzi

Tre casi di “cisti aracnoidee” nel cane: valutazione a lungo termine del protocollo terapeutico Stefano Romussi (I)

CHIRURGIA DEI TESSUTI MOLLI Sessione interattiva Chairman: Carlo Scotti

Citologia pratica per il veterinario. Dalla corretta preparazione all’interpretazione dello striscio citologico (120’)

9,30

GM 1 - Gangliosidosis in Alaskan Huskies Andreas Moritz (CH)

Daniele Cotto (I) e Gianluca Rovesti (I)

A case of canine central diabetes insipida caused by a chromophobe cell adenoma of the hypophysis J.H. Duarte Correia (P)

Problemi in chirurgia toracica (120’) Da una discussione interattiva di casi clinici l’analisi dei principali problemi riscontrati dal veterinario nell’esecuzione delle tecniche di chirurgia toracica R

10,30

CARDIOLOGIA Chairmen: Claudio Bussadori (I) e Chris Lombard (CH) Electrocardiographic features of Deerhounds - A.R. Bodey (UK)

11,00

Valutazione dell’anestesia generale con propofol in cani normali e con compromesse funzioni cardiorespiratorie Antonello Bufalari (I) Clinical trial of pimobendan: a new inotropic/vasodilator drug: Long term survival time study: the results D. Bruyère (B) Correlazione tra dilatazione atriale sinistra, peso corporeo ed insorgenza della fibrillazione atriale nel cane Carlo Guglielmini (I)

12,00

Clinical efficacy of the new inodilator pimobendan, in comparison to digoxin for the treatment of congestive heart failure in dogs - Rainer Kleeman (D)

ell’Arte

Percutaneous balloon valvuloplasty in dogs with pulmonic stenosis M Schneider (D)

Dan Smeak (USA) e Richard A. White (UK)

Corinne Fournel (F)

Sessione Specialistica

Sessione Interattiva

13,00

4 ° C O N G R E S S O F E C AVA S C I VA C

Vercelli/Schiavi Noli/Fabbrini Mechelli/Galeotti Noli/Scarampella Tieghi/Abramo

Neurological findings in Cocker Spaniels with familial vitamin E deficiency and retinal pigment Epithelial Dystrophy - Rodolfo Cappello (I)

Sabato Mattina 20 Giugno 1998

Hill’s* Fissazione con chiodo bloccato: un nuovo metodo di fissazione ossea nei piccoli animali (60’)

8,30

PROGRAMMASC SALA EUROPA 900

SALA ITALIA 350

SALA TOPAZIO 300

DERMATOLOGIA Chairman: Chiara Noli

EMATOLOGIA Chairman: Marco Caldin

NEUROLOGIA Chairman: Marco Bernardini

L’interpretazione dello striscio ematico

Identificazione delle lesioni neurologiche (localizzazione, diagnostica per immagini e altri esami)

14,30 RELAZIONE FECAVA Patologie ungueali nei cani e nei gatti: diagnosi e trattamento (60’)

Alterazioni morfologiche dei globuli rossi e dei globuli bianchi (120’)

Prima parte: Lesioni cerebrali (40’)

Sabato Pomeriggio 20 Giugno 1998

Didier Carlotti (F)

15,30

Hill’s* Approccio diagnostico all’alopecia nel cane e nel gatto (60’)

Dominique Heripret (F) 16,30

Seconda parte: Lesioni del midollo spinale (40’) Terza parte: Lesioni a livello neuromuscolare (40’) Rick LeCouteur (USA) e Simon Wheeler (UK)

Bernard Feldman (USA)

DERMATOLOGIA Chairman: Alessandra Fondati 17,00 Reazioni cutanee da farmaco (60’)

MEDICINA INTERNA Chairman: Tommaso Furlanello

NEUROLOGIA Chairman: Donatella Lotti

Febbre di origine sconosciuta (60’)

Diagnosi e trattamento dell’epilessia nel cane e nel gatto (60’)

Guillermo Couto (USA) Luis Ferrer (E) Simon Wheeler (UK) 18,00 Prurito cronico nel cane e nel gatto e impiego di farmaci antiprurito (60’)

Dominique Heripret (F)

Trattamento clinico e chirurgico del paziente con trauma spinale (60’) Infezioni recidivanti nel cane (60’)

Guillermo Couto (USA)

Rick LeCouteur (USA)

19,00

Livello di Aggiornamento

Livello Avanzato

Relazione sullo Stato de

IENTIFICO SALA BIANCA 200

SALA BLU 120

SALA AZZURRA 100

UROLOGIA E NEFROLOGIA Chairman: Claudio Brovida

CHIRURGIA DEI TESSUTI MOLLI Sessione interattiva Chairman: Carlo Maria Mortellaro

ONCOLOGIA Chairmen: Giorgio Romanelli (I) e Claudio Capurro (I)

Utilità dell’ultrasonografia nella diagnosi delle malattie delle vie urinarie nel cane e nel gatto (60’)

Approccio al paziente con patologie delle prime vie respiratorie (120’)

Su un caso di pseudocisti pancreatica associata a carcinoma acinoso, pancreatite cronica e steatite multifocale necrotizzante in un gatto. Andrea Boari (I)

14,30

Parametri istologici di prognosi nei tumori mammari maligni della gatta Cinzia Benazzi (I)

Claudio Bussadori (I)

A.R. Michell (UK)

Micrometastasi linfonodali nei tumori mammari maligni della cagna Giuseppe Sarli (I) Valutazione dell’erogazione locale di cisplatino in un modello di carcinoma mammario murino Emanuela Morello (I)

Richard A. White (UK)

UROLOGIA E NEFROLOGIA Chairman: Fabio Viganò Insufficienza renale acuta: dall’emergenza alla stabilizzazione del paziente (60’)

Claudio Brovida (I)

CHIRURGIA DEI TESSUTI MOLLI Sessione interattiva Chairman: Giorgio Romanelli

CHIRURGIA E ORTOPEDIA Chairmen: Carlo Scotti (I) e Aldo Vezzoni (I)

Chirurgia plastica ricostruttiva (120’) I concetti pratici per una corretta applicazione dei principi della chirurgia plastica ricostruttiva dall’analisi di casi clinici

Pericardiectomia toracoscopica per il trattamento della pericardite effusiva recidivante: prime esperienze in due casi - Fabio Acocella (I)

A.R. Michell (UK)

ell’Arte

17,00

Systemic response of blood inflow occlusion to the liver in dogs Jani Pecar (SI)

Trattamento della contrattura in flessione del carpo mediante la tecnica di Ilizarov: 4 casi - Gianluca Rovesti (I) Bone defects in dogs treated by a new tissue transplantation Nenad Sesic (Croatia)

Dan Smeak (USA)

18,00

Clinicopathological features of multiple cartilaginous exostosis in three littermate dogs - M. Novales (E)

Approccio terapeutico alle patologie renali (60’)

16,30

Evaluation of “Valtrac” biofragmentable anastomosis ring on thoracal esophagus in the dog - T. Nèmeth (H)

Medial approach for Total Hip Replacement in Dogs: an experimental study - Z. Diòszegi (H)

15,30

Sessione Specialistica

19,00

Sessione Interattiva

4 ° C O N G R E S S O F E C AVA S C I VA C

Parametri istologici di prognosi nei tumori mammari maligni della cagna Marco Galeotti (I)

Tecniche diagnostiche impiegabili per il riconoscimento precoce delle patologie renali (60’)

Sabato Pomeriggio 20 Giugno 1998

Integrazione dei parametri clinici ed istologici nella prognosi dei tumori mammari maligni della cagna e della gatta Ombretta Capitani (I)

PROGRAMMASCI SALA EUROPA 900

SALA ITALIA 350

SALA TOPAZIO 300

CHIRURGIA DEI TESSUTI MOLLI Chairman: Massimo Gualtieri

CARDIOLOGIA Chairman: Gino D’Agnolo

NEUROLOGIA Chairman: Marco Bernardini

Tachicardia sopraventricolare nel cane (60’)

Patologie discali cervicali: approccio diagnostico e modalità di trattamento (60’)

8,30 Concetti attuali nel trattamento della peritonite (60’)

Simon Wheeler (UK) Dan Smeak (USA)

Domenica Mattina 21 Giugno 1998

9,30 RELAZIONE SULLO STATO DELL’ARTE Trattamento chirurgico delle lesioni retto-anali, anali, perianali e perineali (60’)

CHIRURGIA DEI TESSUTI MOLLI Chairman: Carlo Maria Mortellaro 11,00 Approccio chirurgico alle patologie dell’orecchio esterno e dell’orecchio medio (120’)

12,00

Richard A. White (UK) 13,00

Istruzioni per un approccio ragionato alle extrasistoli sull’ECG (60’)

Patologie discali toraco-lombari: diagnosi e trattamento (60’)

Stefano Pizzirani (I)

Cristophe Lombard (CH)

Gert Niebauer (A) 10,30

Karsten E. Schober (D)

CARDIOLOGIA Chairman: Claudio Bussadori

NEUROLOGIA Chairman: Massimo Baroni

Considerazioni terapeutiche sulla cardiomiopatia dilatativa del cane (60’)

Patologie lombo-sacrali (60’)

Karsten E. Schober (D)

Rick LeCouteur (USA)

Cardiomegalia nel gatto: cosa fare dopo la diagnosi (60’)

La Sindrome di Wobbler: considerazioni sul trattamento (60’)

Cristophe Lombard (CH)

Livello di Aggiornamento

Simon Wheeler (UK)

Livello Avanzato

Relazione sullo Stato de

IENTIFICO SALA BIANCA 200

SALA BLU 120

SALA AZZURRA 100

ODONTOSTOMATOLOGIA Chairman: Dea Bonello

CITOLOGIA Sessione specialistica Chairman: Mario Caniatti

MEDICINA INTERNA Chairmen: Tommaso Furlanello (I) e A.R. Michell (UK)

Urgenze in odontostomatologia (60’)

Citologia linfonodale: quadri normali, infiammatori e neoplastici (120’)

Un caso di discinesia ciliare primaria nel cane - Davide De Lorenzi (I) Analysis of morbidity of dogs in the region of the city Kosice, Slovakia during 1995-1997 - M. Kozak (SK)

Frank Verstraete (B)

Preliminary results on the use of cabergoline, a prolactin inhibitor, for the control of mammary tumors in the bitch before surgery J. Verstegen (B)

Corinne Fournel (F)

ODONTOSTOMATOLOGIA Chairman: Simon Kleinjan La radiologia come strumento diagnostico delle patologie del cavo orale (60’)

ell’Arte

Incidence of atopic diseases in dogs in Slovakia Pavol Chandoga (SK)

Sessione Specialistica

10,30

11,00

Granulomatosi linfomatoide cutanea primaria in un cane Leonardo Della Salda (I)

12,00

Efficacy of terbinafine against dermatophytosis in cats an open randomized blind study (preliminary results) R. Wagner (A)

Guillermo Couto (USA)

Efficacia delle permetrine CIS: Trans 25/75 microincapsulate nella terapia delle otoacariasi in cani e gatti Fabrizio Fabbrini (I)

Le leucemie (60’)

Linfomi extranodali nel cane e nel gatto (60’)

Tavola rotonda su casi clinici Etica, limiti e compromessi nel trattamento delle malocclusioni (60’)

DERMATOLOGIA Chairmen: Alessandra Fondati (I) e Luca Mechelli (I)

Guillermo Couto (USA)

Dea Bonello (I), Thomas Eriksen (DAN), Peter Fahrenkrug (D), Frank Verstraete (B), Aldo Vezzoni (I)

ONCOLOGIA Sessione specialistica Chairman: Claudio Capurro

Frank Verstraete (B)

Hill’s*

9,30

Prolactin and antiprolactinic drugs in dogs and cats: relative efficacy and mode of action of the veterinary available drugs - J. Verstegen (B)

Aggiornamenti in odontoiatria felina (60’)

Sessione Interattiva

13,00

4 ° C O N G R E S S O F E C AVA S C I VA C

Diagnosi di glomerulopatia nel cane: valutazione qualitativa della proteinuria - Paola Scarpa (I)

Hill’s*

Domenica Mattina 21 Giugno 1998

Comparative diagnostic imaging of the pelvic cavity in dogs Dieter Malleczek (A)

Frank Verstraete (B)

8,30

Domenica Pomeriggio 21 Giugno 1998

PROGRAMMASC SALA EUROPA 900

SALA ITALIA 350

SALA TOPAZIO 300

CHIRURGIA DEI TESSUTI MOLLI Chairmen: Carlo Maria Mortellaro e Matteo Tommasini

CARDIOLOGIA Chairman: Michele Borgarelli

NEUROLOGIA Chairman: Stefano Pizzirani

Meccanismi patogenetici e trattamento delle patologie pericardiche (60’)

Neoplasie del Sistema Nervoso Centrale (60’)

14,30 RELAZIONE SULLO STATO DELL’ARTE Concetti attuali nel trattamento della dilatazione-torsione di stomaco nel cane (60’) Dan Smeak (USA)

Claudio Bussadori (I) Rick LeCouteur (USA)

15,30

16,30

Polipi auricolari, otite media e sinusite nel gatto (60’) Esperienze e metodi personali di trattamento di queste frequenti patologie chirurgiche del gatto

Ipertensione nel cane (60’) Una patologia difficile da riconoscere e trattare

Dan Smeak (USA)

A. R. Michell (UK)

RELAZIONE SULLO STATO DELL’ARTE Aggiornamenti in chirurgia spinale (60’)

Simon Wheeler (UK)

S A L A C E R I M O N I A D I C H I U S U R A A R R I V E D E R C I A L

17,00

T E R M I N E

D E L

INCONTRA Durante il Congresso, saranno organizzate sessioni di approfondimento con i relatori, durante le quali i partecipanti potranno porre domande ai relatori. Sarà così possibile approfondire un argomento o prolungare una discussione in un contesto rilassato ed informa-

Livello di Aggiornamento

Livello Avanzato

Relazione sullo Stato de

IENTIFICO SALA AZZURRA 100

FARMACOTERAPIA Chairman: Enrico Febbo

ONCOLOGIA Sessione interattiva Chairmen: Claudio Capurro e Richard A. White

ODONTOSTOMATOLOGIA Chairmen: Dea Bonello (I) e Frank Verstraete (USA)

Farmacoterapia pratica: dove possiamo arrivare con un uso più ragionato dei farmaci a nostra disposizione?

Discussione interattiva da casi clinici di oncologia Questo è un caso trattabile o no? (120’) Da una discussione tra i relatori e l’uditorio le linee guida pratiche per un corretto approccio terapeutico al paziente oncologico

Dalla farmacocinetica all’applicazione clinica (40’) David Aucoin (USA)

Sialadenitis and salivary gland infarction in cats and dogs Mahmut Sozmen (UK)

15,30

Utilizzo di una corona tipo Richmond per la ricostruzione del canino inferiore in un cane di razza Boxer Paolo Squarzoni (I) Estrazione di un canino superiore paratopico in un cane Enrico Stefanelli (I)

Paolo Buracco (I) e Giorgio Romanelli (I)

E U R O P A E C O C K T A I L D I L I O N E N E L 1 9 9 9

14,30

Risultati del trattamento di 56 tumori del cavo orale nel cane Emanuela Morello (I)

Criteri di utilizzo dei punti di fulcro per gli elevatori durante le estrazioni dentali nel cane - Paolo Squarzoni (I)

Trattamento antibiotico empirico nelle malattie infettive del cane e del gatto (40’) David Aucoin (USA) Recenti acquisizioni in tema di trattamento con corticosteroidi (40’) Tommaso Furlanello (I)

Valutazione radiologica dei tumori maligni non odontogenici del cavo orale del cane - Dea Bonello (I)

16,30

C O M M I A T O : ! ! ! 17,00

C O N G R E S S O

IL RELATORE

ell’Arte

le. L’elenco dei relatori e gli orari delle sessioni saranno inseriti nella cartella congressuale ed affissi presso gli stand dei main sponsor, grazie al cui sostegno la partecipazione alle sessioni è gratuita anche se limitata ad un numero massimo di 15 partecipanti per sessione. Le iscrizioni avranno luogo presso la segreteria Congressuale fino ad esaurimento dei posti disponibili.

Sessione Specialistica

Sessione Interattiva

4 ° C O N G R E S S O F E C AVA S C I VA C

SALA BLU 120

Domenica Pomeriggio 21 Giugno 1998

SALA BIANCA 200

COMMISSIONESC COMMISSIONE SCIENTIFICA Presidente

GIORGIO ROMANELLI STEFANO BO DEA BONELLO CLAUDIO BUSSADORI ALESSANDRA FONDATI TOMMASO FURLANELLO SIMON KLEINJAN MASSIMO MILLEFANTI CLAUDIO PERUCCIO STEFANO PIZZIRANI ALDO VEZZONI

Coordinatore Congressuale FULVIO STANGA Segreteria Congressuale

Med Vet, Med Vet Med Vet Med Vet, Med Vet Med Vet DVM Med Vet Med Vet, Med Vet, Med Vet,

DECVS

DECVIM-CA

DECVO DECVS DECVS

Med Vet

LUDOVICA BELLINGERI

DIRETTIVI Consiglio Direttivo SCIVAC in carica

CARLO SCOTTI GIORGIO ROMANELLI PIERMARIO PIGA UGO LOTTI GILDO BARONI MARCO CALDIN MATTEO SPALLAROSSA

Presidente Past President Vice Presidente Segretario Tesoriere Consigliere Consigliere

Direttivo FECAVA in carica

BEN ALBALAS MARC BUCHET RAY L. BUTCHER SIMON KLEINJAN

Presidente Vice Presidente Segretario Tesoriere

I componenti dei Consigli Direttivi della FECAVA e della SCIVAC ringraziano le aziende che attraverso la sponsorizzazione hanno sostenuto la realizzazione del Programma Scientifico e del Programma Sociale di questo Congresso. Grazie al loro contributo si sono potute contenere le quote di iscrizione congressuale.

MAIN SPONSORS

MAJOR SPONSORS

Hillâ&#x20AC;&#x2122;s*

Animal Health

4th European FECAVA SCIVAC Congress

SPEAKERS’ CURRICULAE VITAE DAVID AUCOIN DVM, Dipl ACVCP Dr. David Aucoin graduated in 1980 at the Michigan State University. He then attended an Internship in Medicine and Surgery in 1981 until 1983 at the Animal Medical Center of New York. In 1985 he attended a Fellowship at the Cornell University Medical College in Clinical Pharmacology. In 1984-85 he became Associate Staff Professor at the Animal Medical Center in New York then Visiting Assistant Professor at the North Carolina State University Raleigh from 1985 to 1990. From 1990 to 1992 he was Associate Research Professor at the same University. He is a Diplomate of the American College of Veterinary Clinical Pharmacology since 1992 and Board Qualified of the American College of Veterinary Internal Medicine

ELLEN BJERKAS DVM, PhD, Dipl ECVO Graduated from the Norwegian College of Veterinary medicine in 1972. Associate Professor at the Norwegian College of Veterinary Medicine. Head of the outpatient clinic and the ophthalmology section. 1991: PhD degree. Thesis: Inherited eye diseases among dogs in Norway. Founding member of the Norwegian panel for diagnosing inherited eye diseases. ECVO Diplomate.

CLAUDIO BROVIDA Med Vet Graduated in Veterinary Medicine at the University of Turin in 1974. He has always been a small animal private practitioner with main interest in urology/nephrology and respiratory tract. He has spent long periods of updating in veterinary medicine in Great Britain, Holland and USA. Author of articles on national and international scientific reviews and speaker at veterinary conferences. He has been President of AIVPA, President of the Organising Committee of the 7th WSAVA Congress held in Rome in 1992. Currently he is vice President of WSAVA.

LEONARDO BRUNETTI Med Vet Graduated in Veterinary Medicine at the University of Pisa in 1982. His interest has always been on Exotic Animals and he has spent many years carrying out researches in numerous

zoos in Italy and abroad. He has attended the Italian edition of a book on anaesthetics on wild animals and is author of scientific papers on exotic animals. For many years he has been co-ordinator of the SCIVAC Exotic Animal Study Group.

PAOLO BURACCO Med Vet Graduated in Veterinary Medicine at the University of Turin in 1981. In 1987/88 he was “Visiting Professor” at the School of Veterinary Medicine of the Purdue University (Indiana, USA) in the Comparative Oncology Group. Since November 1992 he is Associate Professor of Semiotics Surgery at the University of Turin. He has been speaker at numerous national and international meetings on veterinary oncology and his main interests are on early diagnosis of primitive animal tumours, of their metastasis and of the most effective treatments. He therefore studies mainly skeletal, oral, endonasal, endothoracic and cutaneous neoplasias. He is author of 89 papers, including congress communications and papers published on national and international veterinary journals.

CLAUDIO BUSSADORI Med Vet, Dipl ECVIM Graduated in Veterinary Medicine at the University of Milan in 1982. He is a private practitioner and consultant in cardiology and has carried out numerous cardiological researches for the Universities of Turin and Parma where he has also been lecturer. His main researches are on lung and systemic hypertension, treatment of congenital cardiopathies, experimental echocardiography and cardiac tumours. He is a Diplomate of the European College of Internal Medicine (ECVIM) and since 1990 he is “Study Director” of international research programmes on the use of cardiovascular drugs in veterinary cardiology.

MARCO CALDIN Med Vet Graduated in Veterinary Medicine at the University of Bologna with a thesis on “Instrumental Diagnosis in Small Animal Cardiology”. He has been the co-ordinator of SCIVAC Study Group on Imaging Diagnostics from 1988 to 1990. He has been speaker at numerous meetings, practical courses and seminars as well as lecturer at the University of Pisa and University of Padova. He has also been SCIVAC Board member and co-ordinator of SCIVAC Study Group on

Internal Medicine. He is a private practitioner in Padova at the San Marco Veterinary Clinic.

MARIO CANIATTI Med Vet Graduated in Veterinary Medicine at the University of Milan. In 1990-1994 he worked at the University of Milan in the department of Veterinary Pathologic Anatomy and Avian Pathology. In 1994 he became researcher at the University of Milan. From September 1988 to March 1989 he carried out a research work at the University of California (Davis) at the Department of Pathology on immunoistochemicals of cutaneous neoplasias in the dog with Professor Peter F. Moore. In April/May 1989 he stayed at the University of Barcelona for a research work on immunistochemicals of cutaneous tumours. His current research work is on diagnostic cytology, comparative pathology of cutaneous neoplasias of linphoproliferative diseases. He has published over 40 scientific articles on Italian and international scientific journals.

DIDIER CARLOTTI DVM, Dipl ECVD Dr. Didier Carlotti graduated from Toulouse University in 1977 and has been a private practitioner in Carbon Blanc, near Bordeaux, Aquitaine, France since 1979. He has been a full member of the AAVD since 1985 and was the President of the French Small Animal Dermatology Study Group (GEDAC) from 1985 to 1991. The GEDAC is a specialised group of the French Small Animal Veterinary Association (CNVSPA), of which he was the representative at WSAVA since 1985 and Vice-President since April 1989 until April 1993. He is currently the General Secretary of CNVSPA. He was also the Chairman of the Federation of European Companion Animal Veterinary Associations (FECAVA) from May 1990 to June 1995. He is a founder Member and Past President (1988-1990) of the European Society of Veterinary Dermatology (ESVD). He is a Diplomate (and currently the honorary secretary) of the European College of Veterinary Dermatology (ECVD). He has published about 50 papers and has given numerous lectures in the field of Veterinary Dermatology.

GUILLERMO COUTO DVM, Dipl ACVIM Graduated from Buenos Aires University in 1976. From 1976 to 1981 he was Assistant Professor at the Department of Pathology of the same University. He attended a Residency on Clinical Oncology at the University of California, Davis from 1981 to 1983 and for the following 5 years he was Assistant Professor at the Ohio State University Department of Veterinary Clinical Sciences. He then became Associate Professor at the same University and from 1995 he is Professor at the Department of Veterinary Clinical Sciences of the Ohio State

4th European FECAVA SCIVAC Congress

University. Moreover he is Charter Diplomate of the American College of Veterinary Internal Medicine, Specialty of Veterinary Medical Oncology, co-editor of Essentials of Small Animal Internal Medicine, Editor in Chief of the Journal of Veterinary Internal Medicine and has over 150 scientific publications in the areas of oncology, haematology and immunology. He was President of the Veterinary Cancer Society from 1990 to 1992.

LORENZO CROSTA Med Vet Graduated in Veterinary Medicine at the University of Milan in 1989 with a thesis on avian diseases. He is member of the “Association of Avian Veterinarians” and has attended various stages in avian clinics abroad. Author of papers at international avian meetings and organiser of practical courses and seminars for SCIVAC and for the University of Milan. His current interest is exclusively in avian medicine with a particular interest in problems linked to breeding in captivity. The preferred species are parrots, eagles and ostriches. He is one of the founders of Clinica Veterinaria Fiera, a private practice in Milan.

STEPHEN J. DIVERS BSc (Hons), BVetMed, CBiol, MIBiol, MRCVS Dr. Stephen Divers achieved a bachelor of Veterinary Medicine degree (BVetMed) at the Royal Veterinary College, University of London in 1994 with a distinction in the exotic animal elective. He has been lecturer on MSc degree course in Wild Animal Medicine at the London Zoo and lecturer on the final year elective at the Royal veterinary College (small animals, reptile pharmacology, reptile therapeutics and reptile anaesthesia). Dr. Divers has been speaker at numerous national and International Meetings and is author of over 50 articles mainly on reptile medicine.

BERNARD F. FELDMAN DVM, PhD, Dipl ACVIM Dr. Bernard F. Feldman is currently Professor of Veterinary Clinical Haematology and Biochemistry at the Virginia Maryland Regional College of Veterinary Medicine (VMRCVM). He is formerly Professor of Veterinary Clinical Pathology at the University of California at Davis. Dr. Feldman has received numerous teaching and research awards, has published 3 books and over 250 articles. He has been on the faculty at the Veterinary College of the University of Utrecht, The Netherlands, and the Royal Veterinary College in Copenhagen, Denmark. He was recently nominated as Outstanding Alumnus (1997) of the University of California at Davis, School of Veterinary Medicine. Currently he is Chief of Laboratory Diagnostics Services and Director of the Clinical Pathology Laboratory at the VMRCVM’s Veterinary Medical Teaching Hospital. Dr. Feldman is President of the American

4th European FECAVA SCIVAC Congress

Society for Veterinary Clinical Pathology and on the Board of Directors of the Veterinary laboratory Association.

LUIS FERRER DVM, PhD, Dipl ECVD Graduated in Veterinary Medicine in 1981 in the Veterinary School of Zaragoza (Spain) and obtained the PhD in 1984 in the Veterinary School of Hannover (Germany). Since 1984 he is Professor of Pathology and Dermatology in the Veterinary School of Barcelona (Spain). His major research lines are dermopathology, canine leishmaniosis and the role of mast cells in canine allergic dermatitis.

ANTONIO FERRETTI Med Vet, Dipl ECVS Graduated in Veterinary Medicine at the University of Milan in 1979. He is a private practitioner and has always carried out researches on small animal surgery especially Orthopaedics and Traumatology. In 1982 he began studying the Ilizarov Method and the year after he started its application. In 1988 and 1991 he spent time with Prof. G.A Ilizarov at the Orthopaedic and Traumatological Institute of Kurgan in Siberia to deepen the knowledge on his method. Since 1993 he is a Diplomate of the European College of Veterinary Surgeons and is SCIVAC co-ordinator of the orthopaedics study group. He is currently a veterinary surgeon in a private practice near Milan.

speaker at numerous SCIVAC national meetings and seminars on internal medicine which represents his scientific and professional interest. He has been instructor at SCIVAC Practical Courses on Laboratory Diagnostics and Problem Oriented Clinical Approach. He is co-author of SCIVAC Therapeutical Manual. He is author of numerous scientific papers and has been speaker also at international meetings. He has been lecturer in Infectious Diseases in the Dog and Cat at the University of Padova in the years 1996-1997.

ADOLFO GUANDALINI Med Vet Graduated in Veterinary Medicine in 1998 with honours at the University of Perugia. In 1990/1991 he attends an Internship in Veterinary Ophthalmology at the National Veterinary School of Lyon. In 1993 he is Visiting Assistant Professor at the College of Veterinary Medicine, Ophthalmology Department of the University of Florida. From 1991 to 1997 he attends externships at: Animal Eye Associates (Chicago, Illinois), Animal Ophthalmology Clinic (Dallas, Texas), Ohio State University, Sacramento Animal Medical Group (Sacramento, California), Veterinary Ophthalmology Services (Warwick, Rhode Island), University of North Carolina at Chapel Hill. He is author and co-author of various scientific paper on veterinary ophthalmology . Since 1993 he is Board member of SOVI (Italian Association of Veterinary Ophthalmology). He has been Board member for abroad of AIVPA in 1993/1996.

HERMAN A. W. HAZEWINKEL DVM, PhD, Dipl ECVS CORINNE FOURNEL-FLEURY DVM, PhD In 1978-1980 she was Resident in Internal Medicine and in 1981 to 1986 she has been Assistant Professor in Internal Medicine and in 1991 she became Professor. 1993 she became Chief Internal Medicine Service/Domestic carnivores at the National School of Veterinary Medicine Lyon, France. She has had an intense clinical laboratory activity starting in 1988 with the creation and direction of the Immunopathology - Cytology - Haematology Diagnostic and Research Laboratory and in the same year achieved the specialised studies certificate in immunology and immunopathology. In 1989 she specialised in General Haematology and in 1990 in Cellular Biology Methods and achieved a Master’s in Immunology and haematology biological sciences. Her PhD in 1996 was on “ Morphological and Phenotypical characterisation of canine lymph node lymphoid cells. Application to the study of canine non-Hodgkin lymphomas.

TOMMASO FURLANELLO Med Vet Graduated in Veterinary Medicine at the University of Bologna in 1991. He is a small animal private practitioner at the Clinica Veterinaria San Marco. Since 1992 he has been

Graduated in 1976 at Utrecht University. After working in private practice he joined the University’s Department of veterinary Sciences in Companion Animals. Responsible for education and treatment of referred orthopaedic patients, he became interested in nutritional and hormonal related skeletal diseases. He is member of AO-Vet, Diplomate of the European College of Veterinary Surgeons, Board member of the European Society for Veterinary Orthopaedics and Traumathology, and chaired the organisation of the annual congress of the European Society for Veterinary and Comparative nutrition.

DOMINIQUE HERIPRET DVM, Dipl ECVD Dr. Heripret graduated from the Vet School of Maisons Alfort in 1981, he then completed a PhD on “Use of skin-tests in the diagnosis of FAD: about 169 cases”. From 1987 to 1994 he worked at the referral practice Clinique Fregis in France where he was in charge of the internal medicine service mainly of dermatology and endocrinology. In 1990 he was Member of the scientific comity of GEDAC (French Dermatology Group) and in 1991 he was secretary of the same group. In 1992 he was Board member (Treasurer) of the ESVD and in 1996 he became Diplomate of the European College of Vet-

erinary Dermatology. He has done more than 75 presentations and his main interests include Endocrinology, Non steroid antipruritic drugs and hypersensitivity in dermatology.

RICHARD LeCOUTEUR BVSc, VMD, PhD, Dipl ACVIM (Neurology), Dipl ECVN Rick graduated from the University of Sydney in Australia in January 1975. After a year in private small animal practice in Sydney, he completed an Internship and Residency in Surgery at the University of Guelph in Canada in 1976-78. He then completed a Residency in Neurology and Neurosurgery at the University of California Davis from 1978 to 1980. From July 1980 through January 1984, Rick completed a PhD in Comparative Pathology at the University of California in Davis. The area of Study was spinal Cord Injury. From 1984 to June 1988 he was on faculty at Colorado State University, where he was an Assistant Professor and then Associate Professor until 1989. In September 1989 he returned to Australia to establish a Specialty Practice in Neurology and Neurosurgery in Sydney. In January 1995 he returned to the USA to assume the position of Professor in Neurology and Neurosurgery at the University of California at Davis. he is Diplomate of the American College of Veterinary Internal Medicine (Neurology) and a Diplomate of the European College of Veterinary Neurology. He is currently President of the ACVIM Specialty in Neurology.

CHRISTOPHE LOMBARD DVM, Dipl ACVIM, Dipl ECVIM Dr. Christophe Lombard graduated in 1971 at the University of Zurich Switzerland. From 1972 to 1974 he attended a Residency in Physiology at the University of Zurich - College of Veterinary Medicine - from 1975 to 1977 a Residency in cardiology at the University of Pennsylvania, Philadelphia followed by a Residency of another two years in Internal Medicine at the same University. He then started in 1978 his career as Assistant and Associate Professor of Medicine and Cardiology at the College of Veterinary Medicine of the University of Florida Gainesville until 1991. Since 1991 and presently he is Professor of Medicine at the College of Veterinary Medicine at the University of Bern/Switzerland. His special interests cover clinical cardiovascular medicine especially echocardiography. The Specialty Boards he is currently in are ACVIM and ECVIM-CA. He has currently 67 scientific publications and bookchapters in various professional journals.

GEORGE LUBAS Med Vet Graduated in Veterinary Medicine at the University of Pisa in 1975 where he also specialised in Small Animal Diseases in 1977.

4th European FECAVA SCIVAC Congress

In 1979 he became Assistant Professor and since 1983 he is Associate Professor of Comparative Haematology at the University of Pisa. Since 1985 he is also Professor of Genetics in the Specialisation Section of the University of Pisa. He is author and co-author of about 150 papers on immunohaematology and clinical haematology in the dog, cat , horse and cattle. He has been speaker at numerous veterinary conferences, meetings, seminars and practical courses on the above topics.

LUCA MECHELLI Med Vet Graduated in Veterinary Medicine at the University of Pisa in 1981. In 1982-83 he was Resident at the Institute of Veterinary Medicine, University of Perugia and in 1984-85 Veterinary Pathologist at the Ministry of Health in Rome. In the years 1986-90 he was an instructor pathologist at the Institute of Veterinary Medicine of the University of Perugia and since 1991 he is teaching general pathology at the Institute of Veterinary Medicine, University of Perugia. Author of over 65 scientific papers and reviews on many aspects of companion animal dermopathology and oncology.

DENNY MEYER DVM, Dipl ACVP, Dipl ACVIM Dr. Denny Meyer received a BS and DVM from the University of Minnesota in 1970 and 1972, respectively, followed by an Internship and Residency in Small Animal Medicine at the University California-Davis. While at the University of Florida (1976-1989), he was granted tenure as an Associate Professor , served as Service Chief for both Small Animal Medicine and Clinical Pathology, achieved Diplomate status in both the American College of Veterinary Internal Medicine and the American College of Veterinary Pathologists. This was followed by a career in industry; Associate Director of Veterinary Affairs-Hills Pet Products and Director of Clinical Pathology and safety Pharmacology-Smith Kline Beecham Pharmaceuticals (appointments in both the US and UK). Upon return to academia at the Colorado State University as Professor of Pathology, he served as Service Chief-Clinical Pathology and was awarded the Carl J. Norden Distinguished Teaching Award which complemented six prior teaching awards at the University of Florida. Currently he is a Senior Clinical Pathologist at IDEXX Veterinary Services/California Veterinary Diagnostics. In addition to more than 70 scientific papers and book chapters, he is an author of Veterinary Laboratory Medicine-Interpretation and Diagnosis and is a co-author on Strombeckâ&#x20AC;&#x2122;s Small Animal Gastroenterology, 3rd edition. He has given more than 100 invited lectures. He has served as President of the Comparative Gastroenterology Society and established the Veterinary Liver Study Group. He recently completed terms as Associate Editor of the Journal of Veterinary Internal Medicine and member of the editorial Board-Veterinary pathology Journal. His clinical and investigative interests are haematology, cytopathology, hepatic histopathology, and the

4th European FECAVA SCIVAC Congress

pathophysiology of hepatic disease.

nicians (C.E.F.A., IRECOOP, ITTIOCONSULT, AIVPA, SCIVAC etc.).

A R MICHELL DSc, MRCVS

GERT NIEBAUER Med Vet, PhD, MS, Dipl ECVS

Professor Michell has recently joined the AHT from the Royal Veterinary College (University of London) where he was Professor of Applied Physiology & Comparative Medicine. He is a former President of the Association of Veterinary Teachers & Research workers and a current member of the Council of the British Veterinary Association and the Royal College of Veterinary Surgeons. He received the Blaine Award from the BSAVA in 1991 and shared the George Fleming Prize in 1992. His main interests are the physiology and clinical disturbances of fluids, electrolytes and acid-base balance and the links between renal disease, salt intake and hypertension.

Gert Niebauer has been professor of Surgery at the Small Aninmal Department of the Pennsylvania University at Philadelphia. He is author of numerous scientific publications and various chapters of Surgery texts including the latest edition of the â&#x20AC;&#x153;Slatterâ&#x20AC;?. He is Diplomate of the European College of Veterinary Surgeons of which he is also Chairman of the Credentials Committee.

MASSIMO MILLEFANTI Med Vet Graduated in Veterinary Medicine at the University of Milan in 1982. He is a private practitioner near Milan. His main interests have always been on Exotic Animals especially on rodents, reptiles and fishes. In 1987 he helped with the birth of SCIVAC Study Group of Medicine and Surgery of Exotic Animals of which he is currently the co-ordinator since 1995. He has been speaker at meetings, seminars and practical courses and has written articles for journals, a book on iguanas and one on diseases of ornamental fishes. He has also been invited to TV shows and radio broadcasts.

PIERRE MONTAVON DVM Prof. Pierre Montavon graduated at the University of Zurich and then attended a Residency from 1979 to 1985 at the Ohio State University Department of Clinical Sciences were he then became Assistant Professor. In 1985 he entered The University of Zurich as Assistant and then as Lecturer and since 1994 he is Professor at the Surgery Clinic of the University of Zurich. Since 1980 he has been instructor at the AO Vet Courses in Davos, Waldenburg, Courcheval , Cremona, Columbus and Zurich. He is currently author of over 30 original articles published in National and International Journals.

GIUSEPPE MOSCONI Med Vet Graduated in Veterinary Medicine at the University of Bologna in 1978 and in 1979 started working as fish pathologist at the EUROAQUARIUM of Bologna where he is currently brand manager. He attended two intensive courses (1981-1983) at the University of Hobenheim of Stuttgart on ornamental fish pathology. He has been speaker at numerous post-degree courses for veterinarians, biologists and fish tech-

CLAUDIO PERUCCIO Med Vet, Dipl ECVO Graduated in Veterinary Medicine at the University of Turin in 1970 with honours. Specialised in small animal diseases in 1974 at the University of Milan with the highest marks discussing a thesis on surgery of cataract in the dog. Since 1974 he is employed at the University of Turin at first as Researcher then as Associate Professor. His main interest is small animal veterinary and comparative ophthalmology. Since 1987 is Adjunct Associate Professor at the Department of Clinical Medicine, College of Veterinary Medicine, University of Illinois, USA. Since 1993 he is a Diplomate of the European College of Veterinary Ophthalmologists of which currently he is Vice President. Speaker at numerous national and international meetings and author of 130 papers and numerous text books. Secretary, Vice-President and President of AIVPA in the years 1978-1984; Secretary, Vice-President, President and PastPresident of ISVO (International Society of Veterinary Ophthalmology) from 1980 to 1994; President of SOVI (Italian Society of Veterinary Ophthalmology affiliated to SCIVAC) since 1989; he has been Vice-President of SINVET. He has been in SCIVAC Board and has been director of numerous national and international veterinary journals.

SIMON M. PETERSEN - JONES DVetMed, DVO, Dipl ECVO, MRCVS He completed his undergraduate and ophthalmology residency training at the Royal Veterinary College, London and was awarded a Doctorate of Veterinary Medicine in 1990. He holds Ophthalmology specialist qualifications from the Royal College of Veterinary Ophthalmologists. From 1998 to 1994 he was a lecturer in Veterinary Ophthalmology at the Royal (Dick) School of Veterinary Studies, Edinburgh. Currently he is conducting a research into the molecular genetics of generalised progressive retinal atrophy at the Veterinary University of Cambridge. Additionally he is the current Chief Panellist of the British Veterinary Association/Kennel Club Eye Scheme and also runs a private ophthalmology referral service. In 1994 he was awarded the BSAVA Simon Award for outstanding contributions in the field of veterinary surgery and also a Pfizer Academic Award for young British research scientists. He is a co-editor of the successful BSAVA Manual of

Small Animal Ophthalmology.

STEFANO PIZZIRANI Med Vet, Dipl ECVS Graduated in Veterinary Medicine at the University of Pisa in 1979. In July 1993 he became a Diplomate of the European College of Veterinary Surgeons. Founder in 1984 of SCIVAC where he has been Board Member (1985-86), Vice-President ( 86-87), President (87-89), President senior (89-91). He has spent various periods of updating in neurology at the Veterinary Teaching Hospital of the Colorado State University; in ophthalmology at the Cornell University of the State of New York and in small animal surgery at the North Carolina State University. His main interests are in ophthalmology, neurology and small animal surgery. He has been speaker in more that 50 occasions at national and international meetings and seminars on ophthalmology, neurology, orthopaedic surgery and leishmaniosis. he is author and co-author of articles, manuals and is co-translator of the “Handbook of Small Animal Orthopaedics and fracture treatment”.

ADAM RIJNBERK DVM, PhD Ad Rijnberk graduated from the Faculty of Veterinary Medicine of Utrecht University in 1962. In 1971 he completed a thesis entitled “Iodine metabolism and thyroid disease in the dog”. In 1973 he became reader and in 1976 professor of companion animal medicine at Utrecht University. Over the years his research interests have concentrated on endocrine diseases in dogs and cats, with currently some emphasis on the pathophysiology of the pituitary-adreno-cortical axis and of growth hormone release at pituitary and extra-pituitary sites. Ad Rijnberk is Diplomate of the European College of Veterinary Internal Medicine-Companion Animals. In 1986 he was awarded the Walter Frei Preis of the University of Zurich and in 1993 he received the Scientific Achievement Award at the 18th World Congress of the World Small Animal Veterinary Association.

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has spent various periods at the University of Cambridge (UK), North Carolina (USA) and Purdue-Indiana (USA).

GIANLUCA ROVESTI Med Vet, Dipl ECVS Graduated in Veterinary Medicine at the University of Parma in 1982. Since 1983 he has been working in a private practice for dogs and cats where he is mainly involved in surgery, with a particular interest in orthopaedics, neurology and ophthalmology. In 1992 he spent time at the Colorado State University in the Small Animal Surgery Department, in 1993 at the University of Zurich - Surgery Session of the Kantonales Tierspital and in 1997 at the North Carolina State University Small Animal Surgery, Veterinary Teaching Hospital. He has been speaker and instructor at SCIVAC AO/ASIF Courses, at the SCIVAC Course on Total Hip Replacement in the Dog with Prof. Bardet and Prof. Matis held in January 1997, speaker at SCIVAC Course on Surgery of Limb Distal Extremities with Prof. Jon Dee. He is a Diplomate of the European College of Veterinary Surgeons since June 1997.

ROBERTO SANTILLI Med Vet Graduated in Veterinary Medicine at the University of Milan in 1990. In 1991 he attended a specialisation course on small animal cardiology at the University of Turin and then started his updating periods in small animal cardiology at the North Carolina State University, Ohio State University, University of California (Davis) and Cornell University. He is a private practitioner in a small animal veterinary clinic near Milan. he is an instructor at SCIVAC practical courses on small animal cardiology and abdominal ultrasonography. Author of articles on ultrasonography and echocardiography. His main research is on feline cardiomiopathies and has presented at an annual congress of the European Society of Veterinary Internal Medicine the results of a study on the diastolic functions in feline cardiomiopathies through the doppler method.

KARSTEN E. SCHOBER DVM GIORGIO ROMANELLI Med Vet, Dipl ECVS Graduated in Veterinary Medicine at the University of Milan in 1981. Immediately after the graduation he carries out a research on experimental surgery on the transplantation of the heart and of the pancreas. He is a small animal private practitioner in Milan and his main interests are on general and orthopaedic surgery and surgical and medical oncology. He is a Diplomate of the European College of Veterinary Surgeons since 1993 and has been SCIVAC President in 1993-1995 and is currently Chairman of the SCIVAC Scientific Committee. Speaker at about 40 national and international meetings. He

Graduated at the Leipzig University in 1990 with a degree thesis on Acid-base disorders in venous blood and erythrocytic hemolysate in dogs. From 1990 to 1991 he was scientific assistant (Intern) at the small animal clinic of the University of Leipzig and from 1991 to 1994 he was research student (Resident) at the same University. He then won a grant Award from the above mentioned university and went to attend a clinical work at the Virginia Tech, Virginia Maryland Regional College of Veterinary Medicine, Small Animal Clinic, Blacksburg USA. He then won another grant award of 12 months from the German Academic Exchange Service in Bonn for postdoctoral scientific and clinical work on cardiology at the University of Edinburgh. From 1995 he is assistant

4th European FECAVA SCIVAC Congress

at the Small Animal Clinic, Faculty of Veterinary Medicine, University of Leipzig. He is author of several scientific publications and has been speaker in numerous veterinary congresses. His non professional interests are ornithology, music and art.

PETER W. SCOTT MSc, BVSc, FRCVS Peter W. Scott is a veterinarian with a special interest in birds, fish, reptiles and amphibians. He is recognised by the Royal College of Veterinary Surgeons as a Specialist in both “Zoo & Wildlife Medicine” and “Fish Health & Production” and in 1997 became Fellow of the RCVS in Psittacine Medicine. Since doing field work in Kenya for his MSc, he has worked with exotic species for 20 years. Since 1984 this has been full time and now as the principal of the Zoo and Aquatic Veterinary Group he works with many professional and keen amateur aviculturists, plus many fish keepers and fish farms. He is a member of the Association of Avian Veterinarians, an ex-President of the British Veterinary Zoological Society and Veterinary Adviser to several companies. He is the author of four books (on Axolotls, dogs, livebearing fishes, and the latest The Complete Aquarium), an editor of three conference proceedings and a contributor to many other books including four BSAVA Manuals related to exotic pets, Genus Amazona, and Lories and Lorikeets. He established VETARK PROFESSIONAL, an animal health company dealing especially with exotic species, and also VETGEN EUROPE to provide diagnostic DNA probe technology to veterinarians.

DANIEL D. SMEAK, DVM, Dipl ACVS Graduated with Honours at the Michigan State University, College of Veterinary Medicine in 1979. He then attended a Small Animal Rotating Internship at the Colorado State University in 1980 and a Residency in Small Animal Surgery at the Ohio State University College of Veterinary Medicine in 1983. He became Assistant Professor in Surgery at the Ohio State University in 1984 and Professor in 1989. Since 1995 he is Professor of Surgery at the Ohio State University and Chief of the Small Animal Surgery Section until 1997. As far as publications are concerned he has 61 Peer reviewed articles authored, he is Co-editor of the book “Disease Mechanisms in Small Animal Surgery, he is section editor of the “Manual of Small Animal Practice “ and has 18 Book Chapters Authored.

FRANK J.M. VERSTRAETE DrMedVet, BVSc, MMedVet, FAVD, Dipl AVDC, Dipl ECVS Frank Verstraete graduated as a veterinarian at the University of Gent (Belgium) in 1980. He pursued his graduate stud-

ies at the University of Pretoria (South Africa) where he completed a residency in small animal surgery and became board- certified in surgery in 1985. At Pretoria University he started a Dental Clinic in 1982, which proved to be most successful, and in 1988 he was appointed Associate Professor of Surgery and Head of the Small Animal Surgery Section. Since the end of 1994, he is Chief of the Dentistry Service at the School of Veterinary medicine of the University of California at Davis. His main research interests are comparative dentistry and oral pathology. He is charter fellow of the Academy for Veterinary Dentistry, a Diplomate of the American Veterinary Dental College (and current Secretary) and a Diplomate of the European College of Veterinary Surgeons. He is also a member of the Organising Committee of the European Veterinary Dental College.

ALDO VEZZONI Med Vet, SCMPA, Dipl. ECVS Born in 1947 in the province of Cremona, North Italy, married with Franca in 1972, two sons, Dario 21 years old and Luca 18 yeras old. Degree in Veterinary Medicine in 1975, Veterinary School of the University of Milan, with maximum score cum laude. Specialisation degree in Small Animal Medicine in 1978, Veterinary School of the University of Milan, with maximum score cum laude. In 1976 starts his veterinary practice in Cremona where he is still working with other two colleagues. President of the Italian Small Animal Veterinary Association (SCIVAC) in 1989-1991, member of its Board from 1984 to 1993, its national representative in FECAVA from 1989 to 1994, Chairman of its Scientific Committee from 1987 to 1993, Chairman of its Publication Committee from 1993. Secretary of the European Society of Veterinary Orthopaedics and Traumatology (ESVOT) from 1993. Board Certified by the European College of Veterinary Surgeon in 1993 in Cambridge, and Chairman of its PR Committee from 1994 to 1996. Chairman of the Scientific Committe of the two Italian Scientific Meetings on Canine Heartworm Disease in 1988 and in 1993. Member of the Board of the Italian Federation of Veterinary Orders (FNOVI) from 1994 to 1997 and its Secretary from 1997. President of the Veterinary Order of the Province of Cremona since 1997. Speaker in several national and international meetings on parasitology (heartworm), orthopaedics, surgery and dentistry. Editor and co-Author in 1987 of a book on canine heartworm disease “La filariosi cardiopolmonare”; co-Author in 1991 of “Small Animal Drug Formulary”, 2nd edition in 1995; italian editor of the following american books: 1990 Brinker, Piermattei and Flo “ Handbook of Small Animal Orthopedics and Fracture Treatment” , 1995 S.J.Plunkett “Emergency procedures for the small animal veterinarian”,

1996 W.R.Fenner “Quick reference to Veterinary Medicine, 1996 G.T.Wilkinson &R.C.Harvey “Color atlas of small animal dermatology”, 1998 S.I.Bistner & R.B.Ford “Kirk and Bistner’s Handbook of veterinary procedures & emergency treatment”. Author of several papers on scientific journals on heartworm disease and on small animal surgery and orthopaedics.

SIMON WHEELER, BVSc, PhD, CertVR, Dipl ECVN, MRCVS Graduated from the University of Bristol in 1981, Simon J. Wheeler was appointed House Surgeon at the Glasgow University Veterinary School. Following a year in general practice in Wales, he was appointed Clinical/Research Assistant in neurology at the Veterinary Royal College. He received a Veterinary Research Training Scholarship from the Horserace Betting Levy Board and a Grant from the BSAVA Clinical Studies Trust Fund to pursue his interest in neurological disorders, particularly peripheral nerve and spinal conditions. He was awarded PhD by the University of London in 1988. From 1988-1992 he was assistant Professor of Neurology at the College of Veterinary Medicine, North Carolina State University. Currently he is Senior Lecturer in Neurology and Director of Clinical Training at the Department of Small Animal Medicine and Surgery, The Royal Veterinary College. He is President of the European Society of Veterinary Neurology . He is editor of the BSAVA ‘s Manual of Small Animal Neurology, co-author of Small Animal Spinal Disorders: Diagnosis and Surgery and of Self Assessment Colour Review of Small Animal Neurology. He has published research and continuing education articles and textbook chapters in the USA and Great Britain.

RICHARD A.S. WHITE BVetMed, PhD, DVR, Dipl ACVS, Dipl ECVS, FRCVS Dr. Dick White is a Lecturer in Small Animal Soft Tissue Surgery at the University of Cambridge. He is a graduate of the Royal Veterinary College in London, gaining his doctorate in small animal oncology from the University of Cambridge. His areas of expertise covers all aspects of soft tissue surgery but his particular interests and publications include oncology surgery, wound management and reconstructive surgery, surgery of the upper airways and surgery of the head and neck. He is a Diplomate of the American College of Veterinary Surgeons and the European College of Veterinary Surgeons and an RCVS recognised Specialist in Small Animal Surgery. Dick White was a member of the founding committee and Past President of the European College of Veterinary Surgeons.

4th European FECAVA SCIVAC Congress

SCIVAC EXOTIC ANIMALS STUDY GROUP

Anaesthesia and surgical conditions of reptiles Stephen John Divers BSc (Hons) - C Biol. MI Biol - B Vet Med - MRCVS The Exotic Animal Centre - Essex - United Kingdom

Summary Veterinarians are increasingly been asked to perform surgery on non-domesticated animals. The surgical procedures themselves are often not complicated but successful anaesthesia remains the greatest concern. This paper introduces the clinician to reptile anaesthesia and surgery, highlighting the importance of pre-anaesthetic stabilisation and fluid therapy, suitable environment, monitoring and safe drug regimes. Reptile surgery is discussed using common reproductive disease (dystocia) as examples in snakes, lizards and chelonia.

Starvation. Putrefaction of undigested foods is a hazard of ectothermic anaesthesia and therefore fasting for 24-96 hours is recommended. Larger species, particularly the boas and pythons should be starved for 7-14 days to enable full digestion of their large meals. Pre-existing disease. Metabolic disturbances, cachexia, chronic infections etc must be considered prior to any anaesthetic induction. Handling. Reptiles should be handled as little as possible to prevent bruising and trauma. During induction, skilled staff and correct handling techniques are essential to minimise stress.

Introduction

INDUCTION AND INJECTION SITES

Anaesthesia and sedation permit surgery, but sedation and chemical restraint are equally important to facilitate handling, clinical examination and investigation (e.g. blood sampling, endoscopy, radiography etc) of animals that may be dangerous. The requirements of anaesthesia are restraint, muscle relaxation, analgesia, and uncomplicated recovery.

Induction can be achieved using an injectable agent or an inhalational agent via a mask or induction chamber. Intravenous injection sites for reptiles vary from those commonly employed in mammals. Preferred reptile venepuncture sites: SnakesVentral tail vein, caudal to cloaca; The needle is angled at 45-90° (craniodorsal) and placed in the ventral mid line in-between paired caudal scales. A 5/8”-1” 21-25 g needle is advanced, avoiding the hemipenes of males, while maintaining a slight negative pressure. If the needle hits a vertebral body withdraw slightly and redirect. Avoid the hemipenes of males. Cardiocentesis; The snake is restrained in dorsal recumbency and the heart located at a point 22-33% from the snout to the vent. The heart is palpated and immobilised using the thumb and forefinger and a 23-25 g 5/8”-11/2” needle is advanced at 45° in a craniodorsal direction into the apex of the beating ventricle. Blood often enters with each heart beat. LizardsVentral tail vein; A 5/8”-1” 21-25 g needle is angled at 6090° and placed in the ventral mid line about 1/4 to 1/3 of the way down the tail. The needle is advanced while maintaining slight negative pressure. If the needle hits a vertebral body withdraw slightly and redirect. Ventral abdominal; A 5/8”-1” 23-25 g needle is advanced in the ventral mid line in a craniodorsal direction. The vein lies just below the abdominal musculature and it is difficult to apply post-sampling pressure which makes haemorrhage a concern. Tortoises, turtles and terrapins-

ANAESTHETIC CONSIDERATIONS1,2,3 Body weight. It is vital that an accurate body weight is recorded for drug calculation and assessment of hydration and fluid deficits. Premedication. Atropine is considered unnecessary as salivary secretions are insignificant during surgery, however low-dose ketamine can be used as pre-anaesthetic sedative. Temperature. Reptiles are ectothermic and it is important that they are maintained at their species-specific preferred body temperature at all times i.e. pre-induction, at induction, during maintenance and recovery. Fluid therapy. Dehydration (reduced skin elasticity, sunken eyes, elevated packed cell volume) must be corrected prior to induction and monitored after surgery, especially when recovery is prolonged. Bathing tortoises in warm water for several hours may be sufficient, but intracoelomic fluids (e.g. Hartmanns, lactated Ringers) at a rate of 15-35 ml/kg/24 hours can be easily administered to most species, even chelonia. In cases of moderate to severe dehydration, intravenous or intraosseous fluid therapy is to be recommended.

PRE-CONGRESS DAY MEETINGS

4th European FECAVA SCIVAC Congress

Dorsal tail vein; A 5/8” 21-25 g needle is angled at 45-90° and placed, as cranial as possible, in the dorsal mid line of the tail. The needle is advanced while maintaining a slight negative pressure. If the needle hits a vertebral body, withdraw slightly and redirect. The exact position, size and even presence of this vessel may vary between species. Right jugular; A 5/8” 23-25 g needle is positioned lateral at the level of the tympanic scale, and directed caudally midway down the neck. It is important to maintain post-sampling pressure to avoid haematoma formation. Subcarapacial vein; The head is pushed inside the coelomic cavity and a needle (bent to 60-75°) is inserted in the mid line just caudal to where the skin of the neck attaches to the cranial rim of the carapace. Advance the 5/8”-1” 2325 g needle in a dorsal direction and maintain slight negative pressure. It is important to maintain post-sampling pressure to avoid haematoma formation. There are a variety of other venepuncture sites including the brachial plexus and femoral plexus, however they usually provide smaller samples which are more often contaminated by lymphatic fluid. CrocodiliansVentral tail vein; A 1-3” 18-23g needle is angled at 6090° and placed in the ventral mid line about 1/4 to 1/3 of the way down the tail. The needle is advanced while maintaining slight negative pressure. If the needle hits a vertebral body withdraw slightly and redirect. Larger crocodilians (over 1.5 m in length) may require chemical restraint using a neuromuscular blocking agent (e.g. 0.4-1.0 mg/kg gallamine, reversable with neostigmine), and it may be necessary to use large spinal needles (3-8”) to reach the vein. Supravertebral vein; A 1-2” 20-23 g needle is inserted at 90o in the mid line just caudal to the occiput. The needle is advanced to just dorsal to the spinal cord, while maintaining a slight negative pressure. Larger crocodilians (over 1.5 m) may require chemical restaint using a neuromuscular blocking agent (e.g. 0.4-1.0 mg/kg gallamine, reversable with neostigmine). Intramuscular injections can be given into the epaxial muscles of snakes and proximal forelimb muscles of chelonia, lizards and crocodilians.

INHALATIONAL ANAESTHESIA Inhalational anaesthesia can be induced via a face mask (e.g. iguanas and other large lizards) or by conscious intubation (e.g. snakes). Endotracheal intubation is recommended in all species. Open, semi-closed and closed circuits (Ayre’s T-piece, Bain Co-axil) can be used giving considerations to circuit resistance and animal size. Assisted ventilation (IPPV) is often required and therefore artificial ventilation, either manual or mechanical should be available. Anaesthetic chambers can be used for the induction of small or venomous species, but beware that prolonged breath holding can occur. Intubation using a standard uncuffed endotracheal tube is preferable but often not possible. A dog urinary catheter cut down to size makes a suitable ET tube for many species, and even the smallest specimen can be intubated using an intravenous catheter.

4th European FECAVA SCIVAC Congress

MONITORING ANAESTHESIA ECG machines can be utilised in reptiles to monitor cardiac function. The heartbeat of snakes is visible ventrally about a third of the way caudal to the head while the heart beat of many lizards can be seen within the axillae. Reflexes and muscle tone diminish as the depth of anaesthesia increases. Muscle relaxation progresses in an anterior to posterior direction. The righting reflex is lost during the later stages of anaesthesia but this may not represent a surgical plane. Loss of the corneal reflex is a good indicator of deep anaesthesia, except in the snake and certain gecko lizards which possess a spectacle covering the cornea. In snakes the tongue withdrawal reflex and the ventral muscle reflex can be used to good effect, while the deep pain withdrawal reflex of the tail or foot can be used in lizards and chelonia. The authors preferred method of monitoring is pulse oximetry which provides information on peripheral pulse and pulse strength, and possibly an indication of blood oxygen saturation.

POST-OPERATIVE CARE Post-operative recovery requires maintenance at the animal’s preferred body temperature. Respiration must be monitored during recovery, especially following the use of ketamine, halothane or methoxyflurane. Respiratory stimulants can be used to reduce post-operative observation, e.g. doxapram (Dopram, Willows Francis) at 0.25 ml/kg i/v, i/o. Recovery is considered to have occurred when the righting and pedal reflexes have returned. Hydration status should be assessed and it is good practice to give i/c, i/v, i/o or oral fluids up to 35 ml/kg/24 hours. Antibiotics may also be indicated but until the culture and sensitivity results are obtained, broad spectrum antibiotic cover can be provided using enrofloxacin (Baytril 2.5%, Bayer) at 10 mg/kg i/m, i/o, po q 24 hrs or ceftazidime (Fortum 500 mg, Glaxo) at 40 mg/kg i/m i/v, i/o q 72 hrs.

SURGICAL PROCEDURES5,6,7,8 A wide range of surgical and medical procedures are now commonly performed thanks to the safer, modern anaesthetics; jugular cut-down and catheter placement in snakes, cardiac catheterisation in snakes, pharyngostomy tube placement, lung catheterisation and pulmonary lavage, joint lavage/aspiration, abscess removal, tumour removal, wound debridement, fracture repair, limb/tail amputation, enucleation, hemilaminectomy in large lizards, exploratory coeliotomy, cystotomy, enterectomy, enterotomy, pneumotomy, biopsy, endoscopy (diagnostic, biopsy and sexing), rib removal in snakes, bone marrow aspiration in lizards and chelonia, prolapse repair, penis amputation, etc etc. In general, the surgical techniques are similar to those established for mammals, however certain anatomical differences peculiar to reptiles must be considered by the surgeon prior to operating. As an example reproductive disease (dystocia) and their surgical treatments will be described.7,8

Injectable anaesthetic and immobilisation regimes for reptiles DRUG

DOSAGE

COMMENTS CHELONIANS

Ketamine HCl

20-60mg/kg s/c, i/m

Useful and safe. Doses less than 50mg/kg produce tranquillisation, while doses above 50mg/kg produce anaesthesia. Recovery time proportional to dose, often several hours. Ketamine (50mg/kg) and xylazine (10mg/kg) combination has been recommended. C/I - debilitated or dehydrated reptiles, hepatic or renal dysfunction.

Alphaxalone/ alphadolone

6-9mg/kg i/v 9-15mg/kg i/m Rapid, predictable response if given i/v with intubation possible within three mins. I/m route less predictable, induction is slower at 25-40 mins. Anaesthesia lasts 15-35 mins, recovery 1.5-4 hours.

Propofol

14-15mg/kg i/v

Rapid, smooth induction, minimal accumulation, 20 mins anaesthesia, rapid recovery. AUTHOR’S AGENT OF CHOICE

Succinylcholine*

0.25-1.5mg/kg i/m

Very effective at facilitating E/T intubation and diagnostic procedures. Paralysis lasts 20 mins, recovery takes 45 mins.

Tiletamine HCl and Zolazepam HCl 10-20mg/kg i/m

Most suitable for sedation to facilitate E/T intubation. Zolazepam incorporated to reduce convulsions and improve muscle relaxation. Not yet available in UK.

Etorphine

0.3-2.75mg/kg i/m

Used in terrapins up to 5mg/kg.

Ketamine HCl

20-100mg/kg s/c, i/m

Same as for chelonians

Alphaxalone/ alphadolone

6-9mg/kg i/v 9-15mg/kg i/m Same as for chelonians

Propofol

10-15mg/kg i/v

LIZARDS

Same as for chelonians. AUTHOR’S AGENT OF CHOICE

Tiletamine HCl and Zolazepam HCl 30mg/kg i/m

Produces mild to moderate plane of surgical anaesthesia with rapid induction time, recovery may be prolonged. Particularly suited to iguanas. Not readily available in UK. SNAKES

Metomidate*

10-20mg/kg i/m

Very useful sedative to facilitate blood sampling, radiography, intravenous injections. Rapid onset with heavy sedation after 15 mins. Safely used on a daily basis for cleaning, debriding wounds.

Propofol

10-12mg/kg i/v

Same as chelonians. AUTHOR’S AGENT OF CHOICE

Ketamine HCl

20-130mg/kg s/c, i/m

Rapid induction, prolonged recovery. May need to IPPV at higher doses, lower dose for pre-anaesthetic sedation.

Alphaxalone/ alphadolone

6-9mg/kg i/v 9-15mg/kg i/m Same as chelonians

Tiletamine HCl and Zolazepam HCl 10-20mg/kg i/m

Same as chelonians. Fatalities at 55mg/kg

Methohexital sodium

Induction and recovery times rapid, concentration should not exceed 0.5%.

5-15mg/kg i/m, s/c

CROCODILIANS Propofol

10-15mg/kg i/v

Same as for chelonians. AUTHOR’S AGENT OF CHOICE FOR SMALL SPECIMENS

Succinylcholine*

0.4-1mg/kg i/m

Rapid onset of paralysis in American alligators, recovery in 45-90 mins.

Gallamine triethiodide*

0.6-4mg/kg i/m

Good in Nile crocodiles, unsafe in American alligators at 1mg/kg. Reverse with 0.05mg/kg neostigmine i/m and 0.02mg/kg atropine i/m. AUTHOR’S AGENT OF CHOICE FOR LARGE SPECIMENS

Ketamine HCl and Xylazine HCl

20mg/kg i/m 1mg/kg i/m

Good in Nile crocodiles, ketamine given 30 min after xylazine, anaesthesia lasts 50 mins, recovery in 4 hours.

Etorphine

0.3-2.75mg/kg i/m

10-30 mins induction, 45-100 mins of analgesia hence combine with muscle relaxant.

*Provides no analgesia - must be combines with local or general analgesia for painful procedures. It may be necessary to assist respiration, especially at higher doses or in debilitated patients.

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Inhalational anaesthetic agents used in reptiles AGENT Methoxyflurane

INDUCTION/ MAINTENANCE

COMMENTS

3-4%/1.5-2% in oxygen

All species. Excellent relaxation and analgesia, prolonged induction and recovery times, myocardial depressant and nephrotoxic.

Halothane

3-5%/1-3% in oxygen

All species. Rapid induction and recovery times, respiration and myocardium depressed with respiratory and cardiac arrest occurring simultaneously, hepatotoxic, lizards more sensitive.

Isoflurane

3-5%/1-3% in oxygen

All species. Rapid induction and recovery, minimal organ toxicity, ideal for debilitated reptiles. AUTHOR’S AGENT OF CHOICE

Nitrous oxide

1:1 to 1:3 with oxygen

All species. May be used with volatile anaesthetics to reduce induction time and improve muscle relaxation and analgesia.

PRE-OVULATORY OVA STASIS (POOS) In cases where the ova enlarge but do not ovulate and remain within the ovary the term pre-ovulatory ova stasis (POOS) is applicable. In such circumstances the presence of the greatly enlarged ovaries severely reduces the coelomic space available to the gastrointestinal tract resulting in prolonged anorexia particularly in saurians. In most untreated cases affected females usually die from the secondary changes associated with dehydration and anorexia. A diagnosis of POOS can be made by ultrasonography, laparoscopy or more commonly radiography. It is possible for the ova to be spontaneously reabsorbed over a period of 412 weeks. However, if affected animals are completely anorexic and becoming debilitated then further deterioration and death can ensue before the problem resolves naturally. If medical therapy is contemplated then intensive nutritional/fluid support will be required for many weeks and ova reabsorption should be monitored using radiography or ultrasonography. In the author’s experience medical management is seldom successful in lizards presented late in the course of the disease and does not prevent recurrence the following year. Greater success has been seen with short term patient stabilisation using fluid therapy for 1-3 days followed by surgery (ovariosalpingectomy). A case of follicular aspiration as a treatment for POOS has been reported.

POST-OVULATORY EGG STASIS (POES) In cases of post-ovulatory egg stasis (POES), the eggs (usually shelled) or foetuses are located within the shell glands or oviducts but normal laying or birth at term fails to occur because of the lack of a suitable nesting site (temperature, humidity, nest material, seclusion), excessive disturbance by the owner, competition for nesting sites (overcrowding), stress of transportation, metabolic disturbances (particularly involving calcium), systemic or localised infections of the shell glands, oviducts or cloaca and obstructions due to abnormal eggs, foetuses or cloacal prolapse. The space occupied by the eggs/foetuses again compresses the gastrointestinal tract and leads to secondary hypophagia or anorexia.

If there is no indication of infection, metabolic disease or obstruction as determined by radiography, digital palpation and direct visualisation of the cloaca and a limited haematological and biochemical assessment, then conservative treatment should be attempted. Complications including abnormal eggs, abnormal foetuses, cloacal prolapse, suspected infection of the cloaca, shell glands or oviducts will prevent normal laying or birth and in these, and refractory medical cases, surgery is indicated.

SURGICAL TECHNIQUE Once the patient’s hydration status has been returned to normal (as determined by serial packed cell volume, total protein and albumin) surgery can proceed. Preoperative antibiotics, for example 40 mg/kg ceftazidime (Fortum, 500 mg, Glaxo), IM is advisable. The rate of fluid administration can be increased to 5 ml/kg/hour during anaesthesia, surgery and the immediate postoperative period. Anaesthesia is induced with 10-14 mg/kg propofol (Rapinovet, 10 mg/ml, Mallinckrodt Veterinary), IV or IO followed by intubation and maintenance on oxygen and 24% isoflurane. It is vital than the preferred body temperature of the patient is maintained before, during and after surgery. The use of a low wattage heat mat or water bed to maintain a core preferred body temperature is recommended. The subject is connected to an ecg or pulse oximeter (cloacal/oesophageal) and prepared for aseptic surgery. The use of plastic adhesive drapes enables better monitoring and are to be preferred over cotton drapes. Post operative analgesics should always be considered and the author prefers 2-4 mg/kg carprofen IM (Zenecarp, 50 mg/ml, C-Vet).

LIZARDS A standard paramedian or mid-line coeliotomy is performed, avoiding the large, ventral, mid line venous sinus and, often voluminous, saurian bladder. The incision may have to extend from the xiphoid process to just cranial to the pelvis to provide sufficient exposure. The bladder must be

identified to prevent accidental incision, and emptied by cystocentesis if necessary. In cases of POOS, the enlarged ovaries will be immediately obvious, often resembling clusters of yellow-orange grapes. Each ovary, supplied by 4-8 ovarian vessels that branch off the aorta and renal veins, is lifted to expose these vessels which can be clamped using hemoclips, or ligated using vicryl (3/0-5/0). Once clamped the ovaries can be carefully dissected free and removed. The oviducts are usually small and involuted. Theoretically it may be possible to leave the oviducts in place but subsequent infection is always a possibility and therefore removal is recommended. The small blood vessels can usually be sealed using radiosurgery, hemoclips or ligatures as necessary. The oviducts should be double ligated using 3/0-5/0 vicryl as far distally as possible, close to their insertion to the cloaca. In cases of POES, it is the thin shell glands full of eggs that are immediately obvious. Multiple salpingotomy incisions can be made to remove the eggs in an effort to maintain future breeding capacity, however, surgery time is greatly extended. In most cases complete salpingectomy is recommended. The large, numerous blood vessels that supply each oviduct must be ligated or hemoclipped. Hemoclips greatly reduce surgery time and several vessels can often be clamped with a single medium clip. The oviducts must be ligated close to the cloaca and removed as described above. In these cases, the ovaries are often small lying on top of the renal veins. Their removal is considered by some to be unnecessary as it has been suggested that folliculogenesis requires feedback from the shell glands. The author prefers complete ovariosalpingectomy due to the possible danger of ectopic ova in the future. When removing inactive ovaries the ovarian vessels are smaller and shorter and it is generally easier to clamp these vessels with hemoclips than to ligate them. Special care is also required not to damage the closely associated adrenal glands. The coelomic membrane and muscle layers are closed in a routine manner using 3/0-5/0 vicryl. The skin is sutured using 3/0 -5/0 nylon in an everting horizontal mattress pattern. This will prevent the natural inverting tendency of reptilian skin and prevent dysecdysis in the future. The patient is returned to a vivarium at 30-35C to recover. Postoperative antibiotics are not routinely required unless infection was confirmed at surgery but parenteral fluid therapy remains essential for the next 24 hours. Discharge typically occurs the next day with a return to normal feeding within a week. Skin sutures are removed in 6-8 weeks.

SNAKES The procedure is similar in snakes. In general a long incision is made between the ventral and lateral scales over the area of greatest coelomic distension. POOS is rarer in snakes and in most cases the eggs (or foetuses) will be within the shell glands. Dissection is continued through the muscle layer and a standard salpingotomy incision is made in the thinly walled shell gland. The eggs or foetuses can then be removed, and it may be possible to milk eggs or foetuses from further up or further down the shell gland into the surgical site so preventing the need for additional salpingotomies. The shell gland incision is closed using 5/0 vicryl in a single

or double inverting suture pattern. Suturing may be made easier by the administration of oxytocin or vasotocin which causes contraction and thickening of the shell gland wall. Skin closure is routine. A less invasive surgical option is the aspiration of the infertile egg contents through a needle (14-20 g) which is introduced through the coelomic and shell gland walls into the retained egg. The skin surface must be aseptically prepared prior to this technique but there is a danger that egg contents may leak from the egg and into the shell gland or coelomic cavity causing an intense coelomitis. In general, the collapsed egg is voided within 12-96 hours, but this may be facilitated by the use of oxytocin, vasotocin or prostaglandins. Ovariosalpingectomy is more difficult to perform in snakes but is certainly possible and with practice will produce a satisfactory and permanent cure to reproductive problems in these species.

CHELONIA Access to the reproductive tract of chelonians presents an obvious challenge to the surgeon, notably the shell. In those species with large inguinal fossae including the large land tortoises and many species of terrapin and turtle, an inguinal soft tissue approach will provide sufficient access for egg removal and prevent the need for plastronotomy. In species with small inguinal fossae, or in those cases where there are large numbers of retained eggs, or extensive disease that warrants complete ovariosalpingectomy, then a transplastron approach is often indicated. Using an oscillating sector cutter or small diameter circular saw, a plastronotomy with a bevelled edge is performed, making sure that any functional plastron hinges are avoided. It is important that the clinician makes the plastronotomy incision large enough to operate through as it is difficult to subsequently enlarge the incision. The bone segment is carefully lifted and dissected free from the underlying soft tissues and placed in sterile normal saline. In chelonia there are paired ventral abdominal veins, and the coeliotomy incision is made between these vessels to gain access to the coelomic cavity. Ovariosalpingectomy and salpingotomy procedures are carried out in much the same way as previously described for squamates, but the chelonian shell gland is often thicker than that of lizards and snakes. The coelomic membrane is closed in a simple continuous or interrupted pattern. The bone segment is replaced and secured in place using autoclaved fibreglass patches and epoxy resin.

Key words Anaesthesia, surgery, reptile, propofol, isoflurane, dystocia.

References 1.

Bennett, R.A. (1996). Anaesthesia. In: Reptile Medicine and Surgery. First edition (Ed. D. R. Mader). W.B. Saunders, Philadelphia. Pages 241-247. Lawton, M.P.C. (1992). Anaesthesia. In: Manual of Reptiles (Eds.

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3. 4. 5.

4th European FECAVA SCIVAC Congress P.H. Beynon, M.P.C. Lawton, J.E. Cooper). BSAVA, Cheltenham. Pages 170-183. Mader, D.L. (1996) Reptile Medicine and Surgery. WB Saunders, Philadelphia. Malley, A.D. (1997) Reptile anaesthesia and the practising veterinarian. In Practice 19(7):351-368. Lawton, M.P.C. (1992). Surgery. In: Manual of Reptiles (Eds. P.H. Beynon, M.P.C. Lawton, J.E. Cooper). BSAVA, Cheltenham. Pages 184-193.

Bennett, A.R. and Mader, D.R. (1996). Soft tissue surgery. In: Reptile Medicine and Surgery. First edition (Ed. D. R. Mader). W.B. Saunders, Philadelphia. Pages 287-298. DeNardo, D. (1996). Dystocias. In: Reptile Medicine and Surgery. First edition (Ed. D. R. Mader). W.B. Saunders, Philadelphia. Pages 370-374. Divers, S.J. (1996). Medical and surgical treatment of pre-ovulatory ova stasis and post-ovulatory egg stasis in oviparous lizards. ARAV 1996 Proceedings, Pages 119-123.

SCIVAC EXOTIC ANIMALS STUDY GROUP

Diagnostic techniques for reptiles Stephen John Divers BSc (Hons) - C Biol. MI Biol - B Vet Med - MRCVS The Exotic Animal Centre - Essex - United Kingdom

Summary Making a definitive diagnosis is the end point of a clinical journey. This may start with history taking and the clinical examination may provide a list of possible differential diagnoses. However, it is often necessary to take clinical samples, perform laboratory techniques and utilise diagnostic imaging before a definitive answer can be found. This paper attempts to clarify the major aspects of reptile diagnostics from taking a history from the owner to sending a liver biopsy for histopathological confirmation of fungal hepatitis!

Introduction The art of veterinary medicine and making that previously elusive reptile diagnosis rests upon our abilities as clinicians to untangle the complex clinical web and piece together the pathology to determine the underlying aetiology and clinical picture. A logical approach to reptiles will provide the veterinarian with most of the information required to successfully diagnose and treat the majority of ailments. When discussing “diagnostic techniques” it is vital that we do not forget that a thorough history and full clinical examination are important diagnostic aids in their own right and should be performed ahead of any other diagnostic tests. Further investigations include haematology, serum biochemistry, parasitology, microscopy, cytology, microbiology, radiography, endoscopy, ultrasonography, MRI and CT, and exploratory surgery.

History Taking1 Reptiles should be transported to the practice in linen or cloth bags within styrofoam boxes, and their owners encouraged to keep and bring along their own husbandry records. The identity of an unfamiliar species should be ascertained before arrival to permit the clinician to become familiar with the species’ specific husbandry requirements. The vast majority of reptile diseases are due either directly or indirectly to substandard husbandry and therefore a thorough review of husbandry practices, hygiene and nutrition is essential. It is often useful when dealing with an unfamiliar species to have a sample history which can be followed during the consultation. Exotic animals invariably require an

extended consultation period but the extra time taken to obtain a detailed history will be clinically valuable and will often provide a tentative diagnosis. Qualitative and, where possible, quantitative changes in husbandry, food and water consumption, faeces, urine/urates, and behaviour should be identified. Specific changes associated with breeding and hibernation are frequently associated with disease problems and therefore careful questioning is required. Recent additions to the reptile collection are also significant, especially as few owners operate the recommended 3-6 month quarantine period. Sample history form 1).reptile’s name or identification. 2) species, subspecies, native locality, colour morphology. 3) date of birth, age. 4) sex. 5) duration in owners care/captivity. 6) origin (captive bred, wild caught, when imported). 7) details of source (breeder, retailer, importer). 8) enclosure/vivarium specifications: type (arboreal, terrestrial, aquatic). size (length x depth x height). construction (materials, paints, sealant, internal fittings, or purchased ready-made). furnishings (bark, plants, floor material). provision for vivarium ventilation (mesh, air holes). frequency of cleaning. detergents, disinfectants used. 9) environment: vivarium (temperate, tropical). outdoor enclosure (grassland, wooded, overgrown). 10) heating equipment (spot lights, ceramics, heating cables, heat mats). 11) temperature control (thermostat, rheostat) and method of recording (type and position of thermometer). 12) temperatures (daytime air, daytime basking, night time air). 13) lighting equipment (spot lights/fluorescent strip lights). 14) lighting control (photoperiod, manual/timer). 15) humidity level (day, night and seasonal changes, method of provision - spray, sprinkler). 16) diet (varieties and quantities). 17) feeding: amount of food normally offered/actually eaten. frequency of feeding. time food offered (morning, overnight etc). changes in appetite.

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18) method of water provision (bowl, spray). how often is water changed. how often is the water container cleaned. what disinfectant/detergent is used. changes in drinking behaviour. 18) food and water vitamin/mineral supplements. 19) breeding details (recent breeding attempts including changes of temperature, humidity, feeding and animals groupings). 20) other specimens in same vivarium or have shared the same vivarium within the last 6 months. 21) other specimens in same room or that have been in the same room in the last 6 months. 22) disease history of animal in question or any in-contact animals. 23) quarantine protocol for all new additions (length of quarantine period, position of quarantine vivarium in relation to established collection). 24) other details of relevance.

Clinical Examination1,2 Reptiles as a group are relatively easy to evaluate and the standard examination techniques used for domestic pets apply equally to reptiles. Calm specimens should be observed from a distance without handling to observe demeanour, locomotion and any obvious neurological disorders. Nervous or aggressive species are best restrained using appropriate techniques, including towels and gloves, at all times. Observation of reptiles within their vivarium or enclosure is particularly valuable and should be performed whenever possible. Reptiles present no more of a zoonotic danger than domestic animals, however the risks of Salmonella sp, Pseudomonas sp, Rickettsia sp and pentastomids (arachnid lung parasites) does necessitate adequate hygienic precautions at all times. All reptiles should be accurately weighed. It is also worth taking the cloacal temperature of any reptile weighing more than 1 kg which has not been out of the vivarium environment for more than an hour. This temperature will give an accurate indication of a large reptile’s core temperature and consequently an indication of that of its environment. For example, a 5 kg iguana with a cloacal temperature of 15C is unlikely to have been removed from a 30C environment within the last hour. Length is also an important measurement that should be routinely recorded. The snout-vent length of lizards and snakes is usually recorded, while the horizontal carapace length of chelonians is more useful, especially when combined with weight to give a weight-length (Jackson’s) ratio. Useful equipment for the reptile consulting room Electronic scales, 0-2000 g accurate to 1 g, 0-100 kg accurate to 0.2 kg. Handkerchiefs, tea-towels and bath towels. Rubber gloves, thin leather gloves, gauntlets. Snake hooks. Transparent plastic boxes to observe small reptiles unre-

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strained. Plastic or wooden spatulas. Sexing probes. Dedicated auroscope attachment for cloacal examination. Assortment of plastic gags. Focused light source, preferably flexible for transillumination. Digital thermometer with remote probe and a range of 0-50C. Stethoscope with swab attached to diaphragm. A systematic examination from rostrum to tail tip is always indicated, including a thorough palpation of all accessible areas for any abnormalities. It not uncommon for a reptile to void faeces and urates during the clinical examination, and this material should be collected for immediate laboratory investigation. Transillumination using a powerful light source is particularly useful for visualising the internal structures of small lizards and snakes, although care must be exercised due to the heat produced by these appliances. A flexible endoscope is ideal but a far cheaper alternative is the flexible light source recently introduced by Medical Diagnostic Services. The light source can be held against the body of small reptiles or lubricated and inserted into the oesophagus or cloaca and rectum. Transillumination enables coelomic masses to be identified and the cardiac shadow can be located for cardiocentesis in small specimens. Auscultation is possible and useful in reptiles but does require a silent consulting room. The adventitious sounds produced between the shell or scales and the stethoscope diaphragm can be reduced by placing a dampened swab or towel between the stethoscope and the surface of the reptile. Intractable animals are best sedated to facilitate a safer more thorough examination. Ketamine HCl (Vetalar, ParkeDavis; Ketaset, Willows-Francis) at 20-50 mg/kg IM can be employed but greater care must be exercised when using this drug in debilitated reptiles. Snakes Aggressive snakes should be restrained before they are removed from their transportation bag. The head is held behind the occiput using the thumb and middle finger, while the index finger is placed on top of the head. The larger pythons and anacondas can exceed 6 metres and 150 kg and are powerful and potentially dangerous. In such circumstances, a second or even third handler will be required to support the body during the examination. It is usually safer and more convenient to sedate a large pugnacious snake than to struggle on and risk injury to the snake, client or staff. Non-venomous species should be removed from their cloth bag when an assessment of demeanour and muscle tone will quickly become obvious. Sick snakes will usually remain limp while healthy specimens will grip or move over the clinician’s hands and arms giving a sense of strength. A healthy snake that is permitted to wrap a coil around the handler’s wrist while the head is allowed to hang down should be able to raise its head to the level of the tail. Head position, body posture, cloacal tone and righting reflexes can be used to assess neurological function. The integument, particularly the ventral scales, should be carefully examined for any evidence of dysecdysis (poor shedding) and trauma. Skin tenting and ridges may indicate

cachexia or dehydration while ticks and the snake mite (Ophionyssus natricis) may congregate in skin folds, infraorbital pits and corneal rims. The infraorbital pits (where present) and the nostrils should be free from any discharge or retained skin. The eyes should be clear, unless ecdysis is imminent when a bluish haze may be present. The spectacles covering the eyes should be smooth as any wrinkles may indicate the presence of a retained spectacle. Ocular swellings are often due to a build up of lachrymal secretions within the sub-spectacular space because of a blockage within the nasolachrymal duct. Such swellings may become infected resulting in abscessation. The body should be thoroughly palpated for any abnormal masses, and their position related to that of the major organs to identify their likely significance. Depending upon the musculature of the snake the heart and faecal masses are often palpated and erroneously considered pathological. The cloaca should be free from faecal staining and discharge. Examination of the cloaca can be carried out using an auroscope and digital palpation. In the large constrictors it is possible to insert a lubricated gloved hand to perform an internal cloacal and even rectal examination. The sex of the snake can be ascertained by examination of the tail length and probing of the hemipenes. The tail length (and the number of sub-caudal scales) is always smaller in females than males but this method requires access to published information on tail length and scale counts unless both sexes are available for examination. The hemipenes are entered by placing a caudally pointing probe, either side of mid line, just inside the caudal cloacal rim. In males the probe passes to a depth of 6-12 subcaudal scales whereas in females the probe enters a musk sac to a depth of only 2-4 subcaudal scales. Examination of the oral cavity is best left until last as most snakes object to such manipulation. However, even before the mouth is opened the tongue should have been seen frequently flicking in and out of the labial notch. The mouth can be gently opened using a plastic or wooden spatula to permit an assessment of mucous membrane colour and examination for signs of mucosal oedema, hypersalivation, haemorrhage, necrosis and the presence of caseous exudates. The presence of white deposits may indicate uric acid deposition due to visceral gout. The pharynx and glottis should be examined for haemorrhage, foreign bodies and discharge. It is important to observe the glottis during respiration in an attempt to differentiate between discharges originating from the respiratory and gastro-intestinal tracts. Body organ position in boas and pythons Organ

Percentage position from snout

Heart Lung Air sac Liver Stomach Small intestine Cranial pole of right kidney Caudal pole of left kidney

22-33 33-45 45-65 38-56 46-67 68-81 69-77 74-82

Colon

81-100

Figures relate to the percentage distance of each organ from the snout. The total length being that from the snout to the cloaca. The organ positions of other species of snake are broadly similar although differences in anatomy certainly exist between the major serpentine groups. Lizards Lizards vary greatly in size and temperament and therefore a variety of handling techniques are required to cover all situations. The tegus and monitor lizards are renowned for their powerful bites while other species, particularly the green iguana, are much more likely to use their claws and tail to painful effect. The main problem of handling small lizards is restraining them before they flee from the cloth bag. In all cases, the lizard should be transported in a securely tied cloth bag so that the position of the lizardâ&#x20AC;&#x2122;s head can be identified and restrained before the bag is even opened. The large lizards are best restrained with the forelimbs held laterally against their thorax and the limbs held laterally against the tail base. Smaller lizards can be restrained around the pectoral girdle holding the forelimbs against the thorax, although care is required not to impair respiratory movements. Never grasp a lizard by the tail because many species can perform autotomy and shed their tails in an attempt to evade a predator (or in this case clinician!). Restricting the vision of these animals is often the simplest way to facilitate handling and a towel placed over the head will enable the clinician to thoroughly examine the rest of the body and limbs. A useful restraint technique for iguanid lizards utilises the vaso-vagal response: gentle digital pressure is applied to both orbits and in many cases the lizard will enter a state of stupor for up to 45 minutes or until a painful stimulus is applied. This technique can be employed to calm nervous iguanids and monitors but, more importantly, enables the mouth to be gently opened without the need for excessive force. The integument should be examined for parasites and evidence of trauma due to fighting, mating and burns. Lizards tend to shed their skin in a piecemeal fashion and therefore retained skin (often dry and brown) must be differentiated from normal ecdysis (flexible and transparent). Classically, dysecdysis and skin retention occurs around the digits and tail causing ischaemic necrosis. Extensive skin folding and tenting are indicators of cachexia and possible dehydration. The nostrils, eyes, and tympanic scales should be clean and free from discharges, although some iguanids excrete salt through specialised nasal glands which is then expelled through the nostrils. The rostrum should be examined for trauma due to repeated escape attempts from a poorly designed vivarium. The head and limbs must be palpated for masses which may be abscesses or fibrous periosteal reactions associated with metabolic bone disease. Lizards suffering from severe hypocalcaemia due to metabolic bone disease may exhibit periodic tremors and muscle fasiculations. The cloaca should be free from faecal staining, while visual and digital examination should be considered routine. The mouth can be opened using a spatula to examine the oral cavity as described previously. In addition, the internal ex-

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tent of any rostral abrasions can be evaluated. Many species of lizards are sexually dimorphic, although sexing juveniles can be very difficult. Adult males tend to be larger, more colourful, exhibit more courting (head bobbing) and aggressive behaviours, possess paired hemipenal bulges at the tail base and more developed femoral or pre-anal pores. Tortoises, turtles and terrapins The commonly presented tortoises such as the spurthighed and Hermann’s (Testudo spp) are not difficult to handle, although a persistently withdrawn head can hinder the examination. A little patience while holding the tortoise upside down will usually persuade a shy individual to protrude the head from the shell when the thumb and middle finger can be placed behind the occipital condyles. The mouth can then be opened by applying steady distractive pressure to the maxilla and mandible, and once open the index finger can be inserted into the corner of the mouth to prevent closure. This method enables the handler to keep the mouth open using one hand, leaving the other free to examine the buccal cavity, remove foreign bodies, and take samples for laboratory investigation. The limbs can also be withdrawn by applying steady traction. The coelomic space within the shell is restricted and therefore, gently forcing the hindlimbs into the shell, leads to protrusion of the forelimbs and head, and vice versa. The more aggressive species, especially the terrapins and turtles should be held at the rear of the carapace. Some larger species (snapping turtle, Chelydra serpentina; soft shelled turtles, Trionyx spp) can deliver an extremely powerful bite and so great care is required at all times. Certain species also possess functional hinges at the front and back of the plastron. The box tortoises are becoming increasingly common since the importation ban on Mediterranean tortoises, and care should be exercised not to trap a finger when the hinge closes. The chelonian shell presents an obvious barrier to a thorough clinical examination, however much can still be achieved in the consulting room before resorting to imaging techniques. The head must be extended and the mouth opened to permit a thorough buccal examination including an assessment of the mucous membranes and tongue for signs of stomatitis. The glottis should be examined for signs of discharge suggestive of pneumonia. The eustachian tubes enter the lateral walls of the pharynx and any solid deposits in this area may indicate otitis or urate deposition. The nostrils should be clear and free from any discharge. The eyelids should be open and not obviously distended while the eyes should be clear and bright. The tympanic scales should be examined for any swellings indicative of ear abscessation. The neck and limbs should be palpated for masses and signs of skin damage, parasites and dysecdysis. The inguinal fossae should be palpated with the chelonian held upright. Gently rocking the animal may then enable the clinician to palpate eggs, uroliths or other coelomic masses. The shell should be examined for poor conformation, trauma and infection. Pyramiding or softening of the shell is often caused by inappropriate nutrition while shell infection may present as loosening and softening of the scutes, erythema and haemorrhages within the shell, and discharges from shell lesions.

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Prolapses through the cloaca are obvious but it is necessary to differentiate between prolapses of the cloaca and those of the male penis. Internal examination using digital palpation and an auroscope or endoscope is recommended. Male chelonians can be differentiated from females by their longer tails and the position of their cloaca caudal to the edge of the carapace. A detailed history and clinical examination will usually indicate which further investigations may be necessary to make a definitive diagnosis. Radiography, ultrasonography, MRI and CT, endoscopy, haematology, blood biochemistry, microbiology, cytology and parasitology are all proven techniques that are used extensively in reptile medicine.

Haematology and biochemistry There is now a great deal more clinicopathological data available for many of the common pet reptile species and so blood sampling offers a great wealth of information. Unfortunately, venepuncture is often blind in reptiles but with practice it can be efficiently and consistently performed. Preferred reptile venepuncture sites: SnakesVentral tail vein, caudal to cloaca; The needle is angled at 45-90° (craniodorsal) and placed in the ventral mid line in-between paired caudal scales. A 5/8”-1” 21-25 g needle is advanced, avoiding the hemipenes of males, while maintaining a slight negative pressure. If the needle hits a vertebral body withdraw slightly and redirect. Avoid the hemipenes of males. Preferred site for larger specimens. Cardiocentesis; The snake is restrained in dorsal recumbency and the heart located at a point 22-33% from the snout to the vent. The heart is palpated and immobilised using the thumb and forefinger and a 23-25g 5/8”-11/2” needle is advanced at 45° in a craniodorsal direction into the apex of the beating ventricle. Blood often enters with each heart beat. Preferred site for smaller specimens. LizardsVentral tail vein; A 5/8”-1” 21-25 g needle is angled at 6090° and placed in the ventral mid line about 1/4 to 1/3 of the way down the tail. The needle is advanced while maintaining slight negative pressure. If the needle hits a vertebral body withdraw slightly and redirect. Preferred site for all lizards. Ventral abdominal; A 5/8”-1” 23-25 g needle is advanced in the ventral mid line in a craniodorsal direction. The vein lies just below the abdominal musculature and it is difficult to apply post-sampling pressure which makes haemorrhage a concern. Tortoises, turtles and terrapinsDorsal tail vein; A 5/8” 21-25 g needle is angled at 45-90° and placed, as cranial as possible, in the dorsal mid line of the tail. The needle is advanced while maintaining a slight negative pressure. If the needle hits a vertebral body, withdraw slightly and redirect. The exact position, size and even presence of this vessel may vary between species. Preferred site for those aggressive chelonians that possess a well de-

veloped dorsal tail vein. Right jugular; A 5/8” 23-25 g needle is positioned lateral at the level of the tympanic scale, and directed caudally midway down the neck. It is important to maintain post-sampling pressure to avoid haematoma formation. Preferred site for most chelonians. Subcarapacial vein; The head is pushed inside the coelomic cavity and a needle (bent to 60-75°) is inserted in the mid line just caudal to where the skin of the neck attaches to the cranial rim of the carapace. Advance the 5/8”-1” 2325 g needle in a dorsal direction and maintain slight negative pressure. It is important to maintain post-sampling pressure to avoid haematoma formation. Preferred site for very small specimens. There are a variety of other venepuncture sites including the brachial plexus and femoral plexus, however they usually provide smaller samples which are more often contaminated by lymphatic fluid. CrocodiliansVentral tail vein; A 1-3” 18-23 g needle is angled at 6090° and placed in the ventral mid line about 1/4 to 1/3 of the way down the tail. The needle is advanced while maintaining slight negative pressure. If the needle hits a vertebral body withdraw slightly and redirect. Larger crocodilians (over 1.5 m in length) may require chemical restraint using a neuromuscular blocking agent (e.g. 0.4-1.0 mg/kg gallamine, reversed with neostigmine), and it may be necessary to use large spinal needles (3-8”) to reach the vein. Preferred site for smaller specimens. Supravertebral vein; A 1-2” 20-23 g needle is inserted at 90o in the mid line just caudal to the occiput. The needle is advanced to just dorsal to the spinal cord, while maintaining a slight negative pressure. Preferred site for larger crocodilians (over 1.5 m) but chemical restraint using a neuromuscular blocking agent (e.g. 0.4-1.0 mg/kg gallamine, reversed with neostigmine) must be considered for both animal and operator safety.

Haematology3 Some species are sensitive to EDTA as an anticoagulant and so lithium heparin is the anticoagulant of choice. Reptiles possess nucleated red and white blood cells and so differential cell counts must usually be performed manually using either the Eosinophil Unopipette or Toluidine blue technique. • Erythrocytes ✓ nucleated ✓ blood parasites common but not usually significant • Thrombocytes ✓ smaller than erythrocytes ✓ dense basophilic nucleus ✓ often found in clusters • Lymphocytes ✓ most common leucocyte ✓ variable in size and colour ✓ eccentric nucleus ✓ reactive lymphocytes are called plasma cells • Monocytes ✓ large in size but rare in number

✓ bluish-grey fine granular cytoplasm with vacuoles ✓ indented or U-shaped nucleus • Azurophils ✓ non-segmented nucleus ✓ basophilic cytoplasm with azurophilic area but without granules ✓ reactive azurophils may contain vacuoles, granules, phagocytosed material ✓ often considered an acute inflammatory cell • Heterophils ✓ variable nucleus ✓ spiculate eosinophilic granules ✓ reptilian equivalent of the mammalian neutrophil ✓ elevated during bacterial infections and tissue necrosis • Eosinophils ✓ may be difficult to distinguish from heterophils ✓ eosinophilic granules are usually more rounded • Basophils ✓ small but common leucocyte ✓ intensely basophilic granules ✓ fragile cells that may disintegrate during slide processing. Interpretation may be difficult and requires experience so try to locate an experienced, preferably avian and exotic haematologist. When developing an in-house haematology service there are various normal ranges scattered throughout the literature that can be employed, but nothing is superior to developing your own series of normal ranges. In cases of emergency, haematocrit (PCV) estimations and qualitative evaluations of the buffy coat and stained blood smear may be very useful until a full haematology can be obtained.

Biochemistry3 Various biochemical parameters and electrolytes can be routinely used to assess organ damage and metabolic disturbance. Heparinised plasma or serum can be should be used for most estimations. The author uses two main biochemistry profiles for reptile; Mini-profile: Calcium, phosphorus, uric acid, AST, total protein, albumin and globulin. Extended profile: Calcium, phosphorus, uric acid, AST, ALT, GGT, bile acids, cholesterol, triglycerides, CPK, glucose, total protein, albumin, globulin, sodium, chloride, potassium. Normal blood ranges for green iguanas (Iguana iguana).4 Biochemical parameter Total protein g/l Albumin g/l Globulin g/l Uric acid mmol/l Alkaline phosphatase u/l Alanine aminotransferase u/l Aspartate aminotransferase u/l g-Glutamyl transferase u/l Cholesterol mmol/l Triglycerides mmol/l Glucose mmol/l

Normal range 50-78 21-28 25-43 70-140 50-290 5-68 5-52 0-3 2.7-8.6 0.6-7.8 9.4-16.0

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Calcium mmol/l Phosphorus mmol/l

2.2-3.5 1.5-3.0

Haematological parameter

Normal range

Total red blood cell count x10^12/l Packed cell volume l/l Haemoglobin g/dl MCV fl MCH pg MCHC g/dl Total white blood cell count x10^9/l Heterophils x10^9/l Azurophils x10^9/l Lymphocytes x10^9/l Eosinophils x10^9/l Monocytes x10^9/l Basophils x10^9/l

1.0-1.9 0.25-0.38 6.0-10.0 165-305 48-78 20-38 3-10 0.35-5.2 0.0-1.7 0.5-5.5 0.0-0.3 0.0-0.1 0.0-0.5

mogenous predominant bacterial population • Faecal floatation - use a concentrated floatation medium and examine for helminth ova • Faecal culture - Mixed bacterial/fungal growths are less clinically important (even if Gram-negative) than a heavy pure growth of a single bacteria or fungus • Beware of pseudo parasites e.g. pollen, prey parasites etc Urine tests; • Direct wet mount • Dip-stick tests • Specific gravity • Cytology • Microbiology

Faecal and urine examination6,7 Reptiles will often void faeces and urates during the consultation, usually all over the veterinarian who should be grateful for this gift of clinical material. When dealing with an anorexic reptile that may not be voiding faeces it is a simple process to perform a cloacal wash; ✓ insert a lubricated catheter (attached to a syringe containing warm normal saline) into the cloaca and advance into the colon ✓ Instil up to 1% body weight of normal saline and repeatedly flush and aspirate until a sample is obtained Faecal tests; • Direct wet mount

- examine under x400 for flagellate protozoa, helminth larvae and ova • Mix with eosin - examine under x400 for encysted amoeba • Acid-fast (ZN) stain - examine for acid fast Cryptosporidia spp • Gram-stain - examine Gram-positive and Gramnegative bacteria. Most reptiles possess G- bacteria, look for ho-

- examine under x400 for protozoa (e.g. Hexamita sp) - blood, leucocytes (glucose, protein) - not very useful as reptile urine is isosthenuric - active inflammation, renal casts - bladder urine is not sterile but heavy pure growth may be clinically significant.

Radiography8,9 Radiography is an important tool in reptile diagnostics that should be utilised more often. It is important to remember that lower kV values will be required for smaller exotic species. Adequate restraint is vital to facilitate proper positioning; ✓ place conscious lizard in radiolucent cloth bag or box ✓ place conscious snake into restraint tube ✓ place chelonian on a raised column to keep limbs clear of table ✓ use the vaso-vagal response in larger lizards ✓ consider chemical restraint and anaesthesia ✓ use tape to secure animals in position Standard views for various species are as follows; Snakes: dorsoventral views of straight body (not coiled) horizontal beam laterals of straight body remember to use markers along body length Lizards: dorsoventral views of whole body or particular part horizontal beam lateral Chelonia: dorsoventral view of whole body

Observed normal haematological and biochemical ranges used to assess dehydration and biochemical imbalances in selected reptiles (adapted from references 4 and 5, and the author’s unpublished observations)

Green iguana

Gila monster

PCV (l/l) TP (g/l) Urea (mmol/l) Creatinine (mmol/l) Uric acid (umol/l)

25-38 50-78 0-0.7 42-80 70-140

Glucose (mmol/l) Sodium (mmol/l) Chloride (mmol/l) Potassium (mmol/l)

9.4-16.0 140-183 102-125 1.3-5.2

25-30 60-85 na na 100-1000 0 2.5-6.0 150-190 114-130 4.1

Tortoise (Testudo sp)

Box tortoise

Boa constrictor

Rat snake

Caiman

19-40 50-75 0.25-6.70 20-150 75-200

20-38 40-50 na na 100-200

20-32 46-80 0-1.67 0-26.5 75-250

20-30 40-70 na na 75-250

26 50-65 na na 175

2.6-5.2 120-158 98-128 4.0-7.0

2.0 130-149 104-108 4.6-4.7

0.6-4.0 130-152 104-124 3.0-5.7

na 130-160 125-147 4.1-5.2

4.1-6.3 139-150 109-132 3.8-7.9

horizontal beam lateral horizontal beam anterior-posterior view

Ultrasonography8,9 Ultrasound permits the visualisation of soft tissues and may be most useful in the chelonia. 7.5 and 10 MHz transducers with stand-off are usually better at providing good resolution in small reptile patients. 5 and 3.5 MHz transducers can be used for larger reptiles. Copious contact gel must be applied to the reptilian scaly skin, especially in heavily keeled species. In some cases a water bath may be more appropriate. Organ position will change with rotation of the reptile and therefore (as with radiography) try and maintain the animal in a normal body posture. Chelonia: sector scanners can be used in the soft tissue spaces between the carapace, plastron and limbs. The reproductive tract, heart and liver can all be assessed for major abnormalities, but identifying subtle differences in tissue structure may be more difficult. Lizards and snakes: the ribs of snakes almost extend along the whole body-length and will be a hindrance to ultrasound. Nevertheless, gonads, ova, eggs can be assessed and masses can be differentiated.

veterinary use.

Cytology and microbiology Cytology2 The submission of clinical material (e.g. impression smears, skin scrapes, fine needle aspirates, lung washes, stomach washes, faeces, urine, spinal fluid, tissue biopsies or post mortem tissues) for microscopy, histopathology and microbiology is often the best means of obtaining a definitive diagnosis. However, the often unique tissue structure of reptiles does necessitate the services of a pathologist with experience in reptile pathology. This is especially true when submitting small biopsies obtained from endoscopy. When time permits full histopathology is to be preferred, but in cases of emergency cytology offers the clinician a good second best. Cytology will usually not provide a complete diagnosis and therefore cannot replace histopathology, however it can provide a working diagnosis while histology is pending. Impression smears from skin lesions, fine needle aspirates, lung wash smears, stomach wash smears etc can be stained using Diff Quik stains and examined under a microscope.

Microbiology11 10

Endoscopy

Fibre-optic endoscopy is the diagnostic imaging and sampling technique of choice in the author’s experience. The use of small flexible and rigid endoscopes (1-2 mm) enable the clinician to get “inside” the animal and depending on the reptile’s size, permits; • visualisation of the gastro-intestinal tract via the mouth and cloaca • visualisation of the respiratory tract via the glottis • laparoscopy ✓ visualisation and biopsy of kidneys ✓ visualisation and biopsy of liver ✓ visualisation and biopsy of pancreas ✓ visualisation and biopsy of spleen ✓ visualisation of the heart ✓ visualisation of the lungs ✓ visualisation of the reproductive tract ✓ visualisation of the bladder (where present) ✓ visualisation of the gastro-intestinal tract ✓ visualisation and biopsy of any masses, neoplasia etc With new endoscopic operating equipment such as the Storz endoscopic scissors, forceps and injection needle it is also possible to debride, cut, retrieve foreign bodies, aspirate and execute remote local injections.

MRI and ct8,9 These sophisticated imaging techniques are unlikely to be easily accessible to most clinicians or financially unacceptable to most clients. However, the quality of the images are excellent and some hospitals may be prepared to tolerate

Gram-negative bacteria are common (often commensal) organisms in reptiles, but heavy pure growths of a single predominant bacteria is often significant. Anaerobic bacteria are often important pathogens that are simply overlooked on routine microbiological culture. Mycotic infections also appear to be more common in reptiles than domesticated mammals. In summary request aerobic, anaerobic and fungal culture with appropriate sensitivity testing. Viruses are becoming more clinically apparent. Aspirates used be sent on dry swab while tissues are best transported fresh on ice. Scanning electronmicrscopy may reveal virus particles while virus culture and isolation is now possible in many labs using reptile and avian cell lines.

Post mortem examination12,13,14 No clinician can save every animal. Death, however unfortunate to the animal and owner, does provide the clinician with a huge resource for not only making an elusive diagnosis but also for learning the pathogenesis of reptile disease. Every reptile clinician needs to familiarise themselves with normal reptile anatomy and post mortem examination is invaluable. A systemic approach is vital and useful histopathological and microbiological information will only be obtained if the submitted tissues are fresh at sampling and stored correctly.

Key words Reptile, diagnostics, history, clinical examination,

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haematology, biochemistry, faecal examination, radiography, ultrasonography, endoscopy, cytology, microbiology, post mortem.

References 1. 2.

Divers, S.J. (1996). Basic reptile husbandry, history taking and clinical examination. In Practice 18(2): 51-65. Jackson, O.F. and Lawton, M.P.C. (1992). Examination and diagnostic techniques. In: Manual of Reptiles (Eds. P.H. Beynon, M.P.C. Lawton, J.E. Cooper). BSAVA, Cheltenham. Pages 32-39. Campbell, T.W. (1996). Clinical pathology. In: Reptile Medicine and Surgery (Ed. D. R. Mader). WB Saunders, Philadelphia. Pages 248257. Divers, S.J., Redmayne, G. and Aves, E.K. (1996). Haematological and biochemical values of 10 green iguanas (Iguana iguana). Veterinary Record 138:203-205. Stein, G. (1996). Hematologic and blood chemistry values in reptiles. In: Reptile Medicine and Surgery, p473-483 (Ed. D. R. Mader). WB Saunders, Philadelphia. Lane, T.J. and Mader, D.R. (1996). Parasitology. In: Reptile Medicine and Surgery (Ed. D. R. Mader). WB Saunders, Philadelphia. Pages 185-202. Frye, F.L. (1991). Applied clinical nonhemic parasitology of reptiles. In: Biomedical and Surgical Aspects of Captive Reptile Husbandry (Ed. F.L. Frye, second edition). Pages 281-325. Silverman and Janssen, D.L. (1996). Diagnostic imaging. In: Reptile Medicine and Surgery (Ed. D. R. Mader). WB Saunders, Philadelphia. Pages 258-264. Rubel, A., Kuoni, W. and Frye, F.L. (1991). Radiology and imaging. In: Biomedical and Surgical Aspects of Captive Reptile Husbandry (Ed. F.L. Frye, second edition). Pages 185-208.

10.

11.

12.

13. 14.

Jenkins, J.R. (1996). Diagnostic and clinical techniques. In: Reptile Medicine and Surgery (Ed. D. R. Mader). WB Saunders, Philadelphia. Pages 264-276. Rosenthal, K. and Mader, D.R. (1996). Microbiology. In: Reptile Medicine and Surgery (Ed. D. R. Mader). WB Saunders, Philadelphia. Pages 117-125. Cooper, J. E. (1992). Post mortem examination. In: Manual of Reptiles (Eds. P.H. Beynon, M.P.C. Lawton, J.E. Cooper). BSAVA, Cheltenham. Pages 40-49. Mader, D.R. (1996). Euthanasia and necropsy. In: Reptile Medicine and Surgery (Ed. D. R. Mader). WB Saunders, Philadelphia. Pages 277-281. Frye, F.L. (1991). Euthanasia and necropsy. In: Biomedical and Surgical Aspects of Captive Reptile Husbandry (Ed. F.L. Frye, second edition). Pages 513-528

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Diagnostic and therapeutic approaches to neutropenia and neutrophil dysfunction The neutropenic and pyrexic cat

Bernard F. Feldman DVM, PhD, Dipl ACVIM Department of Biomedical Sciences and Pathobiology - Virginia-Maryland Regional College of Veterinary Medicine - Blacksburg, Virginia - USA

OVERVIEW Neutropenia Neutropenia may indicate excessive tissue demand for neutrophils, decreased production, or immune-mediated destruction. Neutropenia is as great a concern as neutrophilia and is possibly a more serious a problem because neutrophils are the bodyâ&#x20AC;&#x2122;s first line of defense against invading microorganisms. Neutropenia is any decrease in neutrophil numbers below the reference interval. However, clinical signs associated with neutropenia are seldom observed unless the neutrophil count is below 1000 per microliter and, perhaps, less than 500 per microliter. Neutropenia is associated with infection, drugs, immune dysfunction, acquired immunodeficiency, neoplasia, and may be idiopathic.

Fever Temperature, like so many biologicial functions, normally displays circadian rhythmicity. In the cat, temperatures are often lowest in the morning and highest in the afternoon. Temperature is regulated by homeostatic mechanisms that strike a balance between heat production and heat dissipation. Abnormal elevation in body temperature, or pyrexia, can occur due to hyperthermia or fever. Hyperthermia is treated with physical cooling methods whereas fever is often treated with drugs. Fever is often a positive response and, in most instances, is simply noted. Interleukin-1 is produced by mononuclear phagocytes and directly acts upon the hypothalamic control center causing fever.

Fever of undetermined origin Fever of undetermined origin (FUO) is an unusual presentation of a usual problem. FUO is caused by infection, immune dysfunction, or neoplasia

CLINICAL AND THERAPEUTIC APPROACH Diagnostic Evaluation of Granulocytopenia (less than 5000 cells per microliter in the dog and less than 3300 cells per microliter in the cat).

Diagnostic evaluation should include an extensive history of current and recent (including the past 6 weeks) drug therapy and physical examination to evaluate or estimate splenic size. 1. Hematologic evaluation - the total white blood cell count and differential in absolute terms with or without relative lymphocytosis. 2. Bone marrow aspiration (and/or biopsy) is necessary when the white cell count is persistently below 3000 cells per microliter. This is especially needed when another cell line is also abnormal to determine marrow cellularity or arrest in cell maturation. 3. Screening tests for antinuclear antibodies in both systemic lupus erythematosus or rheumatoid arthritis. Again, this is especially required when rheumatoid arthritis is suspected of being associated with hypersplenism. 4. Radiographic, ultrasound or cytologic examination of the spleen to evaluate size, and potential for cellular sequestration since hypersplenism may be associated with leucopenia as well.

Neutropenia Leucopenia is most often caused by neutropenia. Neutropenia may be the result of overwhelming inflammatory processes which shorten circulating neutrophil survival especially when myelopoiesis -specifically neutrophil production - is ineffective, or when there is bone marrow myelosuppression. Neutropenia and toxic morphologic alterations of neutrophils may be anticipated in Gram-negative sepsis or endotoxemia. If mature neutrophils are fewer than immature cell forms, this is regarded as a degenerative left shift. Degenerative left shifts may appear with both neutrophilia or neutropenia and indicate inappropriate - deficient - bone marrow response. Increased neutrophil margination, adherence of neutrophils to microvascular endothelium pseudoneutropenia - may result from endotoxemia or from anaphylactic reactions. Viral infections, a wide variety of disparate drugs and environmental toxins, and neoplasia (especially during chemotherapy) may induce severe neutropenia as well as affecting other cell lines in a similar manner. Feline immunodeficiency virus (FIV) infection is characterized by moderate to severe leucopenia, neutropenia, and often, lymphopenia and eosinopenia. Appropriate myeloid activity or mild bone marrow myeloid hyperplasia

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with a left shift to progranulocytes often accompanies the neutropenia. Chronic infection is characterized by intermittent neutropenia and lymphopenia. Viral infection of bone marrow myeloid precursors may be involved with the cytopenias. Feline immunodeficiency virus induces progressive immunodeficiency, opportunistic infections, nutritional deficiencies, as well as some forms of neoplasia. The cytopenias that develop during the symptomatic disease induced by FIV may play a significant role in these processes. Experimental inoculation of canine parvovirus in the cat induces a decrease in total numbers of both myeloid and erythroid cells in the bone marrow. Feline leukemia virus infection (FeLV) is a retrovirus (oncovirus subfamily) that causes immunodeficiency and neoplastic disease in domestic cats. The physiologic systems affected are the hematopoietic, lymphatic, and immune systems possibly by neuroendocrine dysfunction, resulting in immunosuppression with secondary infections and/or development of neoplastic disease. Anemia is often severe. Lymphopenia and neutropenia may be present; however neutrophils can be elevated in response to secondary infections. Serology and bone marrow examination are indicated among diagnostics. Feline panleucopenia is an acute, enteric, viral infection of cats characterized by sudden onset, depression, vomiting and diarrhea, severe dehydration, and a high mortality caused by feline parvovirus. The systems affected are the hematopoietic, lymphatic, and immune systems with loss of all white blood cells and atrophy of the thymus. Panleucopenia is the most consistent finding with total leucocyte counts between 500 and 3000 cells per microliter. Immunoassays and serology are the only useful diagnostics. Supportive treatment is indicated as specific therapy is not usually successful. Bacterial-induced myelonecrosis occurs in dogs and cats. Reduced survival neutropenia can be caused by bacteremia (pneumonia, peritonitis, pyothorax), immune-mediated destruction, drug-induced destruction, hypersplenism (sequestration), and paraneoplastic syndrome (the precise mechanism is unknown). Drug/Chemical-induced Neutropenia is often caused by chloramphenicol or benzene ring compounds in cats - eucalyptus oil, menthol, camphor. Mitoxanthrone is a chemotherapeutic agent which induces myelosuppression. The myelosuppression has been successfully treated with recombinant canine granulocytecolony stimulating factor (rcG-CSF). Administration of zidovudine (> 30 mg/kg) in cats resulted in dose dependent progressive neutropenia and anemia. Griseofulvin administration has been associated with the development of absolute neutropenia in cats. This is especially apparent in cats infected with FIV. Cephalosporin administration may induce bone marrow suppression in both dogs and cats as the result of ineffective marrow erythropoiesis and myelopoiesis. Other potential drugs include gold salts, thiacetarsamide, meclofenamic acid, quinidine gluconate, captopril, and penicillamine. Recombinant canine G-CSF (2.5 ug/kg q 12 h) administration had been observed to be effective in stimulating

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myelopoiesis in dogs.

Cyclic neutropenia Cyclic neutropenia is an inherited disease in Grey Collies (Grey Collie Syndrome; Cyclic Hematopoiesis) and is suspected in other canine breeds. It is characterized by recurrent episodes of neutropenia lasting 12 to 14 days. Thrombocytopenia and anemia may accompany cyclic neutropenia. Neutrophil functions are also impaired and frequent infections are therefore anticipated. Affected dogs given low dose rcG-CSF continued to have neutropenic cycles but the degree of neutropenia and the clinical signs were ameliorated. Cyclic hematopoiesis has been described in the cat as an acquired disease possibly related to feline leukemia viral infection (FeLV).

Chronic idiopathic neutropenia syndrome Persistent neutropenia has been described in the cat that resembles chronic idiopathic neutropenia syndrome of man. Decreased numbers of mature granulocytic cells and colony forming units-granulocyte macrophage (CFU-GM) have been observed in bone marrow and in bone marrow culture respectively.

Diagnostic evaluation of functional granulocytic defects Neutrophils function as phagocytes by a complex interaction of immunoglobulins, complement, and neutrophil enzymes. Total evaluation involves evaluation of patients who exhibit an inability to handle infections. 1. Chemotaxis may be tested in agar media or in a three part Boyden chamber. 2. Quality and quantity of immunoglobulins and complement must be determined. Quantity is determined my immunoelectrophoresis and determination of the presence of various complement components. Quality of immunoglobulins may be tested similarly to chemotaxis in agar media. A screening test of complement function is the total lytic complement test. 3. The nitroblue tetrazolium dye test (NBT) is a test of nonimmune phagocytosis and measures the contribution of peroxidase qualitatively. 4. The myeloperoxidase stain which measures the presence of the enzyme in neutrophil cytoplasm also provides qualitative measures.

Functional defects of granulocytes Neutrophil function involves chemotaxis, phagocytosis, and bacterial killing. Problems with neutrophil function can involve one or all of these functions. Chemotaxis and phagocytosis are dependent on external factors involving immune (antibody) globulin and complement opsonins C3a, C5a, and C567. Bacterial killing involves production of hydrogen per-

oxide intracellularly by anaerobic glycolysis and the hexose monophosphate shunt and utilizes myeloperoxidase of granulocytic primary granules. Diseases associated with functional defects of granulocytes are characterized by repeated bacterial or fungal infection beginning early in life or infections with otherwise lowvirulence organisms in patients with appropriate granulocyte counts. Most involve inherited disorders of immunoglobulins, complement, or the hexose monophosphate shunt. Acquired transient deficiencies secondary to drugs are poorly understood. Leucocyte dysfunctions in small animals include the Chediak-Higashi Syndrome, canine granulocytopathy, and defective neutrophil function of the Doberman Pinscher. Neutrophil dysfunctions may also be associated with complement or immunoglobulin deficiencies. Defective humoral immune components include specific IgA deficiency of German Shepherds, Beagles, Shar Peis, and other breeds, IgM deficiency of the Doberman Pinscher, C3 deficiency of the Brittany Spaniel and possible IgG deficiency of the Weimaraner. The Pelger-Huet Anomaly is in inherited defect observed in dogs and cats as well as numerous other species. Mature neutrophils of affected individuals have nuclear hyposegmentation and, possibly, moderate dysfunction associated with diminished migratory capabilities. Myeloproliferative disorders - leukemias - often have associated neutrophil dysfunction and/or neutropenia. Decr-

reased production of neutrophils (or other hematopoietic cells can occur from infiltrative bone marrow diseases leukemia, nonhematopoietic neoplasia metastatic to the marrow cavity, myelofibrosis or ostesclerosis, disseminated granulomatous disease, or myelodysplasia.

Suggested reading Gabbert NH: Cyclic neutropenia in a feline leukemia-positive cat: a case report. J Amer Animal Hosp Assoc 20:343, 1984. Helton KA, Nesbitt GH, Caciolo PL: Griseofulvin toxicity in cats: literature review and report of seven cases. J Amer Animal Hosp Assoc 22:453, 1986. Latimer KS, Rowland GN, Mahaffey MB: Homozygous Pelger-Huet anomaly and chondrodysplasia in a stillborn kitten. Vet Pathol 25: 325, 1988. Obradovitch Je, Ogilvie GK, Stadler-Morris S et al: Effect of recolmbinant canine granuloctye colony-stimulating factor on peripheral blood neutrophil counts in normal cats. J Vet Intern Med 7: 65, 1993. Breitschwerdt EB, Brown TT, de Buysscher E et al: Rhinitis, pneumonia, and defective neutrophil function in the Doberman Pinscher. Am J Vet Res 48:1054-1062, 1987. Withbread TJ, Batt RM, Garthwaite G: Relative deficiency of serum IgA in the German Shepherd dog: a breed abnormality. Res Vet Sci 37:350352, 1984. Hansen P, Clercx C, Henroteaux M et al: Neutrophil phagocyte dysfunction in a Weimaraner with recurrent infections. J Small Animal Practice 36:128-131, 1995. Mandell CP, Jain NC, Farver TB et al: The significance of normoblastemia and leucoerythroblastic reaction in the dog. J Amer Animal Hosp Assoc 25, 665-672, 1989.

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Feline anemia: practical investigation and management Bernard F. Feldman DVM, PhD, Dipl ACVIM Department of Biomedical Sciences and Pathobiology - Virginia-Maryland Regional College of Veterinary Medicine - Blacksburg, Virginia - USA

Summary Red blood cell production and its control are intrinsic to understanding anemia. Anemia is a sign of underlying disease. Complete physical examinations are complemented by complete hemograms. Responsive anemias are caused by hemorrhage and hemolysis. Nonresponsive anemias are more common in the cat than are responsive anemias. The prior use of drugs must be considered. Retroviral diseases are another consideration. Bone marrow examination may be beneficial. Treatment of anemia is directed against the underlying cause.

The erythroid cell system comprises the population of circulating red blood cells (RBCs) and their nucleated precursors located in the bone marrow of normal feline adults. A complex and not yet fully understood homeostatic mechanism (involving in part the hormone erythropoietin) operates upon marrow precursors to maintain a circulating RBC population at a size and hemoglobin content adequate to preserve normal tissue oxygen tensions. The critical factor in the homeostatic mechanism that regulates the production of erythropoietin is tissue oxygen tension, not RBC number or blood hemoglobin concentration.1-3 RBCs traditionally have been considered to be solely oxygen-carrying and oxygen-delivering cells, functions certainly of critical importance. These cells are now being reexamined in terms of their role in physiologic defense. The surface area of RBCs is enormous - and is known to be adsorptive. The redefinition of RBC function has to do with this adsorptive capacity and the intrinsic ability of RBCs to remove or cleanse the plasma component of blood. RBCs adsorb many microscopic materials, which are removed by the phagocytes of the mononuclear-phagocyte system (MPS) located primarily in the liver and spleen. The RBC membrane is thus cleansed, and for the most part the cleansed cell is returned to the circulation. This phagocytic processing also has an impact on the RBC in terms of its longevity (or senescence). Repeated phagocytic incursions does affect the shape, viability, and longevity of the RBC.1,2,4,5

ANEMIA IN PERSPECTIVE Anemia, defined as a lower than normal blood hemoglobin (Hb) concentration or packed cell volume (PCV; hematocrit

[HCT]), occurs if RBC production is acutely or chronically insufficient to replace RBC losses, which may be caused by normal RBC senescence, accelerated RBC destruction (hemolysis), or extracorporeal blood loss (bleeding). Some examples of anemia result from relatively uncomplicated alterations in single factors, for example, transient anemia following an acute hemorrhagic event in an otherwise healthy individual. In most cases, however, the pathophysiology of anemia involves the interplay of several disturbances in RBC homeostasis, including limitations of production as well as abnormal red cell survival. Our first obligation is to examine these factors in a general sense and to evaluate the significance and limitations of the techniques for distinguishing and quantitating them.1-3

RED BLOOD CELL PRODUCTION Basic knowledge about feline RBC production is intrinsic to understanding how the cat responds to a lowered red cell mass (i.e., anemia). In the normal adult, RBC production is confined to the axial skeleton. When erythropoiesis is required, the volume of active marrow may expand into the distal long and flat bones, that is, into the fatty marrow and at the expense of bony matrix. Under extreme and prolonged stress or when marrow is replaced by pathologic tissues, extramedullary sites such as spleen, liver, and lymph nodes may develop foci of erythropoiesis. All of these tissues including the marrow are capable of a six- to eightfold increase in RBC production in response to the stimulus of anemia. Thus even under conditions of accelerated red cell destruction, blood Hb concentration may remain nearly normal as long as the rate of destruction does not exceed the capacity for compensatory expansion of the RBC precursor population.6

ERYTHROPOIETIN Erythropoietin (EPO) has a number of effects. High concentrations of EPO, in concert with granulocyte macrophage colony-stimulating factor (GM-CSF), stimulate the erythroid progenitor to become an erythroid burst forming unit (BFU-E), an explosive erythroid productive cell. In low concentrations EPO together with GM-CSF and interleukin 3 (IL-3) convert the BFU-E to an erythroid colony-forming unit (CFU-E), a cell capable of producing colonies of red

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cell precursors. Low concentrations of EPO also convert the CFU-E into the first recognizable RBC precursor in the bone marrow. In addition, EPO accelerates RBC production and maturation, internal cell Hb production, and finally modulates the movement of marrow reticulocytes into peripheral blood reticulocytes. To summarize, EPO activates erythropoiesis, accelerates erythropoiesis, and is intrinsic to the successful delivery of RBCs to peripheral blood.2

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aggregate reticulocytes greater than 50,000/Âľl is evidence of regeneration.7 Basophilic stippling, a dark bluish stippling of some immature RBCs, is commonly found in some RBCs released into peripheral blood in response to anemia. This finding has no special significance insofar as the etiology of anemia in the cat is concerned.6

FELINE HEMOGLOBIN MORPHOLOGY OF ERYTHROPOIESIS The process of red cell production from blast to adult RBC takes from 4 days to 1 week. The first morphologically identifiable bone marrow erythroid precursor is the rubriblast. In this cell is the initiation of characteristic RBC protein production (Hb and enzymes), as well as surface antigens and metabolic machinery. One of these cells can have as many as 16 to 32 progeny erythrocytes. When this cell divides giving rise to the prorubricyte (which in turn leads to the formation of the basophilic rubricyte) loss of replicative function and loss of the nucleus itself begins. The basophilic rubricyte gives rise to the polychromatophilic rubricyte, a cell in which morphologic recognition of cytoplasmic hemoglobin production is first possible. Whether the polychromatophilic rubricyte is the last of the dividing RBC precursors is arguable, but from it arises the metarubricyte, in essence the nucleated RBC (nRBC) often observed in peripheral blood smears of anemic patients. The nucleus of this cell is almost nonfunctional, and when extruded the metarubricyte becomes the earliest bone marrow reticulocyte. Under normal circumstances bone marrow reticulocytes mature in the marrow for approximately 3 days and then move from the extravascular hematopoietic space to the intravascular space via the bone marrow venous sinus. Here the cell is simply called a reticulocyte. After approximately 24 hours the reticulocyte loses its intracellular materials (which stain with new methylene blue). The cell is now an adult RBC destined to live approximately 80 days in a normal blood volume of about 70 ml/kg (a number different than in other common domestic animals).6 Nucleated RBCs may appear in peripheral blood of adult cats without evidence of intensified erythropoiesis and may be a sign of systemic stress of disease or splenic inactivity. This finding is unique to the cat. Nucleated RBCs do acutely accompany increased reticulocyte numbers in early, active erythropoiesis. The presence of increased nRBCs without reticulocytes or in nonanemic states also suggests bone marrow disease or cardiopulmonary dysfunction. These cells are often observed in myeloproliferative disease.6

FELINE RETICULOCYTES Feline RBCs retain stainable reticulum for several weeks. Type I forms have a punctate reticulum staining and are not counted in traditional peripheral blood reticulocyte counts. Types II and III with dense aggregates of reticulum and conforming to the morphologic appearance of reticulocytes of other species are counted in peripheral blood as a gauge of erythroid response.6 A reticulocyte concentration of

Two hemoglobins, designated major and minor, in the cat differ from other mammalian hemoglobins in that they have the largest number (eight) of reactive sulfhydryl groups. The physiologic occurrence of small eccentric refractile bodies (erythrocyte refractile bodies; Heinz bodies; Schmauch bodies) indicates the unusual propensity for hemoglobin denaturation in cats. This is most probably related to the unique structure of feline hemoglobins.6 This may also be related to the fact that cats have a unique nonsinusoidal spleen, which does not readily remove atypical RBCs.8

ADULT FELINE RED BLOOD CELL ANALYTES With respect to PCV, Hb, and RBC number as well as RBC indices, cats generally attain adult values by 4 or 5 months of age. There are significant differences between kitten and adult values, as discussed in more definitive texts on the subject.6,9

PHYSICAL EXAMINATION A thorough physical examination is essential in the diagnosis of feline anemia. For example, icterus can be caused by hemolysis, cats with lymphatic diseases often have concurrent or associated anemia, and cats with petechiae and/or ecchymoses most probably have thrombocytopenia and/or thrombocytopathia or vasculitis.

ANEMIA AS A DIAGNOSTIC SIGN Anemia is the result of only a few processes and when these processes are considered, a series of diagnostic steps may be set in motion, often revealing the underlying cause. Iron- deficiency anemia in kittens may result from portosystemic shunts (microcytosis without evidence of RBC regeneration), all milk diets, or from external or internal parasitism: in adults parasitism would be lower on a differential list and blood loss through ulceration or neoplasia would be more common causes. Decreases in total protein (TP) and the RBC indices along with decreases in serum iron (SI) and increases in total iron-binding capacity (TIBC) would be anticipated. Anemia of inflammatory disease (AID; anemia of chronic disease) is mild if detectable and is associated with decreases in both SI and TIBC. Anemia associated with hemorrhage is not difficult to diagnose and is usually associated with a history of trauma.

Hemorrhagic anemia and hemolytic anemia are unique in terms of increasing reticulocyte percentage once the bone marrow reaches increased productive status 3 to 4 days after the insult. Often in intravascular hemolysis or hemolysis induced by Heinz bodies, the mean corpuscular hemoglobin concentration (MCHC) is above the reference interval. Whenever this analyte is increased, the preceding causes should be considered. Hypohormone anemia, which is anemia associated with renal disease, hypothyroidism, and hypoadrenocorticism, requires specific and incisive testing. Anemia associated with bone marrow disease is usually accompanied by cytoses or cytopenias in at least one other cell line.

EVALUATING LABORATORY TESTS A complete hemogram complete with all three RBC indices (mean cell volume [MCV], hemoglobin concentration by percentage [MCHC] and hemoglobin by weight [MCH]), HCT, Hb, RBC number, reticulocyte and nRBC numbers, TP, examination of RBC, white blood cell (WBC) and platelet morphology, and a differential in absolute numbers is the first step in solving the mystery of anemia. Regenerative anemias are those with elevated reticulocyte counts (see above) and are indicative of hemolysis or hemorrhage. Only when they are accompanied by large numbers of reticulocytes can nRBCs be associated with RBC regeneration. All other forms of anemia are considered nonregenerative or hypoproliferative. When these anemias are severe, transfusion is indicated.

dogs because the occurrence of natural isoantibodies is common. Approximately 70% of all type B cats have anti-A antibody in a high enough titer to cause decreased RBC survival and acute hemolysis. As little as 5 ml of incompatible blood is enough to cause a fatal reaction. In 35% of all type A cats anti-B is present but usually in low titer; reaction in these animals is less frequent. Although the incidence of type B cats in the United States is low, many purebred cats (excepting the Siamese) such as the Cornish and Devon Rex, British shorthair, Abyssinian, and Himalayan cats have a high frequency of B blood types. Crossmatching is strongly recommended for all cats about to receive blood or blood products. The presence of natural isoantibody always result in decreased RBC survival posttransfusion. Mean RBC survival is approximately 30 days in cats of the same blood type and less than 10 to 14 days in cats with differing blood types.10 Donor cats should be screened for red cell parasites, heartworms and feline leukemia virus (FeLV), feline infectious peritonitis (FIP), and feline immunodeficiency virus (FIV). At 2 week intervals 10 ml/kg can be collected. The use of citrate-phosphate-dextrose-adenine (CPD-A1) is the recommended anticoagulant. Heparin is contraindicated as it activates platelets and antithrombin III and can result in many unwarranted and disparate reactions including hemorrhage. When delivering feline whole blood taken in a citrate anticoagulant care must be taken not to cause hypocalcemia, which may be severe and even lethal. Citrate is a strong calcium chelator. Caution must also be used not to induce volume overload. Generally if less than 20% of blood volume is delivered to a normovolemic but anemic feline patient during an 8 hour period, volume overload does not occur. As mentioned, cats have a normal blood volume of approximately 70 ml/kg.6

BONE MARROW BIOPSY Bone marrow aspiration or core biopsy is reserved for any unexplained cytopenia or when neoplasia is staged. When bone marrow examination is used to help explain cytopenia, it is imperative that the bone marrow preparations be accompanied by a concurrent hemogram (i.e., blood drawn at the same time as the marrow sampling). Because normal diurnal and day-to-day variation is quite significant and the hematologistâ&#x20AC;&#x2122;s diagnostics are always referable to peripheral blood numbers, it is incorrect and poor science to draw information from a bone marrow aspirate without reference to a concurrent hemogram. A core biopsy is indicated when attempts at aspiration do not yield bone marrow particles or sufficient cells. Bone marrow aspirate or core biopsy are helpful in the diagnosis of myelofibrosis, myelophthisis, and myeloproliferative diseases in general. These samples may also aid in the diagnosis of pure red cell aplasia or aplastic pancytopenia, which are often drug induced.

FELINE BLOOD GROUPS AND FELINE TRANSFUSION MEDICINE Three feline blood groups have been described: A, B, and AB. The feline blood group system is different than that in

CONSIDERATIONS11 Acepromazine, Chloramphenicol, Trimethoprim Sulfa, Griseofulvin These are drugs that can cause hemolytic anemia in the cat or cytopenias due to bone marrow suppression. Pancytopenia commonly occurs in cats when griseofulvin is used in the treatment of dermatomycosis. Oxidative RBC Injury Denaturation of feline hemoglobin and Heinz body anemia results from excessive doses of Vitamin K. In dosages in excess of 5 mg/kg/day vitamin K results in severe Heinz body hemolysis. Other drugs that can cause oxidative injury are benzocaine, acetaminophen, methylene blue, and acepromazine. Onions can also cause Heinz bodies. Severe Heinz body hemolysis can result when tiny amounts of lidocaine are sprayed into the oral cavity before intubation or when urinary antiseptics containing methylene blue are used. MPS removal of these cells leads to dramatic and severe anemia.11 Propylene Glycol in Semi-Moist Cat Foods These materials cause Heinz bodies in cats. In cats receiving these foods red cell masses are generally lower than

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in other cats.

Retroviruses FeLV and FIV induce a variety of bone marrow diseases including anemia. These viruses also cause erythroid dysplasia. The peripheral blood manifestations of these viral incursions are macrocytic RBCs that are not reticulocytes and nucleated cells that are unclassifiable. These anemias are not regenerative, but often the MCV is elevated significantly above the reference interval.

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but not observed, the examiner should place the ethylene diamine tetracetate (EDTA) anticoagulated blood in the refrigerator for 8 to 10 hours and look for autoagglutination on the test tube walls or hemolysis in plasma. Doxycycline is the drug of choice in treating hemobartonellosis in cats and it has the advantage of once a day dos-

Table 1. Effects of erythropoietin Direct activation of stem cells and erythroid precursors

Immune-Mediated Hemolysis Positive direct antiglobulin test (DAT; direct Coombs’ test), albeit useful in detecting immune-mediated hemolysis, is positive when there is a detectable concentration of immunoglobulin on the red cell surface for any reason.4,5 For example, hemobartonellosis can cause a positive DAT, which will remain so until this organism is cleared from the body.10 In treating immune-mediated hemolytic anemia (IHA) in the cat, prednisone at 2 to 4 mg/lb (in contrast to the dog in which low dosage glucocorticoid is successful), is administered every 12 hours. In confirmed cases of IHA in the cat, chlorambucil, which is not expensive and has few side reactions, has also been reported to be successful as a second drug. Chlorambucil comes in 2 mg tablets; typically, cats receive 2 to 3 tablets of chlorambucil once every other week. It is an excellent immunosuppressive agent. Azathioprine is not recommended as an immunosuppressive agent in the cat.

Increased erythroid precursor hemoglobin production Decreased bone marrow erythroid maturation time Increased (earlier) release of bone marrow reticulocytes

Table 2. Classification of anemia Nonregenerative, hypoproliferative anemia Iron deficiency Anemia of inflammatory disease Early stages of hemolysis and hemorrhage Hypoendocrine diseases Bone marrow disease

RBC Morphologic Changes There are numerous morphologic changes in RBCs that are diagnostically helpful. Unfortunately, spherocytes are difficult to recognize in feline blood smears. Schistocytes, (fragmented RBCs) are recognized in disseminated intravascular coagulation (DIC). Leptocytes and acanthocytes, which are suggestive of hepatic diseases in other domestic species are rare in the cat. Basophilic stippling, although rare, may be associated with lead toxicity. Howell-Jolly bodies (remnants of nuclear materials), are observed when erythropoiesis is active and suggest bone marrow activity in the erythroid cell line. Often Howell-Jolly bodies are associated with increased reticulocyte numbers in a new methylene blue stain or with polychromasia in a Wright’s stained smear. Heinz bodies (sometimes described as “signet ring cells”) are evidence of hemoglobin denaturation and may involve certain drugs as has been described. They may also be seen in anorectic cats that are not receiving vitamin B complex in their diets. Although not common, autoagglutination is indicative of immune-mediated hemolytic processes, most probably involving immunuoglobulin M or some forms of immunoglobulin G. Hemobartonellosis The DAT is often positive in cats with hemobartonellosis. This disease is always secondary to another physiologically stressing event, and an infectious etiology must be considered. Most commonly these are viral- or bacterial-induced primary processes. If hemobartonellosis is suspected

Regenerative, hyperproliferative anemia Hemolytic disease: after 3-4 days Acute hemorrhage: after 3-4 days

Table 3. Feline hematologic reference intervals Analyte

Interval

Hemoglobin Hematocrit Red blood cells MCV MCHC MCH Reticulocytes White blood cells Neutrophils Band neutrophils Lymphocytes Monocytes Eosinophils Basophils Platelets Total protein Fibrinogen

6.9 - 9.6 nmol Hb(Fe)/L 33 - 46 L/L 7.55 - 10.87 (1012/L) 38.2 - 48.0 fL 19.7 - 22.5 nmol/L 0.81 - 1.02 fmol 0.2% - 1.6% 5.7 - 16.3% 109/L 2,500 - 12,500/µl 0 - 300/µl 1,500 - 7,000/µl 0 - 800/µl 0 - 1,500/µl Rare 140 - 500 x 109/L 6.0 - 8.0 g/dL 0.1 - 0.3 mg/dL

*Modified from deBruijne JJ, Feldman BF: Referentiewaarden van laboratoriumonderzoek bij hond en kat. Analyse 38:11, 248 - 252, 1983.

ing. Tetracycline generally suppresses the feline appetite and sometimes induced fever. Hypersalivation and vomiting are other feline tetracycline reactions. Total Protein, Total Bilirubin, Urine Bilirubin In cats hemorrhaging is associated with decreases in total plasma or serum proteins accompanying the decreases observed in red cell mass whereas hemolysis is characterized by normal to increased total proteins. Increases are often artifactual and are caused by the amount of hemolysis or red cell membrane debris in the plasma or serum. Cats with hemolysis often have increases in both total bilirubin and urine bilirubin. Cats that are hemorrhaging would not have increases in these analytes.

ic renal disease. Dosage is 100 to 150 units/kg subcutaneously every 2 to 3 days. As it is a human recombinant product, about one fourth to one third of cats receiving this hormone will produce antibodies against it in 6 to 8 weeks. Care must be taken against overzealous use of this product, which can lead to as polycythemia with severe to fatal results. As the Hct reaches the reference level, the interval dosage of erythropoietin is reduced to every fourth of fifth day. The underlying renal disease is unaffected, but the quality of life is markedly improved.12

References 1.

Zinc The ingestion of zinc containing pennies and the resultant intravascular hemolysis is seen more often in dogs than cats. Nevertheless, many of the cat carriers have zinc containing materials in the carrier locks or clamps. Stressed or angry cats that chew on these could be subject to severe intravascular hemolysis. Insulin Cats that are being aggressively treated with insulin for diabetes mellitus have reduced serum phosphate content, often to a concentration incompatible with RBC integrity. When intracellular phosphorus is reduced, the adenosine triphosphate ion and water exchanges are also reduced, causing spherocytosis and intravascular hemolysis.

2. 3. 4.

6. 7. 8. 9.

Erythropoietin as a Therapeutic Agent Erythropoietin (Epogen[TM] - Amgen) is used almost exclusively in treating anemia associated with feline chron-

10.

Rifkind RA, Bank A, Marks PA, Nossel HL: Fundamentals of Hematology, Chicago, Year Book Medical Publishers, 1976, pp 7 - 24. Schrier S: Hemopoiesis and red blood cell function. Scientific Am Med 5(1): 1-8, 1988. Hillman RS, Finch CA: Red Cell Manual, ed 5, Philadelphia, FA Davis Company, 1985, pp 33 - 55. Jones DRE, Gruffyd-Jones TJ, Stokes CR, et al: Investigation into factors influencing the performance of the canine antiglobulin test. Res Vet Sci 48:53 - 58, 1990. Jones DRE, Stokes CR, Gruffyd-Jones TJ, et al: An enzyme-linked antiglobulin test for the detection of erythrocyte-bound antibodies in canine autoimmune haemolytic anemia. Vet Immunol Immunopathol, 16:11-21, 1987. Jain NC: Schalmâ&#x20AC;&#x2122;s Veterinary Hematology, ed 4 Philadelphia, Lea & Febiger, 1986, pp 126 - 139. Kociba GJ: Feline anemia, in Kirk RW (ed): Current Veterinary Therapy X, Philadelphia, WB Saunders Co, 1989, pp 425 - 429. Weiss L, Blue J: Anatomy of the spleen, in Lichtman MA (ed): Hematology and Oncology. New York, Grune & Stratton, 1980, pp 49 - 53. Mackey L: Haematology of the cat, in Archer RK, Jeffcott LB (eds): Comparative Clinical Haematology. Oxford, Blackwell Scientific Publications, 1977, pp 441 - 482. Giger U: Feline blood groups and incompatibility reactions. Proceedings of the 8th ACVIM Forum, Washington, DC, 1990, pp 319 - 321

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Diagnostic approach to canine and feline autoimmune skin diseases Dominique Heripret Dr Vet, CES DV, Dip ECVD Private Practitioner, Arcueil, Paris - France

Auto-immune skin diseases are rare dermatoses (less than 1% of canine dermatoses). Even if the clinical presentation of these dermatoses is often suggestive, the suspicion must be established only after a good differential diagnosis, elimination of frequent other dermatoses by routine diagnostic procedures (mainly pyoderma, dermatophytosis, demodicosis), and the final diagnosis must be established based on compatible history, clinical aspect and histolopathological findings. Direct immunofluorescence or immuno-histochemical testing may also be helpful but these procedures have relatively poor diagnostic sensitivity and specificity

A - Classification (Suter M - Olivry T) 1) Autoimmune diseases with cutaneous target • Autoimmune disease with keratinocyte surface molecules as targets: - Pemphigus foliaceus (PF): far most frequent autoimmune skin disease in the dog. It is a crusting and scaling dermatitis starting bilaterally symmetrical at the face and/or paws, sometimes spreading as a general disease. Antigen: Desmoglein 1 - Pemphigus erythematosus: it is a variation of PF. A linear deposition of immunoglobulins at the basement membrane (in addition to the keratinocyte membrane fluorescence) as seen on immunopathological staining is the difference with PF. - Pemphigus vulgaris (PV): it is the most severe form but is very rare. Oral and mucocutaneous junctions lesions (with ulcerations) are seen. Antigen: Desmoglein 3 (in man). - Panepidermal Pustular Pemphigus: it has been recently described based on the location of the lesions within the stratified squamous epithelium. - Paraneoplastic Pemphigus: frequently described in human medecine Pathogenesis of Pemphigus (Suter MM): binding of autoantibody to desmosomal cadherin adhesion molecules (Desmoglein 1 or 3) - Activation of keratinocytes - Disruption of intercellular adhesion. • Autoimmune diseases with basement membrane targets: - Bullous Pemphigoid (BP): it resembles PV with blisters

and ulceration in the oral cavity and at the mucocutaneous junctions. Histopathology: subepidermal cleft formation within the lamina lucida. Antigen: BPAG II (collagen XVII) Pathogenesis: autoantibody binding to collagen XVII Cytokine production by keratinocytes - Attraction of eosinophils and neutrophils - Cytokine and protease secretion - Lesion formation. - Acquired Epidermolysis bullosa: a case of suspected collagen type VII subepidermal bullous dermatosis as been described (Olivry) - Linear IgA dermatosis of Dachshund • Miscellaneous: - Alopecia areata: in man, hair keratines are antibodies target, but in the dog, it seems that trichohyalin may be the target. - Vitiligo and uveo-dermatologic syndrome (VKH-like syndrome) are autoimmune diseases of pigmentation. Antimelanocytes antibodies have been described in vitiligo.

2) Autoimmune diseases with circulating auto-antibodies non specific of cutaneous antigens - Systemic Lupus Erythematosus: it is an autoimmune disease with cutaneous immuncomplex deposition. It is a systemic disease. - Chronic Discoid Lupus Erythematosus: in classical cases, depigmentation and ulceration of the nose and planum nasale. There is no circulating auto-antibodies. - Vasculitis: they may be related to various antigens (infectious, neoplastic, drug induced, vaccination, chemical). Pathogenesis of vasculitis involves type III hypersensitivity. - Cold Agglutinin disease

B - Biopsy site selection (Gross TL) • Pustular autoimmune dermatitis: because of the fragile and transient nature of primary lesions (pustules, vesicopustules), early lesions should be obtained. If no pustules are available, crusted lesions or sites directly adjacent to early pustules should be sampled. Crusted lesions should be procured carefully and the veterinary pathology service should be instruct-

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ed to include any dissociated crusts in the slide preparation. If a low number of pustules or vesicles or bullae are present, they should be removed carefully, preferably by excisional biopsy. â&#x20AC;˘ Non bullous autoimmune skin diseases: - Discoid Lupus: recent sites of depigmentation, with partial lost of pigment, are optimal sites for skin biopsy. Traumatized lesions or lesions with severe crusting, ulceration or scarring should be avoided. Lips, dorsal muzzle and planum nasale are the best sites for skin biopsy. - Systemic Lupus: erythematous areas adjacent to ulcers are the best sites since an intact epidermis is necessary to yield diagnostic results. - VKH-like syndrome: areas of depigmentation, erythema and scaling are beneficial sites. Lips and dorsal muzzle are preferred sites. Secondary infected or self-traumatized lesions should be avoided. â&#x20AC;˘ General considerations: - multiple biopsies should be taken - samples should be selected from the most representative lesions of the suspected disease - excision biopsy should be prefered in bullous diseases - if possible, biopsy specimens should be taken when the animal is not under the effects of glucocorticoid or immunosuppressive therapy - dermatopathologic examination should be performed by a veterinary pathologist.

C - Direct immunofluorescence (DIF) and Immunohistochemical testing (IHT) DIF and IHT are methods used to detect the presence of abnormal antibody or immune complex deposition on tissue

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specimens. In human medecine, these procedures are considered highly valuable for many of the immune-mediated dermatoses. however, their value in veterinary medecine is considerably less. There are many false negative (glucocorticoid treatment, low quality of biopsy site selection, small biopsy, technical problems) and many false positive (intercellular and basement membrane zone deposition of immunoglobulins or complement can be detected in a wide variety of chronical inflammatory dermatoses, and are physiologicaly found in footpads and planum nasale). For exemple, DIF is positive in 100% of cases of sarcoptic mange, 73% of superficial chronical pyoderma, 67% of dermatophytosis, 50% of Demodicosis. Results of immunopathologic testing can never be appropriately interpreted in the absence of histopathologic findings. For DIF, biopsy site selection is the same as for histopathological examination but biopsy specimens should be snap-frozen or placed in Michelâ&#x20AC;&#x2122;s fixative. IHT is performed on formalin-fixed, routinely processed tissues (immunoperoxidase methods) or on frozen sections. Generally, biopsy specimens should be selected from areas not secondarily infected and representing the earliest lesion typical for that disease. Planum nasale (dogs and cats) or footpads (dogs) should not be sampled or should be interpreted with great caution. Intercellular intraepidermic autoantibody deposits: Pemphigus (95% IgG in Pemphigus foliaceus). Linear dermo-epidermal autoantibody deposit: Bullous Pemphigoid, Discoid and Systemic Lupus, Linear IgA dermatosis of Dachshund Because of the high incidence of false positive, DIF or IHT are of low interest, except in the differential diagnosis between Bullous Pemphigoid and Epidermolysis bullosa, and in the differential diagnosis of interface dermatitis.

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Discoid and systemic lupus erythematosus Dominique Heripret Dr Vet, CES DV, Dip ECVD Private Practitioner, Arcueil, Paris - France

Systemic and Discoid Lupus Erythematosus are dermatosis associated with circulating auto-antibodies, non specific of cutaneous antigens.

A - SYSTEMIC LUPUS ERYTHEMATOSUS SLE is a circulating immune complex disease characterized by multisystemic involvment and the presence of a wide variety of autoantibodies.

1) Etiology Although the etiology of Lupus is unknown, most reports emphasize the interaction of various factors: - a genetic predisposition - hormonal factors - viral factors - inducing drugs - UV light • Genetic predisposition: it has been proven in man (familial studies, relationship with MHC, ...), in mice (NZB et NZW, SWAN, ...) and in dogs (Manathos family, German shepherd, Lyon Vet School, France). When crossing infected dogs, 70% of second generation dogs are ill, 15% are ANA positive but healthy and 15% are ANA negative and healthy. This crossings have been able to demonstrate a positive relationship between Ag DLA-A7 (Dog Leukocyte Antigen = DLA) and SLE, and a negative relationship between Ag DLA-A1, DLA-B5 and SLE. Actual research in human and in dogs are looking for the gene involved in SLE transmission. A close relationship between SLE and TcR gene (Lymphocyte T - antigen receptor) seems to exist in human. • Hormonal factors: in human, there is a strong predilection of young women before 40 years old (90%); in dogs results show no sexual predisposition or male predisposition (50-68%). Androgens may increase suppressive T lymphocytes activity (and be protective) and oestrogens may induce abnormalities of antigen presentation. Hormonal treatments (androgens or anti-oestrogens) in human have given various (desappointing) results • Viral factors: C-type viruses have been involved. The SP 104 virus (retrovirus) has been found to contain an antigen that cross-reacts with an antigen present on the surfaces of

circulating lymphocytes of humans and dogs with SLE. But the mere presence of such a virus is not sufficient to provoke the expression of clinical disease. A study has shown a higher incidence of SLE in owners of dogs with SLE; this result has not been confirmed by other studies. • Inducing drugs: drug-induced SLE is a well recognized syndrome in human (hydralazine, procainamide, methyldopa, penicillins, tetracycline, griseofulvin, sulfonamides, ...). Experimental dogs treated with hydralazine developed a similar syndrome to SLE. In a dog, SLE appears after a routine vaccination, and in hyperthyroid cats, SLE has been described after giving propylthiouracil. For the moment, in animals, it is better to name it SLE like drug reaction than drug induced SLE. • UV light: in dogs, cutaneous lesions are mostly localized on the face, suggesting an action of UV light, which may change cutaneous nuclear antigens. Actually, SLE occurs in the presence of a disturbed immune system in a genetically susceptible host, and with various favourable environmental factors (viral, UV).

2) Pathogenesis In human and animals, most lesions are due to type III hypersensitivity reactions. Antibodies (IgG) are formed secondarily to increased circulating antigens (mainly nuclear antigens). Circulating soluble Ag-Ac immune complexes are set down along epithelial and vascular basement membrane zones inducing complement activation which induces neutrophiles chemotactism. Lysosomial enzymes and free radicals create local lesions. In SLE, deposition of immune complexes in joints, muscles, renal glomerules, CNS, ... is responsible of problem in the affected organ.

3) Immunological abnormalities Various and numerous auto-antibodies are produced in SLE. • antinuclear antibodies (ANA). - Total ANA: they are present in 97-100% of SLE , but their presence is not specific for SLE. For exemple, dogs with Leishmaniasis would present frequent positive ANA.

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There is a wide variety of ANA depending on the target (nuclear antigen): anti native DNA, anti-histones, antiENA, ... - Anti native DNA antibodies: Antibodies against DNA (double chain) are quite characteristic of the human disease (80%), but in dogs their presence is very rare (< 5%). This is the main difference between canine and human SLE. - Anti-histones antibodies: in human, anti-histones antibodies are frequently reported(30-70%) but mainly in drug induced SLE; anti-H1, anti-H2B, anti-H3 are frequent. In dogs, they are frequently reported too (55-65%) but have been found in non lupoid dogs; moreover, antiH3, anti-H4 et anti-H2A are frequent. - anti-ENA antibody (ENA = Extractable Nuclear Antigens): these antigens come mainly from nucleoplasmic constituants and for a small part of them from chromatin molecules. Positive anti-ENA is an other difference between dogs and human; in dogs anti-type I (20%) and anti-type II (9%) are found but not in human, anti-Sm is found occasionaly in dogs (16%) but frequently in human (70%). Moreover, other known anti-ENA in human (anti-SSA and anti-SSB) are not found in dogs. - other nuclear antibodies: non histone proteins like HGM (High Mobility Group) type I and II have been seen in canine SLE. Important facts in canine SLE: - high frequency and elevated titer of ANA - rarely or no anti-nDNA - anti-type I and anti-Sm highly diagnostic • other auto-antibodies Auto-immune response in SLE is not exclusively directed against nuclear antigens. Other antibodies have been found: - seric auto-antibodies * rhumatoid factors: low title in canine SLE * anti erythrocyte antibodies, detected by Coomb’s test, but hemolytic anemia is only a criteria of SLE (2030%) and each AIHA with positive Coombs test is not linked to SLE. - fixed antibodies * on skin biopsies, detected by direct immunfluorescence (IFD) * on renal biopsies (in case of glomerulonephritis), detected by IFD • other abnormalities - lymphocytic abnormalities: in dogs, some recent works show * lymphopenia * decrease of peripherical population of CD8+ T cells and increase in CD4+ * decrease suppressive activity of T cells * increase in CD5+ when there is no activity of the disease - NK cells, Ag presentating cells, cytokines: no study in canine SLE

4th European FECAVA SCIVAC Congress

* localized CLE * generalized CLE * oral LE * lupus panniculitis - LE-non specific skin disease * vasculitis * vesicobullous lesions • Systemic LE (SLE) - SLE without CLE - SLE with CLE

5) Epidemiology and history Male dogs seem overrepresented (different from human condition) in some studies (70%) but equallly in others (51%). Medium class of age is 5 years old (6 months to 14 years old) but we have to consider the moment when symptoms began or when diagnostic was made because SLE is a slow evoluting disease (episodic evolution), worsening with time. SLE begins in young adults and may be very severe at 5 years. Breed predilection: German shepherd, Belgium shepherd, Shetland sheepdogs, collies, beagles, ...

6) Clinical presentation SLE is evoluting subacutely or more often chronically with episodic attacks and remission periods. Symptoms are numerous but non erosive polyarthritis (76-90%), proteinuria (50-65%) and cutaneous lesions (54-65%) are the principles figures. All these symptoms are not present at the same time but more often successively. • lameness: non erosive polyarthritis (no radiologic signs), beginning intervertebraly with difficulties to stand up and jump, amyotrophy of lombo-dorsal muscles. Then carpus and tarsus are involved with “turning” lameness. At the end of evolution, temporo-mandibular joint is sytematicaly involved. • skin lesions: they are often erythematosus and seborrheic in nature and commonly involve the face, ears and limbs. Erythema is also frequent in less hairy areas. Mucocutaneous ulceration or erosion and nasal depigmentation are also seen. The “butterfly” pattern often referred to in human medecine, is common to many canine dermatosis. Chronic ulcerative stomatitis may be the only “cutaneous” manifestation. • others: glomerulonephritis with proteinuria (50-65%), hemolytic anemia (10-20%), thrombocytopenia (< 5%) and purpura, spleen and lymp nodes enlargment, central neurologic symptoms, pleural and pericardic inflammation (10%).

7) Diagnosis 4) New classification (T Olivry) • LE related skin disease: - LE specific skin disease (Cutaneous LE = CLE): acute or chronic

• Diagnosis is based upon ARA (American Academy of Rhumatology) criterions: 1) facial erythema (butterfly appearance) 2) disoid lupus

3) 4) 5) 6) 7) 8) 9)

UV sensitivity oral ulcerations polyarthritis pleural or pericardic inflammation renal troubles (proteinuria) neurologic disturbances haematological disturbances: hemolytic anemia, leucopenia, lymphopenia, thrombocytopenia 10) immunological abnormalities: LE cells, anti-nDNA Ab, anti-Sm Ab 11) ANA positive Suspect SLE: 2 positive criterions. Possible SLE: 3 positive criterions or polyarthritis + ANA positive. SLE: 4 positive criterions. This list of criterions is a human one and not perfectly adapted to canine SLE: - criterion 11 is an obligation because there is no SLE without positive ANA (97-100%); - anti-nDNA create many false ANA positive in human, but these Antibodies do not exist in dogs; - transposition from human to dogs of criterion 1 (butterfly appearence), 3 and 8 , is difficult; - episodic hyperthermia is very frequent in dogs and is a missing criterion; - anti-type I is very specific of canine SLE; - Leishmaniasis should be excluded before just thinking of SLE (be careful, there are many cases of canine Leishmaniasis with positive ANA). It seems better to interpret ARA criterions in this way: - positive ANA is mandatory (with exclusion of Leishmaniasis) with high titer + 3 criterions: diagnostic + 2 criterions: possible SLE; perform analysis of ANA (anti-type I or anti-Sm highly suggestive of canine SLE) • An other classification of criterions has been proposed by Halliwell (1989) with major and minor symptoms . Definitive diagnosis is made with: positive ANA + 3 majors symptoms or positive ANA + 2 major symptoms + 2 minor symptoms: - major symptoms * non infectious polyarthritis * compatible skin lesions with characteristic histopathology * hemolytic anemia * severe thrombocytopenia * glomerulonephritis and proteinuria * neutropenia * polymyositis - minor symptoms * hyperthermia with unknown origin * CNS symptoms * pleural inflammation • Cutaneous histopathology: avoid ulcers and erosions for biopsy site selection; intact erythematous epidermis adjacent to ulcers may yield diagnostic results. Histopathology reveals: * patchy, mild to moderate vacuolar degeneration of the basal cell layer * colloid (Civatte) body formation is a consistent finding but may be rare

* lichenoid mixed inflammatory dermal infiltrate * pigmentary incontinence • Indirect immunofluorescence of skin biopsies (Michel’s medium) reveals: deposition of granular and irregular deposits of immunoglobulin (usually IgG) and complement at the dermal-epidermal junction. One must be aware that similar but normal IgM deposits are found in normal canine and feline nose and footpath. • ANA: high title is required (> 1/256°), but ANA are not specific of SLE because they are found in other diseases (Leishmaniasis).

8) Treatment: (see therapeutic protocols) Prednisolone 2 mg/kg/day tapered slowly after clinical remission + levamisole 2-5 mg/kg each other day (max 150 mg/day) 4 months. Heamatological control after 10 days (neutropenia). Results: 57% in remission for months or year(s) (no longer than 3 years) without treatment. Other treatments (mainly if severe side effects of glucocorticoids): azathioprine 2 mg/kg/day, cyclophosphamide 50 mg/m2 four days a week, vincristine if severe thrombocytopenia (0,7 mg/m2 once a week). Prognosis is always guarded, especially when renal lesions are severe.

B - DISCOID LUPUS ERYTHEMATOSUS DLE is a cutaneous form of SLE without involvment of internal organ. It has been described in human, dogs, cats, horses, seals. • epidemiology: there is no real age predilection but must animals presenting this dermatoses are young adults. Breed predilection: Collie, German shepherd, Siberian Husky, Shetland Collie. • clinical signs are mostly localized on the face, the nose, and periocular areas. Oral and pinnae lesions are very rare. Podal lesions are seen. Lesions: hypopigmentation, erythema, scales, erosion, ulceration, crusts. • diagnosis - histopathology: best sites for skin biopsy are areas of early depigmentation with partial loss of pigment; traumatized lesions or lesions with severe crusting or ulceration should be avoided. Histopathology reveals:same lesions as SLE with less severe basal cell vacuolisation. - immunofluorescence: see SLE - ANA are negative and there is no haematological or biochemical abnormalities • treatment - mild cases: sun screen, vitamin E, avoid sun exposure, topical glucocorticoid - more severe cases: glucocorticoids until remission (1-2 mg/kg/day), then nicotinamide-tetracycline - very severe cases or refractory cases (large ulcerations, spontaneous bleeding, pain): glucocorticoids and immunosuppressive drugs

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Clinical differential diagnosis of autoimmune skin diseases Dominique Heripret Dr Vet, CES DV, Dip ECVD Private Practitioner, Arcueil, Paris - France

Clinical aspects and localizations of auto-immune skin diseases (AISD) are common with a great number of other dermatosis. Because of the low incidence of this diseases, we must always rule out other more common dermatosis before thinking to AISD. Clinical differential diagnosis depends on the lesions (crust, ulcerations, erosions, depigmentation, pustules) and on their localizations (facial, podal, generalized).

FACIAL DERMATOSIS Virtually any skin disease may affect the face, but AISD are often symmetrical, involving periocular areas, lips, nose and pinnae. Pruritus is generally mild but secondary pyoderma or Malassezia dermatitis may be pruritic. * If pruritus is present: - atopic dermatitis: erythema, lesions of self trauma, often secondary pyoderma and crusts - food allergy: erythema, secondary pyoderma, erosions or ulcerations in cats - contact allergy or irritation: erythema, macules, papules, rarely erosions (plastic dish contact allergy) - eosinophilic furonculosis of the face: papules, pustules - eosinophilic granuloma complex (cats) - sarcoptic mange (dogs) - pyoderma - mucocutaneous pyoderma - demodicosis with secondary pyoderma - dermatophytosis: some dermatophytes may creat an autoimmune like dermatosis (M persicolor) - Malassezia dermatitis - Mucocutaneous Candidiasis - Juvenile cellulitis of the adult dog - Zinc responsive dermatitis - Drug reaction * If pruritus is absent or mild: - Leishmaniasis - Nasal hyperkeratosis - Superficial necrolytic dermatitis - Neoplasia (cutaneous lymphoma, mycosis fungoides) - Vitiligo

- Demodicosis - Dermatophytosis - Dermatomyositis - VKH-like syndrome * Facial dermatosis which may affect the planum nasale - Vitiligo - VKH-like dermatosis - Nasal hyperkeratosis - Dermatophytosis - Drug eruption - Leishmaniasis - Neoplasia

PODODERMATITIS - Pyoderma - Demodicosis - Dermatophytosis - Malassezia dermatitis, Candida dermatitis - Peladora and hookworm infestations - Leishmaniasis - Hypersensitivities (atopic dermatitis, food allergy, contact allergy) - Superficial necrolytic dermatitis - Irritant contact dermatitis - Trauma - Zinc responsive dermatitis - Digital hyperkeratosis - Sterile pyogranuloma - Neoplasia (squamous cell carcinoma, metastasis of pulmonary adenocarcinoma in cats) - Plasma cell pododermatitis (cats)

LESIONS OF THE NAILS AND NAILBED - Dermatophytosis - Candidiasis - Leishmaniasis - Superficial necrolytic dermatitis - Lupoid onychodystrophy - Drug eruption

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PUSTULES AND CRUSTING PAPULES - Primary or secondary pyoderma - Sarcoptic mange and other ectoparasitic infections - Hypersensitivity

4th European FECAVA SCIVAC Congress

- Drug eruption - Contact irritant dermatitis - Sub corneal pustular dermatosis - Sterile eosinophilic pustular dermatitis - AISD

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Therapeutic protocols of autoimmune skin diseases Dominique Heripret Dr Vet, CES DV, Dip ECVD Private Practitioner, Arcueil, Paris - France

Management of autoimmune skin diseases requires changing, varying or adjusting the immune response by pharmacological therapy. Suppressing the immune response is often easy to do, however, controlling the degree of immunosuppression can be difficult. Prior to use an immunosuppressive drug, there are important pretreatment considerations: - ensure that the diagnosis is correct - ensure that there is no contraindication to immunosuppressive treatment - control secondary pyoderma, Malassezia dermatitis - precribe the less toxic drug as possible - avoid predisposing factors (UV, some drugs, ...) Selection of an immunosuppressive treatment and then control of the disease on a long term basis is individual and the main rule is: don’t do worse with the treatment that the disease would do alone. The goals of immunosuppressive treatment are: - decrease production of autoantibody - decrease or suppress activation of cytotoxic lymphocytes - suppress the migration or activation of inflammatory cells

tolone) are indicated when lesions are small or well circumscribed (Discoid lupus erythematosus). Owners have to wear glothes. Unsing topicals q12h the first week, q24h the second week and q48h the third week is recommended to avoid systemic side effects or localized reactions (atrophy). • dosages: induction with prednisolone/prednisone 2-4 mg/kg/day for dogs, 4-6 mg/kg/day for cats; if there is no change in 10 days, increase the dosage by 30%. Use maintenance therapy when the lesions regress: decrease frequency of administration to every other day (same dosage) and the step down doses 20-30% every two to four weeks (depending on the speed of regression speed of lesions). If regression of lesions is complete and quick, it is possible to try to stop treatment after a few months (4-6 months); otherwise, look for the lower efficious dosage to control lesions with minimum side effects (0,5-1 mg/kg AD). • side effects: iatrogenic Cushing’s disease, polyuria polydipsia, steroid hepatopathy, feline skin fragility syndrome, gastric ulceration, secondary infections (ITU, pyoderma), diabetes mellitus.

A - DRUGS

2) Alkylating drugs: cyclophosphamide and chlorambucil

1) Glucocorticoids: Glucocorticoids (GC) represent the first choice treatment of most autoimmune skin diseases. • mechanism of action: paralyze Fc receptors on macrophages, suppress immunoglobulin production (high doses), suppress leukocyte accumulation at inflammatory site, decrease lymphoblastogenesis, decrease abnormal auto-antibodies production, decrease neutrophils function. • compounds: - prednisolone and prednisone, methyl-prednisolone (1,6 mg/kg/day for dogs): may be used on alternate day basis - methyl-prednisolone succinate: used for “pulse therapy” (10-30 mg/kg IV 3 consecutive days) - dexamethasone (0,25-0,75 mg/kg/day), triamcinolone (0,2-0,7 mg/kg/day): may be more effective in cats but cannot be used on an alternate day basis - injectable methyl-prednisolone acetate: is only indicated in cats unwilling to accept oral medications - topical therapy: the potency of topical GC can be geared to the severity of lesions. High power GC (clobetasol, flucor-

• mechanism of action: interaction with DNA of cells under divison: they replace an hydrogene by an alkyl group which create a wrong lecture or DNA breaking. They affect induction and effector phases of immune response, suppress antibody formation and production, affect neutrophil and macrophage function. They act slower than GC (10 days). • drugs: - cyclophosphamide 50 mg/m2/day, po, 4 consecutive days each week; during maintenance therapy with GC, every other day cyclophosphamide may be used. Treatment of more than 2 months must be prescribed with great caution (sterile hemorrhagic cystitis). - chlorambucil (0,1-0,2 mg/kg/day po for cats, 2-6 mg/m2/day initially then q 48h for dogs). Chlorambucil’s action is slower (4 weeks) than cyclophosphamide’s one (10 days). • indications: Cyclophosphamide is indicated mostly in dogs, in severe or non-responsive AID. Chlorambucil is excellent for cats requiring cytotoxic drugs in combination with glucocorticoid.

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• side effects: bone marrow suppression with neutropenia, sterile hemorrhagic cystitis (cyclophosphamide but not chlorambucil), gastroenteritis, anorexia, alopecia.

3) Thiopurines: azathioprine and 6-mercaptopurine Azathioprine is metabolized in the liver to 6-mercaptopurine. • mechanism of action: these drugs are antimetabolites which inhibit enzymes contribuating to the synthesis of puric basis and so interfering with DNA and RNA synthesis. They are active on rapidly developping cells, affecting mainly the effector phase of immune response and are more effective in modifying T lymphocyte responses. • dosage: 50 mg/m2 or 2 mg/kg/day in association with GC during the induction phase (4 weeks minimum) and then on an alternate day basis with GC. After a few months, some dogs would only require azathioprine. • side effects: azathioprine is CONTRAINDICATED IN CATS. There is a very strong bone morrow suppression, leading to death in a few weeks. In dogs, azathioprine is very well tolerated. Platelet count must be checked every 2 or 3 months.

4) Gold salts: chrysotherapy • mechanism of action: inhibition of chemotaxis, suppression of autoantibody formation, inhibition of complement activation, inhibition of phagocytosis. • Drugs: - aurothioglucose: 1 mg/kg IM q7days for induction then q30days as maintenance therapy. Test doses of 0,25 and then 0,5 mg/kg are recommended on weeks 1 and 2 respectively. - auranofin: 0,05-0,2 mg/kg q12h for induction • Side effects: cutaneous drug eruption, thrombocytopenia

5) Cyclosporin This is a very potent immune suppressor. • mechanism of action: inhibition of IL2 and gamma-interferon production, inhibition of cytotoxic T cells, decreased production of sensitized cytotoxic T cells. • dosage: 5-10 mg/kg/day po • side effects: gastroenteritis, gingival hyperplasia, surinfections, ... This drug is very expensive and has been reported to be rather unsuccessful for autoimmune skin diseases treatment (Rosenkrantz 1989).

6) Others • Tetracycline/niacinamide: this treatment seems to be interesting in Discoid Lupus Erythematosus (25-64% positive results).

4th European FECAVA SCIVAC Congress

Dosages for dogs less than 10 kg: 250 mg tetracycline and 250 mg niacinamide po, tid for induction. For dogs greater than 10 kg: 500 mg tetracycline and 500 mg niacinamide po, tid for induction. For maintenance therapy, doses are decresed incrementally. Side effects are minimal (occasional vomiting). • Methotrexate: it is a competitive enzyme inhibitor of folic acid reductase. Used in SLE in human medecine (0,5-0,8 mg/kg IV q7-14 days or 2,5 mg/m2 po q 48h). Side effects include leukopenia, vomiting, renal tubular necrosis with high doses. • Heparin: it has been used in one case of Pemphigus vulgaire (Olivry, Héripret) with GC at a dose of 100 UI/kg/day SC. Heparin seems to inhibit proteases involved in acantholysis. • Vitamin E: mechanism of action is unknown but its efficacy may be related to anti-oxydant properties (stabilization of lysozomial membrans against effects of free radicals and superoxides ions). Used in DLE and PE with GC (200400 mg/kg/j or 400-800 UI bid po). Vitamin E is a relatively benign drug that may reduce the need for other therapy. Some authors have found vitamin E to be rarely effective by itself. • Levamisole: it seems to have immunostimulating properties (not in normal dogs but in immunodepressed dogs) by increasing production of T Helper lymphocytes. Used in SLE in conjonction with GC: 2-3 mg/kg every other day. • Sulphones (dapsone): mechanism of action: inhibition of lysosomial enzymes and prostaglandines synthesis. It has been used in Pemphigus cases (1 mg/kg bid or tid) with some good results (less than 50%) and in immune complexing vasculitis. Side effects include: anemia, neutropenia, thrombocytopenia, hepatotoxicity, gastrointestinale disorders. • Antimalarial drugs: quinacrine, chloroquine, hydroxychloroquine have been use in the treatment of DLE in humans but they have not been evaluated in dogs. • Sun avoidance: sun screen or dog kept indoor between 10 am and 5 pm.

B - TREATMENT OF AUTO-IMMUNE DERMATOSIS 1) Superficial Pemphigus (PF and PE) Treatment should be individualized depending on severity and extension of lesions. Secondary pyoderma should be treated (empirical selection of agents effective against coagulase positive Staphylococcus). Crusts have to be removed, lesions have to be cleaned (often under general anesthesia). Systemic glucocorticoids is the treatment of choice (prednisone 2 mg/kg/day in dogs, 4-5 mg/kg/day in cats). If the response to GC is good, the dose is tappered on an alternate day basis as previously described. If the response is poor (recheck after 10-15 days of treatment), a cytotoxic drug may be added for at least one month (delay of activity of these drugs): azathioprine (dogs only), chlorambucil (cats). When lesions regress, GC are slowly

stopped and azathioprine or chlorambucil given 3 then 2 then 1 time a week. If the response is still weak or if undesirable side effects develop (polyuria polydipsia), alternate GC (dexamethasone, triamcinolone) may be tried. Some individuals may be cured after more than 4 months of treatment, others should be treated all their life long. In PE, sun avoidance is indicated; nicotinamide-tetracycline may be used too. If drugs were given previously to diagnosis (antibiotics, antifungal therapy, ...), they have to be stopped in case of drug induced Pemphigus like reaction. NB - The benefit of association between GC and cytotoxic drugs is not realy proven in auto-immune skin diseases.

quires long term therapy. Ocular examination is recommended every 4 months even though the cutaneous component is controlled.

7) Disoid lupus erythematosus This is a cutaneous disease with a rather good prognosis. GC must be used carefuly. In mild cases, when lesions are localized and superficial, topical therapy (high power GC at the beginning, then low power GC) + sun avoidance or sunscreen are prescribed. When ulcérations or spontaneous bleedings are present, GC are prescribed until remission, then niacinamide + tetracycline are indicated. Vitamin E may be added. Spontaneous total remission have been described.

2) Deep Pemphigus (PV) Treatment must be very potent because PV is a life threatening condition. GC have to be associated to cytotoxic drug at the beginning of treatment (cyclophosphamide). Antibiotic treatment is important because lesions are deep and sepsis is always possible. Pronostic is guarded and total remission very rare. If GC and cyclophosphamide fail, heparin may be tried.

8) Systemic lupus erythematosus Treatment should be individualized but initial treatment of choice is large doses of systemic GC. Some cases respond to the only GC therapy but most dogs need a combined therapy with levamisole and cytotoxic drugs. Prognosis is poor: Over 40% of the dogs are dead within 1 year after the diagnosis is made.

3) Bullous Pemphigoide (BP) 9) Vasculitis In human medecine, relationship between internal diseases (neoplasia) and PB has been proven in a majority of cases. Complete work up is indicated (haematological, biochemical, radiographs, ...). Previous drugs should be stopped (PB like drug reactions). Otherwise the treatment is the same as in PV.

Prognosis and treatment depend on the underlying problem, affected organs and disease severity. All previous treatments should be stopped at the time of diagnosis.

Conclusion 4) Alopecia aerata No treatment; lesions may regress in a few months.

Therapy of auto-immune skin diseases have to follow two rules: - treatment should not been worse than the disease - treatment should be individualized, depending on the precise diagnosis of the disease, the animal and the owner

5) Vitiligo No treatment; lesions are only cosmetic ones.

6) VKH-like syndrome (uveo-dermatologic syndrome) Treatment should be aggressive because of the possibility of blindess; moreover, cutaneous lesions may be reversible if therapy is started early in the disease progress: GC + cyclophosphamide, topical ocular treatment (ocular topical dexamethasone 0,1% or prednisolone 1% qid + mydriatic/cycloplegic like 1% atropine quid at the beginning). Prognosis is guarded. Control of the disease usually re-

Readings HALLIWELL (REW), GORMAN (NT) - Anti-inflammatory drugs, immunosuppressive agents, and immunomodulators. In Veterinary Clinical Immunology, Halliwell and Gorman, WB Saunders Co, Philadelphia, 1989, 493-507. KUMMEL (BA) - Medical treatment of canine Pemphigus-Pemphigoid. In Kirk’s Current Vet Therapy XII, Bonagura and Kirk, WB Saunders Co, Philadelphia, 1995, 636-638. SCOTT (DW), MILLER (WH), GRIFFIN (CE) - Immunologic skin diseases. In Muller & Kirk’s Small Animal Dermatology V, WB Saunders Co, Philadelphia, 1995, 484-626. ROSENKRANTZ (WS) - Management of immune mdeiated disorders. In Manual of Small Animal Dermatology, Harvey Locke P Ed, BSAVA, 1993, 270-275.

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SCIVAC EXOTIC ANIMALS STUDY GROUP

Survey of the resident flora of the upper respiratory tract in psittacine birds and its antimicrobial sensitivity S.O.T.S. Jesus DVM, MSc Dept. of Pathology and Infectious Diseases, Royal Veterinary College, University of London

To try to clarify the hypothesis that the resident flora of the upper respiratory tract of psittacine birds can behave as opportunstic pathogens, this project was set out to study, by means of a survey, its resident flora and compare it with that of birds with upper respiratory infections. Swabs were taken from the choanal slit of nineteen healthy psittacines and four birds with upper respiratory disease - three with sinusitis and one with an unspecified upper respiratory pathology. The isolation and identification of bacteria and fungi was accomplished by standard microbiological methods and the use of commercial identification systems. A total of 44 isolates were recovered from the choanae of the 23 psittacines sampled. Twenty six precent of the isolates recovered from the choanal slits of healthy birds were grampositive bacteria, 62% gram-negative and 12% fungi. From sick birds, 60% of the isolates were bacterial and 40% fungal. Fifty eight percent of the healthy birds yielded more than one isolate, whereas in sick birds 75% had more than one isolate.

Among other organisms, Streptococcus spp., Staphylococcus spp., Alcaligenes sp., Klebsiella pneumoniae pneumoniae, K. oxytoca, Pasteurella spp., Pseudomonas alcaligenes, P. stutzeri and Xanthomonas maltophila, all considered to be potential pathogens to the respiratory tract, were isolated from the choanal slits of healthy birds, suggesting that these animals can harbour in their upper respiratory tract microorganisms which can behave as opportunistic pathogens. From the choanal slits of sick animals the following potential organisms were isolated: Streptococcus sp., Staphylococcus sp., Escherichia coli, Klebsiella pneumoniae pneumoniae, K. oxytoca, Proteus mirabilis, Candida albicans and Aspergillus flavus. All of them have been reported to be associated with upper respiratory disease under certain circumstances. The sensitivity testing showed the drugs of choice, for gram-positive and gram-negative organisms, to be, in decreasing order: gentamicin, amikacin, enrofloxacin, tetracycline, ticarcillin, kanamycin and sulfamethoxazole+trimethoprim.

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EUROPEAN SOCIETY OF FELINE MEDICINE - ESFM

Feline vestibular disorders Richard A. LeCouteur VMD, BVSc, PhD, Dipl ACVIM (Neurology), Dipl ECVN Professor of Neurology and Neurosurgery Department of Surgical & Radiological Sciences - School of Veterinary Medicine University of California, Davis, California - USA

Summary Vestibular disorders produce varying degrees of loss of equilibrium, causing imbalance and ataxia. Strength is not lost and therefore paresis is not observed. Most commonly the disturbance is unilateral and the clinical signs are those of asymmetrical ataxia without the loss of strength. Unilateral vestibular signs may result from either central (brain stem) or peripheral (labyrinth) disease. It is important to differentiate central from peripheral disease, because of the difference in treatment and prognosis. Signs of vestibular disease include falling, rolling, head tilt, circling, nystagmus, positional strabismus, and asymmetrical ataxia. Hearing disorders are often associated with vestibular dysfunction (and vice versa) as the auditory and vestibular systems are closely associated anatomically.

tympanic cavity of cats and dogs. In dogs the tympanic cavity is composed of a small dorsal epitympanic recess and a large ventral tympanic bulla. The auditory ossicles are located in the middle portion of the tympanic cavity of dogs. The feline tympanic cavity is divided into two compartments by a thin, bony septum that arises along the cranial aspect of the bulla and curves to attach to the mid-point of the lateral wall. The majority of the lateral wall of the smaller craniolateral compartment is formed by the tympanic membrane. These compartments communicate through a narrow fissure on the caudomedial aspect of the bony septum. Near this fissure the sympathetic nerves form a plexus on a structure called the promontory. Because of their location, these sympathetic nerves are easily traumatized during surgical curettage of the feline middle ear, resulting in a Hornerâ&#x20AC;&#x2122;s syndrome.

Receptors - General information INTRODUCTION The vestibular system has 2 main functions: (1) to maintain the visual image by stabilizing the eyes in space during head movements; the stabilization is performed utilizing phasic or tonic vestibulo-ocular reflexes; and (2) to stabilize the position of the head in space - thus ensuring that the position of the body is stable. The stabilization is performed utilizing phasic or tonic vestibulospinal reflexes.

ANATOMICAL CONSIDERATIONS

Two sets of mechanoreceptors are involved in vestibular function: (1) a set responsive to angular (rotational) acceleration (or deceleration); these receptors are located in the membranous semicircular canals; and (2) a set responsive to linear acceleration (or deceleration) and gravity. These receptors are found at 2 locations, one in the utriculus and one in the sacculus. The mechanoreceptor generates a receptor potential that results in the development of a generator potential in the primary afferent fibre. The cell bodies of the primary afferent fibers are bipolar cells located in the vestibular ganglion. The primary afferent fibers comprise the vestibular part of the vestibulocochlear (VIIIth) nerve.

Gross anatomy The ear is composed of three parts: (1) the inner ear, which consists of a membranous and bony labyrinth, and which functions for hearing and balance, (2) the middle ear, which comprises the tympanic cavity, and communicates with the nasopharynx by means of the auditory tube (eustachian tube), and (3) the external ear, formed by the auditory meatus and a short canal. The middle and external ears are separated by the tympanic membrane, and the opening of the horiziontal canal into the middle ear is called the external acoustic meatus. The theree auditory ossicles (stapes, malleus, and incus) connect the tympanic membrane to the inner ear. There are important diferences between the air-filled

Receptors for angular acceleration These receptors are located in the petrous portion of the temporal bone. The vestibular organ consists of interconnecting canals in the bone called bony (or osseous) labyrinths, and a single large cavity within the bone to which all canals connect, called the vestibule. Within the bony labyrinths are fluid-filled membranous tubes called the membranous labyrinths. These membranous labyrinths contain a fluid called endolymph. Surrounding the membranous labyrinths, filling the osseous labyrinths, is a fluid called perilymph. Three membranous semicircular canals form the mechanism for detection of angular (or rotational) accelera-

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tion. These 3 canals join the utriculus located in the osseous vestibule. On each membranous semicircular canal is an enlargement called the ampulla. Running transversely across each ampulla is a connective tissue crest with receptor cells (hair cells) on its surface - called the crista ampullaris. The receptor cells have cilia protruding from them in stepwise gradations of length. The largest cilium is called the kinocilium and the rest are called stereocilia. The cilia project into a gelatinous substance called the cupula. The cupula extends across the entire ampulla. Endolymph does not flow past the cupula. The hair cells produce receptor potentials, that give rise to generator potentials, that produce action potentials in the vestibular portion of the vestibulocochlear nerve. The vestibular fibers show a tonic discharge even at rest. When the head is rotated, the inertia of the endolymph places a shear force on the cupula. This bends the cilia. If the shear on the cupula bends the stereocilia towards the kinocilium, the tonic nerve impulse rate from all of the nerve fibers supplying that crista is changed from a tonic to a phasic response. If the rotation is slight, the resting tonic rate is quickly resumed. If the rotation is a sustained movement, the friction of the endolymph on the walls of the membranous labyrinth results in acceleration of the movement of the endolymph until the velocity of the endolymph equals the rotational velocity of the head; thus the shear exerted on the cupula is removed. The tonic firing rate is then resumed as though the head were not rotating. If the head rotation is stopped, the momentum of the endolymph places a shearing force on the cupula in the opposite direction. This bends the kinocilium towards the stereocilia and this inhibits the generation of nerve impulses. As soon as the friction of the endolymph on the walls slows down the movement of the endolymph, the cupula returns to the non-rotational position and the tonic rate of discharge is resumed. If the rotation of the head is in the opposite direction so that the kinocilium is first displaced towards the stereocilia, the tonic rate of discharge will be first inhibited and then accelerated at the end of head rotation. There are 3 semicircular canals on each side of the head - a rostral, a caudal and a lateral. Each pair of semicircular canals works in a “push-pull” arrangement. When the rate of discharge from the crista on one side is increased, the rate of discharge from the opposite crista is decreased. Note that the hair cells are excited only when acceleration (velocity is increasing) or deceleration (velocity is decreasing) of the endolymph is occurring.

Receptors for linear acceleration and gravity These receptors are located in raised areas called the macula utriculus in the utriculus, and the macula sacculus in the saccule. The cilia of hair cells project into a gelatinous mass in which small granules, called otoliths (or otoconia) are embedded. The mass and its contents are together called the otolithic membrane. The macula in the utricle is horizontal, and the macula in the saccule is vertically orientated, when the head is upright. If the head is tilted to one side or the other, the force of

4th European FECAVA SCIVAC Congress

gravity slightly displaces the otolithic membrane towards the tilted side. This places shearing forces on the cilia. If the head tilt is such that the movement of the otolithic membrane forces the stereocilia toward the kinocilium, then an increase in the tonic rate of discharge results. If it is in the opposite direction, a decrease in the tonic rate of discharge results. These discharges continue for as long as the pull of gravity displaces the otolithic membrane. For this reason, these receptors are often referred to as statolithic organs. The maculae respond to linear acceleration because the otolithic membrane has an inertia during acceleration of the linear movement of the head. If acceleration does not continue (i.e. velocity remains constant), the otolithic membrane returns to its resting position, and the frequency returns to the resting rate. During deceleration of the head, the otolithic membrane has momentum; thus, a shearing force is exerted on the hair cells until the momentum ceases. In linear acceleration, acceleration (or deceleration) is necessary to alter activity in the vestibular fibers. Velocity (movement of the head at a constant speed) will not stimulate the maculae. There is no “push-pull” effect from left and right maculae as occurs relative to the semicircular canals.

Central vestibular connections Primary afferent fibers from the crista of the semicircular canals and the maculae directly terminate in 2 central nervous system (CNS) sites: (1) cerebellar cortex of the flocculonodular lobe of the cerebellum; (2) 4 vestibular nuclei (rostral, medial, lateral, caudal). Primary afferent fibers from the crista ampullaris of the semicircular canals (angular acceleration) terminate in rostral, medial, and caudal nuclei. Primary afferent fibers from the macula (linear acceleration and gravity) terminate mostly in the lateral vestibular nuclei.

Central pathways and reflex connections of the vestibular nuclei These connections descend via the lateral vestibulospinal tract to lower motor neurons of neck muscles, and muscles of thoracic and pelvic limbs; they descend via the medial vestibulospinal tract to the neck muscles and ascend to motor nuclei of the eye muscles via the medial longitudinal fasciculus. Other pathways include connections to the cerebellum via the caudal cerebellar peduncle, to the reticular formation, to the ventrobasilar nucleus of the thalamus, to the post-sigmoid gyrus of the cerebral cortex, for conscious processing of vestibular inputs (vestibulothalamic pathway) and to the hypothalamus via the medial longitudinal fasciculus.

Lateral vestibulospinal tract This is an important tract for posture and locomotion. Cells of origin of this pathway are located in the lateral vestibular nucleus (Dieter’s nucleus). The cells in this nucleus are organized topographically. Afferents to the lateral vestibular nucleus include: (1) macula (gravity and linear ac-

celeration - tonic input); (2) crista cells of rostral semicircular canal (tonic input); (3) cerebellar nuclei (tonic input); and (4) collaterals from ascending pathways, particularly muscle spindles and Golgi tendon organs. All fibers of the lateral vestibulospinal tract produce EPSP’s at their synapses. This tract establishes monosynaptic connections with lower motor neurons innervating neck, back, thoracic and pelvic limb antigravity muscles (mostly extensors). It is the largest (and thus the fastest) of all the descending pathways. It also has facilitatory polysynaptic connections with other extensors and inhibitory polysynaptic connections with flexors. It modulates segmental reflexes and it is an ipsilateral tract.

Medial vestibulospinal tract This pathway originates from the medial and caudal vestibular nuclei, with some fibers coming from the lateral vestibular nucleus. It descends in the medial longitudinal fasciculus. Afferent inputs to this pathway mainly come from the semicircular canals (angular acceleration), cerebellar nuclei (tonic input) and the cerebellar cortex (tonic input - inhibitory). Terminations of the medial vestibulospinal tract include monosynaptic inhibition of ipsilateral and contralateral lower motor neurons (LMN’s) to extensor muscles of the neck and to some back muscles, and monosynaptic excitation of contralateral LMN’s supplying extensors of the neck.

Ascending vestibular fibers Fibers from all vestibular nuclei synapse with LMN’s of the III, IV, and VI cranial nerves. Some are crossed and some uncrossed. They all ascend via the medial longitudinal fasciculus. These fibers are involved in the vestibulo-ocular reflexes, such as compensatory rolling of the eyes when the head is moved. Vestibular fibers also go to the flocculonodular lobe of the cerebellum.

Reticular formation There are numerous projections from vestibular nuclei into the ascending and descending reticular formation. Some of these descending reticular projections are involved in the vomiting and cardiovascular reactions that may occur in vestibular disturbances.

CLINICAL SIGNS OF VESTIBULAR DISEASE Vestibular disease produces varying degrees of loss of equilibrium causing imbalance and ataxia. Strength is not interfered with, and therefore paresis is not observed. As a rule, the disturbance is unilateral or asymmetrical, and the signs are those of an asymmetrical ataxia with preservation of strength.

Unilateral vestibular signs may result from either central (brain stem) or peripheral (labyrinth) disease. It is important to differentiate central from peripheral disease because of the differences in treatment and prognosis. Signs of vestibular disease include: falling, rolling, tilting of the head, circling, nystagmus, positional strabismus (deviation of one eye in some head positions), and an asymmetrical ataxia.

Nystagmus The sign of disturbed vestibular input to the neurons that innervate extra-ocular eye muscles is abnormal nystagmus. Nystagmus probably occurs at some time during all types of vestibular disease. Nystagmus is an involuntary rhythmic oscillation of the eyeball, that nearly always affects both eyes equally. Typically, nystagmus consists of a slow phase in one direction and a fast phase in the other. n cats, oscillations of the head that are synchronous with the nystagmus will frequently be seen. It is customary to describe nystagmus clinically in terms of the fast phase, despite the fact that in most cases the slow phase will be directed towards the affected side. Nystagmus tends to occur early in the course of peripheral vestibular disease, and to disappear later, which means that nystagmus may not be obvious at the time of clinical examination in all acts with vestibular disease. Nystagmus may be induced in normal animals, where it may be termed physiological nystagmus. For example, it occurs with normal turning of the head from side to side, or up and down (vestibular in origin), or when watching the passing scenery from a railway carriage (visual in origin). Also, it occurs normally after rotation, and is then called post-rotational nystagmus. If nystagmus occurs when the head is still, and there is no rotation or movement of the surroundings, it is called spontaneous nystagmus. Spontaneous nystagmus is usually pathological in origin. Spontaneous nystagmus may be horizontal, rotatory, or vertical in direction. If nystagmus occurs only when the head is placed in an unusual position (e.g. laterally or dorsally), it is known as positional nystagmus. Nystagmus that consists of eye movements of the same velocity in each direction is termed pendulous nystagmus, and is not of vestibular origin. Pendulous nystagmus is usually associated with visual deficits. Caloric testing consists of irrigation of the external ear canals with warm or cold water. This sets up currents in the endolymph, stimulating nystagmus and head tilt. It is difficult to interpret the results of this test in an animal already showing clinical signs of vestibular disease. The test may have some value in demonstrating whether or not the labyrinth or VIIIth nerve is functional, since a complete absence of response to caloric stimulation usually indicates total loss of receptor function or nerve function. Nystagmus in an inappropriate direction, and dissociated (disconjugate) nystagmus, are abnormal responses to caloric testing, and suggest a lesion of the vestibular nuclei or of the medial longitudinal fasciculus.

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Abnormal posture and ataxia

Central vestibular disease

Loss of co-ordination between head, trunk, and limbs, results in loss of balance. This is reflected in a head tilt, with the more ventral ear directed towards the side of the vestibular disturbance. The trunk may fall, or even roll, towards the side of the lesion. The trunk may be flexed laterally, with the concavity directed towards the side of the lesion. The animal may tend to circle towards the side of the lesion. These are usually circles with a small radius. It may be possible to elicit mild hypertonia and hyperreflexia in the limbs on the side of the body opposite to a vestibular system lesion. An animal will often fall when attempting to shake its head. Vision will assist an animal to compensate for a vestibular system deficit. Blindfolding an animal with a vestibular lesion will accentuate the clinical signs.

Any signs of brainstem disease in association with vestibular signs indicate that central involvement is present. The most frequent differentiating feature is a deficit in postural reactions, as central vestibular lesions most often result in paresis or loss of conscious proprioception. Alterations in mental status, or deficits in Vth or VIth cranial nerves, are also indicative of central disease. Nystagmus may be a key to differentiating central from peripheral disease. Nystagmus occurs in most central syndromes, and appears to be a permanent deficit. It is a positional nystagmus; therefore it may be present in some head positions (with respect to gravity), but not in others. Also the nystagmus may vary in direction with change in head position. Vertical nystagmus in any head position is most consistent with central vestibular disease.

Postural reactions - Strabismus When the head is extended in a tonic neck reaction, the eyeballs should remain in the center of the palpebral fissure in dogs and cats. This often fails to occur on the side of a unilateral vestibular disturbance, and results in a ventrally deviated eyeball. Occasionally, in vestibular disease, an eyeball is noticed to deviate ventrally or ventrolaterally without extension of the head and neck. This appears as a LMN strabismus, and can be corrected by moving the head into a different position or by inducing the patient to move its eyeballs to gaze in different directions. This is referred to as vestibular strabismus. The ventrally deviated eyeball is on the side of the vestibular lesion. Occasionally, the opposite eyeball will appear to be deviated dorsally.

Peripheral vestibular disease Peripheral lesions involve the middle and inner ear. Middle ear (bulla ossea) lesions usually produce head tilt (ipsilateral to the lesion) only, in the absence of other signs. Horizontal or rotatory nystagmus may be seen occasionally. Inner ear disease, which actually involves the receptors and vestibular nerve within the petrosal bone, usually produces other signs in addition to the ipsilateral head tilt - falling, rolling, circling, nystagmus, positional strabismus, asymmetrical ataxia. Horner’s syndrome (miosis, ptosis, enophthalmos) of the ipsilateral eye may be present with either middle or inner ear disease in dogs and cats, because the sympathetic trunk passes through the middle ear in close proximity to the petrosal bone. The facial nerve may be affected in inner ear disease, as it courses through the petrosal bone in contact with the vestibulocochlear nerve. The primary characteristics of unilateral peripheral vestibular disease are: asymmetrical ataxia without deficits in postural reactions, and a horizontal or rotatory nystagmus that does not change in direction with different head positions. The fast phase of the nystagmus is directed away from the affected side.

Paradoxical central vestibular syndrome Unilateral lesions of the peripheral vestibular system produce a head tilt towards the side of the lesion. With few exceptions, the same occurs with lesions of the central components of the vestibular system. Exceptions to this rule are therefore termed “paradoxical”. Some unilateral lesions of the central vestibular pathways, especially unilateral involvement of the flocculonodular lobe of the cerebellum or the supramedullary part of the caudal cerebellar peduncle, produce a head tilt and ataxia directed toward the side opposite to the lesion, and a nystagmus with the fast component towards the side of the lesion. Such lesions are usually space-occupying lesions. Usually these lesions will produce postural reaction deficits or additional cranial nerve abnormalities on the affected side, which aid in determining on which side a lesion is located.

Bilateral vestibular disease Bilateral peripheral vestibular disease with complete loss of function is characterized by symmetrical ataxia and loss of balance of either side, with strength preserved. There is no postural asymmetry. A characteristic “side-toside” head movement often accompanies these signs. Abnormal nystagmus is not observed, and with bilateral destruction of the receptor organs, normal vestibular nystagmus cannot be elicited by head movement or caloric testing.

DISEASES OF THE VESTIBULAR SYSTEM PERIPHERAL VESTIBULAR DISEASES Otitis Media-Interna (or Labyrinthitis) Etiology & Pathogenesis. Labyrinthitis refers to inflammation of the inner ear that results in dysfunction of the membranous labyrinths. This disorder is almost always an extension of otitis externa. Retrograde infection may occur via the auditory tubes. Another source of infection of middle ear structures is hematogenous spread. Medial extension of mid-

dle ear infection to involve meninges is not uncommon in cats. The majority of infections are caused by bacteria, including Staphylococcus spp., Streptococcus spp., Proteus spp., Pseudomonas spp., Enterococcus spp. and Escherichia coli. Occasionally, yeast infection (e.g. Pityrosporon spp. and Candida spp.) is observed. Rarely, fungal infection may be confined to the middle ear (e.g.. Cryptococcus sp.). Foreign bodies such as grass awns may initiate inflammation and predispose to secondary bacterial infection. Cinical Findings. Varying degrees of vestibular dysfunction accompany otitis media-interna or labyrinthitis. Ipsilateral head tilt, nystagmus (usually rotatory), and ataxia are almost always present. Circling, falling, and rolling, may be seen in more severely affected animals. Ipsilateral facial paresis/paralysis and Horner’s syndrome may occur. Because the facial nerve contains the parasympathetic preganglionic neurons that modulate lacrimal gland secretion, animals with labyrinthitis may have decreased tear production and develop ipsilateral keratoconjunctivitis sicca. Ipsilateral hemifacial spasms, resulting from “irritation” of the facial nerve, have been reported in dogs in association with otitis media. Deafness, resulting from involvement of the cochlear nerve, may accompany otitis interna. Diagnosis. The diagnosis may be confirmed by otoscopic examination and skull radiography. Otoscopy may reveal otitis externa, and evidence of erosion or rupture of the tympanic membrane. Fluid in the middle ear may produce discoloration or bulging of the tympanic membrane. Inflammatory exudate or fluid should be submitted for culture and sensitivity testing. Fluid may be obtained by either aspiration or myringotomy. Radiographic examination of the temporal bones may reveal fluid within the tympanic cavity, or osteitis, sclerosis, or erosion of the tympanic bulla. Computed tomography (CT) images are more sensitive in outlining these alterations. Magnetic resonance imaging (MRI) is useful when central extension of otitis media/interna is suspected. Myringotomy procedure: Myringotomy is a surgical puncture of the tympanic membrane to relieve pressure or to obtain samples for analysis. The procedure should be completed under general anesthesia. Positioning - lateral recumbency, with affected ear uppermost, or if fluid is difficult to obtain, there may be an advantage in having the affected ear on the down (lowermost) side. The tympanic membrane consists of a loose dorsal section (pars flaccida) and a larger more rigid ventral portion (pars tensa). Whereas the pars flaccida is pink or white and contains small branching blood vessels, the pars tensa is tough, glistening, pearly gray, and often striated. The ear canal should be gently flushed with dilute (1:10) aqueous povidone-iodine solution several times until the ear canal is clear of debris. A myringotomy is then done using a 20-gauge or 22-gauge spinal needle. The use of a needle permits both collection of fluid for cytology and culture, and introduction of a small volume of sterile saline (0.2-0.4 ml) for lavage of the middle ear cavity when a fluid sample is not abtained following aspiration through the needle. The needle should penetrate the tympanic membrane in the ventral and caudal aspect of the pars tensa, in order to avoid the bony ossicles. Some authors recommend the routine flushing of the middle ear cavity with dilute povidoneiodine after fluid for

cytologic examination and culture has been withdrawn, followed by a saline flushing and introduction of a broad spectrum antibiotic. This author recommends a gentle flushing with saline only after a myringotomy procedure, followed by the use of systemic broad spectrum antibiotic therapy. Treatment. The prognosis is usually favorable with prolonged oral antibiotic therapy, where selection is based on culture and sensitivity studies. Some authors recommend the use of repeated ear cleanings and irrigation, and topical antibiotic therapy, in cases of otitis media/interna. This author recommends these procedures for otitis externa associated with otitis media/interna only when the tympanic membrane is intact. In addition, the use of topical therapies should be avoided for four or five days following myringotomy. Cats with concurrent mite infestation should be treated with a topical miticide. In more chronic cases, surgical drainage of the middle ear cavity may be required by means of lateral or ventral bulla osteotomy.

Idiopathic peripheral vestibular disease Etiology & Pathogenesis. This is an acute vestibular syndrome of unknown etiology of cats of all ages. A similar condition occurs in older dogs. There is no evidence of inflammatory disease in affected animals. Some affected cats have had a concomitant or recent upper respiratory tract infection, suggesting that previous viral infection may directly (due to seeding of virus in the inner ear) or indirectly (because of altered antigenicity) cause inflammation of the vestibular sensing apparatus. Pathological or immunological confirmation of this hypothesis is lacking, however. In one study of 75 affected cats, 80% were diagnosed in the months of July and August, suggesting an environmental factor may be involved, however none was identified. The syndrome in cats has been compared to Ménière’s disease of humans, a disorder characterized by recurrent bouts of vertigo, nystagmus and tinnitus. Abnormal flow of endolymph within the membranous labyrinth apparently contributes to the pathogenesis of Ménière’s disease in humans, and an increased concentration of potassium ions within the perilymph (separating the bony and membranous labyrinths) may also have a role. Considering that, unlike Ménière’s disease of humans, the feline syndrome spontaneously resolves and generally does not reoccur, it is not clear whether these factors have a role in the development of the problem in cats. Clinical Findings. A breed or sex predilection does not exist for feline idiopathic peripheral vestibular disease. The median age of affected cats is approximately four years. Both cats and dogs exhibit signs of peripheral vestibular involvement. The signs of vestibular dysfunction usually are unilateral, however occasionally bilateral signs may be seen in affected cats. In addition to neurological deficits of peripheral vestibular disease, some affected cats may have vomiting or anorexia. The signs appear suddenly, and often result in severe dysfunction and inability to stand and walk. In a few days the affected animals tend to stabilize and improvement continues for 4-6 weeks. Residual deficits such as mild head tilt may persist, and blindfolding or darkness

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will cause a re-occurrence of signs well after apparent recovery has occurred. Diagnosis. A diagnosis of idiopathic feline peripheral vestibular disease is made by excluding other causes. There is not a definitive antemortem or postmortem finding. It is important to distinguish this idiopathic benign disorder, which resolves spontaneously without therapy, from otitis media-interna, which requires vigorous therapy, and may produce recurrent or persistent signs. The idiopathic disease is characterized by a peracute onset of head tilt, asymmetrical ataxia, and horizontal or rotatory nystagmus, in the absence of facial paresis, Hornerâ&#x20AC;&#x2122;s syndrome, or signs of CNS involvement. An absence of otitis externa, normal tympanic membranes, and normal radiographs of the temporal bones, further support this diagnosis. Treatment. While the cause of this idiopathic disorder remains undetermined, prognosis for spontaneous recovery is good, however, recovery may require 4-6 weeks. Re-occurrence may be seen, especially in dogs, either on the same side or the opposite side. There is no evidence that treatment of any type alters the course of the disease. Cats with concurrent otitis externa or otitis media/interna should be treated for these problems as previously described. Antiemetics may be considered in cats that vomit.

following retraction of the soft palate. Diagnosis. Polyps should be suspected in cats with appropriate clinical signs, particularly in young cats. Most polyps can be visualized with a thorough otoscopic or pharyngeal examination. Opacitiy of the tympanic cavity, associated with sclerosis of the tympanic bulla, may be seen on plain skull radiographs. Computed tomography provides precise information regarding location and extent of polyps. Bony lysis is rarely seen in association with nasopharyngeal polyps. Cerebrospinal fluid analysis may be abnormal in cats with extension of inflammation to brain or meninges. Excised polyps are variable in size, red in color, and of smooth appearance. Many have a stalk or pedicle of attachment. Microspcopically, there is a central core of well-vascularized fibrous tissue that is covered by epithelium (varying from stratified squamous to pseudostratified columnar cells). Glands composed of goblet cells may be seen within the fibrous tissue. There may also be an infiltration of a mixed population of inflammatory cells within the polyp. Treatment. Many polyps in the external ear, or in a nasopharyngeal location, may be removed by means of gentle traction, thus avulsing the stalk from its attachment. Bulla osteotomy with curettage has been advocated to remove residual polyps from within the tympanic cavity.

Nasopharyngeal polyps

Neoplasia

Etiology & Pathogensis. Inflammatory or nasopharyngeal polyps are benign masses that may be located in the nasophaarynx, auditory tube, and/or the tympanic cavity. Rarely the polyp may rupture the tympanic membrane and protrude into the external ear canal. Polyps consist of wellvascularized fibrous tissue lined by epithelium. The site of origin of the polyps has not been determined. It has been speculated that some polyps may arise subsequently to otitis externa or otitis media, however otitis media appears to frequently be a complication of auditory tube obstruction by the polyp, rather than an initiating factor. Vestibular dysfunction follows extension of otitis media into the labyrinth (otitis interna). Occasionally there may be further extension of infection into the brain, resulting in central vestibular signs and brainstem dysfunction. In one published report, calici virus was isolated from one of three young cats affected in a household. Another report suggested a congenital origin, as two young cats affected with polyps were siblings. Clinical Findings. The majority of cats affected with polyps are less than two years of age at the time of initial clinical signs (age range 2 months to 15 years). There is no apparent breed or sex predilection. Clinical signs in affected cats vary widely, depending on the location of the polyp or polyps. Polyps originating within the auditory tube or middle ear cavity may interfere with drainage of middle ear secretions, resulting in signs of otitis externa and/or middle ear involvement and subsequent otitis interna and signs of peripheral vetsibular disease. Polyps may be seen by means of otoscopic examination. Cats with a polyp or polyps in a nasopharyngeal location have signs of upper respiratory compromise (coughing, dyspnea, sneezing, stertorous respiration). Polyps in a nasopharyngeal location usually are seen

Neoplasms that involve the temporal bone may produce peripheral vestibular disease, often in association with facial paralysis or paresis. Fibrosarcoma, osteosarcoma, chondrosarcoma, and squamous cell carcinoma have been reported. Squamous cell carcinoma and ceruminous gland adenocarcinoma may involve adjacent soft tissues. It has been reported that squamous cell carcinoma is the most frequently occurring tumor affecting the middle ear of cats, whereas papillary adenomas and extension of adnexal or ceruminous gland tumors appear to be more common in dogs in this location. Rarely, middle ear tumors may extend directly into brainstem. Neurofibroma or lymphoma of the vestibulocochlear nerve usually cause signs of unilateral vestibular disturbance prior to signs associated with compression of brainstem.

Congenital vestibular syndromes Signs of peripheral vestibular disease, usually in the absence of deafness, have been observed in several breeds of dog (including English cocker spaniels, German shepherd dogs, and Tibetan terriers), and in cats (Siamese and Burmese kittens). Severe head tilt, circling, and falling or rolling, may be noted from birth to 4 months of age. Nystagmus is rarely present. The cause is undetermined. Pathological lesions have not been demonstrated. Prognosis is guarded, as clinical signs may regress completely, re-occur, or remain static. There is no effective treatment. Congenital pendular nystagmus has been recognized in Siamese cats. The head may oscillate synchronously with the nystagmus. Signs of vestibular dysfunction are not ap-

parent, and lesions of the visual pathways are responsible for this syndrome.

Toxicity Prolonged therapy with aminoglycoside antibiotics may result in degeneration of the labyrinth receptors of the vestibular or auditory systems, or both. Vestibular dysfunction may be fully or partially reversible, however hearing may be permantly affected. In the southeastern U.S.A., acute peripheral vestibular signs may follow ingestion by cats of the tail of the blue-tail lizard.

Trauma Cranial trauma may result in signs of peripheral vestibular disease secondary to fractures of the temporal bone or tympanic bulla. Facial paralysis may accompany petrosal bone injury.

CENTRAL VESTIBULAR DISEASES Any cause of meningo-encephalitis may result in involvement of central vestibular structures. The vestibular deficits may occur alone, or with signs indicating involvement of other areas, such as spinal cord, cerebellum, or cerebrum. Reported causes in cats include feline infectious peritonitis, toxoplasmosis, and cryptococcosis. Aberrant parasitic migration may produce severe signs of vestibular disturbance. Neoplasms of the cerebellomedullary angle affect the vestibular system. Neoplasms may be located at the surface of the parenchyma (e.g. meningioma, neurofibroma, choroid plexus papilloma or malignant lymphoma), or may be located within the parenchyma (e.g. astrocytoma or lymphoma). Neoplasms at these locations occur in cats of all ages. Thiamine deficiency may produce a mild vestibular ataxia as the earliest sign of degeneration.

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EUROPEAN SOCIETY OF FELINE MEDICINE - ESFM

Feline spinal cord disorders Richard A. LeCouteur VMD, BVSc, PhD, Dipl ACVIM (Neurology), Dipl ECVN Professor of Neurology and Neurosurgery Department of Surgical & Radiological Sciences - School of Veterinary Medicine University of California, Davis, California - USA

Summary The spinal cord may be divided into four major longitudinal divisions. These divisions are : 1) cervical (C1 to C5); 2) cervical enlargement ( C6 to T2); 3) thoracolumbar ( T3 to L3); 4) lumbar enlargement (L4 to Cd5). Diseases of each of these regions results in a combination of neurological signs that is specific for the region involved. Recognition of a characteristic group of clinical signs is essential in the accurate localization of the spinal cord lesion. This lecture will review the clinical signs in cats associated with spinal cord disease and localization of the lesion to a particular level of the spinal cord. The lecture will also review the congenital, degenerative, metabolic, infectious, parasitic, traumatic, vascular, and idiopathic causes of feline spinal cord disorders.

INTRODUCTION Motor, sensory, reflex and sphincter abnormalities may be used to determine the location of a lesion within one of four major longitudinal divisions of the spinal cord. The divisions are cervical (C1 to C5 spinal cord segments), cervical enlargement (C6 to T2), thoracolumbar (T3 to L3), and lumbar enlargement (L4 to Cd5). It is essential to remember that these divisions refer to spinal cord segments, not vertebrae, and that spinal cord segments do not correspond exactly with vertebrae of the same number. Some variations may be encountered due to slight differences between animals in segments that form cervical or lumbar enlargements. A disorder of each of the four regions of the spinal cord results in a combination of neurologic signs that is specific for the region involved. Recognition of a characteristic group of clinical signs therefore allows accurate localization of a spinal cord lesion. The presence of neurological deficits indicative of involvement of more than one region of the spinal cord is highly suggestive of multifocal or disseminated spinal cord disease. The functional differences between upper motor neurons (UMNs) and lower motor neurons (LMNs) may be used to localize lesions to one of the functional regions of the spinal cord. Cell bodies of spinal cord LMNs are located in the spinal cord gray matter. Their axons leave the spinal cord via the ventral nerve roots to become part of a peripheral nerve, and

to terminate on a muscle. The LMNs of the thoracic limb have their cell bodies in C6 to T2 spinal cord segments that form the cervical enlargement, while LMNs of the pelvic limb arise from the L4 through S1 spinal cord segments of the lumbar enlargement. Anal and urethral sphincter LMNs originate from S1 through S3 spinal cord segments. Signs of LMN dysfunction, which in diseases affecting the spinal cord reflect damage to the spinal cord segment(s) from which LMNs originate, are: depression or loss of voluntary motor activity, normal or depressed segmental spinal reflexes, depression or loss of muscle tone, and rapid, severe atrophy of an affected muscle due to denervation. Upper motor neurons arise from cell bodies located in the brain. Their axons form descending pathways of the spinal cord, and terminate on interneurons that in turn synapse with LMNs. Lesions affecting UMNs result in UMN signs. These UMN signs result from an increase in the excitatory state of LMNs. Upper motor neuron signs include: depression or loss of voluntary motor activity, normal or exaggerated segmental spinal reflexes, appearance of abnormal spinal reflexes (e.g., crossed extensor reflex), increased muscle tone, and muscle atrophy due to disuse. Unilateral signs resulting from spinal cord disease are unusual, however signs frequently are asymmetrical. In the majority of cases, a lesion resulting in asymmetrical signs will be located on the side of greater motor and sensory deficit.

CERVICAL (C1 to C5) Fatal respiratory paralysis resulting from interruption of descending respiratory motor pathways or damage to motor neurons of the phrenic nerve (C5 to C7 spinal cord segments) occurs in a complete transverse myelopathy. Lesions that are less than complete may not affect respiration, and in such cases other signs may be detectable. Ataxia and paresis of all four limbs usually are seen. Tetraplegia rarely is seen, as lesions of sufficient severity to cause tetraplegia also produce respiratory paralysis. Hemiparesis occasionally may be present in association with a cervical lesion. Lesions of the cervical spinal cord may result in paraparesis with minimal neurologic deficits in thoracic limbs. The reasons for this are poorly understood. Spinal reflexes and muscle tone are intact in all limbs, and may be normal or exaggerated. Muscle atrophy general-

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ly is not present, however disuse atrophy may develop in cases that have a chronic course. Anal reflexes are intact and anal tone usually is normal. Bladder dysfunction may occur with normal or increased urinary sphincter tone, and loss of voluntary control of micturition. Reflex dyssynergia may also be seen. Although voluntary control of defecation may be lost, reflex defecation will occur when faeces are present in the rectum. Horner’s syndrome (ptosis, miosis, and enophthalmos) rarely may be present in an animal with a severe destructive, cervical lesion. Conscious proprioception and other postural reactions usually are depressed or absent in all limbs. It should be remembered that complete loss of conscious proprioception may be present without detectable loss of pain perception. Cervical hyperesthesia (“spasms”, apparent pain on palpation, cervical rigidity, and abnormal neck posture) may be seen in some animals with cervical myelopathy. Occasionally an animal may hold a thoracic limb in a partially flexed position, a posture that may be consistent with C1 to C5 nerve root or spinal nerve entrapment (“root signature”), although this posture is seen more commonly with a disorder of the cervical enlargement. Disorders that affect the cervical region of the spinal cord must be differentiated from brain lesions that result in tetraparesis. This may be accomplished by doing a complete neurological examination, however occasionally this distinction may be difficult. In most circumstances a cervical lesion does not result in neurological deficits attributable to involvement of the medulla oblongata, however, there are several notable exceptions to this rule. Positional strabismus resulting from loss of the vertebral joint proprioceptive input to the attitudinal reflexes, may be seen in association with a cranial cervical lesion (C1 to C3 spinal cord segments). A cranial cervical lesion may also cause facial hypesthesia as a result of involvement of the spinal nucleus and tract of the trigeminal nerve. Cranial cervical trauma often results in clinical signs referable to injury of the caudal brain stem (head tilt, pharyngeal paresis, facial paresis) or cerebellum. The Schiff-Sherrington sign (syndrome or phenomenon) consists of hypertonicity of thoracic limb muscles and hyperextension of the neck, and is seen in association with spinal cord lesions caudal to the cervical enlargement. It is essential to differentiate this sign from thoracic limb hypertonicity caused by a cervical lesion, or an injury rostral to the foramen magnum.

CERVICAL ENLARGEMENT (C6 to T2) Ataxia and paresis of all four limbs usually are present. Occasionally paresis of thoracic limbs and paralysis of pelvic limbs may be seen. Spinal reflexes and muscle tone may be normal or depressed in thoracic limbs, and normal or exaggerated in pelvic limbs. The nature of thoracic limb reflex alterations depends on the exact craniocaudal location of a lesion within this region. Muscle atrophy often is severe in thoracic limbs. Panniculus reflex may be depressed or absent unilaterally or bilaterally due to interruption of the LMNs involved in this reflex (C8 and T1 spinal

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cord segments). Should bladder dysfunction occur it is similar to that observed with a lesion in the cervical region, with loss of voluntary control of urination. Anal reflexes and anal tone most often are normal although voluntary control of defecation may be absent. Unilateral Horner’s syndrome commonly is observed with a spinal cord lesion of the cervical enlargement, particularly a lesion involving T1 to T3 spinal cord segments or nerve roots. Conscious proprioception and other postural reactions usually are depressed in all four limbs. Alterations in these functions may be more pronounced in the pelvic limbs than in thoracic limbs. Occasionally conscious proprioception will be absent only in a thoracic and pelvic limb on the same side. Severe depression or loss of pain perception rarely are seen in association with a lesion of the cervical enlargement, except in intrinsic myelopathies (e.g., ischemic myelopathy). Hyperesthesia at the level of a lesion of the cervical enlargement, thoracic limb lameness, or apparent neck pain may be present.

THORACOLUMBAR (T3 to L3) The majority of spinal cord lesions of dogs or cats occurs in this region. Typically thoracic limb gait is normal, and paresis and ataxia, or paralysis, are seen in pelvic limbs. Thoracic limb spinal reflexes are normal. Pelvic limb spinal reflexes and muscle tone are normal to exaggerated, depending on the severity of the lesion. Muscle atrophy is not seen in thoracic limbs. Pelvic limb muscle atrophy, if present, is the result of disuse and is seen in animals with a severe, chronic lesion. Anal reflexes and anal tone usually are normal or exaggerated. Voluntary control of defecation may be lost. Reflex defecation will occur when the rectum is filled with faeces, however may not be at an appropriate time or place. Degree of bladder dysfunction varies depending on the severity of a spinal cord lesion. There may be loss of voluntary control of urination, detrusor muscle areflexia with normal or increased urinary sphincter tone, or reflex dyssynergia where initiation of voiding occurs and is stopped by involuntary contraction of the urethral sphincter. The bladder may be manually expressed in some animals, and not in others, due to increased tone of the urinary bladder sphincter. This is often referred to as an “UMN bladder”. Although “overflow” incontinence may occur with lesions of the spinal cord in this region secondary to overfilling of the bladder, detrusor muscle tone and urinary sphincter tone are present, distinguishing this type of incontinence from that due to lesions of the lumbar enlargement and cauda equina (“LMN bladder”). Conscious proprioception and other postural reactions are normal in the thoracic limbs, and depressed or absent in the pelvic limbs. Pain perception is normal in the thoracic limbs and may be normal, depressed or absent in the pelvic limbs. Panniculus reflex may be reduced or absent caudal to a lesion. In the lumbar region the panniculus reflex may be present in le-

sions caudal to L3 due to the pattern of cutaneous innervation of lumbar spinal nerves. There may be an area of hyperesthesia at the level of a lesion. The Schiff-Sherrington sign may be seen with a lesion in this region. Usually it is an indication of an acute and severe spinal cord lesion, although such a lesion may be reversible.

LUMBAR ENLARGEMENT (L4 to Cd5) and CAUDA EQUINA Involvement of this region by a pathological process results in varying degrees of pelvic limb paresis and ataxia, or paralysis, and is often accompanied by dysfunction of bladder, and paresis or paralysis of anal sphincter and tail. Thoracic limb function is normal. Pelvic limb reflexes and muscle tone are reduced or absent. Muscle atrophy often is present in pelvic limbs. Conscious proprioception and other postural reactions are reduced or absent in pelvic limbs. Anal tone and anal reflexes are reduced or absent. The rectum and colon may become distended with feces, and fecal incontinence, with continual leakage of feces, often is seen. Constipation may result from the inability to void feces. Paresis or paralysis of the urethral sphincters and detrusor muscle result in overfilling of the bladder and “overflow” incontinence. Affected animals have a large residual volume of urine in the bladder, and the bladder is easily expressed manually. The Schiff-Sherrington sign occasionally may be seen with an acute lesion affecting this region of the spinal cord. The term cauda equina is used to describe the lumbar, sacral, and caudal nerve roots and spinal nerves as they extend caudally from the caudal tip (conus medullaris) of the spinal cord within the vertebral canal. Lesions that affect cauda equina result in clinical signs that are indistinguishable from lesions that affect the spinal cord segments from which the nerves of the cauda equina arise (L6 to Cd5).

ALPHABETICAL LISTING OF FELINE SPINAL CORD DISORDERS Bacterial or Fungal meningomyelitis Etiology and Pathogenesis. Bacterial or fungal meningitis and/or myelitis occur infrequently in cats. Several routes of infection exist. Direct implantation of organisms may occur following a bite wound, spinal puncture, or surgery, or may accompany migration of a foreign body such as a grass awn. Extension may occur from a focus of infection such as a paravertebral infection or diskospondylitis. Infection may also result from hematogenous spread of systemic infection such as endocarditis. As clinical signs produced by bacterial or fungal agents depend more on the neural structures affected than on the agent responsible, these agents are discussed together. Meningitis may be accompanied by infection of the underlying parenchyma of the spinal cord (myelitis). Meningitis and/or myelitis may be focal, multifocal, or disseminated

in distribution and are frequently accompanied by meningoencephalitis. Pathologically, meningitis is characterized by infiltration of inflammatory cells into the leptomeninges. Inflammation may occur throughout the entire subarachnoid space of the brain and spinal cord. Myelitis is characterized by necrosis and infiltration of inflammatory cells within spinal cord parenchyma. Bacteria that have been isolated from cats with meningitis and myelitis include Pasteurella multocida, Actinomyces viscosus, Fusobacterium sp, Eubacterium sp and Bacteroides sp. The most common fungi that infect the CNS of cats are Cryptococcus neoformans, Blastomyces dermatitidis, and Cladosporium bantianum. Cryptococcus neoformans is found ubiquitously and frequently causes infection in immunosuppressed animals. Cryptococcosis is more common in cats than dogs and infection may result from extension of nasal infection through the cribriform plate. Blastomyces infections are found in certain geographic areas in the United States and in such cases the CNS is infected by hematogenous spread. Focal epidural infections have been reported to occur, generally as a result of migrating grass awns or penetrating wounds. Proliferation of inflammatory tissue may result in an extradural space-occupying lesion causing spinal cord compression and clinical signs of a transverse myelopathy. Abscessation may occur within the spinal cord and may have the radiographic appearance of an intramedullary mass. Clinical Findings. Clinical signs of meningitis include apparent spinal pain, hyperesthesia, and cervical or thoracolumbar rigidity, occasionally manifest as a “sawhorse” posture. Irritation of the numerous nerve endings in the meninges results in reflex muscle spasms when affected animals are stimulated. Fever is intermittent and is more likely to occur in association with concurrent bacteremia or disseminated fungal infection. Fever may occur in association with primary CNS infections due to presence of leukocytic pyrogens in the CSF or in the hypothalamic circulation. Neurologic deficits are indicative of associated myelitis or radiculitis, and abnormalities depend on the location and extent of infection. Focal myelitis may result in signs of transverse myelopathy. Disseminated bacterial meningomyelitis often is associated with meningoencephalitis, and clinical signs usually are acute and rapidly progressive. Focal bacterial meningitis and/or myelitis and fungal meningomyelitis may be associated with development of more slowly progressive clinical signs. Paraparesis and pelvic limb ataxia are common presenting signs in cats with cryptococcal meningitis and/or myelitis. Progressive paralysis of a single pelvic limb has been reported in two cats with cryptococcal infection of the lumbar spinal cord. Cats with CNS cryptococcal infections may show an acute onset of clinical signs despite chronic destruction of nervous tissue. Clinical signs of bacterial or fungal meningitis and myelitis are indistinguishable from other causes of meningitis and myelitis in cats. Causes include CNS toxoplasmosis, FIP meningomyelitis, intervertebral disk protrusion (especially in the cervical spine), spinal fracture, diskospondylitis, polymyositis, and polyarthritis.

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Diagnosis. A diagnosis of bacterial or fungal meningitis and/or myelitis is made on the basis of results of CSF analysis, and isolation of a causative organism by culture of CSF. Clinical signs may reflect meningeal irritation or myelopathy that may be indistinguishable from signs caused by other noninfectious myelopathies such as intervertebral disk disease. Presence of fever or abnormal hemogram cannot be relied upon for diagnosis of meningitis/myelitis, as neither may be present in affected animals. Bacterial or fungal meningitis has been reported to result in moderate to severe CSF pleocytosis. More than 5000 white blood cells/ill may be present in some cases. Polymorphonuclear (PMN) cells predominate. Mixed mononuclear and PMN pleocytosis occurs with fungal meningitis, and eosinophils may be present, especially in cases of cryptococcal meningitis. The CSF appears turbid if the cell count is greater than 500 white blood cells/ill. In our experience, disseminated bacterial meningomyelitis is rarely recognized antemortem in dogs or cats. Focal bacterial epidural, meningeal, or parenchymal infections more commonly occur. Cerebrospinal fluid findings in affected animals reflect the degree of leptomeningeal or ependymal involvement, and the CSF white blood cell count may be normal or only slightly elevated (less than 50 white blood cells/u1). Cerebrospinal fluid protein is usually moderately to markedly elevated due to increased capillary permeability and leakage of serum proteins into the CSF, and probably also due to local production of immunoglobulins. If CSF protein content is high, fibrin clots may develop. Cerebrospinal fluid pressure is usually normal but occasionally is elevated, especially in animals with cryptococcal meningitis. Hemorrhage into the CSF may occur; a red or pink supernatant is indicative of recent hemorrhage. Xanthochromia develops if more than 48 hours have elapsed following hemorrhage. Cerebrospinal fluid glucose content may be decreased (CSF glucose is normally 60 to 80 per cent of a simultaneously determined plasma glucose concentration) as a result of glucose utilization by microorganisms and possibly by PMN leukocytes. However, low CSF glucose concentration is not a consistent finding in animals with bacterial meningitis. Bacteria or fungal organisms may be identified by Gram’s stain or acridine orange stain of sedimented or centrifuged CSF. Cryptococcal organisms often are observed in cell preparations of CSF and can be identified by staining with Wright’s stain or Gram’s stain, or using a wet mount preparation with India ink. Cerebrospinal fluid from all animals with CSF abnormalities consistent with meningitis should be submitted for both aerobic and anaerobic bacterial culture, and antibiotic sensitivity testing of any cultured bacterial isolates. Because of the prevalence of anaerobic bacteria in CNS infections of cats, anaerobic culturesare essential when bacterial meningitis is suspected. Cerebrospinal fluid fungal culture may also be done. Negative CSF cultures are common, even in those animals in which bacteria or fungal organisms can be identified in CSF. Culturing the sediment of centrifuged CSF, or filtering CSF and culturing the filter, may increase the likelihood of obtaining a positive CSF culture. Causative organisms may be isolated from blood cultures of animals that are bacteremic or have systemic fungal infection. It is recom-

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mended that a large volume of CSF, preferably 2 or 3 ml, be collected for bacterial and/or fungal culture. If a delay in processing of a CSF sample is anticipated, CSF can be aseptically inoculated into a blood culture bottle for submission to a diagnostic laboratory. Serology may also be useful in diagnosis of CNS fungal infections. The titer of antibody-coated latex agglutination to cryptococcal (capsular) antigen may be useful in the diagnosis of cryptococcal meningitis and in assessing the response to therapy. The latex cryptococcal agglutination titer (LCAT) is more sensitive than the indirect fluorescent antibody test and can be used on CSF. However, animals with localized CNS infection may have a negative titer. Focal epidural inflammatory lesions may appear as an extradural mass on myelography. Chronic focal meningitis may result in obstruction of CSF flow and blockage of contrast material on myelography due to arachnoid adhesions. Treatment. Bacterial Infections. In treating bacterial meningitis and/or myelitis it is desirable to use an antimicrobial that is specific for the causative organism, and that crosses the blood-brain barrier (or blood-spinal cord barrier) in therapeutic concentrations, in order that drug concentrations may be maintained after the acute phase of inflammation has subsided. The bloodbrain, blood-spinal cord, and blood-CSF barriers are most permeable to antimicrobials with high lipid solubility, low ionization potential, and low protein binding affinity. Antibiotics may be administered to animals with suspected bacterial meningitis prior to obtaining results of culture and sensitivity testing. Selection should be based on tentative organism identification (by Gram’s stain or acridine orange stain) from CSF, the suspected source of infection, and the ability of an antibiotic to reach effective tissue concentrations in CNS. High-dose intravenous therapy with a bactericidal drug should be used when possible, although many bactericidal drugs penetrate poorly into the CSF. Penicillin and penicillin derivatives in high doses have been recommended for the treatment of CNS infections caused by gram-positive cocci (e.g., penicillin G 5000-10,000 units IV every 6 hours for at least 7 days). Oxacillin may be used for the treatment of meningitis caused by penicillin-resistant strains of Staphylococcus. Most cephalosporins penetrate poorly into the CNS. Several third-generation cephalosporins (e.g., cefotaxime) reach effective CNS concentrations and are considered the drugs best suited for treatment of gramnegative meningitis. Firstand second-generation cephalosporins do not reach effective CSF concentrations, and should not be used in treatment of CNS infections. The cephalosporins largely have replaced the aminoglycosides, which penetrate poorly into the CNS. Metronidazole is useful for treatment of most anaerobic infections, is bactericidal, and diffuses well into all tissues including the CNS. Metronidazole has had an increasing role in the therapy of brain abscesses of humans. Metronidazole is used in combination with high doses of penicillin when aerobes are present. Toxicity (central vestibular signs and cerebellar dysfunction) has been reported in dogs treated with metronidazole. Chloramphenicol reaches higher CSF concentrations

than most other antibiotics; however, it is bacteriostatic, and many strains of Staphylococcus have been shown to be resistant to this drug. Chloramphenicol may be given at a dosage of 20 mg/lb IV four times a day or 25 mg/lb orally three times a day in dogs, and 5 to 10 mg/lb/day divided twice a day in cats. Adverse effects of chloramphenicol include gastroenteritis in dogs and cats, and bone marrow depression in cats. Because of the high frequency of adverse effects, and as bactericidal drugs are preferred for treatment of CNS infections, use of chloramphenicol is restricted to infections caused by susceptible organisms that are resistant to other agents. Most sulfonamides penetrate effectively into the CSF. Sulfadiazine (which is less protein-bound than other sulfonamides) penetrates into the CSF and nervous tissue better than sulfamethoxazole and is effective if given orally. Data are not available regarding the concentration of trimethoprim in CSF of dogs; however, CSF concentrations may be as high as 35 per cent of serum concentrations in other species. Trimethoprim-sulfadiazine combinations usually are bactericidal in action, and are effective for treatment of some bacterial CNS infections. In general, tetracycline, a broad-spectrum bacteriostatic drug, only reaches effective CNS concentrations when meninges are inflamed. However, newer tetracyclines (minocycline, doxycycline) penetrate the CNS better than tetracycline and have better activity against anaerobes and some aerobic organisms. Intrathecal administration of antibiotics has been used in humans. Although possible for use in dogs, multiple CSF punctures, each requiring anesthesia, are needed. Some drugs are toxic when directly introduced into the CNS (e.g., penicillin may cause seizures), and drugs may not diffuse freely through CSF especially if there is a blockage of CSF flow. Treatment with antibiotics should be started as soon as possible after submission of CSF for culture. After results of culture and sensitivity are known, therapy may be altered. Treatment is continued for 2 to 4 weeks; however, treatment for longer periods is often necessary and relapses are possible. It is also important to identify possible sources of infection outside the CNS (endocarditis, diskospondylitis, paravertebral abscess). Localized spinal cord or meningeal infections that are well encapsulated may be resistant to antibiotic therapy. Surgical exploration is indicated if focal meningeal or epidural infection refractory to medical therapy is suspected. Use of corticosteroids in cases of bacterial meningitis and myelitis is controversial. Corticosteroids may decrease inflammation and thereby decrease the resulting spinal cord and nerve root damage; however, such treatment may also decrease host defense mechanisms, and in turn may result in worsening of clinical signs and in a higher incidence of relapse. Prognosis in cases of bacterial meningitis and myelitis depends both on the ability to eliminate the causative organism, and on the extent of neurologic deficits. Neurologic deficits occurring as a result of spinal cord or nerve root inflammation may be permanent. Fungal Infections. Fungal infection of the CNS of cats is extremely difficult to eliminate. The disease is often multi-

systemic, and is seldom recognized in the early stages of CNS involvement. Amphotericin B is frequently used to treat systemic fungal infections, although it is poorly absorbed into the CSF and nervous tissue. Intrathecal administration of amphotericin B has been recommended, especially in animals with Coccidioides immitis meningitis, but may result in arachnoiditis and cranial nerve toxicity. Combinations of drugs have been recommended. Amphotericin B, ketoconazole (poor CNS penetration), and flucytosine (good CNS penetration) are the main agents used. Rifampin has been used to enhance amphotericin B activity. Combined treatment with amphotericin B and 5- fluorocytosine (SFU) has been recommended for use in cases of cryptococcosis. Long-term, high-dose ketoconazole therapy is reported to be effective for treatment of cryptococcosis in cats. Because of the difficulty in obtaining therapeutic concentrations of antifungal agents within nervous tissue, the prognosis for CNS mycotic infections is poor. In the future, newer generation imidazoles (e.g., fluconazole, itraconazole) that are currently under investigation may be efficacious for treatment of fungal infections of the CNS.

Congenital vertebral anomalies Etiology and Pathogenesis. Congenital anomalies frequently occur in the vertebral column of cats; however, the majority of such anomalies are not clinically significant. If a vertebral anomaly causes instability or deformity of the vertebral canal, spinal cord compression and associated clinical signs may result. Clinical Findings. Clinical signs related to anomalous vertebrae are not present in the majority of affected animals. In most animals in which clinical signs develop, trauma to the spinal cord has occurred secondary to vertebral instability or progressive deformity with growth. Block vertebrae and butterfly vertebrae most often are stable and rarely are associated with clinical signs of spinal cord dysfunction. Hemivertebrae are more often associated with neurologic dysfunction than are other vertebral anomalies. Hemivertebrae may result in vertebral instability and/or narrowing of the spinal canal, especially in the dorsoventral plane, owing to moderate to severe angulation of the spine, which can result in spinal cord compression or intermittent trauma to the spinal cord. Clinical signs produced depend on the location of the anomaly and usually reflect a progressive or intermittent transverse myelopathy. Diagnosis. Diagnosis of a vertebral anomaly is made by means of radiographs of the vertebral column. Radiographically, hemivertebrae and adjacent vertebrae appear to be formed of normal bone, and disk spaces are usually well formed or widened. Vertebral bodies appear to have a portion absent and do not appear to be compressed. Adjacent vertebrae frequently have an altered shape that conforms to the defect found in the congenitally affected segment. Vertebral end- plates are smooth and of normal thickness. In most cases, myelography is necessary to determine the presence of spinal cord compression resulting from a congenital

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anomaly. Treatment. Vertebral anomalies resulting in spinal cord compression and instability of the vertebral column may be treated by means of surgical decompression and stabilization. It is important to determine that a congenital anomaly is the cause of an animalâ&#x20AC;&#x2122;s myelopathy by ensuring that the clinical signs are consistent with the observed abnormality. Caution must be exercised in completing surgery on an animal with a vertebral anomaly, and prognosis must be guarded. Animals may have more than one spinal abnormality, and vertebral anomalies may be associated with congenital spinal cord anomalies that are not amenable to surgical treatment.

Degenerative myelopathy Etiology and Pathogenesis. Degenerative myelopathy has been described in a 6-year-old cat. Histologic examination of spinal cord confirmed diffuse demyelination and marked astrocytosis in white matter. The etiology of the myelopathy was not determined; however, the cat was FeLV positive, and the possibility of virus-induced myelopathy was considered. Retroviruses have been associated with the development of chronic progressive myelopathy in humans. In light of this information, all cats with progressive myelopathy should be tested for both FeLV and FIV.

Diskospondylitis (spondylitis, vertebral osteomyelitis) Etiology and Pathogenesis. Diskospondylitis has been reported to occur in cats. Bacterial or fungal infection of the intervertebral disks and adjacent vertebral bodies (diskospondylitis), or of only the vertebral bodies (spondylitis), may result in extradural spinal cord or cauda equina compression due to extension of granulation tissue and bony proliferation within the vertebral canal, or due to pathologic fracture or luxation of an infected vertebra or vertebrae. Hematogenous spread of bacteria or fungi is probably the most common cause of diskospondylitis. Sources of infection include bacterial endocarditis and sites of dental extraction. Urinary tract infections have been implicated as a primary focus of infection. Retrograde flow in the vertebral veins has been suggested as a possible route of infection to the vertebral column. Affected intervertebral disks may have evidence of degeneration (collapsed disk space, spondylosis deformans) or trauma (traumatic disk protrusion, vertebral luxation). Prior disease or injury to the disk has been suggested as a factor in the pathogenesis of diskospondylitis. Clinical Findings. Diskospondylitis may occur at any level of the vertebral column, and multiple lesions may be seen. Diskospondylitis occurs more commonly in thoracic and lumbar spine than in cervical spine. The lumbosacral disk space frequently is involved. Clinical findings depend on the location of the affected vertebra or vertebrae. The most common clinical signs are weight loss, anorexia, depression, fever, reluctance to run or jump, and apparent spinal pain (which may be severe). Hyperesthesia may be

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present only over the site of the lesion or may be poorly localized, especially with involvement of multiple sites. Diagnosis. Diagnosis may be difficult, as clinical signs often are nonspecific. Diskospondylitis should always be considered in an animal with fever of unknown origin. Clinical signs commonly are present for several weeks or months before a diagnosis of diskospondylitis is made. Neurologic deficits associated with spinal cord or cauda equina compression may be present, and may reflect either a transverse or a multifocal myelopathy. Neurologic deficits associated with a transverse myelopathy (T3-L3) occur most commonly and include paraparesis, decreased conscious proprioception, exaggerated spinal reflexes, and much less commonly, paraplegia. Cervical lesions most commonly cause only apparent cervical pain, and lumbosacral lesions may cause neurologic deficits due to compression of nerves of the cauda equine. Affected animals may have a normal or elevated peripheral white blood cell count. Typical radiographic findings are destruction of the bony end-plates adjacent to an infected disk, collapse of the intervertebral disk, and varying degrees of new bone production. Early lesions may consist only of lytic areas in affected vertebral endplates. More advanced lesions show a mixture of bone Iysis and extensive new bone production, with osteophytes bridging adjacent vertebrae containing a central destructive focus. Affected vertebral bodies may be shortened, and bony proliferation may result in fusion of one or more vertebrae. Dogs with paravertebral grass seed migration may have radiographic abnormalities suggestive of paravertebral abscess formation and periosteal bone formation on the ventral aspect of vertebral bodies. This occurs most frequently in the cranial lumbar region. Collection of CSF is indicated in animals with neurologic deficits. Cerebrospinal fluid may be normal, or may have an increased protein content in cases in which diskospondylitis lesions cause extradural compression of spinal cord or result in meningitis and/or myelitis. The CSF white blood cell count may be normal, or may be elevated, with an increase in PMN neutrophils in CSF from animals with meningitis or myelltls. Myelography is indicated in animals with neurologic deficits indicative of spinal cord compression and is mandatory in cases in which decompressive surgery is considered. Myelographic findings usually indicate extradural compression, which results from extension of granulation tissue and bony proliferation within the spinal canal. Clinical signs do not always correlate well with the degree of compression seen on myelography, and depend on factors such as rate and duration of compression as well as degree of compression. Aerobic, anaerobic, and fungal cultures of blood and urine should be done prior to treatment in an attempt to isolate causative organisms. Surgical biopsy may be indicated in affected dogs in which a causative organism is not isolated from blood or urine, and/or animals that are unresponsive to treatment with broadspectrum antibiotics. Treatment. Treatment consists of long-term use of an antimicrobial that is effective against the causative organism(s) determined by results of blood and/or urine cultures. If an organism is not cultured, cats without severe neurologic

deficits may be treated empirically, assuming infection with the most common organism isolated from animals with diskospondylitis (coagulase-positive Staphylococcus sp). Antibiotics that are most effective for this purpose are cephalosporins, or (beta- lactamase resistant penicillins such as oxacillin and cloxacillin. A trimethoprim/sulfonamide combination or chloramphenicol is less effective but is less expensive, and may be effective in some cases. Clinical signs may recur if the infection is not completely eliminated prior to cessation of antibiotic therapy, and repeated cultures of blood and urine and ongoing treatment with an appropriate antibiotic may be necessary. Treatment is continued for at least 6 weeks, and vertebral radiographs are done every 2 to 3 weeks to monitor progression/ regression of a lesion. Antibiotic administration may be necessary for up to 6 months before radiographic evidence of resolution of lesions is seen. Obtaining radiographs to monitor response to therapy is important also to monitor for development of new lesions. Clinical improvement in animals with diskospondylitis (resolution of fever, improved appetite, reduction of apparent spinal pain) should be seen within 2 weeks of starting antibiotic therapy. If clinical improvement is not seen, treatment should be reevaluated. Antibiotic therapy should be reviewed, and surgical biopsy of a lesion may be considered. Use of analgesics and restriction of exercise during the first weeks of treatment may be helpful. Prognosis for animals with diskospondylitis depends on the ability to eliminate the causative organism(s) and on the degree of neurologic dysfunction. Animals with severe neurologic deficits have a guarded to poor prognosis.

Feline infectious peritonitis (meningitis and myelitis) Etiology and Pathogenesis. Pyogranulomatous meningitis and myelitis may occur in cats with FIP. Feline infectious peritonitis results from a coronavirus infection and is most commonly seen in younger cats between 6 months and 5 years of age. Infected cats may also have concurrent FeLV infection. Meningeal and spinal cord lesions are probably the result of immune complex-mediated vasculitis. Involvement of the CNS is more frequently observed in the noneffusive (dry) form than in the effusive (wet) form of FIP. Multifocal and diffuse involvement of the CNS is common, and a consistent clinical course is not associated with FIP. Clinical Findings. Feline infectious peritonitis may result in focal, multifocal, or diffuse involvement of the spinal cord, brain, and meninges, and clinical signs reflect the location of these lesions. Leptomeningitis with infiltration of spinal nerve roots has also been reported. The most commonly recognized neurologic signs are pelvic limb ataxia, hyperesthesia (especially over the back), and generalized ataxia. Affected animals usually manifest other clinical signs indicative of disseminated disease such as persistent fever (frequently greater than 105째 F), weight loss, enlarged kidneys, chorioretinitis, panophthalmitis, or anterior uveitis. Diagnosis. Diagnosis is made on the basis of clinical signs, clinical pathology (blood, CSF), and serology. Hema-

tologic changes include neutrophilia, Iymphopenia, and elevated serum fibrinogen and gamma globulins. Cerebrospinal fluid usually is abnormal with an elevated white blood cell count and protein level. The differential CSF white blood cell count is variable but PMN cells, Iymphocytes, and monocytes usually are present. Polymorphonuclear cells may be the predominant cell type in CSF. Protein concentration may be very high (greater than 2000 mg/dl), and CSF may be viscous and may clot. This should be taken into consideration when a CSF puncture is performed, as fluid may flow into the needle very slowly. Results of cytologic examination of CSF depend on the degree of meningeal involvement. Meningeal inflammation may be extensive, and CSF in these cases is generally highly abnormal. In the presence of focal or parenchymal inflammation, CSF may be normal. Cats with FIP generally have a high antibody titer. Presence of a positive antibody titer is not diagnostic of FIP, but in the presence of clinical signs, hypergammaglobulinemia and abnormal CSF findings consistent with FIP, a positive antibody titer is highly suggestive of FIP infection. Similarly, a low antibody titer does not rule out FIP. The differential diagnosis list for CNS FIP includes toxoplasmosis, cryptococcosis, and lymphosarcoma. Treatment. Prognosis for cats with FIP of the CNS is poor. The FeLV status of cats suspected to have FIP should be determined prior to commencing treatment, as the prognosis for cats with both viruses is hopeless. The most effective treatment protocols combine high levels of corticosteroids (prednisolone, I to 2 mg/lb orally once daily in the evening), cytotoxic drugs (either cyclophosphamide, 1 mg/lb orally once daily for 4 consecutive days of each week, or melphalan, 1 mg orally every third day) and broad-spectrum antibiotics (ampicillin, 10 mg/lb orally q8h), together with maintenance of nutrient intake and electrolyte balance. Cats receiving cytotoxic drugs should be routinely monitored for evidence of kidney dysfunction or bone marrow suppression. If a positive response to therapy is seen, treatment should be continued for at least 3 months. Cats with neurologic disease associated with FIP usually respond poorly to treatment.

Feline polioencephalomyelitis (feline non-suppurative meningencephalomyelitis) Etiology and Pathogenesis. Feline polioencephalomyelitis is a chronic, slowly progressive encephalomyelitis of unknown etiology described in immature and mature cats. Histopathologically, the disease is characterized by neuronal degeneration and perivascular cuffing by mononuclear cells. Demyelination and axonal loss are most conspicuous in the ventral and lateral columns of the spinal cord and most severe in the thoracic spinal cord segments. Lymphocytic meningitis, neuronophagia, and glial nodules also have been described, and lesions may be found in the cerebral cortex, diencephalon, midbrain, and medullary nuclei. The pathogenesis of the disease is unknown. A viral etiology is suspected on the basis of the histopathologic changes, although a specific viral agent has not been isolated The

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chronic clinical course, distribution of lesions, and lack of inclusions distinguish this disease from rabies, pseudorabies, and FIP. Feline panleukopenia virus, FeLV, and arboviruses have been suggested as possible agents in the pathogenesis of lesions. Further virologic and serologic tests are needed to determine the role of viral infection in the pathogenesis of this disorder. It has been proposed in a recent study that a tickborne virus may be the causative agent in Sweden. Clinical Findings. Clinical signs include ataxia, paraparesis, tetraparesis, hypermetria, head tremors, and localized hyperesthesia. Spinal reflexes, pupillary light reflexes, and postural reactions may be normal or depressed. Two animals have been described as having episodes of hallucinations, clawing, hissing, and biting at imaginary objects during sleep. These seizures preceded other clinical signs by more than 2 years in one cat. Clinical signs usually are indicative of multifocal CNS disease but may be suggestive of focal transverse myelopathy in the thoracolumbar region or lumbar enlargement. Clinical signs are slowly progressive over several months. Diagnosis. Antemortem diagnosis is difficult and is made by ruling out other multifocal CNS diseases. Two affected cats have been reported to be leukopenic, and one affected cat had an elevated CSF protein concentration (40 Treatment. Treatment of affected cats has not been reported.

Hypervitaminosis A of cats Etiology and Pathogenesis. Hypervitaminosis A in cats is characterized by extensive confluent exostosis that is most prominent in the cervical and thoracic spine. It is caused by a chronic excess of dietary vitamin A and is usually a result of feeding a diet consisting largely of liver. Exostosis may extend to involve the entire spine, ribs, and pelvic and thoracic limbs with complete fusion of the spine and joints. Compression of spinal nerve roots or nerves may occur if new bone formation extends into intervertebral foramina. Clinical Findings. Clinical signs in affected cats include apparent cervical pain and rigidity, thoracic limb lameness, ataxia, reluctance to move, paralysis, and hyperesthesia or anesthesia of the skin of the neck and forelimbs. The three most proximal diarthrodial joints of the cervical spine are almost always first affected. Osseous lesions develop insidiously, and clinical disease usually is advanced in cats older than 2 years of age before significant clinical features are recognized. Diagnosis. Radiographic evidence of extensive exostosis of the cervical vertebral column and a history of excessive dietary intake of vitamin A or liver are necessary for diagnosis. Treatment. Reduction of dietary intake of vitamin A prevents the development of further exostosis, however it may be difficult to persuade affected cats to eat anything other than liver.

Intervertebral disk disease Etiology and Pathogenesis. Degenerative disk disease

occurs in cats, although the incidence of clinical signs associated with disk protrusion is low compared to that in dogs. Degenerative changes and distribution of disk protrusions are similar to type II disk protrusions in nonchondrodystrophoid dogs. Clinical signs seen usually are indicative of a slowly progressive transverse cervical or thoracolumbar myelopathy. Type I disk extrusion associated with calcification of intervertebral disks and an acute onset of neurologic deficits have been reported in cats. Diagnosis and treatment are similar to that described for dogs. Clinical Findings. Clinical signs seen with intervertebral disk disease vary, depending on whether type I or type II disk herniation is present, the location of the lesion, and severity of the spinal cord lesion. Clinical signs seen in association with type I disk extrusion include apparent pain and/or motor and/or sensory deficits. Clinical signs associated with type II disk protrusion generally are slowly progressive over a period of months, but may develop acutely over days in some animals. Neurologic deficits usually are indicative of a cervical or thoracolumbar myelopathy. Paraparesis or tetraparesis, depending on the site of the lesion, is the most common clinical finding, and deficits may be asymmetric. In the cervical spine, type II protrusions most commonly occur in caudal cervical disks. In some cases, caudal cervical type II disk protrusion may be part of the spectrum of abnormalities associated with cervical spondylomyelopathy. Apparent neck or back pain may or may not be a feature of type II disk protrusion. Diagnosis. The differential diagnosis in animals with type II disk protrusion includes other causes of progressive transverse myelopathy, the most likely being neoplasia or degenerative myelopathy. Spinal radiographs and, in almost all cases, CSF analysis and myelography are necessary to confirm a diagnosis of disk extrusion or protrusion. General anesthesia is required to achieve the precise positioning needed to obtain radiographs of diagnostic value. Foam wedges or sandbags are usually needed to align the vertebral column parallel to the table top for lateral projections. Care must be taken, however, in anesthetizing and positioning animals that have acute type I disk extrusions, as further extrusion of disk material and further spinal cord compression may occur with manipulation and movement of the spine. Type II disk protrusion may be associated with narrowing of the disk space, osteophyte production, and end-plate sclerosis. Calcification of disk material rarely is seen in association with type II disk protrusion. In some animals with type I or type II disk herniation obvious abnormalities are not seen on noncontrast vertebral radiographs. Myelography is almost always necessary to confirm that disk material has herniated into the spinal canal resulting in spinal cord compression. Myelography is most important in determining the site (or sites) of disk herniation and in lateralization of disk material within the spinal canal prior to surgical decompression. Myelography is necessary for diagnosis in most cases of type II disk protrusion in order to distinguish disk protrusion from other causes of slowly progressive transverse myelopathy, such as spinal neoplasia and degenerative myelopathy. Cerebrospinal fluid should be collected and analyzed pri-

or to myelography to rule out inflammatory or infectious disease of the spinal cord and/or meninges. Clinical signs in animals with GME, distemper myelitis, FIP, spinal lymphoma, and other disorders may mimic those of cervical or thoracolumbar disk disease. The characteristic myelographic findings in both type I and type II disk herniation into the spinal canal are extradural compression of the spinal cord with displacement of the spinal cord and narrowing of the subarachnoid space on lateral and/or ventrodorsal views, depending on the location of the compressive mass. Type II, and most type I, disk herniations result in a ventral or ventrolateral epidural mass that causes dorsal displacement of the spinal cord. Treatment. Type I Disk- Extrusion. The appropriate treatment for animals with type I disk extrusion depends on the animal’s neurologic status. Each animal should be evaluated individually. Medical treatment directed at decreasing spinal cord edema may be appropriate for animals with apparent pain only or animals that have mild neurologic deficits but are ambulatory and have not had previous clinical signs associated with disk disease. These animals should be strictly confined to a small area such as a hospital cage or a quiet place away from other pets for at least 2 weeks. Very cautious use of analgesics or anti-inflammatory agents occasionally may be indicated; however, strict confinement followed by a period of restricted exercise is imperative. Surgical decompression of the spinal cord and removal of disk material from the spinal canal should be considered in animals with neurologic deficits such as paresis or paralysis with deep pain perception intact. Surgical decompression should be done as soon as possible to prevent further spinal cord damage incurred as a result of sustained compression or further extrusion of disk material. In addition, if surgery is delayed 2 to 3 weeks, disk material hardens and becomes adherent to dura mater, and becomes difficult or impossible to remove from the spinal canal. Regardless of whether medical or surgical treatment is instituted, animals that are paretic or paralyzed require intensive nursing care. Neurologic improvement may take weeks or months and this requires owner cooperation and enthusiasm regarding care and physical therapy. Manual expression, intermittent catheterization, and /or indwelling catheterization of the bladder are often required to ensure emptying of the bladder. Weekly urinalysis, especially in animals that do not have voluntary control of micturition, is important in monitoring for urinary tract infection. It is also important to keep animals well padded, clean, and dry to prevent formation of pressure sores, and to ensure that caloric and water intake is adequate. Type 11 Disk Protrusion. Treatment with corticosteroids may result in neurologic improvement for variable periods of time in animals with type II disk protrusion. However, corticosteroid therapy is not curative. The reason for this improvement is not clear as intramedullary hemorrhage and edema seen in cases of acute spinal cord injury are not a feature of chronic spinal cord compression.

Ischemic myelopathy due to fibrocartilaginous embolism

Etiology and Pathogenesis. Fibrocartilaginous embolism and ischemic myelopathy have been reported in a cat Ischemic myelopathy results from ischemic necrosis of spinal cord gray and white matter associated with fibrocartilaginous emboli that occlude arteries and/or veins of the leptomeninges and spinal cord parenchyma. This disease is characterized by an acute onset of neurologic deficits and is generally nonprogressive after several hours. The substance occluding spinal cord arteries and veins has histologic and histochemical properties similar to fibrocartilage of intervertebral disks and is presumed to originate from the nucleus pulposus of an intervertebral disk. Pathogenesis of the fibrocartilaginous embolism is not known. Clinical Findings. Ischemic myelopathy is characterized by an acute onset of neurologic deficits that may be severe. Clinical signs may progress over several hours but are generally not progressive after 12 hours. Affected animals usually do not have a history or evidence of trauma but may have a history of exercise prior to the onset of clinical signs. Apparent pain usually is not present at the time of examination or during the course of the disease, although dogs are often reported to “cry out” at the onset of clinical signs. Diagnosis. Ischemic myelopathy should be suspected in any cat with an acute onset of nonprogressive neurologic deficits that are not associated with apparent spinal pain, especially if deficits are asymmetric or indicate that at least several spinal cord segments are involved. A diagnosis is made by ruling out other causes of myelopathy. Spinal radiographs are normal. Cerebrospinal fluid may be normal or may have an elevated protein concentration as a result of leakage of protein through damaged vascular endothelium. The white blood cell count of CSF may be normal or may be mildly increased in the early stages, probably as a result of an inflammatory response triggered by spinal cord ischemia. Xanthochromia may be present 48 hours or more after a subarachnoid hemorrhage. Appearance on a myelogram usually is normal, although mild intramedullary swelling as a result of spinal cord edema may be seen for as long as 24 hours after the onset of clinical signs . Treatment. Corticosteroids (as recommended for spinal trauma) may be given initially to reduce any secondary spinal cord edema; however, after several days, edema usually is resolved. Good nursing care is essential in recumbent animals to prevent pressure sores, urinary tract infections, and contracture of denervated muscles. Prognosis depends on the severity of an animal’s neurologic deficits. Animals that retain pain perception in affected limbs and tail usually regain neurologic function, although recovery may take several weeks to months and LMN signs may persist (muscle atrophy and/or paresis). Animals with absent pain perception for 24 hours are likely to have irreversible spinal cord damage and have a poor prognosis for return of function in affected limb or limbs. Many animals show improvement within 2 weeks of onset of signs, unless extensive gray matter destruction has occurred. Clinical improvement seen in the first 2 weeks may be accounted for by resolution of edema and hemorrhage, and establishment of collateral circulation to areas that were is-

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chemic but not necrotic. Later clinical improvement is proably due to compensation by remaining spinal cord neurons.

Mucopolysaccharidosis Etiology and Pathogenesis. The mucopolysaccharidoses are a group of genetic diseases that result from defects in the metabolism of glycosaminoglycans. Two subclasses have been recognized in cats, and paraparesis associated with spinal cord compression has been reported in Siamese cats with mucopolysaccharidosis VI (MPS VI). Mucopolysaccharidosis VI is the result of a deficiency of the lysosomal enzyme arylsulfatase B and, in addition to causing characteristic physical deformities, can result in skeletal changes, including fusion of the cervical vertebrae, variable fusion of thoracic and lumbar vertebrae, bony proliferation and bony protrusion into the vertebral canal in the thoracic and lumbar spine causing compression of the spinal cord, and bony proliferation in the intervertebral foramina causing nerve root compression. Bony proliferative changes and associated spinal cord compression occur prior to, or at the time of, epiphyseal closure (about 9 months of age) and are probably nonprogressive after this time. Mucopolysaccharidosis VI is an inherited abnormality and has an autosomal recessive mode of inheritance. Mucopolysaccharidosis I due to a deficiency in alpha-Liduronidase has been reported in a domestic shorthaired cat. The clinical features were similar to MPS VI, but bony proliferative changes and associated spinal cord compression were not found. Although vacuolar changes were observed in neurons of brain and cervical spinal cord, presumably as a result of storage of glycosaminoglycans, neurologic deficits were not found clinically. Mucopolysaccharidosis I probably has an autosomal recessive mode of inheritance. Clinical Findings. The characteristic physical findings in cases of MPS VI are small head, flat broad face, widely spaced eyes, corneal clouding, small ears, depressed bridge of the nose, large forepaws, and concave deformity of the sternum. Affected kittens are smaller than normal littermates, and physical deformities are noticeable by 8 weeks of age. Neurologic deficits due to skeletal changes and spinal cord compression are seen between 4 and 7 months of age and progress over 2 to 4 weeks. Neurologic findings are indicative of a transverse myelopathy between T3 and L3, and include absent conscious proprioception, normal to exaggerated pelvic limb reflexes, and decreased pain perception in the pelvic limbs. The thoracic limb gait may be normal or affected cats may have a crouching posture. Spinal reflexes in the thoracic limbs are normal. Diagnosis. Radiographs of the spine show vertebral fusion and bony protrusions into the spinal canal and intervertebral foramina of the thoracolumbar spine. However, bony proliferation is not an indication of neurologic dysfunction. Myelography is necessary to demonstrate spinal cord compression. Subarachnoid CSF puncture may be difficult due to proliferative changes around the vertebrae. MPS VI can be confirmed by measurement of arylsulfatase B activity in leukocytes.

Treatment. As skeletal changes are nonprogressive after about 9 months of age, decompressive surgery may result in improvement in neurologic signs. However, spinal cord compression may be present at more than one site. The underlying lysosomal enzyme deficit is not amenable to treatment at present. Bone marrow transplantation is being investigated as a possible therapy for MPS VI.

Neoplasia Etiology and Pathogenesis. The spinal cord may be a site of primary or metastatic neoplasia, or may be compressed or invaded by primary or metastatic tumors arising from the vertebrae and surrounding tissues. Primary neural tumors include astrocytoma, glioma, ependymoma, neuroepithelioma, malignant nerve sheath neoplasm (schwannoma, neurofibroma, neurofibrosarcoma), meningioma, meningeal sarcoma, and reticulum cell sarcoma.Tumors of spinal nerves that extend into the spinal canal or spinal nerve roots may cause extradural or intradural compression of the spinal cord. These tumors may also invade the spinal cord parenchyma. Lymphosarcoma may also involve peripheral nerves and extend along spinal nerves and nerve roots into the spinal canal, resulting in clinical signs of spinal cord disease. Meningeal sarcomatosis is a rare condition characterized by diffuse infiltration of the leptomeninges by neoplastic mesenchymal cells. In one reported case in a dog, clinical signs were lameness, reluctance to sit, apparent spinal pain, seizures, and urinary incontinence. The spinal cord may also be compressed by tumors originating from surrounding structures. Most commonly these tumors arise from bone, cartilage, fibrous tissue, and blood vessels of vertebrae, and less commonly from the hemopoietic elements of bone and tissue outside the vertebral column including muscle, fat, and paraganglia. Secondary tumors result from hematogenous or Iymphatic spread of tumor emboli and include hemangiosarcoma, lymphosarcoma, mammary adenocarcinoma, pulmonary carcinoma, prostatic carcinoma, and malignant melanoma. Epidural Iymphosarcoma is the most commonly occurring spinal tumor in cats. Primary intramedullary tumors rarely occur in cats. Etiology of vertebral and spinal cord tumors is unknown. Lymphosarcoma in cats may be associated with FeLV or FIV infection; however, not all cats with spinal Iymphosarcoma test positive for FeLV or FIV. Clinical Findings. Clinical signs depend on the location of the tumor. Tumors may involve more than one spinal cord segment and more than one spinal tumor may be present, resulting in multifocal signs. However, most animals present with clinical signs referable to a transverse myelopathy. Tumors may occur anywhere within the spinal cord or spinal canal and usually result in progressive neurologic deficits. The duration of clinical signs may vary considerably (from one week to one year in one study). Animals may present with the following signs: an acute onset of severe neurologic deficits associated with pathologic fracture of a vertebra, resulting in spinal cord compression; epidural, subarachnoid, or intramedullary hemorrhage; or spinal cord ischemia associated with tumor expansion. Neurologic deficits are

usually bilateral but may be asymmetric. Tumors of nerves of the brachial plexus initially cause progressive LMN signs in the ipsilateral thoracic limb, including muscle atrophy and paresis. The affected limb is often painful on palpation or movement; cutaneous sensation generally remains intact. If the tumor extends into the spinal canal, UMN signs to the pelvic limbs may become apparent. Tumors of the nerves of the cauda equine or lumbosacral plexus, with extension into the spinal canal, may cause unilateral or bilateral LMN signs in the pelvic limbs, tail, perineum, urinary bladder, and anal sphincter. Apparent pain is a common finding associated with extradural and intradural tumors. Apparent pain may be intractable, especially in animals with a tumor affecting spinal nerve roots. This may be due to stretching or inflammation of the meninges surrounding the expanding tumor. In general, however, extradural, intraduralextramedullary, and intramedullary tumors cannot be distinguished on the basis of clinical findings. Diagnosis. A tentative diagnosis of spinal tumor can be made on the basis of radiographic, CSF, and myelographic findings. Definitive diagnosis can only be made after biopsy of a suspected lesion. Radiography. Bone lysis with a cortical break is the most common radiographic finding in animals with vertebral tumors. Other radiographic findings include destruction of vertebral end-plates, collapse of an adjacent disk space, collapse and shortening of a vertebral body, pathologic fracture, bone sclerosis and bony production, cystlike expansile lesions, or adjacent soft tissue masses. Vertebral lesions may also occur with spread of tumors from surrounding soft tissues into the vertebrae. Bone tumors are not always easily detected by means of radiography, owing to inconsistent vertebral shape, overlying rib and soft tissue shadows, and improper patient positioning. Other diseases, such as bacterial or fungal diskospondylitis, spondylitis, or vertebral osteomyelitis, must be considered in the differential diagnosis of vertebral tumors. Expanding tumors within the spinal canal may result in widening of the vertebral canal and loss of bone density due to ischemia and necrosis of overlying bone. Similarly, tumors of spinal nerves extending into the spinal canal may cause widening of intervertebral foramina. Cerebrospinal fluid analysis. Cerebrospinal fluid may be normal or may have an increased protein concentration and/or white blood cell count. A mild to moderate increase in CSF white blood cell count may occur in animals with tumors arising from or invading the leptomeninges. Polymorphonuclear cells may predominate, probably as a result of meningeal inflammation and necrosis. Tumor cells rarely are found in CSF, except in CSF from animals with lymphosarcoma, in which abnormal lymphocytes are often present in association with meningeal infiltration. Collection of CSF from the lumbar subarachnoid space may yield more cells than cisternal collection, owing to probable caudal flow of CSF in animals. Inability to demonstrate tumor cells in CSF may be the result of the methods used to analyze CSF. The use of cell concentrating techniques that yield a greater percentage of cells present in CSF may result in the preservation of more neoplastic cells. Xanthochromia, suggesting

previous subarachnoid hemorrhage, occasionally is present. Cerebrospinal fluid protein concentration may be increased due to abnormal permeability of blood-spinal cord or bloodmeningeal barrier, as a result of extradural compression or meningeal or parenchymal tumor infiltration. Myelography. Myelography may be helpful in differentiating intramedullary, intradural-extramedullary, and extradural tumors. Cisternal and lumbar injection of contrast material may be necessary to outline both the cranial and caudal extent of a tumor. It is important to obtain survey radiographs of the entire vertebral column prior to and after injection of contrast, as more than one tumor may be present and the neurologic deficits of one tumor may â&#x20AC;&#x153;maskâ&#x20AC;? those produced by another. Several radiographic views (at least lateral and ventrodorsal) are necessary to determine whether a tumor is intramedullary, intradural-extramedullary, or extradural. Tumors may have a mixed myelographic appearance, with extradural, intradural, and/or intramedullary components (e.g., nerve root tumors, meningioma, and spinal cord blastoma). Other Diagnostic Tests. As many spinal tumors are secondary tumors and primary vertebral tumors commonly metastasize, careful attention should be directed toward eliminating the presence of other tumors by performing a thorough physical examination, survey thoracic and abdominal radiographic examinations, rectal examination, complete blood count, and other diagnostic tests as necessary. For example, animals with Iymphosarcoma may show abnormal circulating lymphocytes and/or hypercalcemia, and animals with plasma cell myeloma may show aplastic anemia, myelophthisis, hypercalcemia, elevated serum protein, monoclonal gammopathy on serum electrophoresis, and/or Bence Jones proteinuria. Both CT and MRI aid in exact determination of location and extent of spinal tumors. Use of these advanced imaging modalities aids in precise surgical planning and radiation therapy planning. Biopsy. Biopsy of suspected lesions is necessary to differentiate neoplasms from other vertebral and spinal cord abnormalities and to determine histologic type. An open surgical technique is most often used to obtain an adequate specimen of most spinal tumors; however, in the future, fluoroscopy- or CT-guided needle biopsy techniques will become available for use in dogs and cats. Treatment. The majority of vertebral tumors are not surgically resectable, owing to the malignant characteristics of the tumor and the decreased stability of the vertebral column that may result from extensive surgery. Surgical decompression of the spinal cord and debulking of tumor mass may be palliative in some cases. Some tumors within the spinal canal are surgically resectable, including some tumors that appear intramedullary on myelography, such as spinal cord blastoma. There is not a direct relationship between tumor size and rate of progression or severity of clinical signs. The spinal cord is able to compensate for pressure applied gradually, and animals with spinal tumors may remain ambulatory despite having little normal spinal cord tissue remaining. Compression applied to the spinal cord rapidly, such as may occur with a pathologic fracture, may cause severe and irre-

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4th European FECAVA SCIVAC Congress

versible spinal cord damage. Corticosteroids may decrease spinal cord edema associated with spinal cord tumors and result in clinical improvement for a variable period of time. Radiation therapy and chemotherapy may be helpful in animals with spinal lymphosarcoma. Most chemotherapeutic agents do not cross the blood-spinal cord or blood-CSF barrier in concentrations to eliminate tumor cells in the meninges or spinal cord. Several chemotherapeutic agents, including methotrexate and cytosine arabinoside, may be given intrathecally and have been used in the treatment of meningeal lymphosarcoma and leukemic meningitis. Complications of intrathecal use of chemotherapeutic agents include arachnoiditis and seizures. Chemotherapy may be helpful in the treatment of plasma cell myeloma. Chemotherapy and radiotherapy have not been used in the treatment of a sufficient number of primary spinal cord, nerve root, and meningeal tumors to assess results; however, initial experience suggests that further use of radiation therapy is warranted. Various chemotherapeutic regimens have been used in the treatment of various bone tumors and tumors that metastasize to bone, generally with poor results. Chemotherapy regimens in the future may offer more hope in the treatment of vertebral tumors. In general, the prognosis for animals with nonresectable spinal tumors is poor.

Osteochondromatosis (multiple cartilaginous exostoses) Etiology and Pathogenesis. A skeletal osteochondroma is a cartilage-capped exostosis arising from the surface of a bone formed by endochondral ossification. An animal with a monostotic lesion has a solitary osteochondroma. Polystotic skeletal involvement is called osteochondromatosis (synonyms: multiple cartilaginous exostoses, hereditary multiple exostoses , multiple osteochondromatosis , diaphyseal aclasis, dyschondroplasia, and hereditary deforming chondrodysplasia). There are consistent differences between cats and dogs regarding age of onset of lesions, patterns of skeletal involvement, and pathogenesis. The incidence of feline osteochondromatosis is unknown. Feline osteochondromatosis is characterized by an initial appearance of lesions in the skeleton of mature cats (2 to 4 years of age). Growth of the lesions is progressive. The disease has no apparent sex or breed predilection in cats, and a hereditary pattern has not been demonstrated in cats. Malignant transformation to osteosarcoma has been reported to occur in an osteochondroma of a cervical vertebra in a cat. The incidence of osteochondromatosis in dogs remains undetermined. The disease is frequently demonstrated in the skeleton of dogs radiographed for unrelated reasons. Onset of clinical disease is usually in dogs less than 18 months of age. Onset in mature dogs is infrequently recognized. A hereditary basis has been indicated in dogs, although a sex or breed predilection is not apparent. Continued growth or reactivation of growth of exostoses in dogs is suggestive of neoplastic transformation. The etiology of canine osteochondromatosis is unknown. The current view regarding pathogenesis of feline osteo-

4th European FECAVA SCIVAC Congress

chondromatosis is that the disease is virus-related, and probably virus-induced. The random distribution of lesions is compatible with a hematogenous distribution of a virus. The virus may be FeLV, feline fibrosarcoma virus acting in an atypical manner, or another member of the feline retrovirus family. Clinical Findings. Osteochondromatosis may occur anywhere in the vertebral column but most commonly is found in the thoracic and lumbar spine. The disease may result in spinal cord compression and clinical signs indicative of a progressive transverse myelopathy between T3 and L3. Neurologic deficits are often asymmetric. Diagnosis. Radiographically, vertebral lesions tend to be circular and smooth, with sclerotic borders. Lesions are usually multiple and may be cystic or proliferative, with an increased radiodensity. Myelography is necessary to demonstrate associated spinal cord compression. Extension of exostoses into the spinal canal results in extradural compression of the spinal cord. Surgical biopsy is necessary to differentiate osteochondromatosis from benign bone tumors (osteomas), neoplastic lesions, or infectious processes. Treatment. Treatment of canine osteochondromatosis affecting the vertebral column is unnecessary unless a lesion results in clinical sequelae. An osteochondroma should be removed if it impinges on spinal cord, or if malignant transformation is suspected. Surgical excision of cartilaginous exostoses and spinal cord decompression are the recommended treatments for lesions causing spinal cord compression and neurologic deficits. Intraoperative spinal stabilization may be indicated following lesion removal. The prognosis for dogs that have stopped growing is good; however, the prognosis for animals that are still growing is guarded, as lesions may continue to expand and subsequently result in spinal cord compression. Treatment of feline osteochondromatosis is complicated by the association with FeLV and the progressive nature of lesions in cats. It seems that at best the surgical removal of a lesion may provide only temporary relief to a cat, because of the tendency for excised lesions to recur and for new lesions to develop.

Protozoal myelitis Etiology and Pathogenesis. Toxoplasma gondii infection may cause a focal or disseminated myelopathy in cats. Animals are infected after ingesting meat containing toxoplasma bradyzoites and/or tachyzoites, after ingesting cat feces containing sporulated oocysts, or by transplacental or congenital infection. The infective organism is spread hematogenously to most organs of the body, including the CNS. The incidence of disease associated with Toxoplasma gondii is thought to be low; however, opportunistic infection in immunosuppressed animals may be more widespread than previously reported. Immaturity and concurrent CD virus infection may result in an increased susceptibility of dogs to toxoplasmosis. In dogs with systemic toxoplasmosis, the incidence of CNS involvement is high. In cats, concurrent infection with FeLV or FIV or administration of corticosteroids may predispose to the development of clinical signs

of toxoplasmosis through immunosuppression and reactivation of latent infection. Pathologically, CNS toxoplasmosis lesions are characterized by diffuse perivascular cuffing, infiltration of tissues by inflammatory cells (predominantly mononuclear cells), hemorrhage, necrosis, edema, and neuronal degeneration. Granulomatous reactions may be seen. Encysted or free forms of Toxoplasma gondii may be present. Observed tissue reactions may occur as a result of cell rupture, immune complex deposition, delayed hypersensitivity reaction, or degeneration of toxoplasma cysts. Clinical Findings. Affected animals usually have clinical signs of progressive multifocal or disseminated CNS disease. Clinical signs indicating a focal transverse or diffuse myelopathy only may be seen initially. Neurologic deficits depend on site of involvement and may be UMN or LMN. If lower motor neurons are involved, denervation may result in severe muscle atrophy. Animals with CNS toxoplasmosis may or may not have other clinical signs indicative of systemic infection (fever, Iymphadenopathy, pneumonia, apparent muscle pain, gastrointestinal tract disease, iritis, or chorioretinitis). Diagnosis. Antemortem confirmation of CNS toxoplasmosis in dogs or cats is extremely difficult. Results of routine hematologic and biochemical tests may be abnormal in cats or dogs with acute systemic toxoplasmosis; however, such results reflect only the organ systems involved and are not specific for toxoplasmosis. Cerebrospinal fluid may be normal, or may have an elevated white blood cell count with a mixed mononuclear pleocytosis, and an elevated protein concentration. Xanthochromia may be present if subarachnoid hemorrhage has occurred. Radiography of the thorax or abdomen of animals with acute disease may demonstrate effusion, pneumonia, or abdominal masses. Toxoplasma organisms may be identified in cytologic preparations of thoracic or peritoneal effusions, or in biopsies of Iymph node or muscle examined by conventional histopathologic techniques, or by other methods such as immunoperoxidase staining. It is difficult, however, to be certain of the association between clinical disease and demonstration of organisms. Numerous serologic tests have been used in the diagnosis of toxoplasmosis. Serologic testing for antibody (immunoglobulin G or IgG) is of limited use for determining active infection, unless paired titers done 2 to 3 weeks apart demonstrate a fourfold increase. Certainly, a negative titer does not rule out a diagnosis of toxoplasmosis. Currently it is recommended that for serologic diagnosis of toxoplasmosis in dogs or cats a single serum sample should be submitted for immunoglobulins G and M (IgG and IgM) determinations, and for calculation of levels of circulating antigen to Toxoplasma gondii. Further, in cats suspected of having toxoplasmosis, both FeLV and FIV titers should be determined. Fecal examination for oocysts is the most practical method for determining the public health risk of a cat suspected to have toxoplasmosis. Oocysts are shed in feces of infected cats for only a short time (5 days to 2 weeks postinfection). Treatment. Several antibacterial agents have been recommended for treatment of toxoplasmosis and neosporosis in

dogs and cats. Available drugs are effective in CNS tissues only against actively proliferating forms of the organism, and are not active against encysted forms, which are dependent on host humoral and cell-mediated immune responses for eradication. Clindamycin is currently recommended for treatment of systemic infection of dogs or cats. Oral therapy at a total daily dosage of 12 mg/lb (25 mg/kg) divided ql2h appears effective in cats, whereas a daily dose of 5 to 18 mg/lb (10 to 40 mg/kg) divided q6h or q8h should be effective in dogs. Therapy should be continued for 2 to 4 weeks. The effectiveness of clindamycin in penetrating CNS tissues of dogs or cats has not been determined, and it is therefore recommended that sulfadiazine or triple-sulfas be given orally at a daily dosage of 50 mg/lb divided ql2h for CNS toxoplasmosis. Addition of pyrimethamine at a daily dosage of 0.25 to 0.5 mg/lb permits reduction of the sulfadiazine dosage by half. Hematologic monitoring for bone marrow suppression is essential for cats placed on this therapeutic regimen. The public health risk posed by a cat with active Toxoplasma gondii infection must be considered prior to and during treatment for toxoplasmosis.

Sacrocaudal dysgenesis in manx cats Etiology and Pathogenesis. Manx cats have varying degrees of taillessness associated with sacral and/or caudal vertebral deformities. Some tailless cats have a normal sacrum, spinal cord, and cauda equina. Others show varying dysgenesis or agenesis of the sacral and/or caudal vertebrae that may be associated with spine bifida and/or malformations of the terminal spinal cord and/or cauda equina. Spinal cord malformations include absence or partial development of sacral and caudal spinal cord segments or cauda equina, myelodysplasia, meningocele, meningomyelocele, diastematomyelia of sacral segments (duplication), myeloschisis (cleft within the spinal cord), syringomyelia in the lumbar and sacral spinal cord segments, shortening of the spinal cord, and subcutaneous cyst formation. These spinal cord and cauda equina malformations are associated with variable neurologic deficits. Sacrocaudal dysgenesis is inherited as an autosomal dominant trait and may be lethal in some homozygote cats. Sacrocaudal dysgenesis and associated malformations have been recognized in most breeds of cats, many not of true Manx breeding. Sacrocaudal agenesis in a Maltese kitten has been reported. Clinical Findings. Clinical signs are variable depending on the degree of spinal cord and cauda equina malformation and include paraparesis, paraplegia, megacolon, atonic bladder, absent anal and urinary bladder sphincter tone, absent anal reflex, urinary and fecal incontinence, and perineal analgesia. Affected cats often walk plantigrade in the pelvic limbs with a â&#x20AC;&#x153;bunny-hoppingâ&#x20AC;? gait. Vertebral abnormalities may be palpable in the lumbosacral region, and in some cats a meningocele, congenital or the result of necrosis of the overlying skin, may exit through the skin and drain CSF. Clinical signs usually are evident soon after birth and may remain static or may be progressive. Worsening of neurologic deficits may be due to progressive syringomyelia in

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the lumbar and sacral spinal cord. Diagnosis. Diagnosis is made on the basis of clinical findings and radiographic findings indicative of dysgenesis or agenesis of the sacral and caudal vertebrae. Myelography may demonstrate meningocele or attachment of spinal cord to subcutaneous tissues in the lumbosacral region. The degree of spinal deformity does not always correspond with the degree of neurologic impairment. Clinical findings are the most important factors to consider in determining prognosis. Treatment. Prognosis for severely affected cats is hopeless and treatment is not available. Cats with urinary and fecal incontinence may be managed with manual bladder expression and fecal softening agents; however, recurrent urinary tract infection, megacolon, and chronic constipation are common problems. Meningocele in cats with minimal neurologic deficits may be surgically correctable. Many tailless cats do not have neurologic deficits, and sacral and caudal deformities often are an incidental radiographic finding.

Spina bifida Etiology and Pathgogenesis. Spina bifida is a term used to describe a group of developmental defects characterized by failure of fusion of the vertebral arches with or without protrusion or dysplasia of the spinal cord, meninges, or both. It has been described in cats. Malformations have been variously named spine bifida occulta, cystica, manifesta and operta, depending on whether vertebral arch only, vertebral arch and spinal cord, and/or meningeal abnormalities are present. Anomalies of the vertebral arch and spinal cord are influenced by the development of the neural tube. Normally an area of embryonic ectoderm thickens along the dorsal midline to form the neural plate. The neural plate subsequently folds (forming the neural groove and then the neural tube that separates from the ectoderm and develops into the spinal cord) and is surrounded by the sclerotomic masses that form the vertebrae. Spina bifida is a midline cleft in one or more vertebral arches. The cleft may consist of only nonfusion of the dorsal spinous processes, or most of the vertebral arch of one or several adjacent vertebrae may be absent. The spinal cord and meninges may be normal (spine bifida occulta) or may be abnormal and there may be protrusion of the meninges and/or spinal cord through the vertebral defect. Spina bifida may be caused by nonfusion of the two halves of the primordial vertebral arch due to failure of the neural tube to close as the result of overgrowth of the cells of the neural tube, or may be due to cleft formation in the neural tube after closure. It has been suggested that after formation of the neural tube, clefts split its dorsal wall and a neuroschistic bleb encroaches on the somites and prevents fusion of the vertebral arches. If the neuroschistic bleb is retained, defects of the spinal cord occur. Healing of the bleb may also occur and result in spine bifida occulta (vertebral arch defect without concomitant spinal cord abnormalities). Myelodysplasia consisting of hydromyelia, syringomyelia, anomalies of the dorsal septum, anomalies of the central gray matter, abnormal position of the central gray

4th European FECAVA SCIVAC Congress

matter, anomalies of the dorsal and ventral horns, and myeloschisis (cleft in the dorsal part of the spinal cord) may occur in association with spine bifida. The most severe defects involve myelorachischisis, with superficial location of the neuroectoderm that is continuous with the skin. Myelorachischisis may be due to failure of the formation of the neural tube or rupture of the neuroschistic bleb after neural tube closure. Spina bifida with myelorachischisis has been reported to occur in dogs and cats. Etiology of spine bifida is unknown and probably multifactorial with genetic and environmental components. Nutritional factors may have a role in the neural tube defects. Spina bifida can be induced in the offspring of laboratory animals by exposing pregnant females to a variety of chemical or environmental toxins. Clinical Findings. Spina bifida is usually an incidental radiographic finding; however, if associated with spinal cord malformations, it may result in clinical signs of spinal cord or cauda equina dysfunction. Large dorsal arch defects are most often associated with spinal cord abnormalities. There is a high incidence of spine bifida in English bulldogs. Spina bifida may occur anywhere in the spinal column but occurs most commonly in the caudal lumbar spine where clinical signs are indicative of a transverse myelopathy from L4 to S3 spinal cord segments (pelvic limb ataxia or paresis, complete paraplegia, fecal and urinary incontinence, decreased or absent anal and urinary bladder sphincter tone, perineal analgesia, and decreased spinal reflexes in the pelvic limbs). Clinical signs usually become evident when affected animals start to walk. Spina bifida also has been reported in the thoracic spine of a dog and may be associated with other spinal deformities such as scoliosis. Other associated anomalies include dimpling of the skin or â&#x20AC;&#x153;streamingâ&#x20AC;? (abnormal direction) of the haircoat over the affected region or a palpable abnormality in the spinal column. Meningoceles may cause necrosis of the overlying skin and drainage of CSF. Meningoceles may be present in the absence of clinical signs associated with spinal cord malformation. Diagnosis. Absence of the vertebral arch or failure of fusion of the dorsal spinous processes in one or more vertebrae may be evident on plain radiographs. Myelography may demonstrate meningocele. Treatment. Treatment is not effective for affected animals with clinical signs of spinal cord malformation. Meningocele may be amenable to surgery if neurologic abnormalities are not evident. Treatment is not necessary for animals with vertebral defects in the absence of spinal cord dysfunction (spine bifida occulta).

Spinal cord trauma Etiology and Pathogenesis. Acute spinal cord injuries of dogs or cats result most commonly from direct physical trauma such as missile injury or vertebral fracture or luxation. Also, spinal cord trauma is the underlying cause of neurologic signs in numerous myelopathies (e.g., intervertebral disk protrusion or extrusion). Chronic spinal cord compression usually is seen in association with chronic progressive

diseases such as neoplasia or type II disk protrusion. Following injury, the spinal cord may undergo sustained compression, distraction, or both. The severity of a spinal cord injury, as determined by the eventual degree and quality of recovery, is related to three factors: the velocity with which the compressive force is applied, the degree of compression (transverse deformation), and the duration of the compression. The relative roles of these factors in determining the severity of a spinal cord injury have yet to be determined. An understanding of differences between acute and chronic spinal cord injury is essential for effective management and determination of prognosis in cats or dogs with spinal trauma. Extensive experimental work has been done in order to elucidate the mechanisms involved in the production of lesions following spinal cord trauma, and results of such research provide information that is essential for effective therapy of spinal injuries. Acute Spinal Cord Injury. It has long been recognized that blunt traumatic injury to the spinal cord causes neurologic deficits through both direct and indirect mechanisms. The direct effects are due to immediate disruption of neural pathways in spinal gray or white matter produced by the trauma. These effects have also been termed “immediate” effects and have been considered by most investigators not to be amenable to therapy. Indirect effects develop during the first few hours following injury, and result in delayed secondary injury to the spinal cord. The mechanisms of this secondary process remain largely undetermined, however, it is likely that they result in part from release of endogenous pathophysiologic factors in response to the initial trauma. It has been hypothesized that such factors produce injury by reducing spinal cord blood flow or by altering the local metabolic environment within injured spinal cord tissue. The secondary damage has been considered potentially reversible through the use of either physical (e.g., hypothermia) or pharmacologic interventions. Trauma to the spinal cord triggers a progressive series of autodestructive events that lead to varying degrees of tissue necrosis, depending on the severity of the injury. Pathologic changes that occur in traumatized spinal cord tissue include petechial hemorrhages that progress to hemorrhagic necrosis, lipid peroxidation, lipid hydroxylation with subsequent prostaglandin and leukotriene (eicosanoid) formation, loss of calcium ions from the extracellular space and loss of potassium ions from the intracellular space, ischemia with consequent decline in tissue oxygen tension and energy metabolites and development of lactic acidosis, and inflammation and neuronophagia by PMN leukocytes. In spite of extensive investigation, the mechanisms responsible for the initiation and propagation of these pathophysiologic and biochemical events remain undetected. Recent evidence suggests, however, that the overall initiator of this autodestructive cascade of events is mechanical deformation of any type (i.e., impact or compression injury), and that the primary sites of injury are the cellular and subcellular membranes of glia, neurons, and vascular endothelial cells. Lipid peroxidation and activation of membrane lipases, with release of fatty acids leading to production of eicosanoids, are the earliest mechanically stimulated bio-

chemical events described at the present time. The sequence of pathologic alterations that occurs following spinal cord injury has been reviewed by several authors. Within 5 minutes of injury postcapillary venules become congested. This is followed by opening of endothelial gap junctions here and at the capillary level, resulting in diapedesis of red blood cells and extravasation of fluid proteins and electrolytes through the “leaky” vasculature. Within 30 minutes of injury, microscopic hemorrhages appear in the central gray matter, and coalesce over the following several hours (central hemorrhagic necrosis). Vacuolization develops within endothelial cells, indicating a profound ischemic or hypoxic insult, which subsequently leads to coagulative necrosis of the neuronal population. Adjacent white matter is relatively less severely affected; however, periaxonal swelling and retraction balls may be observed. These events may lead to autodissolution of the spinal cord within 24 hours, even in the absence of ongoing mechanical compression. A special feature of spinal cord injury is progressive hemorrhagic myelomalacia. This condition occurs following spinal cord trauma and appears to be a progression of central hemorrhagic necrosis and edema to areas of the spinal cord not directly involved in the initiating injury. Chronic Spinal Cord Compression. It has been shown experimentally that when slow compression of the spinal cord is compared to dynamic (or rapid) compression of an equal amount, the extent of spinal cord dysfunction is determined by the contact velocity of compression. The major pathologic substrate for neural dysfunction after slow balloon compression is thought to be physical injury to the neural membranes, irrespective of blood flow changes, and the ability of that membrane to recover appears to be related to rapidity and duration of compression. Clinical observations support the conclusion that spinal cord conduction is resistant to slow compression. Further, it has been demonstrated that levels of compression that do not have an effect when applied slowly cause an immediate loss of conduction through the injured site when applied rapidly. Chronic spinal cord compression results either from a slowly developing lesion (e.g., neoplasia), or from an acute compression that is sustained. In contrast to acute spinal cord injury, chronic compression affects white matter more severely than it affects gray matter. Hemorrhage and edema, the major findings of acute trauma, are not significant in chronic compression. Characteristic lesions are degeneration of myelin, focal areas of malacia, vacuolization, and loss of white matter axons. Mechanical deformation is likely to be the major factor in pathogenesis of these lesions; however, ischemia and venous obstruction also may be important considerations. Clinical Findings. Acute Spinal Cord Injury. Dogs or cats with a spinal injury frequently have serious injuries to other organ systems. A primary concern is to balance the relative urgency of non-neurologic injuries (hemorrhage, shock, airway obstruction, or limb fractures) and the need for early treatment of spinal cord injury. A complete neurologic examination is done to localize the site(s) of injury and to determine severity. Careful palpation of the vertebral column may aid in identification of a vertebral fracture or luxation. Administration of tranquiliz-

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ers or analgesic drugs should be delayed until completion of the neurologic examination, as such medications may alter an animalâ&#x20AC;&#x2122;s responses. A neurologic examination should be done with care to prevent further injury resulting from excessive movement of a vertebral instability. Several aspects of the neurologic examination are of special importance in assessment of a dog or cat with a spinal cord injury. Recognition of the Schiff-Sherrington sign is important. Following trauma, this sign must be differentiated from other postures associated with cranial injury (e.g. decerebrate rigidity or decerebellate posture). Both deep and cutaneous pain perception should be assessed, as results of these tests are important in determining prognosis. It should be remembered that vertebral column injuries may be multiple, and that a neurologic examination may not indicate presence of a second lesion. Chronic Spinal Cord Compression. Clinical signs of chronic spinal cord compression may progress over weeks or months, or may be seen to occur acutely. Acute onset of neurologic signs with chronic spinal cord compression frequently is seen in association with such disorders as spinal neoplasia or type II disk protrusion. Sudden onset of signs may accompany pathologic fracture of a vertebra, and spinal cord hemorrhage or infarction. In some cases sudden decompensation of chronically compressed spinal cord may occur in the absence of pathologic changes. In these cases it is assumed that compensatory mechanisms within the spinal cord are exhausted, and that sudden decompensation has occurred. Diagnosis. Acute Spinal Cord Injury. Results of a neurologic examination are used to determine the site and severity of a spinal injury. Radiographs of the entire spinal column should be done. Two radiographic views are essential. Ventrodorsal views may be accomplished by means of a horizontal beam. Evoked spinal cord potential testing may be of use in determining location and severity of a spinal cord lesion in animals following trauma. The objectives of radiographic examination of an animal following acute spinal trauma are the following: precise determination of location and extent of a lesion, demonstration of multiple lesions that may not be apparent on the basis of a neurologic examination, and assessment of the need for surgical therapy and determination of the most appropriate surgical procedure to be used. Accurate interpretation of radiographs depends on a knowledge of results of a neurologic examination. We recommend that a myelogram be completed in animals that have sustained spinal trauma. Results of a myelogram may determine the extent of spinal cord swelling resulting from concussion in animals without evidence of a spinal fracture or luxation, and may confirm that surgical decompression by means of laminectomy is not necessary in animals with a fracture that is evident on plain radiographs. In the diagnosis of intervertebral disk disease a myelogram is considered essential prior to surgery. Chronic Spinal Cord Compression. Methods for diagnosis of chronic spinal cord compression are the same as for acute spinal cord injury. A myelogram is considered essential in all such cases. Treatment. Management of an animal with spinal trauma

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follows a list of priorities, with the focus of treatment being prevention of secondary spinal cord damage that occurs after the initial injury. Immediate treatment of nonneural injuries is limited to those problems that are life-threatening, such as shock or hemorrhage. Acute Spinal Cord Injury. Treatment of acute spinal cord trauma should always be instituted as soon as possible following injury. The specific objectives of therapy are the following: relief of edema, control of intra- or extramedullary hemorrhage, relief of spinal cord compression, and, in cases of vertebral fracture/luxation, removal of bone fragments from the spinal canal and stabilization of the vertebral column. Treatment of acute spinal cord trauma may be medical, surgical, or a combination of both. Based on experimental findings in a large number of experimental models in animals, a variety of medical treatments have been advocated for the treatment of acute spinal cord injury. Recently, interest has focused on the use of antioxidants and free radical scavengers. Unfortunately, the role of these numerous therapies in the management of a dog or cat with a spinal injury remains to be determined. The large number of suggested therapies underlines the fact that the mechanisms responsible for delayed secondary effects in the injured spinal cord are incompletely understood. Corticosteroids are routinely and widely used in the treatment of acute spinal cord injury. Despite a positive clinical impression that corticosteroids have beneficial effects, their use is controversial. Some studies have failed to demonstrate significant improvement of neurologic recovery in association with corticosteroid administration. The use of low or high doses of corticosteroids in the treatment of spinal trauma also has yielded conflicting results. Use of high doses of corticosteroids may result in complications leading to increased morbidity and mortality (e.g., gastrointestinal bleeding, pancreatitis, colonic perforation); therefore, low-dose regimens are recommended. Dexamethasone sodium phosphate should be given at an initial dosage of 0.25 to I mg/lb IV, and may be repeated at a dose of 0.1 mg/lb q6h or q8h. Immediate post-trauma administration of methylprednisolone sodium succinate (60 mg/lb divided q8h) has been demonstrated to be effective in preserving feline spinal cord tissue following injury. A decision regarding surgical therapy must be made as soon as non-neural injuries have been treated and medical management has been instituted. Ideally, this is within 2 hours of injury. Indications for surgery following spinal cord injury are the following: moderate to severe paresis, or paralysis, associated with myelographic evidence of spinal cord compression; progressive worsening of neurologic signs despite adequate medical therapy; and luxation or fracture of the vertebral column, in association with distraction, malalignment, instability, or myelographic evidence of spinal cord compression. Any animal with sustained compression of the spinal cord following injury, regardless of the cause, must be considered a candidate for surgical decompression of the spinal cord. In general, it is best to initiate surgical therapy in any animal in which there is uncertainty regarding the indications for surgical versus medical therapy. Neurosurgical procedures require specialized knowledge and equipment, and prompt referral to a qualified surgeon

may be indicated. The major objectives of surgical management of spinal trauma are decompression of sustained spinal cord compression and realignment and stabilization of vertebrae if necessary. Surgical decompression by means of laminectomy is beneficial when there is myelographic evidence of extradural spinal cord compression. Laminectomy alone is not sufficient for decompression in most cases, and the compressing mass (e.g., disk material, hematoma, bone fragments) should be removed when possible. In cases in which spinal cord swelling is the major source of compression, or in which there is discoloration of the spinal cord, durotomy or myelotomy may be combined with laminectomy. The most effective methods for alignment and stabilization of the vertebral column require surgical exposure and can therefore be done at the time of decompression. Satisfactory methods of external fixation of spinal fractures do not exist. Methods of surgical fixation have been reviewed by several authors. Use of polymethyl methacrylate and Steinmann pin fixation for the majority of spinal fractures or luxations is favored by these authors. Surgical management of spinal cord injury of animals provides the best opportunity for rapid and complete recovery in animals with sustained compression or instability, and facilitates postinjury care, as the risk of further injury resulting from movement of an unstable vertebral column is minimized. However, conservative management, including strict confinement for 4 to 6 weeks, may be efficacious in animals with minimal neurologic deficits and without myelographic evidence of sustained spinal cord compression or vertebral displacement or instability. Regardless of the type of stabilization used, strict confinement is recommended for 2 weeks after surgery. Potential complications encountered in dogs or cats with a spinal injury include development of a urinary tract infection or pressure sores. Careful attention to nursing care is essential regardless of the type of therapy. Prognosis for an animal with an acute spinal cord injury depends on numerous factors; however, results of a neurologic examination should be the main determinant. Assessment of pain perception is essential for accurate prognosis. Perception of a painful stimulus must be differentiated from reflex activity that is mediated at the level of the spinal cord. Owners of affected animals should be made aware at the outset of therapy of factors such as prognosis, expense involved, expected time from treatment to recovery, and the need for prolonged physical therapy in most cases. Following a severe spinal injury, an animal may require many months to recover, and residual neurologic deficits may persist. Chronic Spinal Cord Compression. The approach to treatment of chronic spinal cord compression is different from that for acute spinal cord injury. As previously stated, hemorrhage and edema usually are not prominent factors in chronic compression. Therefore medical management by means of corticosteroids would not be expected to be efficacious; however, many animals with chronic spinal cord compression improve clinically following corticosteroid administration. The reason for such a response is undetermined; however, it may be due to effects of corticosteroids at the

membrane level resulting in improved conduction in remaining axons. Occasionally, animals may be maintained for months or years by means of corticosteroid therapy alone. Surgical decompression of the spinal cord should be approached with caution in animals with chronic spinal cord compression. Pathologic alterations within the spinal cord may be irreversible, in which case the most that may be achieved is to arrest progression of neurologic deficits. In some cases compensation for the irreplaceable loss of neural tissue may occur. Neurologic status may be worsened by surgical decompression, even with meticulous surgical technique. Such deterioration may be the result of reactive hyperemia that follows decompression, which in turn results in vascular protein leakage in the affected spinal cord segment. However, surgical decompression should be considered in most animals that have neurologic deficits associated with chronic spinal cord compression.

Syryngomyelia and hydromyelia Etiology and Pathogenesis. A distinction cannot be made clinically between syringomyelia (cavitation of the spinal cord) and hydromyelia (dilation of the central canal). Syringomyelia may occur secondary to hydromyelia (communicating syringomyelia) or may not communicate with the central canal (noncommunicating syringomyelia). Syringomyelia may be associated with spinal cord tumors, myelitis, meningitis, and spinal cord trauma. The cause of syringomyelia is not known, but the condition may result from venous obstruction or distention, or may be due to mechanical disruption or shearing of spinal cord tissue planes. Hydromyelia with or without syringomyelia may be associated with congenital malformations such as myelodysplasia; meningomyelocele or hydrocephalus; or lesions resulting in obstruction of CSF flow into the spinal subarachnoid space at the foremen magnum such as chronic arachnoiditis, trauma, congenital malformations, and vascular malformations; or it may be idiopathic. Hydromyelia and syringomyelia in these animals probably results from intracranial and spinal cord venous or arterial pressure changes and associated CSF pressure changes. Syringomyelia in Weimaraner dogs with myelodysplasia may be the result of progressive hydromyelia, abnormalities in the central canal, or abnormal vascular patterns in local areas of the spinal cord leading to low-grade ischemia, degeneration, rarefaction, and cavitation in the spinal cord. Regardless of the cause, cavitation can be progressive, probably along planes of structural weakness such as the gray matter of the dorsal horns, and subsequent necrosis and edema of spinal cord parenchyma around such a cavitation (or dilated central canal) can result in the onset and progression of clinical signs. Clinical Findings. Clinical signs depend on the location of the lesion and whether or not other spinal cord lesions are present. Clinical findings include progressive spinal deformity (scoliosis, torticollis), LMN or UMN signs, depending

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on location, and apparent spinal pain. Clinical signs may be acute or may be progressive over weeks to several years. In Weimaraner dogs with myelodysplasia, clinical signs do not appear to be progressive. Diagnosis. Myelography may show obstruction of the flow of CSF at the foremen magnum if hydromyelia or syringomyelia is due to chronic arachnoiditis or arachnoid adhesions. Cisternal puncture for the collection of CSF is contraindicated in these animals owing to likely inadvertent puncture of the spinal cord. Lumbar CSF may show evidence of chronic inflammation. Myelography in other cases may be normal or may show intramedullary swelling of the spinal cord. Computed tomography of the spinal cord may be useful in the diagnosis of cavitary lesions of the spinal cord. Treatment. Treatment in dogs has not been reported. Surgical drainage of cavitary lesions in humans has resulted in improvement in some cases.

4th European FECAVA SCIVAC Congress

EUROPEAN SOCIETY OF FELINE MEDICINE - ESFM

Feline neuromuscular disorders Richard A. LeCouteur VMD, BVSc, PhD, Dipl ACVIM (Neurology), Dipl ECVN Professor of Neurology and Neurosurgery Department of Surgical & Radiological Sciences - School of Veterinary Medicine University of California, Davis, California - USA

Summary Neuromuscular diseases are generally classified according to the disease location, that is disease involving 1) peripheral nerves, 2) neuromuscular junctions, or 3) muscle. Feline neuromuscular diseases produce signs of lower motor neuron disease, however significant variation in clinical signs may occur depending on the location of the lesion. Hyporeflexia, hypotonia, ataxia, and proprioceptive positioning deficits are most characteristic of feline peripheral nerve disease. Some primary muscle diseases may be characterized by muscle hypertrophy rather than atrophy, and neuromuscular junction disorders result in a variety of clinical signs, that range from flaccid paralysis to exercise-induced weakness. Diagnosis of feline neuromuscular diseases requires a complete neurological examination, minimum data base, electrophysiological evaluation, and muscle/nerve biopsies.

INTRODUCTION Feline neuromuscular diseases may be classified according to their location as (1) those involving peripheral nerves and/or nerve roots, (2) those involving the neuromuscular junction, and (3) those that involve muscle. Each of these neuromuscular diseases will produce lower motor neuron (LMN) disease, however significant variation in clinical signs may occur. Peripheral nerve and muscle diseases result in varying degrees of paresis, muscle atrophy, hyporeflexia, and hypotonia. Hyporeflexia, hypotonia, ataxia and proprioceptive positioning deficits are most characteristic of peripheral nerve disease. Some primary muscle disorders may be characterised by muscle hypertrophy rather than atrophy. Neuromuscular junction disorders (â&#x20AC;&#x153;junctionopathiesâ&#x20AC;?) result in a variety of clinical signs, that range from flaccid paralysis to exercise-induced weakness. Cervical ventroflexion is a dramatic sign of generalised neuromuscular weakness in cats.The chin usually rests near the thoracic inlet, with the eyes positioned dorsally to maintain a straight-ahead gaze. Other common physical examination findings are a slight protrusion of the dorsal aspects of the scapulae when weight is placed on thoracic limbs, and a stiff thoracic limb gait. A crouched, wide-based stance is often seen in pelvic limbs. Possible causes to consider for this posture are: subacute or chronic organophosphate toxic-

ity, potassium-depletion myopathy, thiamine-responsive neuromuscular weakness, hyperthyroidism, immune-mediated (idiopathic) polymyositis, myasthenia gravis, polyneuropathy, hypernatraemic polymyopathy, ammonium chloride toxicity, hereditary myopathies (Burmese, Devon rex), hypocalcaemia, and portosystemic encephalopathy. Megaoesophagus has rarely been reported in cats, although a predisposition has been noted in Siamese and Siamese-related breeds. In most cats the cause of acquired megaoesophagus is unknown; however, the condition has been associated with several systemic neuromuscular disorders, such as myasthenia gravis, botulism, polymyositis, polyradiculoneuritis, tick paralysis, lead toxicosis, feline muscular dystrophy-like conditions, laryngeal paralysis/polyneuropathy complex, and glycogen storage diseases. Diagnosis of feline neuromuscular diseases requires a complete neurological examination, minimum data base (full blood count, serum biochemistry panel, urinalysis, thoracic radiographs), electrophysiological evaluation, and muscle/nerve biopsies.

NEURONOPATHIES Feline Dysautonomia Feline dysautonomia (Key-Gaskell syndrome) is a generalised disorder of autonomic ganglia recognised in cats in the United Kingdom in 1981, and more recently in other countries. There is no age or breed predilection for this disease. The disorder is a neuronal disorder; however, clinical signs relate more to autonomic dysfunction, and are largely gastrointestinal in nature. The most common signs are depression, anorexia, constipation, dry external nares and oral mucosa, reduced tear production, regurgitation, protrusion of the membrana nictitans, mydriasis, and bradycardia. These signs usually occur acutely, but may progress insidiously over a week or more.

Tetanus Although cats are supposedly resistant to the effects of the Clostridium tetani exotoxin, several cases of tetanus have been reported in this species. The toxin interferes with re-

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lease of neurotransmitters from inhibitory interneurons in the spinal cord. Local tetanus has been reported in cats, where the disease is characterised by tonic rigidity of a single limb.

4th European FECAVA SCIVAC Congress

first noted in cats at 8-10 weeks of age. Affected cats fell frequently and had a tendency to stand and walk on their hocks, which they held in an adducted position. The gait was characterised by a slight hypermetria in all limbs and there was progressive pelvic limb ataxia.

INHERITED POLYNEUROPATHIES Sphingomyelinase-deficiency polyneuropathy

ACQUIRED POLYNEUROPATHIES

Niemann-Pick disease (NPD) is an autosomal-recessive lysosomal-storage disease characterised by a deficiency of sphingomyelinase. A NPD-associated primary polyneuropathy has been described in 3 Siamese cats (25 months of age). Neurological signs included a progressive tetraparesis and ataxia, a plantigrade/palmigrade stance, fine generalised tremors, and hypo- or areflexia. Hepatosplenomegaly was also present in affected cats. This disease is progressive and fatal.

Diabetic polyneuropathy A distal polyneuropathy has been reported in cats with uncontrolled or poorly controlled diabetes mellitus. Neurological abnormalities include a plantigrade stance, progressive paraparesis, muscle atrophy, and patellar hyporeflexia. The cause of this polyneuropathy is incompletely understood.

Ischemic neuromyopathy Hyperchylomicronemia-associated neuropathy Inherited primary hyperchylomicronemia is a suspected autosomal-recessive disease characterised by fasting hyperlipemia, lipemia retinalis, and peripheral neuropathy. Clinical signs are usually not seen prior to 8 months of age. Compression by lipid granulomas of peripheral, cranial, and sympathetic nerves, especially at the level of the intervertebral foramina, results in neurological signs. Resolution of neurological signs and decrease in blood-lipid levels occurs following 2-3 months of dietary management.

Hyperoxaluric peripheral neuropathy Primary hyperoxaluria is a suspected autosomal-recessive disease of domestic short-hair cats in Great Britain. Acute renal failure, in cats between 5 and 9 months of age, results from renal tubular deposition of oxalate crystals. Severe generalised LMN weakness accompanies the renal failure. Weakness is attributed to accumulation of neurofilaments in ventral nerve roots, proximal axons, and intramuscular nerves. All reported cats died before 12 months of age. The pathogenesis of peripheral nerve lesions is unknown.

Hypertrophic polyneuropathy Hypertrophic polyneuropathy has been described in 2 unrelated 12-month-old cats. Affected cats had intention tremors, decreased postural reactions, hyporeflexia, and mild sensory loss.

Birman cat distal polyneuropathy A degenerative polyneuropathy has been reported in several litters of Birman cats bred from the same parents. A recessive mode of inheritance is suspected. Clinical signs were

Ischemic neuromyopathy occurs in cats with cardiomyopathy, subsequent to thrombosis of the caudal aorta or its principal branches. The ischemic injury to both muscle and peripheral nerve is produced by collateralcirculation vasoconstriction induced by substances such as serotonin and thromboxane A2 released by platelets trapped in the thrombus.

Trauma Brachial plexus avulsion produced by severe thoracic limb abduction with secondary stretching or tearing of nerve roots is a commonly occurring peripheral nerve injury of cats. Sacroiliac fracture/dislocation, sacral fracture, or caudal vertebral fracture/luxation may result in damage to the sixth and seventh lumbar and first 2 sacral nerve roots. Mononeuropathies of radial nerve and sciatic nerve occur in cats following mechanical blows, gunshot wounds, fractures, pressure and stretching.

Neoplasia Feline malignant lymphoma, often associated with FeLV-infection, may involve nerve roots or peripheral nerves. Other primary peripheral nerve neoplasms are rarely seen in cats.

Toxic neuropathies Drug-induced neuropathies are not well defined in dogs and cats. It is likely that as chemotherapeutic treatment of neoplasia becomes more aggressive, more drug-induced neuropathies will be recognised (e.g. vincristine). A delayed neurotoxicity may occur in cats days or weeks after minimal exposure to organophosphates. Lesions are associated with distal degeneration of motor nerves that begins in the periphery (dying-back axonopathy). Peripheral neuropathy may occur

sporadically with spontaneous lead-poisoning. Megaesophagus and partial laryngeal paralysis, believed to be due to leadassociated neuropathy, have been reported in a cat.

The association of acquired myasthenia gravis and thymoma in cats is a good example of a paraneoplastic junctionopathy.

INHERITED MYOPATHIES Laryngeal paralysis Muscular dystrophy Acute laryngeal paralysis was diagnosed in 3 cats with signs of upper airway obstruction, including dysphonia, absence of purring, and progressive inspiratory dyspnea. Varying degrees of paralysis of vocal folds and arytenoid cartilages were noted. One cat was positive for FeLV. Underlying responsible mechanisms were not defined.

Miscellaneous peripheral polyneuropathies Single case reports exist of a variety of peripheral neuropathies in cats. These include: 2 cats with histologicallyconfirmed inflammatory polyneuropathy (a chronic relapsing polyradiculoneuritis) and an acute polyneuritis, an idiopathic chronic relapsing polyneuropathy responsive to immunosuppressive glucocorticoid therapy and an acute brachial plexus neuropathy with a suspected relationship to a previous vaccination. It is reasonable to expect that there will be future reports regarding FeLV and FIV infections and their association with neuromuscular diseases of cats, particularly polyneuropathies. Paraneoplastic neuropathies and radiation-induced neuropathies of cats are likely to be reported in the future.

“JUNCTIONOPATHIES” Myasthenia gravis Myasthenia gravis is a condition that results from either a congenital or an acquired reduction of acetylcholine receptors of neuromuscular junctions. Both forms have been reported to occur in cats. Two of the acquired cases were associated with thymoma, and another with a cystic thymus. Acquired myasthenia gravis has been reported frequently in Abyssinians and Somalis (closely related to Abyssinians), which may suggest a possible association with the major histocompatibility complex, as in humans. The most consistent signs in cats include tremors, initial stiffness with progression to generalised weakness on exercise, cervical ventroflexion, dysphagia, dysphonia, ptyalism, facial weakness, and dyspnea. Overt megaesophagus or esophageal hypomotility is common.

Miscellaneous “Junctionopathies” Abnormalities in neuromuscular junction function may also result from tick paralysis, administration of certain drugs, selected toxins, or from envenomation. Botulism has not been reported as a clinical entity in cats, however, it may be produced experimentally in cats. Paraneoplastic junctionopathies are likely to be reported in cats in the future.

Muscular dystrophy-like disorders of cats have been reported in the Netherlands and the U.S.A. To date all affected cats have been males, which suggests an X-linked inheritance. Clinical signs may first be seen in cats at 5-6 months of age, and include generalised skeletal muscle hypertrophy, excessive salivation, reduced exercise tolerance, stiff gait and “bunny-hopping” when running, difficulty in jumping, adducted hocks, cervical rigidity, vomiting/regurgitation, and partial protrusion of the tongue.

Hereditary myopathy of devon rex cats This is a congenital myopathy of Devon rex cats. Characteristic clinical signs, including ventroflexion of the head and neck, protrusion of the scapulae, and esophageal weakness, all reflect dysfunction of striated muscle, while skeletal muscle pathology is suggestive of a muscular dystrophy.

Nemaline myopathy A suspected inherited myopathy has been described in 5 related cats between 6-18 months of age, with an onset of reluctance to walk and a forced, rapid, abrupt, hypermetric gait. Other signs included muscle tremors, hyporeflexia, and muscle atrophy which was more pronounced in proximal limb musculature. This myopathy is characterised by large but variable numbers of nemaline rods within myofibres.

Myositis ossificans Generalised ossifying myositis, a non-neoplastic form of heterotopic ossification affecting skeletal muscle and fibrous connective tissue, has been described in 2 young cats with a history of progressive weakness, stiffness, difficulty in jumping, decreased range of limb motion, and pain on forced movement.

Miscellaneous inherited myopathies Glycogen storage diseases (or glycogenoses) are rare disorders of cats. Deficient activity of one of the enzymes involved in glycogen degradation or synthesis results in inadequate glycogen utilisation, and in glycogen accumulation within various tissues, including muscle. There are several reports of glycogenoses in cats. Glycogen storage disease Type IV has been reported in 3 young related Norwegian forest cats.

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ACQUIRED MYOPATHIES

Potassium-depletion polymyopathy

Infectious polymyositis

This acute feline polymyopathy, resulting from a severe total body potassium depletion, is usually secondary to a reduced potassium intake and increases in the fractional excretion of potassium in urine (due to renal dysfunction). Clinical signs include muscle weakness, cervical ventroflexion, stiff and stilted gait, and muscle pain. A similar syndrome with a suspected hereditary basis has been reported to occur in Burmese cats.

Infectious myositis may occur in association with bacterial infection, migrating parasites, or protozoan disease. Whilst cats are the only definitive hosts for Toxoplasma gondii (and a majority of cats may have serum antibodies to this organism) muscle involvement is not an outstanding feature of Toxoplasma infection of cats. Experimental inoculation of cats with the protozoan Neospora caninum may produce fatal, necrotising encephalomyelitis, polymyositis, pneumonia and hepatitis. Naturally-occurring feline neosporosis has not been reported to date.

Immune-mediated (or Idiopathic) polymyositis Polymyositis occurs sporadically in cats, occasionally in association with thymoma. Inflammatory infiltrates are predominantly mononuclear with small lymphocytes and macrophages. Neutrophils are seen infrequently. Eosinophils are rarely seen. Clinical signs are characterised by a persistent cervical ventroflexion, appendicular weakness, painful muscles, and exercise intolerance. Serum levels of creatine kinase and aldolase are elevated. A report of polymyositis in a cat in association with myasthenia gravis and thymoma further supports an immune-mediated aetiology.

Miscellaneous myopathies There are a number of case reports of muscle-related diseases of cats. Descriptions include: nutritional myopathy secondary to vitamin E deficiency myositis secondary to Clostridium chauvoei and Clostridium septicum infections fibrotic myopathy of the semitendinosus muscle and quadriceps contracture secondary to trauma. Episodic weakness and signs of depression have been noted in young domestic short-hair cats (less than 1 year of age) with hypernatraemia secondary to hypodypsia. The most common clinical sign of hypernatraemic myopathy is ventral flexion of the neck. Causes of hypodypsia include lesions of the hypothalamus, and mechanical inability to swallow - a potentially serious complication of hypertrophic feline muscular dystrophy. The association between myositis and malignant neoplasia (paraneoplastic myopathy) is likely to be reported in the future. Myopathies in cats may occur in association with FeLV or FIV infections (e.g. FeLV-associated immunosuppression may enable encystment of Sarcocystis spp. in muscle).

EUROPEAN SOCIETY OF COMPARATIVE GASTROENTEROLOGY

The pathophysiology of retained bile acids Denny Meyer DVM, Dipl ACVIM, Dipl ACVP NeXstar Pharmaceuticals, Boulder, Colorado - USA

Summary Bile acids of mammals and birds are amphipathic steroids (hydroxy cholanoic acids) containing monoanionic side chain and hydroxyl groups in various numbers and positions resulting in a variety of individual bile acids in different species. They are planar molecules with hydrophilic groups on one side and the hydrophobic steroidal part of the molecule projecting on the opposite. This arrangement facilitates micellar formation and permits them to act as biological detergents for the solubilization of lipids in bile and aid in the digestion and absorption of fats in the intestine; physiologically good news. These same physiochemical properties also enable bile acids to solubilize biological membranes when left in prolonged contact resulting in cytotoxicity; pathologically bad news.

Cytotoxicity of retained bile acids Prolonged retention of bile has been shown to be associated with a variety of deleterious subcellular events within the hepatocyte (damage to mitochondria, endoplasmic reticulum, Golgi apparatus) which exacerbate intrahepatic injury. Recently, this ultrastructural toxicity has been attributed to selected bile acids. The more hydrophobic ones, defined by their HPLC migration, have the greatest potential to cause injury. The dihydroxy bile acids, chenodeoxycholic acid and deoxycholic acid can attain high serum and intrahepatic concentration secondary to cholestasis. In vivo and in vitro studies have shown that these bile acids can cause hepatocelluar dysfunction and necrosis at concentrations attained in prolonged cholestasis. Hepatocytes are at greatest risk of bile acid-induced injury due to their function of concentrating the bile acids prior to secretion through the canalicular membrane. By analogy, the liver can be considered to treat bile acids as sticks of dynamite with burning fuses of varied length. There is no harm if they are efficiently eliminated. However, the longer they are retained within hepatic tissue the greater the risk of injury. One bile acid, ursodeoxycholic acid, has been shown not only to be devoid of cytotoxicity but actually protected hepatocytes from the toxic effects of the other bile acids. It is being used in numerous clinical studies for the management of chronic liver disease in human beings. There are a variety of proposed mechanisms its beneficial effects. The contem-

porary areas of investigation are: (1) hypercholeresis, (2) direct cellular protection against the more hydrophobic bile acids or their displacement from the enterohepatic circulation, (3) antioxidant effect, and (4) immunomodulation. As mentioned previously, bile acids provide the predominant driving force for bile flow (choleresis). Unconjugated ursodeoxycholic acid has been shown to actually cause hypercholeresis, amplified bile flow compared to the physiologic effects of other bile acids. This is thought to be related to its ability to enhance biliary [HCO3–] and excretion via a hypothetical mechanism referred to as cholehepatic recycling. The displacement of cytotoxic bile acids from the enterohepatic circulation would theoretically decrease the prolonged exposure of hepatocytes to their high concentrations. The high concentration of orally administered ursodeoxycholic acid has been shown to effectively compete with chenodeoxycholic acid and deoxycholic acid for ileal absorption, thereby displacing them from the enterohepatic circulation. In the canine patient treated with ursodeoxycholic acid, serial determinations of the serum bile acid profiles with HPLC demonstrated a remarkable increase in the ursodeoxycholic acid concentration and a decrease in the chenodeoxycholic acid and deoxycholic acid concentrations. Ursodeoxycholic acid may afford direct hepatocellular protection by “partitioning” into the lipid-rich membrane and excluding the cytotoxic hydrophobic bile acids. In vitro studies with ursodeoxycholic acid in rats have found a moderate to marked reduction of substances produced as a consequence of oxidative injury suggesting a potent antioxidant effect. The beneficial effects associated with ursodeoxycholic acid in certain chronic liver diseases may be related to immunomodulation. Cytokines appear to be involved in the initiation, modulation and/or perpetuation of the immune responses in the liver. Ursodeoxycholic acid has been shown to reduce the aberrant major histocompatibility complex class I expression on hepatocytes in human beings with primary biliary cirrhosis and other studies have shown suppression of interleukin-2, interleukin-4 and interferon-g using test systems which employed mononuclear cells from the peripheral blood of human beings with primary biliary cirrhosis. In summary, the determination of the total serum bile acid concentration provides an index of hepatobiliary function and assesses the integrity of the portal circulation. Beyond their use as a diagnostic test, recent research has demonstrated that there are “good” and “bad” bile acids. Prolonged retention of certain endogenous bile acids appears

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to amplify intrahepatic pathology while others, notably ursodeoxycholic acid, appear to offer a novel alternative in the management of chronic liver disease without adverse sideeffects. Ursodeoxycholic acid clearly generates excitement with its potential multifaceted beneficial modes of action in the management of the complex pathophysiologic alterations associated with the diseased hepatobiliary microenvironment known as chronic liver disease.

Table 1. The enterohepatic circulation of bile acids The primary bile acids (cholic acid and chenodeoxycholic acid) are synthesized and conjugated by the hepatocyte —> excreted by the canalicular membrane into the biliary system —> carried to the intestinal tract —> participate in the emulsification of lipids for absorption —> move to the ileum during which time bacteria dehydroxylate a portion of the primary bile acids forming secondary bile acids (cholic acid to deoxycholic acid and chenodeoxycholic acid to lithocholic acid) —> reabsorbed into the portal circulation —> carried to the liver and removed by the hepatocyte for “recycling”. Hepatocellular excretion of bile acids into the biliary system is the primary driving force for bile flow; termed bile acid-dependent flow.

Supplemental reading Hoffman AF: Pharmacology of ursodeoxycholic acid, an enterohepatic drug. Scand J Gastroenterol 1994;29:S1-S15. Meyer DJ, Thompson MB, Senior DF: Use of ursodeoxycholic acid in a dog with chronic hepatitis: Effects on serum hepatic tests and endogenous bile acid composition. J Vet Intern Med 1997;11:195-197.

SCIVAC EXOTIC ANIMALS STUDY GROUP

Anaesthesia of pet birds Peter W. Scott Msc, BVSc, FRCVS RCVS Specialist in “Zoo & Wildlife Medicine” and “Fish Health & Production” Zoo & Aquatic Veterinary Group, Winchester - United Kingdom

Summary Anaesthesia of birds with isoflurane has become a safe and routine procedure in practices whether or not they consider themselves avian practices. It is important to gain an understanding of the unique anatomy and physiology of the avian respiratory tract to appreciate the value of particular circuits, or to contemplate the use of intubation or air sac tubes. As with any species the aims of anaesthesia should be to provide a smooth, reliable induction with adequate restraint, muscle relaxation, and analgesia, followed by a fast, complete and uneventful recovery (Lawton 1996 a&b). This paper will discuss the options available for the more conventional companion species.

Introduction Anaesthesia of birds with isoflurane has become a safe and routine procedure in practices whether or not they consider themselves avian practices. It is important to gain an understanding of the unique anatomy and physiology of the avian respiratory tract to appreciate the value of particular circuits, or to contemplate the use of intubation or air sac tubes. As with any species the aims of anaesthesia should be to provide a smooth, reliable induction with adequate restraint, muscle relaxation, and analgesia, followed by a fast, complete and uneventful recovery (Lawton 1996 a&b). This paper will concentrate on the more conventional companion species, Heard (1997a) provides a wider review introducing the literature covering other species.

Anatomy & physiology Birds do not have a functional diaphragm, they draw air into the lungs by a cranio-ventral movement of the ribs to expand the lungs and air sacs. Because of the importance of the ribs in this process it is vital not to restrict their movement during handling (or by wrapping tightly for recovery. The trachea is made up of complete interlocking cartilaginous rings (ossified in some species). Because of this when using endotracheal tubes, plain tubes are generally preferred to avoid damaging the trachea. Most birds have nine air sacs associated with the lungs, paired cervical, single clavicular, and paired cranial thoracic,

caudal thoracic and abdominals, depending on species some of these pneumatise bones. Total volume of the respiratory tract is of the order of 100-200 ml/kg body weight (as compared to 45 ml/kg in the dog), with only approximately 12% of this being lung. The air sacs are functionally grouped, the anterior group (cervical, clavicular and anterior thoracic), and the posterior group (caudal thoracic and abdominal). The avian lung is fixed in place and does not move appreciably during breathing, air is cycled through the system of air sacs and lung by active inspiration and expiration. The lung is divided in the vast majority of birds into paleopulmo and neopulmo, the relative proportions varying between species (penguins and emu have no neopulmo). There are no alveoli, they are replaced with a system of parabronchi, leading to infundibulae and air capillaries. Gaseous exchange primarily occurs in the air capillaries of the paleopulmonic area. The air flow appears to be unidirectional in the paleopulmo and bi-directional in the neopulmo. Details of air flow through the avian lung and air sacs has been the subject of debate and may vary with activity and between species. The existence of anatomic valves is in doubt, there do however seem to be aerodynamic flow controls dependent on the anatomy. There is a very efficient exchange system operating in birds, due to a high gas exchange surface-to-volume ratio and the use of a countercurrent system of opposing air flow through air capillaries and blood flow. This makes induction and recovery when using gaseous agents very rapid. James et al (1976) suggest that avian lungs can be considered 10X more effective than mammalian lungs. Birds are extremely sensitive to CO2 levels, to the extent that they will become apnoeic if the blood becomes depleted of CO2. The CO2 is carried in blood as plasma HCO2–, and in the lungs carbonic anhydrase in the red cells splits the HCO2–, into H+ and CO2. The CO2 has no direct effect on oxygen/haemoglobin binding although the released H+ exerts and influence through the Bohr effect ( a rise in H+ leads to reduction in O2 affinity). A rise in tissue temperature also decreases the O2 affinity of the haemoglobin. The net effect of both effects is that active tissue, respiring and producing CO2, warmer than the lungs encourages the release of oxygen from the haemoglobin. It is suggested that a deeply anaesthetised bird may not generate sufficient muscular movement to ‘pump’ air around this circuit. This may be particularly acute in species with a large pectoral muscle mass. Sinn (1994) advises the routine use of gentle positive pressure ventilation (20-40/minute at 15 mmHg) to overcome any potential hypocapnoea and

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maintain adequate oxygenation. Air is drawn in during inspiration and is divided between the paleopulmo and the caudal air sacs via the neopulmo. Air leaving the paleopulmo enters the anterior air sacs. During expiration the caudal air sacs empty via the neopulmo into the paleopulmo. Air leaves the paleopulmo mixing with spent air from the anterior air sacs, this air is expired. Duncker,H.R. (1971).

lection, radiography, fluid administration, endoscopy or bandaging. The type of assessment used for these short procedures is normally limited to the taking of a history and a physical examination. Prior to a prolonged anaesthetic it may be advisable to consider any or all of the following: PCV, WBC & differential, TP, AST, LDH, UA, bile acids, grams stains of faeces and choana, platelets, clotting time and bile acids. Other tests may be indicated in particular cases. Liver dysfunction is not uncommon, and its presence would make the use of most injectable agents, plus halothane and methoxyflurane contraindicated. Patients which are toxic due to egg retention may require stabilisation for a day or two prior to surgery. Obese pet birds are serious anaesthetic risks and prior to elective procedures a diet is indicated. Suspect Aspergillus cases can be pre-oxygenated before induction.

Fluid therapy There are good grounds in assuming birds suffering from trauma or disease are dehydrated, often in the region of 10%, maintenance requires 50 ml/kg/day ie. 5% body weight. Lactated ringers i/v or i/osseous are recommended. 5% dextrose is regarded as inappropriate by Phalen et al (1997) who suggests that it may cause serious electrolyte imbalances. Sinn (1994) suggests that subcutaneous or oral fluids are not as effective at restoring circulating volume.

Duncker, H.R. (1971)

Pre-anaesthetic

Fasting

Mammalian-type pre-anaesthetic drugs are not normally used in birds, atropine is contra-indicated in avian patients because it thickens respiratory mucus and increases the heart rate. In general a pre-anaesthetic evaluation is important to assess whether supportive treatment is indicated prior to embarking on an intervention. Isoflurane anaesthesia is however often used simply as an aid to restraint to minimise the stress associated with minor procedures such as blood col-

In general terms it is usually advisable to fast the bird long enough to empty the gastrointestinal tract, in small birds this may be 3-6 hours and in large birds overnight. Always check the crop before inducing anaesthesia, passive regurgitation may block the larynx. Special care is needed if the crop contains food, anaesthetise with the patient upright, block the choana with a swab while the crop is emptied, clean the area and intubate.

Volatile anaesthetics BLOOD GAS PARTITION COEFF AT 37OC

PHYSIOLOGICAL ASPECTS

Halothane

2.3

15-20% metabolised

Poor muscle relaxation and analgesia. Causes bradycardia, sensitises the heart to catecholamines. Respiratory and cardiac arrest tend to happen together.

Isoflurane

1.4 low solubility makes induction & recovery very rapid

0.3% metabolised MAC (1.5-2%)

Good muscle relaxation and analgesia. Less respiratory and cardiac depression than halothane, if problems then respiratory arrest usually precedes cardiac arrest. Rapid induction and recovery.

0.68 quick induction etc

MAC (2-3%)

Potentially expensive, similar to isoflurane, good control over planes of anaesthesia.

12.0

50% metabolised, â&#x20AC;&#x153;hang-overâ&#x20AC;?

Sevoflurane Methoxyflurane

Lawton 1997, Heard 1997b, Greenacre 1997.

GENERAL COMMENTS

Organ toxicity, highly blood soluble so long induction and recovery.

Commonly used agents Isoflurane has achieved pre-eminence as the anaesthetic of choice for birds, it has revolutionised avian medicine, making much more possible. It is much safer than halothane and the data is now so good that it would be difficult to defend the continued use of halothane in birds. A relatively high flow rate needs to be maintained, it should be a minimum of three times the normal minute volume. ie. approximately 3 ml/g bodyweight. (an African grey weighing 350 g needs 1.1 litres/ minute. As a rule of thumb

2 lpm is sufficient for birds of up to amazon parrot size, macaws need 3-4 lpm. The normal system used for all but the shortest procedures is to intubate and use a Mini-Ayres or Bethune T-piece system, this then allows scavenging of waste gas or ventilation should a problem occur. Cooks Veterinary Products manufacture specialist endotracheal tubes. Nitrous oxude is still used by some veterinarians for its analgesic properties, it reputedly accumulates within the air sacs and should only be used during induction, usually at 50/50 with oxygen and never more than 80%.

Injectable anaesthetics DOSE RATE

COMMENTS

Alphaxalone/alphadalone

5-10 mg/kg i/v 36 mg/kg i/m, i/p

Alphaxalone/alphadalone is a relatively good anaesthetic agent but with a transient apnoea following intravenous administration, the preferred route due to the large volumes required. This can be alarming and, when compared to other anaesthetic agents, is a major disadvantage. Despite this, there is a wide safety margin but only a short chain of action (Mandelker, 1987).

Ketamine

20-50 mg/kg s/c, i/m, i/p

Used in birds since 1972 (Mandelker, 1972). It is a good sedative but a poor anaesthetic, with poor muscle relaxation and little analgesia. The dose rate of ketamine is inversely proportional to the body size (Boever and Wright, 1975). Ketamine is eliminated by the kidneys in birds, as it is in mammals.

Ketamine with diazepam or midazolam

25mg/kg ketamine + 1-2 mg/kg diazepam or 0.2mg/kg midozolam s/c, i/m

The addition of diazepam/midazolam produce better relaxation than ketamine alone.

Ketamine with medetomidine

1.5-2mg/kg ketamine + 60-85 mg/kg medetomidine (reversed with atipamazole Antisedan, 250-380 µg/kg i/m)

Medetomidine has sedative and analgesic properties, but it also has hypotensive, bradycardic, and hypothermic effects. Medetomidine and ketamine combination provides deep sedation and good muscle relaxation with no arrhythmias or respiratory depression (Jalanka, 1989). This combination is particularly good in waterfowl.

Ketamine with xylazine

Various combinations; 30-40mg/kg K+ 0.5-1.0mg/kg X or 4.4/kg K + 2.2mg/kg X (xylazine is reversed with yohimbine HCl, 0.1-0.2mg/kg i/v, or atipamezole 250-380 µg/kg i/m)

Once reversal agents became available the use of higher doses of xylazine and correspondingly lower doses of ketamine were possible. Ketamine/medetomidine is considered a better combination, although xylazine is cheaper. Unreversed there is prolonged recovery and post operative depression that can result in birds being unable to feed or drink.

Propofol

1.33mg/kg i/v

Dose dependent cardio-vascular and respiratory depression, low therapeutic index in pigeons and chickens. Metabolised and eliminated too quickly to be of any major use in birds. Potential use only in larger birds in good health, when respiratory support is available but mask induction is considered inappropriate.

Xylazine

1-20 mg/kg i/m, i/v (Reversed with yohimbine HCl, 0.1-0.2mg/kg i/v, or atipamezole 250-380 µg/kg i/m)

Xylazine by itself is unreliable, causes bradycardia and A/V block, and can cause serious respiratory depression (Mandelker, 1987).

Refs: Lawton 1997, Heard 1997b

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Injectable agents still have a place, especially in the field. For use where isoflurane is not available this author would use ketamine/xylazine or ketamine/medetomidine in preference to inducing with halothane and oxygen.

Analgesics Work on pigeons suggests both kappa and mu receptors are active in pain perception, but that they are kappa dominated (76%). Analgesics have not yet been thoroughly studied in avian species but butorphanol certainly appears useful.

mask first. In an respiratory-emergency situation oxygen can be given by mask whilst the tube is placed under restraint rather than anaesthesia. A large gauge tube (French gauge 14) is used, Cook Veterinary Products actually make a tube specifically for the purpose. Positive pressure ventilation is usually required because the CO2 falls below the level which stimulates breathing, and apnoea results. Birds begin breathing spontaneously one the CO2 levels rise after the oxygen flow ceases. It is possible if necessary to leave the air sac tube in situ in cases where a respiratory obstruction is still a potential problem.

Monitoring Injectable anaesthetics DOSE RATE

COMMENTS

buprenorphine

0.02mg/kg i/m

Opiate analgesic which can cause some respiratory depression, not very effective in birds even at higher doses Butorphanol 1-2mg/kg i/m Appeared effective in African greys and cockatoos but not amazons. Has been used in parakeets Carprofen 5-10mg/kg s/c Very effective analgesic which can be used in conjunction with buprenorphine to have a synergistic effect in cases of severe pain Flunixin meglumine 1-10 mg/kg i/m Has been used but carprofen is considered more effective Ketoprofen 5-10 mg/kg i/m Better than flunixin but not as good as carprofen Meloxicam 200Âľg/kg p.o Effective and useful for long term use Lawton 1997, Paul-Murphy 1997, Bauck 1990, Malley (pers comm).

Maintenance Birds are less efficient than mammals at retaining body heat, during anaesthesia they cool rapidly so special care is needed. Phalen et al (1997) showed the importance of heat supplementation during surgery. Hypothermic birds become acidotic. A warm room >23oC is advisable, the anaesthetic gases themselves are cold and also have a cooling effect on the patient. Sparing use of skin disinfection minimises the cooling effect on the skin. Heater water circulating pads are useful or my preference is the Vetbed type materials on a reptile heater pad in a warm room > 25oC.

A safe anaesthetic is one which is appropriately monitored, even isoflurane which is considered extremely safe should be treated with respect. Suitable reflexes for monitoring are the palpebral, corneal, cere, toe pinch and wing twitch. As is expected, these slow and eventually are abolished. The toe, cere and wing reflexes disappear at a medium plane of anaesthesia, while the corneal reflex remains into deep anaesthesia. Jaw tone and leg withdrawal can also be assessed, they are reduced in a medium plane of anaesthesia, jaw tone is also rather difficult/dangerous to assess in a parrot being masked. Electronic respiratory monitors are available but only when using intubation. My own experience suggests that the probes are not sufficiently sensitive to use via a mask. I suggest anyone contemplating purchase of monitoring equipment should arrange to test it in the way they wish to use it before they buy it. Changes in pattern (becoming more rapid) are indicative of recovery, or that the bird is feeling pain. Normal respiratory rates have been reported as budgerigars 55-75/min, larger parrots 10-20, and 2-20 for ostrich. Doppler probes can be a relatively simple means of at least ensuring that there is still a pulse. Heart rate monitors can be useful to assess changes in rate or especially when xylazine is used to detect possible A/V block. Monitors need to have a wide range of sensitivities, budgerigars may have an average of 600 bpm, and ostriches 60 bpm Lawton (1996a) cites painful interventions in a cockatiel resulting in a rise from 300 to 700 bpm. Pulse oximetry is becoming an extremely valuable tool with probes on the wing web or tongue, cloacal probes are also being developed. Validation of the equipment is not yet complete, although there is a lot of interest. Readings below 80% are considered life threatening, most birds will maintain 80-85% when self ventilating hence the advice to use gentle positive pressure ventilation (Sinn 1994).

Air sac intubation Emergency respiratory arrest This route has proved useful if surgery on the head and neck is contemplated, or if the patient is suffering from an obstructive problem of the airway. The normal site is just behind the ribs on the left side, in the same position used for endoscopic sexing. Routinely a bird would be induced by

Disconnect the bird from the anaesthetic. Press the chest 40-50 x per minute, ensuring that the legs are free to move. Intubate or fit an air sac tube and IPPV through tube.

References BAUCK, L. (1990) Analgesics in avian medicine. In: Proceedings of the Association of Avian Veterinarians Annual Conference, 1990. AAV, Lake Worth. BOEVER, W.J. and WRIGHT, W. (1975). Use of ketamine for restraint and anesthesia of birds. Veterinary Medicine/Small Animal Clinician 70, 86. DUNCKER, H.R. (1971) The lung air sac system of birds. A contribution to the functional anatomy of the respiratory apparatus. Ergeb. Anat. Entwicklungsgesch 45 (6) 1. JAMES, A.E., HUTCHINGS, G., BUSH, M., NATARANJAN, T.K., and BURNS, B. 91976). How birds breathe: correlation of radiographic with anatomical and pathological studies. Journal of American Radiological Society 17, 77. GREENACRE,C.B. (1997) Comparison of sevoflurane to isoflurane in Psittaciformes. In: Proceedings of the Association of Avian Veterinarians Annual Conference, Reno.1997. AAV, Lake Worth. HEARD, D.J. (1997a) Anesthesia and analgesia In: Avian Medicine and Surgery. (Eds R.B.Altman, S.L.Clubb, G.M.Dorrestein & K.E.Quesenberry. W.B.Saunders, Philadelphia. HEARD, D.J. (1997b) Avian anesthesia: Present and Future Trends In: Proceedings of the Association of Avian Veterinarians Annual Conference, Reno.1997. AAV, Lake Worth. KING, A.S. & McLelland, J. (1984). Birds, their structure and function. 2nd ed. BailliĂ¨re Tindall, London.

87 MCLELLAND, J. (1989) Anatomy of the lungs and air sacs. In Form and Function in Birds. Vol 4 (eds. A.S.King and J.McLelland). Academic Press, London. LAWTON, M.P.C. (1996a) Anaesthesia. In Manual of Psittacine Birds. (eds.P.H.Beynon, N.A.Forbes and M.P.C.Lawton). BSAVA, Cheltenham. LAWTON, M.P.C. (1996b) Anaesthesia. In Manual of Raptors, Pigeons and Waterfowl. (eds.P.H.Beynon, N.A.Forbes and N.Harcourt-Brown). BSAVA, Cheltenham. LAWTON, M.P.C. (1997). Anaesthesia. In: Core Day Proceedings of the 4th Conference of the European Committee of the Association of Avian Veterinarians. EAAV,1997. London. MANDELKER, L. (1972) Ketamine hydrochloride as an anaesthetic for parakeets. Veterinary Medicine/Small Animal Clinician 67, 55. MANDELKER, L. (1987) Anesthesia and surgery. In Companion Bird Medicine (Ed. E.W.Burr) Iowa State University Press, Ames. PAUL-MURPHY, J. (1997) Evaluation of analgesic properties of butorphanol and buprenorphine for the psittacine bird. In: Proceedings of the Association of Avian Veterinarians Annual Conference, Reno.1997. AAV, Lake Worth. PHALEN, D.N., LAU, M.T. & Filippich, L.J. (1997) Considerations for safely maintaining the avian patient under prolonged anesthesia. In: Proceedings of the Association of Avian Veterinarians Annual Conference, Reno.1997. AAV, Lake Worth. SINN, L.C. (1994) Anaesthesiology. in Avian Medicine: Principles and application. (eds.B.W.Ritchie, G.J.Harrison, and L.R.Harrison). Wingers, Lake Worth.

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SCIVAC EXOTIC ANIMALS STUDY GROUP

Diagnostic techniques for birds Peter W. Scott Msc, BVSc, FRCVS RCVS Specialist in “Zoo & Wildlife Medicine” and “Fish Health & Production” Zoo & Aquatic Veterinary Group, Winchester - United Kingdom

Summary Avian medicine has developed rapidly in the last 10 years, improved analytical techniques have improved the applications for blood biochemistry. DNA techniques have been applied for the determination of sex, and then for various diagnostics. Improvements in anaesthesia have lead to the extension of endoscopic sexing into the taking of endoscopically guided biopsy samples.

In avian medicine laboratory workups are extremely valuable in diagnosis. Much is best sent to specialist laboratories since bird blood is significantly different - not least the nucleated erythrocytes! Avian haematology requires specialist training and a good throughput to produce consistent and meaningful results. In-house testing has a major role for referral practices where quick results are valuable in stabilising patients while specialist lab tests are ‘in the post’. Appropriate samples should be taken, if necessary speak to the lab while you still have the patient! Lane (1992a) has covered some of the problems of sampling. Spenser (1994) and Carpenter (1996) are recommended).

is found running down the middle of the neck, in psittacines there is usually a featherless apterylae over it making visualisation fairly simple. In small birds it is often the only vein large enough for venipuncture. This is my preferred route.

Blood tests Haematology Haematology is a very valuable tool in avian medicine, blood can be collected into heparin and EDTA. Microtainers are preferred since the larger tubes contain too much EDTA which may cause cell lysis. EDTA should not be used with corvids, ratites, cranes, penguins or kookaburras as it causes erythrocyte lysis. A blood smear should be made at the time of collection for a differential leucocyte count using blood which has not been exposed to any anticoagulant. Making full use of avian haematology really calls for experienced technicians and clinicians. Stress haemograms occur but vary between species. In cockatiels, african greys, cockatoos and macaws the stress haemogram is heterophilic, whilst in amazons it appears lymphocytic. Summary of changes

Blood sampling Blood can be collected from the brachial/cutaneous ulnar vein (running across the ventral surface of the humero-radial joint - under the wing) in many species including pigeons, raptors and waterfowl. The vessel is quite small and mobile and blood collection will often result in haematoma formation. It is often necessary to pluck the site and poor restraint may result in wing damage. The metatarsal vein is often used in waterfowl and ratites, although some avian veterinarians like the site for routine use in a wide range of species. The vessel is on the medial aspect of the intertarsal joint, venipuncture is usually carried out proximal to the joint, first plucking a few feathers. If the vein is accessed through the scaled area the bleeding may be difficult to stop. Exponents of the brachial and metatarsal routes suggest not drawing blood with the syringe plunger, rather let the blood flow by capillary action. Avian blood clots slowly so blocked needles are rarely a problem. The right jugular vein is a larger less mobile vessel and

CELL TYPE

COMMENTS

Heterophils

Band cells - rise in severe inflammatory disease such as clamydiosis toxic heterophils - especially in chronic equilibrated disease degranulated seen in low grade or chronic conditions

Eosinophils

These are rare, seen with Giardia in cockatiels, and with worms in other species

Basophils

Rare, some in respiratory infections

Lymphocytes

Large - cf. monocytes, small predominant cell type in amazons

Monocytes

Chronic illness esp. Chlamydia, lead poisoning, Aspergillosis

Serology At present there are not many useful serological tests for birds in Europe. In the USA there are now tests for poly-

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omavirus, Pachecoâ&#x20AC;&#x2122;s disease, Aspergillus, chlamydia. There are a number of chlamydia serology tests available. In UK PMV serology is available. Serum iron assays can be useful in toucans. Biochemistry Biochemistry tests are widely available and can be extremely valuable. In-house systems such as VetTest 8008 can

be used, even though some doubt has been cast on the validity of the results but their great value is that results are available quickly. Plasma or serum can be used, gel-separation tubes are very useful to prevent haemolysis when samples must be sent to distant laboratories. Specialised PCR / DNA tests Sex determination by DNA probe single drop of blood

TEST

COMMENTS

ALT

Although useful for assessment of liver disease in mammals this is of no value in avian work.

AST / SGOT

Used as an indicator of liver damage, although it is non-specific sources of AST are liver, skeletal and cardiac muscle. When it is elevated by hepatocellular damage and eventually returns to normal this does not indicate that liver function has returned to normal. Bile acids may give a better prognostic measure for liver function.

Bile acids

Birds excrete biliverdin, not bilirubin (they lack bilirubin reductase), so bilirubin measurements are meaningless. Unconjugated biliverdin does not accumulate in tissues, discolouration of avian plasma (or skin) is more likely to be due to carotenoids than pathological changes). Samples should be tested within 24 hours. Post-prandial levels are higher than pre-prandial since they are reabsorbed after eating

Calcium

This is an important parameter to measure in many birds. Low levels can be associated with breeding failure, egg binding or fractures. Never collect samples into EDTA.

Cholesterol

This can be a useful measure in cases of hepatic lipidosis, hypothyroidism, atherosclerosis and in assessing obese birds on high fat diets.

Creatinine

Not considered to be a useful test in birds. Has been seen to rise associated with high protein foods.

CK / CPK

This is found in all muscle tissue and c an be found at high values associated with activity, fights, fits etc. Rough technique in capture and blood sampling can result in elevation. It is useful in helping to interpret raised AST levels, ie a raised AST with normal CPK is strongly indicative of liver damage.

GLDH

This is fairly liver specific (within the hepatocyte mitochondria), there is reported to be some present in kidney.

LDH

This is non-specific, found in liver, muscle, kidney and erythrocytes. Limited value, prone to elevation due to haemolysis.

Phosphorus

In theory an elevation can be associated with renal failure, but in practice changes are not seen very often.

Protein

Changes in albumin and globulin levels are not well documented in birds, although direct parallels have been drawn with mammalian results. Dry chemistry systems are said to be unreliable for measurement of avian albumin.

Triglycerides

These can be a useful indicator in investigating egg related peritonitis, elevations will also be seen during starvation.

Urea

Birds manufacture very little urea and it is not a useful test, elevations may occur with pre-renal dehydration.

Uric acid

Used as a guide to renal function, but is not absolute. It is synthesised in the liver and excreted by the medullary nephrons independent of urine flow rate, dehydration etc. Raised uric acid levels do not indicate dehydration, they rise when renal function is reduced to less than 30% of normal. A rise is seen with prolonged fasting 48-72 hours due to catabolism.

TEST

COMMENTS

Sex determination

Can be carried out on blood samples or feathers.

Parrot Circovirus (Psittacine Beak & Feather Disease)

Infected birds appear to remain viraemic (except for a small number which appear to eliminate the virus) and so blood samples will provide suitable target DNA in the majority of cases. Clinical cases are often immunosuppressed so feather pulp should be included since such cases can be negative on blood test. Feather pulp or 1 drop of blood in the collection vial. Fixed material or paraffin embedded tissues can also be used.

Avian Polyomavirus (Budgerigar Fledgling Disease)

This test can only detect virus from birds which are actively shedding the virus, birds do not remain viraemic. In the clinical situation this is particularly likely at times of stress such as moulting or breeding, or following transportation. Cloacal swabs or faeces from live birds appear to be the most reliable sample for detection of this virus. Fixed material or paraffin embedded tissues. Or fresh liver, spleen or kidney tissue from post mortems in collection medium. Blood samples have been rather unreliable until recently but improved molecular techniques are now showing that these might well be suitable for carrier detection.

Chlamydiosis / Psittacosis

This test can detect organisms when even very few are being shed, developments in molecular echniques are making this suitable for examining blood.

required. PCR diagnostics for PBFD and Polyomavirus. It is recommended that before any samples are sent veterinarians should speak to the laboratory and ensure that the collection materials are appropriate. Special media may be required.

Faecal tests There is a lot of useful evidence in a simple examination of the droppings in the cage. A ‘normal’ dropping will contain a coiled, semi-solid faecal component, a white/creamy urate component and some liquid urine. Diet will influence faecal colour and consistency considerably, seed diets usually produce compact, green faeces, “formulated diets” tend to produce bulkier brown coloured faeces. Items such as beetroot, blueberries and pomegranate will also cause alarming changes. Apparent haematuria is a feature of lead (or other heavy metal) poisoning in amazon parrots. This topic has been reviewed by Bauck 1995. Consistent discolouration green or yellow discolouration of urine or urates is cause for concern and investigation. Microbiology In-house microbiology in my opinion is often of very limited value, in my experience few practice laboratories do it thoroughly enough, cutting corners with media ranges to keep costs down. Lane (1992b) gives a review of techniques for the practice laboratory. Gram stains Although referred to often as faecal gram stains it is more useful to look at cloacal smears, these can be useful at a basic level for assessing levels of yeasts, presence of megabacteria or the ‘gram positive/gram negative’ (GP/GN ratio). Small passerines usually have no gram negative organisms present while psittacines have very few. In general megabacteria will be seen if clinically significant, the organism is difficult to find in carriers. Microbiological culture is suggested on birds with more than 10% gram negative organisms, observations by Brown (1996) suggest poor correlation between staining and culture. Choanal smears are also examined by grams stains, there are often more gram negative organisms in choanal than cloacal samples.

Endoscopy Direct visualisation of organs is an extremely useful technique, the 2.7mm rigid endoscope used routinely for surgical sexing of birds can be utilised in a range of approaches. Taylor and Harrison 1997 have produced a superb reference work on CD-ROM showing anatomy and surgical approaches for all of the organs. This also covers the necessary approaches for endoscopically guided biopsy.

Biopsy Crop biopsy has proved a useful means of obtaining a diagnosis in cases of proventricular dilatation (Doolen, 1994).

Endoscopic guided biopsy techniques have become popular and the Stortz system has been designed specially for the purpose. Hunter and Taylor (1992) describe a technique for lung biopsy, they stress that this is not a routine procedure but one which is valuable in cases where a diagnosis cannot be made otherwise. Renal biopsy has also been investigated (Murray & Taylor,1997) since renal disease is difficult to assess by blood sampling techniques, this is a more routine procedure than lung biopsy, most haemorrhage is minor and self limiting. Specialist Laboratories DNA sexing, PBFD, Polyomavirus and Chlamydia PCR tests. University Diagnostics Ltd, South Bank Technopark, 90 London Rd, London, SE1 6LN. Tel: 0171-401-9898, fax: 0171-928-9297

References BAUCK, L. (1995) Abnormal droppings and their workup. In: Proceedings of the Association of Avian Veterinarians Annual Conference.1995. AAV, Lake Worth. Carpenter, J.W. (1996) Ed. Avian and exotic parasitology. In. Seminars in Avian and Exotic Pet Medicine. 5, (2). DOOLEN, M. (1994) Crop biopsy - a low risk diagnosis for neuropathic gastric dilatation. In: Proceedings of the Association of Avian Veterinarians Annual Conference, Reno.1994. AAV, Lake Worth. GRIMES,J.E. (1993) Interpretation of avian host Chlamydial titers using various serologic methods. In. Seminars in Avian and Exotic Pet Medicine. 2, (4). HUNTER, D.B., & TAYLOR, M. (1992) Lung biopsy as a diagnostic technique in avian medicine. In: Proceedings of the Association of Avian Veterinarians Annual Conference, New Orleans.1992. AAV, Lake Worth. JOYNER, K.L. (1991) The use of gram stain results in avian medicine. In: Proceedings of the Association of Avian Veterinarians Annual Conference, Chicago.1991. AAV, Lake Worth. LANE, R.A., (1992a). Microbiology practical tips. In: Proceedings of the Association of Avian Veterinarians Annual Conference. New Orleans.1992. AAV, Lake Worth. LANE, R.A., (1992b). Sampling procedures: Do’s & Don’ts. In: Proceedings of the Association of Avian Veterinarians Annual Conference. New Orleans.1992. AAV, Lake Worth. MURRAY, M.J., & TAYLOR, M. (1997). The use of endoscopy and endoscopic biopsy as aids in the diagnosis. In: Proceedings of the Association of Avian Veterinarians Annual Conference, Reno.1997. AAV, Lake Worth. Niagro, F.D., Ritchie, B.W., Latimer, K.S., Lukert, P.D., Steffens, W.L., and Pesti, D. (1990) Polymerase chain reaction detection of PBFD virus and BFD virus in suspect birds. In Proceedings of the Annual Conference of the Association of Avian Veterinarians. Phoenix: 25-37, 1990. SCOTT, P.W. (1993). DNA Technology: Practical applications for the avian veterinarian. in Proceedings of the 1993 European Conference on Avian Medicine & Surgery. Utrecht, Netherlands. European Committee of the Association of Avian Veterinarians. 178-190. SPENSER, E.L. (1994) Ed. Clinical Pathology: Blood testing. In. Seminars in Avian and Exotic Pet Medicine. 3, (1). TAYLOR, M., & HARRISON, G.J. (1997). Diagnostic Application of Avian Endoscopy. Wingers Publishing Multimedia Series, Lake Worth, Florida. WORELL, A. (1991) Serum iron levels in Ramphastids. In: Proceedings of the Association of Avian Veterinarians Annual Conference, Chicago.1991. AAV, Lake Worth.

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From pharmacokinetics clinical application Empirical antibiotic treatment in infections diseases David Aucoin

Summary Avoiding antimicrobial failure involves initially ensuring that the patient has treatable infection. Antimicrobial selection can be based on probabilities and input from flexible labeling guidelines. A clinician who is familiar with the efficacy of each antimicrobial can avoid therapeutic failure and use therapy as a diagnostic tool.

Treatment failure can be regarding in two different lights. On one hand, true antimicrobial failure results from using an inappropriate agent, incorrect dosage and or duration of treatment. However, a much greater reason for failure, is absence of a treatable infectious pathogen. Our perchance to use antibiotics frequently in situations where antibiotics have no efficacy or in situations where infectious pathogens are not even present leads to our greatest failures. Even though most patients receiving antibiotics get better during treatment, it is this inappropriate use of antibiotics that has lead many lay people to call for greater restrictions on antimicrobial use, especially in animals. This paper will address the specific issues regarding true antimicrobial failure in a patient with treatable infectious disease as well as address more social issues regarding appropriate antimicrobial use and avoiding misuse on antimicrobial.

Patient selection The presence of an antimicrobial responsive infectious disease is usually readily apparent. Localizing signs, history and a good physical examination are often sufficient. Fever has been the most frequent indication for antimicrobial use, however, there is little indication that most fevers seen in the dog or cat are caused by bacterial or rickettsial infections.

Moreover, most fevers associated with upper respiratory or gastrointestinal infection sin the cat are viral infections. These common infections do not require a fever to be diagnosed but do point out that fever of unknown diagnosis is not likely, based on more common infections, to result in a fever. The point is most practitioners use antibiotics because there MAY be a bacterial cause. Herein lies the problem: If you are trying to rule out a bacterial infection the choice of antimicrobial agent must be based on predictable efficacy against the most probable pathogen(s) you are trying to rule out. Terms such as “broad spectrum” are of little use in this situation since spectrum does not indicate efficacy within that spectrum. The tetracyclines have a broad spectrum of activity from bacteria, mycolplasma, rickettsiae and chlamydia. However, their efficacy against rickettsial species is excellent while against most common gram negative bacteria they’re fair to poor. It’s appropriate using tetracyclines to rule out an unexplained fever caused by rickettsiae but would be inappropriate to use it to rule out any bacterial infection. Ampicillin is a broad spectrum antimicrobial with excellent activity only against streptococci. Using it to rule out a possible bacterial infection would be illogical. It would only eliminate a systemic streptococcal infection. A rare disease in the dog or cat. To use an antimicrobial with a higher degree of success depends on two principals. If an infection is readily apparent (pyoderma), then antimicrobial choice, dose and duration is important in avoiding failure. If an infection is possible but not apparent (i.e fever of unknown origin), then an antimicrobial(s) must be selected to rule out a wide variety of pathogens. Again, selection, dose and especially duration of therapy is important here but very different, since the antimicrobials are being used as a diagnostic tool as well as potential therapy.

Table 1. Presence (+) or absence (-) of fever in the presence of common infections.

Pyoderma

Otitis Externa

Lower UTI

Upper Respiratory

Lower Respiratory

Gastrointestinal

Canine

+/-

Feline

+/-

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DVM, Dip ACVCP Santa Monica, California - USA

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Antimicrobial selection

Antimicrobial dosing

Selection in a known infection should be based on that antimicrobial which has a high degree of predicable efficacy against the most common pathogens at that site. Again, it can be appreciated that even in the most commonly infected body sites, the infection is not always bacteria and rationale antimicrobial use against these infections is impossible. Selecting an antimicrobic with excellent predicted efficacy against these pathogen at these sites is the first step. It is illogical in my opinion to use an agent that “usually” works only to confront that owner again after failure to then prescribe an agent that “will” work. Treatment failure is very costly to the owner, the pet and to your practice. Table 3. Is based solely on in vitro efficacy and does not take into account costs, toxicity, ease of use or in vivo factors which may favor one family vs. another.

The advent of flexible label dosing in the USA has finally made antimicrobial use more rational. Antimicrobial activity may be over a wide concentration range. Enrofloxacin is effective against most Pasteurella spp at <0.006 ug/ml while requiring 1-2 ug/ml to have similar in vitro efficacy against 90% of P. aeruginosa. That’s a 300 fold difference in effective concentrations! It would only be logical to assume the dose for treating pasteurellosis would be lower than treating a Pseudomonal infection. Antimicrobial like enrofloxacin now have flexible dosing labels, however, all antimicrobial should be dosed according to pathogen requirements. Frequency of dosing depends on whether an antimicrobial in vivo activity is better correlated with its peak serum levels (Concentration dependent) or time during a dosing interval serum levels are above the inhibitory concentration (MIC) of the pathogen (Time Dependent). B-lactams (like amoxi-clav and cephalexin) are time dependent while quinolones and aminoglycosides (enrofloxacin, mar-

Table 2. Most common bacterial pathogens at commonly infected sites.

Pyoderma Canine

Staphylococci

Feline

Pasteurella

Otitis Externa

Lower UTI

Upper Respiratory

Lower Respiratory

Proteus/ Pseudomonas

Coliforms

Not Predictable

Coliforms

Not Usually Bacterial

Usually Viral

Anaerobes Pasteurella

Not Usually Bacterial

Gastrointestinal

Table 3. Antimicrobial families with excellent predicted in vitro efficacy (> 90%) against these pathogens.

Antimicrobial

Staphylococci

Coliforms

Pseudomonas

Anaerobes

Rickettsia

Cephalosporins Quinolones Potentiated, Penicillins

Quinolones

Quinolones Aminoglycosides

Metronidazole

Tetracyclines Quinolones

Table 4. Author suggested dosing guidelines based on pathogens and maximizing in vivo activity. Amoxicillin clavulanate Staphylococci Streptococci Pasteurella Coliforms Pseudomonas Anaerobes Rickettsiae

10-15 BID 10 BID 10-15 BID 15-30 TID

Enrofloxacin

Marbofloxacin

Cephalexin

Gentamicin

5 SID

2 SID

6 SID

5 SID 5-10 SID 10-15 SID

2 SID 2-4 SID 4-8 SID

10-15 BID 10 BID 10-15 BID 15-30 TID

10-15 BID

10-15 BID 5 SID

4 SID 6 SID 8 SID

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Antimicrobial dosing duration Duration of treatment is empirical and based upon how well the patient responds. However, to short a treatment period does increase the emergence of resistant bacterial strains and too long a treatment increases unnecessary costs and may delay alternative treatments or diagnostics. Acute treatments should be continued 3-5 days past clinical cure which usually respond quickly with 5-10 days of treatment adequate. If no clinical response is noted within a few days it is unlikely a response will be seen in after 10 days. Treating acute infections for 2-3 weeks awaiting a response is illogical and the patients needs to be reevaluated. Chronic infections can be treated for 2- 6 weeks. Length of treatment is designed to keep bacteria from colonizing and replicating while local tissues heal and normal antibacterial defenses are operational. Without local healing, it will be impossible to prevent further bacterial infections. Many pyoderma and lower UTIs are frequently recurrent requiring frequent treatments. I prefer pulse therapy, treating these patients for short periods but frequently.

Ruling out a treatable bacterial infection Antimicrobial can be used as diagnostic tools. A therapeutic trial is only effective if the response to therapy gives high probability of a yes or no answer. Selecting an antibiotic depends on the rule outs (rickettsia vs. bacteria) and the probability of knowing which pathogen is present. A post op patient following a bowel resection is likely to coliforms, enterococci and anaerobes present if leakage is suspected while a dog with an aspiration pneumonia could have any number of potential pathogens. Select an antimicrobial with an excellent activity rating against the suspected pathogens administer at a dose to maximize its effect. Observe for positive changes in clinical signs which should occur within 24 hours. If no effect is observed after 48 hours it is unlikely that he patient has treatable bacterial infection. The patient may have peritonitis or pneumonia but antibiotics alone will not likely be efficacious. Changing antibiotics is illogical and has a high degree of failure. If the pathogen(s) are known, use a four quadrant approach to effectively choose agents that are effective against all gram positive and gram negative aerobes and anaerobes. Combining a fluoroquinolone with a potentiated penicillin or an aminoglycoside with a penicillin are effective protocols. If no clinical response is noted within 24-36 hours, it is highly unlikely that the patient has treatable infection and further diagnostics are warranted.

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bofloxacin and gentamicin) are concentration dependent. Simply put, to maximize a time dependent antimicrobic you must give it more frequently (not just higher dose) while for a concentration depend antimicrobic increasing its dose is more efficacious than increasing its frequency of delivery.

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Cataracts in dogs: etiology, development and clinical findings Ellen Bjerkås

Summary The definition of cataract is any light-scattering opacity in the lens, regardless of the initial cause, but not necessarily with any demonstrable effect on vision. This definition may also be extended to include opacities of the lens capsule. The end result of cataract formation is destruction of lens tissue with loss of transparency, either partially or completely. Developmental cataracts initially affects cortical fibres, while nuclear cataracts are most often congenital. The nucleus may, however, be affected in more extended developmental cataracts as well. A special form of nuclear cataract is the pulverulent type. Causes of primary cataract include congenital malformations, nutritional deficiencies, toxins, radiation, UV-light, trauma, inheritance and ageing. Secondary cataracts may be caused by systemic diseases as well as other diseases within the eye.

Definition of cataract The word cataract is derived from the greek word katauraktos which means «waterfall». The definition of cataract is any light-scattering opacity in the lens, regardless of the initial cause, but not necessarily with any demonstrable effect on vision. This definition may also be extended to include opacities of the lens capsule1.

Development of the lens - malformations In early embryogenesis, the optic vesicle comes in contact with the surface ectoderm, stimulating the ectoderm to form the lens vesicle. The lens vesicle later separates from the ectoderm. In fetal life the lens is surrounded by a plexus of vessels, the tunica vasculosa lentis, which normally disappears shortly after the puppy is born2. Remnants of the tunica vasculosa lentis may occasionally be visible on the posterior lens capsule. The primary vitreous and tunica vasculosa lentis may also be hyperplastic, this condition is termed PHTVL/PHPV (persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic primary vitreous). PHTVL/PHPV is seen as an inherited condition in some dog breeds, the dobermann being most frequently affected. The changes range from only small pigmented dots on the posterior lens

capsule, not affecting vision, to major changes of the lens including lenticonus (a bulging of the posterior lens capsule), cataract and intralenticular hemorrhage3-5. In front of the lens the mesodermal tissue will differentiate to form the eyelids, conjunctiva, cornea, anterior chamber and the iris. Defective differentiation of the structures may lead to many forms of malformations, including persistent pupillary membranes (PPM) which may attach to the anterior lens capsule and cause opacities6. Other malformations affecting the lens include: aphakia no lens at all, microphakia7-abnormally small lens, anomalies of the lens shape (colobomas, lenticonus and lentiglobus)8 and congenital cataract. Congenital cataract may be present in an otherwise normal eye, or may be associated with other malformations, most commonly microphthalmia.

Lens anatomy and physiology The normal lens is a clear structure, the oldest part being the nucleus. The lens is surrounded by a collagenous lens capsule freely permeable to water, ions and other small molecules. This lens capsule forms the basement membrane of the lens epithelium. The lens epithelial cells which cover the anterior part of the lens are a simple layer of cells, lying side by side, but not tied together by «tight junctions». Thus, there is no major barrier across the epithelium into the extracellular spaces between the lens fibres. This is of potential importance to the effects on the lens of drugs delivered topically to the eye, and also to changes in the composition of the aqueous9. The germinative zone of the epithelium is in the periphery, at the equator, and mitoses here give rise to new rows of cells. These differentiate into secondary lens fibres (cortical fibres) by elongation and loss of their nucleus. The layer of secondary lens fibres is termed the lens cortex. The cortical fibres meet and form suture lines anteriorly and posteriorly. The anterior suture lines form an Y, whereas at the posterior pole they form an Y upside down. The lens steadily grows throughout the whole life of the animal, adding layers of cortical fibres to the already existing lens tissue. The lens can only expand to a very limited extent, therefore the result of this growth is that the lens fibres become more densely packed with increasing age, giving the lens a blueish appearance. The increased density of the lens is termed nuclear sclerosis and is a normal age

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DVM, PhD, Dipl ECVO Norwegian College of Veterinary Medicine - Department of Small Animal Clinical - Norway

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change which should not be confused with cataract. True senile cataracts with loss of transparency may occur in dogs as in other species, however. The cortex is the most metabolic active part of the lens, and cataractogenic factors are most likely to influence the cortical fibres initially. In comparison, congenital abnormalities will more probably affect the nucleus which after birth is far less metabolic active than the cortex. The aqueous transports nutrients to the lens. Glucose is the main source of energy, with certain amino acids providing an additional source. Glucose enters the lens by simple diffusion and is mainly metabolized by anaerobic glycolysis. The glycolysis route is regulated by the enzyme hexokinase, which is found in a limited supply within the lens and thus serves as a rate limiting step for glycolysis. A small amount of glucose is also metabolized by the hexose monophosphate shunt which also depends on hexokinase for control rate. Excess glucose is shunted into other pathways, mainly the sorbitol (polyol) pathway. The sorbitol pathway converts glucose to sorbitol which is a sugar alcohol. Normally, the sobitol pathway accounts for only about 5% of the lens metabolism. Hyperglycemia causes more glucose to enter this pathway. The accumulation of sorbitol within lens cells causes an osmotic gradient that draws water into the lens fibres10.

The biochemical causes of cataract The lens fibres are normally held in a relatively dehydrated state. This is important to provide the organized structure of the lens proteins (crystallins). The normal intracellular protein structures are maintained mainly by certain essential amino acids like methionine and cysteine. Low levels of these essential amino acids may therefore lead to destruction of the protein structures and cataract formation11. This is not a condition normally seen in dogs, but may occur in other animal species as well as humans in the third world. In short, it can be said that the biochemical cause of cataract is both water entrying the cells, and the unfolding of the regular protein structures, thus enabling the proteins to form aggregates. Both factors may cause rupture of cell membranes with destruction of lens fibres and production of cellular debris. The result of these structure alterations is scattering of light. The effect of the protein aggregates is especially of significance in cortical cataracts. A major cause of damage to the lens is oxidative stress, and ascorbate, vitamin C, plays an important role in protecting the lens from oxidative damage 1. This is also the reason why vitamin C eyedrops have been tried as cataract treatment, without any effect, however. Another anti-oxidant is glutathione which is present in high concentration in the lens and which acts co-operatively with ascorbate. A third antioxydant which has aroused interest is vitamin E, since in vitro administration of vitamin E on lenses has been shown to slow cataract progression12. Topical administration of vitamin E in vivo has not shown any effect, though.

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Morphologic changes Regardless of the initial cause of cataract formation, the end result is destruction of lens tissue with loss of transparency, either partially or completely. When a cataract develops in previously clear mature lens fibres, there are a limited number of forms that the opacity can take. These forms are determined by the anatomy of the lens fibres and their arrangement within the lens, so-called fibre-based cataracts. Thus, when fibres within a particular perinuclear cortical fibre shell are affected, a lamellar cataract is formed. When limited groups of fibres are affected, the appeareance is that of spokes13. This is seen for instance in the late form of developmental cataract in the Boston terrier14. If the tips of the fibres are affected, the opacity forms the branching pattern of the sutures as the fibre tips enter the suture lines. Such opacities are usually subcapsular and situated at the posterior pole. Lens vacuoles are often found in connection with cataract and are considered to represent early changes of lens fibres. Transient vacuoles have been reported in humans15 and may well be occurring in dogs as well. However, in dogs they will most often just represent a stage of cataract development, indication that the cataract is progressing. In addition to the described changes of the originally normally developed lens fibres itself, the epithelium may loose the ability to produce normal lens fibres. This may be the explanation of posterior polar cataracts in dogs, and also of radiation cataracts in humans. Abnormal fibres first appear in the posterior subcapsular region of the lens periphery, where the changes may be difficult to detect. The abnormal fibres then move axially in the direction normally taken by the growing lens fibres. Eventually they will form a subcapsular cataract around the posterior pole. At a later stage of cataract development, fibrous metaplasia of epithelial cells may also occur. There may also be proliferation of the epithelial cells, which gives rise to abnormally shaped bladder cells. Nuclear cataracts are most often congenital, but the nucleus may also be affected in more extended developmental cataracts as well. A special form of nuclear cataract is the pulverulent type, the name borrowed from human ophthalmology. Early changes occur early in life as small opacities along the suture lines, just behind the fetal nucleus. At the age of 4-5 years, a ball of small opacities appear in the nucles, giving the nucleus a candy-floss appearance. The changes do not involve the whole nucleus, the outer adult nucleus is unchanged. This type of cataract has been described in the Norwegian buhund 16, but occurs also in other breeds, like the German shepherd and the Leonberger.

Description of cataract Cataracts can be divided into primary and secondary cataracts. Secondary cataracts occur because of other changes within the eye. These include uveitis, glaucoma, lens luxation and retinal degeneration. Cataract may also be

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Description according to localization of the changes: - nuclear cataract - anterior/posterior polar cataract - equatorial cataract - cortical cataract - complete cataract - subcapsular cataract - capsular cataract

Causes of cataract • Malformations (see above). • Nutritional deficiencies, not as important in dogs as in certain other animal species. • Toxins. Cataract is a common indicator in toxicity studies18. Long-term topical administration of steroids has been proven to cause cataract in humans and in laboratory animals19. The effect in dogs is uncertain. • Radiation. UV-light is one factor causing cataracts in humans. The effect of UV-light and oxidative damage on the dog lens has not been thoroughly studied. • Trauma. The changes in traumatic cataract depend on the type of injury. Blunt trauma to the eye may cause complete cataract that does not become obvious until a couple of weeks after the accident, since the initial changes are subtle and difficult to observe. Smaller injuries, like a stab by a cat claw through the lens capsule may result in only a focal opacity, especially if the capsule seals rapidly after the injury and the destruction of lens fibres is limited. • Inheritance (see below). • Ageing • Secondary cataracts Systemic diseases. These will be covered in a separate lecture. Other diseases within the eye.

Hereditay cataract Hereditary cataracts are of particular importance in dogs, and there is a long list of breeds with cataracts proven or suspected to be inherited. Despite a considerable number of affected dogs within certain breeds, establishing the modes of inheritance has proven difficult. Evidence for autosomal recessive inheritance are convincing in the two types of cataract in the miniature schnauzer and in cataract in the Afghan hound. Otherwise convincing information on modes of inheritance is lacking. There is also limited knowledge as to what is actually inherited, that is whether it is the lens changes per se or some initiating factor. Criteria for classifying cataract changes as hereditary cataracts17: • Hereditary cataract has previously been described in the breed. • The age of appearance and the localization of the lenticular changes correspond to those described in this breed. • The cataract occurs bilaterally (there may be exceptions). • The cataract is progressive, although slowly in certain cases. The problem arises when cataract is diagnosed in a «new» breed. The advise would be not to breed the affected animal(s). Re-examination of the dog for signs of progression of the cataract, as well as examination of littermates, offspring and parents should be performed. Unilateral cataracts suspected to be hereditary may also be difficult to evaluate, and affected animals should be re-examined at a later stage for signs of bilateral involvement. Examination of the colsest family of the affected dog is also advised. As the genetic lines within breeds differ from country to country, there will be variation in the cataract incidences. Information on affected breeds and cataract incidence can be obtained from the national eye panels for inherited eye diseases in each respective country20-21.

Secondary cataracts Other eye diseases may cause secondary cataracts. These diseases include uveitis, lens luxation, glaucoma and retinal disease. The cause of cataract is the change in composition of the aqueous, with the presence of inflammatory or other products acting toxic to the lens. In addition, there may be a direct effect on the lens capsule of the adherence of iris to the lens in uveitis. Ocular signs, including cataract, secondary to systemic disease will be covered in a separate lecture.

Lens induced uveitis Leakage of the smallest crystallins (d crystallins) through the lens capsule occurs to a minor degree in normal eyes, but the rate of leakage is increased in the presence of cataract22. The reason for this is that breakdown of the fibre membranes can release crystallin sub-units or proteolytic fragments of appropriate size to leak into the aqueous. These substances are considered foreign material by the eye and will cause an inflammatory reaction.

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associated with microphthalmia. Primary cataracts develop in an eye otherwise normal. Cataracts can be described according to stages of development17: • Incipient cataract describes focal opacification(s) of the lens and/or its capsule. Vision is not impaired. This cataract may or may not progress. • Immature cataract. The opacity is more or less diffuse, but the fundus can still be examined. Vision may or may not be impaired. The changes are mostly progressive. • Mature cataract. The fundus cannot be inspected, as the opacification is complete and dense. Vision is severely impaired. If a mature cataract takes up fluid and swells it is referred to as intumescent. • Hypermature cataract. Dissolving of the cataract may occasionally occur. The content of the lens capsule is more or less liquefied. Lens protein can be resorbed, leading to shrinkage of the lens with wrinkling and dimpling of the capsule. The nucleus will dissolve to a lesser extent and may migrate inferiorly in the capsular bag to form what is termed a Morgagnial cataract.

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Clinical signs of lens-induced uveitis are those of a lowgrade chronic uveitis: - «red eye» - moderately lowered intraocular pressure - moderately miotic pupil - darkened iris Lens-induced uveitis is treated with anti-inflammatory therapy. The inflammation should preferably be controlled before attempting cataract surgery.

10.

References

13.

11. 12.

14. 1. 2. 3.

Brown NP, Bron AJ, (1996), Lens disorders, Butterworth-Heinemann Ltd, Oxford, 91-132. Glaze MB, Carter JD, (1995), Veterinary Pediatrics, WB Saunders Philadelphia 1995: 297-336. Boevé MH, van der Linde Sipman T, Stades FC, (1988), Morphogenesis of persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous, Invest Ophthalmol Vis Sci, 29: 1076-1086. Boevé MH, Stades FC, van der Linde-Sipman, Vrensen GFJM, (1992), Persistent hyperplastic tunica vasculosa lentis and primary vitreous (PHTVL/PHPV) in the dog: A comparative review, Progr Vet Comp Ophthalmol, 2: 163-172. Leon A, Curtis R, Barnett KC, (1986), Hereditary persistent hyperplastic primary vitreous in the Staffordshire bull terrier, J Am Anim Hosp Assoc, 22: 765-774. Strande A, Nicolaissen B, Bjerkås I, (1988), Persistent pupillary membrane and congenital cataract in a litter of English cocker spaniels, J Small Anim Pract, 29: 257-260. Molleda JM, Martin E, Ginel PJ, et al, (1995), Microphakia associated with lens luxation in the cat, J Am Anim Hosp Assoc, 31: 209-212.

15. 16. 17.

18.

19. 20. 21. 22.

Narfström K, Dubielzig R, (1984), Posterior lenticonus, cataracts and microphthalmia; congenital ocular defects in the cavalier king charles spaniel, J Small Anim Pract, 25: 669-77. Brown NP, Bron AJ, (1996), Lens disorders, Butterworth-Heinemann Ltd, Oxford, 53-90. Basher AW, Roberts SM, (1995), Ocular manifestations of diabetes mellitus: diabetic cataracts in dogs, Vet Clin North Am, Small Anim Pract 25: 661-676. Whikehart DR, (1994), Biochemistry of the eye, Butterworth-Heinemann Ltd, Oxford, 1-30. Kojima M, Shui YB, Murano H, Sasaki K, (1996), Inhibition of steroid-induced cataract in rat eyes by administration of vitamin-E ophthalmic solution, Ophthalmic Res 28: 64-71. Brown NP, Bron AJ, (1996), Lens disorders, Butterworth-Heinemann Ltd, Oxford, 133-160. Curtis R, (1984), Late-onset cataract in the Boston terrier, Vet Rec, 115: 577-578. Brown N, (1971) The visibility of transparent objects in the eye by retro-illumination, Br J Ophthalmol 55: 517-524. Bjerkås E, Haaland M, (1995), Pulverulent nuclear cataract in the Norwegian buhund, J Small Anim Pract, 36: 471-474. Peiffer RL, Petersen-Jones SM, (1997), Small animal ophthalmology: a problem-oriented approach, WB Saunders, Philadelphia, 85165. Martin CM, Christmas R, Leipold HW, (1072), Formation of temporary cataracts in dogs given a disophenol preparation, J Am Vet Med Assoc, 161: 294-301. Urban RC, Cotlier E, (1986), Corticosteroid-induced cataracts, Surv Ophthalmol, 31: 102-110. Rubin LF, (1986), Inherited eye diseases in purebred dogs, Williams & Wilkins, Baltimore. ACVO Genetics committee (1996), Ocular disorders presumed to be inherited in purebred dogs. Van der Woerdt A, Nasisse MP, Davidson MG, (1992), Lens-induced uveitis in dogs: 151 cases (985-1990), J Am Vet Med Assoc, 201: 921-926.

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Ocular signs of systemic diseases in dogs Ellen Bjerkås

Summary Ocular change is a prominent feature of many systemic diseases. The ocular signs may accompany changes elsewhere in the body, or may be the only present sign of systemic disease. Thus, a complete history and a thorough clinical examination of the whole animal are essential in all dogs presented with eye disease. The age of the animal should also be considered. Malformations, as for instance portosystemic shunts causing hepatic encephalopathy, affect young animals, whereas other diseases, like diabetes mellitus, usually occur in middle-aged animals. Systemic diseases causing ocular signs may be divided into: • Infectious diseases • Immune-mediated diseases • Metabolic diseases • Diseases of the cardiovascular system • Neoplasias • Nutritional deficiencies

Ocular change is a prominent feature of many systemic diseases. The ocular signs may accompany changes elsewhere in the body, or may be the only present sign of systemic disease. Thus, a complete history and a thorough clinical examination of the whole animal are essential in all dogs presented with eye disease. The age of the animal should also be considered. Malformations, as for instance portosystemic shunts causing hepatic encephalopathy, affect young animals, whereas other diseases, like diabetes mellitus, usually occur in middle-aged animals. Systemic diseases causing ocular signs may be divided into: • Infectious diseases • Immune-mediated diseases

CAUSE OF DISEASE

• Metabolic diseases • Diseases of the cardiovascular system • Neoplasias • Nutritional deficiencies The initial ophthalmic signs of systemic disease may be divided into two main groups: «Red eyes» and visual disturbance. «Red eyes» are caused by inflammation, either of the extraocular or the intraocular structures. Inflammation of extraocular structures is associated with conjunctival hyperemia, while inflammation of deeper structures is also associated with episcleral hyperemia. One should always remember that the eye is highly susceptible to inflammation which may lead to loss of vision. Thus, a correct diagnosis both of the ocular disease as well as of the possible underlying cause is of importance. Unilateral ocular manifestations do not exclude the presence of a systemic disease. Some diseases may initially cause inflammation, with later progression to blindness. In some infectious diseases the age of the animal when infected determines the ocular signs. Canine herpesvirus is an example of this, as puppies infected perinatally may develop retinal dysplasia, while adults only develop mild conjunctivitis1. Sudden blindness may occur because of ocular change, but one should always also remember that diseases of the brain can cause visual disturbance. Changes in the innervation of intraocular and extraocular structures, presenting with ocular signs, may also be a result of damage to the brain as well as to the actual cranial nerve. Below there is a detailed list of common and less common systemic diseases associated with ocular signs. The most important of these diseases will be discussed in the lecture.

OCULAR SIGNS

Infections Virus Canine distemper2 Infectious canine hepatitis2

Conjunctivitis, KCS, chorioretinitis, optic neuritis. The end-stage of a slowly progressing multifocal chorioretinitis may resemble PRA. Blindness may also be associated with encephalitis. Uveitis. Corneal edema due to endothelial damage, «blue eye», is a prominent feature. This may also occur after vaccination with live hepatitis virus. Some breeds are reported to be more susceptible than others: Afghan hound, basset hound, Siberian husky and St.Bernard.

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Canine herpesvirus1

Conjunctivitis, keratitis, uveitis. Usually mild signs in adults. More serious signs including retinal dysplasia in perinatal infection.

Rabies2

Chorioretinitis, optic neuritis. Central blindness.

Bacteria Leptospira spp.3

Episcleral injection, yellowing of the sclera due to icterus, conjunctival petechia, uveitis.

Brucella canis3

Uveitis. Ocular signs are rare.

Clostridium tetani4

Enophthalmos, protrusion of the third eyelid.

Borrelia burgdorferi5

Uveitis, chorioretinitis. Ocular signs are rare in dogs.

Sec. to systemic bacterial disease3

Uveitis, endophthalmitis. Examples of bacterial diseases: Pyometra, prostatitis, severe otitis externa.

Protozoa Toxoplasma gondii2

Uveitis, chorioretinitis. More common in cats, but should be considered in chorioretinitis.

Leishmania donovani5,6

Blepharitis (ÂŤspectacle blepharitisÂť) with skin surface desquamation and hair loss. Keratoconjunctivitis, keratouveitis. Endemic disease in Southern Europe.

Babesia spp.2

Chorioretinitis. Rare.

Neospora caninum7

Uveitis, chorioretinitis.

Rickettsia Rickettsia rickettsii8 (Rocky Mountain spotted fever)

Conjunctivitis, keratitis, uveitis, petechial (Rocky Mountain spotted fever) retinal hemorrhage.

Ehrlichia canis9 (tropical canine pancytopenia)

Conjunctivitis, conjunctival hemorrhage, hyphema, uveitis, keratic precipitates, retinal detachment. Widespread in Europe.

Fungi and algae3 Blastomyces dermatitidis10 Cryptococcus neoformans Histoplasma capsulatum Coccidioides immitis Aspergillus fumigatus11 Prototheca Parasites Toxocara canis12

Granulomatous uveitis and chorioretinitis Cryptococcus neoformans Systemic mycoses are more common in America than in Europe.

Visceral larvae migrans may cause choroidal granulomas, intraretinal hemorrhage and retinal necrosis. End-stage may present as generalized retinal degeneration.

Dirofilaria immitis4

Uveitis, vitritis, larvae may be visible in the anterior chamber. Death of larvae within the eye may cause severe uveitis resulting in blindness.

Fly larvae, Cuterebra, Oestrus, Hypoderma13

Uveitis, vitritis, larvae may be visible in the anterior chamber. Occasionally reported.

Demodex canis3

Non-pruritic blepharitis with periocular hair loss. Most common in young animals.

Immune-mediated diseases Uveodermatologic syndrome14

Uveitis, depigmentation of uvea. Pigment loss of the skin on eyelids, lips, paws and occasionally elsewhere on the body as well as depigmentation of hair in the same regions. Breed predisposition in the Akita inu, Samoyed, Siberian husky, also reported in other breeds. Comparable with Vogt-Koyanagi-Harada syndrome in humans.

Pemphigus complex15

Ulceration of mucocutaneous areas, including eyelids. KCS.

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Systemic lupus erythematosus15

Ulceration of mucocutaneous areas, including eyelids. KCS, uveitis. Glomerulonephritis may cause hypertension (see cardiovascular diseases).

Immune-mediated thrombocytopenia15

Petechiae in conjunctiva, hyphema, retinal hemorrhage.

Atopy15

Blepharitis, conjunctivitis, chemosis

Diabetes mellitus16

Cataract, bilateral. Rapid development may cause swelling of the lenses and lens induced uveitis. Diabetic retinopathy is rare in dogs.

Hypoparathyroidism (hypocalcemia)17

Linear cataract reported in a few dogs.

Hypothyroidism18

Corneal deposits, KCS, signs of hyperlipoproteinemia. Facial paralysis may cause secondary exposure keratitis.

Hyperlipoproteinemia19

Primary or secondary. Lipemia of ocular blood vessels, corneal opacities, lipemic aqueous.

Hyperadrenocorticism (Cushing’s disease)20

Sudden acquired retinal degeneration (SARD)? An association with SARD has been found in some patients.

Ceroid lipofuscinosis (CL)21 (lysosomal storage disease)

Hereditary diseases. Deposits of lipofuscin (lysosomal storage disease) in ganglion cells and RPE cells. Secondary retinal degeneration. CL diagnosed in many breeds, not all of them show ocular changes. Affected English setters have normal retinas. Retinal changes described in the Tibetan terrier and the Polish owczarek nizinny.

Other lysosomal storage diseases22

Group of hereditary storage diseases. Corneal opacities, CNS signs.

Hepatic encephalopathy (liver failure)22

Central blindness.

Ehler-Danlos syndrome23

Rare congenital disease. Corneal edema, KCS, cataract, lens luxation.

Diseases of the cardiovascular system Hypertension24

Primary or secondary to other systemic disease, most commonly chronic renal failure. Mildest signs often not noticed: tortuosity of retinal vessels, «cotton wool spots» due to ischemia of vessels in the nerve fibre layer of the retina. More severe changes include retinal hemorrhage, retinal detachment and edema of the optic nerve head. Dogs are most often presented with acute loss of vision.

Coagulopathies (deficency of clotting factors)25

Conjunctival hemorhage, hyphema, retinal hemorrhage. Also see immunemediated thrombocytopenia.

Hyperviscosity syndrome26

Tumors producing plasma cells may cause monoclonal gammopathies which lead to increased levels of plasma immunoglobulins and increased viscosity of the blood. Distention of retinal vessels, retinal hemorrhage, retinal detachment, hyphema.

Neoplasias (metastases) Malignant lymphoma / malignant fibrous histiocytoma27,28

Tumor infiltration in lymphoid tissue in conjunctiva. Tumor infiltration of uvea. Uveitis, retinal detachment, retinal hemorrhage.

Other tumors29

Metastases from other tissues. Adenocarcinomas from the mammary glands most common.

Nutritional deficiencies Vitamin A deficiency2

Rare in dogs. KCS, keratomalacia, retinal changes. Nyctalopia.

Riboflavin (vitamin B) deficiency2

Keratitis. (Retinal degeneration reported in fish).

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Metabolic diseases

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Vitamin E deficiency (experimental)30

Ophthalmoscopic changes of the retina similar to «central PRA». Affection of pigment-epithelial cells.

Zinc deficiency33

Dry, scaly skin, blepharitis. Siberian husky reported to be especially susceptible. (Cataract reported in fish).

References 1.

2. 3. 4. 5. 6.

9. 10.

11. 12.

13.

14.

15. 16.

Albert DM, Lahav M, Carmichael LE et al, (1976), Canine herpes-induced retinal dyplasia and associated ocular anomalies, Invest Ophthalmol 15: 267-278. Ettinger SJ, (1997), Textbook of Veterinary Intenal Medicine, 4th edition, Saunders, Philadelphia, 524-533. Gelatt KN, (1991), Veterinary Ophthalmology, 2nd ed, Lea and Febiger, Philadelphia, 357-395. Morgan RV, (1992), Handbook of small animal practice, 2nd ed, Churchill Livingstone, New York, 1119-1123. Roze M, (1997), Les uvéites, Prat Med Chir 32 (suppl): 129-147. Gothe R, (1990), Leishmaniosen des Hundes in Deutschland: Erregerfauna und -biologie, Epidemiologie, Klinik, Pathogenese, Diagnose, Therapie und Prophylaxe, Kleintierpraxis, 36: 69-84. Dubey JP, Koestner A, Piper RC, (1990), Repeated transplacental transmission of Neospora caninum in dogs, J Amer Vet Med Assoc 197: 857-860. Davidson MG, Edward BB, Nasisse MP, (1989) Ocular manifestation in Rocky Mountain spotted fever in dogs, J Amer Vet Med Assoc, 194: 777-781. Woody BJ, Hoskins JD, (1991) Ehrlichial diseases of dogs. Vet Clin North Am Small Anim Pract 21: 75-98. Bloom JD, Hamor RE, Gerding PA, (1996), Ocular blastomycosis in dogs: 73 cases, 108 eyes (1985-1993), J Amer Vet Med Assoc, 209: 1271-1274. Gelatt KN, Christmas CL, Samuelson DA, et al, (1991), Ocular and systemic aspergillosis in a dog, J Am Anim Hosp Assoc, 27: 427-431. Johnson, BW, Kirkpatrick CE, Whiteley HE et al, (1989), Retinitis and intraocular larval migration in a group of border collies, J Am Anim Hosp Assoc, 25: 623-629. Gwin RM, Meredith R, Martin CL, (1984), Ophthalmomyiasis interna posterior in two dogs and a cat, J Am Anim Hosp Assoc, 20: 481486. Murphy CJ, Bellhorn RW, Thirkill C, (1991), Anti-retinal antibodies associated with Vogt-Koyanagi-Harada-like syndrome in a dog, J Am Anim Hosp Assoc, 27: 399-402. Ettinger SJ, (1989), Textbook of Veterinary Internal Medicine, 3th edition, Saunders, Philadelphia, 2283-2327. Basher AW, Roberts SM, (1995), Ocular manifestations of diabetes

17. 18. 19. 20.

21.

22. 23.

24. 25. 26.

27.

28.

29. 30. 31.

mellitus: diabetic cataracts in dogs, Vet Clin North Am, Small Anim Pract 25: 661-676. Mannerfelt T, (1997), Primär hypoparathyroidism hos hund, Sv Vet T, 49: 473-478. Crispin SM, Barnett KC, (1978, Arcus lipoides corneae secondary to hypothyroidism in the Alsatian, J Small Anim Pract, 19: 127-142. Crispin SM, (1993), Ocular manifestations of hyperlipoproteinaemia, J Small Anim Pract, 34: 500-506. van der Woerdt A, Nasisse MP, Davidson MG, (1991), Sudden acquired retinal degeneration in the dog: Clinical and laboratory findings in 36 cases, Progr Vet Comp Ophthalmol, 1:11-18. Wrigstad A, Nilsson SEG, Dubielzig R, Narfström K, (1995), Neuronal ceroid lipofuscinosis in the Polish owczarek nizinni (PON) dog. A retinal study, Doc Ophthalmol, 91: 33-47. Oliver JE, Lorenz MD, (1993), Handbook of veterinary neurology, Saunders, Philadelphia, 322-373. Barnett KC, Cottrell BD, (1987), Ehler-Danlos syndrome in a dog: ocular, cutaneous and articular abnormalities, J Small Anim Pract, 28: 941-946. Bartges JW, Willis AM, Polzin DJ, (1996), Hypertension and renal disease. Vet Clin North Am- Small Anim Pract, 26: 1331-1345. Ettinger SJ, (1989), Textbook of Veterinary Intenal Medicine, 3th edition, Saunders, Philadelphia, 2246-2279. Lane IF, Roberts SM, Lappin MR, (1993), Ocular manifestation of vascular disease: hypertension, hyperviscosity and hyperlipidemia, J Am Anim Hosp Assoc, 29: 28-36. Krohne SG, Henderson NM, Richardson RC, Vestre WA, (1994), Prevalence of ocular involvement in dogs with multicentric lymphoma: prospective evaluation of 94 cases. Prog Vet Comp Ophthalmol, 3: 152-157. Scherlie PH, Smedes SL, Feltz T, et al, (1992), Ocular manifestation of systemic histiocytosis in a dog, J Am Vet Med Assoc, 201: 12291232. Dubielzig RR, (1990), Ocular neoplasia in small animals. Vet Clin North Am. Small Anim Pract, 20: 837-849. Riis RC, Sheffy BE, Loew E, et al, (1981), Vitamin E deficiency retinopathy in dogs, Am J Vet Res, 42: 74-86. Van Den Brock AHM, (1988), Diagnostic value of zinc concentrations in serum, leukocytes and hair of dogs with zinc-responsive dermatosis. Res Vet Sci, 44: 41-44.

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Ocular signs of systemic diseases in cats Ellen Bjerk책s

Summary In cats, many systemic diseases show ocular manifestations. The importance of a complete work-up in cats presented with diseases of the eye or adnexa should therefore not be under-estimated. When examining the animal, one must determine whether there are signs of concurrent systemic disease. Conversely, if a cat is presented with a systemic disease that is frequently associated with ocular changes, a careful examination of the eyes is necessary to detect changes which should be treated. Uveitis with or without chorioretinitis is one of the most frequent and significant ophthalmic diseases in cats.The most important causal agents are coronavirus (feline infectious peritonitis), feline leukemia virus, Toxoplasma gondii and feline immunodeficiency virus, but other factors may also cause uveitis. The other important group of systemic diseases causing ocular changes is the infectious upper respiratory tract diseases.

In cats, many systemic diseases are associated with ocular manifestations. The importance of a complete work-up in cats presented with diseases of the eye or adnexa should therefore not be under-estimated. When examining the animal, one must determine whether there are signs of concurrent systemic disease. Conversely, if a cat is presented with a systemic disease that is frequently associated with ocular changes, a careful examination of the eyes is necessary to detect changes which should be treated.

Uveitis Uveitis with or without chorioretinitis is one of the most frequent and significant ophthalmic diseases in cats. In recent reports, between 38% and 70% of the cats with uveitis have concurrent systemic disease1. The most important causal agents are coronavirus (feline infectious peritonitis), feline leukemia virus, Toxoplasma gondii and feline immunodeficiency virus2,3. Feline herpesvirus is also a suspected cause of uveitis, since diagnostic tests (polymerase chain reaction -PCR) has revealed herpesvirus-DNA in the aqueous of a number of cats with so-called idiopathic uveitis. FIP may present in a granulomatous (dry) and a produc-

tive (wet) form. The granulomatous form of FIP, which is caused by a partial cell-mediated immune response, is most often associated with ocular signs, and uveitis may even be present without concurrent signs of systemic disease. Ocular changes linked to FeLV are related to the ability of the virus to induce immunosuppression, hematologic changes and tumor formation4. Ocular signs include retinal dysplasia, tumor formation, retinal hemorrhages and pupillary changes. Perinatal infection can result in retinal dysplasia, which occurs seconday to diffuse retinal inflammation. Spontaneous retinal hemorrhage is the result of anemia-induced hypoxia of small retinal vessels followed by increased capillary fragility and rupture of the vessels. Abnormalities in pupil shape include spastic pupil, D-shaped pupil and reversed D-shaped pupil5. These changes probably represent FeLV infection of the autonomic ganglia for the parasympathetic portion of the third cranial nerve which delivers one branch to each of the two pupillary constriction muscles of the iris. Feline immunedeficiency virus may cause a mild uveitis that can be aggravated by co-infection with Toxoplasma gondii. The prevalence of toxoplasmosis has been difficult to determine, but the demonstration that IgM titers to the organism can be found in many uveitis-affected cats has led to heightened interest in toxoplasmosis as a cause of feline uveitis6.

Upper respiratory tract infections The other important group of systemic diseases causing ocular changes is the upper respiratory tract diseases. By tradition, four infectious agents have been associated with conjuntivitis: Feline herpesvirus, Chlamydia psittaci, Calicivirus and Mycoplasma spp. Mycoplasma is a common finding in the normal conjunctival flora of cats7. This may suggest that mycoplasma species are rarely pathogenic unless the animal is immunosuppressed or very young. Calicivirus-infection has also been associated with conjunctivitis. Experimental inoculation with calicivirus in cats has not produced ocular signs as response to infection, however2. The significance of this virus in conjunctivitis may therefore be worth further studies. Chlamydia psittaci is a primary conjunctival pathogen in cats, and spread to other cats within a household is not un-

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common8. After infection, organisms are shed for a long period of time. Although different from the human strain, there are similarities enough for the feline strain to cause infections in humans. The zoonotic aspect should therefore be considered when treating affected anmals. Perinatal chlamydial infection is also considered a cause of ophthalmia neonatorum in cats. Feline herpesvirus (FHV-1) is a very common pathogen, studies in the USA have shown that abut 75% of the adult cat population is seropositive. Latency is established in the trigeminal ganglia, and a chronic carrier state develops with intermittent virus shedding9. Recurrence is common, especially with stress or other systemic disease. Newborn kittens may develop ophthalmia neonatorum if infected before the eyes are opened. The infection may also progress to affect the cornea and cause a keratitis which may result in corneal perforation, endophthalmitis and phthisis. Older kittens develop a serous conjunctivitis with chemosis and subsequent conjunctival epithelial necrosis. Corneal changes are seen as superficial branching ulcera, socalled «dendritic ulcera». These changes are often too superficial to be diagnosed by staining with fluorescein, however staining with rose-bengal may show the corneal

DISEASE

changes. Symblepharon formation (adhesion of conjunctiva to itself or to the cornea) is not an uncommon sequela of primary FHV-1 infection. The ability of herpesvirus to produce epithelial necrosis is presumably responsible for the symblepharon formation in young cats. Older cats with signs of recrudescent herpesvirus-infection show only moderate signs of systemic disease. The ocular changes are often more severe than in primary infection, however. Corneal changes are often unilateral and present as superficial keratitis with dendritic or geographic epithelial defects due to virus replication, or as stromal keratitis. Stromal keratitis is probably not caused by active viral replication, as virus is rarely isolated from these ulcers. The changes of the corneal stroma may, however, be the result of a hypersensitivity reaction to viral antigens in the stroma. Corneal sequestration (corneal necrosis - «black body») is a non-specific response to keratitis, but FHV-1 is considered a contributing factor in many cats. Chronic conjunctivitis may cause keratoconjunctivitis sicca because of obstruction of the lacrimal gland ducts. Below there is a detailed list of both common and less common systemic diseases which may cause ocular changes. The most important of these diseases will be discussed in the lecture.

OCULAR SIGNS

Infectious diseases Virus Feline herpesvirus2

Perinatal infection: ophthalmia neonatorum. Young kittens: serous conjunctivitis, conjunctival epithelial necrosis, «dendritic» corneal ulcera, symblepharon. Recurrent infection: superficial or stromal keratitis, corneal sequestration, KCS, uveitis (?)

Calicivirus2

Conjunctivitis. Significance?

Coronavirus (Feline infectious peritonitis)10

Granulomatous uveitis, chorioretinitis, keratic precipitates.

Feline Leukemia virus2

Tumor cells in uvea, uveitis, retinal hemorrhage, keratic precipitates, change in pupil shape. Retinal dysplasia in perinatal infection.

Feline immunodeficiency virus2,11

Any ocular change, serious eye changes probably due to secondary problems caused by immunosuppression.

Panleukopenia virus12

Conjunctivitis, chorioretinitis. Fetal or perinatal infection: retinal dysplasia, optic nerve hypoplasia.

Borna disease virus (staggering disease)13

Central blindness.

Pox virus2

Blepharitis, conjunctivitis.

Bacteria

Mycobacterium tuberculosis14

Uveitis, chorioretinitis, retinal detachment.

Chlostridium tetani

Protrusion of third eyelid.

Chlamydia psittaci2

Conjunctivitis, chemosis. Ophthalmia neonatorum.

Mycoplasma spp.7

Conjunctivitis, chemosis. Significance?

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Rickettsia Hemobartonella felis15 (feline infectious anemia)

Anemic retinopathy, retinal hemorrhage.

Protozoa Toxoplasma gondii16

Uveitis, chorioretinitis.

Cryptoccus neoformans4,17

USA. Occurs occasionally also in other parts of the world. The most common of the systemic mycoses in cats, but systemic mycoses are generally rare in this species. Uveitis.

Histoplasma capsulatum4,18

Endemic disease in temperate and tropical regions. Uveitis.

Blastomyces dermatitidis4

America, Africa. Uveitis.

Coccidioides immitis4

America. Uveitis.

Microsporum spp.2

Blepharitis.

Parasites2 Notoedres cati

Blepharitis, pruritic.

Demodex spp.

Non-pruritic periocular hair loss.

Toxocara cati

Intraretinal hemorrhage, retinal necrosis, choroidal granulomas.

Dirofilaria immitis

Uveitis, vitritis, larvae may be visible in the anterior chamber.

Fly larvae, Cuterebra, Oestrus, Hypoderma

Uveitis, vitritis, larvae may be visible in the anterior chamber.

Thelazia californiensis

Conjunctivitis, nematodes found in conjunctiva.

Immune-mediated diseases2 Pemphigus complex

Ulceration of mucocutaneous junctions.

Allergies (especially food allergies)

Blepharitis.

Metabolic diseases Diabetes mellitus19

Ocular manifestations are rare in cats. Cataract and diabetic retinopathy have been reported.

Hepatic encephalopathy (liver failure)20

Central blindness.

Renal failure

See hypertension.

Hyperthyroidism

See hypertension.

Hyperparathyroidism21

Cataract.

Hyperlipemia, familial hypercholesterolemia22

Lipemia retinalis, lipemic aqueous.

Lysosomal storage diseases23

Corneal opacity, accumulation in ganglion cells, retinal lesions, central blindness.

Chédiak-Higashi syndrome2

Color dilution, cataract.

Diseases of the cardiovascular system Hypertension24,25

Primary or secondary to chronic renal failure or hyperthyroidism. Mildest signs often not noticed: Tortuosity of retinal vessels, «cotton wool spots»

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due to ischemia in vessels in the nerve fibre layer of the retina. More severe changes include retinal hemorrhage, retinal detachment and edema of the optic nerve head. Animals are most often presented with acute loss of vision. Feline infectious anemia (Hemobartonella felis)

Retinal hemorrhage, hyphema. Also listed under infectious diseases.

Coagulation disorders2

Hyphema, conjunctival hemorrhage, retinal hemorrhage.

Hyperviscosity syndrome2

Periarteritis nodosa2

Fibrinoid necrosis of small arteries, formation of granulation tissue leads to vascular occlusion. Exudate in anterior chamber, uveitis.

Diseases of the nervous system Dysautonomia26

Dilated pupils, KCS.

Feline spongiform encephalopathy27

Central blindness. Retinitis in other species.

«Haws syndrome»

Bilateral protrusion of third eyelid. Secondary to infectious diseases.

Nutritional deficiencies Taurine deficiency28

Feline central retinal degeneration progressing to complete retinal degeneration.

Thiamin deficiency29

Mydriasis, peripapillary edema.

Arginine deficiency30

Cataract.

References 1.

2. 3.

4. 5. 6.

8. 9.

10. 11.

12. 13.

Gmensky A, Lorimer D, Blanchard G, (1996), Feline uveitis: a retrospective study of 45 cases. Transactions Am Coll Vet Ophthalmol, 27: 49. Gelatt KN, (1991), Veterinary Ophthalmology, Lea and Febiger, Philadelphia, 529-575. Heider HJ, Pox C, Loesenbeck G, Egberink H, (1997), Ophthalmologische Befunde im Zuzammenhang mit verschiedenen Virusinfektionen der Katze, Kleintierpraxis, 42: 887-900. Barnett KC, Crispin SM, Feline Ophthalmology, (1998), Saunders, London. Gelatt KN, (1991), Veterinary Ophthalmology, Lea and Febiger, Philadelphia, 706-743. Chavkin MJ, Lappin M, Powell CC, Roberts SM, (1993), Seroepidemiologic and clincal observations of 93 cases of uveitis in cats, Prog Vet and Comp Ophthalmol, 2: 29-36. Nasisse MP, Guy JS, Stevens JB, et al, (1993), Clincal and laboratory findings in chronic conjunctivitis in cats: 91 cases (1983-1991), J Am Vet Med Ass, 203: 834-837. Dorin SE, Miller WW, Goodwin JK, (1993), Diagnosing and treating chlamydial conjunctivitis in cats, Vet Med, 325-330. Weigler, BJ, Babineau CA, Sherry B, Nasisse MP, (1997), High sensitivity polymerase chain reaction assay for active and latent feline herpesvirus-1 infections in domestic cats, Vet Rec, 140: 335-338. Davidson MG, Nasisse MP, English RV et al, (1991), Feline anterior uveitis: a study of 53 cases, J Am Anim Hosp Assoc, 27: 77-83. Loesenbeck G, Drommer W, Heider H-J, (1995), Augenbefunde bei serologisch FIV (felines Immundefizienzvirus)-positiven Katzen, Dtsch Tierärztl Wschr, 102: 348-351. Percy D, Scott F, Alberts D, (1975), Retinal dysplasia due to feline panleukopenia virus infection J Am Vet Med Assoc, 167: 935-937. Lundgren AL, Borna disease virus infection in cats. On the etiopathogenesis of feline non-suppurative meningoencephalomyelitis (staggering disease), (1995), Academic thesis, Swedish University of Agricultural Sciences, Uppsala.

14. 15. 16.

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24.

25. 26. 27. 28.

29.

Formston C, (1994), Retinal detachment and bovine tuberculosis in cats, J Small Anim Pract, 35: 5-8. VanSteenhouse JL, Millard JR, Taboada J, (1993), Feline hemobartonellosis, The Compendium, 15: 535-544. Chavkin MJ, Lappin MR, Powell CC, et al., (1991), Seroepidemiologic and clinical observations of 93 cases of uveitis in cats, Prog Vet Comp Ophthalmol, 2: 29-36. Gerds-Grogan S, Dayrell-Hart B, (1997), Feline cryptococcosis: A retrospective evaluation, J Amer Anim Hosp Assoc, 33: 118-122. Peiffer RL, (1979), Ocular manifestations of disseminated histoplasmosis in a cat, Feline Practice, 9: 24-29. Peiffer RL, Gelatt KN, (1974), Cataracts in the cat. Feline Pract, 4: 34-38. Oliver JE, Lorenz MD, (1993), Handbook of veterinary neurology, Saunders, Philadelphia, 322-373. Stiles J, (1991), Cataracts in a kitten with nutritional secondary hyperparathyroidism, Prog Vet Comp Ophthalmol, 1: 296-298. Crispin SM, (1993), Ocular manifestations of hyperlipoproteinaemia, J Small Anim Pract, 34: 500-506. Aguirre G, Stramm L, Haskins M, (1983), Feline mucopolysaccharidosis VI: general ocular and pigment epithelial pathology, Invest Ophthalmol Vis Sci 24: 991-1007. Stiles J, Polzin DJ, Bistner SI, (1994), The prevalence of retinopathy in cats with systemic hypertension and chronic renal failure or hyperthyroidism, J Amer Anim Hosp Assoc, 30: 564-572. Sansom J, Barnett KC, Dunn KA et al., (1994), Ocular disease associated with hypertension in 16 cats, J Small Anim Pract, 35: 604-611. Blaxter A, Gruffydd-Jones TJ, (1987), Feline dysautonomia, Feline Pract, 9: 58-61. Gruffydd-Jones TJ, Galloway PE, Pearson GR (1991), Feline spongiform encephalopathy, J Small Anim Pract, 33: 471-476. Sturman JA, Gargano AD, Messing JM, Imaki H, (1986), Feline maternal taurine deficiency: Effect on mother and offspring, J Nutr 116: 655-667. Ettinger SJ, (1997), Textbook of Veterinary Intenal Medicine, 4th edition, Saunders, Philadelphia, 524-533.

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Acute renal failure: from emergency to patient stabilisation Claudio Brovida

Summary Acute renal failure: from emergency to patient stabilisation. Acute ranal failure (ARF) may be recognized by an abrupt onset of azotemia or oliguria, rapidly progressive azotemia or sudden onset of clinical signs of uremia in a previously healty patient. Several life threatening complications may occur in patients with ARF, they are hyperkalemia, metabolic acidosis, severe anemia, volume depletion, sepsis. Patients may die of the diseases process which initiated ARF (e.g.: acute pancreatitis, sepsis, shock, hypercalcemia, ethylen glycol intoxication) rather than from ARF or its complications. Therefore diagnosis and initiation of specific therapy for diseases which may have precipitated ARF should be a high priority. The history, physical examination and urinalysis are usually sufficient to rule out pre-renal and post-renal causes of azotemia. Although therapy designed to eliminate the cause(s) of ARF will not directly result in repair of renal lesions, it will minimize the severity and extent of renal damage. Symptomatic and supportive therapy designed to minimize deficits and excesses in fluid, electrolyte, acid-base and nutritional balance, will often allow life to be sustained until the body can restore adequate renal structure and function.

Acute renal failure (ARF) is a rapid onset of azotemia over hours to days (two weeks), or pathologic oliguria which could not have been present for more than a few days, that indicates rapid deterioration or loss of renal function. While ARF may not by itself constitute an emergency, its causes (hypovolemia, shock, urinary obstruction, sepsis, etc.) often are life threatening. In addition, the potential for enhancing reversibility of renal lesions and return of renal function may be lost if therapeutic intervention is delayed. In contrast to CFR, rapid diagnosis and initiation of therapy may greatly enhance a favourable prognosis in ARF. ARF may result from diverse renal diseases and injuries. The syndrome of acute tubular necrosis (ATN) accounts for the majority of cases. With ATN there is a rapid reduction in GFR resulting from an ischemic or toxic renal insult. Reduced GFR is thought to result from a combination of vascular and tubular effects. The clinical course of oliguric ATN may be characterized by three sequential phases:

1) initiation and development, 2) maintenance, 3) diuresis (recovery). The initiation phase begins with onset of renal injury and continues through onset of oliguria (reduction in urine output below 0.5-1 ml/kg/hour). Glomerular filtration rate may begin to fall immediately following the renal insult (as in the case of shock), or it may be delayed for hours to days (as in the case with exposure to nephrotoxic drugs). The duration is highly variable, but it usually persists about 1 or 2 weeks. The oliguric phase is characterized by predictable fluid and electrolyte imbalances including alterations in hydration, hyponatremia, hyperkaliemia, metabolic acidosis and hyperphosphatemia. Clinical signs typically develop during the oliguric phase of ATN, including gastrointestinal, hematological and neurological manifestations. Gastrointestinal disorders are common and include anorexia, vomiting, mucosal ulceration and hemorrage. This hemorrage results primarily from defective platelet function, but may also be associated with thrombocytopenia, decreases in various coagulation factors and defects in capillary function. Progressive anemia and neurological disorders characterized by lethargy, depression, stupor and coma may occur during the oliguric phase. Transition from the oliguric to the diuretic phase heralds the onset of re-establishment of tubular continuity, dissolution and/or mobilisation of intratubular casts, and return to near normal patterns of renal perfusion.

Diagnosis of acute renal failure ARF may be recognized by an abrupt onset of azotemia or oliguria, rapidly progressive azotemia, or sudden onset of clinical signs of uremia in a previously healthy patient. A preliminary diagnosis of ARF is based on evidence from medical history, previous data concerning renal function and lack of phisical evidence of CFR (e.g. weight loss, poor haircoat condition, â&#x20AC;&#x153;rubber jawâ&#x20AC;?, growt retardation in puppies). Usually, physical examination of patients with ARF typically reveals good nutritional status. Diagnostic plans should be directed toward:

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1) identifying life-threatening complications, 2) localizing the cause of ARF (e.g. pre-renal, post-renal or primarly renal failure), 3) determining urine volume, 4) differentiating ARF from CRF, 5) determinig the etiology of ARF, 6) monitoring patient response to therapy. It is particularly important to obtain an urine sample for analysis and culture before initiating fluid therapy because fluid therapy may cause concentrated urine to become dilute, making diagnosis of prerenal azotemia difficult. In addition, fluid therapy may alter the urine sediment causing erroneous interpretation.

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to less than 7.10, acidosis may: 1) reduce cardiac contractility and the inotropic response to catecholamines, 2) predispose to ventricular arrhytmias, 3) promote neurologic signs ranging from lethargy to coma.

Volume depletion At the time of diagnosis, most patients with ARF have some degree of volume depletion. Although volume depletion can usually be detected by physical examination, physical changes can be subtle, particularly when fluid loss has occurred quickly and recently.

Medical emergencies in ARF Infection Several life threatening complications may occur in patients with ARF, they are hyperkaliemia, metabolic acidosis, severe anemia, volume depletion, sepis.

Hyperkalemia Hyperkalemia is a common complication of oliguric acute primary renal failure and urinary tract obstruction. It is less commonly associated with non-oliguric acute primary renal failure and is rarely associated with prerenal azotemia unless prerenal azotemia results from Addisonâ&#x20AC;&#x2122;s disease. Detection of bradycardia or other cardiac dysrhytmias should alert one to the possibility of hyperkalemia. Hyperkalemia is confirmed by determination of serum potassium concentrations; however, electrocardiography provides a rapid means of detecting hyperkalemia. Typical electrocardiographic changes observed with mild to moderate hyperkalemia include tall, peaked T waves, slowing of the heart rate, flattening of P waves and prolongation of the P-R intervals and QRS complex. Patients with azotemia, hyperkalemia, hyponatremia may have hypoadrenocorticism (Addisonâ&#x20AC;&#x2122;s disease), in this case the major disadvantage of administering hormone replacement therapy for ARF is that the catabolic effect of corticosteroid administration may increase the magnitude of azotemia.

Metabolic acidosis Metabolic acidosis is a relatively common finding in ARF. The magnitude of renal dysfunction appears to be a poor predictor of metabolic acidosis. Acidosis may be more common in patients with oliguric ARF than nonoliguric ARF, but not all patients with oliguric ARF have significant metabolic acidosis. Therefore diagnosis of metabolic acidosis should be based on evaluation of blood bicarbonate (or total CO2) concentration and, if available, blood pH. Urine pH is not reliable guide to systemic acid-base status. Clinical effects of acidosis are usually minimal unless blood pH is less than 7.20U. However, when blood pH drops

Infection may be a cause or complication of ARF. Dilute urine, oliguria, anuria and urinary obstruction predispose to urinary tract infection. Furthermore uremia is characterized by reduced immunocompetence. Because of these factors, infection is an important cause of morbidity and mortality in uremic patients. Often infections are related to invasive diagnostic and therapeutic procedures such as vascular and expecially urinary catheterisation. Careful attention to detail and intelligent decisions regarding application of use of catheters and invasive diagnostic and therapeutic procedures will dramatically reduce the incidence of infection-related mortality. Examination of urinalysis, urine culture, and a complete blood cell count are indicated to rule out infection as a cause or complication of ARF. When fever, physical examination, or laboratory findings indicate the probability of infection, its location and cause should be vigorously sought so that the most appropriate and least nephrotoxic antimicrobial therapy may be initiated.

Underlying disease processes Patients may die of the diseases process which initiated ARF (e.g. acute pancreatitis, sepsis, shock, hypercalcemia, ethylene glycol intoxication) rather than from ARF or its complications. Therefore, diagnosis and initiation of specific therapy for diseases which may have precipitated ARF should be a high priority. The history, physical examination and urinalysis are usually sufficient to rule-out prerenal and postrenal causes of azotemia.

Renal biopsy Renal biopsy may help to differentiate acute from chronic renal failure. In addition, it may provide an etiologic diagnosis and allow assessment of the potential reversibility of renal injury. However, since renal biopsy is an invasive procedure which entails several risks, it should not be performed unless necessary. Not every patient with ARF re-

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Prognosis of acute renal failure The prognosis for dogs and cats with acute primary renal failure has been generally considered poor. It is best determined by response to therapy. However, the outcome may not become apparent for days to weeks following diagnosis. While it is often difficult to offer an accurate prognosis early in the course of acute primary renal failure, severe, progressive hyperkaliemia, metabolic acidosis and uremic symptoms are negative prognostic indicators. In absence of these factors, patient treatment and monitoring should be continued, even if azotemia continues to increase.

Treatment of acute renal failure Although therapy designed to eliminate the cause(s) of ARF will not directly result in repair of renal lesions, it will minimize the severity and extent of renal damage. Symptomatic and supportive therapy designed to minimize deficits and excesses in fluid, electrolyte, acid-base and nutritional balance, will often allow life to be sustained intil the body can restore adequate renal structure and function. Because many of the complications of ARF are medical emergencies, it is often necessary to initiate therapy before diagnostic evaluation can be completed. Furthermore, treatment of ARF should be modified according to patient response to therapy, that is assessed by comparing pre-treatment and serial post-treatment data. Patient with severe metabolic disturbances may require frequent laboratory and clinical evaluation, whereas patients with less severe disturbances generally require less frequent monitoring.

Fluid therapy Most patients with ARF are volume depleted before induction of therapy. However, the decision to administer fluid therapy should be based on clinical assessment of hydration, in order to correct volume depletion, regardless of urine volume. Because hypovolemia and hypotension cause oliguria and may contribute to the genesis of ATN or predispose to further renal damage, volume depletion should be rapidly corrected. Patients should be rehydrated with replacement fluid via an aseptically placed intravenous catheter. In most cases, cristalloids, like lactated Ringerâ&#x20AC;&#x2122;s solution are satisfactory. However, if a large amount of fluid has been lost, in order to help the increase of the blood oncotic pressure, it is advisable to administer plasma-expanders solution (colloids), up to 20 ml/kg of body weight. Urine volume and other contemporary losses (e.g. vom-

iting and diarrea) greatly influence fluid requirements during the maintenance and recovery phases of ARF. Measurement of urine volume may provide a particularly useful guide to fluid therapy during the diuretic phase of ATN. Patients are predisposed to dehydration during this phase because involuntary urine losses are often great. In order to prevent dehydration, the volume of parenteral fluids administered and oral fluids, should consider also the amount of urine volume, contemporary fluid losses and insensible fluid losses (about 20 to 25 ml/kg/day).

Therapy of potassium and acid-base imbalance Hyperkaliemia is commonly associated with oliguric ARF and may cause skeletal muscle weakness, reduce cardiac contractility and cause a variety of cardiac conduction disturbances. If serum potassium concentration exceed 8.0 mEq/l, or if serious cardiotoxiticy occurs, therapy with sodium bicarbonate, glucose, with insulin, or calcium gluconate should be considered. Of these drugs, sodium bicarbonate (0.5 to 1.0 mEq/kg body weight over 15 minutes) is commonly used first because many hyperkalemic patients also require this drug for treatment of concurrent metabolic acidosis. Administration of glucose (20% at the dose of 0.5 to 1.0 gm/kg body weight) and insulin (1 unit each 3 grams of glucose administered) or calcium gluconate (10% solution, not exceed 0.5 to 1.0 gm/kg body weight) are indicated primarily for rapid correction of severe hyperkalemic cardiotoxicity.

Oliguria versus non oliguria Therapy specifically designed to convert oliguria to nonoliguria should be considered only for oliguric patients unresponsive to fluid volume replacement. In this case use of diuretics alone or associated with vasoldilators should be considered. Furosemide has been the most commonly used diuretic in canine and feline patients. Initially it should be administerd intravenously at the dose of 1-2 mg/kg body weight. If no substantial diuresis develops within one hour after administration, the dose may be doubled (4 mg/kg). If this dose also fails to induce diuresis, the dose may be further increased to 6 mg/kg body weight. If diuresis still does not occur, the combination of furosemide and dopamine may be considered. Mannitol is an osmotic diuretic commonly used to treat oliguric ARF. Mannitol has at least three theoretical advantages over furosemide: 1) it may enhance renal function by minimizing renal tubular cell swelling via its osmotic properties, 2) mannitol exerts its diuretic effects along the entire nephron and therefore may directly affect the proximal tubule, 3) mannitol may expand the extracellular fluid volume. The major disadvantage of mannitol is the potential for vascular overload if oliguria persists. Therefore it should be

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quires renal biopsy. Today, with the use of automated biopsy instruments guided by ultrasound inspection of the kidney and a correct anesthesia protocol and technique, kidney biopsy may be performed within a very acceptable margin of safety for the patient.

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avoided in overhydrated oliguric patients. Mannitol (20% 25% solution) is administered intravenously over 5 to 10 minutes at a dose of 0.25 to 0.5 g/kg body weight. If substantial diuresis ensues, administration of mannitol can be repeated every 4 to 6 hours, or administered as maintenance infusion (8 to 10% solution) during the initial 12 to 24 hours of treatment. Because reduced renal flow may contribute to the pathogenesis of ARF, vasodilators are the logical therapy for patients with ARF. Dopamine, a precursor of norepinephrine, has been suggested for patients that are unresponsive to osmotic and/or loop diuretics. Infusion of low doses of dopamine reduces renal vascular resistance and increases renal flow, particularly to the inner renal cortex. Dopamine should be administered by intravenous infusion at the rate of 1 to 3 Âľg/kg body weight/min, using an intravenous fluid administration pump or under close supervision to assure accurate fluid delivery rate.

Dietary management Clinical manifestations of uremia are improved by combination of a correct dietary protein amount and pharmacologic control of uremic gastritis and vomiting. It limits the catabolic effects of starvation and may be performed also using enteral or parenteral feeding.

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Control of uremic vomiting Uremic gastritis is a major cause of vomiting in patients with renal failure. Cimetidine and ranitidine have been recommended for control of uremic hemorragic gastritis because they block gastrin-stimulated gastric hyperacidity. For dogs in uremic crises, cimetidine is given intravenously at an initial dose of 10 mg/kg body weight every 12 hours (5 mg/kg for cats) and ranitidine is administered at 2 mg/kg. Once uremic gastritis has been controlled and oral medication may be tolerated, cimetidine can be administered orally at a dose of 5 mg/kg every 12 hours for 2 to 3 weeks. The dosage is reduced to 5 mg/kg given once daily for 2 to 3 weeks before being withdrawn. Dosage recommendations for cats are approximately one-half of the canine dose. Because uremic vomiting may also result from stimulation of the chemoreceptor trigger, intravenously administered centrally-acting antiemetics may be useful in controlling vomiting. However, hypotension and sedation are potential pitfalls associated with antiemetic therapy. Chloropromazine (0.5 mg/kg), prochlorperazine (0.13 mg/kg q 6 hrs), trimethobenzamide (3 mg/kg q 8 hrs) are centrally-acting antiemetics which may help to control nausea and vomiting in uremic patients.

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Surgical treatment of most common diseases of tortoises Leonardo Brunetti

Carapace and plastron fractures Living in home gardens tortoises are subject to injuries caused by mowers, cars, electric gates, children and pets. As for turtles they can easily fall down from their enclosures or from the balconies. These fractures have to be stabilized as soon as possible, so it’s necessary to advise the owner, even over the phone, how an emergency bandage can be done, that is by binding up the shell with some sticky tape and keeping the animal away from further traumas. As soon as it reaches the veterinary practice, an inspection of the fracture and a clinical examination must be done, to establish the reptile’s general health. If we are in front of prostrate and dehydrated subjects, first we must give some fluids by intraperitoneal or intrabone injection. When it is necessary we must treat the shock and the internal haemorrhage. As a cover, an antibiotic therapy is always advisable. The success of the operation largely depends on the timeliness with which the patient is taken to the veterinary practice. Contaminated but recent fractures (1-4 hours) have a better prognosis than the ones with a small bacterial infection but having taken place a longer time before (>4 hours). The most frequent situation for tortoises living in gardens is when the fracture has happened 1 or 2 days before. In this case it’s better to wait some days before proceeding with orthopaedic treatment, in order to stabilise the patient and control the infection. Before the re-establishment, the patient must be washed with an antiseptic solution (i.e. a soap solution of iodine povidone). Any foreign material (soil, grass, stones) must be removed. We can use an elevator and the anatomic forceps to lift carefully the carapace and the plastron, where it’s possible, spraying the under part with a warm sterile physiologic solution. After having removed the largest foreign materials, the patient must be washed again with an antiseptic solution. Every part of the patient, including the ones not interested in the fracture must be submitted to a surgical scrub, because it will be necessary to handle the whole body of the patient, especially the smallest subjects, in the re-establishment treatment. It may be useful to do an X-ray on the entire animal, to highlight possible fractures on the spine and /or on bones of

the limbs. The X-ray examination may also reveal the presence of foreign materials.

Linear composed fractures These are usually the easiest to treat. After having made a careful curettage in the above described way, we stabilise the fracture trying to keep up some pressure between the ends of the fracture. If the displacement is small or absent, it may be sufficient to put a cerchage wire all around the patient (Fig. 1). However, if between fracture ends there is a certain looseness, it’s possible to put a cerchage wire on detached points along the fracture line (Fig. 2). A different approach is necessary when the composed linear fracture is placed on zones where the animal’s movement operates a particular traction on the edges of the frac-

Figure 1

Figure 2

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ture, as for example it happens when there is a fracture between the humeral and the pectoral scutes of the plastron. In this case itâ&#x20AC;&#x2122;s necessary to join the two techniques: 1) the detached suture stitches by cerchage wire and 2) the application of the cerchage all around the carapace. Once the fracture is stabilized, we can apply some acrylic resin for dental use(with catalyst), or some two components vitrified stucco, normally used for small repairs on boats and cars. This proceeding is necessary to reinforce the structure and to obtain the impermeability of the interested zone.

Decomposed multiple fractures We often must treat subjects with multiple fractures both on the carapace and the plastron. In this case we must behave as if being in front of a puzzle, trying to preserve and put together again the different pieces, in the best way, along the fracture lines. The depressed fragments must be kindly lifted by elevators, and the ones not connected with the vascular system removed. When the mosaic is composed, we can go on putting the single pattern wire suture along the fracture line trying to stabilize the structure. The cerchage wire must be passed through two holes, previously made by a drill, along the edges of the shell bits to be rebuilt with the help of a wire passer or with a suitable diameter needle put in one of the two holes to work as a guide. In this case too, at the end of the rebuilding surgery we must put on some resin or some other suitable material to give a mechanical help to the shell and to keep up impermeability and asepsis in the coelomatic cavity.

loss of matter from the shell, we can hope in a complete recovery of the animal. We use the following technique to repair the matter loss: a surgical sponge is put inside the sinus caused by the trauma, then a piece of X-ray film is put on the sponge. This film has already been exposed, passed in autoclave and cut according to the necessity. Some small cuts will be made along the edges of the film to allow it to fit the shape of the tortoise shell (Fig. 5). The piece of film has to be longer than the shell zone to be recovered and it will be glued along its edges by a histocompatible cianoacrylic glue or by two components epossidic resin glue. The edges of the film are then covered by some acrylic resin (with catalyst) for dental use or vetrified stucco (with hardener) or with a glue containing two components to keep impermeability and asepsis inside the treated area. As an alternative we have used successfully acetate sheets, in place of X-ray film. The desired rebuilding materials are those which offer a low heating, a strong mechanic resistance and a low price.

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Fractures with loss of matter Shell lesions with loss of matter caused by mowers are among the most frequent ones among home tortoises. A complete neurological examination should be performed, in addition to the examination first described, because in chelonians, vertebrae are fused with dermal bones, (Fig. 3) and a dorsal fracture of the carapace can interest the spinal cord and the brachial and lumbosacral plexuses (Fig. 4). If the spinal cord is safe, even in front of an important

Figure 4

CORNEAL SCUTE DERMAL BONE NEURAL ARCH

LATERAL PROCESS CENTRUM SPINAL CORD

Figure 3

Figure 5

LUMBO SACRAL PLEXUS

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Turtles will have to remain in dry zone for weeks or months, until they are healthy again; they are put in a clean water pool only to eat. Tortoises can go back to their gardens a few days after the operation. A chelonian having such an important trauma must not go into hibernation during the first winter following the lesion. Figure 6

It’s necessary to cut the plastron to reach the coelomic cavity in chelonians. The usual approach is through abdominal and femoral scuti but may also be cranial or caudal or lateral, depending on the organs we have to reach and / or possible present fractures. A rectangular wedge must be done on the plastron by a cutting blade. To enable the wedge to turn over, the bone and horny layers of three sides must be completely cut, while the ones of the fourth side must be cut only in some parts, preserving the vascolarization. During the cutting it is vital to cool the plastron by a cold sterile physiological solution dripping on the part. When the bone is drifted and the periostium is taken away the underlying abdominal musculature is showed clearly. Now it is the moment to make an incision on the coelomic membrane, where two venous sinuses run down on each side of the middle line.- Be careful to save the venous sinuses (only for drastic measures one of them may be cut). Celiotomy may be used for a lot of procedures: dystocia, cystotomy for cystic calculi, gastro-intestinal foreign bodies removal, lesions of the coelomic cavity organs following shell fracture traumas. In this particular case we always try to reach the coelomic cavity trough the fracture lines in order to avoid further damage on the patient’s stiff structure. When the surgery is finished and the wedge is placed back in the original position some acrylic resin for dental use has to be put on the surface of the plastron.

Surgical treatment of penis prolapse Penis prolapse is rather frequent both for turtles and tortoises. Normally the organ prolapsed for physiologic or pathologic causes may have an oedema with a probable consequent paraphimosis. If we are lucky and the animal is taken in time to the veterinary practice, so that the paraphimosis interested tissues are in good condition, it is possible to place back the penis. At first it is necessary to wash carefully the wounded area with a chlorhexidine soap solution, then the organ has to be sprayed with a sterile physiologic solution. Now we proceed with a compressive manual pressure to reduce the oedema and contemporaneously we have to push the penis inside the cloaca. This operation is often difficult, but it is necessary to repeat it many times until we are successful. When the organ is replaced we have to put one or two sutures on the cloaca opening to tishten it, in order to avoid another prolapse (Fig. 6). The residue opening cloaca has to be

sufficient to permit the passage of fecal and urinary product. The suture will be left in situ for 2-3 weeks. During this period the original causes of prolapse must be found and resolved. When the patient is taken too late to the veterinary practice and there are some ulcerated and necrotic areas on the surface of the prolapsed penis, it is necessary to cut the organ off. This amputation doesn’t cause any urinary problems because a reptile’s penis has only a copulative function and it doesn’t contain the urethra. The surgical technique is rather easy: the organ which has a seminal groove, being kept in physiological position, is held by an assistant and a continuous pattern mattress suture is applied on its base, then the suture has to be tightened. At this point it is possible to cut off the necrotic part but there are some devices to consider: 1) the suture must be done with very close sutures to control the haemorrhage caused by the resection of penis sinus bodies. 2) an end of suture material must be left to hold it by a mosquito, so as not to lose the organ in the cloaca when we are replacing it back and to control possible haemorrhages of the penis remaining part.

Surgical treatment of cloacitis Female tortoises living in small gardens together with a lot of males often present some cloacitis for the too frequent coupling. Cloacal lesions are often complicated by miasis. The surgical treatment of cloacitis consists in removing necrotic tissues and every larvae by an accurate curettage. Then we have to reconstruct the cloacal orifice. The suture material used is nylon monofilament. Sometimes an anal scutes plastronectomia is necessary, to have easy access to the cloacal zone. Sutures will be left in situ between 20 days and two month, depending on the recovery time. It is opportune to keep only one male with 4-5 females in the same garden to prevent this usual pathology.

Surgical treatment of abscesses Abscesses are rather usual in chelonians where they appear as firm lumps under the skin or under muscles in various zones, especially in the auricular regions (turtles) and in axillary, inguinal and pericloacal zone (tortoises). Surgical treatment is necessary because, unlike mam-

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mals, neutrophili granulocytis are not able to colliquate the pus, permitting a spontaneous draining outside. The abscess will be completely removed, being careful to cut off the capsula. We make an incision on the skin above the lump, and we isolate the lump after drying up the surrounding tissues. The remaining cavity will be sutured with nylon monofilament and the sutures will be removed 2 or 3 weeks after.

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If some delicate structure is present near the lump, we can use an alternative technique. After cutting the skin above the lump we take away the infected solid matter with a Wolkmannâ&#x20AC;&#x2122;s spoon or other adequate instrument. Then we wash the cavity with a solution composed of hydrogen peroxide, iodopovidone (or chlorhexidine) and physiological solution, 1-2 times a day for some days. In this case, it can be unnecessary to suture the remaining cavity.

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Ultrasonography in the diagnosis of the urinary tract diseases in dogs and cats Claudio Bussadori

The ultrasound examination is a rapid and secure technique, which allows a valuation of the position, dimension and the parenchyma morphology of the organ in exam. This methodic by now is large diffused and constitutes the preferential techniques of imagine of the urinary apparatus, as it reveals, respect to the radiology, a major sensibility and specificity in the diagnostics of the urinary and nephrological pathologies. The ultrasound examination can be also used to guide the withdrawal of bioptic samples through percutaneous way, which permits histological examinations in a bloodless manner. The observed pathology alterations can be classified in many standards: in this specific case we applied the classification on the ground of the structural modifications which are pointed out in ecografy, considering the different pathologies who can determine them. Since there are not described some pathology aspects of ultrasound examinations, these are been located in the classification on the ground of the macroscopic or microscopic modifications and the analogy with other pathologies which echografic aspects are known.

tern. The echogenicity is correlated to the cellular type, which are involved, to the vascular system, to the grade of haemorrage and to the presence of necrotic phenomenons. The solid uniform hyperechoic masses can have an aspect similar to the cysts, without demonstrating lateral acoustic shades and posterior reinforcement, but with an evident survey of the internal echoes increasing the gain. The lesion of the lynphosarcoma, the tumor most common of the cat is characteristic of a weak vascular system, are ipoecogen. The hypoechoic lesion has a connective tissue or mineral deposit: among these are part of it, the calcification, the infarct, the fibrous zone and the gathering of gas. The type of complex mass lesion shows a mosaic of different echogenic areas: in differential diagnosis we can distinguish tumors, granulomas, organized haematoms recent infarcts. The most tumor types, described with vary echopattern in small animals are haemangiosarcoma, renal blastoma, adenocarcinoma, condrosarcoma, cancer or papilloma of transit cells.

Diffused lesions KINDNEY Parenchyma modification of the kidneys. Focal cyst lesion The cystic renal lesion includes a group of hereditary and acquired diseases, often verified on occasion. The renal cyst are most roundish with thin and regular walls and the contains without echo frames; they are characterized by the presence of artificials which are the reinforcement of the posterior walls and the refraction. The distinction treated from the human medicine between polycystic autosomic recessive or infantile renal disease and policystic autosomic dominant renal disease or of the adult can be adapted in veterinary medicine to the feline species in which this pathology is frequent. Other tumors localized with characteristics alike the cysts are the haematomas and the abscesses.

The solid focal lesion This kind of lesion can have an hyperechoic, hypoechoic or isoechoic aspect with a regular or subtle sonographic pat-

The renal cortex can present itself hypoechoic, like the lynphosarcomatic infiltration or iperechogenic, like the Ethylene Glycol Toxicity, in the interstitial and glomerular nephritis, in the acute tubular necrosis, in the nephrocalcinosis, and in the renal sclerosis. It has also been signalized in the lynphosarcoma of cats and the infective peritonitis. Sonographic findings includes focal hyperechoic of the corticomedullary junction but it is considerated a characteristic lesion of the Ethylene Glycol toxicity (medullar rim sign). We can also observe it in the vasculitis due to the FIP, in acute tubular necrosis and in interstitial chronic nephritis.

Volume decreasing â&#x20AC;&#x201C; Sclerosis - With loosing of the distinction between the cortical and the medullar. We observe it in the renal displasia, which is the result of a disorganization of the organogenesis probably for a hereditary autosomic recessive character.

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In the policystic kidney with microcysts the presence of lots of little interfaces can determine a diffused hyperechogenicity without any distinction between cortical and medullar. - With decrease of the cortical-medullar correlation. We find it in pathologies with a progressive course, like the tubule-interstitial nephropathology of the Norvegian Elkhound and the Fanconi del Basenji Syndrome.

PELVIS The ultrasound examination is certainly indicated as the gold standard examination when there is a suspect of pathology of the first part of the urinary duct. It is possible to find physiologic symptoms of pyeloectasia (how it happens in the diuresi caused of drugs or pathologic symptoms (how it happens in the case of traumas, obstruction of the urine flow, infective pathologies). An other frequent pathology in cats and dogs is the hydronephrosis, or rather the dilatation of the pelvis and the calyx secondary to the urinary accumulation caused of obstructions: it is important to distinguish the renal vein in the presence of a possible extended urinary duct (control the expectoration of the vena cava). To be able to distinguish the pyeloectasia caused of an obstruction from a pyeloectasia which has not an origin obstructive, like the obstructive pyelonephritis, it has been estimated in the dog the use of the resistivity index (RI) or Pourcelot index (you reach out to it dividing the difference between the systolic top speed with less diastolic speed multiplied with the systolic top speed measured out at the level the arcuate artery): recently the results are pointing out a low sensibility and specificity with an high percent of falsehood negatives, even if it is spotted that the falsehood negatives could be lower in to 24 hours after the obstruction. It is possible to express a diagnosis of pyelonephritis when there are present contemporary two or more of the following signs: dilatation of the pelvis or the proximal part of the urinary duct, presence of an hyperechoic bed in the pelvis or in the proximal part of the urinary duct, hypo – or hyperechoic areas in cortex or medullar, loss of the differentiation corticomedullar.

URINARY BLADDER The bladder for its anatomical position and for its anechoic contents is fit for an ultrasound examination. In the condition of physiological or artificial fullness, constitutes an excellent acoustic window and besides represents an important point of reference.

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mally indicative of cystitis. We can see urinary polyps in the bladder wall, typical of the polypoid cystitis or else a neoplasm eziology: these proliferations have to be differentiated from blood clots adherent to the wall, trying to determinate, with a patient rotation, with localized abdominal wall compression with the sonographic sound or with a bladder washing with sterile saline a neoplasm shifting that happens if it is an haematomic agglomerate. In case of neoplasm it can be associated a certain disorganization of the wall architecture. It’s important that the wall investigation is done accurately, to evidence localized thickness (usually cranioventral) that means cystitis and parietal diverticul presence: these can be hereditary or acquired, have to be accurately analyzed to find the presence of neoplasm or calculus inside the diverticolo. Since infect the diverticulum wall is deprived of the muscular component it results an almost always partial emptiness, favoring the persistence of oncogenic stimulus contact to the diverticolar urothelial mycoses or easier the appearance of chronicle or recidivist infection of the urinary ways. The convex bladder wall determinates the appearance of an artificial due to the sound refraction that simulates a continuous interruption that disappears changing the sound orientation. The vegetating forms appear as solid and homogeneous structures, with an echogenecity lower than the echogenecity of the bladder wall, with plant base such large to interrupt the continuity of the bladder inside jetting out into the inside of the viscera. For now infiltrating neoplasm determinate a thickness and a rigidity of the bladder wall with an alteration of the echografic structure: these can present a redoubt component of the bladder lumen and are difficult to identify. The possibility to evidence a neoplasm depends essentially of the dimension (the sonographic threshold to evidence a neoplasm are 5 millimeter) and of it’s seat (the neoplasm which are localized in the neck of the bladder are difficult to identify). It’s easier to find the neoplasm localized in the caudal part of the urinary bladder and trigone, rarely in the cranial part of the urinary bladder. If we examinate the cranial part of the trigone sometimes it’s possible to recognize the intraparietal part of the urethras which can be confused with neoplasm, because it appears like a little convex form with regular walls: for that it is useful to observe if there are coupled structures and to point out the turbulence created by the urinary peristaltic waves by coming out the uretery outlets. The persistent uraco that goes to the umbilicus can appear as a diverticulum or as an anechogic tubular structure cranial to the bladder; the uracal cysts usually cranial of the bladder have thin walls and anechoic contents.

Contens Bladder wall The bladder wall appears as a reflecting line without any discontinuity, whose thickness varies with the state of fullness: it is important to considerate pathologic only a substantial increasing of thickness in an expanded bladder nor-

Normally the urine is, as said, anechoic: presence of blood or other fine urinary sediment can generate inside diffused, pointed formed echoes, which go slowly to sediment. This phenomenal must not be confused with artificial due to the wrong position in the bladder lumen of echoes borned

outside of the ultrasound bunch periferic portions structure: this artificial shows as an echigenic band parallel to the dorsal bladder wall, similar to sediment deposit, which is not possible to resupend shaking or balloting the bladder, which doesnâ&#x20AC;&#x2122;t move changing animal position and modifies itself with the sound orientation.

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The gas inside the bladder normally hyatrogen origin, is hyperechoic, creates reverb and moves itself to an higher position: if the animal is in a dorsal recumbence it can be confused with the proximal sound reverb; in this case it can be used a spacer or easier it has to be reexamined the animal in standing position.

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Pathophysiology and treatment of pericardial diseases Claudio Bussadori Med Vet, Dipl ECVIM Private Practitioner, Milan - Italy

Anatomy and functions of the pericardium The pericardium holds the heart and is composed by an external part or lamina parietalis pericardii and an internal part or lamina visceralis pericardii: the pericardial space contains normally a small amount of serous liquid (0.5-15 ml in the dog). Although it is not an essential anatomic structure, it is able to perform important functions: containment and protection of the heart, limitation of the acute dilatation, maintenance of the cardiac geometry and of the ventricular compliance, modulation in the ventricular diastolic refilling phase, protection of the heart from infections or adhesions, increasing of the diastolic relation between the two ventricles. The measurements of the intrapericardial pressure of a normal heart is, unfortunately, not easy to obtain: this value is nevertheless very important in the study of pericardial diseases. At this subject it is important to remember that the transmural pressure of each ventricle is obtained by the difference between the diastolic intracardiac pressure and the intrapericardial and is independent from gravity. The intrapericardial pressure is strictly connected to the right atrial pressure and is comparable to the filling pressure of the right ventricle when in a range between 0 and 20 mm/Hg. This value emerged from the utilization of intrapericardial balloon catheter (Santamore) which have been demonstrating how, in a normal heart, the catheters with open lumen were underestimating the values of the pericardial pressure. Moreover the pericardial pressure is not homogeneous in each cardiac segment, but is higher at the level of the free wall of the left ventricle (Hoit). It is not the pressure of a liquid which has to be equal in various regions, but it is a contact surface pressure, which means the pressure of a liquid plus its deformation powers.

Etiology of pericardial diseases The pericardial diseases in the dog are distinguished in congenital (pericardial agenesia, periton-pericardio-diaphragmatic hernia) or acquired: this last ones can be classified depending on the type of effusion, which can be transudative (congestive heart failure, cysts, hypoalbuminemia or other reasons of increased vasal permeability), exudative: infectious diseases, particularly bacterial and mycotic, while the viral pericardial pathologies are more common in bovine and feline species, the pericarditis in uremic syndromes are more frequent in the human species. Bleedings occur in neoplasm: cardiac tumor, tumor of the heart base, hemangiosarcoma, receptoma, pericardial celioma, lymphosarcoma, in idiopathic benign pericarditis, external trauma or heart rupture. In the dog the major causes of pericardial effusion are the neoplasm forms and the benign idiopathic pericarditis. The definition â&#x20AC;&#x153;benignâ&#x20AC;? is refereed to the human pathology while in the dog this pathology frequently causes heart tamponade: the etiology of this form is unknown in both species, even if hyphotesis suggest an immunological genesis in both species.

Pathophysiology The haemodynamic effects of the pericardial effusion are related to the volume of the fluid, the compliance of the myocardium and the time that occurs. The physiological intrapericardial pressure in dogs varies around the values of atmosphere pressure (from -3.8 to 3.8 mm/Hg): this condition enables the cardiac filling especially in the inspiratory phase. After the gathering of fluid in the pericardial cavity the intrapericardial pressure increases, joining first the atmosphere pressure and then further on to higher values, while in the meantime there is an increasing of the right ventricle diastolic pressure. The cardiac tamponade is a clinical syndrome, which generates a cardiac emergency: it develops from an uncontrolled increasing of the intrapericardial pressure, this limits the ventricular compliance which causes a significant obstacle to diastolic filling. The pericardium is extremely resistant to acute stretching, while it is able to extend in a progressive way if the stretching is continued. So this is the reason why even a small increase of pericardial fluid developing suddenly can

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The author describes pathophysiology and the more common causes of pericardial diseases furthermore are described guidelines for clinical and Echo-Doppler diagnosis and staging of pericardial tamponade. For treatment are described the most utilized medical therapy and the technique of percutaneous pericardiotomy using balloon catheter.

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lead to a severe cardiac tamponade, while an effusion of two or more liters which accumulates slowly can associate only with a small increase of intrapericardial pressure causing better tolerated haemodynamic effects. In slowly developing effusions we have at first only clinical signs of right cardiac failure and only in the following phases of the process we have the clinical signs of emergency. The intrapericardial pressure increases then until it causes a critical compression of the outside of the cardiac walls, able to induce a diastolic collapse of the right atrium and ventricle and the reduction of the ventricular volume followed by a systolic deficit of the left ventricle, inducing an hypertension of the venous district and a hypotension of the arterial district with severe compromise of cardiac output.

Clinical signs The symptoms depend on the seriousness of the cardiac tamponade. Slight tamponade in its initial phase can be asymptomatic. During an acute tamponade the clinical signs are particularly severe. We can have the lost of the cardiac impulse at the palpation of the thorax, at the auscultation we have either paraphoniac tones or tones that can not be detectable, noises caused by preexistent murmurs, which sonorous is muffled from the sonorous vibration caused by the passage through the pericardial fluid. A typical symptom is the paradox pulse, a huge decreasing (> 10 mm/Hg) of the arterial systolic pressure during inspiration. This phenomenon follows the reduction of the systemic venous drainage and the filling of the right ventricle followed by reduction of the left filling and output. Central venous pressure can, on the contrary, increase in the inspiratory phase determining a huge distention of the jugular veins. To this clinical signs we can have the symptoms of a backward heart failure like the enlargement of liver and spleen and hepatojugular reflux. The decreased cardiac output causes also a secondary peripheral vasoconstriction, with pallor mucosae, delay in the capillary filling, cold extremities (forward heart failure).

Electrocardiography Electrocardiogram alteration are not pathognomic, but are anyway significative if coupled with clinical signs and enables the doubt of pericardial effusion. We can have voltage reduction of the ventricular complex (R<1 mV in D2) associated to a normal a wave upper level of the ST segment with under level of the P-R tract when even the atriums are compromised. We can also observe phenomenon of electrical alternations, or cyclic variations of the QRS amplitude due to the swinging of the heart inside the overdistended pericardium (swinging heart).

Radiology Moderate or massive pericardial effusions determinate

particular radiological alterations: the cardiac silhouette shows an increasing of the transverse diameter without enlargement of the heart base. The profile of the cardiac shadow assumes a globular aspect without any sign of the auricles or of the atrioventricular junctions. The increased size of the cardiac silhouette with its characteristically pumpkin shape is not proportional to the amount of liquid contented in the pericardium; in the same time the detection of pleural effusions and hepatomegalia suggest a chronic process. At the radiological examination of the thorax we can also see the signs of the venous congestion and of the low range, we can observe evident dilation of the caudal vena cava and the pulmonary veins while the pulmonary arteries are decreased and the lung appears hypovascular and radiolucent. Before the advent of the echocardiography there was a radiological method, called the diagnostic pneumopericardium, in this method there was the introduction, after pericardiocentesis, of atmospheric air or carbon dioxide in the amount of half or less of the drained fluid, in that way it was possible to obtain a good negative contrast for a radiological study of the silhouette. This diagnostic proceeding can be very helpful when there is a suspect of an effusion due to a tumors etiology. In those cases the association of a non selective angiography enables us to evidentiate the profile of the cardiac chambers and of the big vessels, to better define the intrapericardial structure and their anatomical belonging.

Echocardiography The echocardiogram is surely the technique that better shows diagnostic utility, because it is highly specific and sensible in the detection of pericardial effusion. In normal conditions the pericardium is not visible as a distinct structure: if there is an effusion we have an anaechoic space between the echo reflected from the visceral pericardium and the one reflected from the parietal pericardium, while they normally reflect a single echo together. Besides the detection of an effusion, echocardiography consent to see the entity, the distribution and the grossly physical characteristics of the fluid examined (for example corpuscolated material). But an evaluation of the echodensity of the fluid within the pericardium depends too much on the regulation of the echocardiographic instrument to be fully reliable, while the evidence of a lacertus fibrosus suggest chronic inflammatory effusions or sometimes pericardial tumors like celiomas. A solid granular figure can lead to an intrapericardial hematoma, solid masses adherent to one of the layer or infiltrating suggest tumors effusions. Echocardiography also grants an accurate evaluation of the level of the haemodynamic commitment. An important echocardiographic find is represented by an excessive diastolic relation or a variation in concomitance with the respiratory acts and the kinetics of the interventricular septum: the septum in the inspiratory phase, moves towards the left ventricle and in the espiratory phase, towards the right ventricle. In other words, during the inspiration the right ventricular cavity enlarges its volume, due to the in-

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Constrictive pericarditis The diagnosis of chronic cardiac compression presents great difficulties what allows to think that this pathology is in effect more common of what it is believed, and that often it is not identified, but it is important to identify this illness because also if it has a particular severe prognosis in most of the cases, it is surgically treatable. In this illness the clinical signs of a commitment of the systemic and pulmonary venous drainage are evident as in the cardiac tamponade, but only the echocardiography allows an non invasive diagnosis of chronic cardiac compression, the bidimensional exam shows a hyperlucent and a thickened pericardium, although in truth, this report is extremely dependent from the operator, instead there is always an evidenced biatrial enlargements with normal seized ventricles. With the M-mode the left ventricle shows a backward movement of the septum in early diastole (early diastolic dip) and a fast early diastolic excursion of the posterior wall; this aspect of the early diastolic phase shows that the left ventricle suddenly fills in protodiastole while subsequently the filling interrupts. We can see a flattening of the posterior wall in mid and late diastole, which represents the haemodynamic corresponding of the square root sign. The Doppler exam highlights a sharp deceleration of the transmitral and transtricuspidal diastolic flows, this report is common to restrictive cardiomyopathy, but in this last one we do not have an inspiratory reduction of the flows which is quiet evident in the constrictive pericarditis.

Treatment The ultrasound tecnique enables a correct therapeutical approach for the percutaneous pericardiocentesis, which represents the procedure used for the stabilization of the patient in the acute phase and the resolution of the pericardial tamponade. The method we use in those cases provides, if the conditions of the patient allows it, the positioning of the dog in a right lateral recumbency on a special table for echocardiography, if the patient is not able to tolerate the recumbency this procedure can be performed with the animal in a sitting or standing position. Under echographic guide a needle of 18G is connected to a tube extension to a large syringe, the needle is introduced in the right forth intercostal space under the costochondral junction, and through this system it is possible to introduce physiological solution in the pericardial sac in order to contrast the area containing the tip of the needle. We chose the right approach because from this side there is no risk of injury at the coronary vessels. If this should be necessary, due to the relapse of the heart tamponade, a second pericardiocentesis, can be considered. In idiopathic pericarditis in order to obtain a radical resolution of the illness, and to avoid the evolution toward chronic cardiac compression, we suggest a surgical subtotal pericardiectomy, this can be executed in a traditional thoracotomy approach or through thoracoscopy. In older dogs or animals in critical conditions, so that they can not be subordinated to surgery we have used percutaneous pericardiectomy tecnique with a balloon catheter

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crease of the venous drainage in concomitance with the reduction of the left ventricular dimensions, the flattening, and the dislocation of the septum towards the left ventricle. This irregular movement is called the diastolic paradox septum. Unfortunately it is not easy to measure this echocardiographic element and moreover it is not pathognomic for pericardial effusion, but only for a diastolic compromising of the left ventricle, which can occur also in other pathologies that causes an increasing of the right ventricular pressure like pulmonary hypertension, or pulmonary stenosis. Better correlated to the relation between intrapericardial pressure and right atrial pressure are the late diastolic collapse of the right atrium and the early diastolic collapse of the right ventricle: with the increasing of the pericardial pressure the right ventricle tends to remain longer in the diastolic phase. This echocardiographic signs are extremely early and represent the beginning of the real cardiac tamponade, which start to express only when the intrapericardial pressure, equalizing the diastolic pressure of the right atrium causes its compression. Another early echocardiographic sign of pericardial tamponade is the absence of the physiological reduction of the diameter of the caudal vena cava during the inspiratory phase, that should be around 50%: this phenomenon is called â&#x20AC;&#x153;vena cava plethoraâ&#x20AC;?. This fact is strictly correlated with the values of atrial pressure, index of vena cava collapsing lower than 35% is showing high values of right atrial pressure (Pepi). The excursion of the caudal cava vein is appreciable and measurable through a series of monodimensional scans, possibly obtained slowing the speed of sliding and detected at the height of the diaphragmatic caval hiatus during the respiratory phases. The caval plethora is a very sensible echographic sign to point the venous drainage impediment, unfortunately not specific for cardiac tamponade, but only for an important right diastolic dysfunction. Using the Doppler method enables quantitative assessment of the inspiratory reduction of the transmitral and transaortic speed of the fluid, associated to delayed opening of the mitral valve (in correspondence with the atrial systole) and a premature closing of the aortic valve. (Appleton) (Schutzman). Physiologically the aortic and transmitral flow have no respiratory variation or if they have, only minimal (5%). In the heart tamponade we can see respiratory reduction of the mitral and aortic flow more than 25%, clear evidence of the massive diastolic relation that occurs in the heart tamponade. Analyzing the transmitral diastolic flow with the Doppler, we can also highlight a reduction of the amplitude and duration of the E wave, expressing a diastolic impediment in the first phase of the ventricular filling, or like in the severe forms, were this only happens when we have the atrial contraction. In the massive forms the left ventricular filling is almost exclusively caused by the atrial contraction. In physiological conditions the atrial contribution to the diastole is not higher than 25%, while in this cases it determinate over the 50% of the diastolic volume: this phenomenon is detected by the Doppler with a decreasing of the E/A ratio and an increasing of the ratio between the A area and the integral of the whole transmitral flow. (Appellation).

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(Cobb). This tecnique is executed under fluoroscopic control with the dog in right lateral recumbence and after sedation. With the help of the echographic guide the point were the catheter will be introduced is chose, and in this point we practice a local anesthesia, taking care to also include the pleura parietalis. Then we introduce a needle of 16G through the thorax wall to the pericardium, through this needle we introduce in the pericardial sac a metal guide wire of 0.038 inches and 150 cm length, and through this guide we pass a vascular dilator of 8 French until the pericardial sac, finally removed the dilator, through the guide wire we introduce the balloon catheter, the deflated balloon is placed through the pericardial sac. For this use we need balloons that once inflated reach the diameter of 2-3 cm and the length of 4 cm. The inflating of the balloon is executed with a 50% physiological solution and a contrast medium, the balloon is first partially inflated, what enables us to highlight through fluoroscopy the depression on the balloon caused by the pericardial sac, if necessary we can move the balloon back and forth. The balloon is then completely inflated until the waist on it disappears, and kept like that for 2â&#x20AC;&#x2122;. This procedure has given good results as a palliative therapy in tumors pericardial effusions, allowing the liquid formed in the pericardium to pour in the thorax and to be reabsorbed. In the benign idiopathic pericarditis with a possible immunological etiology there have been used many pharmacological therapies in order to reduce the immunitary response, like corticoids, prednisolone 0.5-1 mg/kg. We experienced (10 patients) the administration of azathioprine orally 1 mg/kg SID for a three months period after the first pericardiocentesis or in subjects which presented relapse after a short time from the second pericardiocentesis. During the treatment with Azathioprine we did not highlight secondary effects, besides a modest anemia and leu-

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copenia. At this point of time in neither one of the subjects treated there has been a relapse of important pericardial effusion. The validity of this therapy surly needs further confirmations with treatments for a longer period of time and groups of animals of greater numbers besides groups treated with dummy.

Bibliography Appleton C, Hatle L, Popp R: Cardiac tamponade and pericardial effusion: respiratory variation in transvalvular flow velocities studied by Doppler echocardiography. J.A.C.C. 1988;11:1020-1030. Assanelli D, Lew W, Shabetai R, Le Winter M: Influence of the pericardium on right and left ventricular filling in the dog. J. Appl. Physiol. 1987; 63:1025-1032. Cobb M.A. Boswood, G.M. Griffin and McEvoy F.J. Percutaneous balloon pericardiotomy for the management of malignant pericardial effusion in two dogs. Journal Small animal practice 1996; 37: 549-551. Gibbs C, Gaskell CJ, Darke PGG, Wotton PR: Idiopathic pericardial hemorrage in dogs: A review of fourteen cases. J. Small Animal Pract. 23:483,1982. Lopez-Sendom J, Garcia Fernandez M, Coma Canella I, Sotillo J, Silvestre J: Mechanism of right atrial wall compression in pericardial effusion: an experimental study in dogs; Journal Cardiovascular Ultrasonography 1988; 127-134. Pepi M, Tamborini G., Barbier P., Doria E., Ecografia nello studio della fisiologia e della patologia del pericardio. Giornale Italiano di Ecografia Cardiovascolare. Vol 4, NÂ°1 Marzo 1994. Reed J.R. Pericardial diseases in Fox, Canine and Feline Cardiology Churchill Livingstone 1988. Santamore W, Constantinescu M, Little M: Direct assessment of right ventricular transmural pressure. Circulation 1987;75:744-747. Schutzman J, Obarsky T, Pearce G, Klein A: Comparision of Doppler and two-dimensional echocardiography for assessment of pericardial effusion. Am J Cardiology 1992; 70:1353-1357. Sisson D, Thomas WP, Ruehl WW, Zinkl JG: Diagnostic value of pericardial fluid analysis in the dog. J Am Vet Med Assoc 184:51, 1984.

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Disseminated intravascular coagulation: State of the Art Marco Caldin

Diagnosis of DIC, as well as many other aspects of this fascinating intermediary mechanism of disease, is still a rather complex phenomenon. We learned through the analysis of the DIC cases - as described in literature and through ones we considered - that doesnâ&#x20AC;&#x2122;t exist a single sign either of laboratory or clinic, which can prove the existence of such a clinical condition. Moreover often there are no correlation at all between clinical-laboratory signs and autopsy findings. That is why the diagnosis of DIC is a challenge for the internist who must evaluate critically clinical and laboratory manifestations. For the clinical point of view in order to hypothesise the DIC, there must be a clinical entity able to cause it. From the laboratory side the results must be evaluated in relationship with their sensibility and specificity towards the DIC.

then, exceeds the normal physiologic answers of compensation. Whereas in course of a low-grade DIC (compensatedchronic), the alterations are often only of the laboratory kind, because the comsumption of the coagulant factors is balanced by an increased production. Nevertheless the evolution from a phase to another, such as from normal to fulminant DIC, is very fast. This points out the dynamism of the hemostatic balance. Thrombotic manifestations, which are more difficulty visualized, bring to the production of microthrombes and macrothrombes, that produce damages and sometimes a real failure of the organs involved. Together with organ failure, systemic signs of shock and metabolic acidosis appear deriving from a reduction in the tissue perfusion.

Laboratory features Clinical features Clinical signs deriving from DIC are generally those associated to the thrombohaemorrhagic disease. We must consider that it is quite easy for the physician to diagnose haemorrhagic events while it is more difficult to recognise the thrombotic signs so our comprehension of the problem is only partial. We must add that the clinical picture shows also the clinical signs deriving from the disease that has caused the DIC. For that reason it is sometimes difficult to distinguish between cause and effect, that is to say between the disease and its effects, i.e.,It is common the onset of liver failure when there is a fulminant DIC, but it is also true that liver failure is often the cause of the DIC. The clinical signs combined with the haemorrhagic event can be such as petechiae, ecchymosis, subcutaneous haematomas, hemorrhagic diarrhoea and vomiting, hematuria, excessive post-traumatic (or post venipunctures) bleeding. According to our experience, hemorrhagic body effusions rarely are due to a DIC. When the clinician finds a hemorrhagic body effusion with laboratory signs of DIC he/she must go on looking for the cause of it, since hemorrhagic manifestation depends from specific causes. In this case the DIC emphasises the hemorrhagic events. Tipical example is the spleen hemangiosarcoma with abdominal effusion. Hemorrhagic manifestations are more frequent when there is a fulminant DIC (decompensated-acute), when the dynamic of the coagulation process first, and hemorrhagic

Data base (hemogram-biochemical profile-urynalisis) are essential tools for a interpretation of the coagulative alterations. The data base often point out causes and the effects in the DIC. As we said above, there is no single test able to diagnose the DIC. Nevertheless the laboratory tests are very important to evaluate the existence of the DIC. Unfortunately, as far as we know, in veterinary licterature they are seldom considered in relation to their sensibility and specificity towards the DIC. Besides the increasing number of the diagnostic markers make us evaluate critically not only the new tests but also the more traditional ones which have been revalueted in the light of what we know. The data here reported refer to 71 DIC cases, analysed by one of the authors (M.C.).

Prothrombin time (PT) Prothrombin time represents a global test which measures the extrinsic pathway1 and the common pathway. It represents a direct measure of the factors I, II, V, VII, and X. When one or more of these coagulation factors goes down to an amount considerated critical (50-60 %), there in an increase in PT. In the DIC the PT gets longer for different reasons:

Attualmente la divisione in due cascate coagulative Ă¨ ritenuta sorpassata data la ormai comprovata relazione tra fattore VII e IX.

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Med Vet Senior Lectures, Faculty of Veterinary Medicine, University of Padua - Italy

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A. consumption of the factors involved in the extrinsic pathway and specially in the common pathway (fibrinogen). B. Inactivation of the factors V and IX caused by the plasmin C. Interference with fibrin monomer polymerization caused by the FDP. Sometimes in the DIC we assist also to a shortening of the PT, because of the activated coagulation factors (thrombin and Xa). In our research the PT has demonstrated a sensibility of 29% on 71 cases and it has also demonstrated a specificity of 30%, showing the tendency to be alterated in the fulminant DIC together with the fibrinogen and platelets.

Activated partial thromboplastin time (aPTT) Activated partial thromboplastin time represents a global test which measures the intrinsic pathway 1 and the common pathway. It represents a direct measure of the factors XII, XI, IX, VIII, prekallikrein, HWMK and more approximately of the factors I; II, V and X. In the DIC the lengthening and the shortening of the aPTT occurs for the same reasons described for the PT. In our study the aPTT has demonstrated a remarkable sensibility (73%), in spite of a low specificity (30%), with the tendency to be alterated either in the fulminant DIC or in the low grade DIC. The great sensibility of this test is probably due to the fact that the aPTT evaluates in a more detailed way the intrinsic pathway, which is mainly involved in the consumption of the coagulation factors.

Fibrinogen During the DIC there is the consumption of fibrinogen by the activation of the coagulation system which leads to its trasformation to fibrin with diffuse thrombosis. Even if this event occurs almost steadily, many times it does not determine a recognizable hypofibrinogenemia. This is due to a considerable capacity of the hepatic synthesis in an acute or chronic inflammatory process, when the liver increases the synthesis of this coagulation factor concealing the consumption process. Furthermore collocation of fibrinogen to the acute phase proteins may trasform this coagulant factor in a protein sensible to other events different from the coagulation.When the fibrinogen level reduced at 75-100 mg/dl, there is a lengthening of the PT and aPTT, and the PT seems more sensible than aPTT to the hypofibrinogenemia. In our series of 71 cases of DIC, fibrinogen appears of low sensibility (11%) but with a fairly good specificity (80%). Probably this depends by the low number of diseases that can reduce it (e.g. liver failure). Hypofibrinogenemia becomes evident during the fulminant DIC and it occurs a short time before the platelet’s consumption. If -in order to measure this coagulation factor- we use a laboratory method based on trasformation of fibrinogen to fibrin it can happen that artificious low values are recorded. This is due to the interference of the FDP in the conversion of fibrinogen into fibrin.

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Thrombocytopenia/thrombocytopathia In the DIC the low platelet count is due to the activation of the coagulation process that causes the formation of microthrombes in the vascular bed. However as in the fibrinogen model,the presence of the inflammatory processes causing the DIC, or developping together with the DIC, can produce a reactive thrombocytosis that conceals the low level of platelets. High levels of platelet factor 4 and beta-thromboglobulina, document this fact, also if these markers are not pathognomonics. The alteration of the functional platelet is another aspect following the DIC.This is caused by the FDP coating of platelet membranes or the partial release of platelet procoagulant material. Tests performed to document this fact (bleeding time and platelets aggregation), have a unfavourable relationship between cost and benefit. In our series of 71 cases of DIC, a low platelets count shows a 13% sensibility and a specificity of 90%, with the tendency to appear in fulminant DIC together with hypofibrinogenemia.

Schistocytes Schistocytes, or red cell fragments, are end result of the mechanical damage of the plasmatic membrane of eritrocytes against intravascularly fibrin strands. This event it’s well documented by Bull and coworkers and it is more frequent in low-grade DIC. In fulminant DIC, often, the process it’s so fast that there is not enough time to create a extensive damage of the red cells.Other conditions that can produce schistocytes are Heinz body anemia, iron deficiency, and laboratory artifacts. In our series the sensibility of this test has been 20% and the specificity 90%.

Fibrin(ogen) degradation products (FDP) Plasmin degradation of the fibrin and the fibrinogen produces the FDP. The appearance of these products of degradation in blood shows the presence of plasmin. The FDP’s are constituted by the fragments X, Y, D and E. These fragments D and E are the most important from the diagnostic point of view, and the commercial kit (thrombo-wellcotest) which is generally used for FDP, measures these two fragments only. The FDP are important not only for their diagnostic meaning, but also for their anticoagulant activity that is responsible, together with the consumption of coagulant factors, of the haemorraghic syndrome that appears during the DIC. They are considered ones of the most important inhibitors in blood. The derivation from fibrinogen, other than fibrin, makes this diagnostic test less specific towards the DIC. Nevertheless the DIC represents the clinical condition that more frequently causes an increase of the FDP. There are some other conditions that can produce a high level of FDP through an increased production or a reduced elimination: A. insufficiency of the mononuclear phagocytice system which removes these products.

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D-Dimers The D-Dimers are the products of fibrinâ&#x20AC;&#x2122;s degradation. They are the direct witness of the fibrinolytic activation, secondary to a coagulation process. The D-Dimers are the most specific test to diagnose a DIC, since they come only from the fibrin and not from the fibrinogen as it happens to the fragments X, Y, D and E. With regard to the DIC on 71 cases of DIC our research has demonstrated a 82% sensibility and a 95% specificity. We believe that, as in human medicine, also in dogs, the D-Dimers appears to be the test most likely to be alterated in confirmed DIC.

Antithrombin III (AT III) The AT III, together with protein C, protein S, and components of the fibrinolytics system are physiologically the most important naturally occuring anticoagulants proteins The AT III regulates the blood haemostasis and defends the organism against intravascular thrombosis2. It is an alpha-2globulin, produced by the liver (systemic action in blood) and, to a lesser extent, it is produced by the vascular endotelium (local action). It inactivates thrombin and other serine proteases in a progressive, irreversible manner. Antithrombin also inactivates other serine proteases, including factors Xa, IXa, Xa, XIIa, and kallikrein, although with less efficiency than for the inhibition of the thrombin.The rate of AT III-mediated inactivation clotting factor is markedly enhanced by heparin (i.e., 2,000 folds compared to thrombin). In DIC there is an increased consumption and consequently a low level of AT III in blood. Diseases that can cause a low level of AT III, besides the DIC are: A. liver failure (reduced production). B. Nephrotic syndrome (increased loss). C. Protein loosing entheropathies (increased loss). From a diagnostic point of view the AT III is less specific because there are quite many diseases which can influence it. The low diagnostic aid from the AT III levels in diagnosing the DIC is related to the function of the molecule which belongs to the acute phase proteins. Consequently, the AT III levels undergo to fluctations in relationship to the entity of the process. Since the AT III measures the patientâ&#x20AC;&#x2122;s anticoagulant capacity it must be considered as an indirect test for the diagnosis of the DIC. In our DIC dogs, the sensibility and specificity were respectively 48% and 60%. The AT III levels might have great importance mostly in fulminant DIC, where the consumption is greater than hepatic synthesis. The AT III is a good prognostic indicator. The prognosis is guarded as much as the levels of AT III are reduced in blood.

A list of suggested readings (MS Word97 or html format) will be e-mailed by the authors if requested to sanmarco@iperv.it

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B. Corticosteroids. C. Liver failure. D. Disfibrinogenemia (fibrinogenâ&#x20AC;&#x2122;s molecules not coagulated in test tube, cross-react with the policlonal antibodies towards the fragments D and E). E. Primary hyperfibrinolysis (clinical entity poorly described in veterinary medicine). F. Artifacts deriving from the failing separation of the fibrinogen from fragments D and E cause a cross-reaction with policlonal antibodies and the fibrinogen. Besides positives in a clinical condition, different from the DIC, you can find also some false negatives: A. in the DIC with low activation of the fibrinolysis are produced only X fragments in the very early phase of plasmin degradation, which are not measured out by the traditional assays for FDP. B. In the coagulation process which takes place in the testtube the D and E fragments can be trapped in the clot and they can be present in a small quantity in the serum. C. Excessive release of collagenase and elastase, originated in leukocytes, which degrades the FDP producing false negatives. In spite of these difficulties, in the current veterinary literature the FDP are considered the mainstay of the diagnosis of the DIC. In our study on 71 cases the FDP has demonstrated a 64% sensibility against a 55% specificity.

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Claw diseases in dogs and cats Didier-Noël Carlotti

Summary A figure of the anatomy of the canine claw is first presented. The clinical aspects of claw alterations and the diseases which cause such alterations in dogs and cats are reviewed, with emphasis on particular conditions: trauma, bacterial infection, fungal infection, parasitic diseases, allergies, auto-immune diseases, Raynaud’s disease, keratinization disorders, genodermatoses, naevus and idiopathic onychogryphosis, neoplasia. Claw diseases are often diagnostic and therapeutic challenges. A detailed case history, a thorough physical examination and appropriate complementary examinations are required to establish a diagnosis of claw diseases in dogs and cats. Therapy must be specific. In all cases appropriate follow-up is most important.

Introduction Nail disorders are relatively rare in companion animals, particularly in comparison with nail disorders in man1,2,3,4,5,6. In man, nail disorders are numerous and related to various causes7. These include hereditary nail dystrophies, trauma, bacterial infection, candidiasis, dermatophytosis, psoriasis, eczema, lichen planus, nail disorders observed in systemic diseases, Raynaud’s disease, arteritis, frost-bite.

Anatomy Figure 1 shows the anatomy of the canine claw unit1,8,9. The nail, or claw, is made of a thick stratum corneum. Claws have prehensile, locomotor and offensive/defensive functions3,4. A fibro-myxoid body with an ovoid shape has been discovered between the claw and the third phalanx in dogs and cats9.

nail fold. Usually the area looks erythematous and oedematous. Oozing, crusting, and - less common - erosion and ulceration may be present (e.g. in auto-immune mediated dermatoses). In chronic cases, scaling, alopecia, lichenification and hyperpigmentation may be observed. Onychoschisis means fissuration (splitting) of the nail. It can be caused by many inflammatory processes which alter the nail structure and by trauma. Onychorrhexis is the breaking of a nail which has become brittle for pathological reasons. Onychogryphosis is a deformation of the claw. It appears to be elongated and distorted. Usually this is caused by the inflammation of the digit extremities, coupled with a perionyxis. Onychomadesis is the sloughing off process for nails, it is usually multiple. Claw fracture is sometimes called onychoclasis. Onyxis can affect only one nail (trauma, idiopathic onychogryphosis, neoplasia, and often dermatophytosis, although the latter can affect a few digits, not necessarily all on the same foot). On the other hand multiple onyxis is observed in bacterial infections, leishmaniasis, allergic diseases, auto-immune disorders, Raynaud-like diseases, and keratinization disorders. Pruritus is rarely observed in cases of onyxis. It mainly appears in cases of allergic dermatitis. Pain is more common, particularly in cases of severe perionyxis, onychoschisis, onychorrhexis and onychomadesis, particularly in bacterial infections and immune-mediated disorders. It can be acute in the case of nail fracture. It will only appear belatedly in cases of neoplasia. However, neither pruritus nor pain will be noticeable in many cases, such as onychogryphosis (e.g. dermatphytosis, leishmaniasis, keratinization disorders, idiopathic onychogryphosis and the early stages of neoplasms).

Consideration of particular diseases1,2,3,4,5,6,9,11 Clinical signs1,2,3,4 1 - Traumatic onyxis Onyxis (or onychia) is by definition the disease of the abnormal looking nail. Often, but not always (e.g. trauma, neoplasia), an inflammatory process is responsible for the nail alteration. Onyxis can be proximal (usually at the onset of the disease), distal, or it may involve all the nail. Perionyxis (or paronychia) is the inflammation of the

This is a very common disease in the dog. It usually affects only one nail, in particular the thumbnails (digit 1) on the hind legs. The nail is more or less distally broken and pain is usually observed. Diagnosis is clinically obvious. Therapy consists in promptly removing the distal part of the nail with

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forceps. A bandage is then applied for a few hours. If this is done a few days after the fracture, systemic antibiotics should be used for a week to prevent secondary bacterial infection.

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serology and/or a parasitological examination (skin and/or bone marrow cytology). Comprehensive therapy (Lomidine®, Glucantime®, amphotericin B, allopurinol) and a strict follow-up are mandatory.

2 - Bacterial onyxis 5 - Onyxis of canine ankylostomiasis This disease exists in the dog but is much rarer in the cat. In the latter, it is usually associated with an immunodeficient state (FeLV and/or FIV infection, diabetes mellitus etc...). In the dog it may be idiopathic or secondary to an underlying disease (such as hypothyroidism, or even Cushing’s disease). Perionyxis, onychoschisis, onychorrhexis and onychomadesis are usually seen on several nails, with pain as the primary complaint. Diagnosis is made by cytology - which reveals a bacterial pus (degenerated neutrophils, phagocytosis), bacteriology and the response to therapy. Treatment must be based on the removal of broken nails, topical antibacterial therapy and long term systemic antibiotic therapy (based on bacterial cultures and sensitivity testing, Staphylococcus sp. and Gram negative rods often being cultured). Months of careful therapy are needed, until the distal abnormal part of the nail has disappeared. In all cases, and particularly in chronically relapsing ones, an underlying disease should be suspected and, if found, treated. Bacterial pododermatitis, whatever the cause, often leads to bacterial onyxis. Good examples are interdigital pyodermas due to demodicosis and allergic skin diseases. Perionyxis is a prominent feature in such cases. Therapy appropriate to the causal pododermatitis will cure the nail problem if carried out for long enough.

3 - Dermatophytic onyxis This is a rare cause of onyxis and perionyxis in the dog, usually with one or a few digits being affected. In Aquitaine, Microsporum gypseum and Microsporum canis have been found to be the dermatophytes which most frequently cause fungal onyxis. Alopecia of the corresponding digit is often observed. Diagnosis is made by Wood’s light examination which may reveal the fluorescence of the hair of the digit involved, direct examination and fungal culture of this hair, and histopathology of the nail itself. Skin biopsy and the removal of the third phalanx are unnecessary. PAS staining of the nail is mandatory and reveals the invasion of the nail keratine by the fungal hyphae. Long-term antifungal therapy (griseofulvine, ketoconazole, itraconazole) is necessary until the abnormal part of the nail disappears distally. This may take several months. Other cutaneous lesions should be topically treated simultaneously. Dermatophytic onyxis appears to be extremely rare in the cat. The author has never made such a diagnosis in a feline.

4 - Onyxis of leishmaniasis Onychogryphosis is a classic symptom of canine leishmaniasis. In the the enzootic area such a complaint justifies

Onychorrexis and onychomadesis can be seen in chronic cases of pododermatitis caused by ankyostomiasis12. Diagnosis is made by cutaneous histopathology and coproscopy.

6 - Onyxis of allergic dermatites An inflammatory skin disease of the digits (pododermatitis) is observed clinically in canine atopic dermatitis and food allergy or intolerance. Onychogryphosis is frequent, often associated with perionyxis and redness of the hair on the digits. The nails may appear reddish in dogs whose nails are normally white. A diagnosis is obviously reached by evaluating all the symptoms observed in these diseases, by skin-testing, serology and elimination diets. Therapy includes allergen eviction, hyposentitization and symptomatic treatment (systemic glucocorticoids, antihistamines, essential fatty acids, topical antipruritic agents etc.).

7 - Onyxis of auto-immune dermatoses These diseases usually affect several digits. A - discoid lupus erythematosus/symmetrical lupoid onychodystrophy. Discoid lupus erythematosus is a not so uncommon cause of onyxis in the dog3,9,13. In fact, as the disease is symmetrical, as focal thickening and smudging of the basement membrane zone are not seen and as direct immunofluorescence testing is negative, Danny Scott named this disease «Symmetrical Lupoid Onychodystrophy» in 199511. Onychorrhexis and onychogryphosis are the main features of the disease. Other lesions may be seen in other areas of the body, but this is not always the case. Perionyxis is not always pronounced and skin biopsies of the nail bed area may be unrewarding. Amputation of the third phalanx is often the only way to reveal the typical hydropic and lichenoid interface dermatitis. Immuno-suppressive doses of glucorticoids (prednisolone) may control the disease. Vitamin E and essential fatty acids (omega-3/omega-6 commercial compound) have been reported to be effective in some cases3,11. B - pemphigus vulgaris. Nails and nail beds may be affected in pemphigus vulgaris. Onychogryphosis and onychomadesis can be observed. Severe perionyxis is also present, with erosions around the nail bed which are a source of pain. Diagnosis is made by histopathology either by skin biopsies around the claw or alternatively by amputation of the third phalanx. Biopsies of lesions in other body areas may be diagnostic. Only a guarded prognosis should be made. Immunosuppressive therapy should be carried out (glucocorticoids, azathioprine).

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8 - Raynaud-like disease In Man, Raynaudâ&#x20AC;&#x2122;s disease is due to a spasm of digital arteries due to cold, which may be either secondary (e.g. to SLE) or idiopathic. It is a cyanotic/hyperhaemic and painful disease. Three female dogs (2 Boxers of 3 and 4 years of age and a 5 year-old mongrel) were suspected by the author to have a Raynaud-like disease. The patients were in severe pain from several digts which from time to time looked cyanotic. Onychogryphosis was prominent. Skin biopsies were performed in 2 dogs around the claws and showed non specific superficial dermatitis and a few Malassezia in the stratum corneum in one dog. Direct immunofluorescence testing was negative for IgG and C3. ANA test was negative in the 3 dogs. Long term therapy with isoxsuprine, a vasodilatator, at the dose of 1mg/kg/day, was very helpful.

9 - Keratinization diseases The author has seen severe mutiple onychogryphosis in cases of canine ichthyosis. However, generalized skin lesions were prominent and histopathology of the lesions con-

firmed the diagnosis. Many cases responded partially to retinoid therapy. Some cases of zinc responsive dermatosis observed in nordic dogs involve several digits. Two cases restricted to the digits, with a prominent perionyxis and above all onychorrhexis were observed by the author in Malamutes (of 10 and 12 months of age respectively). Diagnosis was made by histopathology, with biopsies taken around the nail bed. There was a dramatic response to zinc sulfate supplementation (150 mg/kg BID) whereas zinc methionine had not been very helpful. Several cases of idiopathic nosodigital hyperkeratosis in the older dog may be associated with mild multiple onychogryphosis.

10 - Genodermatoses Ichtyosis is a hereditary keratinization disorder. Onychogryphosis can be seen in canine dermatomyositis (Collies, Shetlands, Beaucerons) and epidermolysis bullosa (Beaucerons)14. Glucorticoids, vitamin E and pentoxifylline are helpful. A similar hereditary condition could exist in the cat, with onychomadesis15.

11 - Linear nevus and idiopathic onychogryphosis A case of congenital linear epidermal nevus ending in the paw of a hindleg was diagnosed by the author in a 3 year old Pyrenean shepherd, with a prominent onychogryphosis on 2 digits (and a secondary demodectic pododermatitis as well). The nevus responded well to retinoid therapy (etretinate 1 mg/kg/day during 18 months followed by acitretin, at the same dosage, during 8 months). The author has seen multiple inverted papillomas in a 7 year old mixed French Spaniel associated with a severe onychogryphosis of only one digit. Papillomas can cause the development of cutaneous horns and potentially this claw alteration was linked to the skin disease. Idiopathic onychogryphosis is observed in dogs. It usually affects one digit. Diagnosis is made by the elimination of other possible causes. Regular removal of the nail affected is advisable.

12 - Neoplasms Neoplasia of the nail fold is a common cause of onyxis and onychomadesis in the old dog. Squamous cell carcinoma (which is often misleading since it looks like a non-healing wound), melanoma, and mast cell tumour are relitavely frequent. However keratoacanthoma, inverted papilloma, and eccrine adenocarcinoma may also be observed3. These tumours affect only one digit usually, and necessitate agressive excision therapy. Melanoma and mast cell tumour may metastase, although squamous cell carcinoma has a better prognosis than usually believed if excision is carried out at an early stage. Swelling is often prominent and pain is acute.

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C - pemphigus foliaceus and/or erythematosus. Onychogryphosis and perionyxis can be observed in canine pemphigus foliaceus, particularly in severe forms of the disease. When pemphigus foliaceus is exclusively confined to the foot pads onychorrhexis is often observed. The author has seen 2 cases of pemphigus erythematosus confined exclusively to the footpads, with onychorrhexis. Diagnosis can be made by histopathology. In the extensive forms of the disease, biopsy of the skin lesions may be diagnostic. In the localized forms, biopsy of the foot pads and/or an amputation of the third phalanx may be diagnostic. Immunosuppressive therapy is necessary. In the cat, pemphigus foliaceus is a possible cause of severe perionyxis. A thick pus is discovered in the nail bed. Diagnosis is usually made by skin biopsy of the other skin lesions. Glucocorticoid immunosuppressive therapy is helpful. D - bullous pemphigoid-like skin disease. Severe multiple onychomadesis and/or severe onychogryphosis with ulcerative perionyxis may be seen in the bullous pemphigoid group skin disease (a group of auto-immune disorders with subepidermal clefting as a common feature). They may even be the prominent features of this disease, making it a most painful one. Diagnosis is made by biopsy of the skin lesions, particularly of the digits, if there is ulceration around the nail bed. Alternatively, amputation of the third phalanx of an affected digit may be the only way to diagnose such a condition if only nail disease is present. In one case, the author had the luck to establish a diagnosis of bullous pemphigoid by removing nails from a dog with onychomadesis; a small amount of skin tissue still attached to the claw displayed the typical lesions of dermal-epidermal clefting. Therapy is not easy. Glucorticoid immunosuppression is not always helpful.

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Diagnosis is made by histopathlogy of the removed tumour and radiographs of the digits often reveal bone lysis. Multiple squamous cell carcinomas are seen in black dogs, affecting several digits, with a slow growth rate. Excision therapy is mandatory. Nail bed tumours are rarer in old cats. Those that do occur are squamous cell carcinoma, hemangiosarcomas, and metatasis of primary lung carcinomas3.

inations are required to establish a diagnosis. The latter include cytology, bacteriology, mycology, histopathology (skin biopsy around the nail bed or even third phalanx amputation, sometimes very helpful) and immunological tests such as skin-testing and elimination diets. Therapy must be specific. In all cases appropriate follow-up is most important.

References 1.

Conclusion Claw diseases in dogs and cats are often diagnostic and therapeutic challenges. A detailed case history, a thorough physical examination and appropriate complementary exam-

2. 3. 4. 5. 6.

DORSAL EPIDERMIS 3rd PHALANX

DORSAL MATRIX

7. 8. 9. 10.

11.

12. 13. 14.

VENTRAL FOOTPAD MATRIX NAIL VENTRAL EPIDERMIS

15.

16. Figure 1 - Anatomy of the canine claw

Scott DW, Miller WH, Griffin CE (1995), Muller and Kirk’s Small Animal Dermatology, 5th edition, WB SAUNDERS Company, Philadelphia. Foil CS (1987), Disorders of the feet and claws, Proc. 11th KAL KAN Symposium, 23-32. Scott DW, Miller WH (1992), Disorders of the claw and clawbeds in dogs, Compend Contin Educ Pract Vet, 14: 1448-1458. Scott DW, Miller WH (1992), Disorders of the claw and the clawbeds in cats, Compend Contin Educ Pract Vet, 14: 449-457. White SD (1989), Pododermatis, Vet Dermatol, 1: 1-18. Guaguère E, Hubert B, Delabre C (1992), Feline pododermatitis, Vet Dermatol, 3:1-12. Du Vivier A (1980), Atlas of Clinical Dermatology, Gower Medical Publishing Ltd, London. Mueller RS, Sterner-Kock A, Stannard AA (1993), Microanatomy of the canine claw, Vet Dermatol, 4: 5-11. Carlotti DN (1995), Affections des griffes chez le chien et le chat, Prat Méd Chir Anim Comp, 30: 235-247. Delabre C, Guaguère E, Magnol JP (1993), Mise au point d’une technique de coupe histologique de doigts de carnivores - applications pratiques, Proc. 8es Journées du GEDAC, St-Malo. Scott DW, Rousselle S, Miller WH (1995), Symmetrical Lupoid Onychodystrophy in Dogs: A retrospective Analysis of 18 Cases (19891993), J Amer Anim Hosp Ass, 31: 194 - 201. Gross TL, Ihrke PJ, Walder EJ (1992), Veterinary Dermatopathology, Mosby Year Book, St-Louis. Remy I, Fontaine J (1992), Lupus érythémateux discoïde à localisation unguéale chez un chien, Proc Congrès CNVSPA, Paris, 314. Fontaine J, Remy I, Clerxc C (1992), Epidermolyse bulleuse jonctionnelle familiale chez les chiots Bergers de Beauce, Proc Congrès CNVSPA, Paris, 313. Johnstone I, Mason K, Sutton R (1992), A hereditary junctional mechanobullous disease in the cat, Proc 2nd Word Congress of Veterinary Dermatology, Montréal, 1992, 111-112. Goldschmidt MH, Shofer FS (1992), Skin tumors of the dog an the cat, Pergamon Press, Oxford.

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Itâ&#x20AC;&#x2122;s a coagulopathy. But couldnâ&#x20AC;&#x2122;t it be ehrlichiosis? C. Guillermo Couto

Summary Spontaneous bleeding disorders are common in dogs. Because canine ehrlichiosis can result in thrombocytopenia, thrombopathia, and other coagulopathies, it frequently leads to spontaneous bleeding.

Etiology and epidemiology Canine ehrlichiosis (CE), also known as tracker dog disease, tropical canine pancytopenia, and canine hemorrhagic fever, is caused by Ehrlichia canis, an obligated parasite of the mononuclear cells, and it is distributed worldwide. It appear that in German Shepherd dogs and Dobermann Pinschers, the disease is more severe than in other breeds. This disease became prominent after a large number of military dogs developed CE during the Vietnam war. A neutrophilic strain of ehrlichia has also been identified in dogs. Also, E. risticii (the Potomac horse fever agent) may result in seropositivity without clinical signs in dogs. Recently, it was demonstrated that E. risticii can result in seropositivity and transient fever, lymphadenopathy, and diarrhea in experimentally inoculated cats. Another ehrlichia organism, E. platys, prevalent only in the southeastern United States, can result in cyclic thrombocytopenia in dogs. The vector and main reservoir of E. canis is the common brown dog tick (Rhipicephalus sanguineous), which can transmit the organisms for more than 5 months after engorgement with infected blood; the incubation period varies from 7 to 21 days. The brown dog tick also can harbor Babesia and Hepatozoon spp. This organism can also be transmitted through blood transfusions.

Clinical features Three common clinical phases are recognized for CE: acute, subclinical, and chronic. The acute phase is common in enzootic areas, and rare in other regions. It lasts approximately two to four weeks and consists of mild to severe clinical signs, secondary to lymphoid hyperplasia, pyrexia, and cytopenias. Clinical signs and physical examination findings include presence of ticks, pyrexia, depression, weight loss, evidence of primary hemostatic bleeding, reactive lymphadenopathy and hyperplastic splenomegaly, dyspnea or

exercise intolerance due to pneumonitis, and occasionally, central nervous system (CNS) signs. During this phase, the titer may be negative, since it takes one to two weeks to develop sufficient antibody production (see below). The subclinical phase occurs after the acute phase, may last years, and is usually asymptomatic, although clinicopathologic abnormalities such as cytopenias and hyperglobulinemia may occur. An immunocompetent dog usually eliminates the organism during this phase. The chronic phase develops in dogs who cannot eliminate the organism, and is common in the non-enzootic areas. Clinically, it is also characterized by lymphoreticular hyperplasia, cytopenias, and hyperglobulinemia. The clinical signs begin one to four months post-inoculation, are variable in severity, and include weight loss, pallor, evidence of primary hemostatic defects, generalized reactive lymphadenopathy, hyperplastic splenomegaly with extramedullary hematopoiesis, ocular changes (chorioretinitis, anterior uveitis, hyphema, retinal hemorrhages), limb edema, and occasionally, CNS signs.

Clinicopathologic features The hematologic and serum biochemical findings consist mainly of cytopenias and hyperproteinemia due to hyperglobulinemia. During the acute phase thrombocytopenia due to peripheral destruction of platelets (ie; presumptively immune-mediated), regenerative anemia (due to immune hemolysis), leukocytosis with monocytosis, and a hypercellular bone marrow constitute common hematologic abnormalities; hyperproteinemia is present in a variable percentage of cases, and it usually worsens with time. Hyperglobulinemia and increased liver enzyme activities (with or without hyperbilirubinemia) are the main serum biochemical abnormalities during this phase. During the chronic phase, clinicopathologic changes are dominated by bi- or pancytopenia (with a hypocellular bone marrow), lymphocytosis (up to approximately 15,000 lymphocytes/Âľl), hyperglobulinemia and hypoalbuminemia due to a polyclonal (or more rarely, monoclonal) gammopathy, and proteinuria due to interstitial, lymphoplasmacytic nephritis; in addition to hypocellularity, bone marrow aspirates usually reveal increased numbers of plasma cells. Occasionally, dogs with chronic ehrlichiosis and normal platelet counts experience episodes of primary hemostatic

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bleeding; in those cases, a platelet dysfunction appears to be the cause of the bleeding. Polyarthritis has also been recognized in dogs with chronic ehrlichiosis.

Diagnosis A confirmative diagnosis of CE can be obtained by either: a) identifying the organism on cytologic specimens of lymph node, spleen, or bone marrow; or b) obtaining a positive serology for E. canis. Ehrlichia organisms are rarely identified in cytologic preparations, even retrospectively, once a diagnosis has been confirmed by serology. Serology for E. canis is usually performed by means of indirect immunofluorescent antibodies (IFA), a technique which is highly sensitive and specific. Some degree of cross-reactivity with other ehrlichia organisms occurs, mainly E. equi, E. risticii, and E. sennetsu, but no cross-reactivity exists with Rickettsia rickettsi, the RMSF agent. Titers of 1:10 (the lowest dilution used by most laboratories) are considered diagnostic for infection, and may persist even after successful treatment. Because detectable antibody titers do not occur until after 7 to 21 days post-inoculation, paired serum titers may be necessary in order to diagnose acute CE. Polymerase chain reaction (PCR) is now widely used to diagnose CE. Canine ehrlichiosis, as lymphoma and systemic lupus erythematosus (SLE), can mimic a variety of disorders. However, the main differential diagnoses in dogs with chronic CE include multiple myeloma, lymphoma, chronic lymphocytic leukemia, and SLE. Oftentimes, in a dog that presents with a chronic history of weight loss, splenomegaly, generalized lymphadenopathy, bi- or pancytopenia, bone marrow plasmacytosis, and a monoclonal gammopathy, the only one to differentiate between CE and multiple myeloma is by obtaining a positive serology for E. canis. The same holds true for dogs with chronic weight loss, mild lymphadenopathy and hepatosplenomegaly, lymphocytosis, and a monoclonal gammopathy. Another disorder that is commonly mimicked by acute CE is immune-mediated thrombocytopenia (ie; isolated thrombocytopenia and increased numbers of megakaryocytes in a bone marrow smear); in these cases, immunosuppressive corticosteroid treatment should be initiated in conjunction with tetracycline or doxycycline, until the results of the serology become available.

Treatment and prevention Even though the clinical signs in dogs with CE can be quite severe, response to treatment is usually remarkably good. A notable exception is that of dogs with severe

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chronic CE, in which response to treatment may be minimal. Recovery in dogs with acute forms and in dogs with mild chronic forms occurs in 24 to 72 hours; complete recovery in dogs with chronic infection may take up to four months. As discussed above, elevated titers (and a monoor polyclonal gammopathy) may persist for months or years. Tetracycline, and its derivative doxycycline, constitute the mainstay of treatment (Table 1). They should be administered for 10 to 21 days and usually result in complete resolution of the clinical signs. However, serum titers may persist for several months (or even years). Most textbooks recommend using tetracycline as the first line of treatment; however, since a less expensive generic doxycycline is available, we routinely use it to treat dogs with CE at doses of 5 to 10 mg/kg, PO, SID to BID. Moreover, it appears to be more effective than tetracycline, and it causes less yellowing of the teeth in pups than its parent compound (tetracycline). Doxycycline can also be used intravenously in dogs with severe clinical signs or vomiting. Chloramphenicol can also be used successfully to treat CE. However, given its potential for marked hematologic toxicity it is not the drug of choice for a cytopenic dog. If treatment with tetracycline, doxycycline, or chloramphenicol fails to induce clinical or hematologic remission, imidocarb dipropionate, and anticholinesterase agent not available in the United States should be used. It is administered as a single subcutaneous or intramuscular injection (5 mg/kg), which can potentially be repeated in 2 to 3 weeks. It usually causes transient vomiting, diarrhea, shivering, and coughing, which resolve within minutes to hours of the administration. As a general rule, intramuscular administration of drugs should be avoided in dogs with thrombocytopenia or thrombocytopathia. Supportive treatment in dogs with CE include administration of fluids and/or blood products, and possibly, corticosteroids to treat the underlying immune mediated disorder. Immunosuppressive doses of corticosteroids, equivalent to 2-4 mg/kg of prednisone daily, do not appear to adversely affect the course of the disease when used concomitantly with tetracycline or doxycyline. Anabolic steroids may be used in attempts to stimulate hematopoiesis. Prevention of CE centers around tick control, for which a variety of products are available. Hunting dogs should be tested and treated, since asymptomatic carriers can be a source for continuous infection from ticks. Prophylactic treatment with tetracycline (3 mg/kg, PO, SID) or doxycycline (2-3 mg/kg, PO, SID) during tick season may prevent infection. All canine blood donors should be tested for E. canis by serology.

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Practical chemotherapy C. Guillermo Couto DVM, Dipl ACVIM Department of Veterinary Clinical Sciences - College of Veterinary Medicine The Ohio State University - Columbus, Ohio - USA

Chemotherapy is commonly used in small animals with malignant tumors. The basic principles, indications, contraindications, and practical applications of this treatment modality will be discussed using case examples.

Cell and tumor kinetics The mammalian cell cycle has 2 apparent phases: mitosis and resting phase. The “resting phase” is indeed composed of 4 phases: • synthesis phase (S): DNA synthesis occurs • gap 1 phase (G1): synthesis of RNA and enzymes needed for DNA production occurs • gap 2 phase (G2): synthesis of the mitotic spindle apparatus occurs • gap 0 phase (G0): true resting phase. The mitosis phase is termed M phase. Several terms need to be defined prior to discussing chemotherapy. Mitotic index (MI) refers to the percentage of mitoses in a tumor mass. Growth fraction (GF) refers to the proportion of proliferating cells within a tumor. Doubling time (DT) refers to the time required by a tumor mass to double in size. In dogs they range from 2 days (for metastatic osteosarcoma) to 24 days (for metastatic melanoma), while in humans they range from 29 days (for malignant lymphomas) to 83 days (for breast cancer). The DTs depend upon the time spent in mitosis, cell cycle duration, GF and cell loss from death or metastases. Given our knowledge on tumor kinetics, by the time a pulmonary metastatic nodule is visualized on radiographs, it has 200,000,000 cells and weighs less than 150 mg (and it has already divided 25 to 35 times). As a general rule, most non-neoplastic tissues (with the exception of bone marrow stem cells and intestinal crypt epithelium) have low GF, low MI, and prolonged DT, while most neoplastic tissues have high MI, high GF, and short DT. Surgical cyroreduction (debulking) of a tumor that reached a plateau of growth will decrease the total number of cells, thus increasing the MI and GF, and shortening the DT. This will turn the neoplasm more susceptible to chemoor radiotherapy.

Indications and contraindications of chemotherapy Chemotherapy is primarily indicated for patients with systemic (eg; lymphoma, leukemias) and metastatic neoplasms, although it can also be used for nonresectable, chemoresponsive neoplasms which have been historically refractory to radiotherapy or hyperthermia (primary chemotherapy). It can also be used as an adjuvant treatment following partial surgical debulking of a neoplasm (eg; partial excision of an undifferentiated sarcoma), and is indicated for control of micrometastatic disease following surgical excision of a primary neoplasm (eg; cisplatin therapy after limb amputation in dogs with osteosarcoma; VAC for dogs with hemangiosarcoma). As a general rule, chemotherapy should NEVER be used as a substitute for surgery, radiotherapy, or hyperthermia, or in patients with severe underlying multiple organ dysfunction (the latter will increase the possibility of developing systemic toxicity).

Mechanism of action of anticancer drugs The effects of anticancer drugs on a neoplastic cell population follow first order kinetic principles (ie: the number of cells killed by a drug or drug combination is directly proportional to one variable, the dose used). Anticancer drugs kill a constant proportion of cells, rather than a constant number. Therefore, the efficacy of a drug or drug combination will depend upon the number of cells within a given tumor [eg; a drug combination that kills 99% of the cells in a tumor containing 100,000,000 (109) cells will leave 1,000,000 (106) viable cells]. It should also be kept in mind that different types of anticancer drugs kill tumor cells by different mechanisms (see below).

Types of anticancer drugs Anticancer agents are classified in the following categories: • alkylating agents • antimetabolites • antitumor antibiotics • plant alkaloids (or mitotic inhibitors) • hormones • miscellaneous

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Alkylating agents cross-link DNA, thus preventing its replication. Since they mimic the effects of radiotherapy they are also referred to as radiomimetics. These drugs are active during several phases of the cell cycle (ie; they are cell cycle-nonspecific drugs). Alkylating agents commonly used in pets with cancer include: • cyclophosphamide (Cytoxan®) • chlorambucil (Leukeran®) • melphalan (Alkeran®) • cisplatin (Platinol®) [DO NOT USE IN CATS!] Antimetabolites exert their activity during the S phase of the cell cycle (cell cycle phase-specific drugs). These drugs are structural analogues of naturally occurring metabolites (fake metabolites) that substitute for normal purines or pyrimidines. The following antimetabolites are commonly used in small animal cancer patients: • cytosine arabinoside (Cytosar-U®) • methotrexate (Methotrexate®) • 5-fluoruracil (5-FU®) [DO NOT USE IN CATS!] • 6-thioguanine (6-TG®) • 6-mercaptopurine (PuriNethol®) • azathioprine (Imuran®)* Antitumor antibiotics act by several mechanisms, the most importants of which appear to be cross-linking of DNA and inhibition of protein synthesis. They include: • doxorubicin (Adriamycin®) • bleomycin (Blenoxane®) • actinomycin D (Cosmegen®) • mitoxantrone (Novantrone®) Plant alkaloids are derived from the periwinkle plant (Vinca rosea) and the May apple plant (Podophyllum peltatum ). They disrupt the mitotic spindle and are therefore cell cycle phase-specific (active during M phase). Commonly used plant alkaloids include:

*Commonly used as an immunosuppressive drug.

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• vincristine (Oncovin®) • vinblastine (Velban®) • etoposide or VP-16 (VePesid®) Hormones are commonly used for the treatment of hemolymphatic malignancies or endocrine-related tumors. Commonly used hormones include: • prednisone • testosterone • estrogens • progestagens With the exception of corticosteroids, the use of hormones is not recommended since they are associated with significant side effects in animals. Finally, miscellaneous agents include drugs whose mechanism of action is either unknown or different from the ones listed above. Miscellaneous agents commonly used in small animal cancer patients include: • DTIC (DTIC®) • l-asparaginase (Elspar®)

References • Bech-Nielsen S, Reif JS, Brodey RS: The use of tumor doubling time in veterinary clinical oncology. J Amer Vet Radiol Soc 17:113-116, 1976. • Couto CG: Principles of chemotherapy. In Proceedings 10th Annual Kal Kan Symposium for the Treatment of Small Animal Diseases. 1986, pp 29-36. • Couto CG: Practical chemotherapy. In Nelson RW and Couto CG: Essentials of Small Animal Internal Medicine. St. Louis, Mosby-Yearbook, 1992, p 842-846. • Dorr RT and Fritz WL: Cancer Chemotherapy Handbook. New York, Elsevier, 1980. • Helfand SC: Principles and applications of chemotherapy. Vet Clin North Amer 20:987-1013, 1990.

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Complications of chemotherapy C. Guillermo Couto

Summary Chemotherapy is commonly used in small animal practice. Although this treatment modality is associated with a high prevalence of adverse effects in people, toxicity in dogs and cats is minimal and they usually preserve excellent quality of life. This lecture will discuss the common toxicities of chemotherapy, emphasizing recognition and management.

Most anticancer agents are relatively nonselective in that they not only kill rapidly dividing neoplastic tissues, but also some of the rapidly dividing tissues in the host as well (eg; villal epithelium, bone marrow cells). In addition, they are similar to other commonly used agents (eg; digitalis glycosides) in that they have low therapeutic indices (ie; narrow therapeutic-to-toxic ratios). Because anticancer agents follow first order kinetic principles (ie; the fraction of cells killed is directly proportional to the dose used), increasing the dose of a particular drug will increase the proportion of neoplastic cells killed, but it will also enhace its toxicity. This is commonly seen when a tumor relapses and higher doses of a previously used drug are utilized. Because toxicity is generally directed against rapidly dividing tissues, given the short turnover rate of bone marrow and villal epithelial cells, myelosuppresion and gastrointestinal signs are the most common toxicities encountered in practice. Other rare complications of chemotherapy include anaphylactoid (or anaphylactic) reactions, dermatologic toxicity, pancreatitis, cardiotoxicity, pulmonary toxicity, neurotoxicity, hepatopathies, and nephropathies. Table 1 lists anticancer drugs commonly used in small animals and their toxicities. In addition to the direct effects of the drugs on different organ systems, rapid killing of certain neoplastic cells (ie; lymphoma cells) can lead to rapid metabolic derangements that result in acute clinical signs which mimic those of drug toxicity (ie; depression, vomiting, diarrhea). This syndrome is referred to as acute tumor lysis syndrome (ATLS). Overall, the prevalence of toxicity of different chemotherapy protocols is considerably lower in dogs and cats (approximately 5% to 40%) than in humans (75% to 100%) treated with similar drugs or combinations. A recent survey of owners whose pets had been treated with a variety of chemotherapy protocols at The Ohio State University Vet-

erinary Teaching Hospital revealed that over 80% of those questioned considered their pets’ quality of life to be equal to or better than that prior to initiating chemotherapy.

Hematologic toxicity The high mitotic rate and growth fraction (ie; 40 to 60%) of the bone marrow cells predispose this organ to toxicity from anticancer drugs. Hematologic toxicity represents the most common toxicity of chemotherapy, and oftentimes results in temporary or permanent discontinuation of the offending agent/s due to severe (and often life-threatening) cytopenias. Agents commonly implicated in this type of toxicity are listed in Table 1. When one considers the bone marrow transit times and circulating half lives of blood cells, it is easy to anticipate which cell line will be affected. For example, the bone marrow transit time and circulating half life of RBCs in the dog are approximately 7 days and 120 days, those of the platelets are 3 days and 4 to 6 days, and those of granulocytes are 6 days and 4 to 8 hours, respectively. Therefore, it is anticipated that neutropenia will occur first, followed by thrombocytopenia; anemia induced by chemotherapeutic agents is extremely rare in dogs and cats, and, if it occurs, is of a late onset (3 to 4 months after initiation of therapy). Other patient (eg; malnutrition, old age, concurrent organ dysfunction) and tumor factors (eg; bone marrow infiltration, widespread parenchymal organ metastases) can also effect the degree of cytopenia. Although thrombocytopenia is probably as common as neutropenia, it is rarely severe enough to cause spontaneous bleeding, and it will therefore not be discussed at length. In general, in most dogs and cats with chemotherapy-induced thrombocytopenia the platelet counts remain above 50,000 cells/µl; spontaneous bleeding does not usually occur until platelet counts fall below 30,000/µl. Thrombocytosis is common in cats and dogs receiving vincristine. Neutropenia usually constitutes the dose-limiting cytopenia and occasionally leads to life-threatening sepsis. For most drugs, the nadir usually occurs 5 to 7 days after treatment, and the neutrophil counts return to normal values within 36 to 72 hours of the nadir. Patients with neutrophil counts under 2,000 cells/µl should be closely monitored for the development of sepsis, although overwhelming sepsis rarely occurs with neutrophil counts of ≥1,000/µl.

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Table 1. Toxicity of anticancer agents commonly used in dogs and cats

Drug

Hematologic

Anaphylaxis

Dermatologic Pancreatitis

ALKYLATING AGENTS Busulfan (Myleran®) Chlorambucil (Leukeran®) Cyclophosphamide (Cytoxan®) Melphalan (Alkeran®)

++ +/++/+++ ++

+/++ +/-

+/- A1 +/-A +A +/-A

? ? ? ?

ANTIMETABOLITES Cytosine arabinoside (Cytosar-U®) 5-Fluoruracil (5-FU®) 6-Mercaptopurine (Purinethol®) Methotrexate (Methotrexate®) 6-Thioguanine (Thioguanine®) Azathioprine (Imuran®)

++/+++ ++ +/++ +/+++ +/++ +/+++

+/+/++ +/++ +/+++ + +/++

+A +A +/-H2 +A +/++A +/++A +A

+/? +/++ ? ? +/++

ANTITUMOR ANTIBIOTICS Doxorubicin (Adriamycin®) Bleomycin (Blenoxane®)

++/+++ -

+/+++ -

+/++ -/+

++AH +++S3 +H

+/++ ?

+ +/+/++

+++4

+A ++S +A ++S +A

? ? ?

PLANT ALKALOIDS (MITOTIC INHIBITORS) Vincristine (Oncovin®) +/++ Vinblastine (Velban®) ++/++ Etoposide (VePesid®) +/+++ HORMONES Prednisone Estrogens

+/+++

+/-

(see other) -

++ ?

MISCELLANEOUS Dacarbazine (DTIC®) Cis-platinum (Platinol®)

++/+++ +/-

++/+++ ++/+++

+A +A

+/++ ?

L-asparaginase (Elspar®) Hydroxyurea (Hydrea®)

+/+/+++

+/+/-

+++ -

+/+++A

+++ ?

Other

Cystitis

Liver?

Cardiac Lungs

Cushing’s

Renal Lung5

1A: alopecia; 2H: hyperpigmentation; 3S:perivascular sloughing; 4 when administered IV; 5 in cats.

The pathogenesis of sepsis in neutropenic patients is as follows: chemotherapy-induced death and desquamation of gastrointestinal crypt epithelial cells occurs simultaneously with myelosuppression; enteric bacteria are absorbed through the damaged mucosal barrier into systemic circulation; the numbers of neutrophils in circulation are not sufficient to phagocytose and kill the invading organisms; as a consequence, microbial colonization of multiple organs occurs, and death ensues unless the patient is treated appropriately. From the clinical standpoint, it is important to identify the septic neutropenic patient, since the cardinal signs of inflammation (ie; redness, swelling, increased temperature, pain, and abnormal function) may be absent due to insufficient numbers of neutrophils available to participate in the inflammatory process. The same holds true for radiographic changes compatible with inflammation; for example, dogs with neutropenia and bacterial pneumonia diagnosed on the basis of cytologic and microbiologic findings in transtracheal washes, oftentimes have normal thoracic radiographs.

As a general rule, when a severely neutropenic patient (neutrophil count <500/µl) presents with marked pyrexia (Tº >104), the pyrexia should be attributed to bacterial pyrogens until proven otherwise, and the patient should be treated aggressively with empirical antimicrobial therapy (see below). In addition, neutropenic patients with severe constitutional signs (eg; depression, vomiting, diarrhea) and normal or low body temperature should be regarded as septic and treated aggressively. At the VTH-OSU, every neutropenic dogs and cat with fever or nonspecific clinical signs is considered to be septic until proven otherwise. All patients undergoing chemotherapy should be current on their immunizations. However, hematologic monitoring the patient on chemotherapy constitutes the most effective way to prevent severe, life-threatening sepsis secondary to myelosuppression. Complete blood counts (CBCs) should be obtained weekly or every other week when using myelosuppressive protocols, and the myelosuppressive agent/s should be temporarily discontinued (or their doses decreased) if the neutrophil count is below 2,000 cells/µl or if

the platelet count is below 50,000 cells/µl. Discontinuing the offending agent/s for 2 or 3 administrations is usually sufficient for the cell counts to return to the normal range. When therapy is reinstituted, it is recommended that only 75% of the initial dose be used, escalating doses over 2 to 3 weeks until the initially recommended dose (or a dose which does not result in marked cytopenias) is reached. Clinically, neutropenic patients can be classified as febrile or afebrile. Neutropenic febrile patients should be approached aggressively, since they are usually septic. Thus, fever in a neutropenic patient constitutes a medical emergency. The following protocol is currently used in neutropenic febrile patients at the VTH-OSU (Table 2). The patient undergoes a thorough physical examination in search of a septic focus, an indwelling intravenous catheter is placed aseptically and intravenous fluids are administered as required. All anticancer agents with the exception of corticosteroids are discontinued at once (corticosteroids should be discontinued gradually, since patients on chronic steroid therapy can develop episodes of acute hypoadrenocorticism when the drug is abruptly discontinued). Blood samples for CBC; serum electrolyte, blood glucose, and blood urea nitrogen (BUN) concentrations are obtained immediately; a urine sample for urinalysis and bacterial culture is also obtained. Two to three sets of aseptically collected blood samples can be obtained for aerobic and anaerobic bacterial cultures and antibiotic susceptibility tests at 30 minute intervals (this is usually not necessary, since the bacterial isolates are quite predictable - see below). After collecting the second set of samples for blood cultures, therapy with an empirical bacteriocidal antibiotic combination is instituted. We prefer a combination of gentamicin (2.2 mg/kg, IV, TID) or amikacin (6-10 mg/kg, IV, TID) and cephalothin (40 mg/kg, IV, TID) since most bacterial isolates in these patients are Enterobacteriaciae and staphylococci, organisms commonly susceptible to these agents. Once the neutrophil count returns to normal and the patient is clinically normal (usually within 72 to 96 hours), the antibiotic combination is discontinued and the patient is released with instructions to administer sulfadiazine-trimethoprim (ST) at a dose of 13-15 mg/kg, PO, BID for 5 to 7 days. Neutropenic afebrile asymptomatic patients can be treated as outpatients with discontinuation of the drug/s as

Table 2. Management of neutropenic febrile dogs and cats • search for septic focus (PE, rads, US) • IV catheter • blood for CBC and biochemical profile • LRS solution (40-60 ml/kg for dogs and 20-30 ml/kg for cats) • discontinue chemo drugs (except for corticosteroids) • antibiotics cephalotin 40 mg/kg, IV, tid gentamicin 2.2 mg/kg, IV, tid or amikacin 6-10 mg/kg, IV, tid* • after patient stabilizes, decrease rate of IV fluids to 60-90 ml/kg/day * if the patient is oliguric or anuric, do not administer aminoglycoside until after the urinary bladder is palpable (ie; there is diuresis).

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above plus ST (15 mg/kg, PO, BID); if the patients is afebrile but has constitutional signs, he/she should be considered to be septic and treated as described above. If the neutropenia is not severe (ie; ≥ 2,000 cell/µl), no therapy is needed, and the patient should only be monitored by the owner. Owners should be instructed to monitor their pet’s rectal temperature twice daily, and call the veterinarian if pyrexia develops, in which case the patient is treated as neutropenic and febrile. Sulfa-trimethoprim combinations eliminate the aerobic intestinal flora, but preserve the anaerobic bacteria, which are an important component of the local defense system, due to their ability to produce local antibiotic factors. In addition, ST is active against a large number of pathogens isolated from cancer patients, provide therapeutic blood and tissue concentrations, and also provide high intragranulocytic concentrations. Myelosuppression may be alleviated by using lithium carbonate (10 mg/kg, PO, BID), granulocyte colony stimulating factor (G-CSF) at a dose of 5-10 µg/kg SQ bid, or products which stimulate release of endogenous G-CSF (eg; bacterial products).

Gastrointestinal toxicity Although less frequent than myelosuppression, gastrointestinal toxicity is a relatively common complication of cancer chemotherapy in pets. From the clinical standpoint two major types of gastrointestinal complications can occur: nausea/vomiting and gastroenterocolitis. Although controlled studies are not available, nausea and vomiting are not apparently as common in pets as in humans (when using similar drugs and dosages). Drugs associated with nausea and vomiting in dogs include DTIC, cisplatin, doxorubicin, methotrexate, and actinomycin D; doxorubicin and cyclophosphamide frequently result in nausea/vomiting in cats (Table 1). Acute nausea and vomiting caused by injectable drugs can be alleviated by administering the offending agents by slow intravenous infusions. If they persist despite slow administration, the use of antiemetics such as metoclopramide (Reglan®) at a dose of 0.1 to 0.3 mg/kg, IV, SQ, or PO TID, or prochlorperazine (Compazine®) at a dose of 0.5 mg/kg, IM, BID to TID is indicated. Gastroenterocolitis from anticancer agents is rare. Drugs which occasionally cause mucositis include methotrexate, 5-fluoruracil, actinomycin D, and doxorubicin; it occurs rarely with other alkylating agents such as cyclophosphamide. Of the drugs listed above, only doxorubicin (Adriamycin®) and methotrexate (Methrotrexate®) appear to be of clinical importance. In my experience, Collies and Collie crosses, Old English Sheepdogs, and West Highland White terriers appear to be extremely susceptible to doxorubicininduced enterocolitis. Doxorubicin-induced enterocolitis is characterized by the development of hemorrhagic diarrhea (with or without vomiting), primarily of large bowel type, 3 to 7 days after administration of the drug. Supportive fluid therapy (if necessary) and treatment with therapeutic doses of bismuth subsalicylate-containing products (Pepto Bismol®, 3 to 15 ml or

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1/2 to 2 tablest PO, TID to QID) are usually effective in controlling the clinical signs, which usually resolve in 3 to 5 days. Although anecdotal, if the patient is at risk for gastroenterocolitis (ie; one of the breeds mentioned above, prior history of this toxicity), administration of Pepto-Bismol® from days 1 to 7 of the treatment may alleviate or prevent these signs. Gastroenteritis associated with oral methotrexate administration usually develops after the patient has been receiving this drug for a minimum of two weeks.

Hypersensitivity reactions Acute type I hypersensitivity reactions occasionally occur in dogs receiving parenteral l-asparaginase (Elspar®) or doxorubicin (Adriamycin®), and are common in dogs treated with etoposide (VePesid®). The reaction to doxorubicin does not appear to be a true hypersensitivity reaction, since this agent can induce direct mast cell degranulation independently of IgE mediation. Etoposide can be safely administered orally to dogs. Hypersensitivity reactions to anticancer agents are extremely rare in cats and will not be discussed. Clinical signs in dogs with hypersensitivity reactions are primarily cutaneous and gastrointestinal. Typical signs begin during or shortly after administration of the agent, and include head shaking (due to ear pruritus), generalized urticaria and erythema, restlesness, occasional vomiting, and (rarely) collapse due to hypotension. Most systemic anaphylactic reactions can be prevented by pretreating the patient with H-1 antihistamines (ie; diphenhydramine, 1-2 mg/kg, IM, 20-30 minutes prior to administration of the drug) and by administering certain drugs (such as l-asparaginase) by the subcutaneous, intramuscular, or intraperitoneal route, rather than intravenously. If the agent cannot be given by any other routes (ie; Adriamycin®), it should be diluted and administered by slow intravenous infusions. At the VTH-OSU we routinely pretreat dogs (but not cats) with diphenydramine prior to administering doxorubicin or l-asparaginase. Treatment of acute hypersensitivity reactions includes immediate discontinuation of the agent, administration of H-1 antihistamines (ie; diphenhydramine, 0.2-0.5 mg/kg, slow IV), intravenous dexamethasone sodium phosphate (1-2 mg/kg), and fluids, if deemed necessary. If the systemic reaction is severe, the administration of epinephrine (0.1-0.3 ml of a 1:1,000 solution, IM or IV) is indicated. Once the reaction subsides, the administration of certain drugs such as Adriamycin® may be continued. Intravenous H1 antihistamines should be used with caution in cats, since they can cause acute CNS depression leading to apnea.

Dermatologic toxicity Dermatologic toxicity is rare in small animals. Three types of dermatologic toxicities can occur: local tissue necrosis due to extravasation, delayed hair growth or alopecia, and hyperpigmentation. Local tissue necrosis due to extravasation of vincristine,

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vinblastine, actinomycin D, or doxorubicin is occasionally seen in dogs receiving these drugs; however, it is rare in cats. Although the pathogenesis of this toxicity is poorly understood, these drugs are extremely caustic when given perivascularly, causing marked tissue necrosis 1 to 15 days after the injection (earlier with the vinca alkaloids, and later with doxorubicin and actinomycin D). As a consequence of this, every effort should be made to ensure that these drugs are administered intravascularly. In order to prevent or minimize extravascular injection of caustic drugs, they should be administered through a small gauge (22 G to 23 G) indwelling intravenous catheter (I prefer over-the-needle catheters such as the Terumo Surflo®) or 23 G to 25 G butterfly catheters. I use the former for doxorubicin and the latter for vinca alkaloid administration; in cats, it is safe to administer doxorubicin through a butterfly catheter. Caustic drugs should be properly diluted prior to administration (ie; vincristine to a final concentration of 0.1 mg/ml and doxorubicin to a concentration of 0.5 mg/ml), and patency of the catheter should be assured by intermittently aspirating until blood appears in it. If the catheter is not patent, it should be placed in another vein. Despite careful intravascular injection, some dogs develop mild to moderate local tissue reactions (eg; erythema, moist desquamation, and alopecia). This is common in Golden Retrievers receiving vincristine, vinblastine, actinomycin D, or doxorubicin, and is believed to be due to selfinflicted damage after developing mild phlebitis or thrombophlebitis. These patients are managed as discussed below. Recommendations for management of extravascular injections are listed in Table 3. If despite these precautions a local tissue reaction occurs, it will develop in approximately 1 to 7 days after perivascular injection of vinca alkaloids, and 7 to 15 days after actinomycin D or doxorubicin extravasation. Tissue necrosis is far more severe with doxorubicin, since it is extremely caustic and it persists in the tissues for several weeks to months. Clinical signs include pain, pruritus, erythema, moist dermatitis, and necrosis of the affected area; severe tissue sloughing usually occurs. If mild local tissue reactions develop, they can be treated as described in Table 4. In dogs and cats undergoing chemotherapy delayed hair growth is more common than alopecia. This is in contrast with human patients, in which severe scalp alopecia is a predictable complication of therapy. Excessive shedding is also a common occurrence. Alopecia appears to occur predominantly in wooly (coarse) haired dogs such as poodles and Kerry blue terriers. In short haired dogs and cats, it affects primarily the tactile hairs. Although the exact reason why wooly haired dogs develop chemotherapy-induced alopecia is unknown, a prolonged anagen phase and synchronous hair growth, comparable to that existing in human scalp hair may make these dogs prone to this toxic effect. Drugs commonly associated with delayed hair growth or alopecia include cyclophosphamide, doxorubicin, 5-fluoruracil, 6-thioguanine, and hydroxyurea. Alopecia and delayed hair growth usually resolve shortly after discontinuation of the offending agent. Hyperpigmentation induced by anticancer agents is rare in dogs and extremely rare in cats. Cutaneous hyperpig-

Table 3. Recomendations for the management of perivascular injections of caustic anticancer drugs in cats and dogs 1. Do not remove the IV catheter. 2. Administer 10 to 50 ml of sterile saline solution through the catheter (in an attempt to dilute the agent). 3. With a 25 G needle administer 10 to 20 ml of sterile saline solution subcutaneously (SQ) in the affected area. 4. Inject 1 to 4 mg of dexamethasone sodium phosphate SQ in the affected area (in an attempt to stabilize lisosomal and plasma membranes). 5. Apply cold compresses or ice packs to the area for 48-72 hours (to cause vasoconstriction and prevent local dissemination of the drug, and to decrease local tissue metabolism).

Table 4. Recommended treatment for dogs that received a perivascular injection of a caustic anticancer agent 1. Apply an antibiotic ointment (with or without corticosteroids) to the affected area. 2. Bandage the area (and replace bandages daily). 3. Prevent the patient from causing self mutilation by using an elizabethan collar or a muzzle. 4. If there is no bacterial contamination (ruled out on the basis of negative bacterial cultures or cytology), DepoMedrol速 can be injected subcutaneously (10 to 20 mg) in the affected area to alleviate pruritus and inflammation. 5. If severe necrosis or gangrene due to anaerobic contamination occurs the area should be surgically debrided. 6. In severe doxorubicin-induced soft tissue necrosis, amputation of the affected limb may be required.

mentation affecting the face, ventral abdomen and flanks is quite common in dogs receiving doxorubicin-, actinomycin D, and bleomycin-containing protocols.

Cardiotoxicity Cardiotoxicity is a relatively rare complication of doxorubicin therapy in the dog, and appears to be extremely rare in the cat. Two types of doxorubicin-induced cardiac toxicity are observed in dogs: an acute reaction during or shortly after administration, and a chronic cumulative toxicity. Acute doxorubicin toxicity is characterized by the development of cardiac arrhythmias (mainly, sinus tachycardia) during or shortly after administration. This phenomenon is thought to be related to doxorubicin-induced histamine-mediated catecholamine release, since the sinus tachycardia and hypotension can be prevented by pretreatment with H1 and H2 antihistamines. Several weeks or months after repeated doxorubicin injections, persistent arrhythmias, including ventricular premature contractions, atrial premature contractions, paroxysmal ventricular tachycardia, second degree AV blocks, and intraventricular conduction defects develop. These rhythm disturbances are usually associated

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with the development of a dilated cardiomyopathy, similar to that seen spontaneously in large breed dogs and Cocker Spaniels. The hallmark of chronic doxorubicin toxicity in the dog is the development of dilated cardiomyopathy after surpassing a total cumulative dose of approximately 240 mg/m2. The cumulative cardiotoxic dose in the cat is unknown, but it appears to be approximately 150 to 170 mg/m2. Clinical signs of toxicity in dogs are those of congestive heart failure (usually leftsided). Therapy consists of discontinuation of the drug and use of cardiac drugs such as digitalis glycosides or non-glycoside inotropic agents. Once cardiomyopathy develops, the prognosis is poor, since myocardial lesions are irreversible. For a detailed discussion of treatment of dilated cardiomyopathy please refer to a standard internal medicine textbook. Monitoring dogs receiving doxorubicin is critical to prevent the development of fatal cardiomyopathy. In this respect, dogs and cats with underlying rhythm disturbances or impaired myocardial contractility, as determined by decreased fractional shortening on M-mode echocardiograms should not receive doxorubicin. It is also recommended that patients receiving doxorubicin undergo M-mode echocardiographic evaluation every three doxorubicin cycles (9 weeks) to assess myocardial contractility, and that administration of the drug be discontinued if decreased fractional shortening occurs. The use of endomyocardial biopsies to monitor cardiac toxicity from doxorubicin is impractical in dogs and cats. Several protocols have been devised in an attempt to minimize doxorubicin-induced cardiomyopathy. Unfortunately, only three protocols have shown promise. Of these, weekly low dose doxorubicin showed a significantly lower frequency of histologic changes when compared to the conventional 3-weekly schedule in humans. I have been able to administer total cumulative doses of 500 mg/m2 to two dogs, when using 10 mg/m2 weekly. However, recent evidence suggests that this schedule is not as effective in dogs with lymphoma. A new compound termed ICRF-187 (or ADR 259) offers a promising means of reducing the chronic cardiotoxicity induced by doxorubicin; using this compound, doses in excess of 500 mg/m2 have been administered to dogs without significant cardiotoxicity. Unfortunately, this compound is not commercially available. At the VTH-OSU we administer doxorubicin as a slow bolus (20-30 minutes) of a 0.5 mg/ml solution intravenously. This results in a relatively low peak plasma concentration of the drug, and decreases the risk of developing cardiotoxicity. Using this protocol we evaluate approximately one dog every 18 months with clinical evidence of doxorubicin-induced cardiomyopathy; for reference, we administer approximately 4 gm of doxorubicin per year, and a 70 lb dog receives an average dose of 30 mg.

Urotoxocity The urinary tract is rarely involved in adverse reactions to anticancer agents in small animal patients. Only two specific complications are of clinical importance in pets with cancer: nephrotoxicity and sterile hemorrhagic cystitis.

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Transitional cell carcinomas (TCCs) of the urinary bladder associated with cyclophosphamide (CTX ) therapy can also occur in dogs. Nephrotoxicity is rarely observed in dogs and cats undergoing chemotherapy. Although several potentially nephrotoxic drugs are commonly used in these species, only doxorubicin (primarily in the cat), cisplatin (in the dog), and intermediate- to high-dose methotrexate (in the dog) are of concern to the clinician. Doxorubicin may be a potent nephrotoxin in cats, and the limiting cumulative toxicity in this species may be renal, rather than cardiac. Doxorubicin may cause nephrotoxicosis in dogs with preexisting renal disease, and in those concomitantly receiving other nephrotoxins, such as aminoglycoside antibiotics. Sterile hemorragic cystitis is a relative commmon complication of chronic CTX therapy in dogs, but it is extremely rare in cats. Although rare, hemorrhagic cystitis may also occur acutely or peracutely after the first dose of CTX. Three dogs treated in our clinic with 100 mg/m2 of CTX IV, and 4 dogs receiving 300 mg/m2 of CTX PO developed acute clinical signs and urinalysis changes compatible with sterile hemorrhagic cystitis after the first dose. Sterile cystitis apparently results from the irritating effects of one of CTX metabolites (acrolein). Approximately 5% to 25% of dogs, and 1% to 3% of cats treated with oral CTX develop sterile hemorrhagic cystitis, which usually occurs after 18 weeks. Furosemide administered concomitantly with CTX, appears to decrease the prevalence of cystitis. Forced diuresis appears to prevent or minimize the frequency of this complication. I usually recommend administering the CTX in the morning, allowing the pet to urinate frequently (if he/she is an indoor dog), salting the food, and administering prednisone on the same day that the patients receive the CTX (if the protocol calls for prednisone administration). Clinical signs of serile hemorrhagic cystitis are similar to those of other lower urinary tract disorders, and include pollakiuria, hematuria, and dysuria. Urinalyses are character-

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ized by the presence of blood, with mildly to moderately increased numbers of white blood cells, and absence of bacteria. Treatment of this complication is aimed at discontinuing the offending drug, forcing diuresis, diminishing inflammation of the bladder wall, and preventing secondary bacterial infections. Discontinuation of CTX results in resolution of the cystitis in most dogs within one to four months. In addition to discontinuing the drug, I administer furosemide (Lasix速), at a dose of 2 mg/kg, PO, BID for its diuretic effects; prednisone, at a dose of 0.5-1 mg/kg, PO, SID for its antiinflammatory (and diuretic) effect; and a sulfadiazinetrimethoprim combination (Tribrissen速), at a dose of 13-15 mg/kg, PO, BID to prevent secondary bacterial contamination. If despite this approach the clinical signs worsen, instillation of 1% formalin solution in water into the bladder can be attempted. In two dogs thus treated, gross hematuria resolved within 24 hours and did not reoccur. Intravesical infusion of a 25% to 50% DMSO solution may also alleviate signs associated with cystitis in dogs.

References Couto CG: Management of Complications of Cancer Chemotherapy. Vet Clin North Amer 20:1037-1053, 1990. Couto CG: Complications of cancer chemotherapy. In Nelson RW and Couto CG: Essentials of Small Animal Internal Medicine. St. Louis, Mosby, 1992, p 847. Crow SE, Theilen GH, Madewell BR et al: Cyclophosphamide-induced cystitis in the dog and cat. J Am Vet Med Assoc 171:259,1977. Harvey HJ, MacEwen EG, Hayes AA: Neurotoxicosis associated with use of 5-fluoruracil in five dogs and one cat. J Am Vet Med Assoc 171:277, 1977. Knapp DW, Richardson RC, DeNicola DB, Long GG, Blevins WE: Cisplatin toxicity in cats. J Vet Internal Med 1:29, 1988. Laing EJ, Miller CW, Cochrane SM: Treatment of cyclophosphamide-induced hemorrhagic cystitis in five dogs. J Am Vet Med Assoc 193:233, 1988. Weller RE: Intravesical instillation of dilute formalin for treatment of cyclophosphamide-induced cystitis in two dogs. J Am Vet Med Assoc 172:1206, 1978.

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Fever of unknown origin in dogs C. Guillermo Couto

Summary Persistent fever in a patient in which a diagnosis cannot be obtained is relatively common in practice. Fever of unknown origin can be due to infectious, immune-mediated, neoplastic, or miscellaneous causes. The diagnostic and therapeutic approach to a patient with FUO will be discussed.

The term fever of undetermined (or unknown) origin (FUO) is used quite liberally in veterinary medicine to describe a febrile syndrome for which a diagnosis is not evident. In human medicine, the term FUO refers to a febrile syndrome of more than 3 weeksâ&#x20AC;&#x2122; duration, which remains undiagnosed after one week of thorough in-hospital evaluation. If the term FUO is used as recommended in the human literature, very few dogs and cats will actually fit in that category. Therefore, this chapter will discuss the approach to a dog with fever, which does not respond to antibacterial antibiotic treatment, and for which a diagnosis is not obvious after obtaining a minimum data base (i.e.; CBC, serum biochemical profile, urinalysis). In general, the clinician tends to assume that a dog with fever has an infection, until proven otherwise. This appear to be true in practice, since a large proportion of dogs with fever respond to nonspecific antibacterial treatment. In most of those patients, because the fever responds so promptly to treatment, no clinicopathologic evaluation is performed.

Disorders associated with FUO In humans, certain infectious, neoplastic, and immunemediated disorders are commonly associated with FUO. Approximately one third of the patients have infectious diseases; one third have cancer (mainly hematologic malignancies such as lymphoma and leukemia); and the remaining one third have immune-mediated, granulomatous, or miscellaneous disorders. Ten to 15% of the patients with FUO remain undiagnosed despite intensive efforts to obtain a definitive answer. However, to my knowledge, prospective or retrospective studies of dogs with FUO are lacking in the veterinary literature. Based on the patients evaluated in our clinic and in reports from the literature, the most common cause of FUO appear to be infectious diseases, followed by immune-medi-

ated, miscellaneous, and neoplastic disorders (Table 1). It should be remembered that despite aggressive evaluation, the cause of the fever cannot be determined in approximately 10% to 15% of the patients. Table 1. Causes of fever of undetermined origin in dogs Infectious Bacterial subacute bacterial endocarditis brucellosis tuberculosis Lyme disease suppurative infection abscesses (liver, pancreas, stump pyometra) prostatitis diskospondylitis pyelonephritis peritonitis, pyothorax septic arthritis Rickettsial ehrlichiosis, Rocky Mountain spotted fever, Salmon poisoning Mycotic histoplasmosis blastomycosis coccidioidomycosis Protozoal hemobartonellosis babesiosis hepatozoonosis Chagasâ&#x20AC;&#x2122; disease leishmaniasis Immune-Mediated polyarthritis vasculitis meningitis systemic lupus erythematosus immune-hemolytic anemia (IHA) steroid-responsive fever Neoplastic acute leukemia chronic leukemia lymphoma malignant histiocytosis multiple myeloma necrotic solid tumors Miscellaneous metabolic bone disorders drug-induced (tetracycline, enrofloxacin, penicillins, sulfa) tissue necrosis hyperthyroidism idiopathic

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Approach to the patient with FUO A patient with FUO should be approached in a systematic fashion. In general, a three stage approach is used in our clinic (Table 2). The first stage consists of a thorough history and physical examination, and a minimum data base. The second stage consists of additional noninvasive and invasive laboratory tests. The third stage consists of a therapeutic trial, and is instituted when no diagnosis is obtained after completing the second stage. History and physical examination. Once a febrile patient fails to respond to antibacterial treatment, a course of action must be formulated. A thorough history should be obtained, and a complete physical examination should be performed. The history rarely provides clues regarding the cause of the fever; however, a history of ticks may suggest the possibility of a rickettsial or hemoparasitic disorder, administration of tetracycline (mainly to cats) may suggest the possibility of a drug-induced fever), and traveling to areas where systemic mycoses are endemic should prompt further investigation by means of cytology, serology, or fungal cultures. During a physical examination, it is important to evaluate the lymphoreticular organs, since a number of infectious and neoplastic diseases affecting these organs (eg; ehrlichiosis, RMSF, leukemia, systemic mycoses) may result in fever. An enlarged lymph node or spleen should be evaluated cytologically by means of a fine needle aspiration (FNA); a sample can also be obtained for bacterial and fungal culture and susceptibility through FNA, if the specimen is cytologically compatible with infection/inflammation. Any palpable mass/es or swelling/s should also be evaluated by means of FNA. The oropharynx should be inspected and palpated thor-

Table 2. Diagnostic evaluation of the dog with FUO First Stage CBC Serum biochemical profile and thyroxine Urinalysis Urine bacterial culture and susceptibility FNA of enlarged organs, masses or swellings Second Stage Thoracic and abdominal radiography Abdominal ultrasonography Echocardiogram Serial blood cultures Immune tests (ANA, RF) Serum protein electrophoresis Serology (see Table 1) Arthrocentesis (cytology and culture) Biopsy of any lesion or enlarged organ Bone marrow aspiration (for cytology and bacterial/fungal culture) Cerebrospinal fluid analysis Leukocyte scanning Exploratory celiotomy Third Stage Therapeutic trial (antipyretics, antibiotics, corticosteroids)

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oughly, searching for signs of pharyngitis, stomatitis, or tooth root abscesses. The bones should also be thoroughly palpated, particularly in a young dog, since metabolic bone disorders such as hypertrophic osteodystrophy, can result in fever associated with bone pain. Palpation and passive motion of all joints is also indicated, in search of mono-, oligo, or polyarthritis. A neurologic examination should be conducted to detect signs compatible with meningitis or other CNS lesions. The thorax should be ausculted carefully in search of a murmur, which could indicate the presence of bacterial endocarditis. A thorough ocular exam may reveal changes suggestive of a specific etiology (eg; chorioretinitis in dogs with ehrlichiosis). Laboratory evaluation. A minimum data base consisting of a CBC, serum biochemical profile, urinalysis, and urine bacterial culture and susceptibility should always be obtained in dogs and cats with persistent fever. The CBC may provide important clues regarding the cause of the fever (Table 3). A serum biochemical profile is rarely diagnostic in patients with FUO, although it provides indirect information on parenchymal organ function. However, hyperglobulinemia and hypoalbuminemia may suggest an infectious, immune-mediated, or neoplastic disorder. Pyuria in a urinalysis is suggestive of a urinary tract infection (UTI); however, lower UTIs rarely result in fever. Finally, when a definitive diagnosis has not been obtained, a therapeutic trial of specific antibacterial/antifungal agents or immunosuppressive doses of corticosteroids can be initiated (see below). If a dog presents with chronic fever and severe neutropenia, it must be determined if the neutropenia is the cause or the consequence of the pyrexia (i.e.; which one came first). Several clues from the physical examination and CBC are helpful in establishing this. If the patient is severely ill, and the neutrophils in the blood smear are toxic (or there is a pronounced left shift), the neutropenia is probably the “consequence” of the fever (i.e.; there is neutrophil consumption due to bacterial infection, that initiated the fever). If a dog is “healthy” (other than the fact that he/she has a fever), and if the neutrophils do not exhibit toxic changes, the most likely explanation is that the fever is secondary to the neutropenia. The latter patients are likely to have steroidresponsive neutropenia.

Treatment If a definitive diagnosis is obtained, a specific treatment should be initiated. The problem arises when a definitive diagnosis cannot be arrived at. In these patients, changes in the CBC usually represent the only laboratory abnormality (Table 3). That is, results of bacterial and fungal cultures, serology, imaging, and FNAs are negative (or the studies are normal). If the patient has already been treated with a broad spectrum bactericidal antibiotic, a therapeutic trial of immunosuppressive doses of corticosteroids is warranted. However, prior to instituting this treatment, the owners should be informed of the potential consequences of this approach (mainly, if the dog has an undiagnosed infectious dis-

Table 3. Hematologic changes in dogs with FUO Hematologic change

Compatible with

Regenerative anemia

immune-mediated, hemoparasites, drugs infection, immune-mediated, tissue necrosis, malignancy, endocarditis infection, immune-mediated, tissue necrosis, malignancy, endocarditis leukemia, immune-mediated, pyogenic infection, bone marrow infiltrative disease, drugs infection, immune-mediated, tissue necrosis, lymphoma, endocarditis, histiocytosis ehrlichiosis, Chagasâ&#x20AC;&#x2122; disease, leishmaniasis, chronic lymphocytic leukemia hypereosinophilic syndrome, eosinophilic inflammation, lymphoma rickettsiae, leukemia, lymphoma, drugs, immune-mediated infectious (chronic), immune-mediated

Nonregenerative anemia Neutrophilia with left shift Neutropenia

Monocytosis

Lymphocytosis

Eosinophilia

Thrombocytopenia Thrombocytosis

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ease, death could occur from systemic dissemination of the organism after initiating immunosuppressive treatment). In patients with immune-mediated (or steroid-responsive) FUO, the pyrexia and clinical signs usually resolve within 24 to 48 hours of initiating treatment; in that case, the patient is treated with maintenance immunosuppressive therapy. If no response to corticosteroids is observed, two courses of action remain. First, to release the patient on antipyretic drugs, such as aspirin (10-25 mg/kg, PO, BID in dogs and 10 mg/kg, PO, every third day in cats), with instructions to return to the clinic for a complete reevaluation in one to two weeks. Antipyretics should be used with caution, since as discussed above, fever is a protective mechanism (i.e.; lowering the body temperature may be detrimental in a patient with an infectious disease. Moreover, drugs such as dipyrone and banamine, can result in significant hypothermia, which may have adverse effects for the patient. It should also be remembered that most nonsteroidal antiinflammatory drugs, in addition to their ulcerogenic effects, can cause blood cytopenias and result in tubular nephropathy when the patient becomes dehydrated or receives other nephrotoxic drugs. Second, antibiotic trials can be continued, using a combination of bactericidal drugs (eg; a cephalosporin and an aminoglycoside) for a minimum of 5 to 7 days.

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Recurrent infections in dogs C. Guillermo Couto

Summary Recurrent or persistent infections are usually the result of congenital or acquired abnormalities of the immune system. Some breeds appear to be at high risk for congenital immunologic defects. This lecture will discuss the diagnostic and therapeutic approach to dogs and cats with recurrent infections.

Recurrent or persistent infections are usually the results of congenital or acquired abnormalities of the immune system. Although canine clinical immunology is not a well developed speciality, great progress has been made over the past decade in elucidating the underlying immunologic abnormalities in dogs with recurrent infections. Congenital immunodeficiency syndromes in dogs can affect the humoral, cellular, or phagocytic systems, either singly or in combination. Humoral immunodeficiency syndromes include IgA deficiency in beagles, Shar-pei and, possibly, German shepherd dogs; IgM deficiency in Doberman pinschers (not well documented); C3 deficiency in Brittany spaniels; and transient hypogammaglobulinemia in Samoyeds. These dogs usually suffer from recurrent upper and lower respiratory tract infections, dermatitis, and enteritis; some beagles with selective IgA deficiency also experienced grand mal seizures. Cellular immunodeficiency syndromes are apparently less common; a T-cell abnormality has been documented in Weimaraners with pituitary dwarfism and in Bull Terriers with lethal acrodermatitis. The disease in Weimaraner pups was characterized by retarded growth and recurrent respiratory and gastrointestinal infections. Necropsy findings in the affected dogs included hypoplastic thymuses with absence of thymic cortex. Several related Bull Terriers with growth retardation, progressive acrodermatitis, chronic pyoderma and paronichia, pneumonia, and diarrhea exhibited significantly decreased lymphocyte blastogenesis in response to PHA stimulation. Other diseases with inconsistent cell-mediated immunologic abnormalities include Pneumocystis carinii infection in Dachshunds, systemic aspergillosis, generalized demodicosis, and protothecosis. Abnormalities in the phagocytic system have been well documented in dogs. They may occur as a consequence of decreased numbers of circulating phagocytes (ie; in grey collies with cyclic hematopoiesis), or as a consequence of abnormal phagocytic function (ie; defective neutrophil ad-

hesion in Irish setters with granulocytopathy syndrome; defective bactericidal capacity in Doberman pinschers with recurrent respiratory infections). Setters with deficiency of surface adhesion proteins have recurrent episodes of omphalophlebitis, gingivitis, lymphadenitis, pyoderma, respiratory infections, pyometra, and fulminant sepsis. Affected Dobermans exhibited recurrent episodes of rhinitis and pneumonia that responded transiently to antibiotic therapy. Immunodeficiency syndromes affecting more than 1 arm of the immune system have been documented in a family of Basset Hounds, and in several related Weimaraners. In the former, severe growth retardation and early death were associated with low serum IgG and IgA concentrations, and with abnormal lymphocyte blastogenesis in response to PHA. In the latter, recurrent sytemic or multifocal infections were associated with low serum IgG and IgM concentrations and with impaired neutrophil chemiluminescence. Acquired immunodeficiency syndromes include canine distemper virus and parvovirus infections, and generalized demodicosis. In addition, the use of systemic anticancer agents may result in variable degrees of immunosuppression. The type of infectious agent and the pattern of infection are usually determined by the nature of the defect. For example, defects in the humoral immunity usually result in infections with pyogenic organisms affecting one or more sites; defects in T-cell function result in viral, fungal, or protozoal infections that are usually widespread; abnormalities in the phagocytic system may result in skin, respiratory, meningeal, or systemic infections with pyogenic or enteric organisms. Therefore, the type and pattern of infection will dictate what test/s should be used in these patients. Several diagnostic tests can be used in the evaluation of dogs with suspected immunodeficiency. Some of these tests (ie; neutrophil function tests; lymphocyte blastogenesis) require fresh blood samples (ie; need to be done within 4 hours) and specialized laboratory equipment; they are therefore of limited use to general practitioners and are limited to teaching or research institutions. Other tests, however, can be done of serum samples and can therefore be mailed to referral laboratories. The following are some of the tests that can be used to evaluate patients with recurrent infections: humoral immunity: serum protein electrophoresis, immunoelectrophoresis, radial immunodiffusion for Ig levels, complement levels; cellular immunity: lymphocyte blastogenesis in re-

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sponse to ConA, PWM, and PHA; enumeration of circulating T-cells; NK cell assays; phagocytic system: nylon wool adhesion; migration under agarose; phagocytosis of bacteria, yeasts, or latex; phagocytosis of opsonized particles; chemiluminescence; nitroblue tetrazolium reduction test; bacterial killing assay. Clinical management of these patients includes use of the appropriate antimicrobial drugs on the basis of identification of the etiologic agent. If an infectious agent cannot be isolated and the patient appears to have a bacterial infection, bacteriocidal antibiotics that attain high intraleukocyte concentrations (ie; sulfa-trimethoprim) should be used.

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References Felsburg PJ: Immunodeficiency. In Kirk RW (ed): Current Veterinary Therapy IX. WB Saunders, Philadelphia. 1986, pp 439-444. Degen MA, Breitschwerdt EB: Canine and feline immunodeficiencies Part I. Comp Cont Educ 8:313-323, 1986. Degen MA, Breitschwerdt EB: Canine and feline. immunodeficiencies Part II. Comp Cont Educ 8:379-386, 1986. Couto CG, Giger U: Congentital and acquired neutrophil function abnormalities in the dog. In Kirk RW (ed): Current veterinary Therapy X. WB Saunders, Philadelphia. in press. Guilford WG: Primary immunodeficiency diseases of dogs and cats. Comp Cont Educ 9:641-650, 1987.

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Emergency care of pet birds Lorenzo Crosta

Summary Emergencies are still frequent with avian patients. Pet bird owners must understand the importance of preventive medicine, but they should also be educated by competent professionals. Even more important is for veterinarians and technicians to be trained to deal properly with avian emergencies. This paper takes into consideration the general aspects of these cases, like staff education, patient stabilization and fluid therapy. Afterwards a short list of equipment and tools for avian emergencies is given. Finally the most frequent emergencies in avian medicine are considered.

Introduction Avian medicine is one of the latest veterinary specialization, and the progress and developments in this field have been remarkable in the past few years. What still differentiates avian medicine from other veterinary specializations, is preventive medicine with all those regular appointments, like vaccinations, check-ups and others, which make the relationship between veterinarian and bird owner more constant, therefore increasing the chances for a sub-clinical or still inapparent disease, to be diagnosed. To make matters worse birds have a peculiar way of hiding symptoms of disease; this seems to be a necessity for birds to look healthy to any possible predator. If this attitude is an advantage in the wild, it makes it very difficult to understand how serious a bird’s disease can be, so symptoms seem to appear and develop very suddenly and birds presented to a veterinarian are often emergencies. Obviously many emergencies, like traumas and toxicosis, do not have any relation with preventive medicine, but if the owners of some of these patients could have been trained on good bird management, their pets would not have needed the veterinarian’s help.

Staff training As we’ve just seen with avian emergencies time is often so short that a proper training of all the clinic’s staff is really making the difference. The veterinarian should understand all the physiological and pathophysiological aspects of the avian patient, furthermore she/he must have a good

knowledge of pharmacodynamics in birds, at least of the drugs most frequently used in these emergencies. Technicians should know how to act rapidly and with certain ease with these particular patients, without creating any risk for the bird. Everybody should also know perfectly where all the emergency equipment is located; all these points help achieve the first aim of emergency medicine: patient stabilization. It is also very important for a technician to complete a detailed form regarding the patient’s history. Last but not least, considering the zoological variety of the avian patients, the practitioner should be able to taxonomically locate the presented bird. This could be very important, as the same symptom can have a different diagnostic meaning in different bird species. So while the veterinarian waits for tests’ results and the chance to make a sure diagnosis, she/he can make a presumptive one, which must take into consideration the patient’s species.

Patient stabilization Stabilization of the avian patient follows the same procedures as those of emergency treatment in mammals, but we must not forget that birds are easily stressed and this could depend on the fact that they are always prey to a predator bigger than themselves. This continous condition of vulnerabilty induces a bird to appear healthy, especially when faced with a potential predator like man. For these reasons during emergencies, before handling the bird it is very important to observe it in its enclosure, as this will make it feel less threatened. A first important step is to observe carefully the depth and rate of breathing: a rapid and superficial breathing may show a critically ill and hypothermic bird, as so happens during septicemia; while dyspnoea or laboured breathing may indicate a disease which involves the respiratory system directly. In these cases it is always better to put the patient in a heated cage supplied with oxygen, allowing the bird to rest and calm down before handling. In the meantime, if it has not already been done, a complete clinical history of the bird can be compiled. If the bird can be weighed or we already know its weight, we can be able to calculate the exact dose of the drugs we intend to use; otherwise the bird’s weight can be estimated according to the ideal weight of that particular species. If the bird can be handled it is better not to stress it with forced restraint, but to anesthetize it with isoflurane: this will allow us to proceed without risk, to

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dress wounds, temporarily fix fractures, collect blood, swabs and other diagnostic specimens, and administer the preliminary drug therapy.

Fluid replacement therapy Fluid therapy is a very important tool in the case of avian emergencies, but we must pay attention to some facts that differentiate birds from mammals: normally, a healthy bird’s water intake varies from 5 to 30% of its body weight, according to the bird’s species, body weight and type of food. Theoretically this determines a degree of variability in the fluid requirements of sick birds, too. Anyway, as a general rule, the mean fluid need of a bird can be estimated at 50 ml/kg b.w./day. It is important to assess the dehydration degree of the patient, expressed in percent, together with its ideal body weight, which will allow a good estimation of the fluid requirements per day. Lactated Ringer’s solution is generally used, warmed to 100.4 to 102.2 °F (38 - 39 °C), while the route of administration may change according to many factors. Oral route: this is the easiest way of fluid or drug administration to birds, but it is not suitable for emergencies. Severely sick birds might regurgitate fluids and suffocate. Subcutaneous route: birds do not have much subcutaneous tissue and their skin is not as elastic as that of mammals. However, the subcutaneous route is used to replace fluids in moderately dehydrated birds. Small fluid amounts can be injected in different sites on a bird’s back, or bigger amounts can be injected in the axilla or flank region, where we are less likely to inject fluids in an air sac. For these reasons subcutaneous administration is used primarily for maintenance fluid therapy. Intravenous route: this is the most direct route for administration of fluids in birds too, in a word it is definitively the “emergency route” of fluid administration. The most used vessels for this purpose are the right jugular vein, the ulnar vein and the medial metatarsal vein. Blood vessels of birds are easily visible, but they are very fragile and lack elastic fibers, therefore placing an intravenous catheter in bird is simply done, but to leave it in place for long periods may be difficult. Consequently intravenous catheters are placed during isoflurane anesthesia or in very depressed patients. In this way sufficient fliud volumes can be administered quickly (10 ml/kg b.w. over the first five minutes, to be repeated every 3 - 4 hours for the first 12 hours, then every 8 hours for the following 48 hours). In very calm birds it is possible to leave an intravenous catheter in the ulnar vein; while the medial metatarsal vein is preferred in Anseriformes (ducks and geese), in Columbiformes (pigeons and doves), in various long-legged birds and in some birds of prey. This last vein, if cannulated, can be managed as the cephalic vein of dogs and cats. Intraosseous route: in birds it is considered a very good alternative to intravenous administration; furthermore to leave an intraosseous catheter in place, in a bird, is more easy than to leave an intravenous one. The way to place intraosseous catheters in avian patients is the same as used in mammals; the bones of choice are the ulna and the tibiotar-

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sus: in the first bone a distal access is used, in the latter a proximal one. To avoid the bone cortex blocking the needle channel, spinal needles are preferred. As happens in mammals, the major risk of this procedure are bone infections; furthermore often an infusion pump is often needed to help the fluid pass through the intraosseous catheter.

Equipment for avian emergencies - Incubators - Gram scale - Fluid warming chamber - Nebulizer - Circulating warm-water blanket, Heat lamps - Towels for restraint - Isoflurane anhaestesia machine - Face masks for anhaestesia induction - Respiratory monitor - Small endoscopes, flexible and rigid - Small endotracheal tubes - Sterilized air sac tubes - Radiosurgical unit - Leg band cutter - Haemostatic sticks - Intravenous catheters, 20 - 24 G - Variety of spinal needles - Infusion pump - Microdrip IV administration sets - Parrot mouth speculums - “Vetwrap” like bandages, cut into small sizes - Slides and cover slips - Heparinized microhematocrit tubes - Blood smears stains - Microbiology swabs

Common avian emergiences - shock (septic, toxic, traumatic) - toxicosis - seizures - major wounds - oiled birds - frostbite - head trauma - open fractures - haemorrhagiae - hypoglicemia - hypocalcemia - tight leg band - apnoea - acute dyspnoea - tracheal foreign bodies - beak fractures - tongue lesions - crop wounds - crop burns - g.e. foreign bodies - gastric impaction

- cloacal prolapse - egg binding - oviduct prolapse - phallus prolapse

Literature Crosta L, (1992), Uccelli e inquinamento da petrolio e derivati, metodi di trattamento e rilascio. Ob. e Doc. Veterinari, 12: 27 - 32. Crosta L, (1997), La visita clinica del paziente aviare: principali punti di repere, contenimento manuale e farmacologico e dosaggio di alcuni farmaci di comune impiego. Veterinaria, 11 (2): 115 - 129.

153 Degernes LA: Trauma Medicine. In: Ritchie BW, Harrison GJ and Harrison LR, (1994), Avian Medicine: Principles and Application, Wingers Publishing, Lake Worth, pp. 417 - 433. Heidenreich M, (1997), Birds of Prey, Medicine and Management. Blackwell Science Ltd, Oxford, pp. 98 - 101. Jenkins JR: Avian Critical Care and Emergency Medicine. In: Altman RB, Clbb SL, Dorrestein GM and Quesenberry K, (1997), Avian Medicine and Surgery, W.B. Saunders Company, Philadelphia, pp. 839 - 863. Quesenberry K and Hillyer EV: Supportive Care and Emergency Therapy. In: Ritchie BW, Harrison GJ and Harrison LR, (1994), Avian Medicine: Principles and Application, Wingers Publishing, Lake Worth, pp. 382 - 416. Redig PT: Management of medical emergencies in raptors. In: Redig PT, (1993), Medical Management of Birds of Prey, 3rd ed, St. Paul, pp. 13 - 21.

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Emergency care and medical stabilisation of reptiles Stephen John Divers

Summary The veterinary care of reptiles has progressed a great deal over the past decade or so. Current practice has built upon the foundations laid down by pioneers such that the veterinary surgeon is now able to offer a comparable level of care for reptiles as has been available for the more domestic animals for many years. However, with increasing skill comes increasing expectations, and reptile clinicians are now being increasingly asked to deal with critically sick animals. This paper hopes to introduce the clinician to the important aspects of providing emergency care for reptiles. Emphasis is made of the importance of a through history and clinical examination, diagnostic investigations and medical stabilisation including parenteral fluid therapy. Some common emergency scenarios are also discussed.

Introduction Reptile emergencies do occur; the tortoise attacked by a dog, the iguana with hypocalcaemic tetany, the septicaemic python. The basic approach to emergency reptile medicine follows along similar lines to domestic animal medicine, however reptile medicine also throws up a number of other problems1. Reptiles are ectothermic and have a metabolic rate comparable to 1/7 that of mammals. Their slower metabolism generally results in the slower clinical manifestations of disease. Therefore, the clinician will often be presented with a moribund reptile that was in apparently good health the previous day. Some of these cases are true medical emergencies but many represent the terminal presentation of a chronic illness.

History In cases of true emergency, it may be essential to admit and commence treatment (e.g. oxygen therapy) prior to taking a complete history, but in such cases a history should be taken by a veterinary nurse or the veterinarian at the earliest convenience. The importance of a detailed history must never be overlooked and may actually help in determining whether the current situation is truly acute or merely the terminal stage of chronic disease2. Historical details of interest include:

temperature and thermal environment (power cuts, heater malfunction, electrocution, breeding programme). Lighting (sunlight, artificial UVB lights, how old, lightreptile distance, electrocution). Hide-outs, substrate (wet, mouldy), furniture (fallen rocks or branches). Recent changes in husbandry (last 6-12 months). Other reptiles in direct contact with current patient (their health, clinical signs). Recent additions to collection (last 6-12 months, quarantine). Appetite and food intake (reduced, increased, slow deterioration, complete anorexia, duration, food types, supplements). Water intake and humidity (observed drinking, increase or decrease, unknown). Changes in behaviour (courtship, mating, egg laying/birth, tremors, depression, lethargy). Owners records (weights, snout-vent measurements, Jackson ratio, ecdysis, routine treatments, other medications.)

Clinical examination In cases of true emergency, it may be essential to admit and commence treatment prior to performing a complete examination. Nevertheless a thorough clinical exam is always indicated and should be performed as soon as possible2. The examination should be systematic and cover all available systems. Traumatised areas including severe burns, fractures and wounds must be handled carefully to avoid further damage. During the examination; Confirm species, sex and age. Obtain an accurate weight and length, and an appreciation of overall body condition (pelvic limb and tail muscle coverage, poverty lines). Obtain an appreciation of respiratory and cardiovascular function; head extended and open mouth breathing, glottal discharge, increased respiratory efforts at rest and when unrestrained, buccal mucous membrane colour, demeanour (active or lethargic), auscultation or Doppler for heart rate and peripheral pulse rate. Obtain an appreciation of metabolic disturbances and hydration; tremors, seizures, moribund, urate tophi in mucous membranes of mouth, reduced skin elasticity, skin tenting, swollen limbs/jaw, pyramiding or saddle-like shell.

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Obtain an appreciation of the integument; abscessation, swellings and discharges, erythema and petechial haemorrhages, burns, lacerations and penetrating injuries. Obtain an appreciation of the gastro-intestinal tract; buccal cavity, cloaca, coelomic palpation. Obtain an appreciation of the urogenital system; if possible palpate kidneys, coelomic cavity for bladder stones and eggs. Obtain an assessment of the musculoskeletal system; limbs, jaw, swellings, fractures, muscle loss, cachexia.

Trauma In cases of severe and continued bleeding haemostasis can be achieved by the application of local pressure bandages. Identified vessels may be permanently or temporarily ligated using nylon or vascular clips, or repaired under isoflurane or local anaesthesia to maintain important vascular supplies. The application of calcium or adrenaline impregnated swabs and radiosurgery are also useful in the control of haemorrhage. Prolapses of gastrointestinal tract through penetrating coelomic wounds should be cleaned and replaced as long as the intestinal segment is viable and has no lacerations that will lead to the leakage of gut contents. The wound is then packed with sterile swabs soaked in dilute povidone-iodine solution or metronidazole solution (Torgyl, 5 mg/ml, Rhone Merieux) and bandaged using plastic film. In cases of intestinal laceration, the site should be packed with moist sterile swabs, maintaining the intestine outside the coelomic cavity and the whole area bandaged as before until surgery can be undertaken. Cloacal, penile, colonic and bladder prolapses should be replaced if at all possible. If surgery is thought necessary the area can be bandaged using moist swabs and plastic film to prevent dehiscence until the operation can be safely undertaken. Traumatised soft tissues including limbs, tail, flanks and shell should be treated in much the same way as for domestic animals. If medical stabilisation is required before surgery then immobilising the area, covering with sterile gauze and bandaging will prevent further damage and contamination. Burns are particularly prone to infection and the liberal use of topical silver sulphadiazine cream (Flamazine, 1%, Smith and Nephew) cream is recommended. Bite wounds tend to be superficial lacerations but deep penetrating wounds should not be sutured, but treated as infected wounds.

Drowning Tortoises kept in garden enclosures seem particularly prone to drowning and may not be recovered from the pond for several hours. These animals are often presented in a moribund state. In very unresponsive cases (no deep pain response or corneal reflex) it is wise to obtain e.c.g. evidence that the reptile is still alive before proceeding. Whatever the species, position and tape an endotracheal tube in place, and

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hold the animal head down. Pump the limbs of chelonia, massage the thorax of lizards or lung field area of snakes to aid evacuation of water. This should encourage voiding of any fluid remaining within the lung fields. Inflate the lungs with either air or pure oxygen and give intravenous doxapram (Dopram-V, 20 mg/ml, Willows Francis) at 5-10 mg/kg i.v. to help stimulate respiration. Until spontaneous breathing returns (which may take minutes or hours) the reptile should be maintained on a respiratory monitor and given intermittent positive pressure ventilation 2-4 times every minute. Cases of drowning in freshwater seldom require fluid therapy unless severe cardiovascular or respiratory compromise continues. However, cases of drowning in marine water will often lead to rapid water loss from the lungs and dehydration. In these cases fluid therapy is recommended. The prophylactic use of broad spectrum antibiotics is advisable as secondary pneumonia is not uncommon.

Hypothermia and hyperthermia Severe hypothermia can result from heating failure or more commonly delayed national and international transportation. Slow sustained warming is essential as too rapid a rise in core temperature may cause further compromise. Gradual increase in environmental temperature to the species-specific POTZ (preferred optimum temperature zone) over 4-24 hours depending on degree of hypothermia is usually sufficient. In severe cases fluid therapy using warm fluids may also be beneficial. Hyperthermia is less common than burns, however, constant exposure to temperatures above the POTZ and approaching the species-specific critical high temperature (often 35-45째C) will lead to heat stress. Open mouth breathing, increased respiratory effort and collapse are common signs. Immediate reduction of the environmental temperature to the lower end of the species specific POTZ is required. In severe cases, fluid therapy using cooler but not refrigerated fluids (20-30째C) may be beneficial.

Intestinal obstruction and constipation Gastro-intestinal obstructions may be due to gravel, stones, bark, balls, rubber suction devices, elastic bands, abscesses, neoplasia, intussusception, ileus, renal enlargement, cloacitis, faecoliths and parasites. Characteristic signs include regurgitation, tenesmus and diarrhoea, and less commonly blood in faeces or vomitus. Coelomic palpation may reveal discernible masses within the gastro-intestinal (or reproductive) tract. In such cases electrolyte and fluid imbalances should be corrected. Faecal analysis may reveal parasites that should be treated. In cases of constipation, it is important to consider predisposing factors including renal disease, but until the reptile is stable and a thorough investigation can be undertaken, the use of oral laxatives or water enemas may be tried. Once stable, radiography and endoscopy should be used to diagnose the problem and appropriate measures can then be taken where necessary.

Pneumonia Reptiles lack a functional diaphragm and therefore have great difficulty in coughing. In cases of pneumonia, infectious exudates tend to accumulate reducing the functional area of lung. Once the functional pulmonary reserve has been exceeded the reptile will present with increased respiratory effort at rest, and a possible glottal discharge. Providing a high oxygen environment will help alleviate the signs. In severe cases with confirmed radiographic fluid lines, it is often helpful to insert a small catheter down the trachea into the lung fields and aspirate as much exudate as possible. The exudate should then be submitted for laboratory analysis. In moribund lizards sedation or isoflurane anaesthesia is seldom necessary for lung exudate aspiration.

Medical stabilisation Assessment of dehydration, metabolic disturbances and fluid therapy Hydration status can be assessed in much the same way as other animals, including reduction in skin elasticity, dull and wrinkled skin. This must not be confused with normal ecdysis (skin shedding). Pre-treatment blood samples are very useful in evaluating hydration status and biochemical derangements in reptiles. Although there is relatively little published data on observed haematology and serum/plasma biochemistry values, serial blood samples offer the best assessment of hydration status and response to therapy. Preferred reptile venepuncture sites: SnakesVentral tail vein, caudal to cloaca; The needle is angled at 45-90° (craniodorsal) and placed in the ventral mid line in-between paired caudal scales. A 5/8”-1” 21-25 g needle is advanced, avoiding the hemipenes of males, while maintaining a slight negative pressure. If the needle hits a vertebral body withdraw slightly and redirect. Avoid the hemipenes of males. Cardiocentesis; The snake is restrained in dorsal recumbency and the heart located at a point 22-33% from the snout to the vent. The heart is palpated and immobilised using the thumb and forefinger and a 23-25 g 5/8”-11/2” needle is advanced at 45° in a craniodorsal direction into the apex of the beating ventricle. Blood often enters with each heart beat. LizardsVentral tail vein; A 5/8”-1” 21-25 g needle is angled at 6090° and placed in the ventral mid line about 1/4 to 1/3 of the way down the tail. The needle is advanced while maintaining slight negative pressure. If the needle hits a vertebral body withdraw slightly and redirect. Ventral abdominal; A 5/8”-1” 23-25 g needle is advanced in the ventral mid line in a craniodorsal direction. The vein lies just below the abdominal musculature and it is difficult to apply post-sampling pressure which makes haemorrhage a concern. Tortoises, turtles and terrapinsDorsal tail vein; A 5/8” 21-25 g needle is angled at 45-90° and placed, as cranial as possible, in the dorsal mid line of

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the tail. The needle is advanced while maintaining a slight negative pressure. If the needle hits a vertebral body, withdraw slightly and redirect. The exact position, size and even presence of this vessel may vary between species. Right jugular; A 5/8” 23-25 g needle is positioned lateral at the level of the tympanic scale, and directed caudally midway down the neck. It is important to maintain post-sampling pressure to avoid haematoma formation. Subcarapacial vein; The head is pushed inside the coelomic cavity and a needle (bent to 60-75°) is inserted in the mid line just caudal to where the skin of the neck attaches to the cranial rim of the carapace. Advance the 5/8”-1” 2325 g needle in a dorsal direction and maintain slight negative pressure. It is important to maintain post-sampling pressure to avoid haematoma formation. There are a variety of other venepuncture sites including the brachial plexus and femoral plexus, however they usually provide smaller samples which are more often contaminated by lymphatic fluid. CrocodiliansVentral tail vein; A 1-3” 18-23 g needle is angled at 6090° and placed in the ventral mid line about 1/4 to 1/3 of the way down the tail. The needle is advanced while maintaining slight negative pressure. If the needle hits a vertebral body withdraw slightly and redirect. Larger crocodilians (over 1.5 m in length) may require chemical restraint using a neuromuscular blocking agent (e.g. 0.4-1.0 mg/kg gallamine, reversable with neostigmine), and it may be necessary to use large spinal needles (3-8”) to reach the vein. Supravertebral vein; A 1-2” 20-23 g needle is inserted at 90° in the mid line just caudal to the occiput. The needle is advanced to just dorsal to the spinal cord, while maintaining a slight negative pressure. Larger crocodilians (over 1.5 m) may require chemical restaint using a neuromuscular blocking agent (e.g. 0.4-1.0 mg/kg gallamine, reversable with neostigmine). Intramuscular injections can be given into the epaxial muscles of snakes and proximal forelimb muscles of chelonia, lizards and crocodilians. The daily water requirements for reptiles have not been conclusively determined. Published literature suggests that reptiles may be rehydrated by providing fluids at a rate of 10-50 ml/kg/day, but 15-30 ml/kg/day appears more appropriate for the vast majority of species5,6,7. Rehydration can take several days to a week or more and it is wise to rehydrate slowly. Dehydration in reptiles may be characterised as isotonic, hypotonic or hypertonic5. Hypotonic dehydration is most commonly associated with prolonged anorexia and hypertonic dehydration associated with water deprivation or an inability to drink. Isotonic dehydration can occur following haemorrhage, emesis, diarrhoea and tissue damage. Water balance in reptiles differs from that of mammals as, per unit body weight, reptiles have a higher percentage of total body water (63.0-74.4%) and a higher percentage intracellular water (45.8-58.0%).8 These values appear to be highest in freshwater species, lower in terrestrial reptiles and lowest in marine reptiles, with the concentration of isotonic saline in non-marine reptiles being 0.8%9. This has led to the recommendation that standard 0.9% normal saline solutions be

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slightly diluted for use in reptiles to facilitate the intracellular diffusion of water. Four suggested fluid solutions for parenteral administration in reptiles are: 1) Two parts 2.5% dextrose in 0.45% sodium chloride and one part Ringer’s or equivalent electrolyte solution5. 2) One part 5% dextrose in 0.9% sodium chloride, one part lactated Ringer’s and one part sterile water. 3) Nine parts 0.9% sodium chloride and one part sterile water. 4) 0.18% sodium chloride and 4% glucose. All fluids given by any route must be warmed to the species-specific PBT (often 30-35°C) prior to administration. Bathing, oral, subcutaneous and intracoelomic fluid administration must not be overlooked, however intravenous or intraosseous routes offer the best fluid therapeutic approach in emergency situations. Intravenous catheterisation is not easy in reptiles and cut-down procedures are often required under local or isoflurane anaesthesia. In large lizards, cephalic and abdominal vein catheterisation has been employed, while the right jugular is most accessible in the chelonia. In snakes, the right jugular can be catheterised using a cut-down technique. The incision site is located 12 abdominal scales cranial to the heart and two lateral scales to the right. A 2-3 cm incision reveals the jugular just medial to the ribs, which can then be catheterised with a 50-100 mm (24”) 20-23 g catheter. In larger snakes it is possible to place an intracardiac catheter. The heart is located and immobilised as described previously for blood sampling, and a 2575 mm (1-3”) 22-23 g catheter is inserted just caudal to the heart apex and advanced cranially into the ventricle. In all cases of venous catheterisation, the catheter must be securely sutured to the skin and bandaged in place. Fluid infusion is best controlled by a syringe driver. Most intravenous catheters can be left in place for up to 72 hours, or up to 36 hours in the case of intracardiac catheters. Intraosseous infusion is an easier technique that is available for use in lizards, small crocodilians and chelonia. In lizards and small crocodilians a 19-38 mm (3/4-11/2”) 20-25 g spinal needle (or 16 mm 5/8” 25 g hypodermic needle for very small species) is inserted into the proximal tibia. The limb is flexed and the tibial tuberosity located. The needle is inserted distally while holding the body of the tibia. Correct positioning can be verified by the aspiration of bone marrow, low resistance to flushing with heparinised saline, or radiography. Greater care must be exercised when dealing with osteodystrophic lizards as limb fractures are a potential complication. In chelonians, the intraosseous needle can be inserted into the distal tibia or the medullary cavity of the vertical shell that connects the carapace and plastron. Intraosseous needles are taped in position using zinc oxide tape, incorporating a loop of the extension line to reduce catheter tension. Syringe drivers are used to control the infusion rate. The author has used this intraosseous technique in reptiles as small as 75 grams and considers it the parenteral route of choice. Infusion rates for intravenous and intraosseous administration are similar. As a general guide 0.8-1.4 ml/kg/hour is suitable for rehydration purposes, but in cases of severe dehydration, shock or during surgery the author has used 5 ml/kg/hour for up to 3 hours without ill effect.

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Haemorrhage In cases of severe haemorrhage a PCV evaluation is warranted. If the PCV is below 0.05L/L then a single whole blood transfusion may be indicated. Blood should only be collected from healthy reptiles preferably of the same species and from the same collection to avoid cross-colony infection. However, the author has taken blood from Hermanns tortoises (Testudo hermanni) for transfusion into a leopard tortoise (Geochelone pardalis), and has taken blood from a green iguana (Iguana iguana) for transfusion into a common tegu (Tupinambis teguixin) without obvious ill-effects. Cross matching does not appear necessary, at least for a one-off transfusion. The donor reptile can provide 7 ml/kg blood which can be collected into a heparinised syringe for immediate administration to the recipient. Alternatively, blood may be collected into citrate-phosphate-dextrose and administered later. Catheterisation of the right jugular of donor and recipient tortoises facilitates blood collection and transfusion. In lizards, collection and transfusion via the ventral tail vein appears to work well. In snakes a jugular catheter or cardiac catheter should be utilised. Blood has also been administered via an intraosseous catheter in iguanas. Reptiles are able to cope with much greater blood loss than mammals, and so blood transfusion is only required in dire circumstances when the animal is very depressed following acute and severe haemorrhage. Usually, the administration of intravenous or intraosseous fluids is acceptable. Colloids are less frequently used in reptiles because much of the water loss is from the intracellular space rather than plasma, but in cases of acute haemorrhage their use is commendable.

Laboratory investigation Basic biochemistries can be run on many in-house practice laboratories (e.g. Vettest 8001) with a reasonable degree of accuracy. Uric acid must always be undertaken as a level of over 1000 umol/l in an anorexic reptile tends to indicate severe azotaemia (pre-renal, renal or post-renal). Above 1487 umol/l uric acid may start to precipitate out and cause gout. However, post-prandial elevations of uric acid can occur normally in many species, particularly snakes, and so short-term elevations of uric acid may not carry such a poor prognosis. Consistently high or rising uric acid levels above 1500 umol/l, despite intensive fluid therapy, tend to carry the worst prognosis. Urea and creatinine are poor indicators of dehydration and renal disease and are not considered clinically useful. PCV and total protein are useful for assessing dehydration and are relatively inexpensive permitting serial assessments at a viable cost. The inclusion of glucose in parenteral fluids may be important in supporting cachexic reptiles and should certainly be used in cases of severe hypoglycaemia. Another metabolic disorder, severe hypocalcaemic tetany, will benefit from the inclusion of calcium in the infusion fluid. However, it is important to consider concurrent control of any pre-existing hyperphosphataemia (diuresis, phosphate binders) to avoid soft tissue mineralisation.

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Observed serum biochemistry ranges used to assess dehydration and biochemical imbalances in selected reptiles

PCV (%) TP (g/l) Urea (mmol/l) Creatinine (mmol/l) Uric acid (umol/l) Glucose (mmol/l) Calcium (mmol/l) Phosphorus (mmol/l) Sodium (mmol/l) Chloride (mmol/l) Potassium (mmol/l)

Green iguana

Gila monster

Tortoise (Testudo sp)

Box tortoise

Boa constrictor

Rat snake

Caiman

25-38 50-78 0-0.7 42-80 70-140 9.4-16.0 2.2-3.5 1.5-3.0 140-183 102-125 1.3-5.2

25-30 60-85 na na 100-1000 2.5-6.0 2.2-3.5 1.4-2.9 150-190 114-130 4.1

19-40 50-75 0.25-6.70 20-150 75-200 2.6-5.2 2.7-3.6 0.8-1.5 120-158 98-128 4.0-7.0

20-38 40-50 na na 100-200 2.0 2.5-3.5 0.9-1.7 130-149 104-108 4.6-4.7

20-32 46-80 0-1.67 0-26.5 75-250 0.6-4.0 2.5-5.5 0.8-1.6 130-152 104-124 3.0-5.7

20-30 40-70 na na 75-250 na 2.5-6.3 2.1-3.1 130-160 125-147 4.1-5.2

26 50-65 na na 175 4.1-6.3 2.3-3.8 1.3-2.9 139-150 109-132 3.8-7.9

Electrolyte imbalances will usually resolve as renal perfusion and function is restored, however if carefully monitored the correction of acid-base and electrolyte imbalances may be attempted in a similar manner to mammals. A complete blood count takes time and may well be beyond the capabilities of a practice laboratory, especially outside normal office hours. Nevertheless, a haematocrit tube can provide a PCV, semi-quantitative estimate of total white blood cell count and an idea of plasma colour and character. In a full haematocrit tube, the first 1% of the buffy coat represents approximately 10×109/L and every additional 1% adds a further 5×109/L. This is obviously not very inaccurate but will provide an idea of whether a reptile has a WBC of 5×109/L or 50×109/L. In addition, a fresh blood smear stained with DiffQuik will also permit the rapid assessment of a white blood cell differential, with particular reference to heterophils, azurophils and lymphocytes along with any leukocyte toxic changes. Any discharges, fluids or superficial tissues can be sampled for impression smear cytology using DiffQuik stains. It is important to submit blood, tissues and aspirates for culture and sensitivity before commencing broad spectrum antimicrobial therapy. Enrofloxacin and ceftazidime are safe, broad antibiotics that are commonly employed. In cases of suspected septicaemia, i.v. or i.o. ceftazidime and amikacin may be employed but beware of the nephrotoxic effects of aminoglycosides.

Hospitalisation Once the acute emergency is over and the animal is on continuous fluid therapy it is vital that the reptile is maintained in a suitable thermal environment, at the species-specific POTZ (often 25-35°C). All metabolic and physiological processes are dependent upon environmental temperature and all your hard work will be undone if the animal is left overnight in a cold kennel with a hot water bottle! Oxygen therapy can continue in the hospital vivarium and monitoring using peripheral pulse oximetry is useful.

Nutritional support is usually secondary to rehydration, but in cases of severe starvation complete parenteral nutrition can be attempted. The oral route is preferred although the intravenous administration of lipid emulsions may be feasible. The author prefers Critical Care Formula (Vetark) as an initial oral electrolyte and maltodextrin, protein and amino acid mixture. This can later be replaced by Hills a/d for carnivores and insectivores or commercial human baby foods (vegetable and fruit varieties lacking dairy products) for herbivores. More recently, the use of Pretty Pets complete herbivorous reptile diets (tortoise and iguana) have been utilised with apparent success by simply adding warm water and mixing into a thick slurry. It must be stressed that such exclusive diets should only be used on a short term basis and that once the reptile has started to improve, efforts must be made to provide a more varied, natural diet. Most reptiles will be very weak and therefore food material should be placed directly into the stomach using feeding needles or stomach tubes. The head should be kept elevated for a prolonged period using foam or sand bags to avoid regurgitation. Once stabilised further investigation (radiography, ultrasonography, endoscopy etc.) and surgery can proceed.

Key words Reptile, emergency, trauma, shock, haemorrhage, drowning, gastro-intestinal obstruction, hypothermia, hyperthermia, pneumonia, fluid therapy.

References 1. 2. 3.

Boyer, T.H. (1994). Emergency care of reptiles. Semin Avian Exotic Pet Med 3:210-216. Divers, S.J. (1996). Basic reptile husbandry, history taking and clinical examination. In Practice 18:51-65. Stein, G. (1996). Hematologic and blood chemistry values in reptiles. In: Reptile Medicine and Surgery, p473-483 (Ed. D. R. Mader). WB Saunders, Philadelphia. Divers, S.J., Redmayne, G. and Aves, E.K. (1996). Haematological

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(Adapted from references 3 and 4, and the author’s unpublished observations)

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4th European FECAVA SCIVAC Congress and biochemical values of 10 green iguana (Iguana iguana). Veterinary Record 138:203-205. Jarchow, J.L. (1988). Hospital care of the reptile patient. In: Exotic Animals. (Eds. E.R. Jacobson and G.V. Kollias). Churchill Livingstone, New York. Klingenberg, R.J. (1996). Therapeutics. In: Reptile Medicine and Surgery, p 299-321 (Ed. D. R. Mader). WB Saunders, Philadelphia.

8. 9.

Pokras, M.A., Sedgwick, C.J. and Kaufman, G.E. (1992). Therapeutics. In: Manual of Reptiles. (Eds. P.H. Beynon, M.P.C. Lawton and J.E. Cooper). BSAVA, Cheltenham. Thorson, T.B. (1968). Body fluid partitioning in the Reptilia. Copeia 3:592. Marcus, L.C. (1981). Veterinary Biology and Medicine of Captive Amphibians and Reptiles. Lea and Febiger, Philadelphia.

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Hemogram interpretation revisited Bernard F. Feldman DVM, PhD, Dipl ACVIM Department of Biomedical Sciences and Pathobiology - Virginia-Maryland Regional College of Veterinary Medicine - Blacksburg, Virginia - USA

Time spent critically reviewing all aspects of the complete hemogram is diagnostically rewarding. This, coupled with newer automated technology better enables clinicians to detect sample errors and potential errors as well as graphically depicting cells. Automated technology also improves the identification of appropriate and abnormal cells, and may reduce labor time as well as providing more objective quantitative information about blood samples.

Introduction The following is considered a COMPLETE hemogram: Examining red blood cells 1. Red blood count 2. Hemoglobin concentration 3. Packed cell volume or hematocrit 4. Mean cell volume 5. Mean cell hemoglobin 6. Mean cell hemoglobin concentration 7. Reticulocytes 8. Reticulocyte production index 9. Metarubricytes 10. Red cell morphology and cytograms 11. Histogram of red cell volume distribution 12. Total protein Determining inflammation 12. Fibrinogen 13. Sedimentation rate Examining platelets 14. Platelet count 15. Mean platelet volume 16. Platelet morphology Examining leucocytes 17. White blood cell count corrected for metarubricytes 18. Differential white blood cell count in absolute values Immature forms Neutrophils Lymphocytes Monocytes Eosinophils Basophils Degenerated cells Unidentifiable cells

19. White blood cell morphology 20. Leucocyte cytogram

The relationship between hemoglobin, hematocrit, and the red cell indices plus the histogram of red cell volume distribution The hemoglobin concentration is probably the most accurate (and the red cell count the least accurate) of the three analytes needed to calculate the red cell indices. The packed cell volume is the number derived from packing red cells by centrifugation in a glass tube. It is similar to but not necessarily the same as the hematocrit which is a calculated number. If the red cell indices are within the reference interval (this is the new jargon for normal range), then the relationship between hemoglobin and hematocrit is steady. That is to say, the hemoglobin multiplied by 3 should approximate the hematocrit or the hematocrit divided by 3 should approximate the hemoglobin. Any significant departure from this ratio suggests laboratory error. If the red cell indices are not within the reference interval the ratio is not valid. It is important to recall the red cell indices are MEAN values. Therefore it takes a lot of abnormally sized cells to move the MCV out of range. It takes a significant decrease in hemoglobin production to drop the MCHC. Abnormal indices provide free useful information. However normal indices require further examination of the hemogram. Responsive anemias, responsive to hemolysis or blood loss, usually become macrocytic and hypochromic. Macrocytic normochromic anemias suggest aberrant red cell maturation and are often the first signs of impending marrow dysplasia or neoplasia. Most clinical anemic presentations are normocytic and normochromic requiring additional examination of the hemogram and, perhaps, additional testing. Microcytic hypochromic anemias suggest blood loss. In younger animals this often is associated with parasitism. In older animals ulceration and/or neoplasia is suggested. Histograms of red cell volume distribution is a relatively new measurement allowing visualization of erythrocyte volume variability. Disturbances of red cell production that result in altered red cell size are more readily detected. These histogram abnormalities alert the technologists or clinicians to the presence of unusual red cell volumes when the mean values of the red blood cell indices are within the reference interval.

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Reticulocytes and nucleated red cells Reticulocytes are an index of marrow erythroid production and effective delivery to the vascular space. Reticulocytes are observed in blood smears stained with vital stains. Polychromasia, virtually the same as reticulocytes, is observed in Romanowsky (Wright’s) stained smears. Reticulocytes, to be interpreted properly, in dogs and cats, must be adjusted for packed cell volume and erythropoietin production. The reticulocyte production index is one attempt at understanding how responsive is bone marrow erythropoiesis. Metarubricytes are the only nucleated red cells that should ever be observed in peripheral blood smears. Red cell precursors younger than these often suggest marrow dysplasia or neoplasia. Since nucleated red cells inflate the white cell count, whenever nucleated red cells are present the white cell count should be corrected. Nucleated red cells are never an indication of red cell response unless accompanied by reticulocytes in numbers exceeding nucleated red cells (sans unitage). Clinicians should be capable of developing a diagnostic differential scheme for the presence of nucleated red cells and/or reticulocytes in nonanemic patients as well as anemic patients.

Red cell morphology It is almost too mundane to think of red cell morphology in only terms such as polychromasia, poikilocytosis, anisocytosis and occasional spherocytosis. There are many red cell shapes and sizes that are diagnostically useful. A few include codocytes and stomatocytes which also may be observed in immune-mediated hemolysis, burr cells in advanced glomerulonephritis, acanthocytes in some forms of cholestatic disease, schistocytes associated with disseminated intravascular coagulation, Heinz bodies when hemoglobin is oxidized, and blister cells observed in hypersplenic diseases. There are many more helpful red cell changes...

Red cell cytograms The typical erythrocyte cytogram plots each red cell by the size of the cell and the hemoglobin content. The cytogram is compared to appropriate cytograms for the species in question. This technology allows for the earlier detection of iron deficiency anemia and documentation of active erythropoiesis. These are just several examples.

Total protein, fibrinogen, erythrocyte sedimentation rate, icterus index The only way red cell mass can be viewed critically is with total protein quantitation. Dehydrated patients may mask mild anemias. Blood loss is often clinically obvious and is supported by lowered proteins. Younger animals have lower proteins (less immunoglobulins) than do older ani-

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mals. Fibrinogen and erythrocyte sedimentation rate are helpful additions to our diagnostic armamentaria as regards inflammation. They often increase, preceding changes in the leucogram and return towards normal before the leucogram does. Decreases in fibrinogen are associated with disseminated intravascular coagulation. Marked increases in fibrinogen quantitation and erythrocyte sedimentation rate are associated with renal or neoplastic diseases. Icterus index is a way of making an objective assessment of patient jaundice. Plasma color is compared to potassium dichromate standards and given a number value. Comparative aspects become evident on patient reexamination or when speaking to a colleague about the patient. Regularly inspecting plasma color and clarity often reveals free hemoglobin or lipemia.

Platelet count, platelet morphology, and mean platelet volume Platelet numbers should be critically assessed. It is simply not enough to receive a report that platelet numbers are increased, “adequate,” or decreased. In patients that have primary hemostatic defects, diagnostic and therapeutic decisions must be based on absolute numbers. In addition, large platelets suggest young platelets. Platelet granularity is observably affected by some diseases and some drugs. Oval to cigar-shaped platelets often suggest occult bleeding. Mean platelet volume (MPV) is a new measurement designed to enable us to view platelet size distribution. The detection of microthrombocytosis in immune mediated thrombocytopenia is but one example of the advantage of determining MPV. Another example is the detection of macrothrombocytes and active response to thrombocytopenia.

White cell count, distribution, and morphology White cells counts must be corrected for increased numbers of nucleated red cells. Additionally, the white cell count is use to calculate absolute numbers of individual cell types. Percentage distribution is not informative and often leads to misdiagnoses. Included among the categories of cells in the white cell differential should be cells called “unclassifiable” and “degenerated.” These additional categories are an alert to the presence of neoplastic cells and/or toxic cells. The difference between a stress leucogram - mature neutrophilia, monocytosis, lymphopenia, and eosinopenia - and an inflammatory leucogram - left shift - must be grasped. Regenerative and degenerative left shifts are useful diagnostic academic terms which affect therapies. The neutrophil to lymphocyte ratio is 3:1 in dogs and 2:1 in cats. These differences allow quantification of response comparatively between the two species. Dogs often mount an elegant response to a lesion or process. Cats, given the same degree of insult, mount a lesser response. Ratio inversions are significant. Nonspecific evidence of systemic toxicity is revealed when neutrophil morphology changes. Vacuolation, toxic

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granulation, and hypersegmentation, when observed, require additional patient examination in order to determine the cause of these morphological changes.

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detect toxicity, detect modest eosinophilias, and detect blast cells in early leukemic patients.

Recommended reading There are several leucocyte cytograms now available. These are the peroxidase cytogram and the basophil cytogram. The peroxidase cytogram plots each leucocyte by cell size and peroxidase activity and the computer draws lines around cell clusters that are distinctly different from each other and allows an automated leucocyte differential count. The basophil cytogram strips away leucocyte cytoplasm and plots naked leucocyte nuclear size and density. Interpretation of the basophil cytogram is based on the shape of the cell cluster. The shape can determine individual leucocyte types and numbers, detect left shifts automatically,

Tvedten H. Advanced hematology analyzers interpretation of results. Vet Clin Path 1993; 22:72-80. Weiser MG. Sizing of animal erythrocytes using sulfate-based diluent. Vet Clin Path 1985; 14:7-9. Weiser MG. Modification and evaluation of a multichannel blood cell counting system for blood analysis in veterinary hematology. J Amer Vet Med Assoc 1987; 190:411-415. Northern J, Tvedten HW. Reports of retrospective studies. Diagnosis of microthrombocytosis and canine immune-mediated thrombocytopenia in dogs with thrombocytopenia: 68 cases (1987-1989). J Amer Vet Med Assoc 1992. 200: 368-372. Kocher WD. Autoimmune hemolytic anemia in: Atlas of automated cytochemical cytology. Edited by Simson, Ross, Kocher. Tarrytown NY, Technicon Instruments 1988. 26-27.

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Leucocyte cytograms

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Special hematology diagnostics Bernard F. Feldman

Special hematology diagnostics

Leucocyte cytograms

Hemogram Red cell cytograms Mean platelet volume and cytogram Leucocyte cytograms “In-house” blood typing Feline transfusion medicine Detection of antibodies on red cells Use of erythropoietin Use of granulocyte-colony stimulating factor Hemostasis Primary hemostasis - the buccal mucosal bleeding time Secondary hemostasis - PIVKA Tertiary hemostasis - D-Dimer

There are several leucocyte cytograms now available. These are the peroxidase cytogram and the basophil cytogram. The peroxidase cytogram plots each leucocyte by cell size and peroxidase activity and the computer draws lines around cell clusters that are distinctly different from each other and allows an automated leucocyte differential count. The basophil cytogram strips away leucocyte cytoplasm and plots naked leucocyte nuclear size and density. Interpretation of the basophil cytogram is based on the shape of the cell cluster. The shape can determine individual leucocyte types and numbers, detect left shifts automatically, detect toxicity, detect modest eosinophilias, and detect blast cells in early leukemic patients.

HEMOGRAM

“In house” blood typing

Red cell cytograms

A simple “in-house” card test for feline red cell antigens A, B, and AB and canine DEA 1.1. The dog has eight different blood types identified as dog erythrocyte antigens (DEA) 1.1, 1.2, 3, 4, 5, 6, 7, and 8. The use of DEA 1.1 and 1.2 positive blood products that are crossmatch incompatible may cause hemolysis. Controversy exists as to whether DEA 7 is an important determinant in canine transfusion reactions. Ideally canine blood negative for DEA 1.1, 1.2 and 7 should be used as it conforms with the concept of “universal” donor blood. In random source, first time canine transfusion of noncrossmatched or typed blood the transfusion reaction rate is approximately fifteen percent. Again, transfusion reaction indicates that the materials transfused are not effective and are causing a physiologic burden on an already burdened patient - reasons to blood type and crossmatch. Recently there has been suggestions that the only significant canine antigen is DEA 1.1. Donors blood products negative for DEA 1.1 that are crossmatch compatible have a much reduced chance of transfusion reaction.

The typical erythrocyte cytogram plots each red cell by the size of the cell and the hemoglobin content. The cytogram is compared to appropriate cytograms for the species in question. This technology allows for the earlier detection of iron deficiency anemia and documentation of active erythropoiesis. These are just several examples.

Mean platelet volume Platelet numbers should be critically assessed. It is simply not enough to receive a report that platelet numbers are increased, “adequate,” or decreased. In patients that have primary hemostatic defects, diagnostic and therapeutic decisions must be based on absolute numbers. In addition, large platelets suggest young platelets. Platelet granularity is observably affected by some diseases and some drugs. Oval to cigar-shaped platelets often suggest occult bleeding. Mean platelet volume (MPV) is a new measurement designed to enable us to view platelet size distribution. The detection of microthrombocytosis in immune mediated thrombocytopenia is but one example of the advantage of determining MPV. Another example is the detection of macrothrombocytes and active response to thrombocytopenia.

Feline blood groups and transfusion medicine Three feline blood groups have been described: A, B, and AB. The feline blood group system is different than that in dogs because the occurrence of natural isoantibodies is

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common. Approximately 70% of all type B cats have anti-A antibody in a high enough titer to cause decreased RBC survival and acute hemolysis. As little as 5 ml of incompatible blood is enough to cause a fatal reaction. In 35% of all type A cats anti-B is present but usually in low titer; reaction in these animals is less frequent. Although the incidence of type B cats in the United States is low, many purebred cats (excepting the Siamese) such as the Cornish and Devon Rex, British shorthair, Abyssinian, and Himalayan cats have a high frequency of B blood types. Crossmatching is strongly recommended for all cats about to receive blood or blood products. The presence of natural isoantibody always result in decreased RBC survival posttransfusion. Mean RBC survival is approximately 30 days in cats of the same blood type and less than 10 to 14 days in cats with differing blood types. Donor cats should be screened for red cell parasites, heartworms and feline leukemia virus (FeLV), feline infectious peritonitis (FIP), and feline immunodeficiency virus (FIV). At 2 week intervals 10 ml/kg can be collected. The use of citrate-phosphate-dextrose-adenine (CPD-A1) is the recommended anticoagulant. Heparin is contraindicated as it activates platelets and antithrombin III and can result in many unwarranted and disparate reactions including hemorrhage. When delivering feline whole blood taken in a citrate anticoagulant care must be taken not to cause hypocalcemia, which may be severe and even lethal. Citrate is a strong calcium chelator. Caution must also be used not to induce volume overload. Generally if less than 20% of blood volume is delivered to a normovolemic but anemic feline patient during an 8 hour period, volume overload does not occur. As mentioned, cats have a normal blood volume of approximately 70 ml/kg.

Detection of antibodies on red blood cells The ability to detect antibody in IHA will depend on the characteristics of the antibody. Agglutination occurs readily with IgM antibodies and poorly, if at all, with IgG antibodies. This is due to the fact that the larger IgM molecule can span the distance imposed by mutually repulsive forces that keep rbcs separated. When this happens IgM forms a lattice and agglutination occurs. Additionally a sufficient amount of antibody must be present for this phenomenon to occur. The direct antiglobulin test (DAT; Coombsâ&#x20AC;&#x2122; reaction) involves the species specific production of an antiantibody thus allowing agglutination to occur in vitro. The majority of autoimmune antibodies in human animals and nonhuman small animals are IgG1 and the remainder are predominantly IgG3. The use of antiIgG and anticomplement 3 antisera can aid in the determination the pattern of antibody or complement fixation in IHA. The antiglobulin test results are then of four types: a) antibody alone is fixed, generally antiIgG but no antiC3. In human animals this reaction is generally associated with specific blood groups and with specific drug-induced IHA. b) both IgG and C3 are found to be present on the rbc. This indicates that IgG antibody is capable of fixing

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complement. This pattern in human animals is seen in SLE and in idiopathic IHA. This never occurs when drugs are involved. c) complement only is fixed; antiIgG does not cause agglutination. This kind of DAT reaction has several causes. The antibody may not be IgG. The antibody may have low affinity due to temperature. Papainization of the rbcs may result in a positive immmunoglobulin test because papain will increase the ability of the antibody to interact with the rbc surface antigen. d) the test is negative. This results when the test is not performed in both cold and warm environs, when the affinity of the DAT antibodies is too low, when there are too few antibodies or complement molecules on the rbc surface, or when the DAT antibodies are too avid resulting in the prozone phenomenon that is, too many antiantibodies cover the antigens and lattice structures are prevented. WHAT YOU SHOULD DO! - As the handling clinician you must ask your laboratory a series of questions. First is the DAT being uses species specific? Do they run positive and negative controls on each patient? Was the test run in both cold and warm environs? What dilutions were used to overcome potential prozone phenomena (generally dilutions out to 1:16 will do this)? OTHER MEANS OF DIAGNOSIS - There does not seem to be a major age or sex predisposition to IHA in nonhuman animals. There does seem to be a breed predilection with Cocker Spaniels, Old English Sheepdogs, Poodles, German Shepherds and Doberman Pinschers predominating. The presence of spherocytes helps but there is a caveat here. Unless a trained technologist or cytologist is reviewing the smears, spherocytes often are incorrectly identified. Conversely without training spherocytes are often missed. With feline and equine rbcs spherocytosis is often missed because of the small cell size. Spherocytosis is suggested when the MCV is below normal or at the low end of the reference interval despite the large numbers of reticulocytes which often accompany IHA and when the MCHC is above the reference interval. This results when smaller cells (spherocytes) are present (MCV) and have only lost membrane without loss of intracellular content (MCHC). Slappendel from the State University of Utrecht suggests that performing a standard osmotic fragility test at half strength will reveal increased osmotic fragility in IHA patients. Attempting to cause or disperse agglutination has been singularly unrewarding in this authorâ&#x20AC;&#x2122;s hands. Increased reticulocyte production indices without clinical evidence of bleeding and without hypoproteinemia suggests hemolysis. The caveat here is that nonimmune hemolysis can occur and spherocytosis can occur without IHA (hypophosphatemia often causes spherocytosis).

Use of erythropoietin (Epo) Erythropoietin is synthesized primarily in the peritubular cells located in the inner cortex and outer medulla of the kidney although small amounts are synthesized in the liver. Re-

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combinant EPO has been produced and is commercially available. Like the natural hormone, the recombinant product acts preferentially on the late differentiation of CFU-E. In the clinical trials in dogs it has had remarkable effects. Not only is the anemia of end-stage renal disease effectively treated but activity seems to ameliorate many of the other effects of renal disease such as hypertension, hyperkalemia, and thrombotic tendencies. EPO appears to be a true hormone, acting at a distance from its site of production.

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and hemogram above. Specific examination of the primary hemostatic reaction is accomplished with the buccal mucosal bleeding time (BMBT). The BMBT is accomplished with a bleeding time device and has been described. The BMBT is sensitive to platelet dysfunctional states primarily and to vascular dysfunction secondarily. The BMBT is not performed when thrombocytopenia is pronounced.

Use of granulocyte-colony stimulating factor (G-CSF) G-CSF is most well known in veterinary medicine. G-CSF has a molecular mass of 18 to 22 kilodaltons and is released from fibroblasts and activated monocytes. The effect of GCSF is more restricted than that of GM-CSF and IL-3. G-CSF enhances the differentiation and neutrophil function. G-CSF increases neutrophil killing of tumor targets by a mechanism of antibody-dependent cellular cytotoxicity (ADCC), and also enhances phagocytosis. In clinical trials, G-CSF has been shown to shorten the period of dangerous neutropenia following chemotherapy for neoplasia and the number of days antibiotics must be used to treat some septic processes. G-CSF produces remarkable increases in neutrophil numbers without affecting the numbers of monocytes and lymphocytes.

HEMOSTASIS Examination of primary hemostasis-buccal mucosal bleeding time Primary hemostasis consists of vascular constriction, platelet adhesion and platelet aggregation. It must be distinguished from secondary hemostasis - coagulation (fibrin formation) and tertiary hemostasis (fibrinolysis). Primary hemostasis has been partially examined in the microhematocrit

The PIVKA test (proteins induced by or involved in vitamin K antagonism or absence) is a specific test of vitamin K deficiency. In fact, the PIVKA test often prolongs as much as 24 hours before clinical signs may be observed. The PIVKA plasma is deficient in three of the four vitamin K coagulation proteins, factors II, VII, and X. The test is simple and reproducible. It can be accomplished in-hospital and requires only the deficient plasma and a hot water bath.

Examination of tertiary hemostasis D-Dimers The reference interval assessed for D-dimer in normal dogs was 0.01-0.25 mcg/ml (mean = 0.13 mcg/ml). In the 71 cases of DIC the D-dimer concentration ranged from 0.05 to 3.93 mcg/ml (mean = 0.73 mcg/ml). With a cut-off of 0.25 mcg/ml, the calculated. sensitivity for D-dimers in the DIC group was 82 percent. D-dimer can be detected and utilized diagnositically in clinical canine medicine. D-dimer concentrations appear to be useful in the assessment of uncompensated canine DIC. Further research is needed to determine the usefulness of this analyte in cases where DIC is suspected but not supported by current laboratory testing protocols.

References available on request

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Examination of secondary hemostasis PIVKA

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Clinical approach to anemia Bernard F. Feldman

Case examination A nine month old West Highland White Terrier was presented for elective castration but, during physical examination, the mucous membranes were noted to be pale. Despite this the patient was bright, alert, responsive and afebrile. A biochemical profile was essentially unremarkable but the hemogram had some unusual findings: WBC/µL 14,400 (12,400 neuts; 500 monos; 1000 lymphs; 500 eos) RBC/µL 2,400,000 (MCV 79; MCHC 34; MCH 27) PCV% 19 Hbg/dL 6.5 T.P.g/dL 6.1 NRBCs 5/100 wbcs Retics% 10 Icterus Index - normal ESR (corrected) - negative 12 Polychromasia ++++, Anisocytosis +++++, Poik +, Target ++, Lepto ++, Spherocytes -, Stomatocytes -, Bowls -, Knizocytes -, Schisto -. Abnormal test(s)? _________________________________ Diagnosis? _______________________________________ Why? ___________________________________________

Anemia I. Hypoproliferative (nonresponsive anemia) II Hyperproliferative (responsive anemia) III. Variable response anemia Anemia is NOT a disease, simply a sign of disease. The evaluation of the patient with anemia requires the usual careful history and physical examination, followed by laboratory screening that provides a complete hemogram: Examination of red blood cells 1. Red blood count 2. Hemoglobin (Hc) concentration 3. Packed cell volume or hematocrit 4. Mean cell volume 5. Mean cell hemoglobin 6. Mean cell Hb concentration 7. Reticulocytes 8. Reticulocyte production index 9. Metarubricytes and other NRBCs

10. Red cell morphology and cytograms 11. Histogram of RBC vol. distribution 12. Total protein Determining inflammation 13. Fibrinogen 14. Sedimentation rate Examination of platelets 15. Platelet count 16. Mean platelet volume 17. Platelet morphology Examination of leucocytes 18. White blood cell count corrected for metarubricytes 19. Differential white blood cell count in absolute values Immature forms, neutrophils, lymphocytes, monocytes, eosinophils, basophils, degenerated cells, unidentifiable cells 20. White blood cell morphology 21. Leucocyte cytogram Red Cell Indices - While the red cell indices reflect abnormalities in red blood cell production, changes in the indices are slow to occur (remember, they are mean values!) and often lag behind the pathologic process. Despite the fact that most clinical anemias are normocytic and normochromic, macrocytic normochromic anemias usually reflect maturation abnormalities (vitamin B12, folate, myeloproliferative disease), microcytic hypochromic anemias specifically suggest iron deficiency in small animals, and macrocytic hypochromic anemias are associated with intense red cell regeneration. Reticulocyte Count - The percentage reticulocyte count requires, at least, conversion to absolute values. The reticulocyte count in the dog requires several conversions to account for the “normal” bone marrow response to erythropoietin, and the length of time of bone marrow reticulocyte maturation which is correlated with the degree of anemia. These two conversions are often called the reticulocyte production index (RPI). Hypoproliferative (nonresponsive) anemia - Anemia as a disease sign is placed into one of several categories. Anemia of inflammatory disease is modest, often undetectable, and clinically insignificant. Anemia associated with acute hemorrhage presents little diagnostic challenge and in the early stages is characterized as nonresponsive. Anemia associated with chronic hemorrhage is associated, in general, with parasitism in young animals and ulceration of bleeding neoplasms in older animals and in the early

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stages is characterized as nonresponsive. Microcytosis and hypochromasia, however, are slow to occur. Anemia associated with decreased erythropoietin production suggests the clinician examine renal function, thyroid function or adrenal function. Production deficits, manifested by anemia and or bicytopenia or pancytopenia suggests anemia associated with bone marrow disease. Hyperproliferative (responsive) anemia - Hemolysis or Hemorrhage Hemolytic Anemia is caused by fragmentation, phagocytosis, or intravascular lysis. The most common canine hemolytic anemia is immune-mediated hemolytic anemia (IHA), which may be defined as a premature breakdown of red cells and in the case of immune-mediation, premature breakdown of red cells associated with antibodies. Among the implicated antibodies are immunoglobulin G (IgG) and IgM. When associated with the red cell at 37 degrees they are considered warm reacting. When temperatures are below 35 degrees and antibody is associated with red cell membranes, the reaction is considered cold reacting. Both of the aforementioned immunoglobulins, and especially IgM, can fix complement. Complement- and/or phagocyte-mediated red cell membrane damage result in swelling (spherocytosis) or lysis (hemoglobinemia). When hemolysis is active the erythroid marrow becomes responsive in three to five days. Anemia of hemorrhage also becomes responsive in three to five days. Variable response anemia, anemia which is unpredictable in terms of its reticulocyte response is a maturation abnormality due, most often, to vitamin B12 or folate deficiency. Intrinsic marrow disease, also potentially a maturation abnormality may also present similarly in the early stages.

Causes of anemia - a summary 1. Iron deficiency - always nonresponsive 2. Inflammation - always nonresponsive 3. Marrow damage - always nonresponsive 4. Decreased erythropoietin - always nonresponsive 5. Hemorrhage - nonresponsive early; responsive later 6. Hemolysis - nonresponsive early; responsive later 7. Maturation abnormality - usually nonresponsive but unpredictable

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Initial approach to the anemic patient The reticulocyte count is the only index of effective erythropoiesis. Proper usage requires: 1) conversion to an absolute quantity; 2) adjustment for the reduced hematocrit; and 3) correction for the effect of erythropoietin on marrow reticulocyte release. THESE ADJUSTMENTS RESULT IN CALCULATION OF THE ADJUSTED RETICULOCYTE NUMBERS OR THE RETICULOCYTE PRODUCTION INDEX (RPI). First: figure out the absolute quantity of reticulocytes. If the canine mean red cell count is seven million, one percent reticulocytes is seventy thousand reticulocytes - the reference interval would be thirty-five thousand to one hundred five thousand reticulocytes per microliter. Second: correct for the reduced hematocrit. Multiply the absolute reticulocyte count by the patientâ&#x20AC;&#x2122;s hematocrit and divide the result by the mean species hematocrit. Third: correct for the effect of erythropoietin on reticylocyte release.

Erythropoietin Erythropoietin (Epo) is inversely correlated with the red cell count (or hematocrit). The lower the hematocrit the higher the concentration of erythropoietin (except in renal failure). The effects of erythropoietin include: 1. commits uncommitted stem cells to the erythroid line; 2. decreases the marrow maturation time for red cell development; 3. increases individual cell hemoglobin synthesis; 4. causes premature release of reticulocytes from bone marrow.

Adjusting the reticulocyte numbers the reticulocyte production index (RPI) The average time for reticulocytes to mature in the dog or cat is four and one-half days, three days occur in the marrow and one day in peripheral blood if the hematocrit is appropriate: In the dog:

Laboratory evaluation of anemia The laboratory evaluation of anemia is initiated by examination of the red cell indices - MCV, MCHC, and MCH. If these indices are abnormal, this is essentially free information and gives specific direction. Examples are macrocytic hypochromic anemia which invariably suggests red cell response and microcytic hypochromic anemia which suggests (at least) iron deficiency. However if the indices are normal, normocytic and normochromic, examination of the degree of red cell response - specifically the appropriateness of the reticulocyte response - must be considered.

In the cat:

Hematocrit

Development in Marrow

in Peripheral Blood

45 35 25 15

3.5 days 3.0 days 2.5 days 1.5 days

0.5 days 1.5 days 2.0 days 2.5 days

32 24 16 10

3.5 days 3.0 days 2.5 days 1.5 days

1.0 days 1.5 days 2.0 days 2.5 days

To correct for the effect of erythropoietin on reticulocyte release, after converting reticulocytes to absolute values and adjusting for the reduced hematocrit, divide the final figure

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of 3.5 million/ul, the absolute value is approximately 170,000/ul. 170,000 × 22% (patient’s Hct)/ 45% (mean canine Hct) = 85,000/2.0 = 42,500. This corrected absolute reticulocyte number is within the reference interval observed for dogs with appropriate hematocrits. Thus, this patient must be considered nonresponsive

Initial characterization of anemia is it responsive? nonresponsive? A RPI less than 2.0 = nonresponsive anemia. A RPI greater than 2.0 = responsive anemia i.e., hemorrhage or hemolysis.

References available on request

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by the number of days the average reticulocyte will live as a reticulocyte based on the patient’s hematocrit (see charts above). For example, to determine red cell production over basal rate: If a canine patient’s hematocrit is 22 percent (mean normal is 45 percent) and the patient’s reticulocyte percentage is 5 percent, is this patient responding appropriately to the reduced hematocrit? 5% × 22% (patient’s Hct)/ 45% (mean canine Hct) = 2.5/2.0 = 1.27 basal rate. If 1.0 is basal rate, 1.27 over basal rate is nonresponsive! Only patients with a corrected reticulocyte count over 2.0 are considered responsive, i.e. are responding from either hemorrhage or hemolysis. For example, to determine corrected absolute reticulocyte counts: If the reticulocyte count is 5 percent of a red cell count

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Interpretation of the blood smear. Morphologic alterations of red and white cells Bernard F. Feldman DVM, PhD, Dipl ACVIM Department of Biomedical Sciences and Pathobiology - Virginia-Maryland Regional College of Veterinary Medicine - Blacksburg, Virginia - USA

Case 1 (C6) - Two year old, spayed female cat presented with anorexia, depression, and increased temperature. PCV % Hb g/dl RBC x 106/ul MCV fl MCHC g/dl MCH pg Retics % Nrbcs/100wbc RBC morph WBC morph Plat x103/ul

8 5 3.45 43.5 33.3 15.5 0 0 Heinz bodies Doehle bodies 640

(30-45) (12-18) (5-10) (39-55) (31-35) (12.5-27.5) (0.2-1.6) (0)

(300-800)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Disintegrated cells

6.7 230 2.0 500 0 306 294 0 0 0 0

(6.0-8.0) (50-300) (2-7) (5500-19500) (0-120) (2500-12500) (1500-7000) (0-850) (0-1500) (0) (0)

Case 2 (C8) - One year old intact male cat presented because of weight loss, anorexia and, hemorrhagic diarrhea. On entry the PCV was 21%. These are data accumulated the next day. PCV % Hb g/dl RBC x 106/ul MCV fl MCHC g/dl MCH pg Retics % Nrbcs/100wbc RBC morph WBC morph Plat x103/ul

7 2.3 3.12 44.5 30.3 15.5 0 0 Heinz bodies Doehle bodies 0

(30-45) (12-18) (5-10) (39-55) (31-35) (12.5-27.5) (0.2-1.6) (0)

(300-800)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Disintegrated cells

3.2 320 2.0 3100 0 2330 670 100 0 0 0

(6.0-8.0) (50-300) (2-7) (5500-19500) (0-120) (2500-12500) (1500-7000) (0-850) (0-1500) (0) (0)

Case 3 (282) - Two year old Corgi-Cocker Spaniel spayed female was presented because of episodes of bleeding for the past two weeks. There was gingival bleeding and some petecchiae on mucous membranes and on the abdomen. PCV % Hb g/dl RBC x 106/ul MCV fl MCHC g/dl MCH pg Retics % Nrbcs/100wbc RBC morph WBC morph Plat x 103/ul 38 Plat morph

23 8.0 3.2 117 25.7 36 4 4+ aniso, polychr toxic granulation (200-400) megathrombocytes

(37-55) (12-18) (6-8) (60-77) (31-35) (19-24) (0-1.5) (0)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC (corrected)/ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Metamyelocytes Myelocytes

6.7 250 2.0 43500 9000 21400 4100 2200 800 0 3500 2500

(6.0-8.0) (200-400) (2-7) (6000-17500) (0-400) (3000-11500) (1000-4800) (150-1350) (100-1250) (0) (0) (0)

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During this session we will examine a series of cases and discuss the morphologic alterations seen in blood and bone marrow preparations associated with those cases.

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Case 4 (D13) - Six year old spayed femal Basenji dog presented because of chronic diarrhea. PCV % Hb g/dl RBC x 106/ul MCV fl MCHC g/dl MCH pg Retics % Nrbcs/100wbc RBC morph WBC morph Plat x 103/ul Plat morph

32 10.5 5.4 64 32 21 1.0 4 slight anisocytosis immature 988 variably sized

(37-55) (12-18) (6-8) (60-77) (31-35) (19-24) (0-1.5) (0)

(200-400)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC (corrected) /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Metamyelocytes Myelocytes

6.1 450 3.0 28100 4100 19000 1100 1000 900 0 1500 500

(6.0-8.0) (200-400) (2-7) (6000-17500) (0-400) (3000-11500) (1000-4800) (150-1350) (100-1250) (0) (0) (0)

Case 5 (289) - Neutered male Collie, 4.5 years of age presented because of nervousness, whining, crying, and pacing (will not sleep). PCV % 37 Hb g/dl 10.7 RBC x 106/ul 6.3 MCV fl 58.7 MCHC g/dl 28.9 MCH pg 16. 9 Retics % 4.8 Nrbcs/100wbc 28 RBC morph-slight aniso; polychr WBC morph normal Plat x 103/ul 218 Plat morph normal

(37-55) (12-18) (6-8) (60-77) (31-35) (19-24) (0-1.5) (0)

(200-400)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC (corrected) /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Unclassifiable Damaged

6.2 200 3.5 9900 0 7500 1200 800 400 0 0 0

(6.0-8.0) (200-400) (2-7) (6000-17500) (0-400) (3000-11500) (1000-4800) (150-1350) (100-1250) (0) (0) (0)

Case 6 (298) - Six year old neutered male toy Poodle presented because of persistent diarrhea. PCV % 47 Hb g/dl 17 RBC x 106/ul 5.12 MCV fl 91.7 MCHC g/dl 36.1 MCH pg 33.2 Retics % 0 Nrbcs/100wbc 0? RBC morph-retained nuclei? WBC morph hypersegmented Plat x 103/ul 332

(37-55) (12-18) (6-8) (60-77) (31-35) (19-24) (0-1.5) (0)

(200-400)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC (corrected) /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Unclassifiable

7.1 300 2.0 15100 151 8909 4454 755 831 0 0

(6.0-8.0) (200-400) (2-7) (6000-17500) (0-400) (3000-11500) (1000-4800) (150-1350) (100-1250) (0) (0)

Case 7 (297) - Two year old neutered male mixed breed cat presented with an acute history of anorexia and depression. Temperature was subnormal, pulse 200/minute and respirations 32/minute. Mucous membranes were pale. PCV % Hb g/dl RBC x 106/ul MCV fl MCHC g/dl MCH pg Retics % Nrbcs/100wbc RBC morph WBC morph Plat x103/ul

11 2.6 1.8 95.6 28.2 31 12 15 Heinz bodies Doehle bodies 313

(30-45) (12-18) (5-10) (39-55) (31-35) (12.5-27.5) (0.2-1.6) (0)

(300-800)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Disintegrated cells

6.3 400 8.0 9400 0 8300 700 400 0 0 0

(6.0-8.0) (50-300) (2-7) (5500-19500) (0-120) (2500-12500) (1500-7000) (0-850) (0-1500) (0) (0)

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Case 8 (C15) - Six and one-half year old neutered male cat presented with a two week history of anorexia, two day history of vomiting and diarrhea. Temperature was elevated, there was marked splenic enlargement on palpation and on radiography. The patient was dehydrated approximately 5%. (30-45) (12-18) (5-10) (39-55) (31-35) (12.5-27.5) (0.2-1.6) (0)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Disintegrated cells Unclassifiable cells

7.8 450 10.0 33700 ? 4000 700 ? 0 0 0 29000

(6.0-8.0) (50-300) (2-7) (5500-19500) (0-120) (2500-12500) (1500-7000) (0-850) (0-1500) (0) (0) (0)

Case 9 (C11) - Male intact mixed breed cat presented because of anorexia and depression. Mucous membranes were pale and icteric. On palpation the cat had hepatomegaly and splenomegaly. Temperature was subnormal. PCV % 10 Hb g/dl 3.2 RBC x 106/ul 2.1 MCV fl 65 MCHC g/dl 31 MCH pg 29 Retics % few Nrbcs/100wbc 12 RBC morph some bowl forms WBC morph Doehle bodies Plat x103/ul low Platelet morphology not done

(30-45) (12-18) (5-10) (39-55) (31-35) (12.5-27.5) (0.2-1.6) (0)

(300-800) Unclassifiable cells

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Disintegrated cells

8.2 500 17.0 7900 ? 1700 2500 ? 0 0 0 3700

(6.0-8.0) (50-300) (2-7) (5500-19500) (0-120) (2500-12500) (1500-7000) (0-850) (0-1500) (0) (0) (0)

Case 10 (C14) - Mixed breed neutered male cat presented because of lethargy and poor appetite. Mucous membranes were pale. Temperature was subnormal. PCV % 11 Hb g/dl 3.5 RBC x 106/ul 1.7 MCV fl 54 MCHC g/dl 34 MCH pg 26 Retics % few Nrbcs/100wbc 0 RBC morph aniso; megalo WBC morph bizarre nuclei Plat x103/ul low Platelet morphology not done

(30-45) (12-18) (5-10) (39-55) (31-35) (12.5-27.5) (0.2-1.6) (0)

(300-800)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Disintegrated cells Unclassifiable cells

86.8 250 4.0 12000 200 9800 1500 300 200 0 0 0

(6.0-8.0) (50-300) (2-7) (5500-19500) (0-120) (2500-12500) (1500-7000) (0-850) (0-1500) (0) (0) (0)

Case 11 (7 - 139339) - Two year old, mixed breed, spayed female dog presented because of persistent fever and pale mucous membranes. On palpation and radiography abdominal fluid was found. PCV % Hb g/dl RBC x 106/ul MCV fl MCHC g/dl MCH pg Retics % Nrbcs/100wbc RBC morph normal WBC morph Plat x 103/ul

15 4.5 2.19 68.5 30 20.5 2.0 9

(37-55) (12-18) (6-8) (60-77) (31-35) (19-24) (0-1.5) (0)

toxicity 44

(200-400)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC (corrected) /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Unclassifiable

8.6 400 2.0 3700 1739 370 370 74 0 0 1147

(6.0-8.0) (200-400) (2-7) (6000-17500) (0-400) (3000-11500) (1000-4800) (150-1350) (100-1250) (0) (0)

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PCV % 12 Hb g/dl 4.0 RBC x 106/ul 2.1 MCV fl 64 MCHC g/dl 32 MCH pg 29 Retics % 0 Nrbcs/100wbc 14 RBC morph normal WBC morph Doehle bodies Plat x103/ul clumped (300-800) Platelet morphology not done

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Case 12 (139930) An Irish Setter spayed female, seven years of age was presented because of a swollen right salivary gland (or perhaps, submandibular lymph node). PCV % Hb g/dl RBC x 106/ul MCV fl MCHC g/dl MCH pg Retics % Nrbcs/100wbc RBC morph normal WBC morph Plat x 103/ul

24 8.2 3.26 73.6 34.2 25.3 0.8 2.3

(37-55) (12-18) (6-8) (60-77) (31-35) (19-24) (0-1.5) (0)

toxicity 213

(200-400)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC (corrected) /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Meta- and myelocyte

7.0 700 2.0 20500 3588 8610 1435 3793 102 0 2358: 615

(6.0-8.0) (200-400) (2-7) (6000-17500) (0-400) (3000-11500) (1000-4800) (150-1350) (100-1250) (0) (0)

Case 13 (140469) This patient, a Doberman Pinscher intact female, six years of age was referred because of inappropriate reticulocyte numbers and leucocytosis. PCV % Hb g/dl RBC x 106/ul MCV fl MCHC g/dl MCH pg Retics % Nrbcs/100wbc RBC morph WBC morph Plat x 103/ul

35 4.6 2.03 74.9 32 23.9 4.8 3.5 normal many immature 138

(37-55) (12-18) (6-8) (60-77) (31-35) (19-24) (0-1.5) (0)

(200-400)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC (corrected) /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Unclassifiable

7.1 500 29900 2541 14203 3140 9419 149 0 0

(6.0-8.0) (200-400) 3 (2-7) (6000-17500) (0-400) (3000-11500) (1000-4800) (150-1350) (100-1250) (0) (0)

Case 14 (140682) Pomeranian, 12 year old intact female was presented for pyometritis. She was anorectic, depressed and weak. Temperature was normal. Pulse was 180 per minute. The following data were obtained as a part of the presurgical screen. PCV % 23 Hb g/dl 7.1 RBC x 106/ul 3.61 MCV fl 63.7 MCHC g/dl 30.9 MCH pg 19.7 Retics % 3.8 Nrbcs/100wbc 2 RBC morph poly; microcytes WBC morph many immature Plat x 103/ul 456

(37-55) (12-18) (6-8) (60-77) (31-35) (19-24) (0-1.5) (0) Progranulocytes (200-400)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC (corrected) /ul Band Neutrophils Lymphocytes Monocytes Blasts Myelocytes; metas

7.3 500 2 123900 25400 73720 2478 6195 rare rare 620; 15487

(6.0-8.0) (200-400) (2-7) (6000-17500) (0-400) (3000-11500) (1000-4800) (150-1350) (0) (0) (0)

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Mycobacterial skin diseases Luis Ferrer

Introduction In general, mycobacteria are uncommon causes of skin diseases. Three groups of mycobacterial skin diseases have been recognized: cutaneous atypical mycobacteriosis, cutaneous tuberculosis and feline leprosy. In this lecture we will focus predominantly in atypical cutaneous mycobacteriosis, which is most prevalent in Europe.

Atypical mycobacteriosis Etiology: most cases are due to rapidly growing mycobacteria included in Runyon group IV. These mycobacteria are nonchromogenic, rapidly growing, gram positive, acid fast, aerobic, non-spore forming bacilli. Mycobacterium fortuitum, M. phlei, M smegmatis and M. chelonei are the most common species. They are ubiquitous in nature, specially in water, wet soil and intestines of ruminants, pigs and other animals. They are non-pathogenic for animals under normal circunstances. Infection is usually consequence of trauma or fight wounds.1 Dogs and cats are quite resistent to infection by slow growing atypical mycobacteria (Mycobacterium avium-intracellulare, M. genavense). They are classified as Runyon group III and are acid fast, slender rods; non-chromogens. Most reported cases have described disseminated disease without cutaneous involvement, but cutaneous lesions have been described in a few cases.2 Clinical signs: most patients present with a history of trauma and non-healing lesions that have not responded to antimicrobial therapy. In atypical mycobacteriosis associated with rapidly growing mycobacteria lesions consist in fistulous tracts and purpuric macules and nodules that ulcerate. Ventral abdomen, inguinal region and legs are the most commonly affected body parts. Usually dogs and cats are systemically unaffected and disseminated disease is rare. In atypical mycobacteriosis due to slow growing mycobacteria (M. genavense, M avium-intracellulare) disseminated disease is rather uncommon. Cutaneous disease, when exist, may present as nodules or diffuse subcutaneous swellings. Anorexia, weight loss, lymphadenopathy, splenomegaly and anemia have been reported in dogs and cats with the disseminated form of the disease.3,4,5 Diagnosis: a complete physical examination and bichem-

ical evaluation (complete blood count, chemistry panel and urinalysis) in patients suspected of mycobacterial infections is recommended. If disseminated disease is suspected apropriate imaging techniques (RX, ultrasound) are recommended. In cat, FeLV and FIV infection should be investigated. In most cases the definitive diagnosis is based on biopsy plus culture or PCR. Histopathologic findings consist of vatying degrees of granuloma formation, pyogranulomatous dermatitis, cellulitis and panniculitis. Acid-fast bacteria are observed in approximately 50% of cases. M. avium-intracellulare and M. genavense usually are present in larger numbers and are more commonly identified on cytology and histopathology compared to the rapidly growing group IV mycobacteria. Polymerase Chain Reaction (PCR) is a very sensitive and specific diagnostic tool. Most human hospitals run rapid kits to detect mycobacteria in samples. There are also commercial kits to detect M. avium-intracellulare. The identification of other species can only be made in well equiped, experienced laboratories. The identification of the mycobacteria can also be made from paraffin embedded tissue samples (after DNA extraction) allowing retrospective studies. Treatment: prolonged courses of antibiotics and surgical removal of infected tissue are the most effective treatments. Antibiotic selection should be based, if possible, on culture and senstivity results. Good choices while culture and sensitivity results are pending or lack include enrofloxacine and clarithromycin. Based on published reports fluoroquinolones, aminoglycosides, tetracyclines and clofazimine appear to be most effective. Prognosis: guarded in all patients. Antibiotic resistance in mycobacteria is becoming an increasing problem.

Cutaneous tuberculosis Tuberculosis in dogs and cats has a worldwide distribution. The incidence of the disease, however, has decreased with the decline of the disease in human beings and cattle. Etiology: M. bovis or M. tuberculosis. In the case of M. bovis dogs and cat contract the disease consuming infected meat or milk. In the case of M. tuberculosis the disease is contracted via airborne transmission from an infected human. Probably, the incidence is higher in cats than in dogs. Clinical signs: respiratory and digestive systems are pri-

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marily affected. Cutaneous involvement is unusual but occasionly happens. Patients show draining tracts, noedules, plaques, abscesses or ulcers. Patients usually are systemically ill with fever, weight loss and anorexia. Diagnosis: history, clinical exam, biopsy, culture and PCR. Biopsy specimens show nodular to diffuse pyogranulomatous dermatitis, with few acid-fast organisms. M. bovis and M. tuberculosis are slow-growers and growth may take up to 8 weeks. Intradermal skin testing with 0.1 ml of bacille Calmette-GuĂŠrin or PPD is best performed on the inner surface of the pinna. At 48-72 hours, persistent erythema with necrosis, crusts or ulceration is considered a positive test. However, the test is not 100% sensitive and specific. Nowadays, PCR using exudates or biopsy tissue -fresh, frozen or even paraffin-embedded-is the best diagnostic tool. Treatment: because of the seriousness of the disease and the public health hazard most patients with tuberculosis are euthanized and treatment is usually not recommended.

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winter months and the majority of case reported have been in young cats between 1 and 3 year of age. Lesions are typically single or multiple firm to soft nodules in the skin and subcutis. Lesions are most frequently found on the limbs, head and trunk. Regional lymphadenopathy is common, however, disseminated disease is rare. Diagnosis: is made on the basis of clinical findings in conjunction with the presence of large numbers of acid-fast bacilli on cytology or histology and the absence of growth in routine cultures for Mycobacterium. Treatment: excisional surgery, if possible, is the treatment of choice. Systemic therapy with clofazimine (2-8 mg/kg/day) or dapsone (1 mg/kg/day) are the alternatives. Spontaneous remission in one case of feline leprosy has been described.6

References 1.

Feline leprosy The disease is very rare in Euope (a few cases described in United Kingdom). The prevalence is higher in Canada, USA (NW states), New Zealand and Australia. Etiology: unknown. Some authors believe that Mycobacterium lepraemurium, the causative agent for rt leprosy, is responsible for the disease in cats. tranmission is thought to occur thriugh the bite of infected rats. Clinical signs: most cases appear to present during the

2. 3.

4. 5. 6.

White SD, Ihrke PJ, Stannard AA, et al., (1983), Cutaneous atypical mycobacteriosis in cats, J Am Vet Med Assoc, 182: 1218-1222. Lemarie SL, (1997), Mycobacterial diseases, Proceedings of the Annual Membersâ&#x20AC;&#x2122; Meeting AAVD & ACVD, Nashville, Tennessee. Jordan HL, Cohn LA, Armstrong PJ, (1994), Disseminated Mycobacterium avium complex infection in three Siamese cats, J Am Vet Med Assoc, 204: 90-93. Walsh KM, Losco PE, (1984), Canine mycobacteriosis: a case report. J Am Anim Hosp Assoc, 20: 295-299. Shackelford C, Reed W, (1989), Disseminated Mycobacterium avium infection in a dog, J Vet Diag Invest, 2: 273-275. Roccabianca P, Caniatti M, Scanziani E, et al., (1996), Feline leprosy: spontaneous remission in a cat. J Am Anim Hosp Assoc, 32: 189-193.

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Cutaneous drug reactions Luis Ferrer

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DVM, Dipl ECVD Universitat Autonoma de Barcelona - Spain

Paper not received

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From proper preparation to interpretation of the cytology smear Corinne Fournel-Fleury

Summary

2) Production of smears

The sampling method makes a preliminary distinction between samples taken from solid masses and fluid samples. The necessary equipment consists of slides with frosted ends, a good microscope and a centrifuge. For the cytology of fluids, the preferred equipment is a cytocentrifuge. The principles common to all cytological preparations are intended to favor the quality of the cellular analysis rather than the quantity of material examined, and to obtain a result that is as representative as possible of the tissue sampled. In the cytology of solid masses, fine-needle aspiration takes precedence over scraping and imprint smears. In the cytology of fluids, the centrifugate is spread according to the blood smear technique, in the absence of cytocentrifuge. Rapid air drying is most often used for stains of the “Romanowsky” type. Other cytochemical and cytoenzymological stains, as well as immunostainings, can also be carried out by cytological methods. The quality and representativity of the samples are looked at successively. A hierarchical analysis is then carried out on smears, always bearing in mind, first and foremost, the general cellular context, prior to the analysis at the cellular level. The search for neoplastic cells, as compared to reactive cells, is based on criteria of cellularity and homogeneity or heterogeneity. One must then be sure to determine the histological type of the neoplastic population: epithelial, mesenchymal, hematopoietic or melanocytic. Finally, the analysis of the cytological criteria of malignancy is carried out first at the level of the cell population, then at the cellular level.

Principles

I) METHODOLOGY 1) Equipment Sampling: variable methodology, depending on the tissue aspirated Smears: slides with frosted ends Centrifuges / cytocentrifuges Microscopes / objective lenses

There are some principles which are common to all preparations intended for cytological examination. These are: - to give preference to the quality of the cells collected, rather than to their quantity; and - to obtain, in a limited sample, material which is as representative as possible of the tissue collected.

Conditions For the quality of the cellular analysis, it is indispensable to obtain smears in single-cell layers, since clusters are undecipherable. For the representativity of the material analysed, it is indispensable to carry out dispersed collections in the mass of tissue to be analysed, and to avoid excessive dilution.

Means For solid masses, it is necessary: - to favor aspirations with a fine needle (22 to 24 G) in different directions and at different depths; this gives a limited, but representative, sample of material without causing undesirable bleeding, and also makes it possible to produce thin smears, correctly spread; - as far as possible, in neoplastic cytology, to avoid scrapings, which select superficial inflammatory or hyperplastic tissue, missing the underlying neoplastic process; - not to omit to take imprint smears, in parallel with the histological examination of a nodule, using fresh sections; this is a valuable complement to histological methods; - to limit contamination of fluid or semi-fluid collections by blood, and to end the collection as soon as any appears; - to carry out the centrifugation before spreading a voluminous fluid sample; - as far as possible, to spread the smears to their limits, so as not to lose the largest cells or cell clusters that are drawn to the borders by the spreading process; this means producing smears with a small quantity of the material collected, which in turn necessitates, in most cases, a prior distribution of this material among several slides.

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DVM, PhD Laboratoire d’Immunopathologie-Hématologie-Cytologie, Ecole Vétérinaire de Lyon - France

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Techniques

Rapid staining of the Diff-Quik type

Spreading of fine-needle aspirates Techniques for drawing out material between two perpendicular slides. Techniques for drawing out material between two parallel slides. Imprint smears using sections These are produced after excision biopsy of a solid mass. They involve making a clean, fresh section of the mass, wiping it by gentle application of a swab, then applying it firmly to the object slides in several successive imprints. Imprint smears have the advantage of supplying an approximation of the tissue architecture, and of producing no deformation of cells. However, they often suffer from excessive density, and an excess of exudate in the section. Spreading of fluid collections - A prior centrifugation should always be carried out if the quantity of fluid collected is sufficient. - In the case of classical centrifugations, the concentrate is pipetted and spread according to the blood-smear technique. - In the case of a cytospin obtained with a cytocentrifuge, the smear will be useless except if the disk is very hemorrhagic, in which case it should be spread by drawing out according to the given procedure.

This stain is to be avoided absolutely in cytology, since it induces an artefactual densification of chromatin, and a red-purple stain in cytoplasm, which preclude any fine cytological analysis. In medullary hematological cytology particularly, it can be a source of confusion between erythroid lineages and abnormal lymphoids. Its only use is that it gives the clinician the possibility of carrying out a rapid check on the richness and quality of one of the smears on a control slide before dispatching the others, non-stained, to the cytology laboratory.

Reaction to Periodic Acid Schiff (PAS) This method is used to reveal the constituents of the tissue types characterized by the neighbouring glycol and hydroxyamine groupings. Glycogen, mucin, hyaluronic acid, fibrin, hyaline and other elements give a positive reaction which can go from pink to crimson. In cancer cytology it is essentially of interest in the cytology of effusions, and contributes to the differential diagnosis between histiocytes, mesothelial cells and mucoid-secreting carcinomatous cells. Intracellular mucopolysaccharides give a more or less intense red stain, which may be diffuse, granulous or clumped.

3) Staining / cytochemistry / cytoenzymology / immunostaining Black Sudan B stain May-GrĂźnwald-Giemsa stain (MGG) This is the basic stain for hematological cytology. By comparison with its alternative in cytology, namely the Papanicolaou stain, its advantages are: - considerably more rapid utilization, and a facility of preparation and conservation of reagents; - an increase in the size of the cell and the nucleus; - a much better analysis of the coloring characteristics and the content of the cytoplasm, which is indispensable in hematology. It is inferior to the Papanicolaou stain as regards the evaluation of irregularities in the chromatin and the nucleoli, and especially in terms of cell transparency, which makes it possible, if necessary, to evaluate the three-dimensional organization of cell clusters, by varying the micrometric screw. This is particularly useful in the cytology of effusions, as a way of differentiating certain three-dimensional carcinomatous clusters of the mesothelial layers. The important thing is to be familiar with oneâ&#x20AC;&#x2122;s own particular reference stain. NB: for thick smears, which are frequently understained, it would seem preferable: - to carry out a primary stain, as above; - after a primary examination, to stain the slide a second time according to the same procedure, rather than to choose arbitrarily, according to the appearance of the dry smear, a higher concentration of the Giemsa stain.

This stain allows the revelation of lipids stained black by Sudan B.

Fontana stain This stain is used for revealing argentaffin substances, and in particular melanin granules, stained black for the identification of cells from weakly-differentiated melanomas.

Perls stain This stain is used, essentially in hematology, for the revelation of iron in macrophages and erythroblasts, and in particular for the revelation of sideroblasts in certain preleukemic myelodysplastic syndromes and hemosiderophages.

Enzymatic reactions for the differentiation of blood and medullary cells These stains are used for identifying weakly-differentiated acute leukemias. Only two of them are in routine use by our laboratory.

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Immunostainings Principle - Immunostainings reveal, through the utilization of specific antibodies (Ab), the presence of an antigen (Ag) at the surface of, or inside, a cell, this Ag being characteristic of one or more cell types. Utilization - In cancer cytology, immunostaining is mainly used to assist in the identification of: - solid anaplastic cancers; - undifferentiated acute leukemias; - certain carcinomas, as opposed to mesotheliomas or abnormal mesothelial hyperplasias, in the cytology of effusions. Numerous specific Ags can thus be revealed, provided that one possesses the appropriate Abs for the species under consideration. The range of Abs available is large in human medicine, but it remains limited in veterinary medicine. The procedure necessitates the obtention of polyclonal or monoclonal Abs which are specific to the species, or Abs which are specific to another species (the human species in particular), but which present a cross-reactivity with the animal species being studied. The principal Abs are: - anti-cytokeratin Ab, for the identification of carcinomas; - anti-vimentin and anti-desmin Ab, for the identification of sarcomas; - anti-factor VIII Ab, for the identification of endothelial cells and of the platelet lineage in hematology; - anti-glycoprotein IIIa Ab, which is specific to the platelet lineage; - anti-lysozyme Ab, as a histocytic marker. Finally, certain Abs are particularly used for the typing of lymphoid cells and the characterization of malignant lymphomas: - the polyclonal pan-T anti-CD3 Ab; - the anti-CD5, CD4 and CD8 monoclonal ABs; - the anti-CD79a pan-B Ab (mb1); - Abs which recognize the different immunoglobulins (Ig), surface (sIg) or intracytoplasmic (cIg), and, respectively, the heavy chains (γ or µ) of the IgG and IgM, and the light chains (λ and κ); - an Ab (MIB-1) which recognizes a nuclear proliferation Ag (AgKi67), signifying the entry of the cell into the cycle of cellular division, and thus the blastic character of a cell.

Procedure Most of the Ags detected are fragile, and cannot be subjected to fixation, or to prolonged storage. It is thus necessary either: - to carry out stains within one or two days on fresh smears stored at laboratory temperature; or - to freeze the smears and the cytospin disks at -70°C, with a view to future immunostainings.

II) PRINCIPLES OF EXAMINATION AND INTERPRETATION 1) Quantitative and qualitative analysis/ Principal artefacts 1) Evaluation of the richness of a sample 2) Evaluation of the quality of a smear - excessive thickness - excessive crushing - excessive drawing out 3) Evaluation of the quality of the fixation and the stain - insufficient staining (previous fixation with formalinbased fixatives) - insufficient drying - excessive basophilia (Romanowsky-type stains) - defective staining of the nuclear chromatin, and of certain granules (notably in mast cells), by rapid staining (e.g. the Diff-Quik type) - deposits of stain - absence of stain: exclusive presence of free fat 4) Evaluation of cell degeneration - increased nuclear volume - light staining of the nucleus - thickening of the nuclear membrane - increased nucleolar size - abnormal mitosis (multinucleation) - vacuolar cytoplasm - effacement of cytoplasmic outline 5) Artefacts caused by superposition 6) Evaluation of the representativity of samples

2) Principles of analytic examination 1) Analysis at the level of cell populations - overall cellularity - resident and reactive populations / smear background - inflammatory population - neoplastic population - mitoses 2) Analysis at the cell level - cell size - cell shape - nucleus • number of nuclei • size • N/C ratio • shape

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Peroxidase reaction This reaction is intensely positive in the granular lineage, in the form of brown-black granulations, weakly positive in the monocytic lineage, and negative in the lymphoid lineage. It also has the great merit, for parallel morphological analysis, that it can be combined with an MGG counter-staining. Non-specific esterase and specific monocytic reactions Non-specific esterase (without fluoride treatment) shows up as blue precipitates in monocytic and myeloid cell lineages. In the presence of fluoride, only myeloid esterase remains, monocytic esterase being inhibited.

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• position • chromatin • nucleoli: .quantity: total nucleolar volume .shape .position in the nucleus - cytoplasm • volume • shape • outline • stains • content .granules .vacuoles: secretion phagocytosis degeneration 3) Determination of the cell type of a neoplastic population - epithelial - mesenchymal - round-cell - melanocytic 4) Cytological criteria of malignancy The determination of malignancy most frequently results from the combination of a set of morphological criteria, firstly general, for the suspect population examined, then detailed, at the cell level. These criteria are applicable whatever the sample examined, and thus for cancer cytology as a whole. There is just one factor that varies, according to the type of sample (various fluids or solid masses) and the tissue of origin (hematopoietic organs, liver, serous membranes, nervous system, etc.), and that is the difficulty of making a differential diagnosis for benign, resident or reactive populations and, consequently, the number of criteria required for establishing a cytological diagnosis of malignancy. • Criteria of malignancy at the level of the cell population The general appearance of a malignant population is characterised by: *abnormal monomorphism, by contrast with the polymorphism of the smear background, associated with aniso-

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cytosis and, especially, anisocaryosis giving the impression of a single lineage, but anarchical in its evolution; *a tendency to the formation of voluminous cell layers and three-dimensional “clusters”; *numerous and, especially, abnormal mitoses (which is the distinguishing feature of mitoses that occur within benign populations). • Criteria of malignancy at the cellular level 1) Nuclear anomalies The most interesting nuclear criteria are: - a high N/C ratio; - a large amount of variability of shape; - a configuration which is often abnormal; - irregular chromatin, and occasionally a hyperchromatic nucleus; - finally, the presence of voluminous nucleoli, of variable dimensions, and sometimes veritable nuclei within the nuclei. 2) Cell size One often finds an overall increase in size, going all the way to cellular gigantism. Malignant cells are sometimes multinuclear but, unlike benign cells, are characterized by the nuclear abnormalities already mentioned. 3) Cytoplasmic criteria Cytoplasmic modifications, finally, are less specific, but are frequently observed: - excessive basophilia (“aggressive” basophilia); - vacuolization, going all the way to signet-ring cells; - the presence of abnormal granules or, conversely, the disappearance of specific granules (dedifferentiation). None of these criteria, taken in isolation, is either necessary or sufficient. Only an in-depth, thorough examination of the smear as a whole, bringing together all the observations carried out, can be considered as conclusive. • Indirect criteria • Interpretation - Metastatic cells: the importance of the identification of cells from the original tumor - Variability, according to the tissue sampled - Variability, according to the “smear background”.

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Corticosteroid therapy: an update Tommaso Furlanello

Summary

Which diseases should be treated?

Corticosteroids are among the most frequently prescribed medications, but they often pose a profound quandary for practitioners. These agents have many beneficial and sometimes live saving short-term therapeutic effects. However, they also have a veritable panoply of potential side effects that can involve virtually all organs. Thus, the decision to prescribe corticosteroids is an important one in small animal patient care and deserves due respect. The aim of this short review is to present a balanced view of steroid therapy in veterinary medicine, taking into account efficacy and common side effects.

Apart from Addison’s disease, steroid therapy is always symptomatic and does not act on the causative agent. In the near future, as scientific knowledge on pathophysiology of many diseases of dogs and cats improve, space available for symptomatic therapy should hopefully become more and more restricted. The main indication for steroid therapy are the following: 1) Addison’s disease: in acute cases, IV administrations are preferred. The drugs suggested are prednisolone sodium succinate (5-10 mg/kg) or hydrocortisone hemisuccinate (5 mg/kg). The latter has considerable mineralcorticoid activity. After the addisonian crisis, mineralcorticosteroids should be supplemented with parenteral desoxycorticosterone or fludrocortisone acetate. Many dogs treated with mineralcorticoids need very small “physiological” doses of prednisone (0.1-0.3 mg/kg/day) or could be even glucorticoid-free. 2) Inflammatory diseases: steroids are considered to be the most potent anti-inflammatory drug. Some of the mechanisms are still poorly understood, but they are prominent as inhibitions of phospholipase A2 and of cyclo-oxygenase (COX-2), two critical steps in the pathogenesis of inflammation. Although clinicians are daily tempted to use corticosteroid in the treatment of inflammatory disorders (cutaneous, respiratory, enteric), often only short term responses are obtained if the cause is not controlled or removed. For a durable remission of the disease, longer therapy is sometimes required, with high incidence of adverse reactions. The anti-inflammatory dosage for prednisone/prednisolone is 1 mg/kg/day in dogs. Feline patients are presumed to be “corticosteroids resistant” and it is stated to double the canine dosage. Their anti-inflammatory dose could be about 2 mg/kg/day. 3) Immune-mediated disorders: glucocorticoids are very effective and used immuno-suppressive drugs, both in human and veterinary medicine. They act primarily on cellulardependent immunity. Humoral response is not primarily affected, but many of the pathological effects of an aberrant immune activity could however be controlled. Some of the most common disorders, in which steroids are used as a first line of therapy, are immune-mediated anemia and thrombocytopenia, immune mediated joint disease, immune-mediated skin diseases and others. Although very few objective data are available, suggested immune-suppressive prednisone/prednisolone doses are 2-6 mg/kg/day in the dog and

Introduction Although corticosteroids are widely used by clinicians, scarce scientific information is available about therapeutic protocols in dogs and cats. Also in textbooks, many indications are based solely on anedoctical and sometimes dated information. The aim of this paper is to offer a short update about the clinical pharmacology of corticosteroids and their practical use.

Which preparation? Although many GCS have been developed, the pharmacological activity of this class of drugs remains quite the same. One can obtain the same immunosuppression in a case of immune mediated anemia with 2 mg/kg of prednisone/prednisolone and with 0.3 mg/kg of dexamethasone. If a more potent immunosuppression is required, is enough to increase the b/w dose of prednisolone. It is a myth to consider dexamethasone or other steroids as “extra strong”; the real difference is only in a much longer activity (days) and this in most situations is an unfavorable side effect. Both in human and veterinary medicine it is suggested to use only prednisone or prednisolone, by mouth or in aqueous solutions. If PU-PD is a concern, metil-prednisolone PO is an excellent substitute. If neuroprotection is required, the steroids of choice are metilprednisolone sodium-succinate or prednisolone sodium-succinate (see below). Long acting steroids should be used only in very special cases.

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even more in the cat. Although suggested by some clinicians, the IV dexamethasone therapy is not supported by any scientific evidence, but it is certainly linked to a much higher incidence of gastrointestinal adverse reaction. Practitioners prescribing high immuno-suppressive dose of steroids are often faced with serious adverse reaction. Many other immuno-suppressive drugs (e.g. cyclophosphamide, azathioprine, chlorambucil and others) are available and could be used adjunct to steroids, with the aim of reducing steroid dosages and/or to increase their therapeutic efficacy. 4) Antineoplastic therapy: steroids may be very effective drugs in the treatment of canine and feline lymphoma, but only for a short time. This use, if not scheduled together with rational chemotherapy, should be hardly discouraged, because it induces strong chemo-resistance in the survivor neoplastic cells. Corticosteroids are effective against mastocytomas, in which a systemic action is required. Again, steroids can be successfully utilized in the treatment of some paraneoplastic disorders (primarly hypercalcemia and immune-mediated haematologic disorders). As in human medicine, its use should be also considered in selected situations in which a palliative care of the patient is required, as temporary control of pain associated with cancer development, emesis, cachexia, and others. Spinal trauma: selected steroids are suggested both in human and veterinary medicine in the treatment of acute spinal trauma. Their use in neurotrauma has been based on their theoretical abilities to inhibiy lipid peroxidation, stabilize lysosomal membranes, and modify edema production. This neuroprotective activity is based on the anti-oxidative fraction of the metil-prednisolone sodium succinate (MPSS) molecule. This steroid must be used at a very high dose, in a timely manner, and should not be substituted by any other less expensive glucocorticoids, although a very recent report suggests the alternative use of prednisone sodium succinate (PSS). Although longer therapy is still suggested in veterinary literature, it is wise to follow the following popular protocol, extrapolated from human medicine. If spinal trauma has occurred in the previous 8 hours, administer MPPS in an IV bolus of 30 mg/kg. In the following 23 hours the therapy could be maintained with a constant-rate infusion at 5.4 mg/kg/hour, or with two other boluses of 15 mg/kg after 2 and 6 hours from the first bolus and again a constant-rate infusion at 2.5-5.4 mg/kg/hour for 18-42 additional hours. A newer protocol utilizes PSS at the initial IV dose of 30 mg/kg, followed by the same amount q6h, for a total of 36h. According to his neuroprotective activity, a single IV dose of MPSS is also by some suggested before every myelography or spinal surgery. Apart from laboratory trauma-models, wide clinical studies are lacking in veterinary patients with regards to the true efficacy of MPSS treatment. Considering human experience, any steroid administered after 8h (and surely after 24h) from the initial trauma, it is probably of little value. Steroids are no longer recommended in acute head injuries, because of their lack of activity against cerebral hypertension and the constant induction of hyperglycemia, very detrimental for traumatized neuronal tissues.

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Steroids in critical care patients: facts and myths One of the most popular use of steroids rely on the treatment of the “shock” patient. In human medicine a completely different vision has been elaborated in recent years and no space for steroids is reserved in critical care patients, apart from the acute Addisonian’s crisis. As an example, we would report the statement reported in Goodman & Gilman’s The Pharmacological Basis of Ther., 9th ed. (1996), one of the most authoritative textbook in clinical pharmacology (page 1457): “while corticosteroids are often administered to patients in shock, there is no convincing evidence to indicate that such therapy is efficacious”. In the past steroids were suggested also in the treatment of septic shock, a common and very severe disorder both in human and veterinary medicine. In this regard, we would remember the statements of the Infectious Diseases of America (1992), which deny any role of steroids in the treatment of sepsis and correlated syndromes. Unfortunately shock it is a very complex disorder and the beneficial activity of steroids could be of some help only if administered very early in the pathogenic process. This goal is achievable only in experimental studies, the initiating phenomena (trauma, hemorrhage, sepsis...) is provoked and timed. No clinical studies are available on the use of steroids in canine and feline spontaneous disorders in critical care medicine. Unless newer and convincing data will be presented, the widespread use of any steroids in shock patients should be discouraged, and dated guidelines and medical propaganda ignored.

Adverse reactions of glucocorticoid therapy The toxicity of adrenocortical steroids is well know. In this review we will only list the most important points to remember during any steroid therapy. The incidence and the severity of most of these is proportional to the magnitude of the dose and the length of the therapy and not lastly to the molecule. As an example, dexamethasone is certainly much more ulcerogenetic than other oral steroids such as prednisone/prednisolone and metilprednisolone. 1) Interference with diagnostic tests: although not a true “adverse effect”, this often neglected point must be considered by any clinician. After a few days of steroid therapy, a wide array of haemato-biochemical alterations will (??) become evident (leukocytosis, increase of the activity of liver enzymes, hyperglycemia, reduction of the urinary special gravity and many many others). Many diagnostic tests will be difficult or impossible to be correctly performed (evaluation of the activity of adrenal or thyroid gland, ANA test, Coombs’ test, intradermal skin test and others). 2) Iatrogenic Cushing’s Syndrome: medium or long term steroid therapy could induce in some dogs “classic” biochemical and physically signs of the syndrome. The diagnosis could be gained with an ACTH stimulation test. This form is potentially reversible and should not be treated. 3) Iatrogenic Addison’s Disease: any dogs or cats receiving steroids enter in a sort of “surrenal pause”. In human pa-

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increased activity of ALP rely on the “normal” hepatic isoenzyme. After about 3-4 weeks, a new isoenzyme, called “steroid-induced AP” (SIAP) is dosable. Some dogs are also prone to hepatomegaly, caused by glicogen storage in hepatocytes. This potentially reversible hepatopathy can sometimes evolve into a severe disorder. The severity of SH is related to the length and dosage of drug administered, to the kind of steroids utilized and maybe to an individual predisposition. The cat is much more resistant than dog to steroids’ hepatic toxicity.

Conclusion Corticosteroids are an incredibly useful class of drugs if used in appropriately cases and with rational protocols. In many situations steroids are absolutely indispensable (e.g. immune-mediate diseases) and can be truly life-saving. The “right” dose for every particular patient must be fixed according to the clinical situation, age, intercurrent or past disorders, and other therapy. It is an obvious rule that the clinician administer the less toxic preparation, for the shortest period of time and to taper in a cautious manner, especially after long term administration. Critical reading of current veterinary guidelines is suggested, until newer information is not diffused into the scientific community. A list of suggested readings (MS Word97 or html format) will be e-mailed by the authors if requested to sanmarco@iperv.it

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tients this iatrogenic suppression of the HPA axis is also common and is sometimes linked to various clinical problems, especially when corticosteroid therapy is stopped (corticosteroid withdrawal syndrome). This situation potentially could occur also in veterinary patients, but it is more difficult to recognize. 4) Immuno-suppression: steroids facilitate the pathological action of viruses, bacteria, yeasts and parasites. The immuno-suppression is probably one of the most fearing side effects of steroids. The danger is even increased by the asymptomatic reaction of the patient (because of the anti-inflammatory activity of steroids) to pathogens’ colonization. Classical sites of infections are urinary tract, skin and respiratory tract. In cats latent FeLV infections could be re-actived. The popular prophylactic association steroids plus antimicrobial must be evaluated as ineffective and constantly leads to bacterial multidrug-resistance. Constant surveillance by the clinician, with regards to infectious complications of steroid therapy is mandatory. The only preventive measure is to reduce any unnecessary use of steroids, or to keep as low as possible the amount of drugs utilized. 5) Gastric and intestinal bleeding/perforation: the antiprostaglandin activity of corticosteroids, induce gastric lesions after few days of therapy. In this regard, any association with other gastro-toxic drugs as AINS must be absolutely banned. Spinal patients are also proned to colon perforation. Misoprostol could protect against gastric hemorrhage, while H2-blocker are ineffective as a preventive. 6) Steroid Hepatopathy (SH): in dogs steroids easily induce a notable increase of the serum activity of AST, ALT, GGT and ALP. In the initial phase of steroid liver action, the

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Pigmented and non-pigmented masses at the eye level Adolfo Guandalini

Summary This study takes into consideration all eye pigmented and non-pigmented masses, observable during a clinical examination. At the eyelid level congenital (dermoids), inflammatory (hordeolum, chalazion) and neoplastic masses can be detected. The conjunctiva may show cystic or neoplastic lesions. The third eyelid can present acquired modifications, involving the cartilage (eversion) or the gland with prolapse, cyst, neoplasia. The corneal limbus is usually affected by immuno-mediated (for instance, nodular granulomatous episclerokeratitis) or neoplastic formations (epibulbar melanoma). The cornea sometimes presents congenital masses (dermoids), the outcomes of inflammatory (exuberant granulation tissue) or ulcerative forms (descemetocele, iris prolapse). Besides, can be seen other diseases which can affect the corneal endothelium (bullous keratopathy), cysts (inclusion cysts) or tumors. The uvea may present cystic or tumoral affections, which can be primary (melanoma, adenoma and adenocarcinoma) or secondary (lymphoma).

Eyelid1,2 The dermoids or choristomas are congenital abnormalities, containing many of the skin components. Dog dermoids may involve the eyelid, mainly the lateral side, the conjunctiva and the cornea. However, they can be observed in other sites. German shepherd, Dalmatian and St. Bernard dogs are particularly prone to them. Inferior eyelid colobomas associated to dermoids result in some line of St. Bernard. Some lines of Birman cats are genetically predisposed, as well as Burmese cats seem to get affected on a hereditary basis. The dermoids may appear pigmented or not, uni or bilateral, single or multiple. They are histologically made up of ectopic, layered, squamous epithelium, subepithelial connective tissue and adnexal tissues. The resolution is surgical. The hordeolum is a purulent inflammation of the eyelid glands normally linked to staphylococcal infections. The external hordeolum involves Zeis and Mollâ&#x20AC;&#x2122;s glands. It is detected in young animals, in the form of single or multiple abscesses on the eyelid margin. The chalazion, (inner hordeolum) involves meibomian

glands and is usually found in middle-aged dogs. The meibomian gland duct obstruction causes retention of oily gland secretion which accumulates and spreads into the surrounding tissues. This causes a foreign body reaction resulting in a granuloma. It is observed on the eyelid conjuncitval surface in the form of a thick yellow-colored mass, perpendicular to the eyelid margin. The hordeolum is treated with hot pads and antibiotics topically. The chalazion treatment is made by the incision of the conjunctival surface and surgical curettage. Antibiotics and steroids are postoperatively administered for 5-7 days. The eyelid neoplasms in dogs are mainly represented by adenomas, adenocarcinomas, both benign and malignant melanomas and papillomas. These tumors account for 82% of neoplasms, according to a study on eyelid tumors on dogs. Sebaceous gland tumors, mainly benign, occurr with 45% incidence rate. Histologically, malignant tumors are locally invasive but hardly ever metastasize. They are found in elderly dogs. Beagle, Syberian husky and English setter are breeds at high risk to developing eyelid neoplasms. Papillomas, observed in young subjects, are often selflimiting neoplasms or they can be subjected to surgical resection and then the surgical site is submitted to cryosurgery. Histiocytomas are found in young dogs; they are usually self-limiting. Pseudotumors are processes clinically hard to distinguish from neoplasms. After surgical resection, histological diagnosis is carried out (for instance: nodular fasciitis). Eyelid neoplasms are less frequent in cats, however more malignant than in dogs. Data concerning the incidence rate of these neoplasms have been recently reviewed. Squamous-cell carcinoma is the most common, invasive and potentially malignant. The symptoms are reddened and eroded skin areas. The diagnosis is made with histological examinations. Other cat neoplasms are basal cell carcinoma, mast cell tumor and fibrosarcoma. A histological examination is always needed, as all eyelid tumors in cats are potentially malignant. Eyelid neoplasm treatment, according to the tumor type, may range from the mere observation, in self-limiting tumors, to surgical resection followed by cryosurgery, radiotherapy, chemotherapy. In some cases blepharoplasty may be required.

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Conjunctiva1,2 Dogs can present inclusion epithelial cysts and conjunctival cysts originating from the third eyelid gland, lacrimal gland and zygomatic salivary gland. The conjunctiva neoplasms include the squamous cell carcinoma, fibrosarcoma, papilloma, malignant melanoma3, lipoma, adenoma, histiocytoma, lymphoma, hemangioma and mast cell tumor. These tumors may be primary or secondary, originating from the cornea, the nasolacrimal system, the episcleral and scleral tissue. The diagnosis is made with cytological and bioptic examinations. The treatment consist in surgery, cryotherapy, radiotherapy, immunotherapy and chemotherapy. The fat pad prolapse can be found in dogs, with underconjunctival tumefaction and enophthalmos. Surgery is the treatment4. Cats showing a symblepharon, can also be affected by conjunctival cysts, that must be removed surgically. The conjunctival chemosis associated to many conjunctival diseases sometimes grows noticeably. Several neoplasms may involve the conjunctiva primarily (for instance, the squamous cell tumor and, rarely, benign and malignant melanomas) and secondarily (for instance, the lymphoma).

The third eyelid1,2 Some conditions in dogs and cats are shown as nodular masses on the third eyelid. Dogs in their early months, mainly if they are large breed dogs, may show an inward or outward deviation of the nictating cartilage. Bassethound, Bloodhound, English setter, German shepherd, Pointer, Great Dane, Irish setter, Irish wolfhound, Newfoundland dog, Rhodesian ridgeback, St. Bernard dog and Weimaraner are predisposed breeds. Such cartilage deviation is associated to the third eyelid malfunction and chronic conjunctivitis. The treatment consists in the surgical resection of the folded cartilage. The third eyelid gland prolapse, so called â&#x20AC;&#x153;cherry eyeâ&#x20AC;?, seems to be due to the weak anchorage fibrous system of the gland to the periorbita. Several dog breeds are prone to this disease such as Beagle, Bloodhound, Boston terrier, American cocker, Lahssa apso, Napolitan mastiff, Newfoundland dog, St. Bernard dog and Shar pei. The surgical treatment of this disease has been reviewed over the years. In the past, in fact, the prolapsed gland was surgically excised. As this gland produces from 29% to 57% of the total lacrimal amount, today the gland repositioning is preferred. Several surgical techniques have been described5. Sometime, it is possible to find cysts within the third eyelid gland which must be removed surgically. Nictitating neoplasms are rare. The third eyelid gland adenocarcinomas can be aggressive and highly malignant. If the tumor is extended, the whole third eyelid should be removed. The third eyelid gland prolapse is rare in cats. It was observed in two Burmese cats associated to the cartilage ever-

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sion. Neoplasms are rare [squamous cell tumor, fibrosarcoma, mast cell tumor, lymphoma, third eyelid gland adenocarcinoma6]. Proliferations on the third eyelid external surface have been recently described, as possible manifestation of the eosinophilic granuloma complex7.

Lacrimal apparatus The masses observed can be dacryops8, canaliculops9 and granulation tissue within the lacrimal canaliculus10.

Cornea1,2 The dermoids are usually found within the lateral limbus area; they extend also on the sclera; keratectomy is carried out to remove them. The stromal abscess is caused by the hoard of inflammatory cells within the corneal stroma. It is opaque, yellowwhite colored, slightly raised, at the corneal level. Stromal abscesses are sterile or can contain an infective agent. They are not common in pets. The diagnosis is made by means of cytological examinations and cell culture. The treatment consist in local antibiotics or keratectomy followed by conjunctival flap. The descemetocele is a very deep ulcer, so that the Descemet membrane is involved. Sometimes such membrane protrudes to the point that it can be observed from the ulcer stromal margins. It requires emergency surgery. The deep corneal ulcer or wound with perforation and iris prolapse result in a brown-black mass at the corneal level, usually covered by coagulated aqueous humor. This condition requires immediate surgery. The prolapsed iris is repositioned if the lesion happened less than 8 hours before otherwise it is removed; then, the corneal lesion is sutured and the anterior chamber is reconstructed at last. Bullous keratopathy is an endothelial corneal disease, secondary to inflammation, degeneration or glaucoma which may induce chronic corneal oedema with subepithelial or stromal bullae bulging from the corneal surface. Secondarily, these lesions may turn in epithelial erosions or actual corneal ulcers sometimes even followed by corneal perforation. Cats may present a severe bullous keratopathy; etiopathogenesis is unknown. Young subjects are affected and the disease is usually bilateral. The lesions recover completely or, viceversa, develop in perforation. The application of a pedicle conjunctival flap can be effective to prevent from perforation, if it is carried out in a very short time11. There is another kind of bullous keratopathy, secondary to the stromal corneal dystrophy, observed in Manx cat, and endothelial dystrophy, seen in domestic short-hair cats. Exuberant granulation tissue can bulge into the cornea. Thus a differential diagnosis is to be made to distinguish it from any corneal neoplasia. If it does not decrease using steroids topically, the surgical resection is required (keratectomy). Inclusion cysts mainly involve the epithelial layer and get evident after flap or conjunctival grafts. Some epithelial cells are trapped within the stroma where they develop and

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Limbus1,2 The fibrous histiocytoma is a mass, invading into the temporal cornea in dogs. Histologically it consists in histocytes, fibrocytes, plasma cells and lymphocytes. The therapy envisages the superficial keratectomy followed by the local and subconjunctival application of steroids. Azathioprine is effective to keep under control such diseases. The nodular fasciitis is a solid infiltrating mass, mainly consisting in fibroblasts and reticulin fibres. Surgical resection is effective. The epibulbar melanoma is a usually pigmented, although it can also be amelanotic, neoplasia. It is invasive in young subjects (2-4 years), stationary in old ones (8-11 years). It mostly originates in the dorso-lateral quadrant. The German Shepherd seems to be particularly prone to develop it. Such form must be distinguished from an intraocular melanoma transcleral extension. On this regard, a gonioscopic examination is recommended to avert any possible intraocular neoplasia. The surgical treatment consist in a free corneo-scleral graft, third eyelid cartilage graft, cryosurgery, PTFE transplant13, photocoagulation14. The treatment is indicated in young subjects to protect the eyeball, while recurrent observations are recommended in old subjects. Epibulbar melanoma is rare in cats. The treatment is the same as in dogs. The granulomatous nodular episclerokeratitis (NGE) is represented by single or multiple masses at the limbus level, which spread into the surrounding corneal stroma. The third eyelid is frequently involved. Breeds, such as Collie and Shetland Sheepdog are particularly predisposed to develop it. It is a chronic granulomatous inflammation. Histiocytes, plasma cells, fibroblastic cells, reticulin fibres and neovascolarization with infiltration of polimorphonucleates are histologically evidenced. The treatment consist in Azathioprine administered orally associated to topical steroids. Episcleritis and scleritis: episcleral lesions are usually nodular, painless and rose-colored single lesions. They are mostly located in the temporal limbus. The American cocker and Golden retriever are particularly predisposed breeds. These are granulomatous lesions, containing histiocytes, lymphocytes, plasma cells, and an amount of reticulin fibres. Scleritis becomes evident with painful and red eyes, with lesions and concurrent intraocular inflammation at level of the posterior segment. Histologically, it consists of necrotiz-

ing diffused granulomatous lesions, with a deep infiltration of inflammatory cells (histiocytes, lymphocytes, plasma cells)15.

Uvea1,2 Uveal cysts in dogs may be congenital or acquired. Acquired cysts can have a traumatic or inflammatory origin. However, the cause is usually unknown. They can be either uni or bilateral, single or multiple, oval or globe-shaped; black or brown colored or sometimes transparent. They can be found free in the anterior chamber, adherent to the pupillary margin or to the ciliary bodies. Uveal cysts can be transilluminated, and then distinguished from the uveal melanomas. They have been recently found as the cause of secondary glaucoma in Great Dane16. They are removed by inspirating through a limbal incision or by means of photocoagulation. Nevi are restricted melanocytic lesions appearing over the iris surface. They are mainly observed among young subjects (2 years or younger). Most of melanomas involve the anterior uvea in dogs. According to a study on melanomas the metastasis incidence is 4%. They are more frequent in older dogs (8-10 years). German Shepherd and Boxer seem to be particularly predisposed breeds. These are, usually, nodular in appearence. They can originate from iris or ciliary bodies. Ciliary body neoplasms can derive either from embryonal indifferentiated tissue (medulloepithelioma) or differentiated cellular tissue (adenoma and adenocarcinoma). German shepherd and American cocker seem to be more predisposed to them. Middle-aged and older dogs (8 years average age) are the most affected. They can originate either from the pigmented or non-pigmented epithelium; it seems more likely from the latter. Adenomas are most of times limited to the ciliary body while adenocarcinomas are more invasive and they can metastasize. Two approaches are usually adopted: waiting or the neoplasia surgical removal17. The most frequent secondary neoplasia is lymphoma. It usually involves both eyes. The anterior uveitis is the most frequent clinical sign. Conjunctival infiltrations, interstitial keratitis, hyphema, retinal haemorrhage and glaucoma can be observed. In the cat the most common primary neoplasia is the iris melanoma which differently from the dog shows a trend to the infiltration rather than nodular aspect and adenomas and adenocarcinomas of the ciliary bodies. Lymphosarcoma associated to the FeLV virus is the most common, among the secondary neoplasias.

Orbita1 The zygomatic mucocele is originated by the saliva release with secondary fibrosis and inflammation. The cause is mainly traumatic. A mass can be observed within the ventral conjunctival fornix. Within the mass aspirate, the presence of a viscous fluid containing no inflammatory cells is detected. Surgery is the treatment.

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create a cystic cavity, coated by non-keratinized squamous epithelium. These isolated, white-rosed cysts are usually unilateral. The origin seems to be traumatic. They are surgically removed with a superficial keratectomy12. The squamous cell carcinoma takes origin directly from the cornea and is classified as corneal intraepithelial neoplasia. It becomes evident as a white-rosed multilobulate mass. The treatment consist in a superficial keratectomy combined to cryosurgery or beta-radiation. Papillomas are more frequent in young dogs. They are surgically treated with keratectomy followed by cryosurgery or beta-radiation.

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References 1. 2. 3.

4. 5.

Gelatt KN, (1991), Veterinary Ophthalmology, Lea & Febiger, Philadelphia. Barnett KC, Crispin SM, (1998), Feline Ophthalmology, W.B. Saunders Company Ltd London. Collins BK, Collier LL, Miller MA et al., (1993), Biologic Behavior and Histologic Characteristics of Canine Conjunctival Melanoma, Prog in Vet & Comp Ophth, 3, 4:135-140. Boydell, Paterson S, Pike R, (1996), Orbital Fat Prolapse in the Dog, J Sm Anim Practice, 37:61-63. Guandalini A, Rovesti G, Dâ&#x20AC;&#x2122;Anna N, (1997), Retrospective Evaluation of 49 Cases of the Periorbital Rim Anchorage Technique for Third Eyelid Gland Prolapse in the Dog, Veterinaria, 11, 4:7-11. Komarony AM, Ramsey DT, Render JA et al. (1997), Primary Adenocarcinoma of the Gland of the Nictitating Membrane in a Cat, J Am Anim Hosp Assoc, 33:333-336. Keil SM, Olivero DK, McKeever PJ et Al (1995), Bilateral Nodular Eosinophilic Granulomatous Inflammation of the Nictitating Membrane of a Cat, Vet & Comp Ophthalmology, 7, 4:258-262. Grahn BH, Mason RA, (1995), Epiphora associated with dacryops in a dog, J Am Anim Hosp Assoc, 31:15-19.

9. 10. 11. 12. 13.

14.

15.

16.

17.

Gerding PA , (1991), Epiphora associated with canaliculops in a dog, J Am Anim Hosp Assoc, 27:424-426 Williams DL, Long RD, Barnett KC, (1998), Lacrimal Pseudotumor in a young Bull Terrier, J Sm Anim Practice, 39:30-32. Glover TL, Nasisse MP, Davidson MG, (1994), Acute Bullous Keratopathy in the cat , Vet & Comp Ophthalmology , 4, 2: 66-70. Bedford PGC, Grierson I, McKechnie NM, (1990), Corneal Epithelial Inclusion Cyst in the Dog, J Sm Anim Practice, 31: 64-68. Wilkie DA, Wolf ED, (1991), Treatment of Epibulbar melanocytoma in a dog Using Full - Thickness Eyewall Resection and Synthetic Graft, J Am Vet Med Assoc, 198: 1019-1022. Sullivan TC, Nasisse MP, Davidson MG et al., (1996), Photocoagulation of Limbal Melanoma in dogs and cats : 15 Cases (1989-1993), J Am Vet Med Assoc 208: 891-894. Deykin A, Guandalini A., Ratto A, (1998), A Retrospective Histopathologic Study of Primary Episcleral and Scleral Inflammatory Disease in dogs, Vet & Comp Ophthalmology, 7, 4: 245-248. Spiess BM, Bolliger JO, Guscetti F et al., (1997), Multiple Ciliary Cyst and Secondary Glaucoma in the Great Dane: A Report of 9 Cases, Trans ECVO Meeting, Birmingham. Clerc B, (1996), Surgery and Chemotherapy for the Treatment of Adenocarcinoma of the Iris and Ciliary Body in Five Dogs, Vet & Comp Ophthalmology, 6, 4: 265-270.

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Abnormal new bone formation Herman A.W. Hazewinkel

Summary The practicing veterinarian can be confronted with a variety of orthopedic diseases characterized by new bone formation. Recognizing these diseases is the basis of making a diagnosis and advising a diagnosis, based on the prognosis. Development, nutrition, inflammation and tumor related diseases are discussed including craniomandibular osteopathy, osteoporosis, metaphyseal spurs, panosteitis, hypervitaminosis A, hypertrophic osteodystrophy, osteochondroma, hypertrophic osteopathy and medullary bone infarction.

Introduction Skeletal growth and remodelling is a close interrelated activity of bone forming osteoblasts and bone removing osteoclasts. Osteoblasts originate from the periosteum and are moved to the growth plates by ingrowing blood vessels allowing to form primary spongiosa. Osteoclasts are originating from stem cells which are formed in the bone marrow. Osteoclasts are in particular active at the endosteal side (enlarging medullary cavity), metaphyseal area (decreasing the metaphyseal diameter to the size of the diaphysis) and near bony foramen (enlarging foramen allowing vessels and nerves to pass). In case of increased activity of osteoblasts and/or decreased activity of osteoclasts too much bone may be the result. A variety of diseases characterized by abnormal new bone formation will be discussed related to development, nutrition, inflammation or tumors, whereas new bone originating from fracture healing, osteoarthrosis, malignancies, and in musculo-tendinous tissue are beyond the scoop.

Development related 1. Craniomandibular osteopathy Craniomandibular osteopathy (C.M.O.) is also known under the names mandibular periostitis, lion-, westy- or scotty- jaw, or after the describer of a human disease with some similarities, Caffey Silverman-Syndrome. CMO is most frequently described in terriers (including West Highland White, Scottish, Cairn, Boston), Great Danes, Retrievers, and other dogs of larger breeds of either gender. First signs are seen at 3-8 months of age. In Scottish and West Highland White Terriers retrospective investiga-

tion of pedigree makes an autosomal recessive inheritance, with 25% affected pups, most likely. Others have also reported several dogs from one litter being affected. The expression may be variable since some dogs have only radiological but not clinical signs of C.M.O. The first sign is reluctance to open the jaws. The dog may be in bad condition with intermittent elevated body temperature (to 40.5째), pain reaction upon palpation of the mandible on one or both sides, upon opening of the jaws. Repetitive coughing, lethargy, atrophy of muscles of mastication, enlarged mandibular lymph nodes and sometimes rhinitis, conjunctivitis, otitis externa and stomatitis may be seen. Blood investigation may reveal increased or decreased globulins, increased alkaline phosphatase, negative culture. The clinical signs may totally disappear at the age of 11-13 months1. Radiographs may show typical signs: enlargement and broadening of the rami mandibularis due to periosteal new bone formation, with or without obliteration of bullae tympanicae. Other bones of the skull (os occipitale, parietale, frontale and maxilla) might be affected with or without mandibulas involvement. In exceptional cases proliferations of long bones of the appendicular skeleton are seen. New bone formation is found lateral, ventral and medial to the corpus mandibulae and caudal to the foramen mentalis. The alveolar side is not involved. Bullae tympanicae are filled with new bone and can triple in size, causing tracheal displacement. Osteoclasts remove bone, which is replaced by immature, less mineralized woven bone. The medulla is replaced by highly vascularized fibroblastic tissue. Inflammatory cells invade newly formed bone and surrounding subcutis and muscles are destroyed. A disturbance of the development of the immune system has been suggested, based on the dysproteinemia and the infections found in these patients, although infections are extremely rare. Fewer and periods of pain coincide with periods of the presence of inflammatory cells in the area of new bone formation. The more severe cases need fluid therapy and analgesics, with corticosteroids in case non-steroidal analgesics do not give sufficient improvement. According to some, corticosteroids will diminish the new bone formation. Surgical removal of new bone will not lead to permanent improvement, only in case of joint involvement. 2. Osteopetrosis In a variety of species osteopetrosis (or osteosclerosis

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DVM, PhD, Dipl ECVS Dept. Clinical Sciences of Companion Animals Faculty of Veterinary Medicine - Utrecht University - The Netherlands

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fragilis, or marble bones) is known as an autosomal recessive disease. In this disease, excessive accumulation of bone and mineralized cartilage occurs due to abnormal decreased osteoclastic function, due to defective enzyme systems and morphological abnormalities. In addition, osteoblastic activity is increased. The disease in characterized by bone pain and pathological fractures of affected bones, due to the fact that bone is very bridle. On radiographs affected bones are radiodence at the medullary cavity and cancellous portions of all bones of the axial and appendicular skeleton. The shape of the bones remains normal, and the bones can be normal in size; histologically the growth plates are normal, and endochondral ossification is not disturbed. However, the trabeculae of primary spongiosa extends from the growth plates to the medullary cavity into the diaphyses where it contacts diaphyseal bone formed by the periosteum which is not removed to form a medullary cavity. Therefore, hematopoesis can be disturbed, causing anemia in severe cases. In man, spleen or bone marrow infusion after irradiation to knock out the defence mechanism, results in osteoclastic activity2. Till this can be performed also in dogs and cats with osteopetrosis, there is no cure for these animals available.

Nutritional related 1. Spurs in the cut-back zone The large width of the metaphyseal area should be decreased to diaphyseal width by osteoclastic activity. In young dogs of large breeds, a roughening at the palmar margin of the distal ulnar metaphysis can be noticed on mediolateral radiographs, during the dogs rapid growth phase. This can be seen especially in young dogs with excessive dietary calcium intake, known to decrease osteoclastic bone resorption3. However, also in 16 Great Danes raised on food formulated to meet the recommendations for dogs4, including 1.1% calcium on dry matter base [dmb], these spurs were present in 80% of the cases, especially at the age of 15 weeks. These bony spurs disappear at the age of 6 months. In addition, flattening or indentation of the distal ulnar metaphyses or even cartilage cones were present in these dogs at the age of 15 weeks, and even in 6 dogs still at 6 months of age. In the remaining dogs, a small cartilage cone did not had clinical consequences5. In more severe cases, as are described in research dogs raised on a food with excess calcium (3.3% on dmb), these cartilage cones may exceed 2.5 cm and go together with a disturbed growth in length of the ulna, leading to the radius curvus syndrome3. These findings have led to the conclusion that 1.1% calcium on dmb might cause a too high calcium uptake in fast growing large breed dogs. Although a bony spur in itself does not have clinical consequences, it reflects decreased skeletal remodelling with major complications for young dogs of large breeds. This can be prevented by recommending a commercial dog food specially designed for young, large breed dogs. 2. Panosteitis Panosteitis is also known as enostosis or eosinophilic panosteitis. In young dogs, a high calcium intake causes a

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high calcium absorption, causing a hypoparathyroidism and a hypercalcitoninism and thus a decreased osteoclastic activity. This causes a routing of calcium to the skeleton, where it is stored to be used later. Chronic calcium excess in young dogs causes an increased calcium accretion and a decreased skeletal remodelling, including a decreased adaptation to soft tissue growth. Blood vessels centrifugally running through canals in the diaphyseal cortex do not expend proportionally together. This will result in oedema formation inside the medullary cavity with ultimately new bone formation on the fibrous tissue formed. Increased pressure and finally new bone formation is first seen near the foramen nutritium. Oedema may accumulate underneath the periosteum and thus make the periosteum more vulnerable to pressure and pull and may cause extra lamellar bone formation. So far no other etiologies have been demonstrated but cannot be ruled out. The disease is mainly seen in mediumsized and large-breed dogs, especially in German Shepherds, starting at 6 months of age, and is characterized by a sudden onset of shifting lameness. The lameness is seen in different legs, will become increasingly severe in several days, and can disappear or regress for some time. Dogs may receive dog food supplemented or rich in calcium. Radiographs demonstrate a blurring of the trabecular pattern in the metaphyseal area (especially the proximal ulna) and eventually white areas starting near the foramen nutritium and extending throughout the medullary cavity. In some cases and with special radiographic technique a well-defined subperiosteal cortical thickening can be noticed6,7. Analgesics can be necessary and a calcium-deficient diet for a limited period to increase osteoclastic activity can be advocated, although is not proven to be beneficial yet. In mature dogs, corticosteroids can be prescribed. The disease is self limiting and is not diagnosed in dogs over 22 months of age, till that age relapses can occur. 3. Hypervitaminosis A Vitamin A is one of the fat soluble vitamins, required to prevent a variety of abnormalities including reproductive failure, disorders of epithelia (bronchi, salivary glands, haircoat) and retinal degeneration. Vitamin A is also required for normal skeletal growth and development, especially osteoclastic activity. Vitamin A1 is, present in a variety of foodstuffs originating from terrestrial and seefish, whereas vitamin A2 (which is 30% less effective in mammals) is present in fresh water fish. Since cats cannot transform carotene into vitamin A, they totally rely on vitamin A as present in animal food tissue or supplemented to the food. Dogs, unlike cats, are able to form retinyl esters making the vitamin A biological inactive, as well as to excrete 15-60% of the daily vitamin A intake as retinyl palmitate in the urine. Although massive doses of vitamin A caused hypervitaminosis in kittens and puppies after several weeks, in companion animal practice hypervitaminosis A will be seen especially in the mature cat, starting between 2 and 5 years of age. In dogs the history of massive supply of cod liver oil or vitamin supplements will help to make the diagnosis. In cats the diet has not always been raw liver, fish or supplements: 4 out of 8 of our patients and 3 out of 80 cats did not eat these foodstuffs, reason why an individual predisposition is suggested.

Excessive amounts of vitamin A will reduce chondrocyte proliferation in the growth plates, depress periosteal osteoblastic activity, and stimulate osteoclastic activity, causing osteoporosis in addition to a variety of lipid infiltrations in parenchymal organs including the liver. New bone formation is especially seen at the insertion sides of the tendons of the main muscles, and at the origin of ligament and joint capsules. Periarticular pull-out forces in the osteoporotic bone may induce this new bone formation, which is similar to callus formation, eventually leading to ankylosis. In adult cats the stiff neck and/or larger joints of front or rear legs, dull haircoat, hyper- or hyposensitivity of the skin, impingement of nerves causing function loss, as well as anorexia and weight loss may be noticed. When both shoulder or elbow joint reveal ankylosis, the cat may unload both front legs in a sitting position. When ankylosis of the cervical area occurs, the animal is unable to wash and groom itself. The diagnosis can be made on radiographs of the cervical or thoracal vertebrae and the large joints of the legs: new bone formation without bone loss, leading to ankylosis of vertebrae (at the dorsal or ventral side) and of the joints. Although vitamin A is quit thermolabile and will be destroyed above 70°C, cooking of the liver will destroy most but nor all of its vitamin A. From studies in larger groups of patients it revealed that prognosis improves when, after the diagnosis was made, the diet of the animal was changed completely. Corticosteroids may releave some nerve pain, but can hinder a decrease in plasma vitamin A concentration. Clinical and even radiological improvement is seen. Ankylotic joints will not regain their normal motion, but with drastic change in diet, supportive analgetics when needed and time to heal, a dramatic improvement can be expected. Improvement can be seen 2-4 weeks after the start of the therapy.

Inflammation related 1. Hypertrophic osteodystrophy. Hypertrophic osteodystrophy (HOD) is also known under the synonyms of metaphyseal osteopathy, metaphyseal dysplasia, osteodystrophy and, misleadingly, canine scurvy and Müller-Barlow disease. Although first described in the early thirties, its etiology is still not elucidated completely. It was long hypothesized that hypovitaminosis C, causing inferior collagen formation in bone and blood vessels in primates and guinea pigs, was the cause of HOD in dogs. This has not proven to be the case. Other dietacly factors, including copper deficiency, overfeeding and oversupplementation with minerals, are also proposed as causes, but become less likely. HOD is seen in more than one dog of a litter which does not exclude an inherited factor, but does not exclude environmental factors, either. Recently Mee et al.8 have demonstrated that RNA and mRNA of canine distemper virus were present in osteoblasts, osteocytes and bone marrow cells of dogs infected with this virus. Osteoblasts and osteoclasts within the affected metaphyses of dogs with HOD also contained the virus. These findings all support the finding of Grøndalen that blood of dogs with HOD caused clinical CDV infection in recipient dogs.

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HOD is only seen in young dogs, especially of the larger (fast growing) breeds. Dogs can be depressed, have anorexia, be painful during walking or even unable to stand. Metaphyseal areas, especially of the distal radius and ulna, are swollen. Rectal temperature can be above 40°C. Littermates may also be affected. Often an episode of respiratory or gastrointestinal disease preceded this disease, and the animal may be vaccinated recently against CDV. Radiographic findings are pathognomonic for HOD and include an irregular radiolucent line in the metaphyseal area parallel to the growth plate but a few millimeters away from it. In subacute cases new bone formation, originating from the periosteum in the diaphyseal-metaphyseal area becomes noticeable. In very severe cases, probably when the patient is not kept extremely quit during the period of the disconnection in the metaphyseal area, these bony cuffs can become very massive. Not only in the distal radius ulna and distal tibia, but at almost all metaphyseal area, new bone formation becomes visible. In chronic cases this cuff will be attached to the bone and will either be removed or partially remodeled by osteoclastic activity. The therapy includes good nursing and analgesics on effect. Either the animal will die due to (pain/viremia) shock or will clinically improve within 3-6 weeks. In some dogs the periosteal new bone formation will be remodelled and not noticeable at older age. 2. Osteochondroma Osteochondroma is a benign, solitary or multiple new bone formation arising from cartilage and found to be attached to any bone that develops from cartilage. In dogs, an osteochondroma is growing when the animal grows and is seen predominantly in tibia and femur and vertebrae of large breed dogs. In cats, osteochondroma appear at mature age (>2 years) without predisposition for the bones or the breeds involved, but may be positive for feline leukemia virus (Pool, 1993). Lameness develops especially in case of mechanical hindrance or nerve impingement. The osteochondroma in dogs stops growing when the animal is mature. When indicated, the cartilage cap should be removed together with the new bone formation with good prognosis. In cats, the prognosis is much poorer since the new bone formation might grow autonomously, multiple tumors can be present and the primary viral infection can be fatal9.

Tumor related 1. Hypertrophic osteopathy This fascinating disease was first described by Marie (in 1890) and Bamberger (in 1891), and is also known as hyperplastic osteoperiostitis, hypertrophic (pulmonary) osteoarthropathy. The disease is characterized by bilaterally, symmetrically periosteal new bone formation. It often, but not always, starts at the distal bone ends and looks like oedematous swelling of the feet. However on palpation it is hard and not very painful upon deep palpation. Historically, in human patients this new bone formation was most often seen in combination with, or as a result of, a space occupying process in the thoracic cavity like tuberculosis. In dogs it is described in combination with (primary or secondary) pul-

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monary neoplasia, or abscesses and granulomata, however also together with esophageal granulomas or neoplasias, intra-abdominal neoplasia including liver tumour, bladder tumour or pyometra. The disease is more often seen in middle aged (>8 years), larger breed dogs, with a an over-representation of females10. Lameness and unwillingness to walk are the predominant complains. The typical radiological appearance includes spicules of periosteal newly formed bone perpendicular to the cortex starting at the distal end of the legs (i.e., the metacarpal/tarsal bones) and climbing up proximally including carpal bones, radius-ulna, humerus and scapula as well as tarsal bones, tibia, femur and pelvis. Ribs and vertebrae are less commonly and the skull is never affected. There is no endosteal new bone formation although superposition may suggest this. In less typical cases the periosteal bone formation is at the proximal end of the legs, more smooth and regular. Spicules are not formed in joint spaces, although joint effusion and inflamed synovial tissue may be present. The occurrence of the periosteal new bone formation is explained by increased peripheral blood flow. Regression of the newly formed bone is seen after thoracotomy, after removal of the space occupying process and after a variety of dissections (including vagotomy). The latter indicates a nervous involvement. In literature it is described that first clinical improvement is seen within a month, whereas radiologically regression takes much longer10. Most cases with diagnosed hypertrophic osteopathy have a bad prognosis and will not reach this stage. 2. Medullary bone infarction This is a diseases which is characterized by lameness since 3-20 weeks, pain upon deep palpation and radiologically irregularly demarcated areas of radiopacity in the medullary cavities. It is often seen bilateral in both front and hind limbs, often but not always in conjunction with primary bone tumors (osteosarcoma or fibrosarcoma). Osteosarcomas are in almost all cases solitary and are seen in middleaged, medium-large breed dogs. However, in the here described disease osteosarcomas are most often seen in multiple locations and in Miniature Schnauzers or other smaller sized dogs. Histologically, intramedullary vessels (but no other vessels in the body) are occluded by deposition of abnormal collagen in the vessel walls. The radiopaque lesions

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correspond with abnormal proliferative osteoid on the endosteal bone surface, and bone necrosis in severe cases. The changes can be explained by the occlusion of the nutrient arteries11.

Key words Developmental bone diseases, orthopedics, excessive calcium intake, hypervitaminosis A, panosteitis, bony spur, hypertrophic osteodystrophy, hypertrophic osteopathy, osteopetrosis, medullary bone infarction, craniomandibular osteopathy, osteochondroma.

Literature 1.

5. 6.

10. 11.

Riser WH, (1993) Canine craniomandibular osteopathy Ch 123 in: Disease mechanisms in small animal surgery 2nd ed. Bojrab MJ (ed) Lea & Febiger, Philadelphia pp. 892-899. Woodard JC, Riser WH Hyperostosis and osteopenia Ch 122 in: Disease mechanisms in small animal surgery 2nd ed. Bojrab MJ (ed) Lea & Febiger, Philadelphia pp. 879-891. Voorhout G, Nap RC, Hazewinkel HAW (1993) The development of the antebrachium in Great Dane pups, raised under standardized conditions, a radiographic study. Journal of Veterinary Radiology & Ultrasound 35, 271-276, 1994. Hazewinkel HAW, Goedegebuure SA, Poulos PW, Wolvekamp WThC (1985) Influences of chronic calcium excess on the skeletal development of growing Great Danes JAAHA 21: 377-391. National Research Council (1974), Nutrient requirements of dogs, National academy press, Washington DC. Hazewinkel HAW (1993) Nutrition in orthopedics Ch 149 in: Disease mechanisms in small animal surgery 2nd ed. Bojrab MJ (ed) Lea & Febiger, Philadelphia pp. 1119-1128. Hazewinkel HAW, (1992) Skeletal disease Ch 22 in: The Waltham book of Clinical Nutrition of the dog and cat, Wills JM and Simpson KW eds Pergamon, Oxford, pp. 395-423. Mee AP, Gordon MT, May C, Bennett D, Anderson DC, Sharpe PT (1993) Canine distemper virus transcripts detected in the bone cells of dogs with metaphyseal osteopathy. Bone 14(1):59-67. Pool RR (1993) Osteochondromatosis Ch 116 in: Disease mechanisms in small animal surgery 2nd ed. Bojrab MJ (ed) Lea & Febiger, Philadelphia pp. 821-833. Brodey RS Hypertrophic osteoarthropathy in the dog, a clinicopathologic survey of 60 cases. JAVMA 159: 1242-1250, 1971. Dubielzig RR, Biery DN Brodey RS (1981) Bone sarcomas associated with multifocal bone infarction in dogs JAVMA 179: 64-69.

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The role of nutrition in orthopedic diseases Herman A.W. Hazewinkel

Summary

Clinical and radiological examination

This seminar will focus on a variety of diseases which are more or less of clinical importance, but in all cases important for the every-day practice, since owners ask often advise about the influence of nutrition on skeletal development. For that reason and as differential diagnosis both hypovitaminosis D and low calcium intake are discussed. In addition the harm of excessive food and calcium intake is extensively presented.

The young animal will be raised on an unbalanced food, especially meat or by-products, which are extremely low in calcium content. This etiology explains the synonym of this metabolic bone disease: all meat syndrom. Also food of poor quality, binding calcium to phytate, may cause a chronic calcium deficiency especially in young dogs of large breeds. The animal will reveal a reluctance to stand and walk, abnormal bowing of the long bones and protuberances (i.e. calcaneus, olecranon, tuber ischium) or will even be paralyzed due to spinal compression by pathological fractured vertebrae. The animal will be in good health, but is not willing or unable to stand and walk. Bowed legs, bowed protuberances, kyphosis, pain upon skeleton palpation may be obvious. Blood investigation will not reveal typical abnormalities except for sophisticated determinations (i.e. elevated PTH and calcitriol levels) which will both cost a lot of money and time. Radiography may reveal thin cortices, wide medullary cavities, folding fractures, bowing of protuberances by muscle pull, normal hight of growth plates boarded by relatively white metaphyseal areas and compression fractures of cancellous bone of epiphyses and vertebrae. Biopsies will reveal normal mineralization but increased resorption and thus a thin cortex and thin cancellous bone spiculae.

Introduction Preventing skeletal abnormalities to occur, the dog should not have the potential to develop unwanted skeletal abnormalities (which is a breeding responsibility), should be protected from trauma (the responsibility of the new owners) and should have a proper nutrition. Aspects related to the latter are discussed here, to prevent a variety of skeletal abnormalities to develop.

I. Alimentary hyperparathyroidism In case there is an insufficient calcium intake or absorption during a long period, parathyroid hormone (PTH) will be increased synthesized and secreted. PTH has mainly three actions i.e., increase osteoclastic activity (deliberate calcium and phosphorus from the skeleton), increase calcitriol synthesis in the kidney out of 25 hydroxy vitamin D (and thus increase calcium and phosphorus absorption in the intestine and decrease phosphorus reabsorption in the renal tubuli (and thus cause a hyperphosphaturia). Hyperparathyroidism will normalize the calcium concentration in the extracellular fluid, allowing a variety of extra- and intracellular processes which are of vital importance (blood clothing, nerve action, muscle contraction) to take place. When the increase in absorption of calcium in the intestine is not sufficient for the daily requirements, which is higher in fast growing animals (especially of large breeds), than the only source of calcium is the skeleton. The cortex will be resorbed at its endosteal surface. Cartilage mineralization and endochondral ossification (i.e., the process of new bone formation in the metaphyseal area bordering the growth plates) will be undisturbed.

Differential diagnosis Calcium deficiency can be complicated with vitamin D deficiency when solely lean meat (which is low in calcium and vitamin D) is fed. Especially bone diseases due to an inborn error may resemble alimentary hyperparathyroidism including osteogenesis imperfecta, mucopolysaccharidose and other rare diseases.

Therapy It is extremely important to carry the animal and give it strict cage rest to prevent more pathological fractures (especially of the vertebrae) to occur. No bandages or splints can be applied since the bone just proximal to the end of the splint cannot carry the weight of the leg and will fracture. The skeleton is to bridle for osteosynthesis at this stage.

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DVM, PhD, Dipl ECVS Dept. Clinical Sciences of Companion Animals Faculty of Veterinary Medicine - Utrecht University - The Netherlands

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Analgesics will facilitate early mobility which is not desirable. A normalization of the diet with a calcium content up to 1.1% on a dry matter basis will allow the skeleton to mineralize within 3-4 weeks, since a calcium absorption of almost 100% will take place due to the hyperparathyroid induced high calcitriol activity. An extra amount of calcium as calcium carbonate or calcium lactate (and not calcium phosphate or bone meal) at 50 mg Ca/kg body weight might even accelerate osteoid mineralization. Corrective osteotomies can be planned, when needed, after the skeleton is normally mineralized. Even compression fractures of the spinal cord may lead to full recovery.

II. Rickets Pathogenesis Hypovitaminosis D in young animals is known as rickets, whereas in adults it is called osteomalacia. Vitamin D is absorbed by the intestine as one of the fat soluble vitamins and transported to, and hydroxylated in the liver to 25 hydroxy-vitamin D. It is proven now that dogs and cats are not able to synthesize vitamin D in their skin under the influence of sunlight, unlike many other species including man. A second hydroxylation takes place in the kidney, either to 24,25 dihydroxy-vitamin D or to 1,25 dihydroxy vitamin D. The latter, also known as calcitriol, is the active metabolite which acts in the intestine to stimulate active absorption of calcium (in the proximal intestine) and phosphorus (in the distal intestine). A similar action of calcitriol takes care of an increased reabsorption of calcium and phosphorus from the pre-urine in the renal tubular cells. In addition, vitamin D is necessary for osteoid and cartilage mineralization and thus routes calcium and phosphorus from intestine and kidneys to the bone. The absorption and first hydroxylation of vitamin D is loosely controlled, whereas the hydroxylation into calcitriol is directly and indirectly influenced by serum calcium and phosphorus concentration parathyroid hormone and increased mineral need during growth, reproduction and lactation. When food deficient with vitamin D is fed at an early age, the kitten or puppy will first metabolize the vitamin D from maternal origin (placenta and milk) and will then develop hypovitaminosis. When food highly supplemented with calcium will be fed to young puppies, a hypoparathyroidism will develop with as a result a shut down of calcitriol synthesis. Despite the high calcium and normal vitamin D content of the food, the animal will develop the clinical signs of rickets. These are especially demonstrated by the low mineralization of newly formed osteoid (ground substance formed by osteoblasts) and cartilage (formed by chondroblasts). Since osteoclasts and chondroclasts are only capable of removal of mineralized bone and cartilage, a thickening of the flared area of the bone (metaphyses) occurs. Hypovitaminosis D in adult animals may take place more often than rickets is seen, but does not coincide with obvious clinical signs. It might play a role in chronic renal insufficiency.

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Clinical and radiological examination An unbalanced food (either low in animal fat or enriched with calcium salts) is fed from an early age onwards. The animal has a reluctancy to walk and stand, but is otherwise healthy. On inspection and palpation of the appendicular skeleton bowed legs, bulging metaphyseal areas, painful and even fractured long bones, deformed vertebrae and pelvis bones can be noticed. Radiographs of radius and ulna will demonstrate the thin cortex, bowed and even fractured diaphysis, extremely thickened growth plates. Plasma concentrations of calcium can be normal or low-normal due to hyperparathyroidism. This might also cause a hypophoshatemia together with a hyperphosphaturia (see â&#x20AC;&#x2DC;hyperparathyroidismâ&#x20AC;&#x2122;), Determination of vitamin D and its metabolites is both very specialized and extremely expensive. A decreased level of 25-hydroxy vitamin D will indicate dietary deficiency, whereas normal 25- but low 1,25 metabolite indicates hypoparathyroidism or renal disease. A bone biopsy of cancellous bone and growth plate, for example a core biopsy of the greater trochantor, will reveal a poor mineralization of osteoid, large number of osteoclasts and enlarged columns of cartilage cells in the growth plate.

Treatment First the food will be changed to a commercial dog or cat food of one of the mayor brands, known to contain sufficient vitamin D to cure and prevent rickets (Hazewinkel, 1989). After 3 weeks the patient should be radiographically evaluated: in case of dietary hypovitaminosis D a dramatic improvement will be noticed (i.e, mineralization of cortex, callus and growth plates). Only when not responding on diet change and the diagnosis is certain, either after bone histological examination or determination of the major vitamin D metabolites (i.e. 25, and 1,25 metabolites) extra vitamin D can be recommended. Vitamin D injections carry the risk of over supplementation, causing hypercalcemia and hyperphosphatemia with mineralization of soft tissues, heart valves and kidneys and consequently the animals death.

III. Over nutrition The excessive intake of energy can be harmful for young growing dogs with a cartilaginous skeleton, as well as for adult dogs with arthrotic joints. The increased intake of minerals has especially negative effects on skeletal development since the absorption process is less well regulated in young than in adult dogs. This chapter will focus on the orthopedic effects of overnutrition in young dogs.

Pathophysiology Cartilage surrounding secondary ossification centers, i.e, the growth plate is organized in a structured way, starting with a reserve zone and ending with the lost of chondrocytes

in the hypertrophic zone. The thickness of the growth plates parallels growth velocity. Growth plate growth and closure depend on age, breed, location, as well as on humoral and nutritional factors. Over nutrition, as well as high calcium intake, have been proven to be in a variety of standardized and epidemiological studies, important in the etiology of osteochondrosis. Osteochondrosis is a disturbance in the process of endochondral ossification of growth plates as well as of joint cartilage. The latter will become clinical evident in case fissure lines cause a cartilage flap, i.e., osteochondritis dissecans. In addition, excessive energy intake (either as excessive carbohydrates, fat or proteins) may cause an increase in body weight and thus an overloading of deformable parts of joints, expecially of incongruent joints including the cartilaginous acetabular rim in case of hip dysplasia, and of coronoid process in case of too short radius (as in Bernese Mountain Dogs).

Clinical and radiological examination Osteochondrosis is more often seen in males and faster growing females during the fastest growth phase of large (i.e., fast growing) breeds. The daily ration in these circumstances has great demands on quality and quantity. Not relative but absolute amounts intake per kg body weight (or per kg metabolic body weight) have to be taken into account. Large amounts of calcium (with of without phosphorus) with restricted feeding is as harmful as large amounts of balanced food with as a result the same amount of calcium intake. One or both front and/or rear legs can be affected in the major joints and/or distal growth plates. Inspection of the front and rear legs may demonstrate valgus deformation. Inspection and palpation of elbow, stifle and tibio-tarsal joints may demonstrate overfilling. Hyperextension or -flexion of these joints and/or of the shoulder joints (which are not palpable for effluation) may cause pain reaction in case of osteochondritis dissecans. Radiographs of growth plates (especially of the fast growing distal ulna) may reveal retained cartilage cones. Radiographs of shoulder, elbow, stifle or tibio-tarsal joints may reveal an abnormality in the alignment at the predilection sides for osteochondrosis. Other imaging techniques including arthroscopy may support the diagnosis.

Treatment Young dogs of large breeds should be raised with limited amounts of food, preferably a food of good quality and containing ingredients according to the requirements of growing dogs. Overfeeding and over supplementation must be avoided. The protein and mineral content of good commercial adult dog food is sufficient for raising large breed dogs. In case of valgus deviation and thickening of cartilage without detaching, a prompt correction of food intake may support the healing process. Radius curvus syndrom or osteochondritis dissecans demand surgical intervention.

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In osteochondrosis, maturation of the cartilage cells and its intercellular substance does not allow mineralization to occur. Therefore the cascade of events, including chondrocyte death, capillary ingrowth, osteoblast introduction and bone formation, will not take place. This causes elongated cartilage columns in articular cartilage as well as in growth plate cartilage. The disturbance in endochondral ossification can occur in articular cartilage with osteochondritis dissecans as a consequence. In osteochondritis dissecans a part of the articular cartilage is detached and may be fragmented, mineralized or even ossified together with inflammation of the joint and the endochondral bone in the area of the cartilage lesion. The disturbance in endochondral ossification can also occur in growth plate cartilage, with irregular growth plates and even large cartilage cores and decreased growth in length as a consequence. In addition, the disturbance in endochondral ossification can be manifest in a delay in ossification of the secondary ossification centers. Osteochondrosis is a multi factorial disease in which inheritance and nutrition play a significant role. The disease is frequently seen in a variety of breeds. There is a prevalence for location of osteochondrosis in each breed affected with this disease, although multiple affected animals are frequently seen. Although histologically osteochondrosis can be diagnosed also in non-weight bearing growth plates like that of the rib, micro trauma may play a significant role in causing the fissures as can be concluded from the fact that osteochondrosis dissecans is mostly seen on convex, weight bearing areas. Disturbances in growth plates leading to clinical manifestation including bilateral radius curvus syndrome or rear leg exorotation are especially seen in giant breed dogs. Also the detachment of the anconeal process of the ulna or the supraglenoid process of the scapula can be seen in this respect. Since osteochondrosis is so frequently seen in large breed dogs, a variety of studies are performed in different institutes to elucidate the role of nutrition in the manifestation of osteochondrosis. The original study was performed by Hedhammer et al., (1974) on 12 pairs of Great Danes raised on food rich in protein, calcium, phosphorus and energy. More frequently, skeletal diseases including osteochondrosis and delayed skeletal modeling where seen in the dogs fed this formula ad libitum, whereas the restricted (i.e., 2/3 of the amount of the ad lib. group) fed dogs revealed less severe signs. This opened a whole series of investigations performed by others. Overload, by over nutrition of a basal food enriched with rice or just by suggesting high body weight by sand belts in the scapular region did aggravate the signs of osteochondrosis (Meyer, 1991). In a controlled study in Great Danes with high food intake of more balance commercial foods, the ad libitum fed dogs revealed more frequent osteochondrosis of the shoulder compared to the dogs fed 60% of the ad libitum amount (Lavelle, 1986). In a recent published study, performed in Great Danes raised on food only high in protein, no differences in occurrence nor severity of osteochondrosis occurred when compared with the normal or low protein fed dogs (Nap, 1991). In studies in Great Danes where the food only differed in its calcium content (with or without a constant ratio to phosphorus) more and more severe disturbances of osteo-

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chondrosis were seen in the proximal humerus as well as in growth plates of long bones and of non-weight bearing (i.e., ribs) areas (Hazewinkel, 1985). This leads to the practical conclusion that chronic intake of food rich or enriched in calcium, with or without high phosphorus, protein or energy content, plays a significant role in the development and manifestation of osteochondrosis in dogs of large breeds. It was demonstrated in a study in miniature poodles, raised on a food with high calcium content that minor changes of enchondral ossification occurred. Different research groups investigated the influence of nutrition on the manifestation of osteochondrosis. Ad libitum intake of food (rich in Ca) and high Ca intake alone augmented the signs of osteochondrosis. Increased body weight (by adding of rise) but not high protein intake revealed the same. (*calculated from list of contents). In addition, enforced growth in body weight as well as in height due to ad libitum food intake of food rich in calcium (Hedhammer â&#x20AC;&#x2122;74, Meyer â&#x20AC;&#x2122;92, Lavelle â&#x20AC;&#x2122;87) coincide with more frequent signs of osteochondrosis in the dogs studied. In the study of Hazewinkel the dogs had a high calcium, but not a high caloric intake but revealed severe osteochondrosis. In young dogs, calcium is absorbed in the intestine by means of both uncontrolled passive diffusion and active, controlled absorption. It has been demonstrated that Great Danes raised on a food according to the Nutrient Requirements (i.e., 1.1% Ca) absorbed 45-60% of the ingested amount of Ca, whereas dogs with triple that amount of Ca in their diet, absorbed 23-43%. As a result the dogs with the high Ca containing diet, absorbed considerably higher amounts. Intake of food, and especially of Ca, causes the release of gastrointestinal hormones, some of which will cause calcitonin (CT) release from the thyroid glands. The increased CT concentration prevents calcium release from the skeleton by influencing the bone resorbing osteoclasts. The calcium absorbed, will routed to the skeleton without prandially influencing the concentration of calcium in the extracellular fluid. In the fasting periods and periods in between meals, this loosely deposited calcium is freed and used for a variety of life saving processes. The series of studies in Great Danes have demonstrated that daily food intake of a diet rich in calcium leads to hyperplasia of CT producing cells, a reduced osteoclastic activity and a disturbed enchondral ossification (Nunez, 1975, Hazewinkel, 1985). Although it is not fully understood if calcium plays a direct role in disturbing chondrocyte maturation, or is mediated by CT and/or a relative deficiency of other minerals at a cellular level, there is little doubt on the deleterious effect of high Ca intake on enchondral ossification, with osteochondrosis as a consequence.

Diagnosis In case of osteochondrosis of articular cartilage, without detachment of cartilage, no specific complains will be expected. In case cartilage becomes detached, i.e., osteochondritis dissecans, than osteoarthrosis and inflammation of the subchondral bone will occur. Therefore osteochondritis dissecans coincides with lameness, pain reaction up-

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on (hyper)extension and flexion of the affected joint, joint effusion and subchondral sclerosis boarding an indentation of the articular surface visible on radiographs. In addition, a variety of diagnostic methods (including paracentesis, arthroscopy and other imaging techniques) can be employed. Measurement of circulating concentrations of calcium or phosphorus will not give a good insight in the dietary contents or absorption rate of these elements. It will not give any indication to support the diagnosis of osteochondrosis. This is based on the fact that plasma Ca concentration is very well kept between limits and phosphorus is related with the calcium homeostasis, although its level is more reflected by its intake. Alkaline phosphatase will be increased in case of high calcium deposition into the skeleton, but will be high in all young animals during the period of rapid growth. Ca regulating hormones, i.e., parathyroid hormone (PTH), calcitonin (CT) and vitamin D, can only be determined in very specialized laboratories and will only give insight when measured repeatedly. In summary, blood investigation will not be of great value to support the diagnosis in the acute phase of osteochondrosis development. In case of clinical suspected osteochondritis dissecans, a thorough clinical and radiological investigation will suffice in most cases, with additional techniques required in some. In case of osteochondrosis of growth plates, no special complains will be expected when the cartilage core is small and/or temporarily. In longitudinal radiological studies of the distal growth plate of the ulna of Great Danes a slight flattening or indentation were seen at the age of five months. From clinical experience it can be stated that most of these slight abnormalities will not cause clinical disturbances. When a severe flattening of the metaphyseal area develops, or a deep cartilage core can be seen, an impaired growth in length of the radius and ulna can be expected. The short ulna, the curved radius together with the valgus deformation of the feet complete the radius curvus syndrome.

Prognosis Osteochondrosis in articular cartilage will not develop into osteochondritis dissecans in all cases. Based on controlled studies where both shoulder joints were radiographed, it can be concluded that, although 45-65% of the dogs had disturbed radiological detectable abnormal contours of the humeral head, only 3-5% was clinically affected on both sides. When detached, the period of lameness can be shortened as well as most probable the secondary changes of the joint minimized with surgical treatment (Van Bree, 1992). In case of the radius curvus syndrome, severe shortening of the ulna may cause the irreversible abnormal development of the carpus and/or the detachment of the anconeal process. The latter is only possible when the longer radius pushes the humerus against the still incomplete ossified anconeal process.

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Based on skeletal diseases induced by calcium or vitamin D deficiencies, dog owners and some dog food manufacturers tend to oversupplement the daily ration with calcium, with or without a proportional increase of the phosphate content. In young dogs, a high calcium intake causes a high calcium absorption causing a hypoparathyroidism and a hypercalcitominism and thus a decreased osteoclastic activity. This causes a routing of calcium to the skeleton where it is stored to be used later. Chronic calcium excess causes a chronic decreased osteoclast activity. In growing dogs however, osteoclast play an important role in skeletal maturation in adapting the skeleton to new demands.

Anatomy & physiology Especially in immature dogs, there is a large blood supply of the metaphyseal area, bordering the growth plates. These network of arteriolae receive blood from branches of the periosteal side (i.e. the epiphyseo metaphyseal arcade) and the medullary arteries. The latter enter the bone mainly in the foramen nutritium. The direction of efferent blood flow is through the diaphyseal cortex, centrifugal from medulla to periosteum, and run through rigid bone canals including Volkmannâ&#x20AC;&#x2122;s canals. These course transversely through the cortex, connecting adjacent traversian systems and provide intercommunication between medullar and periosted vessels.

Ethiology Chronic calcium excess in young dogs causes an increased calcium accretion and a decreased skeletal remodeling including a decreased adaptation to soft tissue growth. Blood vessels centrifugally running through the diaphyseal cortex do not expend proportional with blood vessel growth, This will result in oedema formation inside the medullary cavity with ultimately new bone formation on the fibrous tissue formed. Increased pressure and finally new bone formation is first seen near the foramen nutritium. Oedema may be accumulate underneath the periosteum and thus make periosteum more vulnerable for pressure and pull and may cuase extra lamellar bone formation. Degeneration of cytoplasm of adipose bone marrow may prelude the sequence of events, being either primary of secundary. Panosteitis is seen in different studies in Great Danes with high calcium intake. So far no other ethiologies are demonstrated but cannot be ruled out.

Clinical and radiological examination The disease is mainly seen in medium-sized and large-breed dogs, starting at 6 months of age and characterized by a sudden onset of shifting lameness. The lameness is seen in different legs, will become increasingly severe in several days and can disappear for regress for some time. Dogs may receive dog food supplemented or rich with calcium. Clinical investigation reveals pain reaction upon deep palpation of several long bones especially the lateral-proximal ulna, distal humerus and mid tibia. An increased body temperature may be present. Blood investigation or culture of blood or bone are negative. Radiographs demonstrate a blurring of the trabecular pattern in the metaphyseal area (especially the proximal ulna and eventually white areas starting near the foramen nutritium and expending throughout the medullary cavity. In some cases and with special radiographic technique a well-defined subperiosteal cortical thickening can be noticed.

Therapy Since the disease is self limiting and is not diagnosed in dogs over 22 months of age the treatment is limited to supportive therapy and nursing of the dogs. Analgesics can relief pain sufficiently for an episode. The owner should be warned that other episodes will follow. When the dog is mature and other skeletal diseases, especially joint pathology, is ruled out, corticosteroids at a initial dose of 1 mg/kg body weight can be prescribed. Dietary corrections includes a decrease in the amount of calcium and vitamins to the minimal requirements for dogs. A calcium-deficient diet for a limited period to increase osteoclastic activity can be advocated and thus may be considered, although is not proven to be beneficial yet.

Key words Developmental bone diseases, orthopedics, excessive calcium intake, panosteitis, osteochondritis dissecans, all meat syndrome, hyperparathyroidism, hypercalcitoninism, overnutrition, panosteitis.

Literature Hazewinkel HAW (1993) Nutrition in orthopedics Ch 149 in: Disease mechanisms in small animal surgery Lea & Febiger, London, pp. 1119-1128. Hazewinkel HAW, Schoenmakers I (1995) Influence of protein, minerals and vitamin D on skeletal development of dogs Veterinary Clinical Nutrition 2, 93-99.

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Panosteitis (= enostosis = eosinophilic panosteitis)

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Elbow dysplasia Herman A.W. Hazewinkel

Summary Practicing veterinarians are increasingly confronted with young dogs suffering from front leg lameness due to developmental diseases. Screening in different countries demonstrated that large percentages of different breeds including German Shepherd, Labrador, Rottweiler, and Bernese Mountain Dog, suffer from different developmental diseases of the elbow joint all resulting in osteoarthrosis of this joint. These diseases include ununited anconeal process (UAP), fragmented coronoid process (FCP), osteochondritis dissecans (OCD), and elbow incongruity (INC), grouped together under the name of â&#x20AC;&#x153;elbow dysplasiaâ&#x20AC;? (ED) which makes it easier to understand by dog breeders and owners. Here will be discussed the clinical and radiological protocols for diagnosis of UAP, FCP, OCD, and INC; their surgical approaches and, new information on measurements to prevent the occurrence of ED in different breeds.

Introduction Elbow dysplasia (ED) is recognized by veterinarians and breeders as a serious problem for certain populations. Depending on the specific sub-population and the method of investigation, elbow dysplasia is seen in 46-50% of the Rottweilers, 36-70% of the Bernese Mountain Dogs, 12-14% of the Labradors, 20% of the Golden Retrievers, 30% of the Newfoundlanders, and 18-21% of the German Shepherds1 but also in Great Danes, St Bernards, Irish Wolfshoud, Great Pyrenees, Bloodhounds, Bouviers, Chow chows and chondrodystrophic breeds2,3. ED can be separated into different disease entities including ununited anconeal process (UAP), fragmented coronoid process (FCP), osteochondritis dissecans (OCD) of the medial humeral condyle and incongruities of the elbow joint (INC). From recent studies it became clear that OCD and FCP, and also INC and FCP are diseases with a different hereditary background. They should be considered as different diseases, all causing lameness and osteoarthrosis. The success rate of surgical treatment of elbow dysplasia depends on the complete diagnosis before surgery, the correct surgical positioning and on atraumatic surgical approach as well as the careful aftercare by the owner. Here the following topics will be discussed: 1) the clinical and radiological protocols for diagnosis of UAP, FCP and OCD, 2) the later-

al approach to the elbow joint for the removal of the UAP and ulnectomy for fusion of the anconeal process 3) the medial approach to the elbow joint for removal of FCP and OCD, and 4) new information on measurements to prevent the occurrence of ED.

Clinical and radiological investigation The clinical investigation starts with registration of the breed and age of the dog (lameness starts at 4-10 months of age) and inspection of the dog in standing position; in almost 50% of the cases the paw of the affected leg is externally rotated and slightly abducted. On palpation, the elbow is effused. Effusion is usually most pronounced in case of UAP than in FCP or OCD. Effusion of the elbow joint is felt at the side of the anconeal muscle. With the dog in lateral recumbency, the range of motion (ROM) of the elbow joint is examined while the thumb is placed on the anconeal muscle to register crepitation; attention is payed when pain is evoked. In case of a UAP, there is in particular crepitation and pain sensation at a firm hyperextension of the elbow joint. In case of FCP and/or OCD, crepitation and pain reaction can be evoked at prolonged hyperextension, in particular when the radius and ulna are exorotated at the same time. Diagnosis of ED can be confirmed by radiography. Bony union between the anconeal process and the olecranon should be complete at the age of 16-20 weeks3. When a radiolucent area is present at an older age it is suggestive of an anconeal process which is not bony united, i.e., an UAP, due to a partial or complete separation in the cartilage between anconeal process and olecranon. On a mediolateral flexed (MLflexed) view there is no superposition of the humeral condyles over the fusion area between anconeal process and olecranon, therefore this is the preferred view. Sclerosis at the fracture site and osteophytes at the margins of the joint can be visible at a later stage. OCD of the medial humeral condyle is best assessed on anterior posterior medial oblique (APMO) views, whereas on anteriorposterior (AP) views one third of the cases will be missed4. Is a small amount of the cases a carcified flap can be seen located near the indentation of the contour of the medial condyle. For screening elbow joints on the presence of a FCP a variety of views is advocated, including the AP, APMO, MLflexed, MLextended and the ML view with the joint extended plus the exorotation of radius-ulna 15 de-

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DVM, PhD, Dipl ECVS Dept. Clinical Sciences of Companion Animals Faculty of Veterinary Medicine - Utrecht University - The Netherlands

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grees4. In a survey, we studied the value and additional value of each of the first four mentioned views, using the complete set of four views as a golden standard. We demonstrated that the MLflexed and the APMO views had a limited value as a sole view, but their great value as an additional view. False negatives of almost 20% when only a MLflexed view is used in a screening program for FCP, may explain the difference in percentage of positive Bernese Mountain Dogs between countries5,6. In addition, osteophytes and sclerosis of the semilunar notch are taken into account for making the diagnosis. Small osteophytes are especially visible on a combination of at least 3 or 4 of the mentioned views. UAP and FCP occurs bilaterally in 30% and more than 50% of the cases, respectively, and therefore both elbow joints should be investigated, even in case of unilateral lameness. In case there are no radiographic abnormalities visibly, auxiliary techniques (computed tomography, bone scintigraphy, arthroscopy) may be of value. The correlation between radiographic signs of elbow dysplasia and clinical signs depends on the physical demands (working dogs vs. companion animals), the severity of the lesions (FCP plus incongruity is more severe than LPC or incongruity alone, low grade arthrosis does not necessarily goes together with lameness), the age of onset of complaints (lameness at young age is more severe), and breed. The clinical signs due to a comparable coronoid lesion in Retrievers are more severe than in Rottweilers. Read et al (1997) reported that 57% of a group of 55 Rottweilers in a prospective study developed radiographic signs of FCP but â&#x20AC;&#x153;onlyâ&#x20AC;?15% showed physical signs including joint effusion, pain and crepitation during examination and 10% developed lameness7.

Therapy 1. Ununited anconeal process (UAP) Excision The anesthetized dog, is positioned in lateral recumbency with the lateral side of the affected elbow joint upwards. An imaginary line is drawn between the lateral epicondyle and the cranial aspect of the olecranon, just cranial of the insertion of the triceps muscle, and the distance is divided in 3 equal parts8. The incision is made between the first and second part counting from cranial trough the skin, the subcutis, the fascia of the anconeal muscle and the anconeal muscle itself. Care is taken not to undermine the skin. The elbow joint is flexed and with a blunt forceps the anconeal process is freed from the supratrochlear foramen, and with a pointed bone forceps it is fixed and removed. Particularly in more chronic cases the UAP may have migrated to the proximal portion of the joint. The soft tissue attachment is cut in order to remove the anconeal process completely. The joint is inspected for free bodies, the fracture line may be curetted and the joint is flushed with saline. Fascia and muscle are closed with interrupted resorbable sutures, the subcutis is closed carefully without leaving dead spaces which may develop into a seroma. The skin is closed routinely. An elastic ban-

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dage is applied for 3 days starting at the toes and including the elbow joint. Activity is restricted for 3 weeks, thereafter leash activity is allowed for 3 weeks. When necessary, the other elbow may be operated after 6 weeks. Arthrosis formation will continue to develop but probably slower than when an irritating ununited anconeal process remains in place9.

Reattach Especially in case of a partial separation of the anconeal process due to elbow incongruity (see the other contribution in this proceedings), an osteotomy of the ulna (ulnotomy) can be performed to allow the anconeal process to reattach. The spontaneous restoration of elbow congruity after ulnotomy may be expected in dogs under 12 months of age, since at an older age the interosseus muscle becomes to be to firm thus preventing the ulna to shift proximally. The dog is in lateral recumbency with the affected elbow facing upwards and the hairs have been shaved from proximal of the elbow joint till half way the length of the ulna. The skin and muscle fascia are incised at the caudolateral border of the ulna at the level of the proximal and middle 1/3 of the ulna and the ulna is exposed with Hohman retractors10. With an oscillating saw or an osteotome, the ulnotomy is performed perpendicular or in a slight oblique way (i.e., 45) to the axis of the ulna. With the aid of two osteotomes the free movement of the ulna is controlled. The oblique cut allows for less forward tilting of the proximal ulna by triceps pull, but an earlier healing of the osteotomy cap than in case of the perpendicular cut3. Forward tilting can be prevented by an intramedullairy pin, which is especially advocated to use in chondrodystrophic breeds with a physiological flexed elbow joint11. An additional lag screw with or without a K-wire can be placed, which might accelerate re-attachment of the UAP and thus diminish arthrosis formation12. Early healing can be prevented by an ostectomy of half a centimeter and/or by placement of autologous fat in the osteotomy gap3. Fascia, subcutis and skin are closed in a routine fashion. An elastic bandage or Robert Jones bandage is applied to stay in place for 3 days. The dog is allowed to bear weight on the operated leg; analgesics are administered since joint congruity is restored by frequent flexion and extension of the joint. Bony union may be expected within 4-14 weeks3.

2. FCP and/or OCD The dog is positioned with the affected leg on the surgical table with the medial side of the elbow joint upwards and placed at the edge of the table. After routine preparation and draping, the incision line is made starting from the medial epicondyle with a length of 7 cm in the direction of the first phalanx. This incision is deepened through subcutis and fascia. The white aponeurosis between pronator teres and flexor carpi radialis (or the more subtle separation between flexor carpi radialis muscle and the humeral head of the deep digital flexor muscle) is separated by blunt dissection. Using a curved mosquito, the joint capsule is penetrated while the

distal end of the leg is abducted. With a blade #11, the opening is elongated proximally towards the medial epicondyle and distally towards the annular ligament, both caudal and parallel to the medial collateral ligament (MCL). The muscular branches of median nerve are identified and protected. By opening the joint in this way, the MCL should remain intact. The antebrachium is now endorotated (pronation) by an assistant, thus exposing the joint space between humerus and ulna, allowing to inspect the medial coronoid process caudal to the MCL. Using a curved mosquito the medial humeral condyle is palpated: roughening is caused by a FCP (a “kissing lesion”), cartilage in unattached in case of OCD, and completely smooth surface makes the presence of FCP questionable. The cartilage flap is removed when present and the lesion curetted carefully. When kissing lesions were present, the coronoid area of the ulna is inspected for fragmentation, abnormal coloring of the cartilage, or small blood stained fissure/fracture lines indicating a fragmented coronoid process or chondromalacia of the joint cartilage. After 10 minutes of endorotation and abduction of the antebrachium plus retraction of soft tissues, the joint will open sufficiently.2 When the apex of the coronoid process is fractured, it is removed and the edges smoothened with a small curet. When the FCP is sandwiched between the ulna and the medial aspect of the radial head, the intact, medial aspect of the coronoid should be removed allowing the removal of this type of FCP. Removal of the medial aspect is performed with a curet or a small (2-5 mm) osteotome, taking great care not to damage humeral condyle or radius cartilage. When fissures are present in the apex of the coronoid, the apex will also be removed. The joint is frequently flushed with saline to improve the surgical view and remove the debris. In case a partially incised MCL ruptures during enforced endorotation of radius and ulna, Bunnell sutures using PDS or non-resorbable suture material and a Robert Jones bandage for at least 3 weeks, may allow the MCL to heal! However, usually severe lameness will develop due to elbow instability. The joint capsule, the muscle bellies, the muscle fascia and subcutis and the skin are closed in separate layers with interrupted sutures. An elastic bandage is applied including the surgery wound but not the olecranon, allowing free movement and preventing postoperative swelling. Exercise is restricted during 3 weeks followed by 3 weeks leash restriction. The period during which the lameness disappears varies between immediately postoperatively and 6 months after surgery (mean 6 weeks)13. In follow up study, with a follow-up period ranging from 0.5-8 years (mean 2.7 years) the success rate was 78% in a group of 64 Retrievers (with 67.8% males) operated at young age. Only 33% of the conservatively treated dogs with a FCP (i.e., low body weight and controlled activity but no surgery), were not lame13. This stresses the importance of an early diagnosis and surgical treatment.

3. INC with or without FCP Elbow incongruity (INC) due to a short radius is frequently seen in Bernese Mountain Dogs (BMD), but also

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other breeds (Retrievers, Mastiff Napolitano) may be affected. An ad random study in the Dutch BMD population, revealed that 72% of the dogs had INC. A longitudinal study by Bienz (1985) demonstrated that this incongruity may normalize spontaneously and is most probably genetical. The joint surface supporting the humerus is decreased in case of a short radius. This leads to an increased pressure on the remaining joint surface, e.g., the lateral and medial coronoid process. This may be the cause of the fragmentation of the coronoid process. This hypothesis is supported by the finding that INC is seen in 72.6% of the BMD with a fragmented coronoid process (FCP), whereas only 6% had a FCP without INC. Not in all cases, elbow joint incongruity is concurrent with FCP; in 12% INC was diagnosed without evidence of a FCP. Based on a owner’s survey, we found that not all Bernese Mountain Dogs with FCP or with INC were lame, but dogs with LCP and INC were all lame. In dogs with lameness due to FCP we remove the coronoid, in cases with lameness due to FCP and severe incongruity, congruity is restored. In dogs under one year of age this can be performed by a partial (approx. 2 cm) ulnectomy. In animals over one year of age we perform the restoration of elbow incongruity with the aid of the Ilizarov external ring fixator (IERF) after partial ulnectomy, since the interosseus is too rigid to allow for spontaneous correction.

Management of ED affected populations In some breeds a combination of UAP plus FCP, FCP plus OCD, or FCP plus INC is seen. The combination UAP plus FCP may be explained by the smaller diameter of the joint surfaces of the ulna (i.e., the ulnar trochlear notch) than of the humeral trochlea, forcing both bony protuberances from their origin15. A combination of FCP and OCD has been explained by Olsson (1993) as a disturbance of endochondral ossification and as such expressions of the same disease. Osteochondrosis is seen more frequently in certain breeds and sub-populations and can be aggravated by high food intake and excessive calcium intake17. The frequency and severity of the occurrence of osteochondrosis can thus be prevented by dietary management, including a food with a lowered calcium to energy ratio and quantitative restriction of food intake. The radiological findings included in a dendrogram of a Labrador population revealed that FCP and OCD occurred in two different groups of closely related dogs although in one related subgroup both entities were present17. In a dendrogram of the Dutch Berneses Mountain Dog population it became clear that INC and FCP originate from two different groups of non-related ancestors but are now seen in 80% of the Bernese Mountain Dogs with ED. This indicates that there are different diseases (FCP, OCD, INC) which may occur in the same animal. Since there is strong evidence that FCP in Retrievers is a recessive autosomal inherited disease, and therefore dogs which are highly related to an affected animal can have a normal phenotype, the family history should be taken into account before including dogs in the breeding stock18. In 1989 a group of veterinary radiologists, geneticists

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and clinicians founded the International Elbow Working Group (IEWG) with annual meetings in the United States of America and in Europe. The 1998 meeting of the IEWG is organized in conjunction with the SCIVAC/FECAVA meeting in Bologna and is open for all interested veterinarians. The IEWG introduced a scoring system for the evaluation of radiographs, based on the proposal of Audell, (1990) and are adopted by the Federation Cynologique International, the World Small Animal Veterinary Association, and different national kennel clubs. The protocol and additional information is made available on the web site of the IEWG and through its chairman Dr. M. Flückiger (Veterinärklinik Zürich, Switserland). Although the scoring of arthrosis according to the guidelines of the IEWG can be performed on the MLflexed view alone, this underestimates the occurrence of the primary cause of elbow dysplasia with 12-25%, and the presence of arthrosis with approximately 12%5,6. However, the protocol can be helpful for breeders to screen the elbow joints of their stock. Making the results of screening available to all breeders, a significant improvement in elbow status can be achieved as has been demonstrated to occur in Norway and Sweden in Bernese Mountain Dogs, Rottweilers, Labrador Retrievers and German Shepherds3,20. Based on financial or infra structural limitations and differences in legislation regarding radiological investigations in different countries, it is not to be expected that a uniform screening method in Europe will be introduced by the different national kennel clubs. This may not be a reason to limit either the quality or the quantity of elbow screening. As a consequence of the globalization of breeding stock exchange, the differences in level of judging and thus of results warrants a certification which makes clear to breeders and buyers how a particular dog was screened. It is up to the veterinary community to come to these international appointments.

8. 9.

10.

11.

12.

13.

14.

15.

Key words 16.

Fragmented coronoid process, ununited anconeal process, osteochondritis dissecans, incongruity of elbow joint, elbow dysplasia, developmental diseases, dogs, surgical approach radiological investigation, screening program, hereditary diseases.

17.

18.

References 19. 1.

Swenson L, Audell L, Hedhammar A, (1997), Prevalence and inheritance of, and selection for elbow arthrosis in Bernese Mountain Dogs and Rottweilers in Sweden and benefit-cost analysis of a screening and control program. Proceedings International Elbow Working Group, Birmingham, UK, 1997, pp 16-17 and JAVMA 210, 215-221.

20.

Hazewinkel HAW, Kantor A, Meij BP, Voorhout G, (1988), Fragmented coronoid process and osteochondritis dissecans of the medial humeral condyle Tijdsch Diergeneeskunde 113, 41s-46s. Sjöström L, Kasström H, Källberg M, (1995), Ununited anconeal process in the dog. Pathogenesis and treatment by osteotomy of the ulnas. Vet.Comp. Orthop. Traumat. 8:170-176. Voorhout G, Hazewinkel HAW, (1987), Radiographic evaluation of the canine elbow joint with special reference to the medial humeral condyle and the medial coronoid process. Vet. Radiol. 5, 158-165. Hazewinkel HAW, Meij BP, Nap RC, (1995), Radiographic views for elbow dysplasia screening in Bernese Mountain Dogs. Annual Meeting International Elbow Working Group, Constance (Germany) pp 29-32. Busato A, Lang J, (1997), Comparison of two classification protocols in the evaluation of elbow dysplasia in the dog. Proceedings International Elbow Working Group, Birmingham (UK), p 11. Read RA, Armstrong SJ, Black AP, MacPherson CG, Yovich J, Eger C, (1997), Elbow dysplasia in Rottweilers: correlation between lameness, physical signs and radiographic score in growing dogs. Proceedings International Elbow Working Group, Birmingham (UK) pp 7-8. Hazewinkel HAW, Kantor A, Meij BP, (1988), Loose anconeal process Tijdsch Diergeneeskunde 113, 47s-49s. Roy RG, Wallace LJ, Johnston GR, (1979), A retrospective long-term evaluation of ununited anconeal process excision on the canine elbow. Vet. Comp. Orthop. Traumat. 7:94-97 Piermattei D, Greely RG, (1979), An atlas of surgical approaches to the bones of the dog and cat. Philadelphia, USA, WB Saunders Comp. Matis U (1992), Treatment of ununited anconeal process. Proceedings 6th annual congress European Society of Veterinary Orthopedics and Traumatology, Roma (Italy), pp 16. Meyer-Lindenberg A. (1997) Der isolierte Proc. Anconeus: prospektive Untersuchungen zur operativen Behandlung proceedings Deutsche Veterinärmedizinische Gesellschaft, Hannover August 1997 pp. 105-109. Meij BP, Geertsen KMK, Hazewinkel HAW, (1995), Results of FCP treatment in Retrievers; a follow-up study at the Utrecht University small animal clinic. Annual Meeting International Elbow Working Group, Constance (Germany), pp 24-26. Bienz HA. (1985), Klinsche und Radiologische Untersuchungen über den Fragmentierten Processus Coronoideus Medialis Im Ellenbogengelenk des Berner Sennenhundes und der andee SennenhundeRassen Inaug Dissertation Zürich (Switserland). Wind WP (1986), Elbow incongruity and developmental elbow diseases in the dog: part I. J Am Anim Hosp Assoc 22:711-724. Olsson SE, (1993), Pathophysiology, morphology, and clinical signs of osteochondrosis in the dog in: Disease Mechanisms in Small Animal Surgery (M.S. Bojrab ed), Philadelphia (USA) Lea & Febiger, pp 777- 796. Hazewinkel HAW (1993) Nutrition in orthopedics in: Disease Mechanisms in Small Animal Surgery ed 2. (M.S. Bojrab ed), Philadelphia (USA) Lea & Febiger, pp 1117-1128. Ubbink GJ, Hazewinkel HAW, Wolvekamp, (1995), Preliminary results of the genetic analysis of the ED program of the Dutch seeing eyes dogs. Annual Meeting International Elbow Working Group, Constance (Germany) pp 43-45. Audell L (1990), Heredity of elbow dysplasia: can elbow dysplasia be controlled by judicious breeding? Proceedings Amer. Anim Hosp. Assoc. meeting 1990, pp. 730-733. Grondalen J, (1995), Occurrence and genetic aspects of elbow dysplasia. Annual Meeting International Elbow Working Group, Constance (Germany), pp 12-17.

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Dermatological manifestations of internal diseases Dominique Heripret Med Vet, CES DV, Dipl ECVD Private Practitioner, Arcueil, Paris - France

Specific problems in dogs 1) Nodular dermatofibrosis This syndrome has been described first in German Shepherd; the animals present multiple collagenous nevi in association with renal cystadenocarcinoma or renal cystadenoma or uterine leiomyomas in female dogs. Since then, this syndrome has been described in other breeds: Golden retriever (Marks 1994), and a cross Labrador (Heripret, unpublished data). The pathogenesis is uncompletly understood. On the basis of the present knowledge, the hypothesis is that the skin nodules, renal tumors and uterine tumors develop independently, but closely associated, probably through common genetic mechanisms as the syndrome has been proven to be inherited in an autosomal dominant way in German Shepherd (Lium 1985, Moe 1992). In a review of 51 cases (Moe 1997), the authors found no sexual predisposition. Typical chief complaints are skin nodules or depressed general condition. The skin nodules are often numerous, mostly located on the legs. Some nodules may become ulcerative and painful leading to lameness. Fine needle cytology shows no inflammation and often just few cells. Histopathology shows epidermal atrophy and collagen hyperplasia without neoplastic or granulomatous organization, and is diagnostic of collagenous nevi. At this point, renal examination is mandatory: ultrasonography is the investigation of choice and shows hudge hypoechogenic bilateral renal cavities. No effective curative treatment has been found for this disease: chemotherapy has not been evaluated but paclitaxel (Taxol, Bristol Meyers) may have an interest (it inhibits the development of renal cysts in rats that have congenital polycystic kidney disease); there is no report about the dosage and efficacy of this drug in dogs. The prognosis is poor: the time from diagnosis to death is 0,5 year, but the time from the first observation of nodular dermatosis to death is 2,5 years (Moe 1997). It shows the importance of good early recognition of this disease if we want to assess a treatment. 2) Superficial necrolytic dermatosis It is an uncommon necroziting skin disorder of dogs associated with incompletly characterized internal metabolic disease, mainly severe vacuolar hepatopathy (90%) or glucagon secreting pancreatic islet neoplasm (10%). The pathogenesis of cutaneous lesions is not well under-

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The skin may be the reflect of many internal diseases or problems. • Non specific problems: - nutritional deficiencies, excesses or imbalances may result in scaling, crusting, alopecia and a dull haircoat. Notable examples are the Zinc responsive dermatosis type I and vitamin A responsive dermatosis, but these entities may represent genetically related problems rather than true nutritional deficiences. Fatty acids deficiency is uncommon nowadays because of the good quality of most commercial foods. Protein deficiency may be seen in dogs suffering from nephrotic syndrome (hairs are easily epilated, presence of patchy alopecia). - Endocrine diseases: spontaneous hyperadrenocorticism (Cushing’s disease), iatrogenic secondary hypoadrenocorticism (iatrogenic Cushing’s disease), hypothyroidism, Sertoli-cell tumor, may induce alopecia and some specific changes in skin quality (Cushing’s disease), that are well known. - Anagen defluxion: special circumstance (antimitotic drugs, metabolic disorders) may interfere with anagen, resulting in abnormalities in hair follicle and hair shaft. Hair loss occurs suddenly, within days of the insult. - Telogen defluxion: a stressfull circumstance (high fever, pregnancy, surgery,...) may induce an abrupt cessation of growth of many anagen follicles and the synchrinzation in telogen. Within 1 to 3 months after the initial insult, a large number of telogen hairs are shed. • Specific problems: some cutaneous lesions may be considered as cutaneous markers (in some cases specific) of internal diseases. Relationship between cutaneous lesions and internal disease or often badly understood but it is important to be able to recognize these lesions because they often appear before the symptoms of the underlying disease. DOGS - Nodular dermatofibrosis - Superficial necrolytic dermatitis - Dermatomyositis - Calcinosis cutis - Cutanous amyloidosis - Xanthoma CATS - Feline pancreatic paraneoplastic alopecia - Feline skin fragility syndrome - Digital metastasis of pulmonary adenocarcinoma - Exfoliative dermatitis and thymoma - Pseudo sebaceous adenitis

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stood: hypoaminoacidemia (epidermal protein depletion and subsequent keratinocyte necrolysis), low essential fatty acid and Zinc concentrations, high glucagon concentration (inducing a decrease in amino-acid concentrations) have been suggested to be involved. Erosions, ulcerations, exudation, thick and adherent crusts are seen in the footpads and around mucocutaneous junctions. Lesions may also be seen on ears, pressure points, scrotum. Secondary infections (bacteria, Malassezia, dermatophytes) are common. Pain may be severe. Differential diagnosis include: Leishmaniasis, drug reaction, Pemphigus, Systemic Lupus erythematosus (SLE), Zinc responsive dermatosis. Histopathology (choose erythematous plaques with adherent crusts) shows a “pink, white and blue” coloration. Pink layer: parakeratosis and crusting; pale layer: edema and necrolysis of keratinocytes; blue layer: hyperplastic basal cells. Biochemical findings include: hypoalbuminemia, hyper beta and gamma globulinemia, increase ALT and SAP, hypoaminoacidemia (hydroxyproline, proline, glutamine, alanine, arginine, ...); hyperglucagonemia is rarely documented. Ultrasonography is mandatory (pancreas and liver) and hepatic liver biopsies are indicated if lesions are seen. There is no specific treatment except in the case of glucagon secreting pancreatic islet neoplasm in which removal of the pancreatic tumor may be salvatory (Torres 1997). Non specific treatment includes: essential fatty acids and Zinc supplementations, addition of eggs, treatment of infectious complications. The overall prognosis is bad (1,5 month after diagnosis) 3) Canine dermatomyositis Canine dermatomyositis is an inflammatory disease of skin and muscles. Collies and Shetland collies are predilected breeds; the disease appears in young animals (< 6 months) with no sex predilection. Pathogenesis of the disease is still uncompletly understood: there are some evidence for infectious disease and others for an immune-mediated disease: * infectious disease: early age of onset, virus have been detected, the disease develops in pups housed together, frequency of outcome is increasing after national dog show (in USA) * immune-mediated disorder: it looks like systemic lupus erythematosus (SLE) (clinical and histopathologicaly). Cutaneous clinical signs: it is a waxing and waning dermatitis; at the beginning, skin exhibits vesicules, erythema, scaling and crusting, then alopecia, hyperpigmentation, scarring. The face, pinnae, tip of tail (frequent) and bony prominences are often involved. Pruritus is mild or absent. Muscular signs include painful temporal muscle and facial swelling at the beginning, and then, muscle atrophy (usually masticatory muscles); megaoesophagus may be found. Differential diagnosis includes: SLE, epidermolysis bullosa, pyoderma, demidocosis, dermatophytosis, juvenile cellulitis. Skin scrapings may reveal Demodex; CBC and serum chemistry are usually normal; histopathology shows a mild mixed interface and superficial perivascular dermatitis, follicular atrophy with prominent fibrous rootsheath, individual

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keratinocyte necrosis, subepidermal vesiculation with erythrocytes, ulceration and scarring. Examination of muscles biopsies shows: myositis, myofiber atrophy, necrosis and regeneration, fibrosis and occasionally vasculitis. Direct immunofluorescence of skin and muscles biopsies is negative. Electromyography is often diagnostic of muscle disease; motor nerve conduction velocities are normal and repetitive nerve stimulation shows occaional mild decremental responses. Treatment: vitamin E, pentoxifylline (10 mg/kg bid or tid), prednisone at the beginning if inflammation is documented on skin biopsies. Pronostic depends on the stage of the disease: in mild cases in young animals, pronostic is good (spontaneous remission); in more severe cases with muscular problems, euthanasia may be required. 4) Calcinosis cutis Calcinosis cutis is mostly associated with spontaneous or iatrogenic Cushing’s disease. Some rare other cases have been described with severe chronic renal failure with renal hyperparathyroidism and abnormal equilibrium of calcium and phosphorus. Calcinosis is often pruritic and represents a real clinical problem because there is no treatment except treatment of the underlying disease; with appropriate treatment, calcinosis may disappear after a few months, especially in iatrogenic Cushing’s disease. If lesions are generalized, the prognosis may be poor. Non specific treatment includes frequent shampoo or application of colloidal oatmeal with local anesthesic. 5) Cutaneous amyloidosis Amyloidosis is not a single entity and amyloid substance may accumulate as a result of a variety of different pathogenetic mechanisms. Cutaneous amyloidosis have been described in dogs with renal amyloidosis, primary cutaneous disease and monoclonal gammapathy. In the last case, clinical lesions are nodules involving the tongue and ulcerations of digits, footpads and bony prominences. Histopathologic examination shows an amorphous eosinophilic diffuse or perivascular deposit. 6) Xanthoma Xanthoma are cutaneous or subcutaneous yellowish lesions resulting from accumulation of lipids in the dermis. In dogs, it has been associated with diabetes mellitus, hypothyroidism and acute pancreatitis. Lesions are papules or nodules with no special location. Histopathological examination shows multinucleated cells (Touton cells) and spumous histiocytes. When diagnosing xanthoma, biochemical examination is mandatory (glycemia, cholesterolemia, lipidemia, lipoprotein electrophoresis, T4 measurement).

Specific problems in cats 1) Feline pancreatic paraneoplastic alopecia (FPPA) FPPA is characterized by specific cutaneous lesions associated with pancreatic carcinoma or cholangiocarcinoma

(Brooks 1994, Pascal 1996). Cutaneous lesions: rapidly progressive alopecia, beginning by the face and the ventrum extending to the legs and flanks. The alopecia is complete and the skin becomes shiny. Footpads may be involved resulting in pain. Alopecia appears a few days before or simultaneously with non specific general signs: anorexia, asthenia. Prognosis is very poor and the cat die in a few days or weeks. Haematological and biochemical examinations are unremakable or non specificaly altered. Ultrasonography may reveal pancreatic tumor or hepatic metastasis. Histopathological examination of the skin shows: telogen phase and atrophic hair follicles, slight perivascular inflammation, no stratum corneum, severe adnexiel atrophy. Immunohistochemical stainings of the pancreatic tumors have failed to show any endocrine abnormality (insulin, glucagon, somatostatin, ACTH). No treatment is available. The internal disease can be diagnosed on the basis of the cutaneous lesions. 2) Feline skin fragility syndrome (FSFS) FSFS is an uncommon disease of cats. The exact pathogenesis of the lesions si unknown. It has been described with Cushingâ&#x20AC;&#x2122;s disease (spontaneous or iatrogenic), diabetes mellitus, hepatic lipidosis (Diquelou, 1991), neoplastic internal disease (Regnier 1989) and in some cases with no evident cause. There is no sexual or breed predilection and the disease can arise at any age. Skin defects are often catastrophic: large wounds occuring with a minimum trauma and with cutaneous margins that are markedly abnormal (cigarette paper aspect). The lesions are not painful and slightly (or not) hemorragic. Differential is from feline cutaneous asthenia, a congenital syndrome that may predispose to FSFS. It is difficult to biopsy the skin of these animals because of the fragility of the skin. Histopathological examination reveals

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severe epidermal and dermal atrophy, rare collagen fibers. There is no specific treatment; surgical closure may be difficult but must be proposed in case of iatrogenic Cushingâ&#x20AC;&#x2122;s disease. 3) Digital metastasis of pulmonary adenocarcinoma It is a podal dermatosis with uni- or multidigital nodular to ulcerative painful lesions (Moore 1982, Estrada 1992). Local osteolysis is a consequence of these lesions. When facing this kind of lesions, a thoracic radiography must be proposed: it shows a pulmonary mass (carcinoma). This pulmonary tumor is generally asymptomatic at the time of the cutaneous diagnosis. Cutaneous histopathological examination shows neoplastic infiltration of the digit sometimes with local metaplasia (ciliated epithelioma, mucus cells). Pathogenesis of cutaneous lesions is not yet understood but these lesions are specific for a pulmonary carcinoma. Results of surgical excision of the pulmonary tumor (or radiotherapy) has not been evaluated for the moment. 4) Exfoliative dermatosis and thymoma Exfoliative dermatosis has been described in a few cats in association with thymoma (Scott 1995). Clinical cutaneous signs begin with erythema and non pruritic scaling; then scaling becomes more important and alopecia, crusts and ulcerations appear. Head, ears, neck are often primarly involved but extension and generalization occure rapidly. There is no sex or breed predilection. Cutaneous histopathological examination shows a hydropic interface dermatitis (mainly lymphocytic infiltrate) with keratinocyte necrosis, similar to erythema multiforme. Thoracic radiographic reveals a cranial mediastinal mass; ultrasonographic examination of the thorax shows a multilobular cystic mass or hyperechogenic mass. There is one report of resolution of clinical signs after surgical thymoma resection (Forster van Hufte 1997) but the histopathological lesions were slightly different in this report.

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Diagnostic approach to alopecia in dogs and cats Dominique Heripret

Alopecia can be defined as partial or extensive hairloss linked to a decrease in the total amount of hairs (excess shedding of hair) or shortening of hairs without decreased total number of hairs. Alopecia may be focal, diffuse, generalized. Multiple classifications are proposed in the litterature; however two of them are important: the histopathological one and the clinical one which is presented here.

A - Clinical classification 1) Congenital and hereditary alopecias • dystrophy or lack of hair follicle: - alopecia universalis (Sphinx cat) - hypotrichosis (Siamese breeds, Cocker, Poodle, Whippet, ...) • follicular dysplasia: - Color dilution alopecia: seen in blue and other color-diluted dogs (all breeds and mongrels), in association with a color dilution gene. It appears between 4-6 months and 4 years old. - Black hair follicular dysplasia: alopecia is restricted to dark-haired areas. This condition is very similar to color dilution alopecia. - Canine follicular dysplasia: this is a “melting pot” of many unknown conditions gathering congenital and hereditary alopecias and acquired alopecias. In Siberian Husky, follicular dysplasia syndrome may be a castration responsive dermatosis. - Acquired pattern baldness (Dachshund) • hyperkeratotic diseases of epidermis and secondary alopecia - Primary seborrhea (Cocker spaniel, ...) - Vitamine A responsive dermatosis (Cocker spaniel) - Canine ear margin seborrhea (Dachsund) - Ichtyosis - Zinc responsive dermatitis type I (Siberian Huskies, Alaskan Malamutes) 2) Acquired traumatic alopecias • Non cicatricial acquired traumatic alopecias: - secondary to pruritus: all pruritic dermatitis are able to induce alopecia characterized by cutaneous inflammation and/or primary lesions. Hairs are broken. Main causes: allergic dermatosis, sarcoptic mange, feline extensive alopecia (whatever the cause) - secondary to rubbing: alopecia localized to contact

areas (collar). It has to be distinguished from endocrine alopecia. • Cicatricial acquired traumatic alopecias: - secondary to physical or chemical traumas: scars, burns, irritant contact dermatitis - traction alopecia: described in dogs that have barrettes, rubber bands or other methods to tie up their hair. 3) Non traumatic acquired alopecias • Non cicatricial, with follicular arrest - endocrine dermatoses - telogen effluvium: hair loss occurs up to 2 months after the insult - toxic alopecia and anagen defluxion: chemotherapy - post-clipping alopecia • Non cicatricial with follicular dystrophy: seasonal flank alopecia, post-clipping alopecia • Non cicatricial, with folliculitis: bacterial, fungal or parasitic (Demodex); generally, alopecia is multifocal with a moth eaten appearance. • Non cicatricial, with perifolliculitis: - Leishmaniasis - sebaceous adenitis - alopecia areata • Non cicatricial, neoplastic: mycosis fungoides, metastasis of mammary gland adenocarcinoma • Cicatricial - infectious diseases: deep pyoderma - non infectious: dermatomyositis, sclerodermia 4) Miscellaneous - Canine pinnal alopecia (Dachshund, Yorkshire, ...) - Excessive shedding syndrome - Short hair syndrome of silky breeds

B - General diagnostic approach 1) Signalement and history: after the signalement (sex, breed, age), a thorough history should be obtained. The major objectives of the history are to determine whether: - pruritus is present or not and, if pruritus is present, if it is previously to alopecia or not. Determining pruritus can be difficult in cats - alopecia is associated with erythema, scaling, crusts, plaques, nodules - the alopecia area is enlarging

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- any previous medications or injections that may be associated with alopecia have been given (glucocorticoids) - any environmental factors are present that may be involved in lesion development (contact with irritants, outdoor cats, fleas) - the response to any previous treatments - if there is a seasonality of the disease - if there is any other abnormal symptoms (underlying internal diseases: Cushing’s syndrome, feline pancreatic paraneoplastic alopecia, ...) - if there is possible contagion to other pets or to humans 2) Physical examination - aspect of alopecia: focal, diffuse or generalized - localization of lesions - aspect of hairs: broken or easily epilated - presence of inflammation - presence or primary lesions (pustules, papules, erythema) - complete physical examination 3) Establishing a differential diagnosis The list of differential diagnoses should be organised so that the most likely diagnoses comprise the top two or three differentials. 4) Diagnostic procedures: in practice, the approach should include consideration of costs and owner’s willingness to countenance diagnostic tests. The diagnostic procedures (or therapeutic recommendations) will be determined from the differential diagnosis list. • routine examinations: - microscopic examination of skin scrapings - direct examination of hair shafts - Wood lamp examination (+/- fungal culture) - cytological evaluation of impression samples • second intention examinations: - skin biopsies - haematology, biochemistry (FeLV, FIV for cats) - endocrine tests

C - Special considerations in cats 1) Focal feline alopecia Main causes of focal feline alopecia are: dermatophytosis, parasitic diseases, fleas (FAD), post-injection alopecia. These represent more than 90% of causes of feline focal alopecia • history: main points - way of life of the cat (contact with other cats, outdoor environment, stay in cattery, ...) - contagion - pruritus - previous injections or vaccinations (especially when alopecia is on the neck) • routine examinations: - direct examination of hair shafts (broken or not), Wood light - presence of fleas or flea feces - microscopic examination of skin scrapings

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- impression smear: eosinophilia, Malassezia, bacteria, acantholytic cells, abnormal cells - fungal culture • others: - elimination diet (especially when facial involvment and pruritus are present) - skin biopsies - blood examination • aetiological treatment 2) Feline extensive alopecia (FEA) First of all, excessive grooming must be proven (history of self-licking, broken hairs). Main causes of FEA are: FAD, dermatophytosis and psychogenic (stress and anxiety) • history: - previous crisis and seasonality - presence of fleas or possible contact with fleas - general behaviour of the cat during consultation (anxiety) - contagion • look for classical causes - direct examination of hair shafts (broken or not), Wood light - presence of fleas or flea feces - fungal culture • flea control and short term antipruritic treatment (prednisone or prednisolone 2 mg/kg/day 3 to 7 days or chlorpheniramine 10 mg/cat/day 10-15 days) • if recurrency or no benefit (with good flea control): - behaviour consultation or L-Deprenyl (1 mg/kg/day) or haloperidol (if lesions are lasting for more than six months) - or elimination diet (2 months) if possible • if there is no real behavior problem and no benefit of the elimination diet - try intradermal skin testing (but atopic dermatits is not well defined and IDST are not standardized in cats) - try maintenance therapy: essential fatty acids supplementation, antihistamines (chlorpheniramine 510 mg/cat, oxatomide 1,5 mg/kg bid, amitriptyline 5 mg/cat bid), high quality diet, flea control. Elizabethan collar are of no use on a long term basis.

D - Canine symmetrical non pruritic alopecia Main causes of canine symmetrical non pruritic alopecia are endocrine skin disorders; but before performing expensive tests, one must be sure of the endocrine origine of the problem. For exemple, it is no use to perform endocrine tests in a young blue Doberman Pinscher: microscopic direct examination of hair shafts or skin biopsies are mandatory, before assessing thyroid or adrenal status, because color dilution alopecia is very likely. 1) Diagnostic pathway The diagnostic pathway of canine symmetrical non pruritic alopecia has to determine whether the skin condition is associated with endocrine disturbance or not. We must think about cost effectivness of our examinations.

• history: - breed, age, color of the coat: endocrine disorders are common in older dogs, congenital or hereditary problems and demodicosis in younger animals. - evolution of alopecia, seasonality (recurrent flank alopecia) - general symptoms: polyuria, polydipsia, polyphagia, • general examination: pendulous abdomen, amyotrophy, enlarged lymph nodes (Leishmaniasis), enlarged spleen, abnormal testis, feminization of male dogs, ... • dermatological examination - aspect of hair shafts (broken or not), epilation, follicular casts (demodecosis, sebaceous adenitis) - localization of lesions - scaling, crusts, other lesions - skin thickness (thin in Cushing’s disease) • routine examinations: skin scrapings, direct examination of hairs, impression smear • differential diagnosis: at this point one should be able to decide if alopecia is of endocrine origine or not. If there is a doubt, skin biopsies are mandatory, before endocrine testing. • if it is an endocrine alopecia: - non specific blood examinations: chol, SAP, ALT (or more complete if possible) - endocrine measurement is function of differential diagnosis: ACTH stimulation test if elevated SAP are present and if clinical aspect is suggestive of Cushing’s disease (spontaneous or iatrogenic), oestradiol measurement in a male dog with abnormal testis or feminization syndrome, basal TT4 or FT4 (becareful of euthyroid sick syndrome) - if normal: skin biopsies (if not done previously) to rule out non endocrine alopecia - other endocrine procedures: ACTH stimulation test with measurement of adrenal sexual hormones (progesterone, androstendione, ...); HCG stimulation test in male dogs; clonidine test with glycemia measurements - if everything is normal and the dog too: propose neutering of a male dog; female dog: wait and see ... 2) Differential diagnosis • non endocrine non pruritic alopecia - color dilution alopecia - black hair follicular dysplasia

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- demodicosis - dermatophytosis - seasonal flank alopecia - pattern baldness - post-clipping alopecia - sebaceous adenitis - telogen and anagen effluvium - superficial pemphigus - alopecia areata - leishmaniasis - epidermotrophic lymphoma - short hair syndrome of silky breeds - congenital hypotrichosis • endocrine alopecia - spontaneous hyperadrenocorticism - iatrogenic Cushing’s disease - hypothyroidism - testicular neoplasia - idiopathic feminization syndrome - castration responsive alopecia of the male dog - ovarian imbalance (neoplasia, cyst) - hypogonadism - primary adrenal sex hormone imbalance - pituitary dwarfism - GH responsive dermatosis (?) 3) General considerations about endocrine testing • analysis should be performed by a veterinary laboratory or by a human laboratory used to measure canine hormones (with canine normal values which is rare) • samples must be collected and stored with caution • the clinician is the only person able to give a good interpretation of a result, based on clinical findings and suspicion. • no one hormonal test is perfect: a normal ACTH stimulation test does not rule out hyperadrenocorticism, low stimulation after TRH stimulation test is not diagnostic for hypothyroidism, abnormal UCCR may be encontered in normal dogs, ... • most hormones interact with each other: main cause of hypogonadism in adult male dogs is hyperadrenocorticism and hypothyroidism • be aware that many treatments or drugs can alter endocrine measurements: for exemple glucocorticoids decrease basal FT4 and TT4 and decrease normal testicular response to HCG.

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33 Systemic antipruritic therapy Dominique Heripret

While prescribing antipruritic therapy we must have in mind animal’s health, owners’ compliance, diagnosis of the dermatosis, toxicity of the drugs used and price of it, duration of treatment. We must always privilege a specific treatment because in most cases, antipruritic treatment will treat the pruritic crisis but not the underlying cause. Concepts of summation of itch and pruritic threshold are important and complications or secondary dermatosis (pyoderma, Malassezia dermatitis, seborrhea, flea) must be looked for and treated.

Glucocorticoids They represent the treatment of choice of allergic or irritative pruritic crisis but their prescription must follow some rules: - diagnosis or suspicions must be compatible with glucocorticoid therapy. - Pyoderma and/or Malassezia dermatitis must be treated before using glucocorticoid. - If possible, more harmless therapy should have been tried. - Use it for a short period of time to relieve animal’s pain and owner’s impatience before other treatment procedure (antihistamines, flea control, immunotherapy, elimination diet, ...) provides some improvement. - Use it shortly at minimal effective dosage. - In chronical prurit dermatosis, corticotherapy is only palliative and not curative. - Do not use reposital glucocorticoid (even, if possible, in cat). - If long term therapy is mandatory, use alternate day protocol and add other drugs that may low down corticoid dosage (antihistamines, essential fatty acid, topics ...) or duration of treatment. - Secondary effects and contra-indications must be well known. The initial dosage (0,5-1 mg/kg/day of prednisolone in dog and 2 mg/kg in cat) is given to release pruritus and then is rapidly tappered at half dosage or less on an alternate day basis if a long term therapy is needed. In cat, dexamethasone may represent an alternative treatment (0,2-0,4 mg/kg/day). NB: Megestrol acetate, a progestagen compound, is a

potent anti-inflammatory drug, but has stronger side effects than glucocorticoids. We do not recommend their use, except, perhaps, for refractory indolent ulcers in cats.

Non steroidal antipruritic drugs Because of a low rate of secondary effects, these drugs (antihistamines, essential fatty acids, antidepressant drugs) can be used in long term management of chronic pruritic dermatosis especially in atopic dermatitis. The main indications of these drugs are: - atopic dermatitis unresponsive to immunotherapy or at the beginning of immunotherapy. - Acral lick dermatitis and obsessive-compulsive disorders - Other behaviour dermatological troubles. - When corticotherapy is contra-indicated (iatrogenic hyperglucocorticoidsm, demodicosis, diabetes mellitus, ...). In cases of flea allergy dermatitis or food allergy / intolerance, eviction of allergen is the treatment of choice. Antihistamines Only a few antihistamines have been realy studied in dog and cat: there is no study on drug absorption and action on histamine reaction except for ebastine and oxatomide and there are only few papers with placebo control studies. Many authors recommend to consider the efficacy of antihistamines on a 7 or 10 days basis: it seems strange because in atopic children, anti-H1 drugs are given for months before judging the clinical efficacy; moreover, it is thought that antihistamines have more protecting effects than curative ones. They are most likely to be effective when the skin is minimally inflamed, so secondary pyoderma and Malassezia dermatitis should be controled, and pruritus reduced by the use of a short corticotherapy or topical therapy. For the moment, the use of antihistamines is largely empirical and each author has his preference based on his own clinical experience. Drugs more commonly used are: - clemastine (0,05 mg/kg q12h); - oxatomide (1,5 mg/kg q12h); - chlorpheniramine (0,2-0,4 mg/kg q8h in dog, 4 mg/cat q12h); - diphenydramine (2 mg/kg q8h); - hydroxyzine (2 mg/kg q8h); - trimeprazine (1-2 mg/kg q12h);

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- others: terfenadine (5 mg/kg q12h), loratidine (10 mg/animal/day), ketotifen (0,2 mg/kg q24h), cetirizine (10 mg/animal/day). According to some authors, trimeprazine, terfenadine, loratidine seem useless. Essential Fatty Acid (EFA) supplementation Metabolisation of EFAs allows formation of polyunsaturated essential fatty acids, eicosanoids (leukotrienes and prostaglandines) precursors, that may interfer with the inflammatory pathway; they are believed to inhibit leukotriene B4, a potent pro-inflammatory mediator. The use of EFAs supplementation has shown his efficacy in reducing pruritus of allergic dogs and cats but many things remain inconclusive: which fatty acid, whick combination of fatty acids, which ratio of amega-6 to omega-3 and what dose has to be used? Large doses of omega-3 fatty acids (7 times those usually given) effectively controlled pruritus in 30 to 60% of the dogs. Maximal clinical results may only be seen after a long period of time (6 to 12 weeks). Just like antihistamines, ideal cases involve dogs with mild inflammation or pruritus and no infectious complications. For the moment, we know that the use of EFAs may be beneficial and is harmless. We recommend to prescribe them in addition to antihistamines (synergistic effects) and for their significant steroid sparing effect during glucocorticoid therapy. Psychotropics agents as antipruritics - Amitriptyline (1 mg/kg q12h in the dog, 5 mg/cat q24h) and doxepine (1 mg/kg q8h) are antihistamines used as tricyclic antidepressant agents in human. They are contra-indicated in epileptic patients and can induce cardiac arythmias. They are used in atopic dermatitis. - Clomipramine (0,25 mg/kg q12h) is a tricyclic antidepressant used in obsessive-compulsive disorders in the dog such as acral lick dermatitis. - Fluoxetine hydrochloride is a serotonine uptake inhibitor that may be effective in atopic and acral lick dermatitis (1 mg/kg q24h) without side effetcs. - Naloxone (1 mg/kg subcutaneously) and naltrexone (2 mg/kg q12h), endorphins blockers, may improve feline psychogenic alopecia and acral lick dermatitis but is very expensive.

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- Haloperidol has prooved his efficacy (75%) in chronical feline psychogenic alopecia lasting for more than six months (0,5 -1,25 mg/kg bid). Side effects may be important (hallucinatory symptoms, insecure walking, ...) and hospitalisation is recommended at the beginning of therapy.

Adjunctive therapy - Topical therapy: regular application of cleansing shampoos can reduce the bacterial load and keep the skin hydrated. Adjunction of colloidal oatmeal, which has a specific anti-inflammatory effect for a few hours or days, can be beneficial. - Flea control: by the effect of summation of itch, a flea infestation can push a patient over his pruritic threshold. A good flea control (fipronil for the dog or the cat, lufenuron and insect growth regulator or chitin inhibitor for the premises) is mandatory. - Diet: a nutritionaly balanced diet is recommended for dogs with chronic pruritus. Omega-3 supplemented diet seems interesting. - Systemic antibiotics: Staphylococcus intermedius can induce pyoderma and pruritus, but can act as a superantigen in atopic dermatitis and even dogs with no evidence of secondary pyoderma may benefit from the use of an effective systemic antibacterial agent.

Conclusion Appropriate diagnosis is the corner stone of pruritic dermatitis treatment. In chronical cases (especially atopic dermatitis), glucocorticoid is no longer the sole therapy for pruritus: they have to be used on short periods of time, to relieve a pruritic crisis. However, the lack of standardisation of antihistamine or EFAs use, means that treatment of chronical pruritus must be adapted to each particular case. Combination of products and good communication between owner and veterinarian are essential in these cases.

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Identification of lesions (localization & diagnostics) First part: Brain Richard A. LeCouteur

Summary This lecture will review the fundamentals of the organization of the nervous system and the relationship of structures within the nervous system to one another. An understanding of these relationships is essential for a clinician dealing with nervous system disease. The overview of the components of the nervous system begins at the highest level and descends to the lowest and it is hoped that it will provide a basis for understanding the mechanisms involved in the production of clinical signs that appear during the course of a neurological examination. The lecture will also discuss the general characteristics and clinical signs of nervous system disease and localization of a lesion to the brain and to areas within the brain. Diagnostic aids (e.g. CSF analysis) and the various imaging techniques available to diagnose brain disorders will also be discussed.

A. INTRODUCTION - AN OVERVIEW OF THE NERVOUS SYSTEM The fundamental structural units of the nervous system are its cells (neurons and glia) and the fundamental functional units are the reflex arcs into which the neurons are organized. An understanding of the details of cellular, axonal, and synaptic physiology is necessary to understand the mechanisms by which these basic units operate and allow the nervous system to accomplish its functions. One cannot hope for true understanding of the function of this or any other system without understanding the functions of its fundamental parts and their contribution to the function of the total system. In grappling with the mass of data and the concepts that describe the roles of these fundamental units, it is easy to lose sight of the organization of these units into larger units, and the relationship of the larger units to one another and to the system as a whole. Understanding the organization and relationship of structures is essential for a clinician caring for animals with neurologic diseases because a clinician deals with the entire animal and with the entire nervous system. This requires a global approach that is based on an appreciation of how the functions of the various parts contribute to the function of the whole. Normal functions must be known before abnormal functions can be recognized.

Abnormal functions must be recognized because neurological diseases are manifested clinically almost entirely by dysfunction. It is uncommon for the clinical signs to include readily detectable anatomical changes. Therefore, a clinician must rely on signs of abnormal function to identify structures that are malfunctioning. The nervous system lends itself readily to subdivision into major parts, each of which in turn is divisible into smaller parts. There are clinically detectable signs of normal and abnormal function for each of the major parts and their principal subdivisions. General divisions of the nervous system are: 1) brain, 2) spinal cord, and 3) peripheral nerves. Note that peripheral nerves form part of the motor unit (i.e. Iower motor neuron, muscle fibers it innervates, and intervening neuromuscular junctions). Each of these constitutes a higher level of function than the one that follows it, and each is divisible into smaller units that have functional, and therefore clinical, importance. The highest functional subdivision of the brain, and therefore the highest functional level of the nervous system, is the cerebrum. The cerebrum is the seat of consciousness and cognitive functions. It receives all sensory signals that reach consciousness, makes decisions on the most appropriate response, and initiates that response if one is needed. In most cases the response the cerebrum initiates is a movement. This is called a voluntary movement. It is done by muscles innervated by lower motor neurons of the spinal cord or brain stem. The specific movement that is initiated is a phasic (on again, off again) event that may consist of nothing more than movement at one joint of an extremity. However, no matter how simple such movements may be, they require adjustments of other muscles so that opposing muscles relax or so that some joints are fixed while others are moved, or so that weight bearing on the legs is adjusted to accommodate shifts in the center of gravity. The voluntary movement is initiated by the cerebral cortex and may be said to be an event of consciousness. The associated muscle activity is carried out subconsciously by successively lower levels of the nervous system: basal nuclei, midbrain, pons and medulla, cerebellum, spinal cord and brain stem, peripheral nerves and cranial nerves, and effector organ. The function of these lower levels is vital and without them voluntary movements become impossible. In ourselves, we are conscious of the effects of these subconscious operations but we are not conscious of the com-

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VMD, BVSc, PhD, Dipl ACVIM (Neurology), Dipl ECVN Professor of Neurology and Neurosurgery Department of Surgical & Radiological Sciences - School of Veterinary Medicine University of California, Davis, California - USA

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plex neuronal transactions that produce them. These activities can be blocked normally only by very powerful cerebral cortical override and then only incompletely in most cases. Presumably animals also are not conscious of the functions of these subcortical systems and presumably they might have even less success in overriding them if they somehow chose to do so. Abnormalities of movement and posture produce the most common neurological signs in animals. A very large proportion of these signs are caused by diseases that affect the subconscious events that occur in the many structures interposed between the cerebral cortex and the lower motor neurons. Because of the importance of these functions and the structures that produce them, recognizing signs of their dysfunction is an essential feature of that part of the general physical examination that we call the neurological examination. The following paragraphs attempt to provide an overview of the nervous system as a basis for the global approach and understanding that is required for dealing with neurological diseases. The overview simply provides a sketch of the overall plan to help form a conceptual framework. It does not provide many of the details that are essential to interpreting the results of a neurological examination.

B. COMPONENTS OF THE NERVOUS SYSTEM The overview begins at the highest level and descends to the lowest. It is hoped that this will provide a basis for understanding the mechanisms involved in the production of the clinical signs that appear during the course of a neurological examination. The neurological examination actually is conducted in somewhat the reverse order; that is, by beginning with the peripheral nerves and the reflex arcs. This approach is used simply because the latter structures must be functioning before one can determine the function of each of the successively higher suprasegmental levels of organization. The truth of this last statement becomes evident if one considers attempting a neurological examination on an animal paralyzed by curare.

Cerebrum The cerebrum receives all forms of sensory signals. The various types of stimuli can be classed in â&#x20AC;&#x153;sensory channelsâ&#x20AC;?: olfactory, visual, auditory, vestibular, and somatosensory. All of these channels reach consciousness. Olfaction does so without passing through the thalamus but all of the other channels reach the cerebrum after signal processing in the thalamus. A major function of the cerebral cortex is consciousness. Consciousness can be defined as awareness of sensory stimulation. It is said that the cerebrum is responsible for the content of consciousness while the reticular formation sets the level of consciousness. This is true but it should not diminish the importance of the cerebrum in consciousness. The cerebrum is the seat of consciousness and there can be no real consciousness without it. The ascending reticular ac-

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tivating system (ARAS) acts to adjust the level of activity of cerebral operations of consciousness but the ARAS does not itself enter into these operations. The various sensory channels tend to reach specific areas of the cerebral cortex. The most important areas clinically are the visual areas in the occipital regions, the auditory areas in the temporal regions, and the somatosensory areas in the frontoparietal regions. Much of the remaining cortex is association cortex. Information arriving in sensory channels is received and processed by the specific cortical areas and relayed to the association cortex. Cognition and decision making are functions of the association cortex. If a decision is made to move, the association cortex is involved in planning the movement and initiating it. It brings about the movement by signaling the basal nuclei. The latter then process these signals and in turn signal the motor cortex (cruciate region) for execution of the movement (corticospinal tract), and the brain stem and cerebellum for initiation of the necessary associated muscle activity that shapes the body and limbs into a base for movement. Clinical signs of cerebral cortical disease can include: a) disturbances of consciousness, b) paresis of voluntary movement, c) disturbances of all types of sensory function, and d) seizures.

Basal nuclei The basal nuclei are intimately related to movements initiated by the cerebral cortex. They are involved in the details of programming the movement, whereas the cortex as a command center merely plans and initiates the movement. To complete this activity the basal nuclei receive input from the association cortex and send signals to motor cortex and brain stem. The latter structures then signal the lower motor neurons via the corticospinal tracts and other descending pathways. Some of the basal nuclei have an inhibitory effect on the pathways involved in voluntary movement. When these are affected by disease, involuntary movements can occur during rest and there is a tendency for dystonia (hypo- or hypertonia). These disorders are most severe in muscles that are most important in voluntary movement and fine manipulation (e.g. the prehensile muscles). Some basal nuclei disorders produce difficulty in the initiation of voluntary movement. Large unilateral basal nuclei lesions produce circling.

Midbrain locomotor centers Areas in the midbrain and subthalamus contain locomotor regions that are important in triggering locomotion, in setting the rate and strength of locomotor movements, and in coordinating respiratory movements with locomotor movements. They operate on the flexion and extension mechanisms of the spinal cord through the reticulospinal pathways. Clinical signs caused by lesions in these structures are not well described.

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The cerebellum acts to coordinate all of the subsystems that operate in locomotion and posture. In keeping with this, it receives afferents from the cerebral cortex, the basal nuclei, the vestibular system, the spinal cord, and the reticular formation, and it has efferent connections with all of these systems. It is important to realize that the cerebellum has no direct connection with the lower motor neurons. Its powerful influence on posture and locomotion is brought about indirectly through its effects on the cerebral and brain stem structures that produce movement. It is important also to remember that the cerebellum does not initiate movements, but instead coordinates movements that are initiated elsewhere. The clinical signs of cerebellar disease reflect its coordinating functions. Thus, the dysmetria of a cerebellar ataxia reflects loss of the cerebellar influence on phasic movements of the extremities. The disequilibrium reflects the failure of the cerebellum to coordinate the vestibular system with the brain stem and spinal cord systems that maintain equilibrium during the continuously shifting needs of voluntary movement. Note that neither of these signs of cerebellar disease is present at rest when there is no demand for coordination. The cerebellum also participates in the coordination of eye positions and eye movements that occur in response to vestibular stimulation. The tonic deviations of the eyes and head and the positional nystagmus that occur in cerebellar disease reflect disturbances of these functions of the cerebellum.

Medulla and pons Structures in the medulla and pons have major influences on the tone of antigravity muscles, thus serving to adjust weight bearing to compensate for shifts in the center of gravity. They receive afferents from the labyrinths and the spinal cord and they act on lower motor neurons through vestibulo- and reticulospinal tracts. These structures also have a very major influence on the maintenance of the visual axis parallel with the horizon and fixing the eyes on a target during movements of the head. Lesions affecting these systems cause disturbances of righting, abnormalities of muscle tone in the limbs, head tilt, and nystagmus.

reflexes. These signs may be indistinguishable from those caused by lesions of the peripheral nervous system.

C. GENERAL CHARACTERISTICS OF NEUROLOGIC DISEASES Neurologic disease can be acute or chronic, progressive or nonprogressive. Neurologic signs reflect only the location of the lesion(s), not the cause. Neurologic diseases can sometimes cause intermittent signs (as in the case of epilepsy); some peripheral nerve or neuromuscular disease and some myopathies cause signs that fluctuate in severity from moment to moment or hour to hour or that vary in severity with exercise. Aside from these exceptions, the signs of neurologic diseases tend to be continuous and fluctuate very little in severity. The clinical signs of neurologic disease are caused by dysfunction of the neurons. The neuronal dysfunction can be caused by direct effects of the disease on the neurons or by the effects of the disease on the supporting elements (glia) or blood vessels. Neurologic diseases may result from causes inside the nervous system or outside the nervous system. The causes include any of the things that cause diseases in other organ systems.

D. CONCEPTS OF BRAIN LOCALIZATION The neurological examination provides the examiner with a list of clinical neurological abnormalities. These abnormalities reflect dysfunction of a part (or parts) of the nervous system. The examiner is able to attribute observed abnormalities to dysfunction of the appropriate part (or parts) of the nervous system because normal function of these areas is known. When localizing abnormalities to the brain, it is convenient to use the concept of neurological syndromes. The basis of this concept is that a specific group of clinical signs is representative of dysfunction of a specific area of the nervous system. Once a group of clinical signs (or a syndrome) is recognized, and the affected area of the brain identified, then a list of possible causes may be completed. Braund has described this approach in detail in a recent textbook.

E. EXAMPLES OF BRAIN LOCALIZATION Cerebellar syndrome

Spinal cord The spinal cord contains neuronal mechanisms that can produce stepping movements (alternating flexion and extension of the joints of the limb). The supraspinal mechanisms described above end on these mechanisms and shape or mold them according to the needs of the movement by acting directly on primary afferents, interneurons, gamma efferents, or alpha efferents. Disorders of the descending pathways produce paralysis or paresis, and exaggerated reflexes. Disorders of the segmental cells produce depression of

Clinical signs that are seen with lesions involving the cerebellum are as follows: Hypermetric gait, especially in thoracic limbs, with normal strength Truncal ataxia Intention tremors of the head Wide-based stance Exaggerated postural reactions Ipsilateral menace deficit (with normal vision) Anisocoria (contralateral pupil dilated)

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Cerebellum

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Decerebellate posture (rare) Vestibular signs (rare).

Vestibular syndrome Vestibular syndrome is frequently recognized in clinical practice. Signs of vestibular dysfunction may reflect either central (within medulla) or peripheral (vestibular portion of VIII, or vestibular receptors in petrosal portion of temporal bone) involvement. Clinical signs of vestibular dysfunction are as follows: Loss of balance Head tilt Falling/rolling Nystagmus (horizontal, rotatory, vertical, positional) Strabismus (ventrolateral) (Possible) V, VI, or VII deficits (Possible) Hornerâ&#x20AC;&#x2122;s syndrome (Possible) cerebellar signs (Possible) mental depression (Possible) hemiparesis with ipsilateral postural reaction deficits.

Cerebral syndrome Cerebral syndrome is characterized by the following clinical abnormalities: Seizures Altered mental status Change in behavior Abnormal movement and postures (pacing, compulsive walking, circling, head pressing) Postural reaction deficits in contralateral limbs Visual impairment with normal pupillary light reflexes (Possible) papilledema (Possible) abnormal (irregular) respiration.

Midbrain syndrome Clinical signs associated with midbrain syndrome are as follows: Paresis of all four limbs or the limbs on the side of the body contralateral to the lesion Exaggerated segmental reflexes and muscle tone in limbs on the side contralateral to the lesion, or in all four limbs (opisthotonos) Postural reaction deficits in contralateral limbs, or in all limbs Obtundation or coma Ipsilateral deficits of III (ventrolateral strabismus, dilated pupil unresponsive to light with normal vision, ptosis) Altered respiration (hyperventilation) (Possible) bilateral miosis.

Hypothalamic syndrome This syndrome is most often associated with pituitary tumors of dogs and cats. The hypothalamus regulates much of the bodyâ&#x20AC;&#x2122;s endocrine activity, and is involved in autonomic visceral body functions. Abnormalities of this area results in the following signs of dysfunction: Abnormal mental status Changes in behavior (hyperexcitability, aggression) Abnormal postures and movement (trembling, pacing, wandering, tight circling, head pressing) Bilateral II deficits (dilated pupils, depressed pupillary light reflexes, visual impairment) Abnormal temperature regulation Abnormal appetite Endocrine disturbances (diabetes insipidus, diabetes mellitus, hyperadrenocorticism, acromegaly) Seizures.

Multifocal syndrome Pontomedullary syndrome Clinical signs that are associated with dysfunction of this area of the brain are as follows: Paresis of all four limbs (tetraparesis) or of limbs on the same side of the body (hemiparesis). Normal to increased muscle tone and segmental reflexes in all limbs. Postural reaction deficits in the limbs on the same side as a lesion, or in all limbs. Cranial nerve deficits: Depressed palpebral reflex (V, VII) Decreased facial sensation (V) Paresis/paralysis of the jaw (V) Facial paresis/paralysis (VII) Head tilt, nystagmus, falling, rolling (VIII) Laryngeal/pharyngeal paresis/paralysis (IX, X) Tongue paresis/paralysis (XII) Abnormal respiration Mental depression.

Occasionally an animal may have clinical signs that reflect two or more different syndromes. This indicates that more than one lesion site may be present, and is termed a multifocal syndrome.

F. DIAGNOSTIC AIDS IN BRAIN DISORDERS Although it is possible to localize a problem to the brain and sometimes to the approximate location within the brain, on the basis of signalment, history, and the results of physical and neurologic examinations, it must be remembered that these signs may be the same regardless of the underlying cause. Brain tumors, infections, congenital disorders, trauma, vascular disorders, degeneration, immunologic and metabolic disorders, toxicities, and idiopathic disorders may result in similar clinical signs. For this reason it is essential to follow a logical diagnostic plan for a cat or dog with signs of brain dysfunction.

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Cerebrospinal fluid analysis Analysis of cerebrospinal fluid (CSF) is recommended as an aid in the diagnosis of a brain tumor. The results of CSF analysis may help to rule out inflammatory causes of cerebral dysfunction, and in some cases may support a diagnosis of a brain tumor. CSF bathes the entire CNS, both internally (the ventricles and central canal) and externally (the subarachnoid space). CSF composition may be affected by many nervous system diseases and the ease with which this fluid may be collected has made it an important diagnostic tool in the diagnosis of CNS disease. Unfortunately, for cells to be shed into the CSF a disease must involve the ventricular system or the subarachnoid space. Disorders involving deeper brain structures (e.g. neoplasms) may not shed cells into the CSF. Frequently these diseases disrupt the bloodbrain barrier (BBB) allowing protein to leak into the CSF and resulting in an increased protein level. CSF must be evaluated keeping in mind history and clinical signs. Neoplasms and some other non-inflammatory diseases may result in inflammatory changes in CSF composition. CSF composition may also change as a disease becomes more chronic. Also, following various therapies CSF may no longer accurately reflect an etiology. Care should be used in the collection of CSF, because frequently an increased intracranial pressure (ICP) may be present in association with a brain tumor, and pressure alterations associated with CSF removal may allow brain herniation. Because CSF pressure measurements are of limited usefulness, it is often desirable to utilize techniques such as hyperventilation to decrease intracranial pressure prior to CSF collection. CSF may be collected at either the cerebellomedullary cistern or by lumbar puncture. In general the cerebellomedullary cistern is easier to find, allows collection of a larger volume and generally has less blood contamination. All patients undergoing CSF collection should be anesthetized appropriately. If it is suspected that intracranial pressure is elevated the patient should be hyperventilated for several minutes prior to collection as well as during and after collection in order to decrease arterial CO2 and intracranial pressure. Complications of CSF collection include needle injury to the brain and herniation of the brain, usually due to high intracranial pressure. Both these complication

may be fatal if appropriate steps to reduce intracranial pressure (hyperventilation and mannitol administration) are not instituted immediately.

Cerebrospinal fluid collection For CSF collection from the cerebellomedullary cistern, a 20- or 22-gauge 1.5 inch (3.5 cm) spinal needle and a sterile container in which to collect fluid are needed. The hair over the area should be clipped and the skin prepared as for a sterile procedure. The patient is placed in lateral recumbency with the head parallel to the table and an assistant must hold the head flexed at 90o to the long axis of the body. A line drawn down the middle of the patientâ&#x20AC;&#x2122;s face and nose should be parallel to the table. These patients should be intubated to prevent airway obstruction. The landmarks for cisternal CSF collection are the wings of C1 and the occipital protuberance. The needle should be inserted where the line from the occipital protuberance (the midline) intersects a line drawn between the two wings of C1. The needle bevel should face cranially and the needle should be advanced slowly keeping it perpendicular to the long axis of the spine. A sudden loss of resistance may be felt as it enters the subarachnoid space and at that time the stylet should be removed in order for CSF to flow. Care must always be taken to prevent accidental needle movement and the needle should be held firmly with the thumb & forefinger each time the stylet is removed or replaced. In very small animals the fluid volume available may be very small and may take 30-45 seconds to appear in the hub of the needle. If no fluid appears the stylet may be replaced and the needle advanced further. If bone is encountered then the needle tip should be redirected. Failure to find the space is usually due to poor patient positioning, (most often insufficient flexing of the neck or the patientâ&#x20AC;&#x2122;s nose sloping downwards towards the table) or not being on the midline with needle placement. If the cisternal space can not be found the needle should be removed and the entire procedure repeated. If CSF flow is very slow, carefully occluding the jugular veins will increase CSF pressure and flow. Apnea or changes in respiratory rate not associated with anesthetic depth usually indicate brain herniation or damage. The needle should be immediately withdrawn, anesthesia discontinued and the patient hyperventilated until consciousness and normal respiration return. If the patient does not respond within 5 to 10 minutes to these maneuvers then mannitol should be administered. Once CSF begins to flow it should be allowed to drip freely into the container and at least one milliliter collected. If fluid needs to be stored for any length of time prior to cell analysis then it should be stored in a plastic container and refrigerated to stop cellular degeneration.

Cerebrospinal fluid analysis Always note from where the CSF was collected. CSF from the cisternal space has a lower protein than fluid from the lumbar space. Analysis should include gross visual examination, cytologic analysis, protein measurement and pos-

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Following a complete physical and neurologic examination, a minimum data base for an animal with signs of brain dysfunction should include a hemogram, serum chemistry panel, and urinalysis. Survey thoracic and abdominal radiographs help to rule out problems elsewhere. The major objective in doing these tests is to rule out disease elsewhere as a cause of the signs of cerebral dysfunction. Plain skull radiographs are useful for detecting problems of the skull or nasal cavity which have extended to the brain. Occasionally, lysis or hyperostosis of the skull may accompany a primary brain tumor (e.g. meningioma of cats) or there may be mineralization of a neoplasm. Skull radiographs are of little value in detecting dysfunction with the brain.

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sibly fluid culture. Normal CSF should appear clear and colorless. Turbidity may indicate increased white cell numbers and/or protein elevation. A pink color to the fluid may be due to blood contamination. Persistence of this color change after centrifugation of a small amount of sample may indicate the presence of free hemoglobin, suggesting previous subarachnoid hemorrhage, rather than sample contamination. Xanthochromia develops if more than 48 hours have elapsed following hemorrhage. Cytological preparation should be completed as soon as possible (within 30 minutes of collection), since CSF cells undergo degeneration rapidly. WBCs degrade faster than RBCs in the CSF, making interpretation difficult. Refrigeration does help to slow WBC lysis. The cytologic evaluation should begin with a total cell count on the unconcentrated fluid. A slide should then be prepared of concentrated fluid for evaluation of cell morphology and differential cell counts. The two most common slide preparation techniques are cytocentrifugation and sedimentation. The sedimentation technique is easy and reliable and may preserve cell architecture better than centrifugation methods. In normal CSF there should be less than 5 WBC/ul. Cell numbers may increase most commonly with inflammatory disease but also with tumors, necrosis, trauma, and vascular injury. The type and number of cells may reflect the cause of the inflammation. Again CSF is most accurate in acute, untreated illnesses. Correcting the number of WBCs in the CSF for blood contamination is possible only with very mild contamination. The WBC numbers in the CSF increase approximately 1 WBC/ul for each 500 to 700 RBCs/ul. A predominance of polymorphonuclear leukocytes in CSF may indicate a suppurative meningitis probably due to bacterial infection or to severe viral encephalitis. The presence of multiple cell types in CSF, including macrophages, lymphocytes, neutrophils and sometimes plasma cells is generally the result of a granulomatous inflammation, such as occurs with fungal, protozoal, and some idiopathic diseases. Mixed cell populations may also be seen with inadequately treated chronic bacterial infections and in response to foreign bodies. A nonsuppurative inflammation is diagnosed if the increased cell numbers are primarily mononuclear cells, especially lymphocytes. It is most characteristic of viral and rickettsial infections, although it can also be seen with neoplasms. CSF should be submitted for both aerobic and anaerobic bacterial culture and antibiotic sensitivity testing whenever abnormalities consistent with meningitis are found. Negative cultures are common even when bacterial or fungal organisms can be seen. Culturing the sedimented or centrifuged CSF may increase the likelihood of obtaining positive CSF culture. Causative organisms may also be isolated form the blood of animals with systemic infections. It is recommended that a large volume of CSF, preferably 2 or 3 ml, be collected for bacterial and/or fungal culture. Serology may also be useful in diagnosis of CNS fungal infections. In normal cerebellomedullary CSF, protein is less than 25 mg/dl and less than 45 mg/dl with lumbar puncture. Since storage of CSF does not affect protein it can be sent to an outside laboratory for protein evaluation. CSF protein is el-

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evated with many diseases including encephalitis, meningitis, neoplasms, trauma and infarcts. Over 75% of CSF protein should be albumin. With noninflammatory disruption of the blood-brain-barrier, (e.g. neoplasm and infarcts), most CSF protein will be albumin, whereas with increased intrathecal production (e.g. encephalitis) it is predominantly globulin. Where both albumin and globulin are elevated an inflammatory process affecting both the meninges and the CNS (e.g. FIP) should be suspected. Corticosteroid-responsive meningitis (aseptic meningitis) occurs in young dogs and may be the most frequently occurring form of meningitis in dogs. The diagnosis is made on the basis of increased white cells and protein in the CSF, failure to isolate an infectious agent from CSF and response to therapy with corticosteroids. It may be difficult to distinguish this disease form GME on the basis of CSF analysis. In general, increased CSF protein content and a normal to increased CSF white blood cell count have been considered “typical” of a brain neoplasm. In one study, only 39.6% of dogs with a primary brain tumor exhibited “typical” CSF alterations. The results of CSF analysis were normal in 10% of the dogs in this study, while the remaining 50.4% of dogs had a variety of nonspecific CSF changes. The CSF from dogs with a meningioma often may have an elevated white blood cell count (> 50/ul), with more than 50% of these cells being polymorphonuclear leukocytes. In another study, glial cell tumors predominated among those that resulted in CNS inflammation. Neoplastic cells may be present in CSF, particularly when sedimentation techniques are used for analysis. The use of CSF protein electrophoresis, and IgG index of CSF, may aid in the determination of the presence of a brain neoplasm. Little information is available regarding CSF alterations seen in association with feline brain tumors; however, changes are similar to those described for dogs.

Imaging Skull radiographs are useful in patients with suspected bony or cartilaginous changes (e.g. head trauma, bony tumors), but in general plain skull films are of limited value in patients with brain disease. Angiography and venography are amongst the techniques used in the past to try to diagnose brain disorders. These techniques have severe limitations and in most instances fail to define the exact extent of a neoplasm and its precise relationship to surrounding structures. These techniques have now been replaced with computed tomography (CT) and magnetic resonance imaging (MRI).

CT and MRI CT and MRI allow imaging of brain tissue rather than just the surrounding bony skull. Both can distinguish images which have only slightly different densities than the surrounding tissues and this can be further enhanced by contrast agents allowing the identification of masses and other abnormal tissues within the brain. Images obtained by means of MRI may be superior to those of CT especially in

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At the present time, biopsy is the sole method available for the diagnosis of brain tumor type in cats or dogs. Several biopsy methods have been described, including ultrasound-guided biopsy, and CT-guided biopsy. Ideally, an intracranial lesion should be biopsied prior to the institution of therapy of any type; however, biopsy is not always attempted because of practical considerations, such as cost and morbidity.

References for clinical syndromes Braund KG. Clinical Syndromes in Veterinary Neurology. Second edition. Mosby - Year Book Inc., Philadelphia, 1994.

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certain areas such as the brain stem, although CT is usually better for bony lesions (e.g. middle ear studies). While the major tumor types are reported to have characteristic CT or MRI appearances, non-neoplastic lesions may mimic the CT or MRI appearance of a neoplasm, and occasionally a metastasis may resemble a primary brain tumor on CT or MRI images. Patients for either CT or MRI must be anesthetized, intubated, and hyperventilated whenever an increase in ICP is even suspected. Proper patient positioning is extremely important. The animals should be placed in sternal recumbency with the head extended. The entire calvaria should be examined in the non contrast series of images. This should be followed by a post contrast series of images.

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Identification of lesions (localization & diagnostics) Third part: Neuromuscular Richard A. LeCouteur

Summary Some expression of generalized or localized muscular weakness is the principal clinical sign of neuromuscular dysfunction. Neuromuscular diseases are disorders of the motor unit, which is composed of 1) the motoneuron 2) the neuromuscular junctions, and 3) the myofibers innervated by the motoneuron. Based on these anatomic motor unit components, neuromuscular diseases are broadly subdivided into a) neuropathies, b) junctionopathies, c) myopathies, and d) neuromyopathies. This lecture will discuss dysfunction of the motor unit and the resulting variation in clinical signs that may occur. Functional manifestations of neuromuscular weakness may include paresis/paralysis, gait abnormalities, exercise related weakness, dysphagia, regurgitation, and dyspnea. Physical manifestations may include muscle atrophy, hypertrophy, and skeletal deformities. The localization and diagnosis of lesions in these areas will be covered in this lecture.

A. INTRODUCTION Neuromuscular diseases are disorders of the motor unit the basic functional and anatomical organization of neurons and muscle fibers. The essential components of each motor unit include: 1) a motor neuron consisting of its cell body (located within the CNS, either in the cranial nerve nuclei of the brainstem, or in the ventral horns of grey matter in the spinal cord) and its peripheral axon, supported by Schwann cells, 2) neuromuscular junctions, and 3) the myofibers innervated by the motoneuron. The arrival of impulses at the axon terminal causes a calcium-dependent release of acetylcholine (ACh) from the presynaptic axon terminals. This liberated ACh diffuses across the synaptic cleft to become complexed with specific ACh-receptor sites located on the postsynaptic sarcolemma (end-plate) of the myofiber. The formation of ACh-receptor complexes increases the permeability of the end-plate to Na+ and K+ ions and results in a local depolarization of the endplate, which in turn generates muscle action potentials over the entire sarcolemmal surface of each myofiber to initiate their contraction. The action of ACh is reversed by its diffusion away from ACh-receptor sites and its hydrolysis by acetylcholinesterase (AChE) present in the synaptic cleft. The

contraction of each myofiber involves the interaction (sliding) of the actin and myosin myofilaments coupled with the hydrolysis of ATP. The interaction of the actin and myosin myofilaments is modulated by the regulatory proteins troponin and tropomyosin, and the rate of their interaction (speed of shortening) is catalyzed by the activity of myosin ATP-ase. All motor units are not alike and may vary with regard to: 1) size (the number of myofibers innervated by a single motoneuron), 2) histochemical properties of the myofibers, and 3) functional properties related to their speed of contraction and resistance to fatigue. There are at least three and possibly five basic types of motor units based on their contractile and histochemical properties. The myofiber type composition of motor units is homogeneous. Each motor unit is composed of a single histochemical myofiber type, and not a mixture of myofiber types. Individual muscles are usually composed of a mixture of motor unit (myofiber) types, and the relative proportions of each may vary considerably between muscles. Individual myofibers of each motor unit are uniformly distributed throughout a relatively large area in a muscle and myofibers of the same motor unit are rarely contiguous. This scattered distribution results in a mosaic pattern of myofiber types within transversely sectioned and stained muscles. For a given muscle within the same species, the myofiber type composition, and mosaic distribution pattern within a muscle, appears to be reasonably constant and characteristic for that muscle.

B. CLASSIFICATION OF NEUROMUSCULAR DISORDERS A useful classification scheme of neuromuscular disease is based on the anatomic motor unit components which are primarily involved in the pathogenesis of the muscle weakness. Using this classification neuromuscular diseases are broadly subdivided into: 1. Neuropathies - disorders of the neuron, its cell body, axon, and/or Schwann cells (myelin) 2. Junctionopathies - disorders of the neuromuscular junction 3. Myopathies - disorders of the muscle fiber 4. Neuromyopathies - disorders of both the neurons and muscle fibers.

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C. CLINICAL SIGNS OF NEUROMUSCULAR DISORDERS Dysfunction of the motor unit results in lower motor neuron signs, seen clinically as muscle weakness. The expression of this weakness may vary considerably, and may include: paresis/paralysis, gait abnormalities, exercise related weakness, dysphagia, regurgitation, dyspnea, and dysphonia. The distribution of involvement may be local, regional, or generalized. In addition there may be gross deformities of muscle mass (i.e., atrophy, hypertrophy, and skeletal deformities). Any patient presented with some form of clinical weakness, should be viewed as potentially having a motor unit disorder. Conclusions that the patient is “merely weak because it is sick” should not be readily assumed without meticulous evaluations of the motor unit.

D. DIAGNOSIS OF NEUROMUSCULAR DISORDERS Establishing a diagnosis requires an informed and coordinated approach to defining a problem list through associations and direct observations (ie. a diagnostic plan). Since the signs of neuromuscular disease will be the same regardless of the lesion location (i.e. neuropathy, junctionopathy, or myopathy), additional diagnostic tests are needed to confirm the anatomic location. 1. Signalment, History, Physical and Neurologic Examinations Signalment: species, breed, age, sex, use History: congenital/acquired, course of complaint, response to treatment, exposure to toxins, etc. Findings: presence and distribution of abnormal findings on physical and neurologic examinations 2. Minimum Data Base Minimum data base: CBC, biochemistry panel, urinalysis, thoracic radiographs, and abdominal ultrasound. Measurement of muscle specific serum enzymes such as creatine kinase (CK,) as well as aspartate aminotransferase (AST), and lactic dehydrogenase (LDH), are very helpful in identifying neuromuscular disorders in which myonecrosis is a principal pathologic feature. Elevated serum enzyme activities help to differentiate myopathies from other neuromuscular disorders. Also immunologic procedures for the detection of myoglobin are becoming available, and should be a sensitive means of detecting myolysis as well. 3. Specific Diagnostic Tests a. Electromyography (EMG) - involves the detection and characterization of electrical activity (potentials) recorded from the patient’s muscles. A systematic study of individual muscles permits an accurate determination of the distribution of affected muscles. EMG electrodes detect potentials, which are then amplified and displayed on an oscilloscope and a printed record. Potentials are also amplified through an audio amplifier to record sounds, which often have frequencies and amplitudes characteristic of certain disorders. In animals, EMG examinations usually are conducted with the muscles at rest, (i.e., not contracting) and usually under general anesthesia. Under these conditions, resting po-

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tentials across muscle fiber membranes are maintained, and hence, normal muscles are “electrically silent”. With depolarization of muscle fiber membranes, potentials are generated that have a wave form usually consisting of negative and positive phases. The potentials generated are evaluated for amplitude, duration, number of phases and polarity, frequency and repetition. i) Insertional activity - brief bursts of electrical activity (potential charges) are induced by irritation of single muscle fibers caused by insertion of the EMG needles. After insertion and cessation of needle movement, normal muscles become electrically silent. Increased insertional activity (an increase in amplitude and prolonged duration) may be observed in neuromuscular diseases. Affected muscle fibers are hyperexcitable, having a lowered threshold due to diminished membrane potentials. ii) Spontaneous activity - is the spontaneous generation of potentials that are independent of mechanical stimulation. Spontaneous activity is an abnormal finding. The potentials generated include muscle action potentials generated by individual fibers (fibrillation potentials and positive sharp waves), and motor unit potentials generated by fibers of a motor unit (fasciculation potentials). Pronounced and prolonged spontaneous activity may be encountered in which there are repetitive, high frequency potentials generated with needle insertion, or other mechanical stimulation of muscle such as percussion. In myotonia, a condition of delayed relaxation of muscle fibers, there are phases of increasing amplitudes and frequencies of discharges, followed by decreasing amplitudes and frequencies, which convey the sound of diving propeller driven airplanes. These so-called “dive bomber” potentials, are also referred to as “myotonic” potentials. When the tip of the EMG needle is placed near the endplate region, spontaneous small amplitude (miniature) endplate potentials (“mepp’s”) may be detected. These are normal potentials due to the spontaneous release of individual quanta of ACh. This activity is also referred to as end-plate “noise”. b. Motor Nerve Conduction Velocity - provides information about the integrity of nerve fibers in peripheral nerves. Recordings are conducted while the patient in anesthetized. Demyelinating disorders cause slowed conduction in peripheral nerves. Ulnar and sciatic (perineal-tibial) nerves are most often employed for evaluation. c. Evoked Potential Recordings - with repetitive nerve stimulation provides information about the integrity of neuromuscular transmission. d. Nerve and Muscle Biopsy Examination. These procedures provide an opportunity to evaluate the morphology of portions of the motor unit and differentiate between neuropathies, junctionopathies, and myopathies, and in some instances, provides a definitive diagnosis. Since general anesthesia is required for EMG examination and nerve conduction measurements, muscle biopsy procedures should be done at the same time so that a second anesthetic is not needed. Selection of Muscle/Nerve Biopsy. EMG examination aids in identifying affected muscles/nerves for biopsy. Select involved, but not “end-stage” muscle for biopsy. Knowledge of normal muscle fiber type composition for muscles and species is required for biopsy interpretation.

Biopsy Procedures. Special methods of handling and processing are required for proper evaluation of muscle and nerve biopsies. Fresh frozen sections and special staining techniques are essential for light microscopic studies of both muscle and nerve. In addition, special fixatives are required for electron microscopic studies of muscle as well as “teased” nerve fiber studies. Use of formalin fixation of specimens is of limited value. “Open” biopsy techniques are preferred in small animals and “punch” biopsy techniques are preferred in horses.

E. HISTOPATHOLOGIC FEATURES OF NEUROPATHIES 1. General Features a. Angular Atrophy. The histopathologic hallmark of denervation is a characteristic patterns of myofiber atrophy. Myonecrosis is an uncommon reaction to denervation. With minimal denervation in which only a few myofibers are denervated, the denervated myofibers undergo atrophy and these atrophied myofibers tend to be angular in appearance. These angular atrophied type 1 and type 2 myofibers (“angular atrophy points to denervation”) tend to be scattered throughout the section and they are present in many fasciculi. This sign of denervation takes several weeks to develop after the denervating event. The angular morphology develops as a consequence of fiber atrophy occurring between normal or hypertrophied fibers. With greater involvement and progressive course, the angular atrophied fibers become more numerous and tend to occur in small groups (small grouped atrophy). As denervation progresses, healthy muscle fibers undergo compensatory hypertrophy. As a result, biopsies contain a mixture of very small and very large fibers. When most or all fibers in a muscle are denervated at about the same time (e.g., trauma to a muscle’s nerve, avulsions, acute severe disorders such as “coonhound paralysis”), all fibers undergo atrophy (panatrophy) and the angular morphology does not develop. Instead the fibers have a more uniform “puckered” or “scalloped” appearance (large grouped atrophy). b. Differentiation of Neurogenic Atrophy from Other Types of Myofiber Atrophy. Atrophy of muscle fibers is a common, though non-specific, reaction to a variety of disease states and activity levels. As previously described, when myofiber atrophy is selective, fibers undergoing atrophy may be angular to anguloid in appearance, while in nonselective atrophy involving all/most fibers, myofibers tend to be more rounded to polygonal in shape. (i) Cachetic/Disuse Atrophy - tends to affect all fiber types resulting in a rather uniform decrease in fiber size of most fibers; however, quantitative data suggest that type 2 fibers are proportionally more affected. (ii) Fractures/Tenotomy - shortening of a muscle’s resting length, secondary to trauma results in selective/preferential atrophy of type 1 fibers. (iii) Type 2 fiber atrophy - selective type 2 fiber atrophy which may be angular develops secondarily in the presence of excess glucocorticoids. The condition is frequently re-

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ferred to as steroid myopathy. This change has been seen in patients with Cushing’s Disease and patients receiving longterm steroid medication for other disorders. Grossly, muscle atrophy may become severe, particularly the muscles of mastication in the dog, and result in profound weakness. c. Pyknotic nuclear clumps - represent the end-stage of denervation and develop if denervated fibers are not reinnervated. These result from a drastic loss of myofibrils with clumps of myonuclei enclosed within the sarcolemma. A chronic change which takes some months to develop. d. Myofiber type grouping - results when previously denervated muscle fibers are reinnervated. If the new axon is of a different motor unit type than the denervated fiber, the reinnervated fiber will assume the characteristics of the new motor unit (e.g., denervated fast-twitch, type 2 fibers reinnervated by axonal sprouts of slow-twitch motoneurons will convert to the slow-twitch type 1 fibers). These conversions alter the normal mosaic distribution pattern to groups of like fiber types, i.e., muscle “type grouping”. Collateral sprouting and reinnervation results in the formation of larger than normal motor units. The motor unit potentials generated by these enlarged motor units are referred to as “giant” motor unit potentials. Type grouping may be though of as the morphologic equivalent of these giant potentials. These changes take 6 months or more to develop, and they are indicative of a chronic disorder. Denervation of giant motor units results in “large grouped atrophy” in histologic sections. 2. Special Features a. Myofiber Type Predominance or Paucity - describes the predominance of one fiber type over another in a section. This may be normal or abnormal, depending on the specific muscle and the species of animal. In the abnormal state, this may represent an excess or a deficiency of a given fiber type. There are two instances in which muscles commonly have fiber type predominance/paucity: (i) Growing and Developing Muscle - the onset of neuromuscular disease, particularly neuropathies, superimposed on the early growth and differentiation of developing muscle frequently results in type 1 fiber predominance/type 2 fiber paucity. (ii) Thyroid Function - also affects the proportion of fiber types in a muscle. Hypothyroid states result in a transformation of type 2 fibers to type 1 fibers, leading to type 1 fiber predominance. Conversely hyperthyroid states result in the opposite effect (type 1 fibers transform to type 2) leading to type 2 fiber predominance. Polyneuropathies in dogs with hypothyroidism are not uncommon and biopsies from these patients often have type 1 fiber predominance. b. Intramuscular Nerve Branches - are available for evaluation in approximately 40% of the muscle biopsies. Staining techniques applicable to sections of peripheral nerve provide similar opportunities for evaluation of nerve branches in the muscle biopsy.

F. SPECIFIC NEUROPATHIES 1. Motoneuron Disorders Inherited and acquired motoneuron disorders have been

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described in dogs ( e.g. spinal muscular atrophy of Brittany spaniels, swedish Lapland, English pointer, german shepherd, Rottweiler, Cairn terrier). These are chronic progressive disorders resulting from degeneration of motoneurons in the grey matter of the spinal cord and nuclei of the brain stem. Progressive denervation of muscle fibers results in paresis, paralysis, and severe muscle atrophy. 2. Peripheral Neuropathies Polyneuropathies represent the single largest group of neuromuscular disorders. Many are idiopathic (i.e., our diagnostic skills are insufficient to establish etiology). Disorders include: acute and recurrent polyradiculoneuritis, metabolic (diabetes, hypothyroidism, hypoadrenocorticism, hyperinsulinism), toxic, and lysosomal storage disorders (i.e., Krabbeâ&#x20AC;&#x2122;s globoid cell leukodystrophy, i.e., galacto-cerebrosidase deficiency, and Niemann-Pick disease, i.e., sphingomyelinase deficiency). a. Acute idiopathic polyradiculoneuritis An immune-mediated segmental demyelination and degeneration of axons that is found in dogs which usually, but not always, have been exposed to raccoons (so called â&#x20AC;&#x153;coon hound paralysisâ&#x20AC;?). Typically signs of weakness develop in the pelvic limbs and ascend rapidly, resulting in flaccid tetraplegia or paresis 7 to 14 days after exposure. Spinal reflexes are severely depressed or absent. Affected dogs become tetraparetic 24 to 48 hours after signs of muscle weakness first develop and may develop respiratory paralysis. Defecation, urination, and tail mobility are usually normal as the sacral and caudal nerve roots are relatively spared and cranial nerve involvement is uncommon. Although voluntary micturition is preserved it is advisable to help express the bladder in order to get complete emptying. Swallowing, gag reflex, and esophageal function are normal and affected dogs usually maintain an appetite and eat and drink with assistance. Paralysis usually peaks within 10 days of the onset of clinical signs. Although motor deficits are most obvious, many animals seem to experience discomfort on light palpation of their extremities. With proper supportive care prognosis for recovery is good. The course of the disease is 3 to 6 weeks and recurrences do occur. The ventral nerve roots and spinal nerves are primarily affected, resulting in neurogenic muscle atrophy and electrodiagnostic testing usually provides evidence of widespread motor denervation. Fibrillation and positive sharp waves are seen frequently and myotonic bursts occur occasionally. The disease must be differentiated from tick paralysis and botulism, both of which are disorders of neuromuscular transmission (i.e. junctionopathies). b. Hypothyroid neuropathy Cranial and peripheral polyneuropathies have been associated with hypothyroidism in dogs. Laryngeal paralysis, megaesophagus, and peripheral vestibular dysfunction, often in association with other cranial and peripheral nerve deficits, are frequently associated with hypothyroidism. Clinical signs are those of lower motor neuron dysfunction (muscle weakness, intermittent lameness, cranial nerve dysfunction), and affected animals may not have obvious signs of hypothyroidism. The diagnosis is based on the levels of free T4 and TSH. Denervation potentials and nerve conduction velocity delays are seen on EMG examination. Im-

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provement in motor function may take several months of treatment with thyroid supplementation and dogs with severe, generalized denervation may not fully recover. c. Diabetic neuropathy Peripheral neuropathy associated with diabetes has been reported in dogs and cats. Axons are affected primarily with secondary demyelination and distal axons are especially susceptible. In dogs the neuropathy may range from being subclinical to acute paresis. Clinical signs are more consistent in cats and include a characteristic plantigrade stance, depressed patellar reflexes, muscle wasting, and proprioceptive deficits. Clinical signs may take 6-12 months to resolve once the diabetes is controlled.

G. JUNCTIONOPATHIES Histopathologic changes are usually absent or non-specific in disorders of the neuromuscular junction. Diagnoses are usually based on electrodiagnostic, biochemical, immunologic, or toxicologic testing. 1. Presynaptic Disorders a. Reduced ACh Release - weakness induced by inability to activate sufficient numbers of ACh-receptors. (i) Hypocalcemia - release of ACh from axon terminals is calcium ion dependent. Hypermagnesemia causes same effect and stabilizes postsynaptic membrane as well. Cows - post-parturient paresis (milk fever), flaccid paralysis. Principal signs referable to effects on neuromuscular transmission. Dogs - puerperal tetany (eclampsia). Principal signs referable to hypocalcemic effect on lowering threshold of resting membrane potential in neurons thereby causing spontaneous depolarization of neurons and overriding blockade of ACh release. (ii) Botulism - (Clostridium botulinum) - toxin irreversibly binds to presynaptic membrane and blocks release of ACh. Results in functional denervation of all muscle fibers. Tick paralysis may be similar but is reversible upon removal of the tick. (iii) Aminoglycoside Antibiotics - inhibit ACh release. These antibiotics also decrease ACh sensitivity of postsynaptic membrane and are contraindicated for use in patients with postsynaptic disorders such as myasthenia gravis. b. Increased ACh Release - weakness induced by continued depolarization (hyperexcitability) of postsynaptic membrane. (i) Hypomagnesemia - grass and transport tetany of sheep and cattle. Hypercalcemia produces similar effect. (ii) Black Widow Spider Toxin - binds to presynaptic membrane and stimulates ACh release. 2. Synaptic Cleft Disorders Cholinesterase Inhibitors - inhibit breakdown of ACh and thereby prolong action of ACh on postsynaptic membrane. Important pharmacologic agents include edrophonium chloride (ultrashort acting, minutes), pyridostigmine bromide (short acting, hours), and neostigmine bromine (Prostigmin; short acting, hours). Organophosphates are commonly used to control external parasites in dogs and cats and for insect control. Organophosphate toxicity results in

the clinical signs of overstimulation of the parasympathetic nervous system - salivation, lacrimation, bradycardia, pupillary constriction and pronounced gastrointestinal sounds. In dogs clinical signs usually occur within minutes of ingestion of excessive compound, but in cats a delayed neurotoxicity may occur, days or weeks after minimal exposure to organophosphates. 3. Postsynaptic Disorders a. Myasthenia Gravis (MG) Basic lesion is a deficiency of ACh-receptors on postsynaptic membrane. Both congenital and acquired forms of this condition occur in dogs, cats, and humans. To date, studies suggest the pathophysiology of these conditions are similar among these species. (i) Acquired Myasthenia Gravis. Etiology and Pathogenesis. Acquired (immune-mediated) myasthenia gravis is due to antibody-mediated destruction of Ach-receptors and is a common neuromuscular disorder in dogs and sporadically reported in cats. While the immune-mediated destruction of ACh-receptors is well documented, the underlying cause of this immune mediated disorder remains unknown. History and Clinical Signs. Acquired MG affects numerous breeds of dogs older than 1 year of age. There appears to be an age-related incidence, with peaks at 2-4 years and 9-13 years. Signs of muscular weakness may be focal with selective involvement of the esophageal, pharyngeal, and facial muscles, or diffuse, with signs of generalized muscle weakness. In one study it was estimated that one fourth of the canine patients, presented with idiopathic megaesophagus, had focal MG. Signs of generalized muscle weakness may vary considerably, ranging from some intolerance to exercise, which improves with rest, to acute tetraplegia. Patients with focal or generalized signs, and megaesophagus, often present with pneumonia secondary to aspiration. Evaluation of the thorax may reveal the presence of thymomas, which may be implicated in the etiology of this immune disorder. Diagnostic Tests. Pharmacologic Testing - the IV administration of 1-10 mg of edrophonium chloride. A presumptive positive test results in transient improvement in the clinical weakness. Sometimes objective criteria for this test are difficult to establish. Electrodiagnostic Testing - involves recording evoked muscle action potentials during repetitive nerve stimulation at 2-10 Hz. A decline in the amplitude of successive potentials (decremental response), provides a presumptive positive test for MG. Immunologic Testing - screening tests involve: a) incubating the patients biopsy with the immunoreagent SPAHRP (Staphylococcal protein A conjugated to horseradish peroxidase), to stain for IgG localization at neuromuscular junctions, and b) incubating the patientâ&#x20AC;&#x2122;s sera on sections from a healthy dog and subsequently incubating the section with SPA-HRP to detect fixation of circulating IgG to neuromuscular junctions. Specific testing involves the use of an immunoprecipitation radioimmunoassay for the determination of ACh receptor antibody titers. Treatment. This involves improving neuromuscular

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transmission through the use of cholinesterase inhibitors (pyridostigmine, 0.5-1 mg/kg per os, BID to TID as needed) and/or suppression of the immune response with steroids, (Prednisone, 2 mg/kg BID). Monitor treatment with pyridostigmine for signs of excessive cholinergic stimulation (salivation, defecation, weakness, etc). It is not uncommon for dogs to spontaneously abort their immune response, and fully recover without treatment. This disorder in cats appears to be more difficult to manage. (ii) Congenital Myasthenia Gravis. An hereditary disorder resulting in deficiency of ACh receptors on the postsynaptic membrane. It has been reported in Jack Russell Terriers, Springer spaniels, and Smooth Fox Terriers. Onset is usually apparent at 6-8 weeks of age, with signs of generalized muscular weakness associated with exercise. Megaesophagus is not common. Weakness becomes progressively severe, leading to tetraplegia and death. Diagnostic tests consist of pharmacologic and electrodiagnostic tests only. Prognosis is very poor. Treatment with pyridostigmine is helpful and some animals have been maintained for 12-24 months. Genetic counselling is important since the disorder appears to be inherited as an autosomal recessive condition. b. Neuromuscular Blocking Agents (Muscle Relaxants). The effects of two classes of neuromuscular blocking agents commonly used as muscle relaxants during anesthesia should be included here: (i) Non-depolarizing agents - include d-Tubocurarine, gallamine, and pancuronium. These agents compete with Ach for the Ach-receptor. When bound to the receptor, the ion channel does not open, preventing depolarization of the membrane. (ii) Depolarizing agents - included succinylcholine and decamethonium. These agents compete with ACh for the ACh-receptor. When bound to the receptor, the ion channel opens, causing depolarization of the membrane.

H. MYOPATHIES In small animals, myopathies are relatively uncommon and encountered less frequently than neuropathies and junctionopathies, while the converse is generally true in large animals. Myopathies may be generally subdivided into non-inflammatory and inflammatory myopathies. 1. Non-Inflammatory Myopathies The histopathologic changes in non-inflammatory myopathies usually involve the spectrum of myonecrosis, phagocytosis, and regeneration, in which the degree of cellular infiltration is proportional to the extent of myonecrosis present, and its distribution is largely limited to necrotic fibers. Macrophages constitute the principal cell type. Central nuclei are common. In chronic myopathies there may be a mixture of atrophied and hypertrophied fibers, with their morphology being more â&#x20AC;&#x153;ovoidâ&#x20AC;? than angular, and increased endomysial connective tissue. Occasionally necrotic fibers may be calcified. All these changes are relatively non-specific and secondary to agents that result in myonecrosis. In metabolic myopathies the fibers frequently contain storage products which appear as vacuoles.

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a. X-Linked Muscular Dystrophy of Dogs and Cats Etiology and pathogenesis. This is an hereditary myopathy in which there is a deficiency of dystrophin, a cytoskeletal protein associated with the inner face of the sarcolemma. The pathobiology of this disorder appears to be identical to Duchenne muscular dystrophy, affecting young male children. History and clinical signs. The disorder is best recognized and characterized in Golden Retrievers. Other species of dogs include Rottweilers, Samoyeds, and possibly Irish Terriers. In cats it has been documented in domestic short hair cats. In dogs the disorder is usually recognized between 8 and 10 weeks of age. Signs may include generalized weakness, a stiff-limbed, short strided, shuffling gait, some reduced mobility of the jaws, and difficulty with chewing and swallowing associated with excess salivation. The weakness and signs are progressive, with poorly developed muscle mass, body stature, and spinal curvature. In advanced stages some muscle groups may appear grossly hypertrophied. Cardiac muscle may also become involved. Recognition of this disorder in cats is more recent and the findings are similar to those in dogs. While the onset is likely similar to that in the dog, reported cases have been somewhat later in onset, 5 to 25 months of age; however the histories suggest earlier clinical signs. Gross hypertrophy of the tongue and diaphragm have been a common finding. Diagnostic Tests. Diagnostic tests include serum CK, which may be elevated to 300 times normal; EMG examination which reveals repetitive, high frequency discharges; and muscle biopsy examination which reveals multifocal areas of necrosis, necrosis and phagocytosis, and regeneration. In the later stages, muscle fiber hypertrophy and fiber splitting is common along with fibrosis. Specific information is provided through the use of immunocytochemical staining techniques to detect dystrophin in sections (or lack thereof) and/or the muscle may be assayed for the presence of dystrophin. Treatment. Currently there is no cure and lifespan is shortened due to secondary complications. Future research advances in this area will have widespread benefits for both animals and humans. b. Metabolic Muscle Disorders These are relatively uncommon disorders of carbohydrate, lipid, and oxygen metabolism that generally induce muscle weakness by supplying insufficient energy (ATP) to sustain muscle contraction, and other cellular functions with a high energy requirement. (i) Malignant Hyperthermia - is a hypermetabolic and hypercontractile muscle disorder triggered by inhalant anesthetics (e.g., halothane), depolarizing muscle relaxants (e.g., succinylcholine) or other stressors (e.g., exercise). The defect appears to be due to a hypersensitivity of the calcium ion release channel of the sarcoplasmic reticulum (i.e., the ryanodine receptor of the terminal cisternae) that facilitates channel opening and inhibits channel closing. Affected muscle produces excess lactic acid and heat, resulting in myolysis and the release of potassium and proteins (e.g., myoglobin). The elevation in body temperature can cause damage to other tissues (nervous, renal, hepatic) and death. The condition affects humans and swine and it has been reported, but less well studied in other species, such as dogs

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and horses. The condition in pigs is called Porcine Stress Syndrome, and results in pale, soft, and exudative (PSE) pork at slaughter. Capture myopathy in wild animals appears to be a similar syndrome of excessive muscular activity in attempting to escape, however no basic pre-stressor defect is likely to be involved. (ii) Myotonias - are disorders in which there is sustained (tetanic) muscle contraction associated with repetitive depolarization of muscle fibers. In affected individuals, there is involuntary contraction of a muscle that persists after voluntary movement or stimulation. Congenital myotonias occur in goats, dogs, (Chow Chow, Cocker spaniel, labrador retriever, Samoyed, Staffordshire terrier, West Highland white terrier), horses, and humans. The principal defect is an altered chloride conductance causing postexcitement depolarization of the muscle membrane and continued contraction of the muscle. Clinical signs include abnormal stiff gait, abduction of forelimbs, muscle hypertrophy and a characteristic myotonic dimple which persists for 30-40 seconds after direct muscle stimulation (tongue or shaved limb). EMG findings include high-frequency myotonic discharges with continuous insertional activity and possible decremental response. Nerve conduction velocity is normal and muscle biopsy variable (hypertrophy, atrophy and degeneration). There is no treatment for the disease other than avoiding prolonged exercise and the disease is not progressive. (iii) Glycogen Storage Disorders - are rare, usually genetically determined (autosomal recessive), degenerative disorders resulting from a specific enzyme deficiency. As a result there is accumulation and storage of the substrate(s) in cells. Glycogen storage disorders are the result of a deficiency of one of the enzymes involved in glycogen synthesis or degradation. This results in inadequate glycogen utilization, and excess glycogen accumulates in skeletal and cardiac muscle and in the CNS. These are rare disorders in dogs and cats. Glycogen storage disorders have been reported in Swedish Lapland dogs, English springer spaniel dogs, German shepherds, Akitas, toy breed dogs, and cats. (iv) Lipid Storage Myopathies - are sporadically reported in dogs, with lipid storage occurring in type 1 myofibers. In humans, carnitine deficiency results in lipid storage within type 1 myofibers. Carnitine serves as a carrier molecule for long-chain fatty acid transport through the inner mitochondrial membrane for subsequent betaoxidation in the mitochondrial matrix. While a similar pattern of glycogen storage exists in dogs, carnitine deficiency has not been established as the cause. (v) Electrolyte Myopathies - are abnormalities of potassium metabolism involving both hypo- and hyperkalemic states, and frequently result in accumulation of fluid filled vacuoles. Feline Hypokalemic Polymyopathy is a manifestation of chronic potassium depletion and is thought to be one of the most common causes of generalized muscle weakness in cats. The hypokalemia is thought to be a total body depletion of potassium rather than a redistribution between the intracellular and extracellular compartments. A combination of low dietary intake of potassium and increased urinary potassium loss over a period of months may lead to a depletion of body stores. This condition, or a variant of it, has been re-

ported in Burmese cats, which may be more sensitive to the effects of low potassium. Affected cats present with acute onset of generalized weakness, reluctance to walk, persistent ventroflexion of the neck, stiff gait, muscle pain when handled or palpated, muscle atrophy, anorexia and weight loss and in severe cases respiratory muscle paralysis. Abnormal serum chemistry results include: low potassium(<3.5 mEq/L), increased creatine kinase (500-10,000 IU/L), increased creatinine (2.5-5 mg/dl), and mild to moderate metabolic acidosis. Urine specific gravity may be low and fractional urinary excretion of potassium is increased (normal is 4.7-14.3%). EMG abnormalities are found in multiple muscle groups and include frequent positive sharp waves, fibrillation potentials, occasional bizarre high-frequency discharges with normal nerve conduction velocities. Muscle histopathology is usually normal. Potassium administration which initially is usually administered intravenously. High concentrations are usually necessary to start. Oral potassium elixir and potassium gluconate powder may be used for long term supplementation. 2. Inflammatory Myopathies The inflammatory myopathies possess many of the changes described for non-inflammatory myopathies. However, in addition, they are characterized by a disproportionate number of infiltrating cells which may include lymphocytes/plasma cells, polymorphonuclear leukocytes and/or eosinophils in addition to macrophages. In these disorders, the cellular infiltrates comprise an integral part of the disorder’s pathogenesis and not merely a secondary response to cell death. The infiltrating cells often have a perivascular distribution. Identification and characterization of the infiltrating cell type assists in the definition, and recognition of these disorders. The use of the term “myositis” is reserved for inflammatory myopathies. Inflammatory myopathies may be due to infectious or immune-mediated agents. a. Masticatory Muscle Myositis - (formerly called eosinophilic and/or atrophic myositis) is an inflammatory muscle disorder limited to the muscles of mastication in dogs. Muscles of mastication in dogs are composed of 2M fibers, which differ from the 2A fibers in limb muscles. An immune response has been identified in which antibodies are selectively produced against type 2M fibers. The disorder may be acute or chronic. Acute onset usually presents with bilateral swelling of the temporalis and masseter muscles, and possibly exophthalmia, due to swelling of the pterygoid muscles. It usually affects large-breed dogs, with no age or gender predilection. Dogs may be febrile with conjunctivitis, enlarged lymph nodes, tonsils, and splenomegaly. Patients exhibit pain, with opening or manipulation of jaws (trismus). Chronic onset may result front insidious onset, or as a result of repeated acute bouts. Dogs present with masticatory muscle atrophy, which may be marked, leaving the patient with a “skull-like” appearance. Diagnostic tests include measurement of CK; however, elevations may be modest, due to limited involvement of masticatory muscles. EMG examination helps define distribution of involvement, but may be difficult to perform in severely atrophied muscles. Muscle biopsies detect lesions and presence of IgG in type 2M fibers while serologic testing confirms presence of circulating antibodies against 2M fibers.

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Treatment is directed towards the suppression of the immune response with steroids. Long-term medication may be needed to maintain remission. b. Polymyositis - is a generalized inflammatory myopathy caused by infectious agents (viral, bacterial, and parasitic) and ill-defined immune mediated mechanisms. Elevations in CK are usually marked and muscle biopsies are frequently helpful in detecting parasitic cysts in Toxoplasma, Neosporum, Trichinella and Sarcocystis myositis. c. Dermatomyositis - occurs as a familial disorder in Collies, and possibly Shetland sheepdogs. Dermatitis involves the face, ears, and distal extremities. Muscle lesions have been described in muscles of mastication and distal limb muscles. d. Protozoal polymyositis. Toxoplasma gondii is the most common cause of infectious myositis. Neospora caninum causes similar signs and may have been called toxoplasmosis in the past. Both organisms tend to cause more severe signs in very young animals and have an increased likelihood of causing signs in immunosuppressed animals. Toxoplasmosis is often associated with canine distemper infection whereas neosporosis is not associated with concurrent infection. Gait abnormalities are present in affected animals and include a hopping gait, progressive pelvic limb paresis, rigid extension of the pelvic limbs, progressive ascending paralysis is more common with neosporosis, initially severe muscle pain and atrophy as the disease progresses. Stupor, seizures, and chorioretinitis may occur with CNS disease. Creatine kinase is elevated in the active phase of the disease. Histopathological changes in muscle include: pronounced fiber atrophy, severe multifocal necrosis, mononuclear granulomatous inflammation, and severe interstitial fibrosis in chronic cases. The presence of organisms, free or in cysts is definitive, but these are not always found. Single antibody titers are not diagnostic, but rising titers support the diagnosis. Serum with antibodies to N. Caninum does not react with T. Gondii organisms, and vice versa. CSF analysis may reveal mixed pleocytosis, and a high protein content. Indirect fluorescent antibody testing of serum, CSF, or tissue may aid in differentiating N. Caninum from T. Gondii. Clindamycin or trimethoprim/sulfadiazine are the treatment of choice and animals with acute systemic disease may respond well. 3. Idiopathic Myopathies a. Fibrotic Myopathy - is a chronic, progressive disorders that result in severe muscle contracture and fibrosis. In dogs this condition has been reported in the semitendinosus, quadriceps, supraspinatus, infraspinatus, rectus femoris, and gracilis muscles and in the semitendinosus muscle in the cat. The cause is not known and possible etiologies include a primary neuropathy or myopathy, frequent intramuscular injections, exercise-induce trauma, or chronic trauma with tearing and stretching of muscle fibers, or a congenital disorder. Muscle is replaced by dense collagenous connective tissue, resulting in a taut fibrous band and the affected develops a nonpainful, mechanical lameness, the severity of which depends on the muscle involved and the extent of the fibrosis. On physical examination a thin fibrous band can be palpated, which replaces the muscle belly. Histopathology of affected muscles reveals dense collagenous connective tissue

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replacing muscle fibers and there is minimal inflammation. No EMG activity is detected form the fibrous band and bizarre high-frequency discharges may occur with incomplete replacement of muscle fibers. Surgery is not recommended unless the lameness is disabling. If surgery is undertaken the goal is to release the fibrous band, but prognosis must be guarded because of the likely recurrence of the fibrous band within 3-8 months. b. Infraspinatous Muscle Contracture - occurs primarily in hunting or working breeds in dogs and is usually unilateral. The cause is not known, but it is thought to be a primary muscle disorder, possibly associated with trauma, causing incomplete rupture of the muscle, and resulting in progressive fibrosis and contracture over 2-4 weeks. Initially, the dog has an acute onset of pain in the shoulder during or soon after exercise. The lameness gradually subsides, but never resolves. Two to four weeks after the initial injury, a nonpainful mechanical lameness of the foreleg develops and the gait is characterized by adduction of the elbow and abduction of the foreleg, with outward rotation of the antebrachium and carpus. The limb is laterally circumducted with each stride, and the foot flips forward. Palpation of the forelimb reveals that the humerus rotates outward when the elbow joint is flexed and range of motion in the shoulder joint is limited. Disuse atrophy of the infraspinatus, supraspinatus, and spinous deltoid muscles is evident from the prominent scapular spine. Tenotomy of the tendon of insertion of the infraspinatous muscle should allow the forelimb to be more easily adducted and the shoulder range of motion is improved. Activity should be limited for 1-2 weeks after surgery and prognosis for a full recovery is excellent. c. Myositis Ossificans - is the formation of bone in muscle. There is usually minimal inflammation, and muscle is not always involved. It is reported in dogs and cats and has been well described in dobermans, where some authors believe it may be a separate disease entity - von Willebrand heterotopic osteochondrofibrosis in Doberman pinschers. Progressive or generalized myositis ossificans is also known as progressive ossifying fibrodysplasia or progressive or generalized ossifying myositis. It is characterized by the development of excessive fibrous connective tissue, which results in widespread muscle degeneration and ultimately leads to dystrophic calcification and ossification. It has been reported in young to middle-aged cats. The cause is not known and the localized form may be associated with trauma, infection, ossifying hematoma, and metaplasia of muscle and connective tissue to cartilage and bone.

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Localized ossifying myositis results in a palpable, firm enlargement in affected muscles, with chronic lameness, pain after exercise and muscle atrophy. Progressive ossifying fibrodysplasia occurs in young to middleaged cats and results in firm nodules anywhere on the body, but predominantly on the neck and back. Limbs, especially the pelvic limbs may be stiff which may progress to difficulty walking. Proximal limb musculature is enlarged and firm, painful, and has limited range of motion. Affected cats may be disabled within 2 weeks to several months. Soft tissue mineralization occurs within 3-6 weeks of injury and mature bone in soft tissue after 2-6 months. Radiographs of affected areas show multiple mineralized densities. There may or may not be a periosteal reaction. On histopathology there is progressive maturation of bone centrally to peripherally. The central zone contains undifferentiated cells and fibroblasts and may resemble a sarcoma, the intermediate zone contains osteoid and some areas of immature bone and the peripheral zone contains mature bone. It does not invade the surrounding soft tissue. Affected muscle has excessive connective tissue between muscle fibers, mononuclear infiltration and muscle atrophy and hyaline degeneration. If clinical signs are minimal no treatment is recommended for localized ossifying myositis, and rest, compressive bandages, and aspirin may help to relieve the acute pain. Surgical excision is indicated to alleviate discomfort and restore normal limb function. In humans if surgery is performed within 6 months, i.e. when the lesion is immature there is a high rate of recurrence. Post operative physical therapy is important. There is no effective treatment for progressive ossifying fibrodysplasia. 4. Neoplasia Muscle tumors may be primary, originating from skeletal muscle (rhabdomyoma, rhabdomyosarcoma) secondary, metastatic spread from tumors originating elsewhere, or local invasion of tumors into muscle form rapidly expanding cutaneous or bone tumors. Age of onset is variable although secondary tumor spread usually occurs in middle-aged animals. Clinical signs depend on the muscle group affected and firm, nonpainful swelling, distortion of the area, and lameness are common. Diagnosis is confirmed by biopsy and histopathologic assessment. Staging of the disease with lymph node biopsy and thoracic radiographs is important. For primary neoplasia, surgical excision is preferred, but may be ineffectual if the neoplasm is difficult to reach or invasive. Amputation of the limb may be necessary to attain adequate surgical margins. Treatment of secondary neoplasia depends on the therapy indicated for the primary tumor.

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Management of spinal trauma Richard A. LeCouteur

Summary

A. INTRODUCTION

The successful management of a dog or cat with spinal cord injury demands aggressive and prompt attention to both non-neural and neural injuries. Decisions regarding medical and/or surgical treatments must be based on thorough physical and neurologic examinations and careful interpretation of radiographic findings. Accurate serial examinations of the affected animal are essential in order to determine the response to therapy already instituted and the need for more aggressive management. Medical management of animals with spinal cord injuries is effective in many instances, but must be approached rationally with knowledge of drug effects and indications. While medical management alone may be sufficient therapy in some cases, surgical therapy is often required. Surgical decompression of the spinal cord following injury should not be considered a last resort, but should be approached in a timely fashion on the basis of the recommendations outlined above. Neurosurgical procedures require specialized knowledge and equipment, so prompt referral of dogs and cats suffering from spinal cord injury to qualified surgeons is often indicated. Finally, the management of animals with central nervous system trauma requires time, patience, and attention to detail. Owners should be made aware at the outset of treatment of such factors as prognosis, expense involved, expected time form treatment to recovery, and most importantly, the need for prolonged physical therapy.

Management of a dog or cat with spinal injury requires understanding of basic neuroanatomy and physiology. It also demands knowledge of effects produced by pharmacologic agents and other interventions, such as fluid therapy. Most importantly, it requires that a veterinarian establish a list of priorities for management and recognize those situations that are truly life threatening.

Since the vast majority of spinal cord injuries cases are caused by direct trauma, a complete physical examination must be obtained first, as many of these patients will have additional problems (e.g. pneumothorax, diaphragmatic hernia, urogenital injuries, and other orthopedic injuries). Extreme care must be taken at all times to avoid exacerbating any spinal cord injury, especially once the patient is anesthetized and no longer able to protect the affected area. Physical examination and patient stabilization, with management of life threatening injuries, is the initial objective. Radiographic findings must be evaluated in conjunction with the neurological examination findings. This lecture will cover the pathophysiology of spinal cord trauma and the medical and surgical management of these patients.

B. ETIOLOGY AND PATHOGENESIS Spinal cord injuries in dogs and cats result must frequently from direct physical trauma, vertebral fracture or luxation, or from intervertebral disc protrusion/extrusion. Following injury, the spinal cord may undergo sustained compression, distraction, or both. The severity of a spinal cord injury, as determined by the eventual quality of recovery, is related to three factors: the velocity with which the compressive force is applied, the degree of compression (transverse deformation), and the duration of the compression. The relative roles of these factors in determining the severity of an injury to the spinal cord have yet to be determined. The molecular and electrophysiologic events of failed neurotransmission following spinal trauma are not currently understood in detail. Neural tissue may be physically disrupted and fail on a mechanical basis. More commonly, though, the spinal cord remains physically intact but is functionally deranged. Within 5 minutes of experimental injury, the postcapillary venules become markedly congested. This is soon followed by the opening of endothelial gaps here and at the capillary level, resulting in diapedesis of red cells and extravasation of fluid proteins and electrolytes through the â&#x20AC;&#x153;leakyâ&#x20AC;? microvasculature. Within 30 minutes of injury, microscopic hemorrhages appear in the central gray matter and coalesce over the next several hours. Vacuolization develops within the endothelial lining, indicating a profound ischemic or hypoxic insult, which subsequently leads to coagulative necrosis of the neuronal population. The adjacent white matter is relatively less affected, but retraction balls and periaxonal swelling may be observed. These events can progress to autodissolution of the spinal cord within 24 hours, even without ongoing mechanical compression. Extrapolation from morphologic findings, these phe-

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nomena would appear to have an ischemic basis, and considerable effort has been expended in characterizing the associated microcirculatory alterations. Direct measurements of spinal cord blood flow do not reveal a consistent trend until 2 to 3 hours after injury, when the gray matter flow drops to less than half of the control values. Tissue oxygen tension declines over a parallel time course. Vasomotor autoregulation is disrupted within the injured segment of spinal cord, while the blood flow in the adjacent white matter (which ordinarily approximates 40 percent of gray matter mass corrected flow) is maintained or increased. However, these observations fail to explain why an instantaneous physical impact immediately suspends neurotransmission, or how delayed microcirculatory failure occurs. Several lines of investigation have been intensely pursued. The possible roles of free catecholamines, lipid peroxides and free radicals, lysosomal enzymes, Na+/K+ ATP-ase, and endorphins, either in direct tissue injury or in the modulation of microvascular responses, are under active study.

C. CLINICAL FINDINGS Dogs and cats with spinal cord injury frequently have serious injuries of other organ systems. A major component of the clinical assessment of an animal’s condition, therefore, is the determination of the relative urgency of treatment of non-neurologic injuries versus the need for early treatment of spinal cord injury. At the time of presentation, the animal should be placed in lateral recumbency and should remain in that position during subsequent clinical and radiographic examinations. A thorough assessment of the animal’s general condition must be made, looking for major problems such as hemorrhage, shock, pneumothorax, diaphragmatic hernia, or limb fractures. Extreme care must be taken at all times to avoid exacerbating any spinal injury with excessive movement. The most common cause of vertebral fractures is automobile trauma, other causes include bite wounds, gunshot wounds and underlying infectious, metabolic, or neoplastic disorders resulting in bone demineralization. Vertebral fractures may occur at any age, but are more common in younger animals. A complete neurological examination is performed to localize the site of the injury and determine its severity. Careful palpation of the vertebral column may aid in identification of a vertebral fracture or luxation. Administration of tranquilizers or analgesic should be delayed until completion of the neurologic examination, as these agents may alter an animals responses. A neurologic examination should be done with minimal movement of the animal in order to prevent further injury resulting from vertebral instability. The extent of a spinal cord injury usually can be assessed accurately at the time of initial examination, as most spinal injuries are nonprogressive, and as spinal shock (a phenomenon resulting in loss of physiologic functions caudad to a spinal cord injury) is usually not of clinical significance in subprimates. Several aspects of the neurologic examination are of special importance in assessing a dog or cat with a spinal injury.

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Attention given to the animal’s posture may aid in determination of location and severity of a lesion. For example, Schiff-Sherrington syndrome, which results from thoracolumbar spinal cord injury, is of great localizing value and must be differentiated from other postures such as decerebrate rigidity and decerebellate rigidity. Motor function, muscle tone, and spinal reflexes must be assessed carefully. These functions are utilized to localize a lesion to one of four major regions of the spinal cord: cervical (C1-C5), brachial enlargement (C6-T2), thoracolumbar (T3-L3), and lumbar enlargement (L4-Cc5). Pain perception should be assessed by applying a painful stimulus and observing the animal for a brainmediated response. The stimulus applied to a foot may result in withdrawal of the limb by a spinal reflex mechanism (the flexion reflex), even though the spinal cord may have been severed. It is essential to distinguish these spinal reflex movements from brain-mediated responses (e.g. turning the head, vocalizing, increased respirations or some sign that the painful stimulus has elicited a response from the brain). Two types of pain perception are sometimes distinguished in animals. “Superficial” pain perception is manifested by a response to pricking or pinching the skin, and “deep” pain perception is manifested by response to pinching the toes or tail with hemostatic forceps. When multiple spinal fractures occur, the clinical signs of a more caudal lesion may mask those resulting from a second lesion located further cranially. For example, the lower motor neuron signs caused by a lesion at L5-L6 may mask the hyperreflexia that would be caused by a second injury at L1.

D. DIAGNOSIS Results of the neurologic examination usually are extremely revealing in determining the site and severity of spinal cord injury subsequent to trauma. Radiographs of the vertebral column are essential. Ventrodorsal radiographs are best done by means of a horizontal beam, in order to avoid further spinal injury. The entire vertebral column must be radiographed, and proper positioning is required. Twenty per cent of patients with traumatic spinal injuries will have a second spinal fracture/luxation at another location. A logical approach is to anesthetize the animal as soon as possible after completion of the physical and neurologic examinations. This will, of course, be influenced by the severity of nonneural injuries in many cases. Anesthesia permits precise positioning and allows for the completion of myelography. The major values of radiographic studies are in precise lesion localization, discovering unsuspected lesions, and in assessing the need for surgery and the procedure to be used. Extreme care must be taken at all times to avoid causing further injury to the animal, especially once that animal is anesthetized and no longer able to protect the affected area. In some instances it may be prudent not to attempt ventrodorsal radiographs if these can not be accomplished without moving the animal from lateral recumbency. Many dogs and cats with spinal trauma have resultant vertebral fractures or luxations that are evident radiographi-

cally. These fractures or luxations often occur adjacent to area of rigid stability such as the sacroiliac articulation. Fractures usually occur transversely from the intervertebral foramen cranioventrally through the vertebral body or through the vertebral epiphysis in younger dogs. Alternatively, the vertebral body may be compressed (compression fracture). Luxations occur through the intervertebral disk space, with the caudal segment or vertebra usually being displaced cranioventrally. Other animals with spinal trauma and significant neurologic deficits have no radiographic evidence of vertebral fractures or luxations. In some of these cases, vertebral displacement may have occurred at the time of trauma, with immediate return to normal alignment. More commonly, perhaps, these dogs and cats have spinal cord contusion analogous to that occurring in the brain as a result of trauma. The associated intramedullary hemorrhage and edema may cause myelographic evidence of spinal cord swelling at the site of injury. Radiographic findings must always be evaluated in conjunction with neurological examination findings.

E. TREATMENT General considerations Management of animals with spinal trauma should follow a list of priorities, with the focus of the treatment centered on prevention of secondary central nervous system damage. Immediate treatment of non-neural injuries is limited to those problems that are life threatening, such as shock and hemorrhage. Splinting of long bone fractures is indicated, but permanent reduction and fixation should be deferred until initial management of the spinal cord injury is underway. Temperature, pulse, and respiration should be recorded for future reference.

Medical therapy Based on experimental findings, a variety of pharmacologic agents have been advocated in treating spinal cord trauma. Glucocorticoids and osmotic diuretics have been used most commonly in an attempt to reduce edema. Glucocorticoids are considered beneficial in the treatment of spinal cord injury by many researchers. However, highdose steroid therapy may result in complications leading to increased morbidity and mortality (e.g. gastrointestinal bleeding), and, therefore, low-dose regimens are recommended. Glucocorticoids should be administered during the first eight hours following the injury. Dexamethasone may be given at an initial dose of 2 to 4 mg/kg IV and then a dose of 0.2 mg/kg IV may be repeated at 6- to 8-hour intervals. Recent evidence supports the use of methyl prednisolone sodium succinate (MPSS) during the first eight hours after injury. Dosage of MPSS is 30 mg/kg IV followed either by a dose of 15 mg/kg every six hours for 24 hours or a continuous infusion at a rate of 5.4 mg/kg/hour for 24 hours. Osmotic diuretics have been shown to be beneficial in some experimental studies, but probably are not

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of benefit in severely injured spinal cord tissue and may even be injurious. Much attention has been focused recently on the role of free catecholamines in the pathogenesis of acute spinal cord injury and the reversal of these effects through their depletion or pharmacologic blockade. However, the role of catecholamines in spinal cord trauma and treatments directed at reducing their effects have been questioned. Another suggested therapy involves the use of antifibrinolytics to stabilize clots and limit cord hemorrhage. Hyperbaric oxygen and dextran have been employed to augment a sluggish microcirculation. Barbiturates and hypothermic cord perfusion have been used to lessen metabolic requirements and attenuate adverse tissue responses at the injury site. Most recently, naloxone has been administered in an attempt to reverse beta endorphin-induced ischemia. The clinical usefulness of these approaches remains unclear.

Surgical therapy A decision regarding surgical treatment must be made as soon as non-neural injuries have been treated and medical management instituted. Ideally, this is within 2 hours of the time of injury. Surgical decompression by laminectomy is beneficial when there is myelographic evidence of sustained extradural compression of the spinal cord. In cases where extradural compression is not present and spinal cord swelling is the major source of compression, durotomy or myelotomy may be combined with laminectomy. If done, durotomy and myelotomy should be accompanied by saline perfusion of the spinal cord for at least 1 hour. Perfusion with chilled fluids probably is no more helpful than perfusion with normothermic fluids, although hypothermia without perfusion is beneficial experimentally. Alignment and stabilization of the vertebral column is indicated in animals that demonstrate severe displacement or instability of a fracture or luxation. Most fractures or luxations must be considered unstable, even though all such injuries will not result in sustained spinal cord compression or distraction. Satisfactory methods of external fixation of spinal fractures do not exist, so open reduction and fixation is recommended. Surgical reduction and fixation can be readily combined with laminectomy for decompression, if necessary. Surgical management of spinal cord injury in animals must be considered in all cases, as it provides the best opportunity for rapid and complete recovery in cases of sustained compression or instability and facilitates postinjury care. However, conservative therapy, including strict confinement and external splinting for 4 to 6 weeks, may be efficacious in animals with minimal neurologic deficits and little vertebral displacement. Numerous surgical procedures have been utilized in stabilizing the spine in the dog and cat. The use of Steinmann pins and methylmethacrylate is particularly effective at all levels of the vertebral column, especially in large-breed dogs. Regardless of the form of internal stabilization used for vertebral fractures, the stabilizing device may fail if there is excessive motion during the initial postoperative phase. For

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this reason, strict confinement is advisable for a minimum of two weeks after surgery.

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perforation. Intestinal protectants (kaolin-pectin, 1 to 2 ml/kg, PO, qid) and cimetidine (10 mg/kg, PO, tid) are indicated in these dogs.

F. COMPLICATIONS G. PROGNOSIS Potential complications encountered in dogs and cats with spinal cord trauma and associated paralysis include urinary tract infections, urine scalding, and decubitus. The potential for urinary tract infections resulting from urine retention should be of paramount concern. Evacuation of urine form the bladder must be accomplished by either manual expression or catheterization at least three times daily. Indwelling catheters are to be avoided, as they further predispose to infection. Decubitus is mainly a complication of large recumbent dogs and can be partially countered by placing such animals on a padded surface. Presence of urinary incontinence in these dogs may also necessitate that the surface be fenestrated. Because of the routine use of glucocorticoids in animals with spinal trauma, steroid-related complications also are relatively common. The most deleterious of these effects is severe gastrointestinal bleeding and even

Prognosis for an animal with spinal cord injury depends on numerous factors, with results of the neurologic examination being the major determinant. The most important factor in neurologic prognosis is pain perception. The loss of “superficial” pain perception occurs with less severe lesions than those resulting in loss of “deep” pain perception. In general, animals in which any degree of pain perception is detected with certainty can be expected to be restored to locomotion. The more severe the depression of pain perception, the longer the recovery period. In severe injuries, where pain perception has been absent for a brief period, recovery may require months and residual ataxia and paresis may persist. Most animals in which pain perception has been absent for 24 hours or more cannot be restored to locomotion, although occasional recoveries have been seen in such cases.

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Lumbosacral disorders of dogs Richard A. LeCouteur

Lumbosacral disease is often caused by stenosis of the lumbosacral vertebral canal. Stenosis here results in a variety of disorders as a result of compression of the cauda equina. Lumbosacral vertebral canal stenosis may result from several or all of the following: type II disk protrusion (dorsal bulging of the annulus fibrosis), hypertrophy and /or hyperplasia of the interarcuate ligament, thickening of the vertebral arches or articular facets, and (infrequently) subluxation/instability of the lumbosacral junction. The lecture will cover etiology and pathogenesis of the condition, clinical findings, differential diagnosis, diagnostic tools and treatment options.

A. INTRODUCTION The term cauda equina syndrome describes a group of neurologic signs that results from compression, destruction, or displacement of those nerve roots and spinal nerves that form the cauda equina. Disorders of the cauda equina that result in cauda equina syndrome are relatively common and may be either congenital or acquired, or may be a combination of both these categories (Table 1). The nerve roots involved are L7, S1-3, and Cd 1-5.

B. LUMBOSACRAL VERTEBRAL CANAL STENOSIS Etiology and pathogenesis The term lumbosacral vertebral canal stenosis encompasses a spectrum of disorders that cause a narrowing of the

lumbosacral vertebral canal with resulting compression of the cauda equina. The term lumbosacral vertebral canal stenosis is used by this author to describe an acquired disorder of large breeds of dog that results from several or all of the following: type II disk protrusion (dorsal bulging of the annulus fibrosus), hypertrophy and/or hyperplasia of the interarcuate ligament, thickening of vertebral arches or articular facets, and (infrequently) subluxation/instability of the lumbosacral junction. It is likely that several separate disorders currently are included within this single syndrome. Other terms that have been used to describe this disorder are lumbosacral instability, lumbosacral malformation/ malarticulation, lumbar spinal stenosis, lumbosacral spondylolisthesis, and cauda equina syndrome. As stated above, cauda equina syndrome may result from numerous causes other than lumbosacral vertebral canal stenosis; therefore, use of this term to describe this condition is inappropriate. In humans, the term spondylolisthesis refers specifically to a forward (anterior) movement of a lower lumbar vertebra relative to a lumbar vertebra or sacrum directly below it. This problem rarely occurs in dogs, in which the most frequently encountered problem is a ventral “slippage” of the sacrum relative to the body of the L7 vertebra. The term “retrolisthesis” has been proposed to describe this “reverse spondylolisthesis” of dogs. Lumbar spinal stenosis is a term that perhaps is best used to describe a congenital (“idiopathic”) syndrome reported to occur in young dogs. Lumbosacral instability is a misleading term, as instability is not demonstrated consistently in association with lumbosacral vertebral canal stenosis. Certain similarities between vertebral and soft tissue alterations seen in dogs with lumbosacral vertebral canal stenosis and Doberman pinscher dogs with caudal cervical

Table 1. Disorders that result in clinical signs of cauda equina dysfunction in dogs. 1. Congenital disorders a. Vertebral and/or nerve root anomalies (e.g., stenosis of the vertebral canal, spinal dysraphism, transitional vertebra, dysgenesis of lumbosacral vertebrae, and spina bifida 2. Acquired disorders a. Infections (e.g., diskospondylitis) b. Neoplasia (e.g., malignant nerve sheath neoplasia) c. Intervertebral disk disease d. Iatrogenic stenosis (e.g., post-surgical scarring) e. Lumbosacral vertebral canal stenosis (with/without “retrolisthesis”) f. Fractures and/or luxations 3. Combined disorders a. Combination of congenital and acquired disorders (e.g., disk degeneration and lumbosacral vertebral canal stenosis)

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spondylomyelopathy have been noted. As the etiology and pathogenesis for either condition are incompletely understood, such comparisons are of little significance at the present time. An association has been reported between lumbosacral stenosis and transitional vertebrae in German shepherd dogs. In another report, more than 30 per cent of German shepherd dogs with clinical signs of cauda equina compression had radiographic and pathologic abnormalities compatible with osteochondrosis of the sacral end-plate.

Clinical findings Acquired degenerative lumbosacral vertebral canal stenosis occurs most commonly in large breeds of dog. Males appear to be affected more frequently than females. German shepherd dogs appear to be affected more often than dogs of other breeds. Dogs with the congenital (“idiopathic”) form appear to be of the smaller breeds. Affected dogs in both categories are between 3 and 7 years of age, although the problem may occur at any age. Degenerative lumbosacral vertebral canal stenosis rarely is recognized in cats. Signs of cauda equina compression seen frequently in affected dogs include the following: apparent pain on palpation of the lumbosacral region, on caudal extension of the pelvic limbs, or on elevation of the tail; difficulty rising; pelvic limb lameness (often unilateral); pelvic limb muscle atrophy; paresis of the tail; scuffing of the toes; urinary and/or fecal incontinence, or “inappropriate” voiding due to an inability to assume a voiding posture; self-mutilation of the perineum, tail, or pelvic limbs; and rarely, paraphimosis. These signs most often are insidious in onset and progress gradually over months, and they are easily confused with those of hip dysplasia or degenerative myelopathy. Abnormalities detected on neurologic examination include gait deficits related to sciatic nerve paresis (e.g., dragging of toes). In addition, depression or loss of conscious proprioception, normal or slightly exaggerated patellar reflexes (“pseudoexaggeration” related to loss of antagonism to femoral nerve-innervated muscles by sciatic nerve-innervated muscles), depressed or absent flexion reflexes in pelvic limbs, decreased anal tone and anal sphincter reflexes, atonic bladder, hypesthesia of the perineum and tail, and muscle atrophy may be seen. These abnormalities relate to deficits of the sciatic, pudendal, caudal, and pelvic nerves, whose nerve roots comprise the cauda equina.

Diagnosis Characteristic clinical findings may be consistent with a diagnosis of degenerative lumbosacral vertebral canal stenosis. Careful mapping of areas of loss of cutaneous sensation may assist in determining involved nerve roots. However, presence of this syndrome must be confirmed by means of plain radiographs and special radiographic techniques. Diagnosis of this condition requires completion of several specialized radiographic procedures in sequence. Rarely can this condition be diagnosed on the basis of plain radiographic findings alone.

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Electromyography may complement information available from a neurologic examination and from plain spinal radiographs by confirming denervation in muscles innervated by the nerves of the cauda equina. Motor nerve conduction velocity determinations in sciatic and tibial nerves and measurement of evoked spinal cord potentials may also provide indirect evidence of cauda equina dysfunction. Plain radiographic findings include spondylosis deformans ventral and lateral to the lumbosacral articulation, sclerosis of vertebral end-plates, “wedging” or narrowing of the L7-Sl disk space, and secondary degenerative joint disease in the region of L7-S1 articular facets. Ventral displacement of the sacrum with respect to L7 (“retrolisthesis’’) and diminished dorsoventral dimensions of the lumbosacral spinal canal may be seen; however, such findings must be interpreted with caution, as they may be seen in normal dogs in association with slight rotation of the vertebral column on lateral radiographs. Every effort must be made to ensure that such rotation does not occur during exposures for lateral radiographic projections. General anesthesia is mandatory for obtaining radiographs of the lumbosacral vertebral column. A ventrodorsal projection also is recommended. “Stressed” or “dynamic” plain radiographic projections (flexed and extended views), completed with careful attention to avoid rotation, often assist in determining the presence of instability or “retrolisthesis”. Several attempts to separate normal dogs from dogs with lumbosacral vertebral canal stenosis by means of objective measurements made from radiographs have not been successful. Appearance on plain radiographs helps to eliminate other causes of cauda equina syndrome (e.g., diskospondylitis or vertebral neoplasia). Linear tomography, when available, may provide specific information regarding the diameter of the lumbosacral vertebral canal that cannot be obtained from plain radiographs. Several specialized techniques exist for examination of the lumbosacral vertebral canal. Use of such techniques is necessary for demonstration of soft tissue vertebral canal stenosis. 1. Myelography. Myelography is useful in the diagnosis of lumbosacral problems. Although it has been reported that the terminal portion of the subarachnoid space of dogs fills unreliably with contrast material at this level, resulting in misinterpretation of findings, myelography may be reliable when an animal is tilted for sufficient time (up to 15 minutes) to ensure adequate filling of the caudal subarachnoid space. The use of “stressed” radiographs (flexion and extension projections) may be combined with myelography. Myelography also provides a means to “screen” the entire spinal cord for abnormalities, particularly the lumbar enlargement, where a lesion may result in signs of cauda equina dysfunction. Placement of a needle for completion of myelography also provides the opportunity for collection of cerebrospinal fluid. 2. Diskography. A technique that is useful for confirmation of lumbosacral soft tissue stenosis is diskography. Diskography consists of radiography completed following the injection of contrast material into the nucleus pulposus of an intervertebral disk. This technique has special application to the lumbosacral disk space.

3. Epidurography. 4. Computed tomography (CT). Computed tomography is best completed prior to any of the contrast procedures discussed above, as interpretation of CT images is difficult in the presence of epidural contrast. 5. Magnetic Resonance Imaging (MRI). Magnetic resonance imaging may provide further information regarding soft tissue stenosis of the lumbosacral vertebral canal. These images may be generated after contrast procedures have been completed, as the presence of epidural contrast will not affect the images. 6. Surgical exploration. Surgical exploration may be indicated in dogs (with appropriate history and clinical signs) in which results of ancillary diagnostic tests do not provide a definite diagnosis of soft tissue stenosis.

Treatment Some affected dogs in which clinical signs are mild or in which apparent lumbosacral pain is the sole problem improve temporarily after strict confinement and restricted leash exercise for a period of 4 to 6 weeks. Use of analgesic drugs or corticosteroids has been recommended; however, their use must be accompanied by strict confinement. Clinical signs commonly reoccur in affected dogs treated only by means of medical therapy. Dogs with reoccurrence of signs, or dogs that are moderately to severely affected at the time of initial presentation (especially those

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with urinary/fecal incontinence), should be considered candidates for surgical therapy. Dorsal decompressive laminectomy of L7 and S1 vertebrae is recommended. This procedure may be combined with foraminotomy or facetectomy in dogs in which compression of spinal nerves at the level of the intervertebral foramina is suspected. In animals with radiographically confirmed instability or significant retrolisthesis, fusion of the lumbosacral articulation may be necessary. A dorsal approach for fusion has been recommended, and successful ventral lumbosacral fusion by means of a lag screw fixation has been reported. Dogs should be strictly confined for 4 to 6 weeks postoperatively. Postoperative complications include seroma formation at the surgical site and formation of a laminectomy scar at the site of the laminectomy. Both may be avoided by use of appropriate surgical technique and postoperative patient management. Attention to bladder emptying may be necessary in dogs with bladder atony prior to surgery. The bladder should be manually expressed three times daily in such dogs. Urine should be submitted for culture and sensitivity testing prior to and 2 weeks after completion of surgery, and appropriate antibiotic therapy instituted as indicated by results. Prognosis for affected dogs is dependent on the severity of signs prior to surgery. Return to normal function may be expected in dogs that are mildly affected prior to surgery. Dogs with bladder atony or a flaccid anal sphincter prior to surgery have the poorest prognosis.

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Neoplasia of the central nervous system Richard A. LeCouteur

Summary The widespread availability of computed tomography (CT) and magnetic resonance imaging (MRI) during the past decade, have allowed veterinarians to conclusively diagnose brain tumors with far greater frequency than was previously possible. The development of advanced neurosurgical and anesthetic techniques, have also made complete or partial surgical removal of brain tumors a more frequent treatment option. In addition to providing a definitive diagnosis of tumor type, even partial removal of a brain neoplasm may also help to relieve some of the signs of cerebral dysfunction, and may make the animal a better candidate for other forms of treatment, such as radiation therapy. Dogs with spontaneous brain tumors provide a unique model for brain tumor research, as they are immunocompetent, have tumor types with cell kinetics identical to those of people, and they are a large animal with a brain size similar to that of people. Current research focuses on whether new approaches which selectively target brain tumor cells may provide a way to treat brain tumors without damaging normal tissue.

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carcinoma. Skull tumors that affect the brain by local extension include osteosarcoma, chondrosarcoma, and multilobular osteochondrosarcoma. Although brain tumors occur in dogs of all breeds, either sex and any age the incidence increases over 5 years of age and a median age of 9 years was reported in one study of 86 affected dogs. Certain breeds have a higher incidence of some tumor types. Glial cell tumors and pituitary tumors occur commonly in brachycephalic breeds, whereas meningiomas occur most frequently in dolichocephalic breeds. Canine breeds that are over-represented include the boxer, golden retriever, Doberman pinscher, Scottish terrier, and Old English sheepdog. Meningioma is the most commonly reported primary brain tumor of cats. Older male cats appear to be most susceptible and meningiomas in cats may occur without clinical signs. Meningiomas involving multiple intracranial sites occur relatively commonly in cats. Primary brain tumors other than meningiomas rarely occur in cats. Secondary tumors that have been reported to occur in the brain of cats include pituitary macroadenomas and macrocarcinomas, and metastatic carcinomas. Local extension may occur either from squamous cell carcinoma of the middle ear cavity or from nasal adenocarcinoma.

A. INTRODUCTION B. PATHOLOGY The occurrence of intracranial neoplasia appears to be more common in dogs than in other domestic species, but few studies of the incidence of CNS tumors in dogs and cats have been undertaken. In one study the incidence of CNS neoplasia in dogs was reported as 14.5 per 100,000 of the population and as 1-3% of all canine necropsies in another study. The incidence in cats has been reported as 3.5 per 100,000 population. A broad spectrum of tumor types occurs in dogs with gliomas (e.g., astrocytomas and oligodendrogliomas) and meningiomas appearing to be the most frequently occurring primary brain tumors of dogs. Although most primary brain tumors are solitary, multiple primary brain tumors and multiple tumors of different histologic types have been reported. Meningiomas and lymphomas account for the majority of brain tumors in cats. Secondary tumor spread may occur from local extension, most commonly of nasal adenocarcinoma and metastases from mammary, prostatic, or pulmonary adenocarcinoma, hemangiosarcoma, and extension of pituitary adenoma or

The intracranial neoplasms of cats or dogs may be classified as either primary or secondary, depending on their cell of origin. Primary brain tumors originate from cells normally found within the brain and meninges, while secondary tumors are those that have reached the brain by hematogenous metastasis from a primary tumor located outside the nervous system, or by local invasion, or extension, from adjacent non-neural tissues such as bone. Pituitary gland neoplasms (adenomas or carcinomas) and tumors arising from cranial nerves (e.g., nerve sheath tumor of the oculomotor or vestibulocochlear nerves) are considered secondary brain tumors, as they affect the brain by means of local extension. Care must be exercised in the application of the terms benign and malignant to a brain neoplasm. In assessing the malignant potential of a brain tumor, the difference between cytologic and biologic malignancy should be emphasized. Cytologic malignancy is a morphologic assessment of anaplasia, while biologic malignancy is the likelihood that a tumor

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will kill the animal. Most cytologically malignant brain tumors are also biologically malignant, despite the treatments presently available. Cytologically benign tumors of the brain may also be biologically malignant because of various secondary effects such as increased intracranial pressure (ICP). Particular care must be exercised in the use of the term benign when discussing the meningiomas of dogs and cats. Although a canine meningiomas may be classified as benign, it may be locally invasive and have poor demarcation from normal brain tissue. Meningiomas in cats are almost always well defined with a clear demarcation between normal and affected brain tissue. Feline meningiomas appear to grow more slowly than canine meningiomas. Brain tumors cause cerebral dysfunction through primary effects such as infiltration of normal brain tissue, compression of adjacent structures, disruption of cerebral circulation and local necrosis. Secondary effects include hydrocephalus, increased intracranial pressure (ICP), cerebral edema and brain herniation. Primary brain tumors often are slow growing and because the brain is contained within the confines of the calvaria, gradual compression permits surrounding structures to adapt to increasing pressure. This occurs through a process termed compensation. During the time the brain is able to compensate, there may be a prolonged history of vague signs (e.g., subtle behavior alterations). However, even with a very slowly progressive tumor, clinical signs may progress rapidly when compensatory mechanisms have been exhausted. Rapidly growing tumors do not permit compensation to occur to the same degree and in such cases a sudden onset of severe neurologic dysfunction may occur in the absence of premonitory signs. Should a neoplasm erode or obstruct a major blood vessel, causing hemorrhage or infarction, an acute onset of neurologic deficits may ensue. The patterns of spread of brain tumors are different from those of other tumors because of several factors, including lack of a well-developed lymphatic system within the brain. Spread often involves local invasion and CSF seeding. Brain tumors, particularly astrocytomas, have cells that are capable of invading the normal brain. The biology of brain tumors and the role of the immune system is an area of very active investigation. It is well known that human brain tumor patients, especially those with high grade malignancies, have impairments of their immune systems, such as defects of T-cell function, reduced levels of circulating Thelper/inducer cells, and T-cell suppressor factors. Glioma cell lines in vitro can produce a protective mucopolysaccharide coating that impairs the generation of specific cytotoxic lymphocytes.

C. HISTORY AND CLINICAL SIGNS History and neurologic examination are the first steps to a definitive diagnosis in the evaluation of a dog or cat suspected of having a brain tumor. The neurologic signs resulting from a brain tumor depend primarily on the location, size and rate of growth of the mass. Many dogs or cats will have a long history of â&#x20AC;&#x153;vagueâ&#x20AC;? signs that are overlooked, such as not wishing to be handled, hiding during the day, decreased

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frequency of purring or diminished activity levels. One of the most frequently recognized clinical signs associated with a brain neoplasm of a dog or cat is seizures. This may take the form of a generalized seizure, or it may be a focal seizure. Focal seizures may aid in localizing a neoplasm. Should a neoplasm involve the brain stem, cranial nerve deficits in vision, hearing, or smell, may occur. Visual deficits involve the visual pathways from the occipital lobe of the cerebrum to the optic nerve. Hearing loss involves the cerebellomedullary region, the brain stem, or temporal lobes of the cerebrum. Problems with the ability to smell are seen in association with lesions of the cribriform plate, olfactory or temporal lobes of the cerebrum, or other rhinencephalic connections. Difficulties with balance or gait suggest cerebellar or vestibular involvement. The secondary effects of brain tumors, such as increased ICP, represent further advancement of tumor growth. By the time these effects occur, either a large tumor or significant cerebral edema is present. The signs include alterations in behavior (e.g., lethargy, irritability), circling, head pressing, compulsive walking, altered states of consciousness, or associated locomotor disturbances. Unfortunately the majority of cats or dogs with a brain tumor will be presented to a veterinarian with problems that relate to the secondary effects of a tumor suggesting that brain tumors of cats and dogs usually have reached a large size by the time an owner seeks veterinary attention. This is especially true with frontal lobe neoplasms of dogs, which may reach a very large size before causing clinical signs. As in humans meningiomas in dogs are more common in females and again as in humans meningiomas in dogs and cats have receptors for estrogen, progesterone, and androgen, which may influence the growth and behavior of these tumors. In contrast oligodendrogliomas occur twice as often in males as in females.

D. DIAGNOSTIC TECHNIQUES AND WORK-UP On the basis of signalment, history, and the results of complete physical and neurologic examinations, it is possible to localize a problem to the brain and, in some cases, to determine the approximate location. However, it must be remembered that the signs that result from a disease in a given location in the nervous system will be similar, regardless of the precise cause. The categories of disease that may result in clinical signs similar to those of a brain tumor include congenital disorders, infections, immunologic and metabolic disorders, toxicities, nutritional disorders, trauma, vascular disorders, degeneration, and idiopathic disorders. These other categories of disease must be eliminated before a diagnosis of brain tumor may be made. For this reason it is essential to follow a logical diagnostic plan for a dog or cat that has signs of brain dysfunction. A minimum data base for a dog or cat with signs of a brain lesion should include a hemogram, serum chemistry panel, and urinalysis. Survey radiographs of the thorax and abdomen help to rule out a primary malignancy elsewhere in the body. The major objective in the completion of these

tests is to eliminate extracranial causes for the signs of cerebral dysfunction. Plain skull radiographs are of limited value in the diagnosis of a primary brain tumor; however, they may be helpful in the detection of neoplasms of the skull or nasal cavity that have involved the brain by local extension. Occasionally, lysis or hyperostosis of the skull may accompany a primary brain tumor (e.g., meningioma of cats), or there may be radiographically visible mineralization within a neoplasm. General anesthesia is necessary for precise positioning of the skull for radiographs. Analysis of CSF is recommended as an aid in the diagnosis of a brain tumor. The results of CSF analysis may help to rule out inflammatory causes of cerebral dysfunction, and in some cases may support a diagnosis of a brain tumor. Care should be used in the collection of CSF, because frequently an increased ICP may be present and pressure alterations associated with CSF drainage may lead to brain herniation. It is often desirable to hyperventilate the animal to decrease intracranial pressure prior to CSF collection. In general, increased CSF protein content and a normal to increased CSF white blood cell count are considered â&#x20AC;&#x153;typicalâ&#x20AC;? of a brain neoplasm although often CSF may be normal. Neoplastic cells may be present in CSF, particularly when sedimentation techniques are used for analysis. Little information is available regarding CSF alterations seen in association with feline brain tumors; however, changes are similar to those described for dogs. Computed tomography (CT), provides accurate determination of the presence, location, size, and anatomic relationships of intracranial neoplasms. More recently, magnetic resonance imaging (MRI) has allowed these principles to be advanced even further. Images obtained by means of MRI are superior to those of CT in certain brain regions (e.g. the brainstem), and the diagnostic specificity of MRI may eventually render the biopsy of tumors prior to treatment unnecessary. While the major tumor types in dogs are reported to have characteristic CT or MRI features, it must be remembered that non-neoplastic space-occupying lesions may mimic the CT or MRI appearance of a neoplasm and that occasionally a metastasis may resemble a primary brain tumor on CT or MRI. At the present time, biopsy and/or surgical excision is the sole method available for the diagnosis of brain tumor type in cats or dogs. The development of a stereotactic frame that positions the head of a dog or cats so that, using CT imaging, a precise fine-needle biopsy of the animals brain tumor can be taken, has made the biopsy of a brain tumor more routine in our hospital.

E. THERAPY The major goals of therapy for a brain tumor are to control secondary effects, such as increased ICP or cerebral edema, and to eradicate the tumor or reduce its size. Palliative therapy for dogs or cats with a brain tumor consists of glucocorticoids for edema reduction and, in some cases (e.g., lymphoma), for retardation of tumor growth. Some animals with a brain tumor will demonstrate dramatic improvement in clinical signs for weeks or months with sustained gluco-

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corticoid therapy. Should seizure therapy be needed, phenobarbital is the drug best suited for the control of generalized seizures. Four methods of therapy for a brain tumor are available at this time for use in dogs and cats: surgery, irradiation, chemotherapy, and immunotherapy (or biologic response modification). Surgery has become more frequent during the past few years with the availability of CT and MRI, and the development of advanced anesthetic techniques. Neurosurgical intervention is now an essential consideration in the management of intracranial neoplasms of cats or dogs, whether for complete excision, partial removal, or biopsy. The precise location, size, and extent of a neoplasm, determine the extent of removal. The possibility of complete excision is also affected by tumor type. Meningiomas, particularly those located over the frontal lobes of the cerebrum, often may be completely removed, especially in cats. In contrast, there is a significant morbidity and mortality associated with the surgical removal of neoplasms located in the caudal fossa and brainstem of cats and dogs. In addition to providing a tissue diagnosis of tumor type, partial removal of a brain neoplasm may relieve signs of cerebral dysfunction and, may render an animal a better candidate for other forms of therapy, such as radiation therapy. Surgical biopsy of a tumor must be approached with care, as seeding of a tumor to previously uninvolved tissue may result in some cases. The use of radiation therapy for the treatment of primary brain tumors of dogs and cats is well established and it may be used either alone or in combination with other treatments. The objective of radiation therapy is to destroy a neoplasm, while at the same time minimizing damage to any normal tissue that must be included in the irradiated volume. External beam, megavoltage irradiation currently is recommended for the therapy of brain tumors in dogs or cats. Orthovoltage radiation has been used for the treatment of canine brain tumors, but it should be stressed that orthovoltage radiation is not optimal because of poor beam penetration, profile, and limited field configuration. Careful treatment planning by a qualified and experienced radiation therapist is essential to the success of radiation therapy. The selection of a radiation dose is based partly on considerations such as tumor type and location, and partly on tolerance of the tissues that surround the tumor and that have not been invaded by the tumor. Surgical removal of a solitary meningioma in cats results in excellent long- term survival. At this time there are few published reports concerning surgery or radiation therapy of dogs and cats for the treatment of tumor types other than meningioma. Radiation therapy alone has been used for the treatment of caudal fossa neoplasms of dogs, granulomatous meningoencephalomyelitis of dogs, and ACTH-secreting pituitary neoplasms of dogs. The preliminary results of these groups of animals confirm that the prognosis for these animals is greatly improved following radiation therapy. Because current treatments for brain tumors have proven to be of limited effectiveness, the outcome for human and veterinary patients with brain tumors has not improved over the last three decades. New approaches that selectively target brain tumor cells may provide a way to treat brain tumors in the future without damaging normal tissue. These

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new treatment are based on the transfer of DNA to brain tumor cells which, unlike normal adult brain cells, are growing and multiplying. Work is underway at our institution to determine whether genetically engineered viruses are capable of transferring new genes to canine brain tumor cells. After being genetically modified with the viral DNA, the tumor cells may then be killed by drugs that have no harmful effects on normal brain cells. Although experimentally brain tumors may be induced in rats and dogs using nitrosourea and avian sarcoma virus, dogs with spontaneous brain tumors provide a unique model for brain tumor research as they are immunocompetent, have tumor types with cell kinetics similar to those of people, and they are a large animal with a brain size similar to that of people. In the first phase of this research we are studying whether brain tumor cells will incorporate injected DNA. The client-owned dogs in the project first undergo a stereotactically-guided, fine needle biopsy of their brain tumor. Once the presence of the appropriate tumor type has been confirmed, the same fine needle can be used to inject the engineered genes. Each patientâ&#x20AC;&#x2122;s tumor is removed surgically 48 to 72 hours later. The tumor cells are then examined to see if the new genetic material is present.

SPINAL CORD NEOPLASIA A. INTRODUCTION Primary spinal cord neoplasms occur infrequently in dogs. Tumors affecting the spinal cord may be considered as extradural, intradural-extramedullary, and intramedullary. Extradural neoplasms comprise approximately 50% of all spinal neoplasms, while intradural-extramedullary tumors and intramedullary tumors comprise 30% and 15%, respectively. Meningiomas appear to be the most frequently diagnosed primary spinal neoplasm of dogs and have a high incidence in the cervical spinal cord. Primary spinal cord neoplasia, with the exception of lymphoma, is relatively rare in cats. Most cats with spinal lymphoma are young (median age 24 months). In cats, feline leukemia virus (FeLV) is frequently associated with lymphoma and therefore must be considered a risk factor in the development of spinal lymphoma. However, a cat with spinal lymphoma may test negative for FeLV. Spinal lymphoma has also been identified in association with feline immunodeficiency virus infection.

B. PATHOLOGY In dogs the most frequently reported extradural tumors are primary malignant bone tumors and tumors metastatic to bone and soft tissue. Meningiomas and peripheral nerve sheath tumors are the most frequently occurring intraduralextramedullary neoplasms of dogs. These tumors are reported to occur most frequently in older dogs. Intramedullary spinal tumors of dogs occur infrequently. They are predominantly of glial cell origin. Granulomatous meningoencephalomyelitis may also occur as a primary

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spinal cord neoplasm. Intramedullary spinal cord metastases may occur in dogs with systemic malignancy. It appears that hemangiosarcoma and lymphoma have a propensity for intramedullary spinal cord involvement. Extradural lymphoma, either primary or secondary, occurs frequently in cats. Of feline extradural tumors, osteosarcoma is the most common primary vertebral neoplasm.

C. HISTORY AND CLINICAL SIGNS Extramedullary spinal cord neoplasms typically are slow growing and result in gradual spinal cord compression. The signs of spinal cord dysfunction usually worsen over weeks or months. Occasionally, an acute onset of signs may accompany hemorrhage or ischemia associated with a neoplasm. Intramedullary tumors, which may grow more rapidly, are characterized by a higher incidence of ischemia, necrosis, and hemorrhage. The clinical signs seen in association with a spinal cord tumor usually reflect the location of the neoplasm and often are indistinguishable from the signs caused by other transverse myelopathies at the same location. The presence of certain signs should cause suspicion of a spinal cord neoplasm. Extradural tumors may involve the meninges, spinal nerves, or nerve roots, resulting in discomfort that may progress to extreme spinal hyperesthesia. Neurologic deficits (e.g., paresis) may not be seen initially and, when present, may be intermittent (i.e., worsen with exercise). There is usually a progressive worsening of neurologic function caudal to the lesion. Intraduralextramedullary tumors may also result in a prolonged, intermittent expression of clinical signs and hyperesthesia; however, the signs may be alleviated by exercise. Brachial or lumbar intumescence involvement may be evidenced by lameness, holding up of a limb, neurogenic muscular atrophy, and depressed spinal reflexes. Rarely, unilateral spinal cord compression may cause deficits in the contralateral limb. In contrast, intramedullary spinal cord tumors usually cause rapid progression of neurologic dysfunction. Hyperesthesia rarely is associated with such tumors.

D. DIAGNOSTIC TECHNIQUES AND WORK-UP The diagnosis of a neoplasm affecting the spinal cord requires a systematic approach. The procedure is based on the collection and interpretation of a minimum data base that includes appropriate serologic tests (hemogram, biochemical profile), and thoracic radiographs for primary or metastatic neoplasia. Following this, survey radiographs of the vertebral column, CSF collection and analysis, and myelography may be completed during a single period of anesthesia. General anesthesia permits accurate positioning of a dog or cat for survey radiographs of the vertebral column and allows stressed or oblique projections to be done. Primary or secondary vertebral tumors may produce bone lysis or new bone production, or both. The vertebral body and arch are more frequently affected by a neoplasm than the dorsal spin-

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E. TREATMENT A limited number of therapeutic options exist for a dog or cat with a spinal cord neoplasm. Appropriate therapy de-

pends on tumor location, extent, and histologic type. An immediate goal of therapy is to relieve the deleterious effects of sustained spinal cord compression. This may be achieved medically (e.g., glucocorticoids) or surgically. Surgery may permit the complete removal or reduction and biopsy of a neoplasm. In cases in which complete removal is not possible, recurrence is to be expected, and adjunctive therapy such as irradiation is recommended. The development of advanced neurosurgical techniques and the introduction of new biopsy methods has improved the outcome in many cases. Accurate biopsy diagnosis of lymphoma is essential, because lymphoma of the spinal cord may be successfully treated with chemotherapy or irradiation alone, or in combination.

F. PROGNOSIS There are few reports in the veterinary literature concerning the long-term follow- up of dogs and cats with spinal neoplasia. The prognosis depends on the resectability, histologic type, location, and severity of clinical signs. Generally, dogs or cats with an extradural metastatic neoplasm or vertebral neoplasm have a poor prognosis, and palliative therapy only is attempted. Removal of an affected vertebra (spondylectomy), particularly in the cranial lumbar region, may be attempted in selected cases. Occasionally, intradural- extramedullary tumors may be completely resected, and in such cases the prognosis must be considered good.

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ous processes or transverse processes. Plain radiographic abnormalities are uncommon with primary nervous system neoplasms. Expansion of a spinal tumor may result in the enlargement of an intervertebral foremen, widening of the vertebral canal, or thinning of surrounding bone. Cerebrospinal fluid collection and analysis are always indicated especially since plain radiographs may not provide a complete diagnosis. A lumbar puncture is recommended for CSF collection, and the needle may be left in place for myelography, pending the results of the cytologic examination of CSF. The alterations in CSF caused by spinal tumors should be interpreted according to the same criteria discussed for brain tumor diagnosis; however, it must be remembered that the protein content of CSF collected from a lumbar location is normally higher than that of CSF collected from the cerebellomedullary cistern. Lymphoma affecting the spinal cord often results in an elevated white cell count, predominantly abnormal lymphocytes. Myelography is essential for the accurate determination of the location and extent of a spinal cord neoplasm. On the basis of myelography, the tumors may be classified as extradural, intradural- extramedullary, or intramedullary, although this distinction cannot always be made. CT or MRI may provide more exact localizing information.

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Extrasystoles on the ECG: the rational approach Christophe W. Lombard

Summary VPC’s are recognized by a widened and bizarre shaped QRS-complex that occured prematurely among normal sinus beats. The recognition of prematurity is essential to avoid confusion or false diagnosis of the rare ventricular escape complexes occuring with sinus pauses or exit blocks. An important differential diagnosis for very widened, bizarreshaped complexes is bundle branch block; these complexes have however preceeding P-waves and normal PR-Intervals, and are much wider than VPC’s. Once diagnosed to be indeed premature ventricular activity, the determination of the hemodynamic importance and electrophysiologic “danger” should be made. The latter is speculative and stands for the risks of evolving into a severe tachyarrhythmia, leading to possible hemodynamic collapse and so-called sudden cardiac death. The hemodynamic consequences of ventricular tachyarrhythmias can be determined by the severity of the pulse deficit, abnormality of the capillary refill time, reduction of blood pressure, and reduced pulse oxymetry measurements. The determination of the need for therapy, based on these abnormalities, is very empiric; implementation of treatment varies highly among clinicians. I prefer to have additional clinical data such as electrolyte and acid base status of the patient, as well as some data (mostly echocardiographic) about heart size and contractility, before deciding about the need for treatment. As a general rule, ventricular tachyarrhythmias without underlying primary heart disease need not be treated very aggressively, because they very rarely lead to fatalities and have little reduction of blood pressure and cardiac output. Rather, the probable etiologic abnormality leading to hypoxia and/or acid-base and electrolyte abnormality should be treated. When signs of primary myocardial disease (dilated chambers, reduction of fractional shortening, evidence of dyskinesis etc) are present, antiarrhythmic therapy is more likely indicated to improve and normalize the hemodynamic situation. In most clinical situations associated with ventricular tachyarrhythmias, oxygen support can only be beneficial and frequently palliates the irregular rhythm. Then, I like to initiate antiarrhythmic therapy with mexiletine, and lidocaine as my second choice. Mexiletine is preferred because of its high efficacy and availability both as injectable and oral preparations, facilitating a later switch to longterm treatment when necessary. In cases with suspected influence

of high endogenous catecholamine release (stress, anxiety), the drug sotalol with its class II and III antiarrhythmic effects (Vaughn-Williams classification) is a reasonable choice. Severe chronic ventricular arrhythmias, most often associated with some degree of myocardial impairment, can be treated with amiodarone. This drug has a very powerful antiarrhythmic efficacy, but large scale studies of suppression rates and side effects are lacking in veterinary patients.

1. Recognition and differentiation of extrasystoles Extrasystoles are recognized as prematurely occuring heart beats with a different morphology than normally conducted beats originating from the sinus node. In this presentation, we will limit the discussion to ventricular extrasystoles; they do have an broadened, bizarre shaped QRS-T complex, always a discordant T-wave and no relationship to an eventually preceeding p-wave. Ventricular extrasystoles (VES, or better termed ventricular premature contractions, VPC) may occur as isolated events, coupled 1:1 with sinus beats (ventricular bigeminy), in pairs of two (couplets), three (triplets) or as runs of four or more VPC’s; this is called paroxysmal ventricular tachycardia (pVT). Paroxysmal ventricular tachycardia can be further divided into nonsustained tachycardia (runs of less than 20-30 sec) and sustained tachycardia (runs lasting longer than 30 sec), Muir 1991. Uniform or unifocal VPC’s are differentiated from multiform or multifocal VPC’s, where several morphologically different QRS-T-types occur and may suggest that they originate from different foci within the ventricles. This concept is most often correct, but neglects the explanation that unifocal VPC’s may look different from each other if some beats have so-called aberrant conduction. Based on morphology, the origin of the VPC may also be guessed; left ventricular origin VPC’s usually have a more abnormal morphology (inverted QRS-complexes in leads I, II, III and aVF) and greater QRS-duration than sinus beats, while right ventricular or septal origin VPC’s have reasonably normal configuration (upright in leads I, II, III and aVF) together with broadening of the QRS-complex. Ventricular premature complexes must be differentiated from ventricular escape beats that have similar morphological features (broadened and bizarre QRS-T-complex), but occur late, with a greater that usual RR-interval; escape beats or escape rhythms occur with

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DVM, Dipl ACVIM, Dipl ECVIM Klinik für kleine Haustiere - Universität Bern - Berne - Switzerland

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extreme bradycardias or because of failure of the primary pacemaker (sinus node) to maintain a sufficiently high rate. They must not be confused with VES. Their therapeutic approach, if necessary, is totally different.

2. Determination of the severity and its hemodynamic consequences While the detection and the classification of arrhythmias is relatively easy, finding rational reasons to justify treatment is much harder to accomplish. Most often the decision is made based on some arbitrary values indicating the severity or frequency of VES, some impression of hemodynamic compromise of the patient because of the arrhythmia, and some feeling about the danger that the arrhythmia might deteriorate into more life threatening forms such as very fast ventricular tachycardia, torsade des pointes (TDP) and ventricular fibrillation. These extremely dangerous forms of arrhythmias result in a very rapid deterioration of cardiac output and perfusion, peripheral as well as coronary, and to collapse of the patient. Another descriptive term for these events is sudden cardiac death (SCD). If not resuscitated immediately, the patient will die from the lack of perfusion of the essential vital organs (brain, lungs and the heart). It is therefore necessary to determine danger and hemodynamic deterioration of arrhythmias in order to make rational decisions regarding management and therapy. This simply because antiarrhythmic therapy is not without certain hazards itself. Most available antiarrhythmic drugs unfortunately cause either some lowering of the blood pressure or have negative inotropic side effects on the myocardium, or both. Unfortunately, most antiarrhythmic drugs have also been shown to have a low incidence of proarrhythmic side effects under specific circumstances, potentially worsening the cardiac rhythm and jeopardizing the patient. Particularly class 1A and some class 1C drugs may prolong the QT-interval and set up the stage for arrhythmias caused by early afterdepolarisations. The need for any antiarrhythmic therapy, however difficult it may be to establish this parameter, should clearly be shown; the benefits must outweigh the potential risks, and close initial monitoring is essential to recognize any worsening with antiarrhythmic therapy. The parameters that should be considered in evaluating the severity of any cardiac arrhythmia are the following: heart rate changes, frequency and complexity of VES, electrophysiologic “danger” of the VES, resulting reduction of the stroke volume or cardiac output, resulting reduction of blood pressure, resulting reduction in peripheral tissue oxygenation.

2.a. Heart rate changes Any arrhythmia leading to an excessively elevated (our limit 160-180/min) or lowered (our limit 50-60/min) heart rate may cause a reduced cardiac output (CO). This important functional parameter is determined by multiplying stroke volume (SV) with heart rate (HR). Severe bradycar-

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dias simply lack enough heart beats to keep up a sufficient CO, while severe tachycardias cause such a short diastolic filling time resulting in a reduction of the SV that isn’t compensated by the elevated heart rate. It isn’t very practical to measure stroke volume in clinical cases with arrhythmias. With Doppler-echocardiography however, the reduction of the velocity-time-integral of the aortic flow signal (VTI, aequivalent to stroke volume) of a VES in comparison with a normal sinus beat can clearly be documented. It results mostly from a shortened diastolic filling time and additionally from an abnormal sequence of the ventricular depolarisation and therefore diminished systolic emptying of the ventricle with a VES. Recognizing this reduced stroke volume of a VES, It makes sense to consider the frequency of VES as a reliable indicator of the hemodynamic compromise, i.e. the reduction of cardiac output.

2.b. Frequency, complexity, and electrophysiologic danger of VES Holter-electrocardiography (ambulatory longtime recording onto a specialized cassette recorder and afterwards analysis with specialized computer software) is the method of choice for an accurate count of VES per hour or during a 24 hr period. This technique unfortunately is quite time consuming and somewhat expensive; the method is usually found at university hospitals and reserved for research work or special investigations about drug efficacy. In the set-up of private practice, the frequency of VES is simply calculated as a percentage of the sinus beats or as an absolute number per minute, counted from a short ECG-rhythmstrip recorded over 30 to 60 seconds. Obviously, this method is very inaccurate and not very reliable, particularly in patients with intermittent arrhythmias. It is however the only practical method to determine the frequency of VES and the need for antiarrhythmic therapy. Auscultation of the heart and recording the incidence of VES by counting is not practical. In the literature, numbers indicating the severity of an arrhythmia and the need for intervention appear quite arbitrary. Single VES occuring less than 20 to 30 times per minute may be considered not worthy of therapy and could be totally innocuous (Muir 1991). This number is equivalent to approximately 25% of heart beats being of ectopic origin. Personnally, I prefer a lower limit and start therapy with VES-frequencies over 10-15% of the sinus beats (< 20 VES/min). In the Doberman breed however, single VES occuring at very low frequencies (< 1000/24hr) are a reliable early indicator of the impending particular cardiomyopathy of that breed (Calvert 1995). With frequencies between 30 and 75% of ectopic beats (30-100 VES per minute), veterinary cardiologists usually agree that this represents a moderate severity and deserves to be treated. Higher frequencies of VES result in elevated heart rates, are considered severe arrhythmias and should be managed with rather aggressive therapy. Short bouts of fast ventricular tachycardias (heart rates over 180200/min during the episodes) or displaying the feature of sinusoidal twisting of the QRS-axis around the isoelectric point = torsades des pointes (TDP) are equally considered to be severe and treated aggressively).

The occurance of multiple forms of VES (multifocal VES) is generally considered as a worse arrhythmia, with more electrical instability and more potential for electrical deterioration into fatal ventricular fibrillation. Multifocal VES likely indicate more widespread foci of increased automaticity and/or reentry circuits in a heart that is suspected to be suffering from some ischemia or cellular damage. The amount of prematurity, i.e. closeness of the VES to the T-wave of the preceeding normal sinus beat, is important for the determination of electrophysiologic “danger”; the phase of increased or supranormal excitability of the ventricular myocardial cells occurs during the T-wave of the body surface ECG. VES occuring at that particular time, displaying the so-called R-on-T phenomenon, have great potential for inducing ventricular tachycardia and fibrillation (Muir 1991).

2.c. Resulting hemodynamic alterations It is very important to know if the patient with an arrythmia is suffering from heart failure or not. Heart failure, especially insufficient perfusion of peripheral tissues, will be recognized by abnormal clinical signs such as generalized fatigue and weakness, weak arterial pulses, prolonged capillary refill time and an elevated heart rate. Pulmonary congestion is indicated by dyspnea and/or tachypnea, the presence of crackles and usually cough; right sided congestive heart failure is indicated by venous congestion, ascites and sometimes pericardial and pleural effusion. In such cases, radiographs should be obtained as soon as possible and the signs of pulmonary edema and the effusions confirmed. At the same time, the size of the heart is evaluated, and any signs of cardiomegaly interpreted as preexisting underlying cardiac disease that may even be the cause of the arrhythmia. Determination of the hemodynamic consequences of an arrhythmia serves primarily to derive indications and justification for treatment, and to indicate how aggressive the therapy should be. In cases with suspected preexisting cardiac disease and hemodynamic compromise, arrhythmias are likely to compound the poor perfusion and congestion even more. In such cases, a more aggresive approach appears justified. It may not always be possible or practical to measure the hemodynamic depression very accurately, but it should be attempted. The available methods are the measurement of peripheral arterial blood pressure and tissue oxygenation with pulse oxymetry. They are now easily accomplished with simple devices. Especially with intermittant tachyarrhythmias, diminished perfusion and lowered oxygen saturation can sometimes directly be correllated with runs of tachycardia. With echocardiography, diminished ventricular excursions may be demonstrated during runs of tachycardia. Multifocal tachyarrhythmias are usually associated with poorer ventricular function. Diminished aortic flow of VES or tachycardic episodes can be documented with Doppler recordings, particularly the VTI (equivalent to the cardiac stroke volume). During tachycardic episodes, the pulse deficit may be severe. While documentation of peripheral hemodynamic depression may be feasible with pulse oxymetry, one can only speculate on the

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arrhythmia’s effect onto coronary perfusion. Herein lies the danger of many severe tachyarrhythmias; they cause coronary ischemia and hypoxemia of already damaged myocardial cells. If a critical threshold of hypoxemia is reached in areas of electrical instability, new and potentially fatal arrhythmias are facilitated.

3. Evaluation of underlying heart disease Results from a very thorough evaluation of the history and an in depth physical examination should enable the clinician to determine if the patient has preexisting primary heart disease, or if the arrhythmia is more likely caused by extracardiac or systemic problems that affect the heart secondarily. Systemic problems super-imposed on primary cardiac disease may occur and usually result in worse clinical signs and arrhythmias that are more challenging and more resistant to therapy. The prognosis appears to be worse as well. As an example, VES in dogs with vegetative endocarditis, fever and poor general condition appear to cause a high incidence of SCD. Features such as age, breed and particularly the presence of either heart murmurs or additional heart sounds or gallop-rhythms are valuable indicators of preexisting heart disease. If primary underlying heart disease is suspected, a complete cardiovascular data base including a full ECG, thoracic radiographs, blood pressure measurement, blood gases and echocardiography should be established as soon as possible. The ECG should be carefully analysed, the usual intervals measured and dangerous features such as long QT-intervals, evidence of afterdepolarisations, torsades des pointes (TDP) and ST-deviations (signs of ischemia) recognized. Depending on the severity of clinical signs, the data base for critically ill patients should be collected and analysed as the highest priority. This should include a blood count, a complete serum chemistry (especially the electro-lytes potassium, calcium, and magnesium), and the blood gas/acid-base status. In patients without suggestions or evidence of primary cardiac disease, the clinician should concentrate on collecting a complete data base for that particular organ system with dominating signs and obtain cardiac images at a later time. The following diseases are all known conditions associated with cardiac arrhythmias, particularly when cardiac damage is severe and signs of decompensation or failure begin to appear. Primary heart diseases (adapted from Sisson 1988) congenital defects: subaortic stenosis PDA, VSD with signs of CHF, advanced mitral and tricuspid dysplasia tetralogy of Fallot, pulmonic stenosis inherited SCD in German Shepherds (Moise 1992) AV-bundle stenosis in Pugs acquired diseases: special forms of cardiomyopathy: Dobermann (Calvert 1995) Boxer (Harpster 19xx) vegetative endocarditis “regular” cardiomyopathy (esp. hypertrophic,

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specific infections:

neoplasias

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restrictive, dilated) advanced degenerative valvular disease, especially with arteriosclerosis, ischemia and MIMI myocardial failure and hypoxia pericarditis ventricular preexcitation syndromes (Atkins 1995) sick sinus syndromes (Miniature Schnauzers, others) Chagas disease (T. cruzei, granulomatous myocarditis) Rocky Mountain Spotted Fever (Rickettsia rickettsii) Lime carditis (Borrellia burgdorferi) primary right atrial HSA, chemodectoma, lymphoma

Extracardiac causes of arrhythmias (adapted from Sisson 1988) hypoxia severe anemia, hypotension, shock, pulmonary parenchymal disease, pleural disease, airway obstruction, thromboemboli. electrolyte and hyperkalemia, hypercalcemia, any metabolic acidosis acid-base disorders hypomagnesiemia, hypokalemia trauma traumatic myocarditis (Abbott 1995) any trauma leading to shock, hypoxia and excessive sympathetic stimulation metabolic and gastric torsion and volvulus, sepsis, pancreatitis, uremia, endocrine problems peritonitis, hyperthyroidism, diabetes mellitus, Cushingâ&#x20AC;&#x2122;s syndrome, hyperviscosity syndromes, hyperthermia, heat stroke systemic infections infectious myocarditis (all causes, Liu et al 1995): viral, rickettsial, protozoan, spirochaetal, fungal, algae-like drugs/toxins halothane, xylazine, thiobarbiturates, doxorubicin, digitalis glycosides, dobamine/dobutamine, other catecholamines, toad poison (Bufo marinus), oleander, thallium, lead, ethylene glycol, cobalt neoplasias phaeochromocytoma, LSA, other metastatic tumors CNS-disease, increased intracranial pressure, CNS disorders neoplasia, encephalitis, spinal cord of the autonomic NS trauma, autonomic imbalance.

4. Possible mechanisms leading to arrhythmias The two principal mechanisms leading to cardiac arrhythmias are either increased automaticity of a group of diseased cells that is normally not having pacemaking function, or the developement of reentry circuits (abnormal conduc-

tion, i.e. unidirectional block, through diseased cell groups) that can lead to circus or reentrant tachycardias. For practical purposes, differentiation of the two mechanisms is of minor importance. Any damage to the cardiac cell membrane (ischemia, hypoxia, reperfusion injury, acidosis, electrolyte imbalance, excessive sympathetic stimulation, stretch, necrosis) can alter its ionic permeability and stability to an extent where spontaneous depolarisation occurs, or where conduction is altered, Russel and Rush 1995. These predisposing factors or causes of arrhythmias have primarily been recognized in cardiac muscle fiber preparations investigated in organ bath solutions, and the knowledge gained from these experiments was extrapolated to the entire heart. Nervertheless, these basic metabolic derangements are recognized with many systemic diseases, and it appears permissible and logic to speculate that the measured electrolyte and acid base abnormalities of the serum reflect ionic changes occurring at the cardiac cellular level. Recent interest has focussed onto excessive sympathetic stimulation in conditions with fever, hypotension, hypovolemia, shock, neurological and spinal cord disease. Catecholamines are known to increase automaticity of pacemaker cells by increasing the slope of phase 4 cellular depolarization, by increasing conduction through the sodium and calcium channnels. A similar increase in automaticity probably takes place in diseased, partially depolarized Purkinje cells. Catecholamines also increase the amplitudes of afterpotentials, thereby favorizing so-called â&#x20AC;&#x153;triggeredâ&#x20AC;? automaticity. Catecholamines also alter conduction velocity through diseased myocardium present in reentry loops, thereby favorizing reentrant arrhythmias. Additionally, excessive alpha-adrenergic stimulation may lead to coronary vasoconstriction and ischemia. Another area of new interest is reperfusion injury to myocardial cells, known to occur after conditions such as the GDV-complex, and severe trauma with shock and hypotension, Russel and Rush 1995. The superoxide radicals generated during reperfusion are very damaging to myocardial cells and destabilize the normal ionic balance responsible for maintaining normal automaticity and conduction. Myocardial necrosis and subendocardial hemorrhage, facilitating dysfunction and arrhythmias of damaged myocardial cells, have also been seen in trauma (general and spinal cord, Abbott 1995), GDV, and splenic masses. The mechanism of arrhythmogenesis with neurologic disease or injury seems to be mediated through excessive activation of the sympathetic nervous system, Russel and Rush 1995. The importance of an altered electrolyte status for arrhythmiagenesis and maintenance of irregular rhythms should be emphasized. Many of the commonly used class 1A and 1C- antiarrhythmic drugs (Quinidine, Procainamide, and Lidocaine) can not develop their antiarrhythmic efficiency during hypokalemia, occuring with many systemic diseases and prolonged anorexia, Russel and Rush 1995. Hypercalcemia as a cause of cardiac arrhythmias appears to be rare; the arrhythmogenic effect of too rapid calcium-infusions in patients with hypocalcemia however is well known. The influence of magnesium on arrhythmias has gained interest in veterinary medicine; it appears well established in human medicine. It is unfortunate that serum levels do not

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5. Therapy of ventricular tachyarrhythmias

etc.) with buprenorphine at a dose of 0.01-0.02 mg/kg im. During the time of these corrections, the ECG should be monitored frequently and the patient prepared for continuous ECG-monitoring with stick-on electrodes (modified bipolar leads, e.g. base-apex) and an oscilloscope with a strip chart recorder having slow recording speeds (i.e. 5 or 12.5 mm/sec), if this equipment is available.

5.b. Selection of a drug Many protocols about the use of lidocaine, quinidine and procainamide, both as boli and constant rate infusions for VES and ventricular tachycardia, have been published in the specialized veterinary literature, Muir 1991. We have focussed our interest on newer drugs like mexiletine that are supposedly safer with less side effects; Lunney and Ettinger 1991, Gonin and Lombard 1997. Reports in the veterinary literature about these newer drugs are unfortunately sparse. One of the advantages of using mexiletine is that this drug does nor interfere with serum digoxin levels; it may be combined with other antiarrhythmics, and together with quinidine has more than additive antiarrhythmic effects.

5.a. Supportive measures From the discussion above, it is evident that elimination of any predisposing factors leading to ventricular tachyarrhythmias may often abolish abnormal rhythms and already solve the problem. As many of the mentioned metabolic derangements can be corrected relatively easily in an intensive care setup, they should be initiated as soon as they are recognized, before selecting an antiarrhythmic drug. We propose to take the following steps: 1. Oxygen support (nasal catheter etc.) if peripheral pulse oxymetry falls below 95%, or if the patient is tachypneic and/or cyanotic. Transfusion of RBC’s if the packed cell volume is below 20-25%. 2. Rehydration of an exsiccotic patient over a 4-6 hr period; mandatory monitoring of the central venous pressure to avoid iatrogenic pulmonary edema if primary cardiac disease is present. 3. Monitoring of arterial blood pressure with noninvasive devices, if available. 4. Correction of any metabolic acidosis with pH-values below 7.15 or plasma bicarbonate values below 12-15 mEq/l. Standard guidelines about the amount of sodium bicarbonate to be infused should be followed. 5. Correction of an eventual hypokalemia (our normal range 4.0-5.5 mEq/l) through the supplementation of 1-2 mEq/kg/24hr period. With severe hypokalemia, a more rapid supplementation of 1-2 mEq/kg over 6 hrs while monitoring cardiac rhythm and repeating K- measurements frequently is advocated. 6. Correction of an eventual hypomagnesemia (normal range 1.7-2.4 mEq/l) through the infusion of 0.75-1.0 mEq/kg/24hr period. With severe hypomagnesemia, rapid iv-substitution of 0.1-0.3 mEq/kg in D5W or saline over a 15min period can be attempted (Dhupa 1995). 7. Analgesia in cases with known painful conditions (posttrauma, fractures, peritonitis, postoperative situations

5.b.1.Guidelines for using mexiletine We start with a bolus of 2.5 mg/kg intravenously, diluted in saline, D5W or lactated Ringers solution and given over 2-3 minutes. It can be repeated safely once or twice after 105 minutes respectively, and primarily serves to document the efficacy of mexiletine for the suppression of VES. In the meantime, a constant rate infusion (CRI) with a concentration of 250 or 500 mcg/ml (= 0.025% or 0.05%, depending of the hydration status of the patient) in any fluid is prepared, and applied at a loading dose of 30 mcg/kg/min for 3 to 5 hrs. The following formula has proven very simple for the calculation of the drip speed with a suitable infusion pump: mexiletine dose (30 mcg) x body weight (in kg) x 60 min ————————————————— = volume (in ml/hr) drip concentration (500 or 1000 mcg/ml) The original concentration of mexiletine is 25 mg/ml in 10 ml glass vials, so 20 ml (2 full vials) or 40 ml (4 full vials) are placed into 1000 ml of infusion to obtain the desired concentration of 500 (0.05%) resp. 1000 mcg/ml (0.1%). After 3-5 hrs of infusion at the 30 mcg/kg/min rate, the patient is reevaluated and the drip speed reduced to a maintenance dose rate of 5-8 mcg/kg/min, using the above mentioned formula again. With persistance of the VES, the high dose of 30 mcg/kg/min can be kept safely for up to 10 hrs, provided that the patient is intensely monitored. If VES reappear during the maintenance dose of 5-8 mcg/kg/min, the drip can also safely be re-increased to 30 mcg/kg/min for one or several more hours.

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reflect intracellular (cardiac and other body cells) stores accurately. Hypomagnesemia is present in many critically ill human patients in an emergency room setting (Sachter 1992), and magnesium levels likely follow abnormalities of potassium. Magnesium is important for the normal function of the Na+/K+ ATPase pump, which maintains normal intracellular potassium levels. Hypomagnesemia therefore may favorize reduced intracellular potassium levels, leading to partial depolarisation and electrical instability of myocardial cells, particularly if additional digitalis therapy has already reduced the function of the ATPase-pump. Dogs and cats with heart failure receiving vigorous diuretic therapy may have a depletion of both potassium and magnesium. There is circumstancial evidence that magnesium administration may help to abolish supraventricular arrhythmias (PAT, atrial fibrillation) as well as refractory ventricular arrhythmias, especially those associated with myocardial infarction and digitalis intoxication, Russel and Rush 1995.

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Side effects with this protocol are rare. Signs of toxicity may include nausea, vomiting, muscle fasciculations and possibly seizures. They should be managed with diazepam to effect (2.5-5 mg boli iv). We have archieved good control of VES with different etiologies (mostly secondary conditions such as GDV affecting the heart) with this protocol in many patients, Gonin and Lombard 1997. In situations with less severe arrhythmias or less urgent need for suppression, mexiletine can be given as intramuscular injections or at an oral maintenance dose of 3-8 mg/kg 2-3 times daily. Higher doses should only be given with close monitoring of the ECG (prolongation of the QRS-duration and the QT-interval over 30% of initial values may be warning signs of impending toxicity). In our experience, mexiletine has also shown good success in suppressing VES with primary cardiomyopathies, in various breeds as well as in Boxers and Dobermans.

5.b.2. Combination of antiarrhythmic drugs with Beta-blockers In Dobermans, resistance to antiarrhythmic monotherapy has been observed, Calvert 1995. Combinations of class I antiarrhythmic drugs with B-blockers may be necessary for a reasonably high, though sometimes still incomplete suppression of VES. The therapeutic goal in such cases may have to be modified and include only the suppression of dangerous forms of multifocal VES and ventricular tachycardia, thereby hopefully eliminating the danger of sudden cardiac death, rather than intoxicating the patient with dangerously high drug dosages. Such blockage of excessive sympathethic tone may obviously also be tried in other breeds with cardiomyopathy and resistent VES, as well as in cases without primary cardiac disease where the clinician feels that high catecholamine levels may contribute to arrhythmiagenesis. The negative inotropic side effect of the beta-blocker should carefully be considered, and the patient monitored intensively (blood pressure, echocardiography, auscultation of the lungs) when such potentially dangerous drug combinations are applied. The ultrashort acting betablocker esmolol may be tried to test the effect of beta blockade with repeated intravenous boli of 0.1 mg/kg or with infusions (CRI) of 50200 mcg/kg/min. Longacting betablockers used for that purpose in dogs are: metoprolol 0.2-1 mg/kg 3xdaily atenolol 0.5 mg/kg 2xdaily

5.b.3. Propafenone, sotalol and amiodarone Propafenone is a class 1 antiarrhythmic drug and has supposedly very weak additional class 2 (betablocking) and class 4 (calcium channel blocking) effects, Gabriel and Kersten 1993. It was used in a series of dogs with primary and secondary cardiac disease by these authors. Suppression of VES and ventricular tachycardia was good in the majority of cases at oral doses of 3 mg/kg TID, with the effect only developing after a few days because of a relatively long time

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needed for tissue saturation. Using slow intravenous boli of 1 mg/kg or CRI at 0.008 mcg/kg/min showed complete suppression of VES in a few dogs. Sotalol has combined betablocking (class 2) and action potential-prolonging (class 3) antiarrhythmic effects. This may represent certain advantages in patients with suspected high sympathetic drive. We have used the drug in selected cases where mexiletine resulted in only partial suppression of VES, with quasi equal or slightly better results of arrhythmia suppression. There arenâ&#x20AC;&#x2122;t any published reports about veterinary use of the drug. Amiodarone is an extremely powerful antiarrhythmic drug (class 3) that is reserved for the suppression of lifethreating tachyarrhythmias not controlled by other drugs in man because of ist severe and frequent, dose dependant gastrointestinal, neurologic and thyroid side effects. Only anecdotal reports abouts its use in dogs are available. Its indication may be severe arrhythmias resistant to other drug combinations, in primary cardiomyopathies of Dobermans or in the inherited SCD-syndrome of young German Shepherds. The potential benefits must clearly outway the risks in such adrug with unproven safety.

5.b.4. Antiarrhythmic therapy in cats The antiarrhythmic drugs of choice for suppressing VES in cats are either beta-blockers or procainamide.Very little is published about the efficacy, mostly recommendations for therapy. Generally doses should start low and be increased according to tolerance and antiarrhythmic effect. Propranolol 2.5 - 5.0 mg TID po. Atenolol 6.25 - 12.5 mg/24 hr period. Procainamide 3-8 mg/kg po q 6-8hrs.

6. Monitoring With arrhythmias caused by secondary, extracardiac disease, the patient usually improves rapidly with therapy directed at the specific organ dysfunction, and the antiarrhythmic therapy can frequently be switched to oral preparations after 48 hr of intravenous therapy or even discontinued completely. Initially, frequent controls of the electrolyte and acid-base status serves to document such improvement, while the cardiac monitoring should include blood pressure control and frequent ECG-recordings (with measurement of the important intervals). Repeated echocardiography and holter-ECGâ&#x20AC;&#x2122;s are particularly suited for the longterm monitoring of arrhythmic dogs (particularly Dobermans) with underlying primary cardiomyopathy, Calvert 1995. Once the shortening fraction falls under 20%, progressive left ventricular dysfunction seems to accelerate and is best monitored by measuring the indexed left ventricular endsystolic volume (ESVI). The ventricular tachyarrhythmias tend to progress to worse forms despite chronic antiarrhythmic therapy in severely affected Dobermans, and fatal episodes of SCD have been shown to occur in approximately 25% of these dogs, Calvert 1995.

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Dosages of commonly used ventricular antiarrhythmic drugs Class (VW)

iv. Bolus

Constant rate infusion (CRI)

Lidocaine

2 - 4 mg/kg repeat 1-2 x

40 - 80 mcg/kg/min

Procainamide

2 mg/kg q. 5min max 20 mg/kg

20 - 50 mcg/kg/min

Quinidine

Mexiletine

2.5 mg/kg repeat 1-2 x

loading: 30 mcg/kg/min maint.: 5 - 8 mcg/kg/min

3 - 8 mg/kg TID, im. or po.

1c (2 and 4)

1 mg/kg repeat 1-2x

maint. 8 mcg/kg/min

3 mg/kg TID po.

5-10 mcg/kg/min

3-10 mg/kg/ 24hrs

Propafenone

Sotalol Amiodarone

Maintenance

6 - 20 mg/kg TID, im. or po.

5 - 15 mg/kg q 6-8hrs im. or po.

2 and 3 3

References Abbott JA (1995): Traumatic myocarditis. In Bonagura JD Ed: Kirk’s Current Veterinary Therapy XII Ed., WB Saunders Philadelphia, pp 846849. Atkins CE, Wright KN (1995): Supraventricular tachycardia associated with accessory atrioventricular pathways in dogs. In Bonagura JD Ed: Kirk’s Current Veterinary Therapy XII Ed., WB Saunders Philadelphia, pp 807-813. Calvert CA (1995): Diagnosis and management of ventricular tachyarrhythmias in Doberman Pinschers with cardiomyopathy. In Bonagura JD Ed: Kirk’s Current Veterinary Therapy XII Ed., WB Saunders Philadelphia, pp 799-806. Dhupa N (1995): Magnesium therapy. In Bonagura JD Ed: Kirk’s Current Veterinary Therapy XII Ed., WB Saunders Philadelphia, pp 132-133. Gabriel A, Kersten U (1993): Therapy of cardiac rhythm disturbances with propafenone (in German). Kleintierpraxis 38: 485-495. Gonin-Jmaa D, Lombard CW (1997): Therypy of ventricular arrhythmias with mexiletine in 16 dogs (In german). Tierärztl Praxis 25: 506-511. Harpster NK (19xx): Boxer cardiomyopathy, a review of the longterm ben-

10 - 15 mg/kg BID, then 5 - 7.5 mg/kg BID, then 7.5 mg/kg SID po.

efits of antiarrhythmic therapy. Vet Clin North America 21, Nr. 5: 989-1004. Liu SK, Keene BW, Fox PR (1995): Myocarditis in the dog and cat. In Bonagura JD Ed: Kirk’s Current Veterinary Therapy XII Ed., WB Saunders Philadelphia, pp 842-845. Lunney J, Ettinger SJ (1991): Mexiletine administration for management of ventricular arrhythmia in 22 dogs. JAAHA 27: 597-600. Moise NS, Gilmour RF (1992): Inherited sudden cardiac death in German Shepherds. In Kirk RW and Bonagura JD Eds: Current Veterinary Therapy XI Ed., WB Saunders Philadelphia, pp 749-751. Muir WW (1991): Antiarrhythmic drugs: treatment of cardiac arrhythmias. Vet Clin North America 21, Nr. 5: 957-988. Russel LC, Rush JE (1995): Cardiac arrhythmias in systemic diseases. In Bonagura JD Ed: Kirk’s Current Veterinary Therapy XII Ed., WB Saunders Philadelphia, pp 161-166. Sachter JJ (1992): Magnesium in the 1990s: Implications for acute care. Top Emerg Med 14: 23. Sisson DD (1988): The clinical management of cardiac arrhythmias in the dog and cat. In: Fox PR Ed : Canine and feline cardiology, Churchill Livingstone, New York, pp 289-308.

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Substance name

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Cardiomegaly in the cat: what do I do next? Christophe W. Lombard

Summary Prerequisites for a correct diagnosis of cardiomegaly are techniqually adequate radiographs, with proper positioning of the patient, taken in full inspiration. Rotation on the VD or DV-views should only be tolerated to an extent where the spinous processes lie within the borders of the vertebral bodies. Artefacts or conditions leading to a false diagnosis of cardiomegaly may be caused by the following: obesity, masses within the cranial mediastinum (thymus in juvenile patients, thymoma or LSA), malformations of the last few sternebrae, poor inspiration, and fat depositions (primarily at the cardiac apex and along the phrenic nerves). While severe cardiomegaly is easily recognised, borderline cardiac enlargement is more difficult to diagnose. Measurement techniques have been proposed. The vertebral heart score (VHS, using VD and Lateral radiographs, Buchanan 1991), measures the width and length of the heart in number of vertebral bodies, and is an easy procedure to perform. The range for normal hearts varies from 3.5 to 3.8 for the cardiac width and the combined width and length should measure less than 8 vertebrae. I consider it appropriate to use any information from the clinical examination (symptoms, presence of a heart murmur, abnormal gallop rhythms etc) while evaluating radiographic changes of the heart size. In most cases, any tentative diagnosis will have to be confirmed by either angiography or echocardiography and Doppler investigations anyhow. Severe cardiomegaly without any apparent clinical signs is suspicous for a peritoneo-pericardial diaphragmatic hernia (PPDH). Nonspecific signs such a lethargy, inappetence and difficulties with breathing, together with generalized cardiomegaly, may be due to pericardial effusions or dilated cardiopathy. The presence of a loud heart murmur and cardiomegaly in young to middle aged cats redirects the diagnosis towards congenital malformations with shunts or valvular malformations. Differential diagnoses include PDA, mitral and tricuspid dysplasias, subaortic and pulmonic stenoses, atrial and ventricular septal defects, endocardial fibroelastosis and sometimes combined multiple lesions. In middle aged to old cats, nonspecific abnormalities of the history and physical examination may occur together with heart murmurs and/or gallop rhythms. In these cases, the cardiac enlargement is most often caused by one of the

cardiomyopathies, their subtypes being idiopathic hypertrophic, restrictive, hyperthyroid, hypertensive and sometimes non-classifiable. A definitive diagnosis of the pathology and possibly the etiology is only possible with echocardiography/Doppler and additional laboratory examinations.

A. Technical requirements for radiography and patient related, non-cardiac effects Properly exposed radiographs without motion artefacts (rare in cats) are an essential prerequisite for any correct diagnoses of thoracic abnormalities. In addition, the cat must be properly positioned for two views. Rotation of the VD or DV-view is only acceptable to the extent that the spinous processes still lie within the limits of the lateral borders of the vertebral bodies. The DV-position provides less possibility for the cardiac apex to shift to either side, and less variation in the shape of the heart and better vascular detail (Farrow 1994). The VD-position provided however a more constant appearing heart size in normal cats (Farrow 1994). The feline thorax is also very pliable, and fewer compression artefacts of the ribcage can be expected from the VD-view, preferred by some cardiologists for the evaluation of the cardiac silhouette (Buchanan 1991). This view is also less sensitive to obscuring of the cardiac silhouette by small pleural effusions. In a lateral position, the front legs must be pulled forward, and a superimposition of the humeri or elbows over thoracic structures is not acceptable. The images must be generated with a fully inflated lung, as a reduced inspiration leads to a greater cardiac/thoracic ratio and facilitates an incorrect diagnosis of cardiomegaly. The full outline of the cardiac silhoutte must be visible for a proper evaluation. Obviously, any considerable amount of pleural effusion renders a correct evaluation of heart size very difficult and imprecise; the cat should be reradiographed after as complete a drainage of any effusion as possible. Lack of a distinct cranial borderline may be caused by remnants of the thymus in young animals, or by cranial mediastinal masses such as thymic lymphosarcoma or thymomas in adult cats. These conditions cause also a widening of the cranial mediastinum on the VD or DV-view. Malformations of the distal parts of the sternum (pectus excavatus or carinatus) as well as fat deposits at the cardiac apex may be responsible for an obscured view of the tip of the heart. This

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may cause difficulties for the precise evaluation of the length (apico-basal dimension) of the heart. Obesity in general may be responsible for a false diagnosis of cardiomegaly, as it may cause incomplete inspiration; and the fat deposits occur at preferred sites such as the cardiac apex and along the phrenic nerves, causing widening of the cranio-caudal width of the heart. Aged cats tend to have a cardiac long axis more parallel to the sternum, with a resulting wider curving arch of the aorta. Most radiologists like to read radiographs initially without any bias from the history and physical examination. Though this may warrant a more objective analysis of the radiographs, it does not at all reflect the usual procedure in daily practice, where radiographs are taken once the examining clinician has finished performing the physical examination. He or she will also be the one interpreting them as soon as they have been taken. We will therefore, after an initial discussion about radiographic diagnosis of cardiac enlargement, proceed with the knowledge and due consideration of the history and the abnormal findings from the physical examination.

B. Indicators of cardiomegaly B.1. Lateral view: Enlarged hearts are recognized by an increased length of the apico-basal dimension, leading to an elevation of the tracheal bifurcation (carina) and a reduction of the angle formed between the thoracic spine and the trachea. Supporting evidence of cardiomegaly may be gained by an “uphill” course of the caudal vena cava in selected cases. Another indicator, but somewhat more difficult to recognize, is the increase of the maximal width (cranio-caudal dimension, measured at a right angle with the apicobasal dimension). B.2. VD or DV-view: An increase of the length and especially of the maximal width of the cardiac silhouette is supposedly a very reliable indicator of cardiomegaly. This dimension has been compared to the number of thoracic vertebrae in the “vertebral heart score” concept (VHS, Buchanan 1991). Normal cats were shown to have average widths between 3.5 and 3.8 vertebral bodies. When width and length of the heart were combined (as in the canine VHS, in which always both dimensions are used), the number for cats should be less than 8 vertebral bodies. The increase of the width of the heart in this projection is often caused primarily by biatrial cardiac enlargement, i.e. the protrusion of both atria or especially their atrial appendages over the normal silhouette. The cardiac apex usually lies slightly to the left or on the midline of the thorax in this projection. A normal size of the ventricles causes the apex to appear pointed, while a more rounded apex indicates enlargement of the ventricles. Enlargement of all 4 cardiac chambers can therefore be deducted from a widened and elongated silhouette with a rounded apex. B.3. Supportive evidence from vascular structures Enlarged vascular markings (both arteries and veins) indicate overcirculation of the lungs and may give supportive evidence to the diagnosed cardiomegaly in cats with suspected malformations with shunts (VSD or PDA). If only

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pulmonary veins appear large and congested, restriction to left atrial filling as an early sign of congestive heart failure is present. As the left atrium is pliable and easily distended, signs of left atrial enlargement should be searched for on both views. B.4. Differentiation of right sided vs left sided cardiomegaly: Echocardiography will always be superior to radiography for making this differentiation, because the position of the interventricular septum can clearly be identified with the former technique. Nevertheless, radiographs may give some indications about the side of the heart that appears preferentially enlarged. On the lateral view, right sided cardiac structures lie cranially to the line drawn from the carina to the apex of the heart and form a more convex border than the caudal one. The right atrium and right ventricle lie adjacent to each other, and it is nearly impossible to differentiate their respective limits. The caudal border of the heart is more straight and is generated by the left ventricle and the left atrium. The dividing point between them is usually located at the site where the posterior vena cava crosses the posterior cardiac border. Right sided cardiac enlargement can therefore be expected from an exaggerated rounding (increased convexity) of the cranial borderline, leading to an increased sternal contact, and some increase of the cardiac length. In severe cases, the enlarged right heart causes the apex to be lifted up from the sternum and displaced caudodorsally towards the left side. Elevation of the trachea caused by the more cranial parts of the heart base is also supportive evidence of right heart enlargement. Left heart enlargement can be recognized by an increase of the long axis and an elevation of the trachea, resulting in a decreased angle between the trachea and the thoracic spine. The increased length cannot differentiate between left atrial and left ventrical enlargement. Those are indicated by increased convexities of their respective borderlines. On the ventrodorsal view, an elongation of the heart is more common to left heart enlargement; often the apex is shifted towards the midline or even to the right side of the dividing long axis. With right heart enlargement, its borderline becomes more convex, and the apex may be severely shifted towards the left side. As already mentioned, a more pronounced atrial enlargement may be recognized by a more dominant widening of the cardiac silhouette, while the ventricular enlargement is indicated by a more important lengthening of the heart and a simultaneous rounding and widening of the apex.

C. Information and/or bias from the signalment, history and physical examination Most complaints and details from the history (listlessness, inappetence, lethargy, difficulty with breathing, vomiting etc.), are usually not specific enough to firmly point towards cardiac disease. An exception may be the sudden onset of hindleg paralysis, where thromboembolization of the

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rarer Eisenmenger syndrome. In these cases, a hematocrit should be checked immediately for polycythemia (as a sign of chronic hypoxia associated with the chronic R>L-shunt. Based on additional bias from the patients age (under or over 2 years) and certain breed predilections for certain diseases, I tend to assign my patients provisionally to one of the three following groups for further investigation: (primary heart disease)

(sec. heart disease)

- congen. heart disease - cardiomyopathy - acquired valvular disease - neoplasia

- hyperthyroidism - hypertension - metastat. neoplasia - pericardial disease - other

Each of these groups has a slightly different data base or at least a different sequence of the further diagnostic investigations. In the ideal situation, all of the following examination procedures are performed in each feline patient. But the goal should be to obtain the correct diagnosis with the minimum of examinations, in order to keep the clients bill from rising unnecessarily!

Establishing a Data-Base for the suspected condition and proposed sequence: congenital heart disease

primary heart disease: cardiomyopathy or acquired valvular disease

second. heart disease: hyperthyroidism, hypertension, other

thoracic radiographs

hemogram, chemistry panel plus T4, urinanalysis, heartworm serology

ECG

BP-measurement

Echocardiogram ECG

Echocardiogram

thoracic radiographs

hematocrit or hemogram, evt. chemistry profile

Hemogram, chemistry profile, evt. T4, evt. growth hormone

ECG

evt. BP-measurement

echocardiogram

evt angiogram

Rarely angiogram

evt. szintigram

D. Electrocardiography The ECG is quite useful for differentiating tachyarrhythmias in cats with suspected cardiac disease. The usual abnormalities are: sinus tachycardia, ventricular premature contractions and paroxysmal tachycardias. The ECG however is not very useful for an etiological determination of a cardiomegaly. There are only weak correlations between radiographic and electrocardiographic signs of cardiac en-

largement, the latter preferentially providing supportive evidence of hypertrophy. I concentrate on the search for enlargement patterns (left ventricular hypertrophy LVH, right ventricular hypertrophy RVH, p-mitrale and p-pulmonale) or conduction abnormalities such as partial left bundle branch blocs (left fascicular bloc or anterior hemibloc), Presence of one of these 3 major ECG-abnormalities provides strong supportive evidence of primary or secondary cardiac disease in the feline.

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aorto-iliac trifurcation (secondary to cardiac disease: hypertrophic CMP, endocarditis) has to be very high on the list of differential diagnoses. Additionally, in areas endemic for feline heartworm disease, coughing and vomiting in an unprotected cat (not on heartworm prevention) rises the suspicion for dirofilariosis. After the physical examination of most cats with heart disease however, one or more of the following will almost certainly have been recognized: -Tachycardia over 180/min, - some abnormality of the auscultatory rhythm or arterial pulses (caused by either a gallop rhythm or a primary cardiac arrhythmia), or - some heart murmur (mostly systolic, indicating a shunt, a semilunar valvular stenosis, or AV-valvular regurgitation). Diastolic murmurs are extremely rare in cats and very difficult to recognize because of the usually elevated heart rate, making the diastolic time period quite short. Recognition of a machinery murmur already confirms the diagnosis of a PDA, though this defect is very rare in cats. Cyanosis, exacerbating with excitement or exercise, is also very rare in cats and points towards a congenital malformation with a right to left shunt such as Tetralogy of Fallot, or the much

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ECG-criteria of these major abnormalities: LVH

RVH

Left fascicular bloc

R-wave (lead II) > 0.9 mV positive lead I (qR-type) MEA normal or to the left QRS slightly widened evt. p-mitrale

rS-type QRS in II, III, aVF Negative lead I (QS-type) MEA to the right QRS slightly widened evt. p-pulmonale

rS-type QRS in II, II, aVF positive lead I (qR-type) MEA to the left and cranial QRS-duration +/- normal normal p-wave

LVH

RVH

Left fascicular bloc

- hypertrophic CMP

- specif. congen. malformations Tetralogy, PS, TV-dysplasia - dirofilariosis (very rare)

- hypertrophic CMP

Occurrance of these patterns:

- restrictive CMP - hyperthyroidism - dilated CMP (rare)

Differentiating right from left sided hypertrophy is particularly useful for differentiating congenital malformations. Tetralogy of Fallot and pulmonic stenosis almost always have RVH-patterns, while the presence of LVH supports a diagnosis of either subaortic stenosis (SAS), ventricular septal defect (VSD), mitral valve dysplasia or PDA. It must be emphasized that the information gained from the ECG about cardiac enlargement or hypertrophy complements the radiographic information quite often, but a disagreement is not necessarily an error or an incompatibility. Echocardio-graphy will be the deciding judge in these cases.

E. Echocardiography for the differentiation of radiographic cardiomegaly This technique has established itself very well in feline cardiology. It has tremendously facilitated the differentiation of the various forms of cardiomyopathy and acquired valvular disease, and has become an essential part of the work-up of the feline with suspected heart disease. In some diseases, echocardiography provides an instantaneous diagnosis without any cardiac measurements or necessary great skills at sophisticated imaging.

E.1. Severe radiographic cardiomegaly, rather rounded cardiac silhouette Differential diagnoses should include: - peritoneo-pericardial diaphragmatic hernia (PPDH) - other severe congenital cardiac malformations - severe dilated cardiomyopathy - pericardial effusion. In many cases of suspected PPDH, the radiographic diagnosis can be supported by gas shadows (bowel loops or stomach parts) superimposed onto the cardiac silhouette;

- restrictive CMP - dilated CMP (rare) - hyperthyroidism (rare)

other criteria are an incomplete outline of the diaphragm, a suspicously “empty” abdomen with diffulties in recognizing liver and stomach, or the recognition of a dorsal peritoneopericardial mesothelial remnant (DPMR), (Berry et al 1990.) PPDH can be an incidental finding in otherwise asymptomatic felines of a wide age range. In a retrospective comparative study of PPDH, 11% were asymptomatic; the other cats showed non-specific signs varying from dyspnea (32%), inappetence, vomiting (15%), lethargy (12%), weightloss or stunted growth (9%), (Skrodzki 1997). The echocardiographic examination allows an immediate recognition of the “foreign” material (bowel loops with gas-shadows, omentum, liver lobes etc. immediately adjacent to the heart, and in most cases the lack of a continuous diaphragm, separating the thoracic structures from the abdomen. The recommended therapy for PPDH is surgical correction (Wallace et al, 1992). In cats presented with generalized congestive heart failure, the now very rarely recognized dilated cardiomyopathy may be another cause of the radiographic cardiomegaly. The silhouette of the heart may become quite rounded. The echocardiographic signs of severe dilatation of all 4 chambers with additional hypokinesis of both ventricles are very easily recognized and not difficult to diagnose. Therapy of dilated cardiomyopathy consists of diuretics, positive inotropes (digoxin), ACE-inhibitors and dietary modification (switch to a well-known brand name catfood) as well as taurine substitution. The latter is usually done as a therapeutic trial for several weeks without even measuring plasma levels of taurine, which can only be done by specialized laboratories. Pericardial effusions are very easily diagnosed on echocardiograms by recognizing an echofree (fluid-dense) space surrounding the entire heart. In contrast to the canine, the effusions in cats are usually less voluminous and only in very isolated cases so severe to result in tamponade, with the patient having severe jugular distension, hepatosplenomegaly and ascites (Rush et al, 1990). The more common clinical

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ious forms of cardiomyopathy or neoplasia (primary vs metastatic, lymphosarcoma was the most frequent type). Pericardiocentesis needs to be performed with large effusions only; the technique is the same as in the dog. Any effusion should be differentiated into pure transsudate, modified transsudate and exsudate for diagnostic reasons. The treatment is directed against the underlying primary cause; many not too large effusions disappear with diuretics. Inflammatory or septic pericardial effusions should be treated with drainage, lavage, antiinflammatory and where needed antibiotic therapy (Bonagura 1989). The following table provides a simplified echocardiographic differentiation of the 3 conditions:

PPDH

Pericardial effusion

Dilated cardiomyopathy

pericardium not visualized

pericardium very well visualized, separated from the epicardium

pericardium normal

normal chambers, possible abnormal anatomical position of entire heart

echo-free fluid space of varying size surrounding the heart

severe dilatation of all 4 cardiac chambers

â&#x20AC;&#x153;foreignâ&#x20AC;? structures (liver, gas-filled bowel loops etc.) next to the heart

a. chambers normal to small, possible RA- and RV-tamponade (collapse) or b. chambers abnormal according to an underlying cardiomyopathy or c. masses (tumors) with abnormal echodensity

severe hypokinesis of both ventricles

E.2. Moderate cardiomegaly As mentioned earlier, differential diagnoses for these patients include: primary heart disease: cardiac malformations (young animals) cardiomyopathy chronic degen. valvular disease, rare in cats primary neoplasia (very rare) or secondary heart disease: hyperthyroidism, hypertension, chronic renal failure, dirofilariosis, toxoplasmosis, other (infiltrative, neoplasia, etc.). The echocardiogram, together with levels of T4, results of arterial blood pressure measurement, heartworm serology, and evt. growth hormone determination helps to differentiate these conditions. In contrast to the three previous diagnoses of PPDH, pericardial effusion or DCMP, established with very little echocardiographic skills, a systematic and precise, step-by-step echocardiographic approach with detailed measurements of the cardiac structures will be necessary here for differentiating these underlying conditions. Echocardiographic technique: I like to start the echocardiographic examination with an overview or screening of the

heart in both the right parasternal long axis and short axis projections, to get an image of the entire heart and recognize any abnormalities to be primarily right sided or left sided. It is also helpful to have a somewhat systematic approach and organized search for abnormalities, trying to recognize: structural abnormalities: - septal defects - thickening or abnormal anatomy of valves - abnormal papillary muscles and moderator bands - altered echodensity of the myocardium and/or endocardial and subendocardial structures functional changes:

- hypokinesis, hyperkinesis - diminished or excessive fractional thickening of the septum and/or LV-wall

dimensional changes:

- cavities (dilatation, reduction in size) - walls (global or regional hypertrophy, thinning quite rare)

MAIN PROGRAMME

presentation is nonspecific, and their radiographs also lack the very large and rounded pumpkin-shaped silhouette so typical for canines with pericardial effusion. In my own experience, most incidences of finding considerable amounts of free pericardial fluid on echocardiographic examinations of cats with radiographic cardiomegaly come as a surprise. Pericardial effusions are often associated with simultaneous pleural effusions (53%) and ascites (30%), (Rush et al 1990). Feline infectious peritonitis (FIP) was a common cause of pericardial pathology in that retrospective study, however without any indication of the amounts or seriousness of the effusion. Near 30% of cats had some form of structural cardiac disease; it can be expected that these underlying signs dominate and will lead to a proper diagnosis of any of the var-

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Measurements can be generated throughout the echocardiographic examination or en bloc at the end, after a good overview of the heart. Accepted standards for measurement technique and normal values have been published elsewhere, Moise 1988. I consider it essential to compare and verify any cardiac measurements generated from long axis views with those obtained from right parasternal short axis projections. In this plane, a more symmetrical view of the left ventricle is obtained, with an easier placement of the M-mode cursor between the papillary muscle heads for measuring cavity dimensions and septal and free wall thickness. This view has additional advantages for a more precise evaluation of LAsize. The LA/Ao-ratio reflects a section through the atrial appendage only. True left atrial size would probably best be compared to the aortic root by planimetry or at least by an oblique dimension of its greatest width, as was proposed by Hanson et al 1993 for the dog. Structural abnormalities: The long axis imaging plane permits the screening of both the interventricular (membraneous) and atrial septum for defects, and with Doppler investigation (if available) the confirmation of any suspected shunts. Isolated VSD and ASD seem to be very rare in cats. They are frequently associated with other structural abnormalities (e.g. dysplastic or cleft atrioventricular valves) as part of complex cardiac malformations. I find it quite difficult to recognize definite structural valvular abnormalities on feline echocardiograms, because of the small size of the visible valve leaflets and the elevated heart rate, causing very rapid motion patterns. Neither pulmonic nor aortic or subaortic stenosis can be well visualized. Those diagnoses are usually established by Doppler evidence of increased and turbulent outflow velocities and 2D-evidence of secondary ventricular hypertrophy. Most often, a dysplasia of an atrioventricular valve is recognized by simultaneous severe atrial and moderate ventricular dilatation, and additional evidence of severe regurgitation (loud heart murmur, Doppler confirmation). Additional abnormal shapes or positions of papillary muscles may provide supportive evidence for congenital valvular dysplasia. Otherwise, malformed papillary muscles with abnormally echodense moderator bands and chordal network in generally relatively normal sized ventricles, but with areas of hypertrophy and others of thinning and/or dyskinesis, are suggestive of restrictive cardiomyopathy. A clear differentiation between restrictive and other forms of cardiomyopathy is not always possible. Altered echodensity of the myocardium is most often found in areas of hypertrophy, suggesting fibrous invasion of that area. Isolated septal hypertrophy in the region of the f LV-outflow tract may be responsible for a dynamic outfow obstruction, with or without systolic anterior motion (SAM) of the mitral valve. This could also be associated with dyskinetic septal motion, and the generated pressure gradient between the left ventricle and the aorta can be documented with Doppler. CFDoppler shows turbulence in the LV-outflow tract in such cases. Degenerative valvular lesions, secondary to endocardiosis, are also very difficult to recognize; they occur mostly left-sided in aged cats. In general, moderate to severe left

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atrial dilatation with moderate left ventricular dilatation and some hypertrophy is recognized, together with (Doppler proven) mitral regurgitation. Functional changes: It is simple to recognize diminished excursions of the septum and free LV-wall as signs of hypokinesis and (dilated) cardiomyopathy. A normal to elevated shortening fraction (various degrees of hyperkinesis) are found with all other forms of cardio-myopathies; hyperkinesis should always be evaluated together with any dimensional changes of the cavities. Dimensional changes: Right side. Isolated right sided cardiac enlargement is quite rare in the cat, and may be the endstage of a restrictive (or unclassified) CMP. Possibilities include tricuspid valve dysplasia or pulmonic stenosis, heartworm disease causing only mild right cardiomegaly. If severe right atrial and moderate right ventricular dilatation dominate the image and indicate severe volume overload, tricuspid valve dysplasia or acquired tricuspid insufficiency secondary to degenerative valvular disease (old cats, very rare) should be suspected and confirmed with Doppler. If right ventricular hypertrophy dominates the image, pressure overload of the RV and therefore an outflow obstruction (pulmonic stenosis) should be suspected. Left atrium. I like to switch back and forth between the long axis imaging planes showing the entire left atrium and planes showing the left ventricular outflow tract and aortic root. This allows the recognition of left atrial dilatation, based on a subjective impression of LA-size in comparison to the left ventricle and in relation to the aortic diameter. It should be measured with M-mode as an LA/AO-ratio in this projection and later verified in the short axis projection. LA/AO-ratios should not exceed 1.3-1.5 in normal cats (Moise 1988). The left atrium, and especially its atrial appendage, should also be checked carefully for echocardiographic â&#x20AC;&#x153;smokeâ&#x20AC;? (clouding, or spontaneous contrast effects, indicating the danger of thromboembolization) or echodense masses suggesting the presence of a thrombus. Left ventricle. The long axis view also permits the recognition of increased thickness of the septum and LV-free wall, and especially the distribution of any hypertrophy (symmetric, asymmetric, septum only, overall), for a preliminary diagnosis of hypertrophic cardiomyopathy. Moise in 1993 illustrated the various distribution patterns of LV-hypertrophy with this disease. We use 5-6 mm thickness of the septum and LV-free wall as an upper limit of normal, and dimensions greater than 7 mm as definite signs of hypertrophy, irrespective of body size of the patient (Kittleson 1995). The significance of regional versus global LV-hypertrophy remains unclear and its etiology is somewhat mysterious. I am unaware of any difference in treating the various forms of hypertrophy. The fractional thickening of both the septum and LV-free wall (percentage increase between diastolic and systolic thickness, usual range 30 to 50%) should also be evaluated. An excessive thickening points towards hypertrophic cardiomyopathy, whereas diminished thickening is associated with dilated cardiomyopathy. The fractional thickening should however always be interpreted together with the left ventricular dimension. Hypertrophy of the LV-walls, a diminished systolic dimension (under 08 mm) together with an el-

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A variety of abnormal structures (dysplastic valves, additional septal defects) with various degrees of ventricular hypertrophy and atrial dilatation are found with complex cardiac malformations. A careful investigation of each inflow- and outflow-tract with Doppler is needed for a correct diagnosis, which may not be completely possible ante mortem in each case. The following table 1 uses a rather simplified approach, using generalizing statements, for the differentiation of the various etiological forms of left heart enlargement/ hypertrophy in the cat.

F. Therapeutic guidelines Obviously, the underlying problem leading to secondary cardiomyopathy should be eliminated if possible. For example, hyperthyroidism can be treated with either methimazole, surgery or radiation therapy, Salisbury 1991. In feline hypertension, the calcium-channel antagonist amlodipine at a dosage of 0.625 mg, per cat once daily, has been shown to be efficacious, Henik et al 1994.

Table 1. Simplified echocardiographic differentiation of feline myocardial hypertrophy “classic” HCMP

“restrictive” CMP

acquired myocardial hypertrophy

Etiology: unknown, idiopathic (poss. growth hormone excess)

unknown, idiopathic (possible previous myocarditis)

hyperthyroidism, systemic arterial hypertension (CRF) aortic stenosis, mitral regurgitation (chron. valvular degeneration) neoplastic infiltration, acromegaly

LV-Hypertrophy: moderate to severe, concentric, including papillary muscles, varies from global to regional, occasional hyperechogenicity of the myocardium, esp. papillary muscles, in some cases (SAM)

mild to moderate only, more often regional, sometimes involving papillary muscles. Frequent patchy endocardial and endomyocardial hyperechogenicities, esp. with apical hypertrophy

mild to moderate, rarely severe, global, concentric with AS normal echogenicity of the myocardium

LV-cavity: small

normal to small, abnormal chordae and/or moderator bands

normal to slightly large small with AS

Shortening fraction: normal to high

normal to low, possible regional LVW-dyskinesis

normal to high

LA-size: mild to severe increase, somewhat proportionate to the LV-hypertrophy

severe increase, disproportionate to the degree of LV-hypertrophy

normal to moderate increase

Doppler, LV-outflow: dynamic subaortic stenosis

mostly normal (??)

mostly normal, moderate to severe turbulence with AS

Doppler, Mitral valve: mitral regurgitation proportionate to LA-size

mild to moderate mitral regurgitation, restrictive inflow patterns difficult to obtain

mild to moderate mitral regurgitation, in selected cases only (?)

Developement of CHF: moderately frequent, dependant upon the severity of LV-hypertrophy and LA-size

very common and severe

uncommon, mild to moderate only (?)

Thromboembolization: yes

common to very frequent

rare

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evated shortening fraction (over 55%, both subjective judgements), allows a classification of concentric hypertrophy of the left ventricle, which is an essential basis for the diagnosis of the “classic” idiopathic hypertrophic cardiomyopathy, Kittleson 1995. It must be emphasized that other forms, with normal or nearly normal dimensions of the cavities and only some form of septal and free wall hypertrophy, occur frequently in cats and make the diagnosis less clear-cut. Hyperthyroidism for example often presents with mild to moderate hypertrophy (symmetric for the septum and the LV-wall) but normal to slightly large dimensions of the cavities and normo- to hyperkinesis (Bond et al 1988, Moise et al 1986). In some patients, relatively normally sized left ventricles are recognized with very large left atria. The ventricles however show very abnormal echodensities in the endocardium and myocardium and/or unusal trabecular and chordal network. These abnormalities allow a classification of “restrictive cardiomyopathy”. The term is based primarily on the dominant hemodynamic abnormality (abnormal diastolic filling patterns, illustrated with Doppler echocardiography), and not so much upon definite pathologic-anatomical features. This diagnostic group is quite inhomogenous.

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A good number of cats will present with signs of respiratory distress due to congestive heart failure secondary to the severe hypertrophy of the heart. Initially, diuretics at a dose of 1-2 mg/kg 2-3 times daily (intravenously or intramuscularly) are given, Kittleson 1995. These doses should be reduced as soon as the distress abates, in order to avoid dehydration and electrolyte disturbances. We believe that ACE-inhibitors are also beneficial in acute CHF of cats, though experimental evidence is still lacking. Dose rates are 0.25-0.5 mg/kg enalapril twice daily and 0.5 mg/kg benazepril once daily. Recommendations for longterm therapy are still somewhat controversial, Kittleson 1995. Both betablocking drugs and the calcium antagonist diltiazem can be used with good justification, Fox 1991. Both drugs produce symptomatic relief. Diltiazem has shown to reduce pulmonary edema and reduce the need for diuretics, Bright et al 1991. It is thought to improve diastolic relaxation and improve the ventricular compliance; there was also evidence that the ventricular hypertrophy regressed in some cases. Propranolol on the other hand probably reduces the amount of SAM of the mitral valve and the degree of mitral regurgitation, Kittleson 1995. Clinical experience with betablockers is widespread and anecdotally reported to be good. More recent interest has focussed on the use of ACE-inhibitors, not so much because of the plasmatic effect reducing aldosterone levels and volumeoverload, but more because of the tissular blockage of ATII formation and prevention of angiotensin-mediated cardiac remodelling, i.e. induction of cardiac hypertrophy. Preliminary results with enalapril (Rush et al 1998) and Bbenazepril (unpublished own data, 1998) are promising. ACE-inhibitors may also be indicated and a good choice in cats with early restrictive cardiomyopathy without severe signs of failure, Bonagura and Fox 1995. For asymptomatic cats with hypertrophy, either drug may be tried, and their effects should be studied by followup echocardiography, in order to justify longtern administration. With respect to prevention of thromboembolisms, the specific literature should be consulted, Harpster and Baty 1995.

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References Berry CR, Koblik PD, Ticer JW (1990): Dorsal peritoneopericardial mesothelial remnant as an aid to the diagnosis of feline peritoneopericardial diaphragmatic hernia. Vet Radiol 31: 239-245. Bonagura JD (1994): Cardiovascular diseases. In Sherding RG (Ed): The Cat: Diseases and Clinical Management II Ed., Churchill Livingstone, New York, 819-978. Bonagura JD, Fox PR (1995): Restrictive cardiomyopathy. In: Bonagura JD (Ed), Current Veterinary Therapy XII, small animal practice, WB Saunders, Philadelphia, 863-867. Bond BR, Fox PR, Peterson ME, Skavaril RV (1988): Echocardiographic findings in 103 cats with hyperthyroidism. JAVMA 192: 1546-1549. Buchanan JW, Bucheler J (1991): Vertebral scale system to measure heart size. Proc 9th ACVIM Forum, New Orleans, pp. 689-670. Farrow CS, Green R, Shively M (1994): Radiology of the cat Mosby Year Book, Inc. St. Louis, 45-131. Hanson K: Assessment of left atrial enlargement, comparison between thoracic radiography, B-mode and M-mode echocardiography. Proc XII. ESVC- meeting 1993, Berlin, 2-3. Harpster NK, Baty CJ (1995): Warfarin therapy of the cat at risk of thromboembolism. In: Bonagura JD (Ed), Current Veterinary Therapy XII, small animal practice, WB Saunders, Philadelphia, 868-873. Henik RA, Snyder PS, Volk LM (1994): Amlodipine besylate therapy in cats with systemic arterial hypertension secondary to chronic renal disease. Proc. 12th ACVIM-Forum, San Francisco, 976. Kittleson MD (1995): CVT update: Feline Hypertrophic Cardiomyopathy. In Bonagura JD (Ed), Current Veterinary Therapy XII, small animal practice, WB Saunders, Philadelphia, 854-862. Moise NS, Dietze AE, Mezza LE, Strickland D, Erb, HN, Edwards NJ (1986): Echocardiography, electrocardiography, and radiography of cats with dilatation cardiomyopathy, hypertrophic cardiomyopathy and hyperthyroidism. Am J Vet Res 47: 1476-1486. Moise NS (1988): Echocardiography. In: Fox PR (Ed), Canine and Feline Cardiology, Churchill Livingstone, New York, 113-156. Moise NS (1993): Echocardiography of cats with cardiomyopathy. Proc 2nd International Symposium of Veterinary Echography, AcropolisNice/France, 72-76. Rush JE, Keene BW, Fox PR (1990): Pericardial disease in the cat: a retrospective evaluation of 66 cases. JAAHA 26: 39-46. Salisbury SK (1991): Hyperthyroidism in cats. Comp Cont Ed 13: 13991409. Skrodszki M, Allgoewer I, Grevel V (1997): Congenital peritoneopericardial hernias in 16 cats. Part 1: Literature review and cases (in German). Kleintierpraxis 42: 973-996. Wallace J, Mullen HS, Lesser MB: A technique for surgical correction of peritoneo-pericardial diaphragmatic hernia in dogs and cats. JAAHA (1992) 28: 503-510.

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Anaemia in the young dog George Lubas Med Vet Department of Veterinary Clinic - University of Pisa - Italy

Summary RBC indexes in young Beagle dogs 100 80 60 40 MCV (fL)

MCH (pg) 0 birth

MCHC (%) 1st

2nd

3rd

4th

6th

8th

12th 16th 20th 24th

Weeks of age

Figure 1 - Behaviour of the RBC indexes (MCV, MCH, and MCHC) in young Beagle dogs1,7,11

Introduction Before developing an algorithm to reach a diagnosis for anemia, it is important to consider the evolution of the hemopoietic pool in the dog from birth to one year of age; it is only after the age of one year that several hematic parameters are fixed in the adult reference interval. Unfortunately data on the this topic are rather outdated and usually only refer to the Beagle, a purpose-bred dog often used in research where environmental influences are minimal, and studies are often restricted to nutritional or pathological effects. Data so generated, however, potentially could be extrapolated to other canine breeds as long as changes are not over interpreted. In this review, the diagnostic approach to anemia is similar to that already reported in the previous speeches, and is derived from current knowledge in this field. The emphasis here will be on epidemiology and the resulting specific hemopoietic effects in the young dog.

Erythroid and myeloid pool in the young dog At birth the red blood cells (RBCs) of foetal origin are quite large (Mean Cell Volume; MCV; 95-100 fL). As foetal RBCs are replaced, the MCV progressively decreases, so that by 2-3 months of age, the RBC size is similar to that of the normal adult dog. Similarly the Mean Cell Hemoglobin (MCH) is about 33 pg at birth and decreases to approximately 22 pg by 2 months of age. Mean Corpuscular Hemoglobin Concentration (MCHC) differs only slightly with age, being almost 35% at birth and decreasing to 33% at 2 months of age and remains quite constant at approximately 32% despite the fluctuations of hematocrit (Hct; figure 1). This particular index may fluctuate within a normal range by 3-5% due to physiological and technical variations1,3,7,9,11.

As a consequence of the behaviour of the RBC indexes, the values of hemoglobin (Hgb) and Hct are quite high at birth, but fall rapidly as the pup begins to nurse. The decrease in the above parameters continues during the first month of life (see figure 2). Circulating RBC mass is significantly reduced, due to an increased destruction of foetal RBCs as well as to the rapid growth of the puppy (generally it reaches from 3 to 4 times the birth weight by one month of age). Therefore a relative anemic state often exists in the young representing physiologic adaptation to extra uterine environment. At the beginning of the second month of life there is a gradual and steady increase of RBC count as well as in Hgb and Hct values which ends at approximately 1 year of age when adult values are attained. Other influences on these changes include stress and inherent breed differences. The spleen acts as an a RBC reservoir, releasing RBCs into circulation in response to apprehension due often to difficulties in collecting adequate blood for examination, particularly in small or toy breeds2,3,4,6,9,10,14.

RBC values in young Beagle dogs 50 40 30 Hct (%)

Hgb (g/dL)

10 0 birth

1st

2nd

3rd

4th 6th 8th Weeks of age

12th

16th

20th

RBC (M/mcL)

Figure 2 - Behaviour of RBC values (Hct, Hgb, and RBC count) in young Beagle dogs2,4,6,10,14.

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Anemia is considered a frequent clinical finding in the young dog. This sign should be thoroughly examined in order to determine 1) if red cell regeneration is occurring and then 2) assessing, as far as possible the etiology. The hematological reference intervals in the young dog are different than adult canine reference intervals, particularly in the first months of age. This review considers the most important clinical disorders manifesting with anemia, from an epidemiological perspective, in the first months of canine life.

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The rapid replacement of foetal RBCs and physiologic compensation due to rapid body growth result in increased erythropoietic activity manifest by increased circulating reticulocytes. Indeed in puppies up to one month of age the reticulocyte count may be close to 7% as compared to normal adult values of 1-2%. The same observation is noted with nucleated red blood cells (NRBCs), with a peak of about 4 NRBCs per 100 White Blood Cells (WBCs) occurring after 1 week of age. The NRBCs disappear around two months of age. Similarly, during the same period the reticulocyte count falls to about 4% (figure 3). It also reported that young female dogs under 16 months of age have a reticulocyte count lower than males3,5,6,9,11.

RBC regenerative signs in young Beagle dogs 7 6 5 4 3 2

NRBC/100 WBC

Rets (%)

0 birth

1st

2nd

3rd

4th

6th

Very little information are available on the immature canine platelet (Plt) pool; lower thrombocyte count have been reported in young dogs in contrast to adults, while other studies report no association between platelet count and age3,9.

Classification of anemia in the young dog Anemia is defined, even in a young animal, as a decrease in the number of circulating RBCs together with a decrease in Hgb concentration or Hct percentage. The characteristic signs are related to reduced oxygen transport. Anemia can be classified as either regenerative or nonregenerative based on the reticulocyte response observed in peripheral blood3,9,12. Age is always an important consideration because of erythroid physiological behaviour. This review will discuss only the remarkable differences reported in young dogs, focusing on the causative agents and the hereditary component for some hemolytic anemias, as well as the main causes of nonregenerative anemias in this age group. The blood loss anemias (included in the regenerative classification of anemias) donâ&#x20AC;&#x2122;t show any special figures for young dogs, although at this age inherited coagulation disorders should be considered as possible causes of severe blood loss.

8th

Weeks of age

REGENERATIVE ANEMIA Figure 3 - Reticulocyte count and NRBCs in young Beagle dogs5,6,11.

The normal wide ranges reported for canine WBC counts (6,000-17,000/mcL) reflect the effects of age and normal activity. The WBC count is highest in young dogs. As an example, a WBC count of 7,000/mcL is normal in an old dog while it can be suggestive of leukopenia in a dog less than 18 months of age. The gradual decrease of WBC count with age is primarily due to both changes in lymphocyte and neutrophil numbers. In a study on Beagles focused on WBC count modification as well as on the number of leukocyte types from birth up to 24 weeks of age, a neutrophilia was observed at birth (due perhaps to the stress of birth) which disappeared within a week. Neutrophil and lymphocyte counts were similar at the 3rd week of age (caused by weaning, change in feeding, and new antigen exposure), after which neutrophil numbers steadily increased relative to lymphocyte numbers (see figure 4)3,4,9,11.

WBC values in young Beagle dogs (K/mcL) 18 16 14 12 10 total WBC

Neu Band

Puppies of 4 months of age or younger are quite susceptible to Babesia spp. (B. canis, B. gibsoni, and B. vogeli) and frequently have more severe infection than do adult dogs. Mild strains of B. canis may cause apparent disease only in puppies and B. gibsoni has been identified in the blood smear of a bitch and her 3-day old puppies, suggesting that transplacental transmission occurred. These diseases are tick-borne (Rhipicephalus sanguineous, Dermacentor spp. and Hyalomma spp.). The hemolysis induced by these parasites is both intravascular and extravascular with signs of bone marrow regeneration (reticulocytes and, secondarily, NRBCs). Other laboratory findings may include thrombocytopenia, hyperbilirubinemia, bilirubinuria, hemoglobinuria, and azotemia. Metabolic acidosis and disseminated intravascular coagulation (DIC) may develop as a complication. Definitive diagnosis requires a careful examination for Babesia spp. in RBCs. An indirect immunofluorescence (IFA) test may be used in chronic disease because the titers will be detectable 2.5 weeks after onset of infection3,9. Infections by Haemobartonella canis are reported as frequent in dogs of all ages with severe hemolytic anemia occurring in especially young animals3,9.

Neu Seg

Lymp

Mono

0 birth

Hemolytic anemia caused by infectious agents

Eosi 1st

2nd

3rd

4th

6th

8th

12th

16th

20th

24th

Baso

Immune mediated hemolytic anemia (IMHA)

Weeks of age

Note: Neu = neutrophil; Seg = segmented; Lymp = lymphocyte; Mono = monocyte; Eosi = eosinophil; Baso = basophil

Figure 4 - Total and differential WBC values in young Beagle dogs4,11.

IMHA occurs rarely in dogs younger than 6 months of age, and may be induced by many processes including drugs, alloantibody formation, infectious processes, vac-

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Heinz body hemolytic anemia This type of anemia occurs when there is excessive accumulation of oxidised RBC Hgb often as the result of ingested oxidants. This situation may occur in young dogs from ingesting oxidative drugs (methylene blue, topical benzocaine, acetaminophen, vitamin K3 or menadione, and phenylhydrazine) or chemicals (zinc or onions). In addition to Heinz bodies, RBC membrane damage including poikilocytosis and schistocytosis and signs of RBC regeneration may occur3,8,9,12. The RBCs of the Japanese Akita and Shiba have reduced glutathione activity and increased intracellular potassium concentrations that result in an increased sensitivity to onion-induced Heinz body formation and hemolysis occur3,8,9,12. Anemia associated with Heinz body formation will appear nonregenerative if observed within the first 2 to 3 days after the onset, before the bone marrow erythropoietic response. However this disease does not require specific therapy other than removing access to or discontinuing administration of the offending oxidative agent. As an alternative NAcetylcysteine could be used within hours of ingestion of the offending substance at a dosage of 140 mg/kg per os (PO) followed by 70 mg/kg PO every 6 hours for seven treatments. In severe, life-threatening anemia, blood transfusion is indicated occur3,8,9,12.

Hemolytic anemia on inherited basis This type of anemia should be suspected when the animals exhibit persistent reticulocytosis and hemolytic anemia, have negative direct antiglobulin tests (DAT; Coomb’s test), negative examinations for Babesia spp. infection, and a negative history of toxin exposure causing production of Heinz bodies8. Deficiency of Pyruvate Kinase (PK) This deficiency causes a nonspherocytic hemolytic anemia in Basenji dogs as a congenital disorder and in Beagles, West Highland White and Cairn Terriers as isolated occurrences. The mode of inheritance is a simple autosomal recessive trait; matings between carriers of the defect produce normal or anemic or carrier puppies, whereas the offspring of affected anemic parents are always affected. Carrier dogs are not anemic, but can be identified by their notable reduction of RBC pyruvate kinase activity. This deficiency is not often observed until puppies are 4 months to 1 year of age. Premature RBC destruction, with moderate to severe anemia (Hct from 12 to 26%), and evidence of RBC regeneration (polychromasia/reticulocytosis, anisocytosis, increased NRBCs) could be observed. As the dog ages, the early intense erythropoietic response declines until the bone marrow aspiration may be unsuccessful as the hematopoietic compartment is replaced with fibrous tissue (myelofibrosis). This occurs from 2 to 5 years of age as impaired RBC production leads to death from nonregenerative anemia and hepatic failure. There is no effective long term treatment for this type of hemolytic anemia, which could only be corrected by a bone marrow transplantation from normal littermates occur3,8,9,12. Deficiency of Phosphofructokinase (PFK) This deficiency is recognised in the English Springer Spaniel as well as in the American Cocker Spaniel (presumably because of intercrossing between this two breeds), and is inherited as a simple autosomal recessive gene. It is characterised by chronic hemolysis with recurrent hemolytic crisis and mild myopathy. Crises may be precipitated by episodes of hyperventilation induced by extensive exercise, excessive barking, and/or elevated environmental temperature. During the crises, dogs may become severely anemic or icteric with a transient hemoglobinemia, hemoglobinuria, and bilirubinuria that usually resolves with therapy for IMHA. Spontaneous resolution does occur. The activity of PFK is, respectively, about 20% and 5% of the normal concentration of RBCs and muscle. The PFK deficiency results in an early blockage of glycolysis induced by marked reduction 2,3-diphosphoglycerate (2,3 DPG) RBC concentration. This in turn provokes increased Hgb oxygen affinity, increased intraerythrocytic pH and increased RBC fragility as the result of intraerythrocytic alkalosis occur3,8,9,12. Inherited Stomatocytosis of Alaskan Malamute This RBC shape alteration results in reduced RBC life span and is also related to autosomal recessive-transmitted chondrodysplasia (short-limbed dwarfism) in the Alaskan Malamute. The other hematological findings include an appropriate PCV with reduced hemoglobin content; the RBC indices include increased MCV, decreased MCHC, and normal MCH. Despite this macrocytosis few RBCs are reticu-

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cines, or may be ill-defined true autoimmunity3,9,12,13. Neonatal isoerythrolysis results from previous sensitisation of the bitch (exposure to red cell antigens of puppies having the father’s blood type; previous blood transfusions). Indeed alloantibodies against dog erythrocyte antigen (DEA) 1.1 are produced when DEA 1.1 positive blood is transfused into a DEA 1.1 negative bitch and the bitch subsequently is mated to a DEA 1.1 positive dog. Her puppies may experience hemolytic anemia, nursing during the first 48 hours of life as they receive the mother’s colostral antiDEA 1.1 alloantibodies. Puppies with the DEA 1.2 blood group could be also mild affected, while alloantibodies toward other blood group types have not been implicated in causing anemic problems in newborn puppies3,9,12. Neonates that experience isoerythrolysis are generally healthy and normally sized at birth but develop hemolysis within several hours or days after ingestion of colostrum. They exhibit progressive weakness, pale mucous membranes, hemoglobinemia, hemoglobinuria, and icterus. The severity of the hemolytic anemia is variable, depending somewhat on the quantity of colostral alloantibodies absorbed and the nature of the antigen-antibody reaction (direct or indirect agglutination and hemolysis). Severely affected puppies often die within 24 hours from respiratory distress or within 2 to 6 days owing to complications due to DIC or from acute renal failure. The puppies should be separated from their mother for the first 48 to 72 hours and given milk replacer or allowed to nurse from a foster mother with the same blood type as the puppy and not producing colostral alloantibodies. Withholding colostrum from subsequent litters of dams proven or suspected to be sensitised is advisable3,9,12.

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locytes and about 4 percent of the RBCs are stomatocytes. Treatment is generally not necessary as the disease is not life-threatening. Efforts should be made toward to control and eliminate of heterozygous carrier dogs from the breeding population occur3,8,9,12. Nonspherocytic Hemolytic Anemia of the Poodle and Beagle A severe (Hct from 10% to 26%) nonspherocytic hemolytic anemia characterised by a markedly regenerative RBC response, hepatosplenomegaly, bone marrow myelofibrosis and osteosclerosis, with a fatal course has been described in related black miniature Poodles. A similar disease but less severe and without significant fatalities has been reported in Beagles. In these breeds an autosomal recessive mode of inheritance has been postulated altering the RBC membrane and the calcium-adenosine triphosphatase (CaATPase) enzyme, but the cause remains undetermined. In Poodles the unremitting anemia with macrocytosis is most evident by one year of age and often fatal by 3 years of age. In this breed there is no effective, long term treatment for the severe anemia; however, correction by bone marrow transplantation from hematologically normal littermates may be effective occur3,8,9,12.

NON REGENERATIVE ANEMIA Nonregenerative anemia is defined as an anemia longer than 5 daysâ&#x20AC;&#x2122; duration with inappropriately low corrected reticulocyte counts. Based on complete blood count, nonregenerative anemia may also be identified as being a refractory anemia or a component of pancytopenia. In refractory anemia, the WBC and Plt counts are normal or increased, while in pancytopenia the disorder involves these two cell lines as well. Based on the RBC indexes, refractory anemia may be further subdivided in normocytic, normochromic (the most frequent); macrocytic, normochromic; and microcytic, hypochromic. Bone marrow examination and iron studies should be evaluated to delineate the cause of the refractory anemia occur9,12,13.

Refractory anemia Failure of appropriate RBC production Pure red cell aplasia (PRCA) resulting in selective and severe erythroid bone marrow hypoplasia has not been reported in dogs younger than 6 months of age. However, secondary marrow failure as a result of long-standing disease (e.g., advanced renal or hepatic disease, inflammatory disease, malnutrition, Ehrlichiosis) frequently causes refractory anemia (normocytic and normochromic). In particular, the anemia of inflammatory disease is characterised by mild to moderate, poorly regenerative anemia and altered iron metabolism. Low serum iron and total iron binding capacity, as well as increased sequestration of iron in marrow macrophages are described3,9,12,13. Nuclear maturation defects These anemias, characterised by macrocytic and normochromic RBCs, result from defective marrow DNA syn-

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thesis in erythroid precursor cells causing decreased RBC division and the appearance of large NRBCs and macrocytes in peripheral blood. In addition, the disturbance may cause mild reduction in WBC and Plt numbers. This type of anemia is uncommon in young dogs and is associated with vitamin B12 and/or folate deficiency3,9,12,13. A selective cobalamin (vitamin B12) malabsorption in Giant Schnauzers is related to an autosomal recessive mode of inheritance. The disease is characterised by cachexia, dementia, and nonregenerative anemia. Cobalamin is required for purine and pyrimidine synthesis, both precursors of DNA. Nuclear maturation is impaired and results in reduced mitotic division and large NRBCs (megaloblasts) that have asynchronous maturation of nucleus and cytoplasm. Other cell lineages can also be affected. The clinical signs initially appear at 3 months of age and are characterised by lethargy, anorexia, and cachexia. The hematological data include mild to moderate anemia, anisocytosis without reticulocytosis or other evidence of regeneration, poikilocytosis with some macrocytes, neutropenia and hypersegmented neutrophils. The serum cobalamin concentrations are low and an increase of urinary methylmalonic acid is observed. Treatment with cobalamin, 0.25-1.00 mg subcutaneously (SQ) once daily (SID) for one week then once monthly often resolves the defect3,9,12,13. Folate deficiency is more likely to occur due to the administration of drugs which inhibit bacterial folate synthesis (pyrimethamine, and trimethoprim) through a competitive inhibition of tetrahydrofolate reductase, thus inhibiting the reduction of folate to its active form, dihydrofolate and tetrahydrofolate. Generally the drug-induced anemia appears well before any overt signs of illness are noted3,9,12,13. A congenital macrocytosis has been reported in Miniature and Toy Poodles. The affected dogs have normal Hct and Hgb concentrations because of macrocytosis, but they have a slightly reduced RBC numbers. Hypersegmentation of neutrophils in peripheral blood and megaloblastic RBCs in bone marrow may be observed3,9,12,13. Hemoglobin synthesis defects The result of altered hemoglobin synthesis is RBC microcytosis which is initially normochromic and becomes a frankly hypochromic, and then refractory anemia. This commonly occurs secondary to iron deficiency in young malnourished or heavily parasitized dogs (by bloodsucking internal or external parasites). Iron deficiency occurs when iron loss or utilisation exceeds iron absorption from the intestine and rapidly develops in newborn and young animals who have limited iron stores and require a steady increase in their total RBC mass for growth needs. The nonparasitic causes of external blood-loss induced iron deficiency in dogs may include bleeding disorders, infectious enteropathies, and gastrointestinal ulcerations. Other potential but rare causes of microcytic, hypochromic refractory anemia include copper or vitamin B6 deficiency, or iron deficiency as the result of lymphocytic-plasmacytic intramural intestinal disease3,9,12,13. Dyserythropoiesis of English Springer Spaniel A nonregenerative anemia associated with a polysystemic disorder (polymyopathy with megaesophagus and varying degrees of cardiomyopathy) has been reported in a

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Pancytopenia Aplastic Anemia Aplastic anemia is a collective term describing a condition characterised by anemia, thrombocytopenia, and granulocytopenia with an acellular or markedly hypocellular bone marrow. The failure of the hemopoietic activity may be due to marrow necrosis and/or inflammation, a defect in the proliferative capacity of the pluripotential stem cell in the marrow, or a defect in the hemopoietic-inductive bone marrow microenvironment. This disorder could be associated with estrogen or trimethoprin therapy, phenylbutazone toxicity, use of chemicals such as benzene compounds, and infections by several agents including canine distemper virus, canine parvovirus and Ehrlichia canis3,9,12,13. Myelophthistic Disorders Myelophthistic disorders are extremely rare in young dogs but may result from bone marrow infiltration by primary hematopoietic tumors or fibrous tissue (myelofibrosis) or from congenital failure to develop normal bone marrow cavities as occurs in inherited osteopetrosis3,9,12,13. Lead Toxicosis This toxicity is well recognised, affecting dogs from 2 to 8 months of age. At that age dogs often have a curious nature and chewing habits often result in ingestion of strange substances. Moreover lead tends to accumulated more in younger animals. Lead toxicosis induces a nonregenerative anemia that could be misinterpreted as regenerative. Indeed, a large number of NRBCs (from 15 to 40/100 WBCs) may be found in peripheral blood along with a mild normocytic normochromic anemia (Hct around 30%). Other RBC abnormalities include basophilic stippling, poikilocytosis and, sometimes hypochromasia. Lead causes profound alterations in hemoglobin synthesis with an inadequate formation as well as a shortened RBC survival time. The RBC modifications occur very early in lead toxicosis, even before other clinical signs3,9,12. A definitive diagnosis is established by performing a lead analysis, collecting oxalate or heparin whole blood sample in a clean, lead free glass vials. Baseline concentrations for lead generally range between 5 to 25 mcg/dL (0.050.25 ppm); suspicious values range from 30 to 50 mcg/dL (0.3-0.5 ppm) and indicate lead poisoning if associated with typical gastroenteric and neurologic signs and hematologic findings. The findings of concentrations over 60 mcg/dL (0.6 ppm) are diagnostic for lead poisoning. Therapy is based on chelation which effectively removes lead by combining to form nontoxic complexes rapidly excreted via bile or urine. The chelating agent of choice in young dogs is cal-

cium disodium edetate and/or succimer. As soon as chelation therapy is initiated, RBC abnormalities quickly disappear3,9,12.

Conclusions As will be evident from this review, there are many gaps in our knowledge about the evolution of the hemopoietic system in the young dog. Detailed studies are needed in this area, and should include the use of representative breed of the various dogs sizes. It is well known that differences in the hematological reference intervals between breeds such as the Yorkshire terrier and the Great Dane are perhaps even more apparent at a young age. Improved instrumentations in veterinary hematology should improve the accuracy of these determinations. Secondly, there is a need to develop a reporting system for inherited erythrocytic disorders, which at the moment are only reported in certain breeds primarily in USA. It is possible that these defects are present in other breeds and that they are geographically more diverse. In the near future the diagnosis of these diseases should be by specific referral laboratories using genetic biotechnologies. Indeed they should not be considered as exclusive of some kennel clubs or some countries, but are world-wide problems especially considering the constant animal movement possible in the world today. Finally, data on anemic processes in the young animal are not, as yet, widely recognised. Hopefully this review may help. Many of the diseases described herein have been determined relatively recently and are now being recognised by private veterinary clinicians as routine hematologic examination becomes an integral part of clinical practice. It is essential for correct evaluation of a pediatric patient that the proper collection of an adequate sample for analysis be accomplished in order to reach definitive diagnoses.

References (For shortness the books consulted and some publications are only here reported; the extended reference version could be requested directly to the author). 1. Andersen AC & Schalm OW (1970), The beagle as an experimental dog, In: Hematology, Andersen AC, ed. Iowa SU press, Ames. 2. Andersen AC & Gee W (1958), Normal blood values in the Beagle, Vet Med, 53:135. 3. Bounous DI (1995), Hematology of normal dogs and cats and response to disease In: Hoskins JD (ed), In: Veterinary pediatrics: dogs and cats from birth to six months, 2nd edit, WB Saunders, Philadelphia, 337-353. 4. Bulgin MS et al (1970), Hematological changes to four and one-half years of age in clinically normal beagles, JAVMA 175: 1064. 5. Brunk R & Becker-Berger S (1980), Statistiche untersuchungen auf alters- und geschlechsspezifische unterschiede von blutparametern an englischen beagle-hunden, Berl Munch Tierarztl Wochenschr, 93:128. 6. Earl FL et al (1973), The hemogram and bone marrow profile of normal neonatal and weanling beagle dogs, Lab Anim Sci, 23: 690. 7. Ederstrom HE & DeBoer B (1946), Changes in the blood of the dog with age, Anat Rec, 94: 663. 8. Giger U (1989) Hereditary disorders of canine erythrocytes, In: Current Veterinary Therapy X. Small Animal Practice, Kirk RW (ed),

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limited number of this type of dog aged from 3.5 months to 2 years old. The dyserythropoiesis is characterised by abnormal erythroid cells with arrested or abnormal mitosis in the bone marrow and many NRBCs in the peripheral blood without appropriate reticulocytosis. Other RBC abnormalities such as microcytosis, spherocytosis, schistocytosis, and poikilocytosis may occur. Until now the prevalence, underlying mechanism, and mode of inheritance are unknown3,8,9,12.

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9. 10. 11.

4th European FECAVA SCIVAC Congress WB Saunders, Philadelphia, 429. Jain NC (1986), Schalmâ&#x20AC;&#x2122;s Veterinary Hematology, Philadelphia, Lea & Febiger, 103. Lee P. et al (1976), Blood volume changes and production and destruction of erythrocytes in newborn dogs, Am J Vet Res, 37: 561. Shifrine M et al (1973), Hematologic changes to 60 days of age in clinically normal beagles, Lab Anim Sci, 23:894.

12.

13. 14.

Tvedten H (1994), Erythrocyte disorders, In: Willard MD, Tvedten H, Turnwald GH (eds), Small animal clinical diagnosis by laboratory methods, 2nd edit, WB Saunders, Philadelphia, 31. Tyler RD & Cowell RL (1996), Classification and diagnosis of anemia, Comp Haem Intl, 6: 1. Weisse I et al (1971), Das blutbildder englischen beagle-hund in abhangigkeit von alter und geschlecht, Arzneim Forsch, 21: 1703.

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Contemporary application and interpretation of hepatic tests Denny Meyer

“For the study of medical diseases of the liver, it is essential that the pathologist be apprised of the clinical findings and the results of laboratory tests and radiographic studies. The correct diagnosis is most likely to be reached by the pathologist and clinician working as a team”. Kamal Ishak, MD; pathologist. The serum hepatic enzyme tests are grouped into those that indicate hepatocellular injury/repair and those that reflect increased enzyme production stimulated by retained bile or drug induction. The magnitude and duration of increase in plasma enzyme activity is dependent on 1) its innate tissue activity, 2) its cellular location, 3) its rate of removal from the plasma, and 4) the type, severity and duration of the injury/stimulus. The rate of removal seems to have molecule-specific and species-specific properties; neither well-characterized in veterinary medicine. Table 1 lists examples for the dog and cat. Leakage Enzymes. Alanine aminotransferase (ALT); Aspartate aminotransferase (AST). There is a high activity of alanine aminotransferase (ALT) in hepatocellular cytoplasm of the dog, cat, and primate; the equine, bovine, birds, and marmoset are notable exceptions. One can think of each hepatocyte like a little balloon filled with ALT. Altered permeability of the hepatocellular membrane caused by injury or a metabolic disturbance results in a release of this soluble enzyme. Subsequent to an acute, diffuse injury, the magnitude of increase in the plasma crudely reflects the number of affected hepatocytes. A variety of tissues, notably skeletal muscle and liver, contain high aspartate aminotransferase activity (AST). Skeletal muscle injury is best defined biochemically by the measureTable 1. Approximate plasma half-life of hepatic enzymes in the dog and cat Enzyme ALT AST GLDH ALP -hepatobiliary isoenzyme -corticosteroid isoenzyme -intestinal isoenzyme

Dog

Cat

61 (or 40) h* 12 h 18h

3.5 h 1.5 h -

66 h 74 h 6m

6h 2m

*references differ; h = hours, m = minutes.

ment of the serum creatine kinase (CK, CPK) activity, a specific skeletal muscle enzyme. Our experience suggests that there is value in the interpretation of the serum activities of ALT and AST for liver disease in the dog and cat. Following an acute injury resulting in a moderate to marked increase in the serum ALT and AST activities, the serum AST activity will return to normal more rapidly (hours to days) than the serum ALT activity (days) due to their difference in plasma half-lives and cellular location. By determining these values every 2 to 5 days for the dog following an acute insult, a sequential "biochemical picture" indicative of resolution is obtained. Persistent mild to moderate increases of the serum ALT and AST activities (documented multiple times over months) suggest a “smoldering” inflammatory process, chronic hepatitis. The persistent increase in the aminotransferase activities is probably a consequence of increased release subsequent to both cell injury and on-going hepatocelluar reparation (regeneration). Novel Concept-1. Clinically, the decrease in the serum ALT and AST activities is often slower than their plasma half-lives would predict following a one-time release phenomenon subsequent to cellular injury. This is probably due in some cases to the temporary persistence of the insulting agent and the ensuing inflammatory reaction. An explanation that can be more generically applied to explain this discrepancy focuses on the relatively unique regenerative ability of the hepatocyte. Studies in the rat indicate that 24 hours following carbon tetrachloride-induced hepatocellular injury, the expected increase in the plasma ALT and AST activities occurs. If the increase in the plasma was due solely to a one-time release from the damaged tissue, the corresponding hepatic tissue activity would be expected to be decreased. Recent studies demonstrate that the hepatic tissue activities for both aminotransferases are actually moderately increased at 24 hours. The finding suggests that the remaining viable hepatocellular tissue has increased its synthesis of the aminotransferases as a consequence of, and/or in support of, the reparative/regenerative process. This concept is supported by repeating the carbon tetrachloride study and coadministering cyclohexamide, a nonspecific inhibitor of protein synthesis. Following the administration of this ‘cocktail’ to rats, the rise in the plasma aminotransferase activities is blunted by approximately 60% compared to the group that received only carbon tetrachloride. Clinically, a precipitous decrease in the serum ALT and AST activities following

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DVM, Dipl ACVIM, Dipl ACVP NeXstar Pharmaceuticals, Boulder, Colorado - USA

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their moderate increase may be suggestive of insufficient hepatic mass to support repair and a harbinger of fulminant hepatic failure. Novel Concept-2. Hepatic AST appears to be released later and as a consequence of more severe injury than ALT. Perhaps this explains the finding in one study that an increase in the serum AST activity has high specificity (but low sensitivity) for hepatic disease in the dog. The subcellular location of AST activity is divided between a soluble cytosolic form (c-AST) and a mitochondrial form (m-AST). The c-AST is the predominant form. Experimental studies and clinical observations suggest that 1) the magnitude of increase is greater for serum ALT activity than for AST and 2) an increase in serum ALT activity precedes AST. Mitochondrial injury is necessary for m-AST to contribute to the serum AST activity. Since its release is consequent to necrobiosis, measurement by electrophoresis or immunochemistry is being investigated in human patients as an “index” of severity. Markers of Cholestasis and Drug - “Induction”. Alkaline phosphatase (ALP) and Gamma glutamyltransferase (GGT). Alkaline phosphatase and gamma glutamyltransferase (gamma glutamyltranspeptidase, GGTP) show minimal activity in normal hepatic tissue but can become markedly increased in the serum subsequent to increased enzyme production stimulated by either impaired bile flow or drugs. The increased synthesis begins within hours with subsequent appearance in the plasma by release mechanisms that are not clearly defined. These enzymes have a membrane location; ALP associated with the canalicular membrane and GGT associated with epithelial cells comprising the bile ductular system. Alkaline phosphatase is a enzyme located on the membrane of a variety of tissues but only two are diagnostically important; hepatobiliary and bone. Each tissue has an ALP isoenzyme that can be separated by electrophoresis. With the exception of the growing animal or the patient with bone disease, an increased serum ALP activity is of hepatobiliary origin. There is considerable species variation for the diagnostic application of ALP. The reference range is wide for horses and ruminants limiting its diagnostic sensitivity. The hepatobiliary tissue of the cat has a limited capacity for accelerated ALP production. The diagnostic sensitivity and magnitude of increase in the cat is further attenuated by a plasma half-life of 6 hours. In contrast, the dog liver has a robust ability to increase ALP production and a relatively long plasma half-life of 66 hours. There is minimal increase in the plasma following an acute, severe insult (in contrast to ALT and AST). Any initial rise is probably a reflection of enzyme activity on cell membrane fragments released to the plasma as a consequence of the damage. Disruption of the hepatobiliary architecture causes local impairment to bile flow which stimulates increased ALP production within hours. During hepatic reparation following an injury, the serum aminotransferase activity slowly decreases while the serum ALP activity often increases until the “local” cholestasis has resolved. Consequently, the serum ALP activity is usually the last serum hepatic enzyme test to return to normal in the dog following resolution of an acute insult. A primary event that obstructs the flow of bile, whether

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intrahepatic or extrahepatic, is initially associated with an increase in the serum ALP activity. The retention of bile acids is linked to initiation of alkaline phosphatase synthesis by an ill-defined mechanism. If the insult is protracted and severe, increased serum total bile acid concentration, bilirubinuria (notably dog), and finally hyperbilirubinemia resulting in jaundice. The magnitude of increase in the serum ALP activity is not a reliable index for differentiating extrahepatic and intrahepatic cholestatic disorders. Lesser increases in the serum aminotransferase activities often develop either as a consequence of the primary pathologic event and/or the detergent effects of the retained hydrophobic bile acids altering membrane permeability. An increase in the serum ALP activity is associated with the use of glucocorticoids and anticonvulsant medications. There is remarkable individual variation in the magnitude of these increases and there is no concomitant hyperbilirubinemia. In the dog, the increased serum ALP activity associated with corticosteroids has been attributed to a an induction of the synthesis of a novel ALP (CIALP) isoenzyme that can be distinguished from the cholestatically-induced liver ALP (LALP) isoenzyme by several procedures. More recently this variable, unique increase of ALP in dogs associated with corticosteroids may be related to a novel concept pertaining to the formation of the CIALP isoenzyme. The CIALP isoenzyme has been diagnostically used for hyperadrenocorticism. Unfortunately, an increase in this isoenzyme can be associated with hepatobiliary disease, diabetes mellitus, hypothyroidism, acute pancreatitis, and phenobarbital treatment. Its judicial use in the context of the patient’s history and other biochemical findings may have supportive differential diagnostic value for hyperadrenocorticism. A moderate to marked increase in serum ALP activity without concurrent hyperbilirubinemia and minimal increase in the aminotransferases is most compatible with a corticosteroid effect and warrants a review of the patient's history (topical or systemic corticosteroids) or evaluation of adrenal function. Occasionally this biochemical pattern mimics primary hepatic disease, especially early cholangiohepatitis, and a hepatic biopsy is required for the differentiation. Anticonvulsant medications (phenobarbital, phenytoin, and primidone) can increase the serum ALP activity in the dog. The aminotransferase activities may be increased to a lesser magnitude and there is no hyperbilirubinemia. This is important to realize because these medications can occasionally cause chronic hepatitis. A prominence of the serum ALT activity in these patients during treatment, especially if accompanied by an increased serum GGT activity, warrants further investigation, e.g., measurement of the serum total bile acid concentration or biopsy. Novel Concept. The variable, unique increase of ALP in dogs associated with corticosteroids may be related to a novel concept pertaining to the formation of the CIALP isoenzyme. Experimental findings in the dog clearly demonstrate that the hepatic ALP isoenzyme is the one that initially increases subsequent to the administration of corticosteroids. It is the predominant component of the total serum ALP activity for at least 30 days with a smaller contribution by the CIALP isoenzyme after about one week. A fascinat-

ing study measured the rate of clearance for the intestinal ALP isoenzyme by the asialoglycoprotein receptor pathway both in vivo and in vitro using isolated hepatocytes from dogs treated with corticosteroids. The findings indicate that the structurally-related intestinal and CIALP isoenzymes may be metabolically related through the asialoglycoprotein receptor endocytosis pathway. A portion of the intestinal ALP isoenzyme normally endocytosed through this pathway in corticosteroid-treated dogs may be recycled and hyperglycosylated to form the isoenzyme measured as the CIALP rather than being degraded by the hepatocyte. This â&#x20AC;&#x153;abnormalâ&#x20AC;? isoenzyme is not cleared as rapidly as the intestinal isoenzyme (plasma 1/2 life of 74 hours and 6 minutes, respectively) and accumulates in the plasma. The electrophoretically isolated CIALP isoenzyme has been shown to be a product of the same gene as the intestinal ALP isoenzyme with only a slight difference in their carbohydrate moiety. This concept is not new in medicine and has been documented in humans, both juvenile and adult, with viral infections, hepatic cirrhosis, diabetes mellitus, chronic renal failure, and undergoing hemodialysis. The increase of the serum activities of ALP (or GGT) in these conditions has been shown to be due to a decreased clearance. An alteration of the terminal carbohydrate moiety (increased sialic acid content) has been suggested to affect receptor recognition which impairs its clearance. Following a viral infection, for example, the temporary increase of serum ALP activity may last weeks or months. Altered clearance has been shown to occur for the macroenzymes resulting in measurement as increased activity. It is possible that the relatively high serum ALP values in cats with hepatic lipidosis, an intrahepatic disorder, also may be due to delayed clearance. Certainly more studies are indicated. The added message is that increased plasma enzyme activity can be a consequence of predominantly increased release, predominantly formation and release (the traditional concepts), or predominantly decreased removal. Benign familial hyperphosphatasemia refers to an inherited condition in human beings in which a markedly raised serum ALP activity is serendipitously identified in childhood and persists into adulthood. The cause of the increased enzyme activity is not known but it is not associated with underlying pathology, hence the term benign. It is a biochemical curiosity with no adverse effect other than potentially causing an unnecessary evaluation for bone or hepatic disease. A biochemically similar condition has been described in Siberian husky pups. Gamma glutamyltransferase (GGT) is enzyme that is located on the membrane of a variety of tissues. Increased serum GGT activity is associated with impaired bile flow and glucocorticoid administration in the dog. Anticonvulsant medications cause minimal to no increase in the serum GGT activity in the dog which is in contrast to humans and their effect on ALP. The serum GGT activity is a useful marker of biliary tract disease in the horse and ruminant. It may also be more diagnostically sensitive than ALP in the cat. Acute, severe hepatic injury can cause a mild increase in the serum GGT activity in the horse and ruminant because of the relatively high activity associated with the biliary tissue. This in-

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creased serum activity may be a consequence of these enzyme-rich membrane fragments from the damaged tissue reaching the peripheral circulation. The magnitude of this increase is much less than that associated with predominantly cholestatic disease in these species. Bone does not contain GGT, therefore growth and bone disease are not associated with increased serum GGT activity. Colostrum and milk have high GGT activity and nursing animals develop increased serum GGT activity. The renal tubular epithelial cells have a relatively high GGT tissue activity. Acute tubular injury results in a rapid increase in the activity of GGT in the urine (but not the serum). The measurement of urine GGT activity is a useful indicator of early nephrotoxicity secondary to the use of aminoglycoside antibiotics in all species. Macroenzymes. In human patients, unexplained persistent increases in serum enzyme activity has been demonstrated with increasing frequency to be the result of macroenzymes. The hepatic enzymes reported include ALT, AST, ALP, GGT, CK, LD, lipase, and amylase. These highmolecular-mass enzyme forms can be immunoglobulinbound or nonimmunoglobulin-bound. In either case the enzyme clearance is reduced. In dogs with proteinuria, an immunoglobulin-amylase complex (macroamylase) resulting in an increased serum amylase activity without clinical signs of pancreatitis has been reported recently. A raised serum enzyme activity without clinical and/or histomorphologic abnormalities should prompt consideration of a macroenzyme. Function Tests Bilirubin. Bilirubin is a pigmented compound produced largely from the degradation of the heme by the macrophage system (forming unconjugated bilirubin) from aged erythrocytes and excreted by the hepatobiliary system following its conjugation. The uptake site for bilirubin is also shared by other organic anions such as sulfobromophthalein (BSP) but not bile acids. Species variation in the metabolism of bilirubin compared to humans precludes the reliable diagnostic use of the unconjugated:conjugated bilirubin ratio or the magnitude of rise in defining the causation of hyperbilirubinemia. Linking jaundice to the evaluation of the patientâ&#x20AC;&#x2122;s hematology, serum hepatic enzymes, and adjunct procedures is a valuable approach. Accelerated destruction of erythrocytes is associated with a moderate to marked reduction in the packed cell volume (PCV). Biochemically, a marked increase in the serum ALT and AST activities with a mild increase in the serum ALP activity indicates acute, severe hepatocellular injury. Mild to moderate, variable increases in the serum ALT, AST and ALP activities in association with hyperbilirubinemia suggest intrahepatic disease and the need for additional diagnostics. Ultrasonography is a valuable tool for assessing the liver and extrahepatic biliary system when a marked rise in the serum ALP activity is concurrent with hyperbilirubinemia. Novel concept. Biliprotein (originally referred to as delta bilirubin because of its location after separation of the total serum bilirubin with high performance liquid chromatography) is a fraction of conjugated bilirubin that is irreversibly bound covalently to albumin. Its formation as a consequence

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of cholestasis is not completely understood and the amount formed is variable. In jaundiced dogs and cats, it can range from very little to more than 90% of the total serum bilirubin concentration. Because of its irreversible binding to albumin, its degradation parallels that of albumin, approximately 10 to 14 days. Consequently, if it is the predominant component of the total bilirubin, the decrease in the serum total bilirubin concentration following resolution of the disease process will be protracted. Because some of the drychemistry reagent systems can directly measure biliprotein, its determination along with the total bilirubin concentration can provide useful information.

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Supplemental reading Ishak K, (1993), Hepatic histopathology, In Schiff L, Schiff E (eds), Diseases of the liver, 7th ed, J.B. Lippincott Company, Philadelphia, 145-160. Kuhlenschmidt M, Hoffmann W, Rippy M, (1991), Glucocorticoid hepatopathy: Effect on receptor-medicated endocytosis of asialoglycoproteins. Biochem Med Metab Biol, 46:152-168. Lawler DF, Keltner DG, Hoffman WE, et al., (1996) Benign familial hyperphosphatasemia in Siberian huskies. Am J Vet Res, 57:612-617. Pappas NJ Jr, (1986), Source of increased serum aspartate and alanine aminotransferase: Cycloheximide effect on carbon tetrachloride hepatotoxicity. Clin Chim Acta, 154:181-190. Solter PF, Hoffmann WE, Hungerford LL, et al., (1993), Assessment of corticosteroid-induced alkaline phosphatase isoenzyme as a screening test for hyperadrenocorticism in dogs. J Am Vet Med Assoc, 203:534-538.

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The effects of extrahepatic disease on the liver Denny Meyer

“For the study of medical diseases of the liver, it is essential that the pathologist be apprised of the clinical findings and the results of laboratory tests and radiographic studies. The correct diagnosis is most likely to be reached by the pathologist and clinician working as a team.” Kamal Ishak, MD; pathologist. Hepatic “reaction” to extrahepatic disease is being recognized with increasing frequency (Table 1). Both serum hepatic test and histomorphologic abnormalities can occur. The secondary hepatic involvement poses two diagnostic problems: (1) mimics primary hepatic disease and (2) diverts attention from the primary extrahepatic disease process. There are a variety of reasons why extrahepatic diseases secondarily involve the liver. These can be divided into anatomical and functional relationships. The liver has two blood supplies, the hepatic artery and the portal vein. The former provides nutrition and oxygen. The later, which comprises approximately 80% of the total hepatic blood flow, delivers substances absorbed from the gastrointestinal tract and hormones from the pancreas. Consequently hepatic integrity and function can be altered secondary to cardiovascular insufficiency, anemia, portosystemic shunts, and exposure to ingested xenobiotics and intestinal bacteria or their products when the intestinal barrier is violated by disease. Hepatocytes reside in acini composed of three diverse metabolic zones. Blood flows from the portal triad passing through zones 1, 2 and 3 before draining via the hepatic vein. Consequently, hepatocytes in zone 3 are most susceptible to hypoxic conditions such as heart failure and shock. The metabolic diversity of the hepatic zones is necessary to accommodate the numerous homeostatic activities. Many of these functions are related to the intermediary role of hepatocyte metabolism between dietary sources of energy and extrahepatic tissue demands for energy. Therefore metabolic diseases often involve the liver. Examples include hypera-

Table 1. Extrahepatic causes of morphologic or histopathologic changes in the liver Inflammatory intestinal disease Extrahepatic infections (bacterial) Rickettsial infections Acute pancreatitis Diabetes mellitus Congenital portosystemic shunt

Prolonged protein-restricted diet Septicemia Shock Right-sided heart failure Hyperadrenocorticism

drenocorticism, diabetes mellitus, hyperthyroidism, perhaps hypothyroidism and lipid disorders. One qualitatively specific hepatocyte function is bile formation. Another cell type that plays a role in the extrahepatic manifestations of disease is the Kupffer cell; a member of the monocyte-macrophage system. It is involved in the hepatic immune response and "filters" toxins and bacteria which enter the portal circulation. When this role is amplified in response to extrahepatic disease, focal hepatitis can develop.

Cholestasis of sepsis The uptake and excretion of bile acids by the hepatocyte is the primary driving force for bile flow through the biliary ductular system. Bile acids are a class of steroidal substrates that are produced from cholesterol by the liver, carried by the biliary system to the intestinal tract where they contribute to fat absorption. Upon reaching the ileum, bile acids are efficiently absorbed into the portal circulation (< 10% of the secreted bile acids are lost in the feces during any one enterohepatic cycle) and transported back to the liver where their extraction from the sinusoidal blood is remarkably efficient (first-pass clearance is 75-90%). This liver - gut relationship, referred to as the enterohepatic circulation, is critical for understanding the diagnostic application for measuring the serum bile acid concentration for the recognition of hepatic disease and abnormalities of the portal circulation. Cholestasis or impaired bile flow can be classified as extrahepatic or intrahepatic. The accumulation of bilirubin in tissues, jaundice, is a clinical indication of abnormal hepatobiliary function when accelerated erythrocyte destruction is eliminated. Differential considerations include lesions which obstruct the flow of bile in the common bile duct (physical impairment) and, most commonly, a variety of diseases that damage hepatocytes and violate the intrahepatic architecture. Intrahepatic cholestasis can develop in association with extrahepatic bacterial infections. Clinically the patients are icteric, biochemically the hepatic enzyme tests show only mild to moderate increases despite a remarkable increase in the serum bilirubin concentration and relatively unremarkable histologic findings. There may be accumulation of bile pigment, including canalicular plugs, and a mild inflammatory cell component, often round cell and periportal. The intrahepatic architecture remains intact. Pathologic terms such

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as periportal hepatitis, focal hepatitis or hepatitis, chronic, active with bile retention may be used to characterize the microscopic findings. The successful treatment of the extrahepatic infectious process is associated with spontaneous resolution of the cholestasis. The pathophysiologic mechanisms causing this functional cholestasis are multiple and poorly understood. Toxins derived from bacteria may directly or antibodies to bacterial cell wall components that cross-react with the canalicular membrane may “paralyze” the energydependent transport systems of the membrane. It has also been shown that selected acute-phase reactant proteins can interfere with hepatocellular uptake of bile acids. The common pathophysiologic factor is the impaired excretion of bile acids which are the primary driving force for bile flow.

Inflammatory bowel disease Dogs and cats with chronic enteric disease often will have concurrent hepatic changes. The nature of the hepatic changes leads one to speculate that they are secondary to the portal uptake of bacteria or their products. Observations by Pavlov over 100 years ago identified that poisonous symptoms occurred when intestinal toxins are not detoxified by the liver and this theory still remains valid today. The nature of the inflammatory infiltrate (periportal) secondary to intestinal disease has led to the hypothesis that the changes are secondary to bacteremia from intestinal bacterial translocation through the diseased intestinal tract. A concept now in favor is that the endotoxin lipopolysaccharide (LPS), a component of the cell wall of gram negative bacteria, transit the intestinal wall in significant amounts in states of intestinal inflammation. The hepatic reticuloendothelial system (Kupffer cell) is critical for LPS detoxification and impairment of this function may lead to hepatic injury/inflammation. Though endotoxins may directly damage hepatocytes, evidence suggests that a release of a number of substances from the macrophage mediates diverse biological effects. The macrophage products include superoxides, toxic oxygen radicals, tumor necrosis factor and platelet activating factor. Serum hepatic enzyme tests may reflect intrahepatic cholestasis and hepatocellular injury. Rarely will tests of hepatic function be altered. Changes are most often develop in association with long standing intestinal disease. The most common hepatic microscopic findings include mild to moderate periportal inflammatory cell infiltrates consisting of lymphocytes, plasma cells macrophages and neutrophils; these findings prompt the morphologic terms of hepatitis, chronic, active. Inflammation primarily involving the bile ducts is termed cholangitis. Cholangiohepatitis refers to inflammation surrounding bile ducts and extending into the parenchyma. Fibrosis, if present, is usually mild and vacuolar changes.

Acute pancreatitis Acute pancreatitis can secondarily involve the liver through two pathologic processes: (1) impairment of bile flow in the common bile duct and (2) direct intrahepatic

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damage. There is a variable amount of peripancreatic inflammation associated with acute pancreatitis. When the phlegmon is sufficiently severe, it encompasses the common bile duct and can cause clinical, biochemical and histologic findings compatible with extrahepatic cholestasis. If the inflammatory process resolves, often within 7 to 10 days, the serum bilirubin will decrease. However, fibrous tissue formation associated with the resolving inflammation may permanently embarrass the extrahepatic flow of bile necessitating surgical intervention. Biochemical and microscopic findings consistent with hepatocellular injury and intrahepatic cholestasis can also develop in association with acute pancreatitis. There are mild to moderate increases in the hepatic enzyme tests with or without hyperbilirubinemia. Microscopically there may be focal necrosis, Kupffer cell hyperplasia, mild periportal inflammatory cell infiltrates and hepatocellular accumulation of bile pigment. The pathophysiologic mechanism responsible for these changes is not known. Since the portal circulation receives blood from the pancreas, perhaps the release of proteases directly into the portal circulation from the inflamed pancreas plays a pivotal role. Alternately, toxic substances released by the injured pancreas may be “filtered” by the Kupffer cell and stimulate the release of cytokines which amplify intrahepatic injury.

Metabolic disease A variety of metabolic diseases can cause abnormal liver tests and, in some cases, alter hepatic morphology. One of the more widely recognized hormonally-associated diseases that frequently affects the liver is hyperadrenocorticism. The canine liver is uniquely “responsive” to glucocorticoids; highlighted by moderate to markedly increased serum alkaline phosphatase activity (without hyperbilirubinemia) and a foamy change in the hepatocyte cytoplasm caused by glycogen accumulation. The glycogen accumulation can be diffuse enough to cause hepatomegaly. Less frequently the serum alanine aminotransferase and aspartate aminotransferase activities are mildly increased; presumably secondary to drug-stimulated production. Insulin deficiency alters glucose and lipid metabolism. Patients with diabetes mellitus may develop hepatic lipidosis with abnormal liver tests. Hyperthyroidism in cats can cause abnormal liver tests, including hyperbilirubinemia, which spontaneously resolves with management. There is minimal to no microscopic hepatic lesions observed. In dogs with hypothyroidism, we have occasionally associated mild to moderately abnormal hepatic enzyme tests and hepatic hydropic degeneration and Ito cell prominence. There is a complex and poorly understood relationship between thyroid function and hepatic UDP-glucuronosyltransferase (UDP-GT) activity, the enzyme involved in bilirubin metabolism. Multiple isoforms exist. Experimentally, both hyperthyroidism and hypothyroidism have been shown to alter bilirubin metabolism via a UDPGT effect. There is a linear positive relationship between bilirubin UDP-GT activity and the ratio of bilirubin di- to monocongjugates present in bile. Serum T4 concentrations correlate with UDP-GT activity; induction associated with a decreased serum T4 concentration.

Congenital portal vascular anomalies The presence of anomalous portal vessels that by-pass the liver has been described in most domestic species. Hepatic encephalopathy, manifested by a wide variety of neurological signs clinically, is a common sequela. There may be a mild to moderate increase in the serum hepatic enzyme tests, a decrease in the biochemical markers dependent on hepatic formation (albumin, BUN) and a moderate to marked increase in the total serum bile acid concentration without an abnormal serum bilirubin concentration. Histologically, there may be no obvious morphologic abnormalities, mild to moderate vacuolar change, or the apparent absence or paucity of a portal vein in the portal tracts plus an increase in arteriolar-like structures. “Lipogranulomata”, better referred to as foci of pigment-filled macrophages, occur with increased frequency of young dogs with congenital portosystemic shunts. This histomorphologic change is common in older dogs (>10 years of age) without apparent liver disease. The accumulation of hepatic iron is a common event and may be related to the changes for the erythrocytic indices. The pigment-laden macrophage foci will stain notably positive for the presence of iron. Since iron is a potent oxidant, it is possible that oxidative injury to the hepatic membrane is one factor in the formation of these foci. Variable of nonsuppurative inflammatory cells may be associated with the foci, consequently the incorporation of the term “granuloma” into the histologic terminology. However, they are not a true granuloma. The histological finding of increased iron in the hepatic biopsies of a relatively young dog should stimulate the differential consideration of a portosystemic shunt especially if foci of pigment-laden macrophages are present. Liver atrophy develops due to the decrease in total blood flow and diversion of hepatotrophic factors. Microscopically, this is occasionally reflected by the increased proximity of portal tracts and attenuation of the sinusoids and hepatocellular cords. It is unclear if the extrahepatic shunts always develop independent of intrahepatic vascular changes or if an intrahepatic vascular “dysplasia” predisposes to continued function of portal vessels that would normally be dormant. A hepatoportal microvascular dysplasia without extrahepatic shunts has been described in dogs. Most likely, multiple etiopathogeneses are involved in this syndrome. An increase in the plasma cortisol concentration, free cortisol concentration, and free cortisol fraction is present in dogs with portosystemic shunts. Perhaps this metabolic derangement is, in part, responsible for the increased plasma ALP activity, hepatic hydropic degeneration (“vacuolar change”), and polydipsia/polyuria that develops.

Nodular hyperplasia Although nodular hyperplasia is an intrahepatic event, it is included because this relatively benign process may cause an increase hepatic tests and histomorphologic changes that may be suggestive of chronic hepatitis or an extrahepatic disease such as hyperadrenocorticism. The dog shows a propensity for the development of nodular hyperplasia of the liver. It is not known if the proliferative change is a response to

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previous hepatic injury or metabolic disorders. In human patients, nodule formation, which differs histologically somewhat from that described in dogs, has been associated with altered hepatic blood flow and the use of azathioprine. In the dog, the lesion is common and appears to be age-related suggesting, perhaps, a factor common to many dogs or a similar type of hepatic response to a variety of factors. Nodules are present by 6 years of age and, in one study, were present in all dogs older than 14 years. The expansile process compresses existing parenchyma resulting in hepatocellular atrophy and approximation of the reticular fibers. Grossly, their appearance mimics macronodular cirrhosis and neoplasia. Microscopically, hepatocytes can develop a variety of cytoplasmic changes including lipidosis, hydropic degeneration, and glycogen accumulation. This may be problematic in needle biopsy specimens since the identification of nodular regeneration is very difficult due to size limitations and the histomorphologic findings can be suggestive of a metabolic disorder. Nodular hyperplasia is associated with lipocyte prominence and the formation of lipogranulomata. Prussian blue staining demonstrates an abundance of iron accumulation in these foci of pigmented macrophages. We have associated an increase in serum hepatic enzyme activities, notably alkaline phosphatase, with nodular hyperplasia. The etiopathogenesis may be a reflection of two physioanatomical processes. First, the distorted hepatic architecture impairs bile flow and precludes adequate blood supply to hepatocytes and resulting in cholestatic induction of enzyme synthesis (alkaline phosphatase) and compromised membrane integrity (leakage of aminotransferases). Alternatively, the increase in at least the aminotransferases may be directly related to the hepatocyte proliferative process since an increase in the serum aminotransferase activities has been shown to be related to an increased production of these enzymes following an injury. Interesting, an increase in the serum alkaline phosphatase activity and was consistently present in the patients with azathioprine-associated nodular hyperplasia.

Supplemental reading Andrzejewska A, Dlugosz J, Kurasz S, (1985), The ultrastructure of the liver in acute experimental pancreatitis. Exp Pathol, 28:167–176. Arai M, Mochida S, Ohno A, et al., (1993), Sinusoidal endothelial cell damage by activated macrophages in rat liver necrosis. Gastroenterology, 104:166-1471. Bergman JR. Nodular hyperplasia in the liver of the dog: An association with changes in the Ito cell population, (1985) Vet Pathol, 22:427–438. Fong TS, McHutchison JG, Reynolds TB, (1992), Hyperthyroidism and hepatic dysfunction. J Clin Gastroenterol, 14:240–244. Gross TL, Song MD, Havel PJ, et al., (1993), Superficial necrolytic dermatitis (necrolytic migratory erythema) in dogs. Vet Pathol, 30:75–81. Ishak K, (1993), Hepatic histopathology, In Schiff L, Schiff E (eds), Diseases of the liver, 7th ed, J.B. Lippincott Company, Philadelphia, 145-160. Lichtman SN, Sartor RB, Keku J, et al., (1990), Hepatic inflammation in rats with experimental small intestinal bacterial overgrowth. Gastroenterology, 98:414–423. Meyer DJ, Harvey JW, (1994), Hematologic changes associated with serum and hepatic iron alterations in dogs with congenital portosystemic vascular anomalies. J Vet Intern Med, 8:55–56. Taboada J, Meyer DJ, (1989), Cholestasis associated with extrahepatic bacterial infection in five dogs. J Vet Intern Med, 3:216–221.

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The liver biopsy: pitfalls and interpretation of the report by the clinician Denny Meyer

“The establishment of an accurate diagnosis is dependent on sampling an adequate amount of tissue and, most important, on a histologic interpretation by someone well versed in liver histopathology.” E. Schiff, M.D., L. Schiff, M.D., medical pathologists The specimen of liver tissue can be obtained percutaneously by the use of a needle, at laparoscopy using a needle or a clamshell biopsy forceps, and at laparotomy. Each approach has its advantages and limitations. Ultrasonography has increased the use of the needle for obtaining a guided biopsy specimen. There are two general types of hepatic biopsy needles; suction/aspiration (Menghini, V. Mueller Co, Chicago, IL; Jamshidi, Kormed Inc, St. Paul, MN) and cutting (Vim-Silverman with Franklin modification, Baxter, Deerfield, IL; Tru-Cut, Travenol Laboratories Inc, Deerfield, IL). The latter type is more commonly used and provides a more consistently adequate specimen with less fragmentation. The Tru-Cut is an economical, disposable needle that can be gas sterilized and reused 2 to 3 times. It does require a relatively experienced operator for consistent success. Disposable, automated spring-driven cutting biopsy needles are now available that are user-friendly tools and reduce the risk of tissue injury associated with the movement of the diaphragm. These include Monopty (Bard Urological, Covington, GA) and the Temno (Products Group International, Boulder, CO); the latter can be gas sterilized for reuse. Another choice is the Biopty instrument; a reusable gun combined with a disposable needle that can be gas sterilized and reused (Bard Urological, Covington, GA). These biopsy needles can be used for most soft tissue biopsy needs. Prior to obtaining a liver biopsy, it is prudent to evaluate hemostasis. The following should be considered: identify drugs that affect platelet function, determine if the breed is predisposed to von Willibrand’s disease, scan a blood film for platelet numbers (> 8 platelets/oil immersion field), and assess the adequacy of the coagulation factors with either a combination of a prothrombin time (PT) plus an activated partial thromboplastin time (APTT) or a Thrombotest. Even if the results are within the reference range, there is no downside to the subcutaneous administration of vitamin K1 12 to 24 hours prior to the biopsy procedure, especially if icterus is present. Focal disease may be missed with a needle biopsy which provides a core of tissue that represents approximately 1/50,000 of the whole organ. Multiple samples increase the probability of detecting the lesion. Length of an intact nee-

dle specimen is another consideration. Studies in human patients indicate that a length of 0.5 cm can detect the changes associated with acute viral hepatitis but is not reliable for defining the findings indicative of chronic hepatitis. A length of 1.5 cm is usually sufficient for recognition of the latter. Bridging hepatic fibrosis is a important prognostic finding. An intact needle biopsy that is at least 2 cm in length is suggested as minimally adequate for this assessment. A biopsy needle may “glance” off of the fibrous septa of a cirrhotic liver and obtain relatively normal appearing tissue of a regenerative nodule. The spring-driven cutting needles reduce this possibility. Because of its superficial location relative to blood supply, the margin of the liver is predisposed to fibrosis that may mimic changes of hepatic fibrosis/cirrhosis. In this location, fibrous septa join portal tracts to the subcapsular connective tissue or to each other and are sometimes unusually close, erroneously suggesting parenchymal collapse and hepatic fibrosis. A subcapsular specimen of limited depth may give a misleadingly pessimistic impression of chronic hepatitis. Hepatic tissue obtained with a clamshell forceps or an inadequate operative wedge biopsy could give this type of misinformation. The former is also prone to crush artifact. Regardless of the biopsy mode used, lack of uniformity in selecting the biopsy site for repeat biopsies could affect subsequent evaluations for disease progression and therapeutic efficacy.

When to biopsy the liver? The biopsy is obtained to answer a question. The more common ones are: Why are the serum hepatic enzymes persistently raised? Why is the patient icteric? Why is there a transudative abdominal effusion? How “bad” is the liver disease (prognosis)? Is there copper accumulation in a predisposed breed of dog? Is the liver affected by an extrahepatic neoplasm (staging)? What is the nodule or tissue discoloration observed during a laparotomy. What is the cause of the hepatomegaly? Consider initially addressing the latter question by the simpler procedure of fine-needle aspiration biopsy for cytology. How do the serum hepatic test findings aid in the decision to biopsy? When there are biochemical findings indicative of acute, severe hepatic injury, histologic assessment often does not provide additional diagnostic or prognostic in-

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formation. In fact, a biopsy may be contraindicated. Persistently raised serum aminotransferases (ALT, AST) and a rise of the serum total bile acid concentration (BA) support the value of assessing the liver histologically. The hepatic-intestinal “recycling” of bile acids is termed “enterohepatic circulation”. The high extraction efficiency (75-90%) for bile acids limits the quantity that “escapes” into the peripheral circulation. The serum BA is a reflection of the efficiency and integrity of the enterohepatic circulation. The measurement of the serum BA aids in the detection of congenital portosystemic shunts (PSS), identification of chronic hepatitis/cirrhosis prior to the development of jaundice, and monitoring of the progression or resolution of hepatic disease with therapy. A relatively good positive predictive value of histopathologic changes is achieved with values of > 25 umol/L for the dog and > 20 umol/L for the cat. Raising the cut-off of the upper end of the reference range enhances the specificity at the expense of sensitivity. These cut-offs suggest that there is sufficient pathology affecting the enterohepatic circulation of bile acids to be detected with contrast radiology (congenital PSS) or histologically (intrahepatic inflammatory disease) especially when linked with the evaluation of the serum aminotransferase activity for the latter. A persistent mild to moderate rise of the serum ALT +/AST indicates “active” hepatocellular injury/repair (altered cell membrane integrity). A concurrent rise of the serum BA suggests that sufficient alteration of the intrahepatic architecture has occurred to be detected histologically. What Information Should the Biopsy Report Contain? The biopsy report should contain information that provides part or all of the answer to the question that prompted the biopsy. However the histopathologic findings (summated as a morphologic diagnosis) may not provide sufficient information to define a specific clinical diagnosis. In part, this is because the liver responds to a variety of insults with a limited number of morphologic changes. It is also secondarily involved in a variety of extrahepatic diseases that may not be clinically apparent. If the information from the biopsy does not answer the question asked or its applicability to the question asked is not considered helpful, the clinician should discuss the findings with the pathologist in relation to the clinicopathologic information and evaluate the patient for extrahepatic disease. There is terminology that has important interpretative meaning relative to hepatic histopathology. (Refer to Nomenclature and Tables 1 and 2) As mentioned previously, the liver may exhibit a variety of nonspecific secondary changes in response to disease elsewhere in the body or the liver itself. These include a variety of systemic infectious and inflammatory diseases, gastrointestinal diseases, congenital portosystemic shunts, and pancreatitis. Similar changes can occur in proximity to a hepatic abscess or metastatic neoplasms. Liver test abnormalities are usually mild and the serum bile acid concentration is usually within the reference range. The general rubric of nonspecific reactive hepatitis is used but replacing the term “hepatitis” with “changes” is recommended by some authors due to the connoted meaning of the former. The histologic features encompass a variable combination of portal and parenchymal changes that are usually of minor degree and distributed in a patchy, uneven manner. The findings include

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portal infiltration by mononuclear cells (primarily lymphocytes), fatty change, focal hepatocellular necrosis, and lobular inflammation. The latter may consist of enlarged or hyperplastic Kupffer cells (sometimes forming small granulomatoid or lipogranulomatoid clusters), small foci of other macrophages, or lymphocyte aggregates. The distinction from resolving acute hepatitis or a mild form chronic hepatitis may be difficult and arbitrary without clinical information. Photomicroscopic examples of these findings are available. Chronic hepatitis is a poorly defined syndrome in dogs and cats that encompasses a spectrum of histologic activity. A simplified grading system (Tables 1 and 2) has been proposed in human medicine to bring uniformity to the histological assessment of hepatic biopsies. Since the grading system does not use an etiologic classification, it should be applicable to veterinary medicine. The system facilitates the categorization of the disease and can be used as prompts when discussing the interpretation of the biopsy findings with the pathologist.

Table 1. Degree of Activity in Chronic Hepatitis Lesions and degree of injury

Category

Portal area inflammation

Mild mild, patchy Moderate moderate Marked marked Very marked marked

Spotty necrosis

Bridging &/or multiacinar necrosis

absent/mild mild moderate moderate marked marked

absent absent marked absent marked present

Piecemeal necrosis

Table 2. Degree of Fibrosis in Chronic Hepatitis Component lesions

Category Mild Moderate Marked Very Marked

Fibrous expansion of portal areas

Bridging fibrosisa

absent or mild moderate marked marked

absent absentb marked marked

Bridging with nodules (cirrhosis) absent absent absentc present

Refer to nomenclature for the definition Occasional bridging may be present c Occasional nodule may be present (“incomplete cirrhosis”) b

Nomenclature “When I use a word”, Humpty Dumpty said, in a rather scornful tone, it means just what I choose it to mean-neither more nor less.” (Gardner) Acidophilic body - condensed, deeply eosinophilic, refractile structure, with or without a pyknotic nucleus, that is formed from a hepatocyte subsequent to apoptosis. It is a non-specific finding indicative of hepatocellular injury in

many acute and chronic liver diseases. Apoptosis - a form of cell death that results in the shrinkage and fragmentation. Sometimes referred to as “self-programmed cell death”, it occurs in many tissues as a normal process but may be increased by inflammation. The larger apoptitic bodies, sometimes containing nuclear fragments, are frequently referred to as acidophilic bodies in the liver. Acinus - an irregular, anatomical, functionally-derived unit of hepatic parenchyma associated with the terminal hepatic artery and portal venule, likened to a cluster of grapes with the stem representative of the vessels and the grapes parenchymal cells. Three regions are defined going away from the vessels to the periphery in decreasing order of vascular and nutrient perfusion: zone 1 (periportal), zone 2 (mid-zonal), and zone 3 (pericentral). The alternative, traditional, microscopic unit is the classic “lobule” in which the central vein is defined as the center and the portal tracts are located at the periphery. Similar descriptive terminology is used to indicate the parenchymal location with the exception that the term “centrilobular” replaces “pericentral”. Activity - a histological expression of the magnitude (degree) of parenchymal damage and inflammation. Autoimmune hepatitis - a type of chronic hepatitis characterized by a prominent lymphocyte-plasma cell hepatic infiltrate in association with serum antibodies against cellular constituents, e.g., antinuclear antibody (ANA), microsomal, smooth muscle directed against actin. It is a relatively less common cause of chronic hepatitis in humans and is usually responsive to immunosuppressive treatment. The syndrome has not been characterized in veterinary medicine. Bridging necrosis - confluent hepatocellular necrosis resulting in parenchymal collapse that “links” portal tracts with terminal hepatic (central) veins or portal tracts to one another. A reticulin stain is helpful for defining the event.

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Bridging fibrosis - hepatocellular necrosis and inflammation with the subsequent deposition of new collagen that “links” portal tracts with terminal hepatic (central) veins or portal tracts to one another. A trichrome stain is helpful for its recognition. Its presence denotes a poor prognosis. Chronic hepatitis - persistent inflammation of the liver (clinical, biochemical, histopathologic) for > 6 months in humans; the temporal corollary has not been established in veterinary medicine. Ito cell - non-parenchyal cell that lies in the space of Disse; stores vitamin A. It is prominent histologically when distended with lipid. Most recently demonstrated to have the potential to produce collagens that contribute to hepatic fibrosis. (lipocyte, fat-storing cell, stellate cell). Piecemeal necrosis - the destruction of hepatocytes at an interface between parenchyma and connective tissue, together with a predominantly lymphocytic or plasma cell infiltrate. This process often is seen at the borders of portal triads or along the edges of fibrous septa in cirrhotic livers or zone of necrosis.

Supplemental reading Schiff ER, Schiff L, (1993), Needle biopsy of the liver, In: Schiff L & Schiff ER, eds. Diseases of the liver, 7th ed, J.B.Lippincott Co, Philadelphia, 216-231. Ishak K, (1993), Hepatic histopathology, In Schiff L, Schiff E (eds), Diseases of the liver, 7th ed, J.B.Lippincott Company, Philadelphia, 145-160. Meyer DJ, (1996), Hepatic pathology. In: Guilford WG, Center SA, Strombeck DR, et al, eds. Strombeck’s Small Animal Gastroenterology. 3rd ed, W.B. Saunders Co, Philadelphia, 633-653. Ishak K, (1994), Chronic hepatitis: Morphology and nomenclature. Mod Pathol, 7:690-713. Gardner M. The annotated Alice. In: Carroll L, Alice’s adventures in wonderland and through the looking glass. York. Wings Books, 1960; 268.

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Management of liver disease: benefits of ursodeoxycholic acid Denny Meyer

The management of hepatic disease is based on four objectives: 1) treat the specific cause, 2) attend to the metabolic consequences of reduced hepatic function, 3) facilitate hepatocellular regeneration, and 4) impede the progression of hepatic injury and pathologic changes. Removal of known hepatotoxins, e.g., sulfa-containing antimicrobials and anticonvulsant medications, and reduction of hepatic copper concentration and impairment of its absorption are examples attendant to accomplishing the first objective. Unfortunately, the etiopathogenesis of chronic liver disease is not known. Consequently, the recognition and management of the consequences of chronic liver injury has palliative importance. Coagulation factor deficiencies are associated with chronic cholestatic disease due to impaired absorption of vitamin K (needed for Factors II, VII, IX, and X). Periodic subcutaneous administration of vitamin K1 may be required. The abnormal intrahepatic architecture and disturbance of sodium balance through poorly understood mechanisms can cause portal hypertension with the resultant formation of ascites that may require periodic medication (e.g., spironolactone, furosemide). Gastrointestinal ulceration can cause insidious blood loss that may require the use of protectants (sucralfate, H2-receptor antangonists). The blood loss itself can provoke or contribute to an exacerbation of hepatic encephalopathy. Once hepatic encephalopathy develops, the acute signs are managed with antibiotics and lactulose and a diet change to a high quality protein diet is instituted for the long term. The recommended protein amount is variable due to several factors but 17 grams per 400 kcal metabolizable energy is an approximation. However, protein of high digestibility and biologic availability, e.g., cooked eggs and cottage cheese, should be given priority in the diet. Adequate caloric intake is imperative to impede the skeletal muscle wasting. Infections, uremia and hypokalemia should be treated promptly as they exacerbate hepatic encephalopathy. During stress, e.g., infections, surgical procedures, the serum glucose concentration should be carefully monitored. The liver’s ability to contribute to maintaining it normalcy is comprised. The good news pertinent to the liver is that it has the remarkable capacity for regeneration. The bad news is that with chronic injury, the regeneration may take the form of nodules that alter the intrahepatic architecture and probably cannot adequately replace the deficient metabolic deficiencies. Nonetheless, every effort should be made to facilitate

the regeneration through adequate caloric intake. Carbohydrates, e.g., rice and pasta, should be the fuel for supplying the majority of the caloric need. Linked to the dietary strategy is the protein considerations aforementioned. Medical impediments to the progression of chronic hepatic injury are largely conjectural with few clinical studies documenting their benefits. The benefits of prednisolone remain debatable as a first-line treatment for all types of chronic hepatitis and has noteworthy side-effects. Antifibrotic agents, colchicine and zinc supplementation, and anti-oxidants, vitamins E & C, may offer positive contributions to the long-term management of the consequences of hepatic injury as may ursodeoxycholic acid, a bile acid with unique physiologic properties. The primary bile acids are synthesized from cholesterol in hepatocytes and secreted into the biliary system. Most of the bile acids are usually stored in the gallbladder prior to secretion into the duodenum. Approximately 50 to 70% of the newly formed bile is continuously secreted into the duodenum in support of bile acid recycling during the fasting period. This component contributes to the fasting serum total bile acid (FBA) concentration. Within the intestinal lumen, the primary bile acids, CA and CDCA, are dehydroxylated by bacteria to deoxycholic acid (DCA) and lithocholic acid (LCA), respectively. DCA and LCA are referred to as secondary bile acids. Intestinal bacterial enzymes also deconjugate a small percentage of the primary and secondary conjugated bile acids. The bile acids are efficiently reabsorbed by the terminal ileum mediated by a sodium-potassium ATPase active transport system. Only 5 to 10% of bile acids are lost in the feces during any one enterohepatic cycle; the minimal loss replenished by hepatic synthesis of primary bile acids. After their reabsorption into the portal circulation, they are carried to the liver and efficiently extracted from the sinusoidal blood by the hepatocytes located in zone 1 and reexcreted into the biliary system. The physio-anatomical counter-flow relationship of the portal blood and bile in this region of the liver facilitates this process. The relatively bile acid-rich portal blood flows through zone 1 in one direction while the relatively bile acid-poor bile flows in the opposite. As the bile acids as actively transported against a gradient into bile, its counter flow aids in whisking them out of the liver (Table 1). The hepatic-intestinal “recycling” of bile acids is termed “enterohepatic circulation”. The high extraction efficiency (75-90%) for bile acids limits the quantity that “escapes” into the peripheral circulation. The concen-

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Table 1. The enterohepatic circulation of bile acids The primary bile acids (cholic acid and chenodeoxycholic acid) are synthesized and conjugated by the hepatocyte --> excreted by the canalicular membrane into the biliary system --> carried to the intestinal tract --> participate in the emulsification of lipids for absorption --> move to the ileum during which time bacteria dehydroxylate a portion of the primary bile acids forming secondary bile acids (cholic acid to deoxycholic acid and chenodeoxycholic acid to lithocholic acid) --> reabsorbed into the portal circulation -> carried to the liver and removed by the hepatocyte for "recycling". Hepatocellular excretion of bile acids into the biliary system is the primary driving force for bile flow; termed bile acid-dependent flow.

tration of all the bile acids measured in the peripheral blood following a meal is referred to as the postprandial serum total bile acid concentration (PPBA). The FBA and PPBA concentrations are a reflection of the efficiency and integrity of the enterohepatic circulation. Their measurement aids in the 1) detection of congenital portosystemic shunts, 2) identification of chronic hepatitis/cirrhosis prior to the development of jaundice, and monitoring of the progression or resolution of hepatic disease with therapy. The most common indications for the determination of the serum total bile acid concentration include: 1) increased serum ALT and/or AST in a patient with clinical signs suggestive of hepatobiliary disease 2) persistently increased serum ALT (+/- AST) activity in the dog and cat, 3) juvenile animals with clinical signs of hepatic insufficiency (hepatic encephalopathy, poor growth, nonspecific neurological or behavioral signs) consistent with congenital portosystemic shunts, and 4) monitoring patients with known hepatic disease. A hepatoportal microvascular dysplasia without extrahepatic shunts has been described in dogs. These dogs often do not have clinical signs of hepatic insufficiency, have few to no hematologic or serum biochemical abnormalities, only mild to moderate rises in the serum total bile acid concentration, and minimal to no histopathologic changes depending on the hepatic lobe biopsied. A raised serum PPBA concentration has been described in Maltese dogs without congenital extrahepatic portosystemic shunts, hepatic microvascular dysplasia, or inflammatory liver disease. It is possible that an unidentified substance in the serum affects the reaction of a 3-a hydroxy bile acid in the enzymatic spectrophotometric assay.

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ies have shown that these bile acids can cause hepatocelluar dysfunction and necrosis at concentrations attained in prolonged cholestasis. Hepatocytes are at greatest risk of bile acid-induced injury due to their function of concentrating the bile acids prior to secretion through the canalicular membrane. By analogy, the liver can be considered to treat bile acids as sticks of dynamite with burning fuses of varied length. There is no harm if they are efficiently eliminated. However, the longer they are retained within hepatic tissue the greater the risk of injury. Ironically, during studies to define the toxic role of bile acids on cells, one bile acid was demonstrated not only to be devoid of cytotoxicity but actually protected hepatocytes from the toxic effects of the other bile acids. This bile acid, ursodeoxycholic acid, has received considerable clinical attention for the management of chronic liver disease in human beings. The oral administration of 10-15 mg/kg body weight once a day has been associated with encouraging results; improvement in the serum liver tests and clinical disposition. Published studies in the veterinary literature are sparse. A recent case report described the use of ursodeoxycholic acid for the long term management of one dog with chronic liver disease (histologically documented with a serum bilirubin greater than 12 mg/dL (205 umol/L) for 3 months. The patient improved clinically and biochemically (decreased serum liver enzyme tests and serum bilirubin concentration - approximately 6 mg/dl). The patient did well for approximately 8 months at which time it succumbed to end-stage liver pathology. There have been no side effects associated with the use of this drug in human beings or dogs. While it is unknown if the drug facilitates resolution of existing hepatic fibrosis, it does appear to impede the progression of the microscopic changes if initiated early in the course of the disease. Further studies using ursodeoxycholic acid alone and in combination with other drugs in veterinary patients with chronic cholestatic intrahepatic disease is clearly warranted. There are a variety of proposed mechanisms for the beneficial effects associated with the administration of ursodeoxycholic acid. The contemporary areas of investigation are: (1) hypercholeresis, (2) direct cellular protection against the more hydrophobic bile acids or their displacement from the enterohepatic circulation, (3) antioxidant effect, and (4) immunomodulation. As mentioned previously, bile acids provide the predominant driving force for bile flow (choleresis). Unconjugated ursodeoxycholic acid has been shown to actually cause hypercholeresis, amplified bile flow compared to the physiologic effects of other bile acids. This is thought to be related to its ability to enhance biliary [HCO3â&#x20AC;&#x201C;] and excretion via a hypothetical mechanism referred to as cholehepatic recycling. The displacement of cytotoxic bile acids from the enterohepatic circulation would theoretically decrease the prolonged exposure of hepatocytes to their high concentrations. The high concentration of orally administered ursodeoxycholic acid has been shown to effectively compete with chenodeoxycholic acid and deoxycholic acid for ileal absorption, thereby displacing them from the enterohepatic circulation. In the canine patient treated with ursodeoxycholic acid, serial determinations of the serum bile acid profiles

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the management of the complex pathophysiologic alterations associated with the diseased hepatobiliary microenvironment known as chronic liver disease.

Supplemental reading Angelico M, Del Vecchio C, Nistri A: Effect of tauroursodeoxycholic acid on serum liver enzyme and serum lipid levels in patients with chronic active hepatitis. Curr Therap Res 1995; 56:626-634. Anwer MS: Mechanism of bile acid-induced HCO3– -rich hypercholeresis. An analysis based on quantitated acid-base chemistry. J Hepatol 1992; 14:118-126. Counsell LJ, Lumsden JH: Serum bile acids: Reference values in healthy dogs and comparison of two kit methods. Vet Clin Pathol 1988; 17:71-74. Hoffman AF: Pharmacology of ursodeoxycholic acid, an enterohepatic drug. Scand J Gastroenterol 1994; 29:S1-S15. Kurktschiev D, Subat S, Adler D, et al: Immunomodulating effect of ursodeoxycholic acid therapy in patients with primary biliary cirrhosis. J Hepatology 1993; 18:373-377. Rothuizen J, de Vries-Chalmers Hoynck van Papendrecht R, van den Brom WE: Post prandial and cholecystokinin-induced emptying of the gall bladder in dogs. The Vet Rec 1990; 126:505-507. Schmucker D, Ohta M, Kanai S, et al: Hepatic injury induced by bile salts: Correlation between biochemical and morphological events. J Hepatol 1990; 12:1216-1221. Sokol RJ, Winklhofer-Roob BM, Devereaux MW, McKim Jr JM: Generation of hydroperoxides in isolated rat hepatocytes and hepatic mitochondria exposed to hydrophobic bile acids. Gastroenterology 1995; 109:1249-1256. Solter P, Hoffmann W, Hoffman J: Evaluation of an automated serum bile acids assay and the effect of bilirubin, hemoglobin, and lipid on the apparent bile acid yield. Vet Clin Pathol 1992; 21:114-118. Tisdall PLC, Hunt GB, Tsoukalas G, et al: Post-prandial serum bile acid concentrations and ammonia tolerance in Maltese dogs with and without hepatic vascular anomalies. Aust Vet J 1995; 72:121-126. Vlahcevic ZR, Heuman DM, Hylemon PB: Regulation of bile acid synthesis. Hepatology 1991; 13:590-600.

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with HPLC demonstrated a remarkable increase in the ursodeoxycholic acid concentration and a decrease in the chenodeoxycholic acid and deoxycholic acid concentrations. Ursodeoxycholic acid may afford direct hepatocellular protection by “partitioning” into the lipid-rich membrane and excluding the cytotoxic hydrophobic bile acids. In vitro studies with ursodeoxycholic acid in rats have found a moderate to marked reduction of substances produced as a consequence of oxidative injury suggesting a potent antioxidant effect. The beneficial effects associated with ursodeoxycholic acid in certain chronic liver diseases may be related to immunomodulation. Cytokines appear to be involved in the initiation, modulation and/or perpetuation of the immune responses in the liver. Ursodeoxycholic acid has been shown to reduce the aberrant major histocompatibility complex class I expression on hepatocytes in human beings with primary biliary cirrhosis and other studies have shown suppression of interleukin-2, interleukin-4 and interferon-g using test systems which employed mononuclear cells from the peripheral blood of human beings with primary biliary cirrhosis. In summary, the determination of the total serum bile acid concentration provides an index of hepatobiliary function and assesses the integrity of the portal circulation. Beyond their use as a diagnostic test, recent research has demonstrated that there are “good” and “bad” bile acids. Prolonged retention of certain endogenous bile acids appears to amplify intrahepatic pathology while others, notably ursodeoxycholic acid, appear to offer a novel alternative in the management of chronic liver disease without adverse sideeffects. Ursodeoxycholic acid clearly generates excitement with its potential multifaceted beneficial modes of action in

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Early diagnosis of renal diseases A.R. Michell

Summary

Introduction

Chronic renal failure (CRF) is an insidious, progressive, irreversible decline in renal function which results from loss of nephrons. Because there are far more nephrons than are needed to maintain normal plasma composition and sustain the endocrine function of the kidney (e.g. production of erythropoietin), most renal function is already lost before clinical signs become evident; indeed most is lost before the usual markers of renal disease i.e. plasma urea and creatinine rise convincingly beyond the normal range. Markers of renal damage, such as increased enzymes in urine or blood, are more useful in acute renal damage rather than CRF. The hallmark of CRF is the decline in glomerular filtration rate (GFR) which accompanies the progressive loss of nephrons (despite a compensatory increase in the individual GFRs of surviving nephrons). A measure of reduced GFR (e.g. by plasma clearance of technetium labelled EDTA, or iohexol or creatinine) therefore offers the most sensitive alert to compromised renal functions. If traditional markers (plasma urea, creatinine) are used, the latter is more specific but allowance should be made for breed (differences in muscle mass hence in creatinine production) and, ideally, as animal’s readings should be compared with those obtained from it earlier in life, rather than comparing with the wide range of “book normals”. Thus routine screening, e.g. at revaccination, would allow more sensitive detection of asymptomatic renal insufficiency - and alert practitioners to the increased risks associated with anaesthesia and/or dehydration in such cases. Fractional phosphate excretion (a very indirect marker of secondary hyperparathyroidism) has recently attracted considerable veterinary attention but it is a very insensitive test for CRF. Plasma phosphate, on the other hand, needs careful monitoring in established CRF since it influences metastatic calcification and progression of the renal diseases. Not all renal disease causes azotaemia; glomerulo-nephritis, for example, may cause proteinuria without azotaemia in the early stages. Equally, CRF need not cause proteinuria. If we could detect CRF earlier, we could manage it better e.g. by introducing specific diets earlier, when they are likely to be more acceptable, and we could also be aware of the increased risk of decompensation e.g. by dehydration, cardiac failure, hypotension, anaesthesia. We might also learn more about the factors which cause or perpetuate it.

Chronic renal failure (CRF) is the outcome of an insidious, relentless, permanent loss of nephrons. It may take years to progress to a stage where clinical signs are obvious. Meanwhile, however, as nephrons are lost, the glomerular filtration rate (GFR) of the animal falls. Paradoxically, the GFR of intact surviving nephrons, individually, may rise as part of the process of compensation which postpones the onset of clinical signs. Total GFR, however falls. The hallmark of CRF, therefore, is an increasingly subnormal GFR2. GFR is measured, classically, as the “clearance” of a substance excreted solely by glomerular filtration (i.e. neither secreted elsewhere in the nephron nor metabolised elsewhere in the body) and which, once filtered, is not reabsorbed by the rest of the nephron. It represents the rate of excretion as the plasma volume per minute which could be totally cleared of the marker, thus if P = plasma concentration, U = urine concentration and V = rate of urine production GFR = U × V (ml/min) P But, since U x V equals the excretion rate, GFR also equals excretion rate per plasma concentration, thus it is a measure of renal efficiency1. If the plasma concentration of a natural metabole, e.g. creatinine, which is handled solely (almost solely) by glomerular filtration, is doubled, its rate of excretion will be unchanged even when GFR is halved; the reduction of filtration rate is offset by the increased concentration in the filtered plasma. Thus the key consequence of CRF is not the reduction in the excretion of nitrogenous waste but the prize paid for the increased plasma concentration at which excretion is maintained2. It is thus a failure of the kidneys’ vital role in maintaining the normal plasma concentration of a range of molecules and ions. Clinically we may detect the changes in plasma concentration or their consequences, including endocrine responses and, eventually, clinical signs but nothing will adequately represent the extent of the problem except a representation of GFR. This may be either a true measurement, or an estimate based on the rate of disappearance from plasma of a marker, frequently linked to a radioactive isotope to facilitate measurement. Advanced imaging techniques including ultrasound, scintigraphy and MRI can also provide information relevant to the diagnosis of renal disease, by detecting changes in renal form, function or perfusion. To a limited degree, excretion of enzymes in urine (rather than changes in their plasma

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composition) can provide adjunctive information but are more likely to facilitate diagnosis of acute renal damage3,4. Proteinuria is important in the detection of glomerulonephritis and may in itself promote the progression of CRF, increasing the importance of its monitoring (see elsewhere in this volume). In the earliest stages of glomerulonephritis, sensitive measures of proteinuria may detect disease at a stage where GFR is still normal (or even above normal). It is important to emphasise that CRF does not necessarily involve proteinuria. The reason that so much emphasis is placed on proteinuria in the detection of human CRF is that most human renal disease is glomerulonephritis. Of all the important clinical effects of CRF, anaemia is probably the least sensitive for its early detection. Finally, other indices of renal function (e.g. phosphate excretion, concentrating capacity) are affected by CRF but too insensitively for either early detection or quantitative monitoring of its progression. Unfortunately the same is true of the two most readily available indices for general practitioners, plasma urea and creatinine. These issues are now examined in detail.

Plasma urea and creatinine1 If we rely purely on measurements of plasma urea and creatinine, rather than their clearance, we assume not only that glomerular filtration rate is the only factor affecting their excretion but that both are generated at a constant rate; neither is true and this flaw affects urea far more than creatinine. Creatinine, though imperfect, is the best endogenous marker of a reduction in GFR. To illustrate its shortcomings, let us consider the mathematics of CRF. Suppose renal disease, of whatever cause, is progressing slowly and linearly so that half or renal function is lost in the first three years. During this period, GFR is halved and plasma creatinine doubles. That may scarcely take it above the “book-normal” range; thanks to renal compensation the animal remains symptomless. In the next 18 months, GFR halves again, plasma creatinine is now four times the animal’s own original normal value. Thus in this relatively short time, compared with the duration of the disease the animal progresses from being symptomless to severely symptomatic. It progresses from a symptomless increase in plasma creatinine (azotaemia) to symptomatic renal failure (uraemia). At any time in this period decompensation of renal function by dehydration, hypotension or drugs which reduce blood pressure or renal perfusion, could precipitate acute onset of symptoms - “acute on chronic” renal failure, which differs from acute renal failure (ARF) in that there has already been a permanent loss of nephrons, whereas ARF need not cause nephron loss. Another 4-5 months, with a further halving of GFR (to 12% of normal) bring the animal towards terminal uraemia and death. There is thus a mathematical reason why plasma creatinine is so insensitive. The increase is logarithmic, exponential i.e. the early rise is unremarkable especially when compared with “book normal” ranges which encompass a variety of techniques and breeds. Significant breed differences result from differences in muscle mass5 since creatinine is generated from muscle. Moreover, in the late stages of CRF,

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loss of muscle mass may reduce the rate of production and moderate the increase in plasma concentration, compared with the fall in GFR. In advanced CRF, the fact that a small amount of creatinine may be secreted into the renal tubule becomes important because the process may increase but also its relative magnitude is greater in comparison with the reduced GFR. Since GFR itself is affected by time of day and meal pattern it becomes clear that the only useful way of screening plasma creatinine as an index of CRF would be with regular samples after the overnight fast and comparison with the animal’s own normal value (earlier baseline values taken annually at the revaccination visit). Since the rise in plasma creatinine concentration is exponential, a plot of the reciprocal concentration against time tends to be linear. This has, therefore, aroused some enthusiasm as an index of the progression of CRF, both in humans and dogs, but granted the problems with the underlying measurement6 it probably offers little advantage compared with careful serial monitoring of creatinine itself. Urea is a more popular measurement in practice because of its wider availability in simple practice laboratories. It is, however, horrifically imprecise as an index of renal function because its excretion rate varies with that of water as both tend to be reabsorbed simultaneously. Thus in dehydration, urea rises more than creatinine2. Clearly, since it is subject to variable reabsorbtion it can not be a valid marker for GFR. Worse, its production rate depends on hepatic function and dietary protein. If we place animals on a low protein diet their blood urea should fall, not because renal function has improved, but because of the reduced urea production which accompanies a reduced protein intake. Plasma creatinine, by contrast will not fall, reflecting the absence of an improvement in GFR. A drastic reduction in muscle mass, or meat intake, could reduce plasma creatinine6.

Why seek early diagnosis? With any screening technique it is a valid question; what will we do with the information and how will the patient benefit. In my view there are essentially three benefits. Firstly, the sooner renal disease is detected, the sooner dietary modification can begin and the more gradual it can be. This must reduce the problem of non-compliance i.e. rejection by the animal of a novel diet. “Learned aversion” (“bait shyness” in rats) minimises the acceptability to many species of a novel diet which is first experienced when the animal feels unwell. The evolutionary benefit of this is obvious where the novel diet (or a contained toxin) genuinely causes the nausea but it clearly increases the problem of dietary manipulation once an animal feels ill. The second advantage of early diagnosis is that dietary manipulation (or other measures) apart from postponing the onset of azotaemia and, eventually, uraemia, may also genuinely slow the progression of the disease. That is the subject of a separate contribution to this volume. The third, and perhaps the greatest benefit of more regular renal screening would be the early detection of animals with symptomless but substantial renal insufficiency, making them especially vulnerable to the effects of anaesthesia or dehydration and especially the combination of both.

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The best marker now available for plasma clearance estimates of GFR is DTPA (which behaves very similarly to the gold-standard marker, inulin) linked to radioactive technetium (Tc) which is readily measured by a gamma counter7. The beauty of technetium is its safety; since it has a half-life of six hours i.e. only one sixteenth of the original radioactivity survives the first day, few precautions are needed beyond the first voiding and this can safely be discarded after 24 hours. In fact, humans simply use the normal toilets with no precautions at all. For those without the ability to count radioactive emission there are two alternatives; iohexol has been validated in dogs and is a very safe radiographic contrast agent8,9. The only problems are the substantial volume needed in tiny animals and the viscosity which is reduced by warming; the main problem is that the samples, though wonderfully stable (hence suitable for posting to the laboratory) require expensive analytical equipment. The other alternative is exogenous creatinine but, at least in the UK, it is not available in sterile form. Polyfructosan-S may offer a further choice since it behaves similarly to inulin but is easier to dissolve and may also be simpler to analyse6.

for the exposure of animals to procedures (e.g. anaesthesia) and drugs (e.g. ACE-inhibitors, NSAI’s) which can prejudice renal function in susceptible individuals, without at least monitoring plasma creatinine before and after. In the case of ACEI’s, the minority of patients which react adversely improve with the withdrawal of the drug. The problem is that in veterinary medicine, with no coroners court, it is too easy to attribute adverse effects and fatalities to the disease rather than the treatment. With renal function today, as with acid-base balance in previous years, the reason that so few animals appear to die of decompensated renal insufficiency is probably, quite simply, that their death cannot be attributed to changes which we do not measure. If we sought, we would certainly find.

References 1.

Other indices 4.

There has been misplaced enthusiasm for fractional phosphate excretion in recent veterinary literature. Essentially this amounts to an extremely insensitive index of secondary hyperparathyroidism resulting from CRF. As plasma PTH levels rise they reduce the tubular reabsorbtion of phosphate and increase the fraction of the filtered phosphate which is excreted. Since PTH assays are now available there seems little reason to use this insensitive test1,10, except, perhaps, to confirm the effect of dietary phosphate restriction.

7. 8.

Conclusion Even if there are still practical and economic constraints on regular renal screening in animals, there is little excuse

10.

Gleadhill, A. and Michell, A.R. (1996) Clinical measurement of renal function. Ch 9 In: Manual of Canine and Feline Nephrology and Urology. Ed. J. Bainbridge and J. Elliott. BSAVA, Cheltenham (UK) 107-116. Michell, A.R. (1988) Renal function, renal damage and renal failure. In “Renal Disease in Dogs and Cats: Comparative and Clinical Aspects”. Ed. A.R. Michell. Blackwell, Oxford pp 5-29. Jung, K. (1992) Urinary enzymes in renal, renal-associated and urological disorders. Ch. 12 In “Urinary Enzymes”. Ed. K. Jung, H. Mattenheimer and U. Burchardt. Springer-Verlag, Berlin, pp. 170-187. Kerr, M.G. (1989) Veterinary Laboratory Medicine. Blackwell Scientific, Oxford pp 109-120. Gleadhill, A. (1996) Quantitative Assessment of Renal Function in Domestic Animals; Measurement of GFR by the Plasma Clearance of Tc-DTPA. PhD Thesis, Univ. of London. Mitch, W.E. and Walser, M. (1996) Nutritional Therapy for the Uremic Patient. Ch 55 In the Kidney (5th Edn) Ed. B.M. Brenner, W.B. Saunders, Philadelphia. pp 2382-2423. Gleadhill, A., Peters, A.M. and Michell, A.R. (1995) A simple method of measuring GFR in dogs. Res.Vet. Sci. 59:118-123. Gleadhill, A., Michell, A.R. (1996) Evaluation of iohexol as a marker for the clinical measurement of glomerular filtration rate in dogs. Heine, R. (1995) Renal damage in the dog evaluated by urinary enzymes and glomerular filtration rate using plasma clearance of iohexol. PhD Thesis, Norwegian College of Veterinary Medicine, Oslo. Gleadhill, A. (1994) Evaluation of screening tests for renal insufficiency in the dog. J. Sm. Anim. Pract. 35:391-6.

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Clearance measurements

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Management of renal diseases: have we progressed? A.R. Michell

Summary

Introduction: the nature of renal failure

Chronic renal failure (CRF) is the clinical presentation of a variety of diseases, poorly characterised in dogs, but featuring a relentless, irreversible loss of nephrons. As a result, there is a steady decline in glomerular filtration rate (GFR). Since the kidneys have a large functional reserve capacity, i.e. far more nephrons than are needed for most normal functions, the majority of the nephron loss occurs over months or years during which no clinical signs are detectable, thanks to the compensatory changes in the function of surviving nephrons. While this initially benefits the patient it makes it harder to discover the originating cause - or whether CRF is the outcome of a variety of repetitive “insults”, including disease or exposure to toxins, including some drugs. In the 1980s a key tenet of renal medicine was that the factors sustaining progression of renal disease may be different from those which initiate it i.e. that at some stage, CRF becomes a disease characterised by self-sustaining progression. If so, there was the hope that the factors influencing progression might be more amenable to investigation and treatment. In particular, dietary factors attracted attention; lipids, phosphate, sodium and protein for example. Sodium was considered mainly in the context of hypertension, a factor which certainly sustains progression of CRF. Like dietary protein, however, sodium raises GFR and, granted that reduced GFR is the hallmark of CRF, this would seem beneficial. For some 15 years, however, there was a strong suspicion that the adaptive increase in the GFR of surviving nephrons, while sustaining overall renal function, ultimately accelerated their demise i.e. it accelerated progression. In that case, reduced dietary protein offered the chance of not only reducing the effects of CRF (i.e. slowing the increase of azotaemia and postponing the onset of uraemia) but of actually ameliorating the progression of the disease. Except in rats, this now seems increasingly improbable, indeed there is reason to doubt whether progression is self-sustaining, rather than being the outcome of repetitive renal insults. It is, therefore, timely to review current concepts of the factors which influence the progression of chronic renal disease and, in particular, those that are likely to be relevant to dogs and cats. It is also appropriate to consider the role of erythropoietin in alleviating the anaemia of CRF and the present role of transplantation in offering a substitute for lost renal function.

Chronic renal failure (CRF) is an insidious, relentlessly progressive, irreversible disease characterised by progressive loss of nephrons and the consequent fall in glomerular filtration rate (GFR). Clinically, most of the course consists of a silent, asymptomatic phase (compensated renal insufficiency) during which there is a gradual onset of azotaemia (accumulation, in plasma, of the end products of protein breakdown, notably urea, creatinine, and a range of putative uraemic toxins). This is followed by the onset of uraemia, the symptomatic phase. An azotaemic animal may be pushed into symptomatic uraemia by dehydration (e.g. diarrhoea), hypovolaemia (e.g. haemorrhage), hypotension (e.g. anaesthesia, especially with dehydration) or renovascular effects of drugs (e.g. ACEI’s or NSAI’s). This “acute-on-chronic” failure does not necessarily cause additional nephron damage and may be reversible, but only to the pre-existing level of insufficiency. At present, the only way of restoring normal renal function to a patient with CRF is to provide a healthy compatible replacement kidney. Whether it survives depends on the immunogenetic match between recipient and donor, the underlying disease, and the immunosuppresive regimen.

Progression Progression is not necessarily slow, e.g. in “rapidly progressive glomerulonephritis” but typically, we believe, months or more usually years separate the onset from the clinical signs. That is why early diagnosis requires “smoke alarms” which will detect smouldering renal insufficiency, rather than awaiting the clinical signs; once flames break through the roof the diagnosis is clear but it comes too late for damage limitation. The extended period of renal insufficiency reflects not only the underlying pathology but also the huge functional reserve capacity of the kidneys and also the ability of surviving intact nephrons to adapt. Thus while GFR declines, the workload of the remaining nephrons, their single nephron glomerular filtration rate (SNGFR) increases the reserve capacity and the adaptive power of a healthy kidney is well illustrated by renal transplant donors who suffer no adverse effects following abrupt removal of half their nephrons. While GFR is halved initially, it rapidly increases to 75% of normal1.

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Adaptation or exacerbation? The nature and consequences of this adaptive process in CRF has become the central issue of nephrology since the early 1980s. Previously the “intact nephron hypothesis” of Bricker emphasised that the functions of the kidneys in CRF are those of the surviving intact nephrons, with adaptive changes, rather than the distorted function of damaged nephrons. The kidney is perceived as a population of defunct, damaged, non functional nephrons and surviving, hyperfunctioning, hyperfiltrating nephrons, limiting the detectable abnormalities of renal function and postponing the onset of detectable clinical signs. What changed in the 1980’s, was the thesis of Brenner that the adaptive changes in the surviving nephrons hastened their own demise, i.e. that progression becomes a separate, self sustaining process. Initially this was blamed on hyperfiltration itself, more recently on increased intraglomerular pressure (which is not necessarily linked to systemic hypertension)2.

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arise from mediators released during nephron injury which then damage other nephrons; such mediators could also be targets for pharmacological or dietary manipulation e.g. prostaglandins via NSAIs or dietary lipids and specific evidence in dogs, cats, rats or humans; species differences appear to be important and it is possible that dogs are better models for human CRF than rats3 (which are peculiarly prone to glomerular sclerosis if they have glomerular hypertension).

Causes of progression3 Possible factors may include the following or interactions between them Hyperfiltration Glomerular hypertension Systemic hypertension Glomerular hypertrophy

Renal disease Uraemic toxins Catabolism Exogenous mediators Growth factors Proteinuria

Uric acid PO4 Ca PTH NH3 Na

PCV Lipids Coagulation Lipid peroxidation Cholesterol

Clinical implications The clinical implications of this hypothesis are spectacular 1. Elevated SNGFR is not benign compensation but an inherently lethal process for the kidney and ultimately the patient: it postpones terminal renal failure but makes it inevitable. 2. On the other hand, if the perpetuation of CRF is a separate process from its initiation, there are grounds for optimism because, with its extended time - course, it is more amenable to clinical investigation whereas the originating causes may have occurred years earlier. Moreover, if dietary or pharmacological measures can slow or arrest progression, CRF could be halted at an acceptable stage, provided it was detected sufficiently early. Central to this debate has been the role of protein in sustaining progression. The traditional reason for moderating protein intake, reduction of azotaemia, remains unchallenged but merely offsets the effects of CRF. The new concept was that by reducing hyperfiltration, protein restriction slowed progression. Certainly amino acids increase GFR so the logic is plain. Until we remember that the core problem of CRF is the fall of GFR and we remind ourselves that the increase in SNGFR, before 1980, was regarded as adaptive. We should not, therefore, restrict this increase in SNGFR unless we are convinced that it hastens the demise of surviving nephrons. We should also remember that the distinction between the originating causes of CRF, shrouded in mystery, and the sustaining causes of progression, while exceptionally attractive both scientifically and clinically, demands proof. Moreover loss of nephrons is part of the natural ageing of the kidney. The 21st century may regard ageing as a treatable disease but, for the moment, progression could also be an intensification of renal ageing or, quite simply, the cumulative effect of a whole lifetime of nephropathic events, immunological, pharmacological and toxic. The kidney, after all, is matched only by the liver in its exposure to molecules at concentrations far above those which, in plasma may be harmless. Self sustaining progression could

Hyperfiltration and glomerular hypertension The increased SNGFR results from increased perfusion, or increased intraglomerular pressure mediated by reduced afferent tone or increased efferent tone, thus increasing the filtration fraction (FF, the proportion of plasma converted into primitive urine). Efferent tone is increased by angiotensin II hence angiotensin converting enzyme inhibitors (ACEI’s) reduce SNGFR whereas amino acids increase it by reducing afferent tone. Diabetics are peculiarly vulnerable to glomerular hypertension because their reduced afferent tone exposes the glomerulus to higher pressure even when systemic pressure is normal; they also suffer hyperfiltration in the early stages of their disease4. Thus a marginally hypertensive diabetic may have a damaging increase in glomerular pressure. The increased pressure also causes an increase in the normally small degree of filtration of albumin and the resulting trace albuminuria (microalbuminuria) provides a sensitive warning of diabetic nephropathy in humans. The problem in dogs is the wide range of normal urinary protein. Experimentally, diabetic dogs have the reduce afferent tone which underlies glomerular hypertension. A physical consequence of glomerular hypertension is enlargement and increased wall tension, predisposing to sclerosis3. The main clinically controllable factor sustaining progression is systemic hypertension4,5. Nevertheless the beneficial effects of antihypertensives may depend on factors besides those on blood pressure. For example ACEI’s slow progression of human diabetic nephropathy whereas beta-blockers giving similar blood pressure control do not3,6. Angiotensin has local effects on glomerular pore size, glomerular mesangial tension and is a renal growth factor; and ACEI’s also have various metabolic effects. Similarly, heparin and related drugs have renoprotective effects other than those as coagulation. If control of blood pressure is important in moderating progression of CRF it is likely to be in cats, rather than dogs as hypertension is more common perhaps

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mineral by PTH is not accompanied by the appropriate increase in urinary phosphate excretion. That is because GFR is so low that suppression of tubular phosphate reabsorbtion by PTH, no longer promotes the necessary increase in excretion. The importance of phosphate restriction in ameliorating secondary hyperparathyroidism has also been shown in humans with severe CRF14a. Increased plasma phosphate is a major factor in metastatic calcification and for this and other reasons, it is an important determinant of progression in canine and feline CRF. In humans with advanced CRF, those best able to excrete phosphate were those whose disease progressed least3. Since renal phosphate excretion is irretrievably compromised, limitation of dietary phosphate intake and of secondary hyperpathyroidism are key objectives in limiting the progression of CRF15.

Sodium3 Proteinuria Proteinuria is not only a marker of glomerular damage (or, at trace concentrations, of increased glomerular pressure) but it is also an independent risk factor sustaining progression3,8. The link results from tubular injury leading to release of cytokines directly or from inflammatory cells. Proteinuria can also cause further glomerular damage. Loss of plasma albumin predisposes to hyperlipidaemia which may also sustain progression (see below). In dogs, both ACEI’s and calcium channel blockers reduce proteinuria and glomerular hypertrophy, but only ACEI’s reduce glomerular pressure9. Hypercholesterolaemia, which accompanies hypoalbuminaemia (as in severe proteinuria) may nevertheless be an independent risk factor for progression of CRF in humans10.

The role of sodium in CRF is both neglected and misunderstood. There is great enthusiasm for sodium restriction to treat or prevent hypertension. Certainly dogs and cats generally receive a generous excess of dietary salt. But in canine CRF hypertension is rare (see elsewhere in this volume) and whereas a gradual drop in dietary salt may be harmless, a sudden reduction could compromise residual renal function. A more persuasive reason to reduce dietary sodium would have existed when hyperfiltration was seen as the mediator of progression; high sodium intake increases GFR. Perhaps most important, and most neglected, is that sodium reabsorbtion is the main energy consuming work of the kidney and the amount to be reabsorbed is dictated by GFR. Thus while, much nonsense is talked about “resting” the kidney, the most effective way of doing it would be by reducing sodium intake, GFR and reabsorptive workload.

Changes in azotaemic plasma Ammonia is a potent cause of compliment-mediated renal damage; normally the high osmotic concentrations in the kidney are protective but they are reduce in CRF3. The acidosis which accompanies CRF, and lack of dietary antioxidants may both increase renal ammonia production. Azotaemic plasma shows evidence of increased lipid peroxidation and lipoprotein abnormalities11. These may be reduced by dietary manipulation in humans12.

Calcium, phosphate and parathyroid hormone (PTH) Calcium could be involved in progression through its role as an intracellular signal affecting vascular and mesangial tone as well as renin secretion. PTH increases intracellular calcium and has also been considered as a uraemic toxin, apart from its role in exacerbating hyperphosphataemia13,14. The latter reflects the fact that in renal (secondary) hyperparathyrodisim, the mobilisation of bone

Growth factors and cytokines3 Increasingly, the power of molecular biology to identify and synthesis mediators, receptors or receptor antagonists, offers a future in which self perpetuating injury can be blocked by attacking the underlying control mechanisms. In doing so, it will be essential to distinguish between mediators of injury and mediators of repair and to remember that most physiological control systems involve multiple feedback loops so that whatever interference is imposed, the effects may be blunted by counterregulation. Among the cytokines and growth factors which have attracted most attention are interleukins, angiotensin II, endothelins, prostaglandins, tumour necrosis factor (TNF) and growth factors including a IGF-1 (insulin-like growth factor) angiotensin and PDGF (platelet derived growth factor which is also produced by mesangial cells and increases their proliferation). While these factors essentially affect the local environment of and communication between cells, they may be increasing in plasma concentration as a result of CRF.

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because, as long suspected in humans, glomerular disease is more prevalent (and more likely to cause hypertension7). Increased glomerular size is not the same as glomerular hypertrophy. Neither hyperfiltration nor a raised glomerular pressure per se seems sufficient to trigger or sustain progression but evidence from rats suggests that the combination of glomerular hypertrophy and systemic hypertension does predispose. Both in rats and humans it is possible to dissociate beneficial effects on glomerular sclerosis from reductions in hyperfiltration and once sclerosis occurs it is a progressive change. Mesangial cells are important because they alter their tension in response to local and systemic hormones, thus affecting glomerular surface area and efferent tone, but also because they affect local accumulation of macromolecules and matrix synthesis. They release growth factors but their activity is part of the repair process, rather than a cause of sclerosis3.

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Diet and progression Two main dietary factors have attracted the spotlight in recent research and debate on the management of CRF: they are the role of proteins and lipids in sustaining progression. In evaluating the evidence it is important to distinguish not only between species but between spontaneous disease and various induced models. These may involve primary nephron loss (e.g. surgical remnant kidney), primary glomerular damage (immune or nephrotoxic), hypertensive, or spontaneous (genetic) models e.g. hereditary glomerulonephritis in Samoyeds3,16. Perhaps the most discouraging evidence, both from clinical nephrectomy (e.g. for neoplasia) and experimental subtotal nephrectomy, is that self-sustaining progression is highly dependent on the severity of the nephron loss and only occurs when it is extreme. This suggests that far from dominating the clinical course of CRF, self-sustaining progression may be merely a terminal event i.e. progression may be the cumulative effect of various renal injuries, some of which may be self-exacerbating. If so, models that depend on acute intervention are unlikely to be representative though they may throw light on contributory mechanisms. Above all many of the models cause proteinuria or nephrosclerosis without a progressive decline in GFR i.e. in the sense associated with clinical CRF, these models do not cause progression3. Thus in assessing evidence in these controversies, as well as considering whether it relates to models of clinical CRF, and in which species, the criterion of progression is crucial. The problems of detecting and monitoring CRF are considered elsewhere in this volume. Serial measurements of GFR, with due precautions, are the best but as clinical approximations, plasma creatinine or its reciprocal are usually used as indirect indices. Neither is sensitive or reliable.

Protein and progression In non human primates, experimental reduction of GFR to 30% of normal failed to cause progression and low protein diets affected neither blood pressure nor proteinuria but caused a further fall in GFR. In humans, the evidence on protein restriction is that it does not significantly affect long-term progression, even when the restriction is very severe (unless the patient is diabetic4,17,18 or in the advanced stages of the decline in GFR). No benefit was seen in children with CRF19. For the moment, the situation is that evidence of efficacy is inconclusive, rather than there being proof of a lack of efficacy20,21. In dogs, there is little defensible evidence for a beneficial effect of protein restriction on the progressive decline in GFR which characterises CRF3,22-24, though it limits the development of lesions in Samoyeds with hereditary glomerulonephritis16. Most of the evidence on protein and progression arises from rat models. Some of the benefits of protein restriction may reflect an associated reduction of calorie intake, an independent factor in progression25.

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Unfortunately, while both CRF and hypertension are probably both more prevalent in cats than dogs, evidence concerning both is scarce in this species. A recent study by Elliott and Barber26 suggests that anaemia was a particularly important prognostic sign. It also indicated that rather than progressing steadily, severe falls in GFR often occurred suddenly, late in the course of CRF. Neither in cats nor in dogs are presenting signs and measurements a good guide to prognosis27. The influence of anaemia on progression of CRF is a complex question. Clearly, humans benefit greatly from treatment with erythropoietin but there is nevertheless the fear that, at some level, a raised PCV becomes a risk factor through the effects on renal haemodynamics and blood pressure28,29.

Lipids and progression The focus of interest is on the ability of polyunsaturated fatty acids (PUFA), notably those in fish oils or some plant oils, to modify progression, perhaps by affecting the production of cytokines notably prostaglandins and thromboxanes3. Low protein diets may also influence cytokine production. Experimentally, PUFA from fish oils (menhaden oil, omega-3 PUFA) preserved renal function in dogs with induced CRF and humans with clinical CRF30,31,32 whereas plant derived omega-6 PUFA were worse than saturated beef fat. PUFA may also moderate systemic pressure and if so this is likely to be important in cats rather than dogs, where only a minority with CRF are hypertensive33.

Conclusion One of the problems in advising on dietary management of CRF in dogs or cats is not simply the scarcity and uncertainty of the relevant evidence but the lack of information on the altered nutritional requirement in such patients, regardless of progression34. This problem is worst in cats because they are obligate carnivores, unlike dogs, and they are more prone to protein-losing nephropathy. Cats with CRF may, in a minority encounter additional problems due to renal potassium-wasting and the associated potassium depletion may cause, as well as muscle damage, additional renal damage. Such patients require potassium gluconate supplements though the suggested dose34,35 (2-6 mmol/d) seems remarkably low. For a 5 kg cat this is 1 mmol/kg or less, barely equivalent to the extracellular potassium whereas the huge majority, and the site of the main deficits is intracellular. Recently there has been a reawakening of interest in the use of oral adsorbents to remove uraemic metabolites and reinforce the dietary control of progression of CRF36. For the moment, the main basis for dietary manipulation in CRF damage is to restrict the effects of azotaemia and acidosis (which exacerbates azotaemia and bone damage37) and, perhaps through restriction of phosphate and manipulation of specific unsaturated lipids, to moderate its progression.

References 1.

Meyer, T.W., Baboolal, K. and Brenner, B.M. (1996) Nephron adaptation to renal injury. Ch.44 in The Kidney (5th Edn). Ed. B.M. Brenner. W.B. Saunders, Philadelphia pp 2011-2048. 2. Fine, L.G., Woolf, A.S. and Gallego, C. (1991) Of rats and men: the need for more convincing clinical studies on progression of renal diseases. Am. J. Kidney Dis. 17: 258-260. 3. Michell, A.R. (1995) Progression of chronic renal failure: have we progressed. Vet. Ann. 35: 159-176. 4. Neuringer, J.R. and Levey, A.S. (1994) Strategies to slow progression of renal disease. Sem. Nephrol. 14:261-273. 5. Kes, P. and Ratkovic-Gusic, I. (1996) The role of arterial hypertension in progression of renal failure. Kidney Int. (Suppl) 55:S 72-74. 6. Ihle, B.U., Whitworth, J.A., Shahintar, S., Cnaan, A., Kincaid-Smith, P.S. and Becker, G.J. (1996) Angiotensin converting enzyme inhibition in nondiabetic progressive renal insufficiency: a controlled double-blind trial. Am. J. Kidney Dis. 27: 489-495. 7. Buckalew, V.W., Berg, R.L., Wang, S.R., Porush, J.G., Rauch, S. and Schulman, G. (1996) Prevalence of hypertension in 1795 subjects with chronic renal disease: the modification of diet in renal disease study baseline cohort. Am. J. Kidney Dis. 28: 811-821. 8. Burton, C. and Harris, K.P. (1996) The role of proteinuria in the progression of chronic renal failure. Am. J. Kidney Dis. 27: 765-767. 9. Brown, S.A., Walton, C.L., Crawford, P. and Bakris, G.L. (1993) Long-term effects of antihypertensive regimes on renal hemodynamics and proteinuria. Kidney Int. 43: 1210-1217. 10. Washio, M., Okuda, S., Ikeda, M., Hirakata, H., Nasishi, F., Onoyama, K., Yoshimura, T. and Fujishima, M. (1996) Hypercholesterolaemia and the progression of renal dysfunction in chronic renal failure patients. J. Epidemiol. 6: 172-177. 11. Ong-Ajyooth, L., Ong, Ajyooth, S., Sirisalee, K. and Nilwarangkur, S. (1996) Lipoproteins and lipid peroxidation abnormalities in patients with chronic renal disease. J. Med. Assocn. Thai. 79: 505-512. 12. Peuchant, E., Delmas-Beauvieux, M.C., Dubourg, L., Thomas, M.J., Perromat, A., Aparicio, M., Clerc, M. and Combe, C. (1997). Antioxidant effects of a supplemented very low protein diet in chronic renal failure. Free Radic. Biol. Med. 22: 313-320. 13. Massry, S.G. and Smogorzewski, M. (1994) Mechanisms through which parathyroid hormone mediates its deleterious effects on organ function in uraemia. Sem. Nephrol. 14: 219-231. 14. Combe, C. and Aparicio, M. (1994) Phosphorous and protein restriction and parathyroid function in chronic renal failure. Kidney Int. 46: 1381-1386. 14a. Vanholder, R., DeSmet, R., Vogeleere, P. and Ringar, S. (1994) Uremic toxicity: the middle molecule hypothesis revisted. Sem. Nephrol. 14: 205-218. 15. Finco, D.R., Brown, S.A. and Crowell, W.A. (1996) Effects of dietary protein and phosphorus on the kidneys of dogs. Recent Advances in Canine and Feline Nutritional Research: Proc. 1996 Iams International Symposium. Ed. D.P. Carey, B.A. Norton and S.M. Bolser. Orange Fraser Press, Wilmington (Ohio, USA) pp 123-142. 16. Valli, V.E.O., Baumal, R., Thorner, P. et al (1991) Dietary modification reduces splitting of glomerular basement membrane and delays death due to renal failure in canine x-linked hereditary nephritis. Lab. Invest. 65: 67-73. 17. Klahr, S., Levey, A.S., Beck, G.J. et al (1994) The effects of dietary protein restriction and blood pressure control on the progression of chronic renal disease. New Engl. J. Med. 330: 878-884.

293 18. 19.

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Klahr, S. (1996) Role of dietary protein and blood pressure in the progression of renal disease. Kidney Int. 49: 1783-1786. Wingen, A.M., Fabian-Back, C., Schaefer, F. and Mehls, O. (1997) Randomized multicentre study of a low protein diet on the progression of chronic renal failure in children. Lancet 349: 1117-1123. Pedrini, M.T., Levey, A.S., Lau, J., Chalmers, T.C. and Wang, P.G. (1996) The effect of dietary protein on the progression of diabetic and non-diabetic renal diseases; a meta-analysis. Ann. Intern. Med. 124: 627-632. Holm, E.A. and Solling, K. (1996) Dietary protein restriction and the progression of chronic renal insufficiency: a review of the literature. J. Intern. Med. 239: 99-104. Bovee, K.C. (1992) High dietary protein intake does not cause progressive renal failure in dogs after 75% nephrectomy or ageing. Sem. Vet. Med. Surg. (Small Anim) 7: 227-236. Brown, S.A. (1992) Dietary protein restriction: some unanswered questions. Sem. Vet. Med. Surg. (Small Anim) 7: 237-243. Kronfeld, D.S. (1993) Dietary management of chronic renal failure in dogs: a critical appraisal. J. Small Anim. Pract. 34: 211-219. Tapp, D.C., Kobayashi, S., Fernandes, G. and Venkatachalam, M.A. (1989) Protein restriction or calorie restriction? A critical assessment of the influence of selective calorie restriction on the progression of experimental renal disease. Sem. Nephrol. 9: 343-353. Elliott, J. and Barber, P.J. (1998) Feline chronic renal failure: clinical findings in 80 cases diagnosed between 1992 and 1995. J. Sm. Anim. Pract. 39: 78-85. Cook, A.K. and Cowgill, L.D. (1996) Clinical and pathological features of protein-losing glomerular disease in the dog: a review of 137 cases (1985-1992). J. Am. Anim. Hosp. Assocn. 32: 313-322. Lafferty, H.M., Anderson, S. and Brenner, B.M. (1991) Anemia: a potent modulator of renal hemodynamics in models of progressive renal disease. Am. J. Kidney Dis. 17:2-7. Abels, R. (1990) Rate of progression of chronic renal failure in predialysis patients treated with erythropoietin. Sem. Nephrol. 10: (Suppl 1) 20-25. Brown, S.A. and Finco, D.R. (1996) Fatty acid supplementation and chronic renal disease. Recent Advances in Canine and Feline Nutritional Research : Proc. 1996 Iams International Symposium. Ed. D.P. Carey, S.A. Norton and S.M. Bolser. Orange Frazer Press, Wilmington (Ohio, USA) pp 159-170. Brown, S.A., Brown, C.A., Crowell, W.A., Barsanti, J.A. and Finco, D.R. (1996) Does modifying dietary lipids influence the progression of renal failure? Vet. Clin. N. Am. (Sm. Anim Pract) 26(6) 1277-1285. Cappelli, P., Di Liberato, L., Stuard, S., Ballone, E. and Albertazzi, A. (1997) N-3 polyunsaturated fatty acid supplementation in chronic progressive renal disease. J. Nephrol. 10: 157-162. Michell, A.R., Bodey, A.R. and Gleadhill, A.G. (1997) Absence of hypertension in dogs with renal insufficiency. Renal Failure 19: 61-68. Rubin, S.I. (1997) Chronic renal failure and its management and nephrolithiasis. Vet. Clin. N. Am. (Sm. Anim. Pract) 27(6): 13311354. Polzin, D.J., Osborne, C.A. and Lulich, J.P. (1996) Diet therapy guidelines for cats with chronic renal failure. Vet. Clin. N. Am. (Sm. Anim. Pract) 26(6): 1269-1275. Dwada, A. and Shiigai, T. (1996) The effects of oral adsorbent AST120 concurrent with a low protein diet on the progression of chronic renal failure. Am. J. Nephrol. 16: 124-127. Price, S.R. and Mitch, W.E. (1994) Metabolic acidosis and uraemic toxicity: protein and amino acid metabolism. Sem. Nephrol 14: 232-237.

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Canine hypertension: a difficult but fascinating disease A.R. Michell

Twenty years ago, few veterinary students would have learned anything about canine hypertension, yet many medical students would have been aware that the dog was a classic species for the experimental study of hypertension. Now, it is almost assumed that dogs with chronic renal failure (CRF) will require antihypertensive therapy. Yet, only a minority will actually be hypertensive and, in those which are normotensive, such therapy could well decompensate their residual renal function. There has been real progress in recent years with canine hypertension. This comprises 1. Validation of non-invasive measurement techniques for arterial pressure. 2. Establishment of a large epidemiological database - allowing normal values to be defined with regard to breed and age and also showing differences with sex. Most canine hypertension is secondary, unlike human hypertension which is mainly primary hypertension (“essential hypertension”, EHT). Among the causes are diabetes mellitus and Cushings Syndrome (as in man) and hepatic disease (unlike man). Renal disease can also cause hypertension but, unlike man, the majority of dogs with renal insufficiency (reduced glomerular filtration rate) remain normotensive: the basis for this resistance to hypertension merits study. Certain breeds of dog (notably “sight hounds”) have normal pressures in the human hypertensive range and these breeds raise three questions: 1. Are they models for EHT? 2. Why are they resistant to the adverse effects of raised arterial pressure? 3. Is the increased pressure adaptive? These questions will be explored, alongside the epidemiological features of hypertension in other breeds and the importance of sodium intake.

Acknowledgements The primary investigator in this research is Dr Angela Bodey and our work has been generously supported by WALTHAM.

Introduction Dogs have featured in the study of blood pressure and hypertension since the earliest times; Hales in 1733 made

his pioneering observations on blood pressure measurement not only in horses but also in dogs and the classic Goldblatt model of hypertension was a dog model before it became a rat model. Humans with hypertension are susceptible to renal damage and, independently, humans with chronic renal failure (CRF) are likely to develop hypertension. It is not surprising, therefore, that the last decade has seen increasing concern with a hitherto neglected disease - canine hypertension. This has coincided with the availability of non-invasive methods for blood pressure measurement. Twenty years ago, few veterinary students would have learned anything about hypertension yet now many will be taught that dogs with CRF require antihypertensive therapy, including salt restriction. The 1990s have seen a growing concern for “evidencebased medicine” i.e. based on scientific data rather than cumulative clinical experience (however well judged) or textbook assertions, however widely repeated. This review argues that hypertension is rare in dogs, even when they have serious renal insufficiency and that treatment of an animal is likely to further decompensate renal function. Similarly, there is little reason for salt restriction, except insofar as most canine diets present a nutritional excess of sodium; if there is a reason it has more to do with renal energy demand than with hypertension.

What is hypertension The answer is less obvious than it appears. Blood pressure, contrary to the impression given in many textbooks, is rapidly and widely variable1,2. In some sense it is remarkable that patients offer any consistency in their readings especially when, as is often the case in humans, the measurement consists of a single reading3. Reproducible readings require a non-stressful technique, quiet surroundings, a relaxed patient and, preferably, a consistent time of day. Once these are obtained, comparison should be made with the appropriate population i.e. allowing for age and breed. Hypertension is an elevation of resting arterial pressure which significantly exceeds the range for the control population; the “normal” pressure for a middle aged black American will be substantially higher than that for an Italian child.

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DSc MRCVS Head, Centre for Small Animal Studies - Animal Health Trust - Newmarket, Suffolk - United Kingdom

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Measurement of blood pressure Direct measurement of arterial pressure continues to be the “gold-standard” but it is invasive and, while measurements made with telemetric signals from chronic catheters in trained dogs are likely to be consistent1, acute intervention in untrained dogs is almost certain to elevate the reading. Moreover direct readings are only “gold standard” when meticulous attention is paid to the transducer and to the catheter, particularly the position and patency of its tip4. Even subtle stress, let alone pain, elevates pressure as reflected in the concept of “white-coat” hypertension in humans i.e. pressures measured in the surgery are likely to exceed those measured at home. Similar considerations apply in dogs5. Thus blood pressures measured in the clinic exceed those measured in a neutral environment5,5a, transient stress causes a protracted increase of systolic pressure in particular and dogs rated as “stress-prone” have higher pressures than more relaxed dogs5,6. Indirect measurements are non-invasive; they depend on an occluding cuff which alters the arterial pressure at the measurement site and the detection of signals associated with systolic, diastolic and mean arterial pressure. These signals may be sounds detected with a stethoscope, ultrasound, or changes in oscillometric pressure patterns. The latter forms the basis for the DINAMAP, the gold-standard noninvasive blood pressure monitor. Cuff inflation, deflation and recording are automated and a reading usually takes 20 seconds to 1 minute. The cuff-limb interface is crucial. 1. The inflatable cuff width must be correct for the limb circumference (w = 0.4c). 2. The site inherently affects the accuracy and reproducibility of readings (i.e. even in anaesthetised dogs). 3. In conscious dogs, some sites are less acceptable to the animal and this also affects the speed and reproducibility of the measurements. Blood pressure, like adult height shows a wide normal range, and hypertension is like being 2 metres tall; it may be unusual but it is not necessarily harmful and attempts to reduce the measurement to normal are more likely to cause harm. Moreover the “normal” pressure of a Deerhound would be hypertensive for a Labrador and any attempt to reduce a Deerhound’s pressure to that of a Labrador could well be catastrophic. The clinical definition of hypertension rests precisely on the concept of the likelihood of adverse effects. Thus in humans 140/90 (systolic/diastolic) is widely regarded as “normal” but depends on age, race etc. What is implied is that higher levels, according to a body of clinical evidence, are likely to cause secondary damage e.g. strokes, coronary disease, cardiac hypertrophy, retinal and renal damage etc. In fact most clinicians will consider a second, higher, threshold at which the risk of immediate, rather than long-term damage is the concern and therapy becomes urgent. The ability to detect a hypertensive individual depends on the precision (reproducibility) of the measurement technique and the narrowness of the normal range with which comparison is made. The continuing practice of defining canine hypertension with regard to a single “book normal” for

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the entire species is, therefore, preposterous granted the range of breed-specific variation7. Indirect readings are seldom accurate i.e. they usually differ from the “gold-standard”. This does not matter provided that the difference is predictable and reproducible. In conscious animals, direct readings are unsuitable so what matters about an indirect technique is its reproducibillity (i.e. precision) i.e. its ability to give consistent readings, characteristic of the individual patient. Above all, the more reproducible the technique, the narrower the normal range is likely to be and, therefore, the greater the sensitivity with which abnormalities will be detected. In dogs the preferred clinical technique for blood pressure measurement is now the use of the DINAMAP oscillometric monitor with an appropriate-sized tail cuff and at least six readings; the first reading is discarded and the remaining five are meaned. Outliers (which are not usual since the machine has internal controls for artefacts) are discarded. The dog should be standing comfortably, not forced into recumbency, limb cuffs should only be used in conscious dogs where a tail reading is unobtainable - usually in shortdocked individuals. This technique has been validated and calibrated against direct arterial pressure in both anaesthetised and conscious dogs8,9. When the same technique is used in humans, rather than the usual general practitioner’s approach of using a single reading, much greater precision is obtained3. This is hardly surprising, granted that the first reading probably serves simply to properly “bed” the cuff into place. The use of a tail cuff in conscious dogs offers the greatest precision and compliance in the majority of dogs hence its use is preferred in our standard technique to the proximal fore limb cuff site, the best limb site in conscious dogs. Readings are best taken in standing rather than recumbent dogs, because of far better compliance and reduced stress9.

Blood pressure in normal dogs In healthy dogs, systolic pressure depends on age, breed, sex, temperament, diet, obesity and exercise regime7. The rise with age is particularly interesting since it is characteristic of species, such as humans and dogs, which customarily consume excessive dietary salt10,11. Recently Sansom and Bodey (1998) have observed a similar age-related rise in cats (Vet. Rec. In Press). In dogs average pressure (± SE) rises from 108 ± 2.2 below 6 m, to 121 ± 1.6 by one year, to 130 ± 1.3 by 4 years, 141 ± 2.3 by 10 years, 145 ± 2.5 by 13 years and may continue to increase to 153 ± 6.2 though in older dogs, as in very old humans, pressure may fall. Two recent surveys of British dogs (Edney12 and Michell13) suggest that the average age at death is 13, with substantial breed variation. Heart rate also varies with breed, though the usual assumption that smaller breeds have higher rates in unreliable7.

Hypertension in dogs Essential (primary) hypertension is rare in dogs, though an interesting genetic model exists1. The main causes of hy-

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Renal disease and canine hypertension Although dogs are susceptible to hypertension, they are naturally resistant to it, even when renal function is severely comprised. Thus among dogs with reduced GFR the prevalence of hypertension was little higher (9%) than among dogs with normal GFR (6%). Dogs with GFR less than 33% of the normal lower limit (with an average GFR equivalent to 10 ml/min in a 70 kg human) had arterial pressures not significantly above normal, and these dogs showed no correlation between GFR and arterial pressure17. In humans, once GFR falls below 33% of normal (40 ml/kg) the majority are hypertensive; these data were obtained from 310 patients who were normotensive prior to their renal disease18. A recent study of 1795 humans with chronic renal disease found a significantly higher prevalence of hypertension among patients with glomerular disease19. As GFR declined, the prevalence of hypertension rose from 66% at 83 ml/min (b normal) to 95% at 12 ml/min (10% of normal). It is therefore sad to find the continued repetition of the myth that hypertension is a common complication of canine renal disease, combined with an absurd defining threshold of hypertension for all breeds (180/100) and advocacy of the use of ACE-inhibitors without warning of their ability to worsen renal function in a minority of patients20. In the absence of measured hypertension (compared with breed normals), using the standard technique, or of signs of hypertensive organ damage (e.g. retinopathy), it would be negligent to treat dogs with CRF for an assumed hypertension. The most likely effect of lowering a normal arterial pressure in a dog with CRF would be to decompensate what remains

of its renal function. The evidence is clear and, in the interests of welfare, it is time that we treated the CRF that is present in the dogs rather than the hypertension prevalent in the textbooks.

References 1.

2. 3.

4. 5.

5a.

7. 8.

10. 11. 12.

13. 14.

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16. 17. 18.

19.

20.

Bovee, K.C. (1993) Genetic essential hypertension in dogs: a new animal model. In: “The Advancement of Veterinary Science” Vol. 4. Ed. A.R. Michell, C.A.B. International, Wallingford. pp 185-194. Michell, A.R. (1997) Long-term control of blood pressure and sodium balance: is the baseline nocturnal? Perspec. Biol. Med. 40: 516-528. Michell, A.R. (1996) Routine blood pressure measurement: application of the standard canine technique in a human. Blood Pressure Monitoring 1: 385-387. Michell, A.R. (1993) Hypertension in companion animals. Vet. Ann. (Bailliere) 33: 11-23. Vincent, I.C., Michell, A.R. and Leahy, R.A. (1993) Non-invasive measurement of arterial blood pressure in dogs: a potential indicator for the identification of stress. Res. Vet. Sci. 54: 195-201. Kallet, A.J., Cowgill, L.D. and Kass, P.H. (1997) Comparison of blood pressure measurements obtained in dogs by use of indirect oscillometry in a veterinary clinic versus at home. J.A.V.M.A. 210: 651-654. Vincent, I.C. and Michell, A.R. (1996) Relationship between blood pressure and stress-prone temperament in dogs. Physiol. Behav. 60: 135-138. Bodey, A.R. and Michell, A.R. 91996) Epidemiological study of blood pressure in domestic dogs. J. Sm. Anim. Pract. 37: 116-125. Bodey, A.R., Young, L.E., Bartram, D.H., Diamond, M.J. and Michell, A.R. (1994) A comparison of direct and indirect (oscillometric) measurements of arterial blood pressure in anaesthetised dogs using tail and limb cuffs. Res. Vet. Sci. 57: 265-269. Bodey, A.R., Michell, A.R., Bovee, K.C., Buranakurl, C. and Garg, T. (1996) Comparison of direct and indirect (oscillometric) measurements of arterial blood pressure in conscious dogs. Res. Vet. Sci. 61: 17-21. Michell, A.R. (1989) Physiological aspects of the requirement for sodium in mammals. Nutr. Res. RCVS. 2: 149-160. Michell, A.R. (1995) “The Clinical Biology of Sodium”. Elsevier, Oxford. Edney, A.T.B. (1997) An observational study of presentation patterns in companion animal veterinary practices in England. D.Vet.Med. Thesis, Univ. of London. Michell, A.R. (1998) Breed differences and other factors influencing canine longevity (Vet. Rec., submitted). Muirhead, E.E. (1994) Renal vasodepressor lipid:medullipin in: ‘Textbook of Hypertension’ Ed. J.D. Swales, Blackwell Scientific, Oxford pp 341-359. Michell, A.R. (1988) Renal function, renal damage and renal failure. In: ‘Renal Disease in Dogs and Cats: Comparative and Clinical Aspects’. Ed. A.R. Michell, Blackwell Scientific, Oxford. pp 5-29. Michell, A.R. (1994) Salt, Hypertension and renal disease: comparative medicine, models and real diseases. Postgrad. Med. J. 70: 686-694. Michell, A.R., Bodey, A.R. and Gleadhill, A. (1997) Absence of hypertension in dogs with renal insufficiency. Renal Failure 19: 61-68. Buckalew, V.W., Berg, R.L., Wang, S.R., Porush, J.G., Ra. S. and Schulman, G. (1996) Prevalence of hypertension in 1795 subjects with chronic renal disease: the modification of diet in renal disease study baseline cohort. Am. J. Kidney Dis. 28: 811-821. Danielsen, H., Kornerup, H.J., Olsen, S. and Posborg, V. (1983) Arterial hypertension in chronic glomerulonephritis. An analysis of 310 cases. Clin. Nephrol. 19: 284-287. Henik, R.A. (1997) Systemic hypertension and its management. Vet. Clin. N. Am. (Sm. Anim. Pract) 27: 1355-1372.

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pertension - in the sense of a pressure significantly above the normal mean - were, in order of importance, hyperadrenocorticism (155.84 ± 4.4), hepatic disease (152.7 ± 7.6), thyroid dysfunction (142.7 ± 3.3), diabetes mellitus (142.6 ± 3.9), renal disease (140.5 ± 3.0), cardiac disease7. The link with hepatic disease, though seen in only a small number of dogs is interesting because it has not yet been reported in humans, it could perhaps reflect reduced hepatic activation of a renal vasodepressor hormone called medullipin11,14. As a percentage of the normal population, the dogs with these conditions (other than cardiac disease) were few (11.6%). The average age ranged from 7.2 (renal disease) to 10.3 (diabetes) for which the corresponding normal systolic pressures were 133.2 ± 1.8 and 140.2 ± 2.6. The average pressure and age for all normal dogs was 131.3 ± 0.6, 4.4 years. Thus while renal disease raises average pressure beyond the expectation for age, the question remains whether it is an important cause of canine hypertension. Our underlying hypothesis was that dogs were resistant to hypertension, even when they have renal disease15,16 and this proved to be the case17.

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The most common viral, bacterial and parasitic diseases of ornamental fish Massimo Millefanti

I have often wondered why so few veterinarians in Italy are interested in tropical fish medicine. While approximately 15 million cats and dogs give work to several thousand professionals, almost 30 million fish used for ornamental purposes, be they tropical, salt water or freshwater, or cold water fish, stimulate the interest of only a few score of veterinarians. There are, of course, many reasons some of which I list here: • Fish live in water in structures specifically prepared for them (aquaria, artificial lakes) and while the owner can see them he does not come directly into contact with them. He cannot stroke them nor take them for a walk as he could do with his dog, cat, ferret, rabbit etc. Nor can he hear their voice as he could do with his canary, mynah, parrot or other pet bird. It is extremely uncommon that fish are given names. In the majority of cases the relationship between the owner and a pet fish is fairly impersonal. A fish is usually considered as part of the furniture and if it dies, it can be replaced without great sadness or difficulty. This indirect relationship is also the reason why the aquarium lover frequently fails to realise that his fish has an active disease and this has the consequence of delayed diagnostic and therapeutic interventions by a veterinarian. • The majority of freshwater tropical fish are extremely cheap while the cost of a consultation by a professional, who must obviously be paid, is often much greater than the commercial value of the patient to be cured. Due to difficulty in capturing and transporting fish, it is often the veterinarian who must go to the structure housing the sick fish, thus further increasing the cost of the consultation. • The educational programme which leads to a degree in veterinary medicine covers this particular sector only partially and cursorily. The newly qualified veterinarian finds that he must deepen his knowledge in a sector in which he is almost totally ignorant unless he has had a particular interest in aquarium medicine. This may, in fact, be one of the reasons why many experts in aquariological sciences have degrees in subjects other than veterinary medicine. • Since there are still no veterinary clinics, at least in Italy, which care for ornamental fish, numerous owners do not know that in many cases their own sick animals could be easily cured by appropriate, simple and cheap treatment. • Finding pharmacological remedies to use for therapy is often not easy. The use of drugs which must be diluted and the sometimes complicated calculations of the therapeutic doses often discourage an owner from starting treatment of his fish.

• A veterinarian is often called after other people have already given suggestions on what to do. This means the fish to be treated are often debilitated by their disease and, sometimes, their clinical signs have been altered or indeed provoked (poisoning) by the attempted therapies. • Objectively it is sometimes extremely difficult to carry out a treatment. I am thinking, for example, of the large marine aquaria containing, besides fish from the coral reef, many delicate invertebrates and rocks which create cavities in which the patient can easily hide. It is not a simple task to extract one or more sick fish in order to place them in a nursing tank and furthermore the stress and possible lesions that we ourselves could provoke during the capture, must be carefully evaluated. • Many aetiological agents of the common infective and infestive diseases of aquarium fish cannot be found on their host, because they leave it rapidly, immediately after the death of the fish. The process of decomposition of the delicate tissues of a dead fish, if this is left even for a few minutes in a tropical aquarium, begins very quickly and can make the findings difficult to decipher. Freezing a dead fish is of no post-mortem diagnostic help. There are, however, many reasons why the organisers of this veterinary medicine congress have included a section of the programme devoted to ornamental fish. Let us now have a look at some of these: • Many owners (especially young owners) of ornamental fish, particularly goldfish (Carassius auratus) believe that while their animal must live in captivity it has the right to do so in a state of wellbeing and must, therefore, be cared for as well as possible, including care from a veterinarian. • Many ornamental fish of incomparable beauty, for example some kinds of koi (Cyprinus carpio) or discus (Symphysodon discus), now have a commercial value of up to several thousand euro. In these cases the aquarium lover needs regular and qualified assistance from a veterinarian. • When active collaboration has been set up between professionals and importers of exotic fish, particularly as far as concerns prophylaxis of common bacterial, viral, protozoal and parasitic diseases, true fish lovers can acquire healthier fish. • Some zoonoses can be carried by tropical fish and the role of the veterinarian in this field is of paramount importance. One example of this problem is the transmission of myocbacteriosis from fish to immunodepressed humans. • New viruses are being isolated from captured sea fish which

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are then raised as ornamental fish. The potential pathogenicity of these viruses for humans is not yet known. In this case, too, the veterinarian can be directly involved in studies. • In the light of the foregoing, associations which study the science of aquaria ever more frequently require the collaboration of a veterinarian. Before describing, albeit briefly, the main infective and infestive diseases of aquarium fish, it is worth remembering how important it is that the veterinarian who wishes to take care of these animals has a basic knowledge of the anatomy, morphology and biology of the various imported species (and there are very many!), knowledge of the legislation concerning their importation, sale and conditions of captivity and knowledge about the management and function of the various types of aquarium available in shops, from importers or enthusiasts. Aquaria are often incorrectly maintained and the management of the animals within them poor. This is frequently because the owner of an aquarium has not understood the technical details of the filtering or lighting systems or has no knowledge of the biology of the species in captivity. Many diseases are associated with the presence of toxic catabolic substances produced by the fish themselves within the aquarium and could be easily resolved once the cause is understood (overcrowding, exposing the aquarium to direct sunlight for many hours a day, excessive amount or incorrect type of food administered, no control of the filtering system, etc.). A period of quarantine in specifically designed tanks for tropical freshwater fish, particularly if the fish come from the Asian market or are captured sea fish, can be the best weapon for preventing the spread of the infective or infestive diseases which are becoming ever more frequently diagnosed. Cultivating aquatic plants which release natural bacteriostatic substances or which enhance the filtering of the water (for example, the water hyacinth) and giving food containing natural polysaccharides (glucans) extracted from the cell walls of some algae and yeasts which can improve the immune defenses of the reared fish, are useful strategies for preventing diseases which are commonly encountered in every day veterinary practice.

VIRAL DISEASES The best known viral disease of ornamental fish, because of its unmistakable feature, is lymphocystis or lymphocystis virus infection. This disease is caused by an iridovirus and is commonly found in sea fish (eg marine angelfishes) as well as some freshwater fish such as the Asiatic belontiidae (bettas, paradisefishes and gouramis). The disease can be recognised easily; there are small pearl-like whitish or brownishgrey nodules which may be present in groups on the fins and, but less frequently, on the body of the sick fish. The fish may have lost weight and have a fluctuating appetite. This disease is stress-related: indeed it is predominantly found in sea fish captured from the coral barrier reef, imported and then subjected to various changes of food and environment during the transport from importer to buyer. Once the fish with lymphocystis has been transferred to

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a nursing tank, the nodules can be gently removed. Recurrences, however, are frequent. Papillomata due to herpes viruses can be diagnosed in goldfish, koi and sea fish. They present as predominantly greyish-white nodules with a characteristic cauliflower appearance, localized to the head or fins of the ill fish. Viral septicaemic disease or “spring viraemia” is a disease caused by Rhabdovirus carpio. The disease is very common among cyprinides reared for ornamental purposes, for example koi and goldfish. In this case, too, stress (that is, an increase in water temperature or the reproductive period) can favour the onset of the disease in aquaria but particularly in artificial lakes. The phisical examination reveal ocular, gill and skin haemorrhages, cutaneous changes, and (pathologie anatomy) bleeding in the internal organs (intestine, swimbladder) of the sick fish. It is often associated with haemorrhagic bacterial septicaemia which will be described later in this article.

BACTERIAL DISEASES I shall start with the common haemorrhagic septicaemia (or goldfish ulcerative disease) of cyprinides, caused by bacteria such as Aeromonas spp., Pseudomonas spp. and others, which can be associated with a Rhabdovirus infection. Haemorrhagic septicaemia can occur in other exotic freshwater fish, besides cyprinides, for example mollies, gouramis and some cichlids. This disease produces many clinical signs including ascites (gelatinous, yellowish fluid), exophthalmos, ulcers, skin haemorrhages, erosions of the fins and pale gills with puntiform haemorrhages. The treaments of choice are nitrofuranic baths (eg. nitrofurazone at a dose of 10 mg/l for 6 hours for 5-7 days) or oral furazolidone (administered in food) for 7-10 days. Personally, I have had excellent results in goldfish living alone in simple bowls without filtering systems, for example fish bought or won at fairs or markets, using a one week cycle of daily 4-5 hour baths of solutions of sulphamethoxazole and trimethoprim at doses of 50 and 10 mg respectively per litre of water. Columnaris disease, caused by the Flexibacter (ex Chondrococcus) columnaris bacterium, is very widespread particularly in mollies (eg black molly), cyprinides and young cichlids. The clinical signs are small whitish spots which, over a few hours, coalesce to form raised mucus-rich areas (indeed another name for this disease is “cotton wool disease”) at the mouth and caudal parts of the fish. The treatment is oxytetracycline baths (10-50 mg/l) for 1 hour a day for one week. The last bacterial disease I would like to mention is mycobacteriosis (or fish tuberculosis). This disease is caused by Mycobacterium fortuitum, M. marinum and M. chelonei and can affect both freshwater ornamental fish and salt water fish. A fish with mycobacteriosis loses weight and is lethargic and anorexic. It can have exophthalmos, ascites, skin ulcers and sometimes deformation of the dorsal profile. Post-mortem examination reveals greyish-white nodules in the liver, spleen, kidneys and heart. Ziehl-Neelsen stain-

ing of histological preparations of these organs confirms the presence of mycobacteria. Fish tuberculosis is a chronic disease which can also be very dangerous for immunodepressed humans who come into contact with the water from aquaria containing fish affected by the disease. When mycobacteriosis is suspected (that is when a fish with symptoms similar to those just described is refractory to the most common antibiotic therapies) it is worth confirming the suspicion by a post-mortem examination. Since this bacterium is acquired through the gastrointestinal tract, a period of quarantine and correct alimentation with hygienically safe food should prevent the onset of this zoonosis.

PROTOZOAL DISEASES These are the most widespread and well known diseases to affect fish reared for ornamental purposes. One protozoal disease which affects all freshwater fish is “ichthyophthiriosis” or “white spot” or “ich”, caused by a ciliated protozoon: Ichthyophthirius multifiliis. The diseased fish presents with small raised whitish spots all over the body and on the fins and continues to rub against objects in the aquarium because of the pruritic symptoms. The protozoon, with its typical main horseshoe shaped nucleus, is an excellent swimmer, which penetrates the epidermis of the fish with circular movements provoking a cellular reaction manifested by the white spot. The pharmacological treatment used (for example zinc free green malachite at a dose of 0.1 mg/l poured directly into the aquarium) acts only on the free forms swimming in the aquarium before they enter the fish or form reproductive cysts. Cryptocarion irritans causes a disease similar to the one I have just described but different in that it affects salt water fish. Besides the disseminated spots on the body and fins, the diseased fish has characteristic opaque eyes and respiratory distress because the protozoa also invade the gills. Treatment with copper sulphate (0.15-0.20 mg/l) for at least one week is usually effective. It must be remembered, however, that these concentrations of copper sulphate are fatal for invertebrates and toxic for many fish from the chaetodontidae (butterflyfishes) and pomacanthidae (marine angelfishes) families. Amyloodinium ocellatum (sea fish), Oodinium pillularis and O. limneticum (freshwater fish) are dynoflagellate protozoal aetiological agents of the velvet diseases or oodiniasis of ornamental fish. Fish with these diseases have changes in skin colour, lose weight, are anorexic, have pruritus, breathing problems (they go to the column of air bubbles in the tank) and opaque eyes. The skin takes on a characteristic velvety appearance which can be seen easily if the fish is examined in an oblique light. The treatment is similar to that advised for the “white spot”. The protozoon (sporozoon) Pleistophora hyphessobryconis, which is transmitted through the gastrointestinal tract (cannibalism) causes pleistophoriasis in neon tetra

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(Paracheirodon innesi) but also in other small cypridins and exotic freshwater fish. Neon tetra disease is a chronic disease with a very slow evolution. The signs are weight loss, appetite changes, erratic swimming and changes in skin colour. The superb redblue colour of neon fish progressively fades giving room to whitish marks with poorly defined, irregular margins. There is not yet an effective treatment for this common disease. “Hole in the head” disease is nowadays considered a multifactorial disease. The hypothesis that the primary (or only) aetiological agent is a protozoon is now being challenged by some researchers. The disease is characteristic of South American cichlids such as the discus, angelfish (Pterophyllum scalare) and oscar (Astronotus ocellatus) but can also be found in African cichlids. The sick cichlid has skin erosions of the head, above the eyes, covered with whitish mucus from which it is sometimes, but not always, possible to isolate protozoa of the Spironucleus and Hexamita genera. Other signs are weight loss, appetite changes, cloacal oedema and mucus in the faeces. Quarantine and correct care (avoiding stress) of these splendid fish remain the best strategies for prevention of the disease. The recommended treatment is metronidazole baths (1020 mg/l) for 3 days. Other commmon protozoal dermatitides caused by Ichthyobodo (ex Costia) necatrix, Chilodonella cyprini, Cycloachaeta spp. (ex Trichodina), Brooklynella hostilis (treatment: green malachite) and myosites due to Myxobolus spp (for which there is no therapy) can be diagnosed. Further details of these diseases can be found in the works listed in the references at the end of this article.

PARASITIC DISEASES Trematodes of the Dactylogirus genus, transparent organisms less than a millimetre long, can infest the gills and skin of many freshwater fish, particularly goldfish and koi. Affected fish swim erratically because of pruritus, have threads of mucus on the gills and laboured fast respiration with the opercula raised. Microscopic examination of the mucus confirms the suspected diagnosis. Small leaf-shaped trematodes of the Gyrodactylus genus preferentially affect cichlids and sea fish. These flukes predominantly localize in the skin causing increased secretion of skin mucus and ulcers from pruritus and predispose to secondary bacterial infections (erosion of the fins). The treatment is baths of praziquantel (10 mg/l) for 3-5 hours or nitroscanate (0.1 mg/l) 2 or 3 times each week for the Dactylogirus infestation because this worm (in contrast to Gyrodactylus which is ovoviviparous) reproduces by laying eggs in the water. The Camallanus cotti nematode infests many exotic freshwater fish (eg tetras, characins and mollies) and more rarely sea fish. These reddish parasites, which are just over one centimetre long, live firmly anchored to the colonic mucosa of the unfortunate host fish and emerge from the anal opening.

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The treatment of choice for this parasitic disease are fenbendazole administered in food (0.25% or 250 ppm) or in aquarium water (2 ppm) as initial therapy followed by another dose 2-3 weeks later, or baths of nitroscanate (0.5-1 mg/l) for 4-5 hours once a week for 3 to 4 weeks. Lernaea cyprinacea is a copepod crustacean known as the “anchor worm”. It reaches a maximum length of 2 cm. While the male lives free in the water, the female of the species attaches to the gills and skin of freshwater fish (particularly goldfish, koi and cichlids) using a peculiar cephalic structure. The female also has two yellowish ovigerous sacs at her caudal extremity which make diagnosis easy. Fish affected by lernea infestation have respiratory difficulties (raised opercula) because of the abundant mucus in the gills, intense pruritus and secondary bacterial infection (skin ulcers and fin erosion). This disease can be cured by baths of sodium chloride (23 g per litre) for 3-5 minutes for 3 days or with formalin, which is a 37% solution of formaldehyde (0.2 ml per litre of water in a nursing tank), for one hour for 3 consecutive days. If this parasitic disease is ignored, during the summer it can decimate the fish population in a lake within a few days. Finally, I shall finish this brief, schematic list of the common diseases of ornamental fish with the infestations by Argulus spp. These are small crustaceans, 5-6 millimetres long commonly called fish lice. They can be removed from the skin of their hosts, which are preferentially goldfish and koi, by gently using tweezers. The skin is then disinfected with a solution of iodopovidone (1:10). There is a

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fish, Gambusia affinis (mosquitofish), which eats these crustaceans and can live in freshwater aquaria, that can be used to eliminate the disease. I would like to thank my colleagues Laura Torriani, Roberto Granata, Giuseppe Mosconi, Alessandra Cappelletti and Elena Ferlini for their invaluable help.

References 1) 2) 3) 4) 5)

6) 7) 8) 9) 10) 11)

Buchter R.L., (1992), Manual of Ornamental Fish, BSAVA Cheltenham. Carpenter J.W., Mashima T.Y., Rupiper D.J., (1996), Exotic Animal Formulary: Fish, 13-29, Greystone Publ. Manhattan Kansas. Herkner H., (1995), Zierfishe in Krankheiten der Heimtiere: 893-926, Schlütersche Hannover. Millefanti M., (1996), Le malattie dei Pesci d’Acquario, De Vecchi Editore Milano. Mosconi G. (1994), L’insorgenza delle Malattie nei Pesci Ornamentali in Atti del Corso SCIVAC di Medicina degli Animali Esotici: 15, SCIVAC Cremona. Noga E.J., (1995), Fish Disease: Diagnosis and Treatment, Mosby Saint Louis Missouri. Scott P.W., (1991) Ornamental Fish in Manual of Exotic Pets: 272285, BSAVA Cheltenham. Stoskopf M.K., (1993), Fish Medicine, W.B. Saucers Philadelphia. Untergasser D., (1991), Malattie dei Pesci d’Acquario: Diagnosi e Trattamento, Primaris Milano. Zupo V., (1990), le Malattie dei Pesci: come identificarle e curarle in acquario, Ed.Olimpia Firenze. Zwart P., (1992), Diseases Aspects in Ornamental Fish in XVII° WSAVA World Congress Proceedings, Volume I°: 733-736, A.Delfino Editore Roma.

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Alternatives in the treatment of coxarthrosis in dogs: pectineomyectomy, tenotomy of the iliopsoas and neurectomy of the joint capsule (PIN) as a symptomatic treatment for coxarthrosis Pierre M. Montavon

Summary

Technique

Abduction and extension of the hip are reduced in patients with coxarthrosis. Contracture of the pectineus muscle and pressure of the tendon of the iliopsoas over the inflammed joint capsule is painful and reduce the abduction and extension of the hip joint, respectively. Pectinectomy and tenotomy of the iliopsoas result in clinical improvement of the function of the hip joint. Neurectomy of the ventral aspect of joint capsule is aimed at reducing pain for a durable period of time. This symptomatic therapy is relatively simple and can be performed bilaterally. It also allows later insertion of a hip prosthesis. Clinical results are satisfactory.

Knowledge of the local anatomy is required to perform this technique. Important structures in the vicinity are to be respected, such as arteria and vena femoralis with their branches, and the obturatorius and saphenous nerves. Skin incision in form of T facilitates the overview and approach of the deep structures in the proximal area of the wound. First, the pectineus muscle is prepared, transsected and resected, applying exact hemostatic techniques. Care is taken of the obturatorius nerve located caudal to the origin of the pectineus muscle. The arteria and vena femoralis profunda are preserved during the proximal transsection of the pectineus muscle and the femoral vessels, including the arteria and vena femoralis caudalis during its distal transection (Figure 1). The pectinectomy discovers the iliopsoas muscle proximal to its insertion onto the trochanter minor which is palpable over the caudal edge of the proximal femur. The arteria and vena femoralis profunda are retracted proximally over the joint capsule of the hip. The tendon of the iliopsoas is searched from dorsal and under the iliopsoas muscle as this is retracted in a distal direction. The tendon acts as a string in immediate contact with and pressing strongly over the medial joint capsule of the hip. It is retracted in a dorsal direction, over the capsule with the help of a curved instrument such as a mosquito or Hohman retractor (Figure 2). Its transection with a blade liberates the joint capsule of the hip

Coxarthrosis results from instability of the hip joint in dogs. This degenerative disease is present bilaterally most of the time and leads first to synovitis in younger growing animals (6-12 months of age). Patients may then experience acute pain. Afterwards, the symptoms are reduced and affected dogs are able to compensate. Later, chronic coxarthrosis with joint deformation takes place. Typically, one side is more affected than the other. Concommittant degenerative processes may develop to the spine or the stifle joints in older patients. Pain leads to lameness associated with contracture of local muscular groups, resulting in decrease of the functional range of motion of the affected hip joint. The abduction and extension of the hip is reduced and painful. The medial aspect of the hip joint may be sensitive upon palpation and contracture of the pectineus muscle is sometimes evident. Pectinotomy1 and pectinectomy2 have been successful to reduce the pain in coxarthrotic patients. The results have been attributed to the decrease of the degree of hip subluxation, hence reduced tension on the inflammed joint capsule. This intervention did not improve the degree of extension of the affected hip joint. The ventral aspect of the hip joint capsule is associated to the pain in presence of dysplasia. This area is under the greatest load during subluxation of the hip4, and receives a substantial innervation5. The technique presented here uses an iliopsoas tenotomy and ventral neurectomy under visualization in adjunction to the pectinectomy for treatment of coxarthrosis3. This results in durable pain free and improved hip joint extension, in addition to the effet of a classical pectinectomy.

Figure 1 - Pectineus muscle transection, medial view.

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Figure 2 - Iliopsoas tenotomy, medial view.

Figure 3 - Neurectomy of the ventral capsule of the hip joint, medial view.

and improves the extension of the joint. Partial neurectomy of the joint capsule is achieved while preparing carefully its ventral aspect with a periosteal elevator, attempting to severe innervation from the obturatorius nerve ventrocaudally and from the femoralis nerve ventrocranially (Figure 3). After control of the hemostasis, the superficial layers of the wound are only closed in interrupted fashion.

older dogs with concommittant problems. Economical reasons may also lead to the choice of such surgical technique.

Results This intervention can be performed bilaterally simultaneously. The use of this technique in 52 patients has been reported3. The results have been positive, improving immediately and durably the fonction of the operated hip joints to the satisfaction of the owner of the animal. No side effects have been observed. This intervention leaves the possibility for the insertion of hip prostheses at a later date. Its indication is optimal in immature dogs affected bilaterally and in

Literature 1.

4. 5.

Wallace L.J.: Clinical investigations and surgery on the pectineus muscle and its relationship to canine hip dysplasia. In: Scientific Proceedings AAHA, 38th Annual Meeting, Las Vegas: 384, 1971. Richard D.A., Hinko P.J., Morse E.M.: Pectinectomy vs. pectinotomy in the treatment of hip dysplasia. Vet. Med. Small Anim. Clin. 67: 976, 1972. Ballinari U., Montavon P.M., Weiss R.: Die Pectineusmyektomie, Iliopsoastenotomie und Neurektomie (PIN) als symptomatische Therapie bei der Coxarthrose des Hundes. Schweiz. Arch. Tierheilk. 137: 251, 1995. Gardner E.: The innervation of the hip joint. Anatomical Record 101: 353, 1948. Peterson H.A., Winkelmann R.K., Coventry M.B.: Nerve endings in the hip joint of the cat: their morphology, distribution and density. J. of Bone and Joint Surgery 64: 333, 1972.

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Uncemented canine totale hip prosthesis: development and clinical application Pierre M. Montavon

Short summary A cementless total hip prosthesis with screw fixation was developed at the University of Z端rich for treatment of coxarthrosis in dogs. It has been used in over 60 clinical patients with excellent surgical success rate and clinical results. The results with now the longest follow up over 4 years are characterized by absence of: pelvic nerve damage, long term luxation and infection. The procedure is reproducible and lasts less than 2 hours with a trained operating team of 3 persons.

The hip joint is approached performing a craniolateral approach on the dog in lateral recumbency. A T-shaped capsulotomy is made along and at the base of the neck. A burr is used for the excision of the femoral head and neck, reducing the creation of stress riser areas and optimizing the preparation of the proximal femur for insertion of the femoral component. Preparation of this area with a special rasp, acting also as a template, is necessary until the entire instrument can be introduced, granting insertion of the femoral component of the prosthesis. The femur is then maintained caudally with the help of a Mayo retractor and the joint capsule is retracted with finger Meyerding retractors.

Cemented hip prosthesis has been successfully applied for total hip joint replacements in dogs since 15 years1. Several designs have been later introduced2, 3. Cementless prostheses have also been studied based on the press fit principle4, 5. A cementless total hip prosthesis was developed at the University of Z端rich (Figure 1). The goals were: 1) to reduce the risk of nerve damage 2) to diminish the operative infection rate 3) to decrease the possibility of postoperative luxation of the prosthesis 4) to simplify the technique and make acceptable to any well trained orthopedic surgeon, and 5) to allow surgery of revision when necessary. Twelve consecutive cases treated with the last generation of this prosthesis are presented here, in the light of 49 cases operated using the evolving designs of the same prosthesis.

Technique - Prosthesis, instrumentation and implantation After experimental and clinical testing, three different sizes of prostheses resulted, using 3, 4 or 5 screws. This fixation guarantees primary and long-term stabilization of the prosthesis (Figure 1). Titanium-aluminium-vanedium alloy is used for all metal components. The stem of the femoral component is anchored endosteally by a monocortical screw fixation to the medial cortex alone. Screws are inserted blind through access holes in the lateral cortex with the aid of a drill guide fixed to the stem. Tapered heads of the self-tapping screws lock in the matched holes of the stem.

Figure 1 - Cementless total hip prosthesis with screw fixation.

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The acetabulum is now prepared using a reamer of fitting size, until the subchondral layer has been exposed. The cavity is cleaned of any soft tissue remnants and osteostyxis in the caudal and cranial areas of the acetabulum is performed with a drillbit mounted on oscillating device. This reduces the risk of trauma of the nerves present on the medial aspect of the hemipelvis (i.e. sciatic nerve). Hemispherical acetabular cups have an ultra high molecular weight polyethylene insert within a perforated titanium alloy shell, designed to improve osseointegration. They exist in four sizes: 26, 29, 32 and 36 mm outer diameter. The cup mounted on an inserting device is then positioned into the acetabulum. The edge of the ventral half of the cup should match the cranial, ventral and caudal border of the prepared acetabulum. The cup is then hammered down. A hole is drilled in oscillating fashion through the hemipelvis, originating at the central hole of the acetabular cup. A 4 mm cancellous titanium bone screw is positioned for the fixation of the acetabular cup. A guide is fixed onto the femoral component. Both are positioned in slight anteversion (15Â°) after insertion. The use of drill inserts allows exact blind positioning of the holes for the screws into the cortices. Oscillating device placed on the drill machine and the use of three lips drill bits reduces the soft tissue trauma, when exiting the medial cortex of the femur while drilling. The screws are self-tapping and their conical heads lock into the holes of the femoral component. This results in a stable unit consisting of the femoral shaft of the prosthesis and of the screws after their placement in the medial cortex. Once the femoral component is fixed to the femur, the guide is removed. The femur is then moved in a physiological fashion and the distance between the femoral and the acetabular component is evaluated. Femoral head and neck components exist in three sizes of lengths for the neck: 5, 10 and 15 mm. The minimal estimated length is first positioned over the conical peg of the femoral component already in place. The prosthetic joint is reduced with the help of special retraction three positions are tested for impingement and possibility of

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luxation within the physiological range of motion: 1) abduction to test the clearance between medial greater trochanter and the dorsal edge of the cup, 2) outward rotation of the hip with flexed stifle at 90Â° for craniodorsal luxation of the prosthesis and, 3) full flexion and inward rotation of the hip for caudoventral luxation of the prosthesis. In presence of any problem, the prosthesis has to be tested with the next superior neck length, until the prosthesis is judged stable. Impingement of the caudal fibrous joint capsule may be carefully removed with a rongeur (cave: sciatic nerve). If instability of the prosthesis persists, the acetabular screw has to be removed and the cup repositioned in order to cover the area of luxation. After copious flushing, the joint capsule is closed with 2 or 3 far-near-far-near stitches, with synthetic resorbable material (size 2-0). Fasciae, subcutaneous layers and skin are closed in appositional fashion.

Results The range of motion of the prosthesis is greater than the physiological range. Success rate of the surgery and clinical results are excellent. The technique is reproducible. Its duration is less than 2 hours, requiring ideally the presence of 3 persons at the table. Patients recover a normal gait within 46 weeks. If necessary, the second side can be operated after an interval of 8 weeks.

Literature 1.

2. 3. 4.

Olmstead M.L., Hohn R.B., Turner T.M.: A five year study of 221 total hip replacements in the dog. J. Am. Vet. Med. Assoc. 183: 191, 1983. Olmstead M.L.: The canine cemented modular total hip prosthesis. J. Am. Hosp. Assoc. 31: 2, 109, 1995. Bardet J.F., Letournel E.: ProthĂ¨se totale de la hanche chez le chien. Pract. Med. Chir. Anim. Comp. 30: 555, 1995. De Young D.J. et al.: Implantation of an uncemented total hip prosthesis. Technique and initial results of 100 arthroplasties. Vet. Surg. 21: 168, 1992.

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The modification of the Slocumâ&#x20AC;&#x2122;s technique for the repair of cruciate ruptures Pierre M. Montavon

Short summary A modified tibial plateau leveling osteotomy technique is presented, combined with the creation of an aponeurotic fascial sling cranial to the proximal tibia. With this method, partially torn cranial cruciate ligament can be preserved. It is characterized with very good surgical success rate and postoperative results. Radiographic follow-up shows practically no further postoperative evolution of gonarthrosis.

The craniocaudal slope of the tibia plateau leads to cranial tibial thrust of the tibia under compression1. The technique of leveling of the tibia plateau for deficit of the cranial cruciate ligament has been described2 and successfully applied in large populations of clinical patients. A modification of the technique is described here3. Its combination with the creation of an aponeurotic sling cranial to the proximal tibia with the medial and lateral fasciae during closure of the surgical wound4 gives very good results. The goals of the modification of the technique presented here are: 1) to make the surgery possible in any size of dogs; 2) to preserve the tibial insertion of the medial collateral ligament of the stifle intact; 3) to make the osteotomy and its fixation with readily available instruments and implants and 4) to stabilize the persisting cranial drawer sign of the tibia in order to avoid later meniscal damage.

Technique A lateral approach to the stifle joint is performed with parapatellar incision of the biceps fascia from proximal to the patella until the middle of the tibia. The fascia is then freed up and prepared. Lateral arthrotomy allows exploration of the stifle joint. Routine cleaning up of the joint is performed. Partially ruptured anterior cruciate ligament5 is left intact, removing only the torn parts. A parapatellar incision of the pes anserius is then made medially, from proximal to the patella to the middle of the tibia. It is prepared and freed up, especially in the area of the medial femoral condyle4. The joint capsule is also opened on the medial aspect of the stifle joint. The retropatellar fat pad is then totally excised, respecting the cranial aspect of the menisci as well as the bursa located on the tibial tuberosity under the patellar

ligament. The insertion of the cranial tibialis and peroneus longus muscles are elevated from the fossa extensoria and the tendon of extensor digitalis longus is freed up from the sulcus extensorius. Those structures are retracted caudally. A transverse hole is then drilled through the tibia from its caudomedial aspect. The hole is located below the insertion of the medial collateral ligament of the stifle. It is the basis of an angle of 20Â°-25Â° placed between the cranial aspect of both menisci caudally, and the bursa of the patellar ligament located at the proximal extremity of the tibial tuberosity cranially (Figure 1). A template is helpful to first set landmarks over the medial tibial cortex. A transversal wedge defined by this angle is then osteotomized in the proximal tibia using oscillating saw. First a medial monocortical cut is carried out with a smaller saw blade. A longer blade is then used to complete the transverse osteotomy towards laterally, while sparring articular and periarticular soft tissue structures. The bony wedge is then removed. After partial elevation of the M. popliteus, a Hohman retractor is placed along the caudal cortex of the tibia to protect popliteal structures and vessels. Either holes are drilled into caudal tibial cortex or a small cut with the saw is placed at the caudomedial border of the tibia, slightly proximal to the summit of the osteomized wedge. It is then possible to fracture the proximal caudal tibial metaphysis towards cranially, bringing it into contact with the tibial tuberosity, using bone holding forceps. Functional axes of the tibia have to be respected during the leveling of the tibia plateau. Two interfragmentary bone screws of adequate size are placed in position function into a craniocaudal direction through the tibial tuberosity into the caudal metaphyseal fragment in order to stabilize the osteotomy (Figure 2). During the fracturing and the fixation of the osteotomy, the tuberositas tibiae has to be handled carefully in order to avoid fracture into it. The tibial craniocaudal plateau orientation should now come close to perpendicular to the anatomical axis of the tibia. After copious flushing of the tissues, the lateral and medial arthrotomy is closed with monofilament resorbable sutures in appositional cruciate pattern placed into the fibrous joint capsule. The prepared medial and lateral fasciae of the stifle are imbricated over the proximal cranial half of the tibia, using preplaced horizontal mattress suture pattern (Figure 3). The proximal lateral fascia is then imbricated over the patellar ligament tissues with a far-near-far-near pattern (Figure 4). The rest of the fascial incisions, subcutaneous layers and the skin are closed in appositional fashion.

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Figure 1 - Medial aspect of the hindlimb. Transversal wedge to be osteotomized on the proximal tibia.

Figure 2 - Medial aspect of the hindlimb. Fixaton of the osteotomy with two interfragmentary bone screws.

Figure 3 - Cranial aspect of the stifle. Creation of an aponeurotic sling during closure of the wound.

Figure 4 - Cranial aspect of the stifle. Completion of the aponeurotic sling.

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Postoperative x-rays are made. A soft Robert-Jones bandage is applied for the first postoperative day. First control x-rays 4-6 weeks postoperatively. In the meantime, the activity of the dog is restricted with a leash.

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Iatrogenic fracture of the tuberositas tibiae can be avoided. When present in the patients of this series, it was successfully repaired with wire tension band.

Literature Results of this surgery in over 60 patients will be related. Typically, the technique offers good to very good results. The gait was fully functional and the operated stifles stable upon palpation 6 weeks after the surgery. The patients regain the maximal musculature 4 to 6 months after surgery. Partial cruciate rupture did not evolute. Arthrosis appears minimal at later controls (1 year and more).

1. 2. 3. 4. 5.

Slocum B., Devine T.: Cranial tibial thrust: a primary force in the canine stifle. J. Am. Vet. Med. Assoc. 183: 456, 1983. Slocum B., Slocum T.D.: Tibial plateau leveling osteotomy for repair of cranial cruciate ligament rupture in the canine. Vet. Clin. North Am. 23: 777, 1993. Tepic S.: Personal communication. Harrison J.W., Montavon P.M.: Technique extra-capsulaire de stabilisation de la motilitĂŠ antĂŠrieure du tibia. Schweiz. Arch. Tierheilk. 123: 1, 1981. Beck P., Montavon P.M.: Was diagnostizieren Sie? Schweiz. Arch. Tierheilk. 129: 493, 1987.

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Results

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Use of glucans as a nutritional supplement in fish Giuseppe Mosconi

Introduction There are numerous problems associated with the treatment of diseased fish, particularly if the specimens to be treated are delicate and small as in the case of ornamental tropical fish. Treatment with medicated food is often not possible as the diseased fish refuse to eat. The large number requiring treatment (thousands or tens of thousands of fish per tank) precludes individual treatment. The large capacity of the aquatic environment in which the fish live also makes treatment of the water as a whole costly. Catching the fish and placing them in a separate container for rapid bath treatment often damages and stresses them to the point of neutralising the benefits obtained from the treatment itself. The condition of the fish must therefore be such as to enable them to react as efficiently as possible to disease and to fight off the attack of the pathogenic germs by themselves. All forms of stress must thus be eliminated and at the same time their immune system must be reinforced. This enables the infection to be cured, thus reducing the need for chemical treatments.

The immune system of fish Fish have a number of different mechanisms or barriers which assure them immunity to pathogens and thus resistance to disease. Two types of immune mechanisms provide protection against infectious and infesting diseases - non-specific defences and specific defences. The difference between these two defence systems is that in the first category, the defence mechanisms exert a general action not associated with recognition of a specific disease causing agent and there is no “memory” enabling recognition of previously encountered pathogens. In the case of specific defences, however, these are aimed at one foreign agent only and are triggered by the pathogen itself (“adoptive” defence). Alternatively they may be induced by administration of vaccines which produce specific (targeted) resistance to individual diseases. In fish, the non-specific immune system is extremely important. It is based on the chemical characteristics of the skin and mucous membranes, cells specialised in ingesting and destroying pathogens and also various humoral factors with

an antimicrobial action. Non-specific immunity can be stimulated by the presence of pathogens or enhanced by the administration of immunostimulants.

Immunostimulant substances Immunostimulants, otherwise known as immunomodulators, are substances which raise the immune defences of the fish, increasing their resistance to disease. There are many substances able to stimulate the immune system and all induce a rapid response lasting for a number of weeks. According to their derivation, immunomodulators can be divided into a number of groups: • Bacteria and bacteria-derived products (microbacteria, lipopolysaccharides and endotoxins produced by gramgerms); • Complex carbohydrates (glucans); • Synthetic immunostimulants (levamisole, antiviral drugs, etc); • Nutritional factors (vitamin C, vitamin E, lipids); • Polypeptides, animal extracts (fish extracts); • Cytokinin and thymic extracts; • Vegetable extracts and lecithin. In fish farming, treatment based on various types of immunostimulants has been practised for a number of years. In the case of ornamental aquarium or pond fish, the practice is however much more recent. We therefore carried out a number of experiments, investigating the efficiency of a number of plant-derived immunomodulators (glucans and some micronutrients). Glucans are extremely complex polysaccharides extracted from barley, yeast, fungi, a number of plants and algae. The most interesting among the latter is Fucus vesciculosus (which yields a particularly active glucan). These complex sugars interact with vitamin C and a number of micronutrients such as alginic acid and silicic acid to act as catalysts and phase exchangers for oxygen. The transferred oxygen molecules have been shown to stimulate the non-specific immune system of the fish and macrophage activity in particular. Macrophage cells specialise in ingesting (phagocytising) the most diverse of undesirable substances whether organic (viruses, bacteria, protozoa, cell debris) or inorganic (minerals, carbon, silica, foreign bodies, etc) which they may encounter within the tissue.

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Glucans in combination with the above micronutrients and vitamin C stimulate the macrophages which become more aggressive towards the pathogens, improving their capacity to neutralise and kill them. The activated macrophages also stimulate the production of lymphocytes, improving the antibody response to the infecting agents. The result is a raising of the non-specific natural defences of the fish and greater resistance to disease. To sum up, the main action of the glucans is to activate the phagocytosis mechanisms of the white cells which form part of the non-specific immune system and to enhance the action of the lymphocytes, thus also improving the specific antibody reaction. This opposes the immune deficiency caused by stress (immunosuppression effect).

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From the start of the test, the fish were fed with a daily ration equal to 1% of live weight. Three tanks (2, 4 and 6) received normal fish-food, while the other three (1, 3 and 5) received flake food supplemented with immunostimulants Euro Life Immuno +. The food was distributed by means of a mechanical feeder over a period of seven hours per day. Each day, the mortality rate in each tank was noted and subsequently reported in a twice-weekly table. At the end of the test, the surviving fish were examined for typical symptoms of “spring viremia” or bacterial complications.

Results Effect of the immunomodulator “EURO LIFE IMMUNO +” in the prevention of viral and bacterial diseases in goldfish (Carassius auratus L.) The main cause of disease in ornamental fish is stress. Many specimens are the healthy carriers of diseases contracted in the past and show no signs of disease as they possess an efficient immune system which keeps these under control. But if stress or a number of coinciding stress factors weaken the immune system, the disease may emerge in its full virulence. We have carried out various tests on aquarium fish, administering Euro Life Immuno + flakes of food enriched with 2% glucans. The most authoritative experiment was carried out by Professor Paolo Melotti, Director of the Aquaculture Research Centre of the Faculty of Veterinary Medicine at the Università di Camerino in collaboration with Andrea Dees and Oliviero Mordenti of the Zootechnical Institute at the Università di Bologna with Giuseppe Mosconi, Euraquarium SpA veterinarian. The cycle of tests carried out on the goldfish using Euro Life Immuno + was aimed at verifying the product’s efficiency in preventing the development of viral and bacterial diseases affecting this species of ornamental fish. The goldfish came from a breeding establishment where “spring viremia” was endemic with regular spring and autumn outbreaks accompanied by the usual bacterial complications generally associated with microorganisms belonging to the Aeromonas genus. On draining a pool containing about 6,000 three-year-old goldfish in April 1997, about 50% of the fish were found to have symptoms typical of the disease characterised by skin edema, hemorrhages and deep lesions also affecting the muscles. Microscopic examination of the remaining fish without obvious lesions showed a high presence of exoparasites (protozoans and trematodes) affecting the skin and gills, which were eliminated before the test by repeated treatments. Out of this group, a random sample of 300 fish were chosen with a mean weight of 50 g ± 16. These were immediately divided into six 250 litre tanks (50 fish per tank), each with a purification system consisting of a mechanical filter and a biological filter. A thermostat system kept the water at a temperature of 20 ± 2 °C.

Mortality data are given in Table 1 while the presence of symptoms is given in Table 2. As can be seen from Table 1, in all tanks receiving Euro Life Immuno + food, mortality was considerably lower than in the three tanks receiving normal fish-food without immunomodulators. The results relating to the presence of typical symptoms of “spring viremia” observed after 60 days in surviving fish in the various groups were also extremely interesting. In this case, the goldfish treated with “Euro Life Immuno +” were found to have very few symptoms, unlike those not undergoing treatment (Table 2). This could be explained by the gradual effect of the immunomodulator which is reinforced over a period of time with prolonged administration of the

Table 1 - Death rate noted at twice-weekly intervals.

Table 2 - Presence of symptoms noted at 60 days from the beginning of the test.

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food. This theory is confirmed by mortality figures. Over the sixty day period, the number of deaths among fish fed with normal food tended to increase, unlike those fed with Euro Life Immuno +.

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7. To enhance colouring; 8. To reduce the quantity of undigested residues.

Characteristics of Euro Life Immuno + immunostimulating food The in-depth studies carried out by the Universities of Bologna and Camerino into glucans and a number of natural micronutrients used in fish nutrition as immunomodulators have enabled Euraquarium to formulate an innovative line of fish-food - Euro Life Immuno + basic, goldfish and seafish - with the following aims: 1. To provide an appetising food with a high biological value; 2. To reduce or eliminate stress-induced disease; 3. To prevent known or suspected diseases by increasing the resistance of the fish; 4. To help the healing process in the case of infection; 5. To increase the specific immune response; 6. To raise the index of food conversion and use;

Feeding aquarium fish with immunostimulants offers considerable benefits, guaranteeing an immediate improvement in resistance to infectious and infesting diseases. Prolonged administration further reinforces the immune system, guaranteeing a wide-ranging and heterogeneous resistance to attack by pathogenic germs. In the event of disease, the efficacy of chemical treatment is enhanced by using fish-food containing immunomodulators. As a result of the wide range of positive factors inherent in this type of fish-food (appetising, improved conversion of the food, enhanced pigmentation, reduction of undigested residues), natural substances with immunostimulating properties will be used more and more often in formulas of food for ornamental fish, thus guaranteeing a tangible improvement in the quality of life for the inhabitants of the aquarium.

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Conclusions

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Surgical treatment of rectal, anal, perianal and perineal lesions Gert Niebauer

Summary An introduction to the general principles of anorectal surgery will be given, including patient preparation, antimicobial prophylaxis and therapy, antisepsis and the use of surgical drains. The following conditions will be reviewed, with emphasis on an update on disease mechanisms and surgical treatment techniques: congenital anomalies, trauma to anus and rectum, anorectal stricture, anal sacculitis, hidradenitis, perianal fistulae, rectal fistula, hyperplasia of circumanal hepatoid (perianal) glands, neoplasms of perianal glands and anal sacs, neoplasms of the anus and rectum, anal and rectal prolapse, rectal diverticulum and perineal hernia; in the latter condition, a new pathogenic theory, advanced by the author, involving the insulin-like peptide hormone relaxin, will be discussed.

General principles of anorectal surgery Congenital anomalies Trauma to anus and rectum Anorectal stricture Anal sacculitis Hidradenitis Perianal fistulae Rectal fistula Hyperplasia of circumanal hepatoid (perianal) glands Neoplasms of perianal glands and anal sacs Neoplasms of the anus and rectum Anal and rectal prolapse Rectal diverticulum Perineal hernia General principles of anorectal surgery: anorectal surgical procedures are rarely emergencies; sufficient time is usually available for preoperative patient preparation; reduction of stool content in the large intestines and antimicrobial prophylaxis can be initiated prior to most surgical procedures that enter the rectal lumen10. Examples for pre- and postoperative treatment are: neomycin (25 mg/kg body weight) and erythromycin (2 mg/kg body weight) given every 8 hours, or metronidazole given alone (30 mg/kg body weight) once daily for two days preoperatively. Systemic prophylaxis should be initiated immediately prior to surgery and chemotherapy (perhaps per os, if available), using the same

agents, should be continued for several days after surgery or as long as deemed necessary. Antibacterial combinations also can be used: e.g., cefoxitin sodium (15 to 22 mg/kg body weight) plus trimethoprim-sulfadiazine (30 mg/kg body weight); or gentamicin (4.5 mg/kg body weight) plus clindamycin (10 to 40 mg/kg body weight); kanamycin (7.5 mg/kg body weight) plus clindamycin (10 to 40 mg/kg body weight), gentamicin (4.5 mg/kg body weight) plus metronidazole (30 mg/kg body weight). The use of surgical drains (e.g., Penrose rubber drains) is recommended when a communication between the rectal lumen and the perirectal tissues existed preoperatively or had been created during surgery. Postoperative stool softeners may be used to help prevent straining to defecate after surgery. Congenital anomalies: are rare in small animals; can either be an inadequately developed or absent anal orifice (atresia ani, imperforate anus) or rectal aplasia (atresia recti, segmental aplasia) in which the anal orifice is developed normally but the rectum is interrupted by an atretic segment. The mildest form of anal anomaly is congenital stricture. In females with rectal and anal atresia, genitorectal fistulae (rectovaginal fistula, anogenital cleft) may also occur. Trauma to anus and rectum: anus or rectum can be injured from within or without. Ingested foreign objects, such as needles or pieces of bone can become lodged in rectum or anus, and may penetrate the mucosa and underlying tissue layers due to sphincter contractions. Other causes include improper rectal thermometry, rectal tearing during examination, improper use of and enema tubes, impalement or acts of sadism. Laceration of the anus and rectum from without can be due to severe trauma to the perineal region, such as from dog bites, or pelvic fractures with dislocation of sharp bone splinters. Signs - tenesmus, dyschezia and hematochezia. Peritonitis might develop in cases of deep rectal perforation. Treatment - Rectal lacerations should be closed with simple interrupted sutures, preferably with a synthetic monofilament, absorbable material (e.g. polydioxanone). Drainage of the contaminated areas and intensive antimicrobial treatment with broad-spectrum antibiotics (see above) is necessary. Most cases of rectal perforation are, however, retroperitoneal (in the caudal half of the rectum) and usually heal well by second intention. Closure per rectum of these defects should not be attempted. Anorectal strictures or fecal incontinence (damage to the anal sphincter muscles and/or their nerve sup-

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ply) may develop as sequelae to traumatic injuries. Anorectal strictures: can be either functional or anatomical in origin. Functional constrictions (anorectal spasms) can occur as transient or chronic spastic anal sphincter contractions, as a sequel of traumatic lesions or irritations of the rectoanal area. Functional constrictions must be differentiated from strictures due to inflammation, fibrosis or neoplasia, and from the normal narrowing of the rectal lumen, often found on rectal palpation, just caudal of the colorectal junction (functional “sphincter ani tertius”). Pathologic idiopathic anorectal spasms can be seen in nervous excitable animals, especially German shepherd dogs. True, mechanical anorectal strictures can occur as sequelae of traumatic or inflammatory lesions of rectum, anus and/or anal sphincter, chronic anal sac disease, perianal fistulae and/or previous surgical procedures. Circumferential fibrosis causes tenesmus, dyschezia and chronic constipation, with or without secondary megacolon. Rectal neoplasms, which also can cause rectal constriction, must be differentiated from benign rectal or anal stricture. Rectal examination, proctoscopy, radiographic and ultrasuonographic studies and biopsies are helpful to distinguish between these two conditions. Treatment of strictures involves either bougienage, surgical transection of the fibrous ring, or full thickness resection of the scar. Lesions located near the anus can be excised per rectum (intraluminal approach). For more cranial lesions, a dorsal or lateral pararectal approach may be necessary to execute a full thickness 360 degree resection-anastomosis with or without a “pull-through” procedure. A abdominal approach, with or without pelvic osteotomy (symphysiotomy or pubic triple osteotomy), is indicated when rectal strictures extend into the area of the rectocolonic junction. Hidradenitis: is a pyogranulomatous inflammation of the anal glands, apocrine sweat glands and sebaceous glands in the cutaneous zone of the anus and the hairless anal disk. Although initially superficial, the chronic inflammation involves the deep connective tissues surrounding the circumanal hepatoid glands and is thought to be one of the initiating lesions in the development of perianal fistulae. In fact, inflammation of the anal glands in the columnar zone, with subsequent fistula formation in the anal sinuses, in most cases is found concomitant with hidradenitis of the cutaneous zone. Treatment of hidradenitis consists of resection and/or fulguration of the affected anal cutaneous zone including the paired tail folds, if affected. However, since hidradenitis most frequently is an early stage of perianal fistula formation, deeper hidden or developing fistulous tracts usually are detected during surgery. Also, responsiveness of the lesions to systemic corticosteroid treatment has led to the hypothesis that in certain breeds (German Shepherd) an autoimmune mediated inflammatory process may be involved. Anal sacculitis: In many cases it remains unclear whether inflammation is the cause or the result of anal sac disease. Anal sac ducts can become obliterated. Infection aggravates the condition and abscessation of the sac occurs. Anal sac rupture, chronic anal sac abscessation or perianal fistulae are common sequelae of anal sacculitis. Complete surgical excision of the anal sacs is indicated in cases of chronic and recurrent impaction or abscessation, non-healing abscesses, and in all cases of perianal fistulation. Tem-

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porary or permanent fecal incontinence or anorectal stricture are rare potential complications of anal sac extirpation. This might occur when by extensive dissection the nerve supply to the external anal sphincter is inadvertently damaged (especially bilaterally), or if bilateral anal sacculectomy causes undue trauma to the anal sphincter muscles. Perianal fistulae: are chronic perianal inflammatory lesions of dogs. Their etiology is obscure. Pathogenically, infection, originating in the specific glandular structures, in and around the canine anus (see above), seems to be the most important initiating factor of the disease. Most commonly, mature dogs of either sex and of breeds with a long, low-slung tail are affected. The lesion most frequently is seen in German shepherd dogs. Signs - tenesmus, dyschezia, bleeding and malodorous purulent discharge from perianal fistulous tracts. Severe pain is present in most cases of extensive fistulation. Chronic constipation with or without megacolon, lethargy, anorexia and weight loss can occur as complicating factors. Treatment - The disease is progressive in nature and conservative treatment is frequently ineffective, although longterm treatment with systemic corticosteroids and broadspectrum antibiotics has been effective in selected cases. The combination of surgical and medical treatment in early stages of the disease yields the highest rate of cure. Several methods of surgical treatment have been described. None is fully satisfactory. Healing without recurrence can be achieved in approximately 50% of severely affected animals4. The various methods include excision or exterioration of all fistulous tracts, or their destruction by chemical or thermal means. The method of choice depends largely on the extent of fistulation and the preference of the individual surgeon. Regardless of the surgical method chosen, and because of the likelihood of involvement of the anal sacs in the disease, bilateral anal sacculectomy should be performed concomitantly (see above). Complete surgical excision is potentially damaging to vital structures (nervous supply to the anal sphincter and the sphincter itself). Thus, a combination of fistulectomy and fulguration and/or cauterization of remaining tracts by caustic agents such as 10% Lugol’s solution has been advocated11. In very advanced cases, surgical procedures necessarily have to be a compromise between completeness of excision and minimization of trauma to prevent fecal incontinence. Thermal or chemical destruction leads to necrotic tissue and opposes the healing process, at least temporarily, and may predispose to postoperative stricture formation. Laser therapy, however, seems to be a valuable alternative, where available3. Cryotherapy, was advocated by many investigators, but it is not more effective than surgical excision and is potentially dangerous, resulting in a higher incidence of post-treatment stricture than sharp and blunt dissection. The hypothesis that a broad based tail can prevent aeration of the anal region in certain breeds and that this contributes to the development and persistence of perianal fistulae has not been veryfied and thus, tail amputation is not recommended. Rectal fistulae may occur associated with severe forms of perianal fistulation. The fistulous tracts can extend cranially within either perirectal tissues or submucosally with-

in the rectum itself. Rectal fistulae may also develop without perianal fistulation. German shepherd dogs seems to have an anatomical predilection for this, as their anal sacs extend relatively far craniad and are in closer proximity to the rectum than anal sacs in other breeds. Treatment consists of complete excision of the fistulous tract(s) by a pararectal approach, debridement of the mucosal lesion, closure of the rectal defect with simple interrupted, absorbable sutures and placement of a drain. Hyperplasia of hepatoid circumanal (perianal) glands: is a common phenomenon, usually seen in older male dogs. A moderate degree of hyperplasia, without accompanying lesions, is a physiologic response to androgenic stimuli. In cases of extensive hyperplasia, secondary irritation of the perianal skin with anusitis, hidradenitis and tenesmus might develop. Frequently, hepatoid circumanal gland hyperplasia is seen concomitantly with perianal adenomas. Anatomically, these glands are found in the hairless disk encircling the canine anus and are scattered in the skin of the prepuce, inguinal area, hind limbs, sacral region and a well defined area dorsally on the tail of dogs (tail gland)8. Treatment - Because extensive hepatoid circumanal gland hyperplasia (with or without tail gland hyperplasia) is caused by androgenic stimulation, other diseases or lesions related to sex hormone imbalances may be present concomitantly, e.g. prostatic hypertrophy. In male dogs, castration is the recommended therapy for extensive hepatoid gland hyperplasia, and testicles should routinely be examined histologically; androgen-producing tumors (commonly Leydig cell tumors) frequently are found. Occasionally, hyperplasia of the hepatoid circumanal glands may be detected in older, spayed bitches, probably associated with lack of estrogens and a relative increase in androgen hormone concentration. Neoplasms of perianal glands and anal sacs: tumors of the perianal glands originate almost exclusively from hepatoid circumanal glands. Hepatoid circumanal gland tumors are among the most frequently occurring canine tumors. Development and growth of hepatoid gland tumors is related closely to plasma androgen levels. Thus, 85% of hepatoid tumors are found in mature or aging male dogs. The majority of hepatoid circumanal gland neoplasms are benign, thus well encapsulated and not invasive. Yet, hepatoid adenomas often are ulcerated and infected secondarily. Mechanically irritated ulcerating tumors can cause considerable bleeding and their appearance can mimic malignancy. Hepatoid adenocarcinoma shows aggressive local invasion and, occasionally, causes severe hemorrhage. Extension of the malignancy into the perineal region and into the pelvic canal is common and metastasis occurs to the regional (sublumbar) lymph nodes. Treatment - Prior to treatment, benign and malignant tumors have to be differentiated. Clinical distinction is not always easy and biopsy may be indicated. Surgical excision (or cryotherapy) is necessary in cases of large, ulcerating and hemorrhaging adenomas. Castration at the time of tumor excision prevents regrowth, enhances involution of remaining tumor nodules and promotes regression of hepatoid gland hyperplasia. Adenocarcinomas should be completely excised, which only is achievable when tumors are fairly small. Lymph node metastasis can be expected. Radiation

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therapy as an additional treatment modality has shown some effect in selected cases. Hormone therapy and/or castration seem to be ineffective in cases of hepatoid adenocarcinoma. Neoplasms of the anal sacs: canine anal sac tumors appear to be invariably malignant. Adenocarcinomas arise from the apocrine glands of the anal sacs. Female dogs are affected in 95% of the cases. Anal sac adenocarcinoma is the most frequent neoplasm of the perianal and perineal region in older (over 10 years of age) female dogs. Prior ovariohysterectomy seems not to affect the incidence. Most characteristically, anal sac adenocarcinomas (occurring in over 90% of the cases) elicit hypercalcemia by producing a parathormonelike protein (paraneoplastic syndrome). Although the tumors are metastatic, initially, they seem to remain confined to the anal sac. At this stage they may be detected by routine rectal examination. In later stages, when dogs are presented because of related clinical signs (dyschezia, ulceration, hemorrhage), lymph node metastasis to the sublumbar nodes and to distant organs will usually have already occurred8. Treatment - Surgical excision is not curative, in general. Recurrence and/or metastasis, if not already present at the time of surgery, can be expected within weeks to months after surgery. Complete surgical excision at early stages, though not likely to prevent recurrence, reduces the elevated serum calcium concentration and thereby alleviates, at least temporarily, the metabolic effects of severe hypercalcemia. Neoplasms of the anus and rectum: non-glandular tumors from the cutaneous part of the anus are rare. Anaplastic squamous cell carcinomas (cloacagenic type) and malignant melanomas have a very poor prognosis. Primary neoplasms of the rectum are also relatively rare and occur in older dogs (mean age 8.5 years, range 2 to 14 years. Rectal tumors, whether benign or malignant, usually originate from the rectal mucosa. Other primary rectal neoplasms such as leiomyomas (-sarcomas), hemangiomas (-sarcomas), lymphomas (-sarcomas) and plasmacytomas occur occasionally. Epithelial tumors are categorized as benign proliferative polypoid growths and infiltrative and/or ulcerative adenocarcinomas. Adenomatous polyps are raised, broad based, sessile, multiple or focal lesions of varied shapes and sizes. Some rectal polyps invade the muscularis mucosa histologically. In these instances, the polyp is regarded as carcinoma in situ. Both, rectal polyps (adenomas) and adenocarcinomas can grow relatively slowly. Progressively intensifying clinical signs (tenesmus, dyschezia, hematochezia) over a period of several months or more, often are part of the case history. Canine rectal polyps may be regarded as precancerous. Adenocarcinomas feature a variety of growth patterns, including proliferative, friable masses that fill the rectal lumen, and tumors that infiltrate the rectal wall, resulting in stricture. In these latter cases a fibrotic annular (â&#x20AC;&#x153;napkinâ&#x20AC;?) ring can be digitally palpated or detected on positive contrast radiography. Signs - The primary clinical sign is hematochezia. Digital rectal examination, proctoscopy and positive contrast (barium) radiographic studies usually are diagnostic. Infiltrative and anaplastic carcinomas bear a very poor prognosis. Thus, in cases suggestive of rectal cancer, a biopsy and thorough clinical staging is recommended prior to surgical treatment.

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Treatment - Surgical treatment of invasive tumors circling the rectum usually (but not always) is only palliative as these tumors frequently have metastasized to sublumbar lymph nodes or beyond by the time of surgery12. In locally confined rectal tumors, radical excision, following prior biopsy, is recommended. Depending on location, size and extent, an intraluminal or a pararectal approach, with or without pelvic symphysiotomy or pubic triple osteotomy, can be employed. Resection of histologically confirmed malignant tumors usually requires a trans-pelvic or pararectal (dorsal) approach to maximize surgical exposure7. Despite attempts to preserve the sphincter mechanism, fecal incontinence frequently is seen as a sequel to extensive rectal resection1. Sometimes, incontinence is transient. Severe anorectal stricture, or a combination of stricture and incontinence might develop postoperatively. Thus, results of treatment are variable. In a study of 78 cases, the mean survival time of dogs with colorectal carcinoma was 15 months without treatment and 22 to 24 months after surgical excision, while other investigators report considerably shorter survival times2. In cases with infiltrative anaplastic rectal carcinomas and annular lesions the prognosis is very poor. Anal and rectal prolapse: straining to defecate or urinate and any irritative lesion of the lower intestinal tract can cause anal and/or rectal prolapse. Prolapse occurs most frequently in malnourished pups and kittens with intestinal parasitism. In animals of any age, rectal and/or anal prolapse also can occur in association with dystocia, prostatic disease, perineal hernia (especially immediately after its repair), rectal neoplasia, rectal foreign bodies etc. The difference between anal and rectal prolapse is a matter of degree. In anal prolapse, only anal mucosa, engorged and edematous, protrudes. In cases of rectal prolapse an oblong, cylindrical mass, with a dimple, marking the reflecting rectal wall, protrudes from the anus. Diagnosis - Rectal prolapse must be differentiated from prolapsed intussusception. In the latter, a probe can be inserted and advanced far craniad into a circular space in between the cylindrical mass and the anal perimeter. In anal or rectal prolapse, the probe cannot be inserted deep to the anus, lateral to the tubular mass. Prolapsed mucosa is not appreciably sensitive to pain perception by superficial irritation. Thus, automutilation as well as necrosis of mucosal surfaces often occur. Treatment - Treatment should include elimination of causes (e.g., antiparasitic therapy, improved nutrition, etc.), in addition to reducing the prolapsed rectum or anus. After reduction of an anal mucosa prolapse, a purse-string suture can placed around the anus tight enough to avoid recurrence but loose enough to allow defecation of soft feces. The purse string sutures can be left in place for up to one week. In cases of repeated recurrence or severe swelling, the protruding mucosa can be trimmed surgically. For rectal prolapse, the tubular structure usually can be reduced manually. In cases with severely damaged or necrotic prolapsed tissue, resection of the protruding mass may be necessary. Colopexy is recommended to prevent future prolapse when an extensive recurrent prolapse of healthy tissue has occurred. In cases of prolapsed intussusceptions, no attempts should be made to reduce the protruding mass per anus. Reduction should be

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executed via an emergency laparotomy. Rectal diverticulum: occurs unilaterally or bilaterally in the caudal rectum of dogs. Almost always, these lesions are seen in old male dogs in conjunction with perineal hernia, due to breakdown of muscular support. Very rarely, diverticula may occur without apparent perineal herniation. Anal sphincter musculature and rectal muscularis mucosae become atrophic and muscle fibers are separated by bulging of the rectal mucosa. Signs - Tenesmus, chronic constipation and fecal impaction. When rectal diverticula are chronically impacted with fecal material, surgical repair should be attempted. Treatment - Surgical treatment via pararectal approach. In nearly all cases, the diverticulum is merely inverted into the rectum, without opening the rectal lumen, and the defect in the musculature is closed with absorbable sutures. If, during dissection, the lumen is entered, a Penrose drain is placed to drain the wound. When the external and internal anal sphincters are severely affected, such as in cases of coexisting perineal herniation and/or when megacolon exists, the procedure is unlikely to restore normal defecation. In general, surgical reduction will only be attempted when large rectal deverticula are encountered during the repair of a perineal hernia. Perineal hernia: occurs spontaneously and almost exclusively in intact male dogs with animals between 7 and 13 years at highest risk6. Only a few cases are reported in older males that were castrated during their first year of life, or in female dogs or in cats. In affected animals, an idiopathic process, probably associated with a hormone imbalance, weakens progressively connective tissues and muscles of the pelvic diaphragm. Neither testosteron nor estrogen-progesteron seem primarily responsible for the development of hernias, despite the fact that castration reduces the incidence of recurrence after surgical repair. Nearly all dogs with perineal hernia present with cystic prostatic hypertrophy. Recently, the hypothesis of a relaxin-related pathogenesis was advanced by the author9. It was shown that relaxin is produced in canine prostates; it might be that hypertrophic prostates produce excess levels of relaxin which in turn might progressively weaken the pelvic diaphragm. Subsequently, pelvic and abdominal structures and organs, lacking support, herniate through the pelvic canal and lodge in subcutaneous perineal pouches. Perineal herniae can be unilateral, bilateral or, less commonly, circumferential (in relation to the anus). In cases with unilateral perineal hernia, the later appearance of a hernia on the opposite site is likely. Herniae usually contain some peritoneal fluid and characteristic fluid or fat-filled cysts, linked to the prostate. In severe cases, prostate, bladder and occasionally intestines can herniate and incarceration or strangulation can occur. The herniated tissues follow a route that is usually medial to the coccygeus muscle and lateral to the rectum, either lateral between the coccygeus and the levator ani muscle or medial between the levator ani muscle and the rectal wall, coccygeoanalis muscle and the sphincter externus muscle, and the internal obturator muscle ventrally. The loss of lateral support to the rectal wall causes rectal deviation (rectal flexure), or rectal sacculation (rectal diverticulum). Treatment - Several surgical techniques have been de-

scribed for repair of perineal hernias. None of the methods is free of failures, since herniorrhaphy techniques rely on suturing and healing of tissues that are affected by a degenerative process. The repair technique using the transposition of the internal obturator muscle, has the lowest rate of complications (less than 10%) compared to other described procedures5. Castration of male dogs at the time of hernia repair is recommended strongly13. Post-operative complications may include: infection of the hernial region due to intraoperative contamination (proximity of the surgical field to the anus); if the sacrotuberous ligament is employed in the closure and sutures have been placed too deep, inadvertent partial or complete ligation of the sciatic nerve may occur; if the pudendal nerve is inadvertently severed (especially if the nerves are damaged bilaterally), fecal incontinence will develop. Rectal prolapse may occur in animals intensively straining to defecate. Appropriate surgical repair and castration is curative in over 90% of cases.

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References 1.

Anderson GI, McKeown DB, Partlow GD, Percy DH, (1987), Rectal resection in the dog - a new surgical approach and the evaluation of its effect on fecal continence, Vet Surg 16:119-125. Church EM, Melhaff CJ, Patnaik AK, (1987), Colorectal adenocarcinoma in dogs: 78 cases (1973-1984), J Am Vet Med Assoc,

11. 12.

13.

191:727-730. Ellison GW, Bellah JR, Stubbs WP, vanGilder J, (1995), treatment of perianal fistulas with ND:YAG Laser - results in twenty cases, Vet Surg, 24:140-147. Goring RL, Birght RM, Stancil ML, (1986), Perianal fistulas in the dog - retrospective evaluation of surgical treatment by deroofing and fulguration, Vet Surg, 15:392-398. Hardie EM, Kolata RJ, Earley TD et al., (1983), Evaluation of internal obturator muscle transposition in treatment of perineal hernia in dogs, Vet Surg, 12:69-72. Hayes HM, Wilson GP, Tarone RE, (1978) The epidemiologic features of perineal hernia in 771 dogs, J Am Anim Hosp Assoc, 14:703-707. McKeown DB, Cockshutt JR, Partlow GD, Kleer de VS, (1984), Dorsal approach to the caudal pelvic canal and rectum - effect on normal dogs. Vet Surg, 13:181-184. Niebauer GW, (1993), Rectoanal disease, In: Bojrab MJ, Disease mechanisms in small animal surgery, 2nd ed, Lea&Febiger, Philadelphia, 271-286. Niebauer GW, (1991) The potential role of relaxin in canine perineal hernia, Proceedings, Federation of American Societies for Experimental Biology, 75th annual meeting, Atlanta, GA. Penwick RC, (1988), Perioperative antimicrobial chemoprophylaxis in gastrointestinal surgery, J Am Anim Hosp Assoc, 24:133-145. Vasseur PB, (1984), Results of surgical excision of perianal fistulas in dogs, J Am Vet Med Assoc, 185:60-62. White RAS, Gorman NT, (1987), The clinical diagnosis and management of rectal and pararectal tumours in the dog, J Small Anim Pract, 28:87-107. Wilson GP, Hayes HMJr, (1979), Castration for treatment of perianal gland neoplasms in the dog. J Am Vet Med Assoc, 174:1301-1303.

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Clinical interpretation of ocular hemorrhages Claudio Peruccio Med Vet, Dipl ECVO University of Torino - Department of Animal Pathology - Italy

Ocular hemorrhages are among the most frustrating problems presented to the veterinary ophthalmologist. They can be secondary to eye diseases such as glaucoma, uveitis, retinal detachment, trauma, eye surgery etc. or the consequence of systemic diseases (i.e infection, toxicity, neoplasia, vasculopaties, coagulopathies, immuno-mediated disorders etc..). The origin of vascularization in the different anatomical sites where ocular hemorrhages can occur, their characteristics and evolution will be discussed. The differential diagnosis and treatment will be considered.

Origin of vascularization in the different anatomical sites where ocular hemorrhages can occur, their characteristics and evolution Among the domestic animals, the main supply of blood to the eye and orbit is the internal maxillary artery (as a branch of the external carotid artery) which after passing through the alar canal, branches to give rise to the external ophthalmic artery1. The internal ophthalmic artery, a branch of the internal carotid artery, is relatively small and less important than in primates where it provides most of the circulation of the eye. The venous drainage varies among the different species and is mainly via the superior and inferior orbital veins.

If they are the consequence of trauma, their evolution depends upon the entity of tissue damage.

Cornea Being avascular the cornea has no potentiality to develop hemorrhages; just in case of keratitis a small collection of blood can occasionally be localized within the corneal tissue.

Anterior chamber Most intraocular hemorrhages are localized in the anterior chamber causing the so cold hyphema. In many instances clotting is reduced by dilution of the blood by aqueous and the release of plasminogen activator by the surface of the iris. Unclotted blood sediment and exits via the filtration angle3. When reabsorption doesnâ&#x20AC;&#x2122;t occur in 3-4 days, the cause of bleeding persists. Sometime clotting occurs, depending on the cause of hyphema, and all the anterior chamber can be completely filled by clotted blood. This is a more frequent finding when the cause of hyphema are trauma, iridocyclitis and intraocular neoplasia; it does not occur in autoimmune trombocitopenia and in dicoumarin toxicity. Hyphema is a common finding after trauma, severe iritis, infectious diseases, anemia, trombocitopenia, hypertension, retinal detachment, intraocular neoplasia, complications during and after surgery, clotting disorders and chronic glaucoma3,5,6,7.

Conjunctiva Conjunctival petechia and hemorrhages are a frequent finding due to the extensive capillary network. Conjunctival arteries come from the superficial temporary artery, the anterior ciliary artery and the malar and palpebral arteries2. Venous drainage is through the palpebral and malar veins to the facial vein and from the angularis oculi vein to the orbital plexus and superficial temporal vein2. Around the limbus deep and superficial blood vessels anastomose with each other. Blood can easily diffuse within the conjunctiva giving rise to apparently serious clinical situations that can disappear in one -two weeks.

Uvea The uveal tract is the most vascularized ocular structure and for this reason, it is the area of origin of most intraocular hemorrhages. It is composed of iris, ciliary body and choroid.

Iris The iris vasculature is composed of a major arterial circle from which the many vessels extend radially toward the center and the periphery of the iris8.

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The major arterial circle is formed by two arteries that originate from the lateral and medial long posterior ciliary arteries; at the medial periphery of the ciliary zone each artery branches superiorly and inferiorly to pass circumferentially toward the opposite artery. Radial vessels passing retrograde anastomose with the short posterior ciliary arteries and one another to form a functional arterial circle; in the dog radial arteries to the pupil poorly develop transverse anastomosis, so a minor arterial circle does not exist2,8. The thick capillary network favours both bleeding and reabsorbtion of blood; in the final stages the color of the iris changes and is usually dark.

Ciliary body The blood supply of the ciliary body is derived from the two long posterior ciliary arteries and the anterior ciliary arteries that undergo several divisions which anastomose to form the major arterial circle located either in the base of the iris or anterior ciliary body8. The vasculature of the ciliary processes is primarily supplied by the major arterial circle; in carnivores there is a well developed capillary bed responsible for aqueous production.

Choroid The choroid is composed mostly of large veins and scattered arteries. Externally to internally the choroid can be divided into: - large vessel layer with few arteries, mostly branches of the short posterior ciliary arteries (to a lesser extent the choroid also receives blood from the long posterior ciliary arteries and the anterior ciliary arteries9 and many large veins that merge centripetally into four or more prominent vortex veins8; - medium-sized vessel and tapetum layer: the vessels are emissaries between a single sheet of capillaries and the layer of large blood vessels8; - choriocapillaris, a thin layer of fenestrated capillaries.

Vitreous The vitreous body in normal conditions is avascular and hemorrhages can invade it if bleeding occurs in the surrounding structures (retina and uvea) or from the persistent and patent hyaloid system in PHTVL cases. According to their localization vitreous hemorrhages can be classified into subvitreal (subhyaloid or preretinal) and intravitreal hemorrhages1. Preretinal hemorrhages are located in the space between the posterior face of the vitreous body and the internal limiting membrane of the retina and they often have a â&#x20AC;&#x153;boat keelâ&#x20AC;? conformation due to the force of gravity. Intravitreal hemorrhages can be concentrated regionally into strands or sheets or diffused in the vitreous body1. Resolution of intravitreal hemorrhages often takes sever-

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al months and fibrous membranes can be found as a sequela; traction on the retina and retinal detachment can follow. Vitreous degeneration following vitreal hemorrhages can cause syneresis and synchisis scintillans1. The main cause of vitreal hemorrhages are trauma, retinal detachment, Collie eye anomaly, retinal dysplasia, PHTVL, preretinal vascular loops, retinal vasculopaty, retinitis, uveitis, chronic glaucoma, intraocular neoplasia, hemorrhagic systemic diseases, toxicosis, hypertension.

Retina Retinal arterial supply in domestic animals is via the short posterior ciliary arteries (cilio-retinal arteries)8. At the periphery of the optic disc they originate the cilioretinal arterioles, usually three in the cat and about 20 in the dog. A very well developed capillary network provides nourishement to the inner retina, extending to the inner nuclear layer. Four main factors can play a key role in the pathogenesis of retinal hemorrhages: - the blood pressure within the vessels; - the state of the circulating blood; - the state of the vessel wall; - the height of the extravascular / intra-ocular pressure. It is probably exceptional for one single factor to be responsible, but there are cases in which for example elevation of the blood pressure alone may be sufficient to cause hemorrhages from presumably healthy vessels. When hemorrhage has coincided with a sudden rise of blood pressure, the latter is the only or at least the principal cause of the bleeding; whereas in cases where there has been a slowly established pressure rise, the pressure element is of comparative insignificance10. In renal disease with general hypertension all the first three factors are present. Clinically, it is important to determine whether the source of the retinal hemorrhage is to be found in the arterioles, the capillaries or the venules and in which retinal layer it is located. The clinical appearance of retinal hemorrhages varies according to the site of the extravasation of the blood. They are usually most numerous centrally where the retina is thickest and the capillary circulation is more complex than in the periphery. It is to be remembered that the vessels do not penetrate more deeply than the external nuclear layer, the outer layers being avascular. Therefore hemorrhages are confined to the inner layers of the retina unless effusion of blood is large enough to plough up all the tissues. We commonly divide hemorrhages in pre-retinal, retinal or sub-retinal according to their distribution. Pre-retinal hemorrhages appear as dark-red masses, often initially circular in shape but tending to sink owing to the action of gravity, assuming the shape of a boat-keel. Retinal hemorrhages have different patterns according to the layer where they occur. If they have a striate character they must belong to the nerve fiber layer or lie between that layer and the internal limiting membrane. Hemorrhages occurring within the loose retinal tissue

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tend to assume the round droplet form natural of a free fluid; more often they are located externally to the inner nuclear layer, extending to the outer nuclear layer. Ophthalmoscopically they appear as dot and blot hemorrhages. Sometimes they show other patterns, stellate and reticular for example, which indicate that the blood is at liberty to wander horizontally among the vertically disposed neural and supporting fibres. Subretinal hemorrhages between the choriocapillaris and the retinal pigment epithelium, are choroidal in origin; they are dark red in color dimmed by the greyish bloom caused by the overlying retina, they are usually rounded, raised and often extensive; over them the retinal vessels pass unaffected.

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In intraocular surgery hemorrhage is a possible complication. Coumarin derivatives and prostaglandin inhibitors can affect hemostasis and cause intraocular hemorrhage. V vasculopathies and other bleeding disorders Vasculopaties are potential cause of ocular hemorrhages as in hyperviscosity syndromes or hypertension. Hypertension per se is not so important in the pathogenesis of intraocular hemorrhage that can start a long time after the pressure rise if and when concomitant vascular lesions are present at the arterioles, venules, precapillary and capillary level10.

Causes of ocular hemorrhages From the etiological point of view, to make a complete differential diagnosis in case of ocular hemorrhages, we can adopt the acronim DAMNITV. D degenerative diseases Coagulopaties can be secondary to hepatic degenerative processes and a possible clinical sign are ocular hemorrhages. Degenerative processes affecting the kidney can cause hypertension and retinal hemorrhages. A anatomical, congenital defects Collie Eye Anomaly (CEA) and retinal dysplasia are common causes of retinal detachment and secondary intraocular bleeding. The eye can be completely filled by blood. M metabolic diseases Diabetes mellitus is the main cause of retinal vasculopathy in man, causing microaneurisms, neovascularization and hemorrhages. Diabetic retinopathy has been described in the dog, mainly caracterized by microaneurisms; the lesions can be observed in histologic sections, but ophthalmoscopic findings are unusual. N neoplasia Primary or metastatic intraocular tumors are a possible cause of hemorrhage. Intraocular hemorrhages can be secondary to neoplasia localized at different sites in the body when they cause coagulopathies (liver neoplasia), hypertension (feocromocitoma), anemia (many tumors), hyperviscosity syndrome (myeloma), disseminated intravascular coagulopathy (paraneoplastic syndromes). I inflammatory, infectious, immunomediated disases Uveitis of any origin is a common cause of intraocular hemorrhage. Severe inflammatory processes affecting several organs in the body (i.e. pancreatitis), can cause coagulopathies and secondary intraocular hemorrhages. Infectious diseases as rickettsiosis and leptospirosis in the dog and infectious peritonitis in the cat or infestive diseases as leishmaniosis are possible cause of intraocular hemorrhages. Immunomediated diseases as autoimmune thrombocytopenia can have the same effect. T diseases secondary to trauma and toxicity Direct or indirect trauma to the eye can cause intraocular bleeding, usually only in one side.

The treatment depends upon the cause of bleeding. The animal must be kept quiet, if necessary by administering tranquilizers. When necessary, symptomatic treatment is applied; anti-inflammatory drugs, mydriatics, miotics, tPA are the possible choice. The use of mydriatics and miotics is controversial and of no proven value1,3: - atropine 1% - cycloplegic action will reduce filtration angle outflow, therefore increasing danger of glaucoma, but is important in the treatment of anterior uveitis3; - pilocarpine 1%, maintains filtration angle outflow. Miotic action increases the iris surface, enhancing fibrinolysin activity, but increasis the risk of posterior synechia3; - intraocular tissue plasminogen activator (tPA) 25 micrograms, will dissolve clots and fibrin but, if the cause is not removed, rebleeding is likely3; - anti-inflammatory topical corticosteroids can be used in case of uveitis. For the same reason prostaglandin inhibitors could be useful, but their use is not advised because many of them also prolong blood clotting7.

References 1. 2. 3. 4.

5. 6. 7. 8.

10. 11.

K.N. Gelatt - Veterinary Ophthalmology - Lea & Febiger, Philadelphia, 1991. Peruccio C. - Atlante di oftalmologia veterinaria - Edizioni Medico Scientifiche, Torino, 1985. Severin G.A. - SeverinĂs Veterinary Ophthalmology Notes - Severin Edit., 1996. Stades F.C., Wyman M., BoeveĂ M.H., Neumann W. - Ophthalmology for the Veterinary Practitioner - Schlutersche GmbH & Co.KG, Verlag und Druckerei, Hannover, 1998. Barnett K.C., Crispin S.M. - Feline Ophthalmology - W.B. Saunders Company Ltd, 1998. Walde I., Schaffer E.H., Kostlin R.G. - Atlas of Ophthalmology in Dogs and Cats - B.C. Decker Inc. Toronto, 1990. Slatter D. - Fundamentals of Veterinary Ophthalmology - W.B. Saunders Company, Philadelphia, 1990. Prince J.H.,Diesem C.D., Eglitis I., Ruskell G.L. - Anatomy and Histology of the Eye and Orbit in Domestic Animals - Charles C. Thomas, Springfield Ill.USA,1960. Torczynski E. - Choroid and Suprachoroid - In Biomedical Foundations of Ophthalmology, Vol.1, T.D. Duane and E.A. Jaeger Edit., Philadelphia, J.B. Lippincott, 1988. A.J. Ballantyne, I.C. Michaelson -Textbook of the fundus of the eye - E. & S. Livingstone, Edinburgh, 1970. L.F. Rubin - Atlas of Veterinary Ophthalmoscopy - Lea & Febiger, Philadelphia, 1974.

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The eye in the ageing animals Claudio Peruccio Med Vet, Dipl ECVO University of Torino - Department of Animal Pathology - Italy

As the years pass the tissues of the eye undergo ageing processes which are similar to those which take place in other parts of the body The risk of functional deterioration of the eye is increased by the concentration in a single small organ of various structures which are functionally interdependent on each other. It is very important that the vet is able to recognise the clinical signs which are related to ageing of the ocular structures, interpret them, explain the pathogenetic mechanism to the owner in simple terms and, above all, to make a correct choice of therapy when there is one.

Changes in the eyelids Neoplasms Tumors on the eyelid margins are fairly common in elderly dogs, especially adenomas or sebaceous adenocarcinomas of the meibomian glands. Early and radical excision by simple wedge resection is necessary in order to avoid having to operate on larger masses requiring more complicated surgery. It is possible to remove up to 1/3 - 1/4 of the eyelid margin depending on the conformation of the palpebral fissure and obtain a good repair. More extensive tumors require blepharoplastic with sliding skin grafts1. Chronic blepharitis Complicated chronic inflammatory processes can give rise to the formation of pyogranulomas with marked deformation of the eyelid margin. The involvement of the meibomian gland encourages the formation of styes, tarsal cysts and chalazions and lead to abnormal meibom secretion with a subsequent qualitative tear deficiency1. Treatment consists of hot compresses and antibiotics applied to the site of the lesion, if necessary. Once any infection has been eliminated, an antibiotic and cortisone combination should be applied locally in the form of eye solution or ointment either to the fornix or the eyelid margin. Massaging the eyelid margin 2-3 times a day for 10-15 days can also be very useful.

Changes in the tear film and its distribution It is fairly common for production of lacrimal fluid to decrease in elderly animals causing conjunctivitis and keratitis. It is possible to measure tear production by using the Schirmer Tear Test (STT); values below 9 mm/minute are regarded as inadequate and establish a diagnosis of KCS2, one of the most common condition in elderly dogs. There are many causes of this condition resulting in reduced function or complete destruction of the lacrimal gland tissue (idiopathic, immuno-mediated, neurogenic, hypothyroidism, lacrimotoxic drugs as phenazopyridine, sulphadiazine, sulphasalazine etc..). The classical treatment is replacement therapy consisting of instillation of artificial tears many times through the day, in addition to antibiotic base eye ointments in cases of infection and corneal ulceration; corticosteroids are used in selected cases to control the inflammatory process, but may be contraindicated by the presence of corneal ulceration which are not always easy to distinguish. One - two drops of pilocarpine may be administered morning and evening with food in an attempt to induce lacrimation, bearing in mind that this drug is toxic. The most effective drug for treatment of KCS is now cyclosporine, available as a 0,2% eye ointment (Optimmune Schering Plough) or prepared in 1% suspension in corn oil3 applied twice a day. In most cases tear production increases within a few weeks, but if it not succesful the treatment should be continued as long as 12 weeks before giving up. The Schirmer tear test should be performed on a regular basis and additional symptomatic treatment may be necessary. In a short term clinical field trial on the efficacy of cyclosporine eye ointment 80% of cases improved3.

Changes in the cornea Corneal changes secondary to chronic irritation In some elderly dogs, eyelid closure and distribution of the precorneal tear film are not adequate and, in the parts which are more exposed to ambient stimuli, the cornea can become opaque. This is the result of the incomplete protection of the eyelid and the tear film; clinically a slight opacity is observed in

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that area, with pigmentation and sometimes vascularization. It is important to establish the cause of this change, when possible, to prevent further deterioration. Schirmer Tear Test should always be performed. In any case the administration of artificial tears is indicated, to protect the cornea. Mineralization of the cornea or superficial corneal dystrophy in the elderly dog, so called calcific keratopathy4,5. In dogs of advanced age,usually between 13 and 18 years4, mineralization of some superficial areas of the cornea can be observed, with calcium deposits in the superficial stroma and in the subepithelial sector. The phenomenon may be unilateral or bilateral. In the initial stages the animal does not appear to be troubled but gradually, as the deposits increase in size and thickness, ulcers can appear and the eye becomes painful. A chelating agent such as EDTA is used, initially every 2-4 hours, then 1-2 times a day. If a suitable eye solution is not available, it is possible to dilute 1 ml of ethylenediaminetetraacetic acid (EDTA) in 15 ml of artificial tears solution4. In severe cases special attention should be paid to treatment of ulcers and uveitis; if treatment fails and the ulcers persists, lamellar keratectomy must be performed. Changes in the cornea following endothelial diseases5 The main functions of the corneal endothelium are the maintenance of corneal transparency; it acts as an active pump to dehydrate the stroma and as a barrier to prevent penetration of the aqueous humour. If a certain number of endothelial cells lose their function, the cornea hydrates, assuming a blue colour. This situation can occur in elderly dogs when the corneal endothelium has been damaged as a result of anterior uveitis (iridocyclitis), glaucoma, intraocular surgery, trauma etc. Ageing by itself causes loss of cells and the number of functioning cells can be inadequate for maintaining a state of normality. In some breeds of dogs (e.g. the Boston terrier, the Chihuahua etc..) another possible cause is endothelial dystrophy of hereditary origin5. Fluid within the corneal stroma may coalesce resulting in bullous keratopathy with subsequent ulceration. There is no reliable effective treatment: hyperosmotic agents can be used to attract fluid from the cornea towards the exterior; improvement in transparency is only temporary; only functional renewal of the endothelium can change the situation. Therapeutic soft lenses or collagen lenses can be used when there are complicating corneal erosions. A recent study has demonstrated the efficacy of thermokeratoplasty in the management of these situations6. Recurrent superficial corneal erosions These are more common in elderly dogs but not exclusively so; they may be secondary to the corneal edema described earlier, repeated trauma (e.g. through trichiasis, defects in the eyelid etc..), complicated by infection or following dystrophy of the epithelium and basement membrane (E-

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BM-D), more frequently seen in Boxer dogs5. Healing is slow and inadequate. In all cases the objective of treatment should be to eliminate the cause of ulceration and to avoid complications. In E-BM-D the margins of the epithelium do not adhere to the basement membrane, need to be excised and debrided. If necessary a grid or stippled keratotomy may be performed to encourage subsequent epithelial adhesion. Other treatment regimes used by veterinary ophthalmologists include therapeutic soft contact lenses, cyanoacrylate adhesive, epithelial growth factors, aprotinin, conjunctival flaps and stromal keratectomies5,7.

Changes in the uvea Iris In elderly dogs, especially small dogs and in particular in the miniature French poodle, varying degrees of atrophy of the iris are often observed with resultant changes in the diameter of the pupil and anisocoria1,4. The sphincter muscle atrophies, the stroma iridis becomes thinner and, when retroilluminated, the fine iris network can be seen. Ciliary body A number of age related changes occur in the ciliary body: the basement membrane of the non-pigmented and pigmented epiteliums thicken greatly and have a multilaminar appearance8. Also the stroma of the ciliary body thickens while the non-pigmented epithelium thins and the degree of pigmentation of the pigmented epithelium lessens8.

Changes in the iridocorneal angle Also the iridocorneal angle changes with age; these changes appear to reduce the area available for aqueous humor outflow and might make older individuals more susceptible to any kind of insult that could lead to glaucoma8.

Changes in the lens Senile sclerosis4 In the dog, as in other animals, the lens becomes more dense with time. Throughout the animalĂs life-time, lens fibres produced from the lens epithelium at the equator converge towards the centre substantially increasing the size of the nucleus. The nucleus becomes more dense with gradual changes in the optical characteristics from the age of 6-7 years. Senile sclerosis is frequently misdiagnosed as cataract. When the ophthalmoscope is used correctly the back of the eye can be very clearly observed through the dense nucleus and it is possible to exclude the presence of a nuclear cataract.

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Changes related to eye diseases Glaucoma is one of the main causes of blindness in the dog; the retinal changes induced by the presence of glaucoma can occur early but in case of chronic glaucoma complete blindness is often present in aged animals. Vitreous syneresis can be an age related problem and is a possible cause of retinal detachment.

References 1. 2.

Changes in the vitreous

Asteroid hyalosis Asteroid hyalosis is characterized by small, round bodies composed of a calcium-lipid complex suspended in the vitreous humor. This condition occurs principally in old dogs9.

Vitreous syneresis Syneresis refers to an irreversible degenerative process of the vitreous that is characterized by liquefaction. Vitreous syneresis is seen occasionally in older dogs but its incidence is low10.

5. 6.

8. 9.

Changes in the retina

10.

Changes related to systemic diseases Many systemic diseases may involve the retina and their effects are more likely to be seen at a certain age. Systemic hypertension may cause retinal detachment and hemorrhage11,12; the main cause are renal failure, hypothyroidism and hyperviscosity syndromes.

11.

12.

P.J. Smith - Geriatric Ophthalmology - ASVO Proceedings March 1993. F.C. Stades, M. Wyman, M.H. Boeveí, W. Neumann - Ophthalmology for the Veterinary Practitioner - Schlutersche GmbH & Co. KG,Verlag und Druckerei, Hannover, 1998. ESVO & ECVO proceedings, Sept. 1994 - Cyclosporine, veterinary applications in ophthalmic disease. C.A. Fischer - Geriatric Ophthalmology - Vet. Clin.North Am. S.A.P., 19, I, January 1989, 103-123. K.L. Ketring - The aging canine cornea - ASVO proceedings, San Diego, March 1997. C.J. Murphy, T. BurlingS. Hollingsworth - Thermokeratoplasty for the treatment of chronic bullous keratopathy in the dog - ACVO proceedings, October 1993, 21. R.V. Morgan, K.L. Abrams - A comparison of six different therapies for persistent corneal erosions in dogs and cats - V.C.O. 4, 1, 38, 1994. B.K. Collins, C.P. Moore - Canine anterior uvea. In Veterinary Ophthalmology, K.N. Gelatt, edit, Lea & Febiger, Philadelphia, 1991. L.F. Rubin - Asteroid Hyalosis in the dog -Am. J. Vet. Res. Nov. 1963, 1259-1261. R. Curtis, K.C. Barnett, A. Leon - Diseases of the canine posterior segment. In Veterinary Ophthalmology, K.N. Gelatt, edit, Lea & Febiger, Philadelphia, 1991. R.M. Gwin, K.N. Gelatt, T.G. Terrell, C.I. Hood - Hypertensive retinopathy associated with hypothyroidism, hypercholesterolemia and renal failure in a dog - J.A.A.H.A., 14, March/April 1978, 200209. J. Sansom, K.C. Barnett, K.A. Dunn, K.C. Smith, R. Dennis - Ocular disease associated with hypertension in 16 cats - JSAP 35, 604, 1994.

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Cataract1,4 The term ìcataractîrefers to any opacity of the lens. Vets frequently diagnose senile cataract in elderly dogs, but the true incidence of its occurrence is not known because there are many causes of opacification of the lens and very often a localized but progressive cataract remains undetected for years. The opacity will become more evident with advancing age. Surgical treatment of cataracts, including senile cataract, has in recent years undergone the same evolution as in human medicine; in each case a veterinary ophthalmologist should evaluate the risk-benefit ratio and the presence of contraindications to make a correct selection of animals to be treated.

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Recent advances in the understading of generalised progressive retinal atrophy S.M. Petersen-Jones

Summary The generalised progressive retinal atrophies (PRAs) are a group of inherited primary photoreceptor and are a leading cause of blindness in pure-bred dogs but are less important in cats. Most forms are recessively inherited although an X-linked form exists in dogs and a dominant form in the Abyssinian cat. Recently advances in molecular techniques have allowed the identification of gene defects causal for two forms of PRA in the dog and led to the identification of linked DNA markers for two other forms. Rod cone dysplasia type 1 (rcd1) in the Irish setter was found to be caused by a mutation in the gene encoding the beta subunit of cGMP phosphodiesterase. This led to a break down in the phototransduction cascade in the rod cell and an accumulation of the final substrate cGMP probably triggers programmed cell death (apoptosis) of photoreceptors. A mutation in the alpha subunit of the same protein has recently been implicated in PRA in the Cardigan Welsh corgi. Linkage of genetic markers to the genes for progressive rod cone degeneration (prcd) and early retinal degeneration (erd) have been recently reported. Prcd is numerically the most important form of PRA affecting miniature and toy poodles, English and American cocker spaniels, the Labrador retriever and the Portuguese water dog. A linkage test for prcd will be a great step forward in the eradication of PRA.

The generalised progressive retinal atrophies (PRAs) are a group of inherited primary photoreceptor diseases which result in similar clinical signs and ultimately lead to blindness. One recent survey listed 108 different breeds of dog as suffering from PRA, although in many breeds the condition has not been investigated. PRA is also recognised in cats although in far fewer breeds than in dogs. Attempts are being made to develop genetic tests for PRA which can identify which animals will become affected (important for the later-onset forms) and will detect carriers of the recessively inherited forms of PRA. These investigations have used two main approaches, the first has been to make an educated guess, on the evidence, available which gene could be abnormal and then screen that gene for mutations. This is the candidate gene approach. The second approach has been to use genetic markers to try and find a marker which is linked to the disease gene. Recent collabo-

rations to map the dog genome have resulted in markers suitable for this purpose in the dog. A closely linked marker could potentially be used to test for the presence of the disease gene. Both approaches have already had some success in investigations of canine PRA, but there is still a lot of work to be done.

Clinical signs PRA initially causes night blindness, followed by a progressive loss of daytime vision until the affected animal is totally blind. The age at onset of night blindness, and the rate of progression of vision loss, varies both between and within the different forms of PRA. Regardless of the form of PRA the ophthalmoscopic signs are similar. The funduscopic changes result from thinning of the neuroretina, loss of ganglion cell axons, reduced blood supply to the degenerating retina and pigmentary changes involving the retinal pigment epithelium. The initial ophthalmoscopic signs are often a granular appearance to the peripheral tapetal fundus which then progresses into a generalised tapetal hyperreflectivity. In some dogs radial bands of variable reflectivity appear at the periphery of the tapetal fundus, possibly due to variation in tapetal topography due to grooving from underlying choroidal blood vessels. Concurrent with retinal death and thinning, the superficial retinal blood vessels become attenuated. Initially the smaller arterioles become more difficult to visualise and then as the condition progresses larger vessels are obviously thinned. The panretinal atrophy is accompanied by depigmentation in the nontapetal fundus resulting in a grey colour to the fundus (originally described as pavement grey) with interspersed areas of pigment clumping. The loss of the centrally projecting axons of the ganglion cells results in an obvious atrophy of the optic nerve head. This change is less obvious in cats. Secondary changes include a reduction in the pupillary light response and in dogs secondary cataract formation. Secondary cataracts do not develop in cats with PRA.

Functional changes in the neuroretina Electroretinography, the measurement of electrical activity from the retina resulting from light stimulation, is a sen-

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sitive measure of generalised retinal function and in many forms of PRA is useful for the detection of PRA prior to the development of ophthalmoscopic changes. The electroretinographic changes vary between the different forms of PRA and in some cases may give an insight into the failure of retinal function associated with the disease.

Laboratory investigations of PRA Detailed histopathological characterisation of some forms of PRA has been reported, usually where a breeding colony has been established allowing examination of several time points during the progression of the disease. Similarly electrophysiological investigations have been performed on colony animals and give an insight in to the ongoing pathological process. Biochemical analysis of affected retinae has been performed in some cases. Abnormal elevation of cyclic guanine monophosphate (cGMP) levels has been found in some forms of PRA suggesting a breakdown in the visual transduction cascade. Cyclic GMP is the final metabolite of the cascade and accumulates when the cascade is non-functional. Molecular biological investigations have been performed in some forms of PRA. This includes the screening of potential candidate genes for mutations.

Investigation of individual forms of PRA Canine PRA may be broadly divided into early-onset, mid-onset and late-onset forms. Where more detailed histological investigations have been performed a number of the early-onset forms have been further defined as photoreceptor dysplasias and some of the later-onset forms as degenerations. Detailed analysis of the course of the disease is only reported in a small number of breeds, and breeding analysis to show genetic heterogeneity has been performed in still fewer breeds. The majority of forms of canine PRA are inherited in an autosomal recessive manner. An X-linked form in the Siberian husky has been described. in the Abyssinian cat a dominantly inherited form occurs.

Rod-cone dysplasia type one (rcd1) in the Irish setter The gene mutation for this form of PRA has been identified and a DNA-based test developed. Rcd1-affected dogs show night blindness from as early as six to eight weeks of age and ophthalmoscopic signs are detectable shortly thereafter. Day vision may be lost by one year of age although occasionally affected dogs can retained vision up to about six years of age. The electroretinograph of affected Irish setters is abnormal prior to retinal maturation with rod mediated responses being rapidly lost. Histopathological investigations showed that in rcd1 the retina develops normally for the first 13 days of life after which photoreceptor differentiation becomes arrested. The photoreceptors then go on to degenerate. It ap-

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pears that an abnormal accumulation of cGMP triggers this stop in development of photoreceptors and leads them to die by the process of apoptosis. Once the abnormal accumulation of cGMP (the end metabolite of the visual transduction cascade) was identified this pointed to an abnormality in the cascade. Investigators turned their attention to the members of the visual transduction cascade. The break through was the finding that the messenger RNA for the beta subunit of cGMP phosphodiesterase (cGMP-PDEß) was abnormally low before any alterations in the level of the messenger RNA for other transduction cascade proteins. The gene for cGMPPDEß gene was screened and the causal mutation identified. This was a guanine to adenine transition at nucleotide 2420 altering codon 807 from encoding the amino acid tryptophan to a stop codon. This is predicted to have the effect of producing a premature termination of the cGMP-PDEß protein by 49 amino acid residues. Once the gene mutation was identified DNA-based tests were developed which allowed the identification of both rcd1-affected dogs, rcd1 carriers and genetically normal dogs. The mutation which causes rcd1 has not been demonstrated in any other breeds of dog.

PRA in the Cardigan Welsh corgi PRA was first described in the Cardigan Welsh corgi in the 1970’s and is of early onset, causing blindness at about 2 - 3 years of age. Although not studied in any great detail by electrophysiology or at the histopathological level it has been the subject of a molecular genetic study. This study revealed that the disease was due to a mutation in the gene encoding the alpha subunit of cGMP phosphodiesterase. It is the second form of PRA for which the gene mutation has been identified and the second form involving a subunit of cGMP phosphodiesterase. A DNA-based test is under development.

Rod-cone dysplasia type two in the collie Rod-cone dysplasia type two (rcd2) in the collie shows many similarities to rcd1. There is a similar age of onset and a similar breakdown in visual transduction resulting in abnormally raised cGMP levels followed by photoreceptor dysplasia then degeneration. Studies have shown it is not due to the same gene mutation as rcd1. Despite detailed investigation of visual transduction genes the causal gene defect remains elusive.

Early retinal degeneration (erd) in the Norwegian elkhound Affected dogs are nyctalopic by six weeks of age and blind by 12 to 18 months of age. The electroretinogram does not develop normally, the b-wave is abnormal resulting in an a-wave dominated response. The ERG is extinguished at about one year of age. Histopathology shows that rods and cones do not develop normally and have abnormal synaptic termini, they then go on to degenerate. Defective synaptic transmission from photoreceptors to bipolar cells could ex-

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Photoreceptor dysplasia in the miniature schnauzer Photoreceptor dysplasia (pd) is unusual in that the development of photoreceptors is abnormal from as early as 24 days of age and yet ophthalmoscopic signs of PRA are not evident until later in life and vision is maintained until quite late in the disease progression. The age at which an ophthalmoscopic diagnosis can be made varies from under two years of age until over 5 years of age. Changes in the ERG can be detected well before ophthalmoscopic changes. The rod and cone ERGs are abnormal soon after completion of postnatal retinal maturation and from then on deteriorate rapidly. Screening of the opsin and Îą1-transducin genes failed to find and mutation in pd affected dogs.

PRA in the miniature longhaired dachshund PRA in the miniature longhaired dachshund results in ophthalmoscopically detectable changes from about six months of age, although there is quite a wide range in both age at onset and rate of progression. The ERG develops normally as the retina differentiates but by 17 weeks of age some reduction in b-wave amplitudes are present and by 26 months of age the amplitudes are markedly reduced. Screening a variety of genes for mutations has failed to reveal the cause of this form of PRA.

PRA in the Tibetan terrier PRA in the Tibetan terrier was first reported in Sweden in 1974 and then in the UK in 1978. Nyctalopia and ophthalmoscopic signs of PRA are present at about one year of age. Electroretinographic changes, namely a reduction in b-wave amplitude, are detectable at about 10 months of age. The electroretinographic changes suggest that both rods and cones are affected at the same time, but that rods are lost more quickly than cones. Histopathological changes are recognisable in affected dogs from as young as nine weeks of age. Screening a variety of genes for mutations has failed to reveal the cause of this form of PRA.

X-linked PRA in the Siberian husky This recently described form of PRA is the only naturally occurring model for human X-linked RP. Retinal development appears to occur normally and affected males first develop abnormal rod- and cone- mediated ERG responses

between six and 12 months of age. The ERG responses then deteriorate rapidly. Ophthalmoscopic changes are present by 18 months of age. Histologically, hemizygous males develop lesions as early as 12 months of age. There is then a rapid progression of the disease. Carrier females have reduced ERG amplitudes and develop ophthalmoscopic evidence of patchy retinal thinning, presumed to be due to random X chromosome inactivation. Histologically the lesions range from scattered patches of severe rod loss with partial to complete cone preservation, to diffuse and random loss of cells and their nuclei in the outer nuclear layer. Linkage studies are underway to try and localise the responsible gene on the X chromosome.

Retinal dystrophy in the Labrador retriever A photoreceptor dystrophy has been reported in Labrador retrievers in Scandinavia. The first form of PRA described in this breed was shown to be a progressive rod cone degeneration (prcd) (see below). The condition described in Scandinavia would appear to be different on electrophysiological and histopathological grounds, although test matings to show that two different defects are present in the breed have not been performed. The Scandinavian dogs with retinal dystrophy have ERG abnormalities at seven months of age whereas prcd in the Labrador is reported to be detectable by ERG at between one and 1.3 years of age, additionally animals heterozygous for retinal dystrophy, unlike heterozygotes for prcd are recorded as having detectable ERG abnormalities. Histological investigations of the Scandinavian dogs have shown that they have abnormalities of their photoreceptors at any earlier age than the prcd Labrador. Biochemical studies of the retinal dystrophy Labradors has demonstrated that there are slightly raised levels of cGMP at early stages of retinal differentiation, although unlike rcd1 in the Irish setter there was no demonstrable loss of cGMP phosphodiesterase catalytic activity. Screening a variety of genes for mutations has failed to reveal the cause of this form of PRA.

Progressive rod-cone degenerations in the miniature and toy poodle, cocker spaniels, Labrador retriever and Portuguese water dog Progressive rod-cone degeneration (prcd) was first recognised in the miniature poodle, but is now known to occur in cocker spaniels (American and English), Labrador retrievers and Portuguese water dogs. Test breeding has shown prcd to be caused by mutations at the same gene locus in these breeds, although there are some differences in the disease progression between the breeds. Prcd is numerically the most important form of PRA and has been studied in detail in the poodle. Histopathological examinations suggest that the photoreceptors develop normally and then go on to degenerate. The earliest change detected has been a reduction in the rate of

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plain the abnormal b-wave of the ERG. Molecular studies have excluded a number of genes as the site for the erd mutation. Recently a genetic marker linked to erd has been identified.

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renewal of the photoreceptor outer segments. Outer segments are shed from the distal tips of the photoreceptor and reformed at the proximal end of the outer segment and it is this which is slower in prcd dogs compared to normal animals. Changes in circulating lipid levels in prcd- affected poodles has been observed although the significance of this finding is not clear. The ERG of prcd dogs develops normally as the retina matures, but after then the amplitude of rod responses reduce. Molecular investigations have excluded an number of genetic loci as being the site of the prcd mutation. Recently, a linked marker to the prcd locus has been reported and this is likely to lead to the development of a DNA-linkage diagnostic test and eventually to the identification of the causal mutation(s).

Uncharacterised forms of canine PRA As already mentioned there are many forms of PRA which have not been investigated and await a detailed genetic, histological, electrophysiological and molecular biological investigation. Some may prove to be allelic to forms of PRA already identified but others may represent different gene defects.

Feline PRA Progressive retinal atrophy occurs in two forms in the Abyssinian breed and is suspected in some other breeds including the Siamese. One form in the Abyssinian is dominantly inherited and causes a rapidly progressive loss of vision which is obvious from a few weeks of age. The affected kittens also have a fine oscillatory nystagmus and sometimes a nodding head movement. Fortunately this dominantly inherited form of PRA is very rare in the pet population.

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The second form of PRA in the Abyssinian breed is recessively inherited and affects adult cats. Ophthalmoscopic signs are present from about 1.5 to 2 years of age and are slowly progressive. This form of PRA is common in Scandinavia and occasionally seen in the UK. A later-onset form of PRA is suspected in the Siamese breed, with affected cats presenting at about 10 or 11 years of age. The genetic cause of the various forms of PRA in the cat have not yet been elucidated.

Future investigations Future investigations to develop DNA-based tests for PRA are likely to rely more heavily on finding linked genetic markers. Once the closest possible linkage to a marker has been established this will allow screening of the chromosomal location for potential candidate genes to screen. Spin offs from the human genome project should facilitate this approach because there are similarities between the grouping of genes between species. However, even after linkage is established it can still be a considerable amount of work to find the actual mutant gene and within it the nucleotide change which is ultimately responsible for loss of function of the gene or its resultant protein. We can anticipate the identification of many more PRA causing gene defects and therefore the development of further DNA tests for PRA over the next few years.

Further reading Clements PJM, Sargan DR, Gould DJ, & Petersen-Jones SM. (1996) Recent advances in understanding the spectrum of canine generalised progressive retinal atrophy. Journal of Small Animal Practice 37, 155162. Petersen-Jones SM. (1998) A review of research to elucidate the causes of the generalized progressive retinal atrophies. The Veterinary Journal. 155, 5-18.

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An approach to sudden-onset blindness S.M. Petersen-Jones

Summary Sudden-onset blindness may result from serious intraocular disease or lesions involving the central visual pathways. Identification of the aetiology requires careful and thorough examination and in some cases the use of specialist techniques such as electroretinography and advanced imaging. The prognosis for return of vision in some instances is poor and in many is hopeless.

Sudden-onset loss of vision can result from a number of different conditions. Often for the loss of vision to be obvious to the owner it will involve both eyes. The conditions which can result in a sudden loss of vision can be divided into the following three categories: • those which result in ophthalmoscopic signs such as acute glaucoma, acute uveitis, intraocular haemorrhage, retinal detachment • those which result in blindness with dilated fixed pupils e.g. sudden acquired retinal degeneration syndrome (dogs only) and lesions involving both optic nerves, the chiasma or both optic tracts • those resulting in blindness with normal pupillary light responses e.g. bilateral lesions of central visual pathways from lateral geniculate nuclei to visual cortex. The latter two categories can present a diagnostic challenge. In addition to a complete ophthalmic and neurological examination techniques such as electroretinography and computed tomography or magnetic resonance imaging investigation can help identify the site of the abnormality.

The sudden loss of vision in a pet is a very distressing event for owner and animal alike. To the veterinarian it can present a diagnostic challenge, particularly if there are no ophthalmoscopically detectable changes to account for the blindness.

• any other changes noticed, e.g. in appearance of eyes, in behaviour? • was loss of vision associated with any particular event e.g. trauma, illness? • did the owners notice the vision loss after their pet was moved to different surroundings (many animals cope well with failing vision in familiar surroundings)? • how much does the pet normally rely on vision i.e. is it a working dog, a house-bound cat or a lap dog? The owner’s assessment of vision is not always reliable. Many cats and dogs which gradually lose vision cope surprisingly well in familiar surroundings and the owners may not immediately realise there is a problem. In such cases if the animal is moved to unfamiliar surroundings the loss of vision becomes suddenly obvious and the owners assume it is sudden onset.

EXAMINATION Vision testing An assessment of the animal’s vision should be made. From the behaviour of the animal in the consulting room it is usually obvious if it has suddenly lost vision. Additional techniques employed to assess vision include an obstacle course, visual tracking of cotton-wool balls dropped in front of the animal, menace response and placing reactions.

Clinical assessment A general physical examination should be performed as should a thorough ophthalmic and neuro-ophthalmic examination. In cases where a central (CNS) lesion is suspected a full neurological work-up should also be carried out.

Pupillary light reflexes HISTORY As usual a good history can be invaluable. The following points may be useful to consider: • any previous ocular problems or systemic disease? • rate of progression of apparent loss of vision

The pupillary light reflex (PLR) can be an informative part of the examination and should always be checked, however it must be remembered that it is not a measure of the conscious perception of vision. Animals can have a normal PLR and yet be blind due to cortical lesions or alternatively can have an absent PLR e.g. due to atrophy of the pupillary

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constrictor musculature and yet still have normal vision. The extent and speed of pupillary constriction should be noted for both the direct and consensual reflex of both eyes. The direct PLR is the constriction of the pupil in the eye in which the light is shone, the contralateral pupil should also be checked (the consensual PLR). The consensual PLR can be assessed by quickly swinging the examination light from one eye to the contralateral one and if the reflex is normal the pupil should already be constricted. The pupillary responses are often sluggish in normal animals when they are initially examined, due to the action of circulating adrenaline. However, in most animals the speed of the pupillary responses return to normal after a few minutes.

REACHING A DIAGNOSIS The results from the history taking, vision testing and clinical examinations should enable a list of differential diagnoses to be made. The animal presenting with a true sudden loss of vision will fall into one of the following categories: • sudden-onset blindness caused by ophthalmoscopically detectable intraocular disease • sudden-onset blindness accompanied by dilated non-responsive pupils, but no other ophthalmoscopically detectable changes • sudden-onset blindness with normal PLR and no ophthalmoscopically detectable changes These categories will each be considered in turn:

SUDDEN-ONSET BLINDNESS CAUSED BY OPHTHALMOSCOPICALLY DETECTABLE INTRAOCULAR DISEASE There are a number of ocular conditions that can result in a sudden-onset blindness: • Acute uveitis or glaucoma can render the affected eye blind. Usually pain and the altered appearance of the eye are the presenting signs rather than the loss of vision. • Cataracts. In some instances cataracts can progress rapidly and therefore cause a fairly rapid loss of vision. Diabetic cataracts are one example of this. • Intraocular haemorrhage. This can result in a sudden loss of vision in the affected eye. Haemorrhage may result from ocular trauma, neoplastic intraocular changes, bleeding from abnormal vasculature (remnants of embryonic vasculature), or may be secondary to other intraocular disorders such as collie eye anomaly or retinal detachment. Systemic disease including clotting disorders and hypertension, can also result in intraocular haemorrhage. • Retinal detachment. Complete retinal detachments results in a sudden-onset vision loss. Unilateral detachments are not always apparent to the owner and animals may only be presented if the other retina detaches. Aetiologies to consider include trauma, inflammatory or neoplastic posterior segment disease, retinal dysplasia, collie eye anomaly, retinal holes, and vitreous traction bands. Detachment also occurs secondary to systemic disease such as hypertension,

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this is particularly common in older cats. Management consists of treating any underlying conditions and, if their use if not contraindicated, prescribing systemic corticosteroids. Bullous retinal detachments will often resolve with treatment, in many cases restoring useful vision. However the longer the retina has been detached the less likely it is that a successful outcome will be achieved. Generally speaking if a retinal tear or hole is present liquefied vitreous will gain access to the subretinal space through the retinal defect and prevent reattachment. Surgical intervention in such cases may offer the only hope of achieving reattachment, but as yet the success rate in animals is low, the procedures are not widely practised and in some cases the late presentation means that the retinal pathology is already too advanced for successful restoration of vision. • Papillitis. Inflammation involving the optic nerve head (disc) will cause blindness in the affected eye and an absent direct and consensual PLR. The affected disc looks swollen, reddened and may have surface hemorrhages. There is usually oedema of the surrounding retina and possibly haemorrhage. The list of possible aetiologies includes canine distemper, granulomatous meningioencephalitis, and systemic fungal disease such as cryptococcosis. However, the majority of cases are idiopathic, and probably immune-mediated. Treatment is by administration of high levels of systemic corticosteroids, unless contraindicated (e.g. for the systemic mycoses). Prognosis is guarded as recurrence is common and eventual optic atrophy may result.

SUDDEN-ONSET BLINDNESS ACCOMPANIED BY DILATED FIXED PUPILS, BUT NO OTHER OCULAR SIGNS The nerve fibres from the retina which form the afferent arm of the pupillary light reflex accompany fibres for vision along the optic nerve, through the optic chiasma and pass along the optic tract before branching off just before the lateral geniculate body. Therefore lesions affecting the retina or central visual pathways prior to the lateral geniculate body will also alter pupillary responses. Bilateral complete lesions result in dilated, fixed pupils. When the condition is unilateral, affecting only one retina or optic nerve there will be no direct or consensual pupillary light response on the affected side, and yet there will be a consensual response from the other eye. When a unilateral optic tract lesion is present the situation is more complicated because the vision and PLR from both eyes is affected but not equally. The vision and PLR of the eye contralateral to the optic tract lesion are more severely compromised. The differential diagnoses to consider are: • sudden acquired retinal degeneration syndrome (SARDS). This condition typically affects middle-aged, slightly obese dogs and causes a bilateral and rapid loss of vision due to extensive retinal photoreceptor damage. Initially the fundus looks ophthalmoscopically normal, but eventually changes resulting from generalised retinal degeneration become obvious. The aetiology of SARDS is unknown and the resulting retinal damage is permanent. SARDS must be distinguished from sudden-onset blind-

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dents can all affect the central visual pathways and can result in a rapid loss of vision. Advanced imaging techniques such as computerised tomography and magnetic resonance imaging, although expensive and not widely available, are useful for demonstrating the presence of space-occupying lesions impinging on the central visual pathways.

SUDDEN-ONSET BLINDNESS WITH NORMAL PLR AND NO OCULAR SIGNS This results from bilateral lesions involving the higher segments of the central visual pathways; the lateral geniculate nucleus, optic radiation or optic cortex. Bilateral lesions may result from prolonged cerebral hypoxia, encephalitis (e.g. chronic distemper) or hydrocephalus. Other severe neurological signs are likely to be present. Treatment and prognosis depend on the aetiology.

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ness due to bilateral lesions of optic nerves or tracts, or lesions involving the optic chiasma. Optic neuritis involving the retrobulbar portion of the optic nerves is probably the main differential. An electroretinogram (ERG), which is a test to measure the electrical responses of the retina as a result of light stimulation, is useful in making the diagnosis. Dogs with SARDS do not have a recordable ERG, whereas lesions of the central visual pathways do not initially alter the ERG. â&#x20AC;˘ Retrobulbar optic neuritis. This typically presents as a sudden loss of vision accompanied by dilated fixed pupils and no funduscopic changes. It must be distinguished from SARDS by electroretinography. The differentiation is important for prognostic reasons; optic neuritis will often respond to systemic corticosteroids whereas SARDS will not. The potential aetiologies are the same as listed for papillitis and as with papillitis recurrence is possible. â&#x20AC;˘ Other lesions affecting optic nerves, chiasma or optic tracts. Inflammatory lesions, neoplasms and vascular acci-

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Managing corneal ulceration in small animals S.M. Petersen-Jones DVO, Dipl ECVO, MRCVS Department of Small Animal Clinical Sciences College of Veterinary Medicine Michigan State University, East Lansing - USA

Corneal ulceration is a common problem in small animal ophthalmology. Ulcers may range from superficial (just involving the epithelium) to deep and even result in corneal perforation. There are a number of possible causes including trauma, infection (herpesvirus as a primary infective cause in cats or bacteria as a secondary complication in cats and dogs) and secondary to other ocular disease. A full examination of each case presenting with an ulcer should be undertaken looking for predisposing factors and concurrent disease. Refractory or indolent ulcers just involve the epithelium and require specific treatment to encourage healing. This consists of removing all the loose epithelium and performing a grid or punctate keratotomy. Deep or progressive ulcers require a different approach. The possible involvement of bacteria should be investigated and aggressive medical therapy undertaken. Conjunctival pedicle grafts can be a very successful way of dealing with ulcers that are either deep or are progressing despite intensive medical therapy.

Corneal ulceration is a common presenting problem in small animal ophthalmology. An ulcer is defined as a break in integrity of the corneal epithelium. Ulcers range in severity from those which are superficial (just involving the epithelium) to those which may extend deeper into the cornea and may even result in corneal perforation. When ulcers extend to Descemet’s membrane the resulting lesion is known as a descemetocoele. The management indicated for the ulcer depends on the type and depth of the ulcer and the presence of concurrent ocular disease.

PRESENTING SIGNS A break in the integrity of the corneal epithelium results in exposure of corneal nerve endings and hence pain. A trigeminal reflex arc can lead to an accompanying anterior uveitis which adds to the discomfort resulting from some corneal ulcers. The resulting ocular pain is typically manifest by increased lacrimation and blepharospasm. Superficial ulcers can be more painful than deeper ulcers because of the greater number of nerve endings in the superficial layers of the cornea.

In addition to the signs of pain, the owners may also notice the resulting change in appearance of the cornea.

SIGNALMENT & HISTORY A good clinical history should be taken. This may indicate the possible cause of the ulcer, reveal the duration of the problem and indicate if any treatment has already been given.

EXAMINATION As with every case a complete ophthalmic examination must be performed and a general physical examination should also be included. The examination should be both methodical and thorough so as not to miss any predisposing factors which might be contributing to, or even causing, the ulceration. A darkened room and bright pen-torch or transilluminator are necessary for the examination. Unless there is obvious profuse lacrimation a Schirmer tear test should be performed to assess tear production. This test must be performed prior to the addition of any fluid to the ocular surface or undue manipulation of the eye. Confirmation of the presence of corneal ulceration is by the application of fluorescein.

Fluorescein staining • Use a fluorescein impregnated strip, apply one drop of saline to the strip and apply this to the bulbar conjunctiva - the minimum amount of dye should be applied; • flush the conjunctival sac well with sterile saline to avoid any false impression of staining (particularly in eyes with keratoconjunctivitis sicca); • fluorescein passes into any exposed corneal stroma staining it bright green. Use of a blue light enhances the fluorescent appearance of the dye; • fluorescein will not cross an intact (or superficially damaged) corneal epithelium; • fluorescein does not stain Descemet’s membrane; • fluorescein staining may not be obvious in very oedematous corneas.

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Other stains Rose bengal stain can be used to demonstrate damage to corneal epithelial cells. It is commonly use to demonstrate the presence of dendritic “ulcers” in feline herpesvirus infections.

Magnification Closer examination of lesions using magnification is very useful. Without magnification is can be difficult to judge the depth of ulcers and impossible to visualise significant abnormalities such as ectopic cilia. The biomicroscope slit-lamp is the ideal instrument to provide this magnification. It can be used with a full beam of light to examine the lids and conjunctival sac and survey the anterior segment of the eye, but it can also be used with a narrow beam of light directed at an angle from the microscope to achieve a so called “optical section” of the cornea. This optical section is particularly useful for judging the depth of ulcers. Other illumination techniques include the use of retroillumination utilising light reflected from the fundus or the iris. This technique silhouettes corneal opacities. Other ways of examining the cornea using magnification include using a direct ophthalmoscope with a high positive dioptre setting, or a magnifying loupe.

Appearance of corneal ulceration The changes visible on the cornea depend on the extent and depth of the ulcer as well as its duration. In addition to the ulcer itself which may appear as a slight “roughening” of the cornea up to a large crater with liquefaction of surrounding corneal stroma there may be the following: • corneal oedema • corneal vascularisation (superficial and/or deep) • superficial corneal pigmentation • signs of an accompanying anterior uveitis When examining the ulcer the depth and extent should be assessed looking for evidence of corneal stromal liquefaction (due to protease release from bacteria, neutrophils or from damaged keratocytes). Identification of intraocular involvement such as an accompanying anterior uveitis, hypopyon or even corneal perforation is important.

Further investigations Collection of material from the ulcer edge for microscopic examination for the presence of pathogens, culture and possible use of other tests for the detection of pathogens (e.g. polymerase chain reaction tests) may form part of the workup of corneal ulcers, in particular deeper or progressive ones.

AETIOLOGY OF CORNEAL ULCERATION There are several possible aetiologies for corneal ulceration including:

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• Trauma • Foreign bodies e.g. grass seed under nictitating membrane. • Chemical injuries detergents, spirit, alkalis (tend to melt corneal stroma and can rapidly deepen e.g. ammonia, lime), acids (coagulate corneal protein and do not deepen). • Thermal injuries • Cilia abnormalities ectopic cilia (when present often cause ulceration), distichiasis & trichiasis (don’t often cause ulceration). • Lid abnormalities entropion. • Tear film abnormalities keratoconjunctivitis sicca (ulceration is commonest with acute onset KCS), corneal drying during anaesthesia (e.g. cat anaesthetised with ketamine - this is really an exposure problem). • Exposure keratitis an inadequate blink can cause corneal dry spot formation and ulceration. • Neurotrophic keratitis corneal anaesthesia (lesion of ophthalmic branch of trigeminal nerve) will often cause a superficial ulcerative keratitis of the area of cornea exposed within the palpebral fissure. • Secondary to other corneal disease e.g. lipid keratopathy, calcific corneal degeneration. • Refractory (non-healing) or indolent corneal ulcers Some of these types of ulcer may be due to a form of corneal epithelial dystrophy. The hemidesmosomes which anchor the basal epithelial cells to the basement membrane are reduced in number and the epithelial membrane itself is abnormal. Dogs affected in this manner are considered to have a true primary corneal epithelial dystrophy. Classically the boxer and corgi are described as suffering from this condition. A clinically indistinguishable condition is encountered quite commonly in a variety of breeds. These ulcers involve the epithelium only. The surrounding epithelium is often nonadherent and may fold back on itself. • Infected corneal ulcers Feline herpesvirus infection can result in classical dendritic ulcers. When seen such ulcers are considered pathognomonic for herpes, however other forms of ulceration possibly associated with stromal keratitis may also result from herpes infection. When herpes is suspected collecting corneal material for viral culture or preferably polymerase chain reaction tests to demonstrate the presence of viral DNA can be useful. In some geographical locations corneal fungal infections can occur. Most of the significant infective ulcers involve bacteria. Primary bacterial pathogens are not recognised as a cause of ulceration in cats and dogs, however bacterial contamination of corneal injuries can occur. Potentially pathogenic contaminating bacteria adhere to, and therefore colonise damaged epithelial cells and stroma. This leads to infection and possibly a progression of the ulcer. Material collected from the edge of such an ulcer is useful for culture and also direct microscopic examination. One slide should be stained with a stain such as Diff-Quik to demonstrate the presence of bacteria and then a Gram’s stain performed on a second slide to give a rapid guide as to the type of bacteria involved. Pseudomonas aeruginosa is notorious because of its association with melting corneal ulcers. These are ulcers in which there is a rapid liquefaction of the corneal stroma with a real risk of perforation. Proteases

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MANAGEMENT OF CORNEAL ULCERS Superficial abrasions will heal quickly without treatment although a covering broad spectrum antibiotic is usually provided. When one of the predisposing factors listed above is identified this should be treated appropriately. Ulcers which are failing to heal or are deepening may need more specific therapy and are considered below.

ated with gram-positive organisms a fortified solution of cefazolin (33mg/ml) or penicillin G (100,000 units/ml) can be used. Agents to inhibit corneal melting have been suggested and include EDTA and serum. Atropine may be given to treat any concurrent reflex uveitis. Surgical intervention to apply a conjunctival pedicle graft is a very useful line of management and should be used if medical therapy does not lead to a rapid halting of the progression of a melting ulcer. Grafts provides a blood supply (and hence antibacterials and antiprotease substances) and support for the affected cornea. Third eyelid flaps still have a limited role but are not advisable for ulcers deeper than one half of the corneal thickness or those that are progressing rapidly. DO NOT GIVE ‘STEROIDS until the cornea has re-epithelialised. Note that deep ulcers may epithelialise leaving a corneal defect (facet).

Indolent ulcers Conjunctival grafts These are nonhealing ulcers that just involve the corneal epithelium and show little tendency to heal. One potential cause is an epithelial basement dystrophy. The ulcers fail to heal because the epithelium does not form the proper junctions to anchor it to the basement membrane. Indolent ulcers are commonest in dogs but can occur in cats. They can be very frustrating to deal with unless the appropriate management is undertaken. Treatment Indolent ulcers typically require surgical intervention to encouraging healing. The first stage is to strip all the nonadherent epithelium off the cornea. A dry cotton bud can be used for this or a #15 blade (employing a brushing motion rather than a cutting motion). Following removal of all nonadherent epithelium small puncture wounds are made into the anterior stroma using a 23 gauge needle (punctate keratotomy). Alternatively a grid pattern of superficial scratches can be made over the exposed corneal stroma (grid keratotomy). A contact lens can be applied as an adjunct to this therapy.

Deeper ulcers or deepening ulcers Bacterial infection of the corneal surface can lead to progressive ulceration, some initial injury is usually required to allow bacteria to adhere to the ocular surface as the preliminary step in causing infection. Release of proteases from bacteria, polymorphs or corneal keratocytes can lead to liquefaction of corneal stroma and rapid progression of some ulcers. The most severe cases can progress over a matter of hours and are described as melting ulcers. When overlying stroma is removed, Descemet’s membrane may bulge forward (descemetocoele). Note that Descemet’s membrane does not take up fluorescein. A descemetocoele is easily ruptured so a surgical repair will be required. Investigation Swabs for bacteriology and cytology should be performed Treatment Progressive deepening ulcers should be treated aggressively with an appropriate antibiotic applied frequently. If a gram-negative infection is suspected ciprofloxacin may be useful, this is initially applied hourly for six hours then every two hours. For serious ulcers associ-

Conjunctival grafts, free or more usually attached, are very useful for the management of serious sight threatening corneal ulcers and can be readily performed using a minimum of specialised equipment.

Indications for conjunctival grafts Conjunctival grafts are usually reserved for the treatment of corneal ulcers which are deeper than one half of the corneal thickness or where satisfactory healing without surgical intervention is unlikely. Conjunctival grafts can be used to save vision in eyes with descemetocoeles, melting and even perforated ulcers. They offer very significant advantages over techniques such as third eyelid flaps and tarsorrhaphies. The advantages of conjunctival grafts are that they: • provide support for weakened cornea; • provide an immediate blood supply to the ulcer (except for free grafts); • serum contains anticollagenases which are useful for melting ulcers where proteases are active; • serum supplies antibacterial substances; • with the exception of total conjunctival flaps, continued visualisation of the cornea and intraocular structures is possible; • are readily performed and highly successful; • are useful following keratectomy for feline corneal sequestrum removal and it is suggested that they reduce recurrence of the sequestrum. The main disadvantage of their use is the resulting area of corneal opacity at the ulcer site, however this is a minor drawback compared to the risks of corneal perforation and loss of the eye if grafting is not performed.

Types of conjunctival graft The selection of graft depends on the extent and position of the ulcer and the health of the surrounding cornea (for suture placement). The most versatile and useful graft is the

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produced by the bacteria are blamed for this melting effect. However, proteases can also be released from polymorphs and some melting ulcers (from which bacteria are not isolated) are presumed to be due to release of these proteases.

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pedicle graft which can be used on large and even perforated ulcers. Other patterns of conjunctival graft include; bridge, hood and total grafts and free island grafts.

Technique of applying conjunctival grafts Prior to placement of the graft the ulcer site should be gently cleaned or debrided to remove necrotic corneal stroma. Any corneal epithelium which has started to grow down into the depths of the ulcer crater should be removed by gentle scraping using a #15 scalpel blade, taking care to avoid the depths of the ulcer. Failure to do this can mean that the conjunctival flap may detach from the ulcer site. Conjunctival flaps or grafts should be fashioned so that they are as thin as possible and while dissecting them it should be possible to see the dissecting scissors through them. When suturing the conjunctiva to the cornea the sutures should pass to approximately 3/4s of the depth of the cornea. After placement of the graft the conjunctiva will heal into the ulcer site and provide a good blood supply to encourage corneal healing within two to three weeks. After this time the flaps may be trimmed or dissected free. Total and hood flaps usually need to be dissected free as the conjunctiva will have adhered to areas of the cornea which is not epithelialised. Conjunctiva should be left over the deep part of the ulcer to act as a plug for the defect to confer strength to the weakened cornea. Over the subsequent months some degree of remodelling of the remaining graft will occur.

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repairing the corneal defect. The graft is then cut just above the ulcer site and the conjunctival pedicle left to retract and remodel. A piece of conjunctiva will have been left in situ within the ulcer site. In cases with corneal perforation a conjunctival pedicle graft can effect a good repair. Prolapsed iris should be freed from the cornea and replaced into the anterior chamber. The graft should be fashioned and sutured in place. Balanced salt solution (Alcon Ltd) or sodium hylauronate (Healonid, Pharmacia Ltd) can be used to reform the anterior chamber. It can be difficult to achieve a water-tight seal between the graft and the edge of the corneal defect. If this is not achieved aqueous leakage occurs, the anterior chamber can collapse possibly leading to an iris-cornea adhesion (anterior synechiae). A continuous suture pattern may help achieve a water-tight seal.

Other surgical techniques for managing corneal ulcers Small deep ulcers with healthy surrounding cornea may be closed by direct suturing. Larger defects can be repaired by performing a corneoscleral transposition. The advantage of this technique is that is successful there will be less corneal opacity than with a conjunctival pedicle graft. The disadvantage is that the technique does not provide a blood supply to help heal the ulcer and halt any protease action. Other techniques include the use of grafts of frozen cornea.

Conjunctival pedicle grafts Conjunctival pedicles may be fashioned either by dissecting a pedicle of conjunctiva from bulbar conjunctiva parallel to the limbus and then rotating it onto the cornea, or by dissecting a pedicle at 90 degrees to the limbus which extends into the fornix and then is advanced over the cornea. Which ever approach is used the graft should be slightly wider than the defect and be able to reach and cover the defect without being under tension. The sutures to hold the graft in place (e.g. 8/0 Vicryl) are passed into the walls of the ulcer crater ensuring that they pass into relatively healthy cornea. After 3 weeks the graft should have healed in place

FURTHER READING Champagne ES & Munger RJ (1992) Multiple punctate keratotomy for the treatment of recurrent epithelial erosions in dogs. J Am Anim Hosp Assoc 28:213-216. Hakanson N, Lorrimer D & Meredith RE (1988) Further comments on conjunctival pedicle grafting in the treatment of corneal ulcers in the dog and cat. J Am Anim Hosp Assoc 24:602-605. Hakanson NE & Meredith RE (1987) Conjunctival pedicle grafting in the treatment of corneal ulcers in the dog and cat. J Am Anim Hosp Assoc 23:641-648. Parshall C (1973) Lamellar corneal-scleral transposition. J Am Anim Hosp Assoc 9:270.

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Ocular manifestations of feline eosinophilic complex in the cat Stefano Pizzirani

Ocular manifestations of feline eosinophilic complex are several and they involve different ocular structures of the anterior segment (single or associated) and of the orbit. Similar diseases happen in human beings, being included in Histyocitosis X. No obvious link is yet considered with Feline Eosinophilic Granuloma Complex (EGC). Nevertheless some references have been hypothesised with Eosinophilic Plaque (EP)3, Collagenolytic Granuloma (CG)2 and Indolent Ulcer (IU)1. Eosinophilic reaction patterns in cats are multiple and not everyone of them must be included in the EGC. This could be only one of the manifestations or reactions possible in a larger and more complex problem11,20,21. Cause are unknown. Food allergy, atopy and parasite reaction are the most frequent hypothesis and the group of lesion is believed to be an immune mediated reaction (type I or IV hypersensitivity reaction). Clinical manifestations are: - blepharitis - blepharo-conjunctivitis - conjunctivitis - keratoconjunctivitis - keratitis - orbital granuloma (?). Lesions may be mono or bilateral. No sex or breed or age incidence has been described which was statistically significant. But two authors report higher incidence of eosinophilic keratitis in male castrated cats1,9. Maybe a more determined clinical grading with reference to single aspects would be more rewarding. Palpebral lesions show erosive or ulcerative dermatitis, well demarcated, which interests the skin of the lid. The lid margin becomes leukodermic because inflammatory cells infiltration. The palpebral conjunctiva may be interested by an inflammatory process as well. Blepharospasm and ocular discharge may be present. Conjunctival forms present redness, chemosis and/or tickening of the conjunctival layers. Blepharospasm and ocular discharge come along primarily with the oedematous form. We had a case with a severe keratoconjunctivitis sicca because obstruction of the lacrimal ducts. Anyway no investigation was done to ascertain the presence of a lachrymal adenitis too. Nodular raised conjunctival localised proliferations can be met on the outer surface of the nictitans. We had three

cases all in Persian cats as was the only one in literature2 but these data are too few to predict a breed predisposition. Cornea is invaded by proliferative tissue, with neovascularization. It can be localised or diffuse. Usually it is confined to the supero temporal quadrant, starting from the limbus. Ocular pain is rare but sometime the third eyelid is slightly prominent, especially if compared to the normal eye. Fluorescein test is negative but sometime, small positive erosion are seen over the proliferative tissue, corresponding at small disepithelialized foci14. Whitish to yellowish deposits are often seen on the corneal surface. Less commonly on the conjunctiva. Orbital deposition of eosinophilic cells infiltrate cause exoftalmia7. Pruritus is not common, except for those lesions referred as EP. Peripheral eosinophilia is not a consistent finding8,9,10. Contemporary clinical syndromes referred as EGC are rarely seen. No strict relationship has been showed to exists between this group of lesions and FeLVhg or FIV, or internal parasites. Some Authors advocate FHV-1 infection as one of the predisposing factors4,9. Diagnosis is made with cytology or biopsy. Cytology is less invasive, more rapid and usually diagnostic and show an high number of eosinophils with few mast cells. Neutrophils, lymphocytes and plasma cells are also be a possible finding. Variable pattern may be encountered, probably as different evolutions of time. Chronic phases tend to be fibrovascular with increasing number of mononuclear cells and decreasing number of eosinophils. A thorough examination should be performed and dietary elimination trails, intradermal skin tests and/or serological tests (RAST or ELISA)12,22,23 should be proposed. Differential diagnosis include: Chlamidia, FHV-1 and Mycoplasma infections, granulation tissue from corneal ulcer healing, mycotic blepharitis, orbital cellulitis and neoplasia. Treatment uses local and systemic corticosteroids. Cats need higher dosage regimen than other animals because the few corticosteroid receptors. Prednisolone seems to be preferred at prednisone and the dosage stays around 4.4 mg / kg once a day. Methylprednisolone acetate may be used as deposit drug and 4-5 mg/kg should be given every 15-20 days. It is used usually for non treatable animals and chronic therapies. We still anyway prefer for long standing therapies to

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use if possible, injectable prednisolone once or twice a week. Cases of iatrogenic Cushing syndrome are reported. Megestrol acetate seems to have greater efficacy. This is clinically reported but not scientifically proven. This seems also to be the preferred drug by Oculists and the damned one by Dermatologists and Internists. Many side effects have been claimed as adrenocortical suppression, diabetes mellitus, mammary fibroadenomatous hyperplasia, mammary neoplasia, pyometra, personality changes, poliphagia, polydipsia1,3,9,10,16,17,18,19. Anyway many side effects have been also reported with long standing high-dosage corticosteroids treatments. We use Megestrol acetate as first preferred treatment. Its efficacy is clinically better than corticosteroid one and sometime it is efficacious where cortisone was not. We use 5 mg/cat for 2-3 days, than reduce at 5 mg/cat twice a week for 1-2 weeks, 5 mg/cat once a week for 2-4 weeks and then 5 mg/cat every two weeks for 2-4 times. Differences are because different clinical situations and different responses. It should not be used for chronic treatment. Diabetic animal and pregnant female should not be treated. Cyclosporine has variable efficacy and there is no literature on it about the disease. We use it in combination with topical dexamethasone, especially when the Schirmer tear test is low. Very few times we have used it topically as the only treatment but its efficacy was low. Immune modulators have been reported to be used in the treatment of the EGC13,15. Therapeutical response vary. Some lesion never appear again, some do. Some need chronic treatment. Similarly this happens for different degrees of EGC. To understand the cause, making a good staging and grading of the disease, knowing more about immunological status of the patient, proposing a therapeutic protocol could be the way to match the problem and to have good data to interpret. Unfortunately the rarity of the ocular disease makes prospective studies too difficult and retrospective ones too limited.

References

3. 4. 5. 6. 7.

10. 11. 12.

13. 14.

15.

16.

17.

18.

19.

20. 21. 22.

Paulsen M.E., lavach J.D., Severin G.A., Eichenbaum J.D. “Feline Eosinophilic Keratitis: A Review of 15 Clinical Cases.” JAAHA, vol. 23, N° 1, 63-69, 1987. Keil S.M., Olivero D.K., McKeever P.J., Moore F. “Bilateral Nodular Eosinophilic Granuloma of the Nictitating Membrane of a Cat” Pro-

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ceedings of the ACVO Meeting 1995. Latimer C., Dunstan R.W. “Eosinophilic Plaque Involving Eyelids of a Cat” JAAHA, Vol. 23, N° 6, 649-653, 1987 Nasisse M. Personal Communication. ISVO Meeting 1997. Kipnis R.M. “Corneal Eosinophilic Granuloma” Fel. Pract., Vol. 9, N°6, 49-53, 1979. Pentlarge V.W. “Eosinophilic Conjunctivitis in Five Cats” JAAHA, Vol. 27, N° 1, 21-28, 1991. Dziezyc J., Barton C.L., Santos A. “Exoftalmia in a Cat caused by an Eosinophilic Infiltrate” Prog. In Vet. & Comparative Ophthalm., Vol. 2, N° 2, 91-93, 1992. Center S.A., Randolph J.F., Erb. H.N., Reiter S. “Eosinophilia in the Cat: A Retrospective Study of 312 Cases (1975 to 1986)” JAAHA, Vol. 26, N° 4, 349-358, 1990. Morgan R.V., Abrams K.L., Kern T.J. “Feline Eosinophilic Keratitis: A Retrospective Study of 54 Cases: (1989 – 1994)” Vet. & Comp. Ophthalm., Vol. 6, N° 2, 1996. Bedford P.G.C., Cotchin E. “An unusual chronic keratoconjunctivitis in the cat” J.Small Anim. Pract. (1983) 24, 85-102. Rosenkrantz W. “Eosinophilic Granuloma Complex (Confusion)” Veterinary Focus, Vol. 1, N° 1, 29-32, 1989. Power H.T., Ihrke P.J. “Selected Feline Eosinophilic Skin Diseases” Vet. Clinics of North America, Small Anim. Pract., Vol. 25, N° 4, 833-850, 1995. Song M.D. “Diagnosing and treating feline eosinophilic granuloma complex” Veterinary Medicine, pp. 1141-1145, 1994. Prasse K.W., Winston S.M. “Citology and Histophatology of Feline Eosinophilic Keratitis” Vet. & Comp. Ophthalmology, Vol. 6, N° 2, 74-81, 1996. McEwen E.G., Hess P.W. “Evaluation of Effect of Immunomodulation on the Feline Eosinophilic Granuloma Complex” JAAHA, Vol. 23, N° 5, 519-526, 1987. Mansfield P.D., Kemppainen R.J., Sartin J.L. “The Effects of Megestrol Acetate Treatment on Plasma Glucose Concentration and Insulin Response to Glucose Administration in Cats.” JAAHA, Vol. 22, N° 4, 515-518, 1986. Chastain C.B., Graham C.L., Nichols C.E. “Adrenocortical suppression in cats given megestrol acetate” Am.J.Vet.Res., 42, 2029-2035, 1981. Kraus M.S., Calvert C.A., Jacobs G.J., Brown J. “Feline Diabetes Mellitus: A Retrospective Mortality Study of 55 Cats (1982 – 1994)” JAAHA, 33, 107-11, 1997. Middleton D.J., Watson A.D.J. “Glucose intolerance in cats given short-term therapies or prednisolone and megestrol acetate” Am.J.Vet.Res., Vol. 46, N° 12, 1985. Neer T.M. “Hypereosinophilic Syndrome in cats” Compendium, Vol.13, N° 4, 549-555, 1991. Harvey R.G. “Feline hypereosinophilia with cutaneous lesions” J.Small Anim.Pract. (1990), 31, 453-456. Halliwell R.E.W. “Efficacy of Hyposensitization in Feline Allergic Disease Based Upon Results of in vitro Testing for Allergen-Specific Immunoglobulin E” JAAHA, 33, 282-288, 1997. Roudebush P., McKeever P.J. “Evaluation of a Commercial Canned Lamb and Rice Diet for the Management of Cutaneous Adverse Reactions to Food in Cats.” Vet. Dermatology, Vol. 4, N° 1, 1-4, 1993.

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61 Lens dislocation Stefano Pizzirani

The lens maintains its anatomical position due to the suspensory apparatus, which is the zonule, lens equator and ciliary body. Every disease involving these structures may be responsible for partial or total dislocation of the lens (subluxation / luxation). Lens displacement may be congenital, primary (hereditary transmitted) or secondary. Congenital aetiologies are represented by microspherophachia, are rare and often included in multiple ocular anomalies.1,2,3,6,10 Hereditary causes are more frequent in particular breeds as Terrier breeds8, Shar peis12, Border collies9 and Italian Volpino*. However many other breeds can be involved. Curtis describes altered zonular anatomy as main cause in terrier8. Collagen diseases are the basis for similar conditions in human beings4,5. Terriers may show the disease ranging from 3 to 8 years, while Shar peis can be involved earlier. Glaucoma, trauma, cataract, uveitis and senile degeneration13 may cause secondary lens displacement. Early diagnosis is important for reproductive and therapeutic purposes. Clinical signs are reddish limbal conjunctiva and sclera, vitreous hernia, aphachic crescent, variations in the pupillary shape, alterations in the PLR for pupillary block, variations in the IOP and depth of the anterior chamber, with irido and phacodonesis. Later glaucoma develops. Four main mechanisms have been avocated in the pathogenesis of glaucoma in human beeings4: pupillary block caused by an anterior luxated or subluxated lens, peripheral anterior synechiae, postcontusion angle deformities and phacolytic glaucoma (which has not been yet reported in veterinary medicine). Primary glaucoma usually does not exhibits a completed luxated lens. It stays attached at a side of the ciliary processes usually. In primary luxation usually the lens is free at 360°. Anterior luxation is often an acute case with pain and discomfort (increased lacrimation and blepharospasm). Sometime a superficial examination, with a narrowed palpebral fissure, may not be able to recognise the non cataractous lens in the anterior chamber. In our experience it can happen more easily in the cat. A recurrent anterior luxation must be suspected when a central posterior corneal oedema is present. When a complete corneal oedema comes with anterior luxation, ultrasound may be helpful for diagnostic purposes.

*Personal data

Diagnosis can be easily achieved with a slit lamp. Use of a mydriatic agent is strongly advised to pick up the early cases. The other eye must be always thoroughly examined. A gonioscopy must be achieved in the other eye when a glaucoma and lens displacement is present in one eye. It is important to educate the pet owner about the high risk for the normal eye in primary displacement and the importance to have it examined early in case of clinical signs.

i SLIT LAMP EXAMINATION. NORMAL EYE.

K CORNEAL SLIT I IRIDAL SLIT L ANTERIOR CAPSULE SLIT

i k

SUBLUXATION

i k

POSTERIOR LUXATION

Treatment varies depending on the site and degree of the lens displacement. Surgical indications are: • Anterior and posterior chamber luxation. • Mature or hypermature cataract. • Lens induced uveitis. • Inadequate visual function caused by the displaced lens. • Increased subluxation of the lens.

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In case of subluxation conservative treatment may be decided. The animal’s physical activity should be reduced and clinical monitoring should be advised. Myotics may be contraindicated because Blood Acqueous rupture and uveitis, and increasing possibilities of pupillary block. Locally applied NSAID may be used. Flurbiprofen 0.03% was shown to be the most effective topical agent in preventing a rise in IOP along with inflammatory diseases.7 Surgery maybe an option. ICLE is the rule. A 160° keratotomy must be performed to have enough room to extract the lens without damaging the corneal endothelium. Cryoestraction is the preferred method and in this cases the posterior capsule is still well anchored to the patellar fossa and a huge anterior vitrectomy must often be accomplished. An automated vitrector allows best results, decreasing retinal traction and detachment. When the lens is anteriorly luxated an ICLE is mandatory. A partial anterior vitrectomy is usually necessary and the surgery should be made early because pupillary block may develop. Anterior luxations have a less favourable long term prognosis in respect of the posterior luxations. In order to achieve a postoperative emmetropia, intraocular lenses can be inserted with ciliary sulcus fixation.11,14 The most recent lenses have a larger optic part, in order to mechanically maintain the vitreous body at its place. Surgery is not commonly performed with posterior vitreal luxations. Very important is the use of a myorelaxant non-depolarizing agent (atracurium besylate) during anaesthesia. Anaesthesia has to be assisted for ventilation and thoroughly monitorized. This allows a natural esposition of the globe, without any traction or pression on the globe from forceps, stay sutures or extraocular muscles, decreasing the incidence of vitreous prolapse and retinal damages during surgery. Postoperative complications are frequent and widely constituted by glaucoma. Retinal detachments and degenerations are also possible. Cataract develops after a lens displacement. Glaucoma is the main concern in veterinary medicine as

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well in human cases, making a long term prognosis quite poor. Long term follow-ups are lacking in veterinary field. Among the few data available1, the longest follow up was after 12 months on 15 cases out of 57. 47% of these had poor exit, most of them represented by glaucoma development.

References 1.

2. 3.

6. 7. 8. 9. 10. 11.

12.

13. 14.

Glover T., Davidson M.G., Nasisse M.P., Olivero D.K “The intracapsular Extraction of Displaced Lenses in Dogs: a retrospective Sudy of 57 cases (1984-1990)” JAAHA 1995, Vol. 31, 77-81. Martin C.L. “Zonular defects in the dog: a clinical and scanning electron microscopic study.” JAAHA 1978, 14, 571-579. Molleda J.M., Martin E., Ginel P.J., Novales M., Moreno P., Lopez R. “Microphakia Associated With Lens Luxation in the Cat.” JAAHA 1995, 31, 209-212. Jaffe N.S., Jaffe M.S., Jaffe G.F. “Lens Displacement” in “Catarct Surgery and its Complications” Jaffe N.S., Jaffe M.S., Jaffe G.F. 6th Ed., 1997, Mosby Year Book. Wheatley H.M., Traboulsi E.I., Flowers B.E., Maumenee I.H., Azar D., Reed E.P., Whittum-Hudson J.A. “Immunohistochemical Localization of Fibrillin in Human Ocular Tissues” Arch. Ophthalmol. Vol. 113, 1995, 103-109. Aguirre G.D., Bistner S.I. “Microphakia with lenticular luxation and subluxation in cats.” Vet. Med. Sm. An. Cl., pag. 498, Maggio 1973. Opremcak E.M. “Antiinflammatory Agents” in Mauger T.F., Craig E.L. “Havener’s Ocular Pharmacology” 6th. Ed. 1994, Mosby. Curtis R. “Lens luxation in the dog and cat” Vet. Cl. of North Am. Sm. An. Pract. 20, 3, pp 755-773, 1990. Foster S.J., Curtis R., Barnett K.C. “Primary lens luxation in the Border Collie.” J. Small Anim. Pract., 27, pp. 1-6, 1986. Priester W.A. “Congenital ocular Defects in Cattle, Horses, cats, and Dogs” JAVMA, vol. 160, N° 11, June 1, 1972, 1504- 1511 Nasisse M.P., Glover T.L., Davidson M.G., Nelms S., Sullivan T. “Technique for the Suture Fixation of Intraocular Lenses in the Dog.” Vet & Comp. Ophthalmology, vol 5, N° 3, 146-150, 1995. Lazarus J.A., Pickett P., Champagne E.S. “Characterization and Heritability of primary Lens Luxation in a Related Family of Non-Inbred Chinese Shar Peis” Proceedings of the 28th ACVO Meeting, Santa Fe, November 15-18 1997. Fischer C.A. “Geriatric ophthalmology” Vet. Clin. of North Am., 19, 1, pag. 103, 1989. Nasisse M.P., Glover T.L. “Surgery for Lens Instability” Vet. Cl. Of North Am., Small An. Pract., Vol.27, N° 5, 1175-1192, 1997.

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Thoraco-lumbar disc disease Stefano Pizzirani

The commonest site for intervertebral disk disease (IVDD) is the thoraco-lumbar area. Janssens reports 1-2% of all dogs exhibits clinical signs of thoraco-lumbar disk disease (TLDD) during their life time and that 50% of dogs examined at the pathology table have some degree of TLDD. 65-75% of TLDD involves the T11-L2 spaces and T12-T13 and T13-L1 are the commonest. Chondrodistrophic breeds show the highest incidence but even in the non-chondrodistrophic breeds this pathology is becoming frequent because the attention and diagnostic skill is increasing. Anyway the Dachshund accounts for the 45-65% of cases. Hansen’s classification has become too simplistic. Many different ways of IVDD is encountered in all breeds. Protrusion (acute): sudden collapse of the intervertebral space with annular protrusion or intrannular estrusion. The IV space may be reduced or not. This kind of disease is seen in chondrodistrophic and non- chondrodistrophic breeds. Symptoms are acute, with back pain and different degree of impaired limb function. Myelographic signs show different degrees and extension of cord oedema with tapering of subaracnoidal space. Protrusion (chronic): older patients are usually involved. Large breed dogs are usually more commonly interested but it is not uncommon to see this pathology in chondrodystrophic breeds too. Usually signs are much less severe than those encountered with acute protrusion, and often are episodic findings during myelograms performed for other purposes. It is common to find multiple chronic protrusion, especially in the thoracolumbar area and they can be challenging a diagnosis for ataxia in large breed dogs suffering with lumbosacral DJD also and suspected to have also Degenerative Myelopathy. Quite often multiple chronic protrusion are found cranial or caudal to an acute extrusion. Stiffness of the column in the tract interested by multiple chronic protrusion may favour the dynamic stress of the adjacent IV space. Myelographic signs are spinal cord compression, with diminished spinal cord width but with normal evidence of the corresponding subaracnoidal space filled with the dye. Intrannular or subligamentous extrusion: the torn annulus fibrosus is partially or completely invaded by nucleus material, which stays anyway under the dorsal longitudinal ligament (DLL). It is an acute or chronic phenomenon. Acute ones come along with acute trauma to the spinal cord, confined at the intervertebral junction. The extrusion may be perfectly central, that is the main reason because it stays un-

der the DLL. In these cases surgery may be challenging and asks for a dorsal fenestration and decompression; damage to the spinal cord must be reduced to a minimum, but the cord has to be moved and touched anyway in order to cut the windows in the dorsal annular ligament. Surgery is easier for paramedian extrusion. Chronic ones can undergo calcific metaplasia with ossification of the mass in the neuronal channel. They are not a good indication for surgery. Extraligamentous extrusion: nucleus polposus material invades the neural channel, contacting the dura and migrates at different levels long the dorsal bodies of the vertebrae. Most of them are very acute. Some migrate in days or weeks, pointing out it is not the amount of material which it is important for the clinical signs or the prognosis but the velocity with which it hits the spinal cord. In the sagittal plane Protrusion/Extrusion (PE) can be median (1), paramedian (2), lateral (3) and foraminal (4). (Fig 1). Median and paramedian PE are usually under the DLL. Lateral are usually extruded with nucleus material migrating inside the neural channel. Foraminal are less frequent; they show lateral back pain if T-L. A root signature (lameness, limb movement pain) is evident if L4-L5 or caudal spaces are interested.. Neurological signs are not so evident, because one root involvement only. The division is mainly theoretical and mixed forms may be possible. Clinical signs may vary depending on several parameters. The most important is the velocity with which the PE hits the cord. Some protrusion are more invalidating of slow

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Figure 1

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progressive massive extrusion. Depending on the severity of neurological signs, patient are divided into different classes: • Class 1. Only back pain. No neurological signs. Animal show kifosis, reluctance to move, abdominal muscle contraction that can be erroneously misdiagnosed as acute abdomen. Around 10% of spinal cord compression can be detected at myelography in these cases, especially in the chronic ones. • Class 2. Proprioceptive deficits, mild ataxia, ambulatory paraparesis. • Class 3. Non ambulatory paraparesis. If helped can stand. Continent with normal pain sensation. • Class 4. Severe paraparesis/plegia with possible loss of continence. Deep pain sensation is maintained. • Class 5. Paraplegia with incontinence and loss of pain sensation. Perhaps each of the previous classes should be divided into another subclass time related: • A. peracute. Signs appeared within 12 hours. • B. acute. Signs appeared between 12-48 hours • C. subacute. Signs present for more than 48 hours. • D. chronic. Signs present for more than 7 days. In class (4) 5 it is of prognostic relevance the time has past since the occurrence of clinical signs, with less favourable prognostic fate for a time >36-48 hours. Myelomalacia may be a complication in the more severe cases.

Diagnosis Myelography is mandatory. Surgical approaches should not be chosen without a myelogram. 28 – 32 % of fault is reported in correct intervertebral space identification on plain radiograph only. Then, in acute cases, lateralization based on clinical signs shows 35% of inaccuracy, as many are controlateral extrusions. Lumbar puncture is the preferred method for TL-IVDD. L7-L6 space or crania till L4-L5 are the preferred sites. 0.3 – 0.4 ml/kg of ioexol or iopamidol or iotrolan 240 mg/ml (also ioexol or iopamidol 300 mg/kg can be used) are used with slow progression injection. We use lateral positioning of the patient and take our first films after _ - 1/3 of the total calculated dosage, leaving the needle in position with extension tube to the syringe. This allows to finely delineate the contour of the lesion. If high compression force is felt on dye progression, we stop and take an exposure film. This allows not to have epidurography confusing the image obtained. Then we continue to inject the dye until the complete dosage is given. The dye can be forced beyond the compression site, allowing the delineation of the lesion. This cannot be possible with the myelogram performed by cisternal puncture. A swollen cord can avoid the progression of the contrast medium and if the swelling is remarkable, the dye can stop few sapaces before the one interested by the PE. Cisternal puncture may be necessary in cases of large breed dogs with DJD of the articular facets of the lumbar vertebrae, with osteophytes interfering with needle insertion.

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Lateral, ventro dorsal and bilateral oblique projections are necessary to determinate the precise localisation of the compression. When cord swelling does not allow the left or right side, we look at the VD projection and chose the side where the dye column is longer cranially and caudally (see the picture 2).

PE side

Figure 2

Treatment Conservative treatment is usually adopted for cases included in class 1 at the first episode. Conservative treatment means “cage rest” for at least 3-4 weeks. This is not easy to obtain from pet owners who have less tendency to apply the rule of a strict confinement especially after few days or a week when the animal gets better and starts to behave physically normal. Limitation of movement should be adopted for 2 months (leash control, avoiding sport performances and heavy work). Analgesics, NSAID and corticosteroids, although beneficial, may have contraindication in case of free movement. . In fact they reduce pain and the animal looses the spontaneous limitation of movement. They start moving normally and several time this greatly aggravates the case. Theoretically then corticosteroids slow down collagen healing of annular fibers. In acute cases methylprednisolone sodium succinate (30 mg/kg) should be used into the first 8 hours as free radical scavenger. Then 15 mg /kg must be given every 6 hours within the 24 hours from the event in acute grave spinal trauma. 40-48% of relapses are reported in case of conservative treatment. Decompressive surgery should be used for dogs with neurological signs. Surgical therapy consists in different choices and techniques: Dorsal laminectomy: consists in drilling away dorsal lamina of the interested vertebrae. Articular facets should be saved in order to avoid fibrous tissue compression postsurgically. If lateral facets are drilled away it is a very destabilising technique. With this approach it is almost impossible to get access to a ventral disc. Decompression is mostly achieved by giving dorsal room to the cord. Hemilaminectomy: the lateral articular processes are drilled away. The approach at the disc is lateral so a correct rmyelographic localisation is mandatory. Allows often complete disc removal without damaging the cord. In case of intrannular/subligamentous estrusion it is possible to perform a dorsal fenestration.

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Prognosis Prognosis varies upon different factors: • Clinical class • Time past since episode • Weight of the patient and his attitude • Relapse A success rate of 80-96% is reported for classes 2,3,4 if surgery performed within 48 hours from the episode. This rate lowers to 56% for class 5 if within 12 hours, to 25% from 12 to 36 hours and goes to 5% or less if surgery in class 5 is performed after 48 hours. Relapses are from 2.67% to 26.55 for those underwent surgery. 48% for those treated conservatively. These high variations depend on techniques adopted. Standardisation in clinical grading and surgical choices has not been yet achieved. Neuroradiological skill, clinical grading and surgeons’ skills and techniques are factors influencing the outcome.

References 1. 2.

L.A.A. Janssens “Thoracolumbar disc herniation in the dog” Vlaams Diergeneeskd Tijdschr 59, 128-136, (1990). N.D. Jeffery “Treatment of acute and chronic thoracolumbar disc disease by ‘minihemilaminectomy’.” J. Small Anim. Pract. (1988) 29, 611-616. S.T. Simpson “Intervertebral disc disease” Vet. Cl. Of North Am. Sm. An. Pract. 22, 4 889-897, 1992.

S.H.Levine, D.D.Caywood “Recurrence of neurological deficits in dogs treated for thoracolumbar disk disease” J.A.A.H.A. 20, 6, 889894, 1984. 5. J.Harari, S.L.Marks “Surgical treatments for intervertebral disc disease.” Vet.Cl. of North Am., Sm.An.Pract., 22, 4, 899-915, 1992. 6. R.M.Kirberger, C.J.Roos, A.M.Lubbe “The radiological diagnosis of thoracolumbar disc disease in the dachshund” Vet. Rad. & Ultrasound, Vol. 33, N° 5, 1992 255-261. 7. A.M. Lubbe, R.M. Kirberger, F.J.M. Verstraete “Pediculectomy for thoracolumbar spinal decompression in the duchshund” JAAHA, vol. 30, N° 3, 233-238, 1994. 8. S.J. Butterworth, H.R. Denny “Follow-up study of 100 cases with thoracolumbar disc protrusions treated by lateral fenestration” J. Sm. Anim. Pract., (1991), 32, 443-447. 9. J.D. Smith, S.M. Newell, S.C. Budsberg, R.A. Bennett “Incidence of contralateral versus ipsilateral neurological signs associated with lateralised Hansen type I disc extrusion” J. Sm. Anim. Pract., (1997) 38, 495-497. 10. J.C. Yovich, R. Read, C. Eger “Modified lateral spinal decompression in 61 dogs with thoracolumbar disc protrusion” J. Sm. Anim. Pract., (1994), 35, 351-356. 11. J.M. Fingeroth “Treatment of canine intervertebral disk disease: recommendations and controversies” in Bonagura J.D. “Kirk’s Current veterinary Therapy XII – Small Animal Practice” 1995, W.B. Saunders Co, Philadelphia. 12. J.M. Fingeroth “Fenestration: Pros and Cons” in Thacer C. “Intervertebral Disc Disease” problems in vet. Med., Vol. 1 N° 3, 445-466, 1989. 13. T.L. Walker, C.W. Betts “Intervertebral Disc Disease” in Slatter D.H. “Textbook of Small Animal Surgery” 1985, W.B. Saunders Co, Philadelphia. 14. J.P. Toombs, M.S. Bauer “Intervertebral Disc Disease” in Slatter, D.H. “Textbook of Small Animal Surgery” 2nd Ed., 1993, W.B. Saunders Co., Philadelphia. 15. R.M. Jerram, R.C. Hart, K.S. Shulz “Postoperative Management of the Canine Spinal Surgery Patient – part I” Compendium, Vol. 19, N° 2, 147-161, 1997. 16.R.C.Hart, R.M.Jerram, K.S.Shulz “ Postoperative Management of the Canine Spinal Surgery Patient - part II” Compendium, Vol. 19, N° 10, 1133-1146, 1997 17. H.R. Sukhiani, J.M. Parent, M.A.O. Atilola, D.L. Holmberg “Intervertebral disk disease in dogs with signs of back pain alone: 25 cases (1986-1993) JAVMA, Vol 209, N° 7, 1275-1279, 1996. 18. J.P. Bray, H.M. Burbidge “The canine intervertebral disk- part one: structure and function” JAAHA, Vol.34, N° 1, 55-63, 1998. 19. J.P. Bray, H.M. Burbidge “The canine intervertebral disk – part two: degenerative changes – nonchondrodystrophoid versus chondrodystrophoid disks” JAAHA, Vol. 34, N° 2, 135-144, 1998. 20. N.J. Olby, J. Dyce, J.E.F. Houlton “Correlation of plain radiographic and lumbar myelographic findings with surgical findings in thoracolumbare disc disease” J. Sm. Anim. Pract., (1994), 35, 345-350. 21. R.G. Prata “Neurosurgical Treatment of Thoracolumbar Disks: the rationale and Value of Laminectomy with Concomitant Disk Removal” JAAHA, Vol. 17, N° 1, 17-25, 1981. 22. P. Muir, K.A. Johnson, P.A. Manley, R.T. Dueland “Comparison of hemilaminectomy and dorsal laminectomy for thoracolumbar intervertebral disc extrusion in dachshunds” J. Sm. Anim. Pract. (1995), 36, 360-367. 23. A. Schulman, C.L. Lippincott “Dorsolateral hemilaminectomy in the treatment of Thoracolumbar Intervertebral Disk Disease in Dogs” Compendium, Vol.9, N° 3, 305-310, 1987. 24. H.W. Scott “Hemilaminectomy for the treatment of thoracolumbar disc disease in the dog: a follow-up study of 40 cases” J. Sm. Anim. Pract. (1997), 38, 488-494. 25. S.J. Wheeler, N.J.H. Sharp “Small Animal Spinal Disorders. Diagnosis and Surgery” Mosby-Wolfe, London, 1994.

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Durotomy: Dura opening is performed when cord oedema or myelomalacia or intradural hematoma is suspected. Inspection and swelling relief may be possible. It is important to open the dura as long as 1 o 2 vertebral body length. Pediculectomy (minihemilaminectomy): Less destabilising technique. Removal of vertebral accessory process is a less invasive technique but allows very limited channel exposure and inspection. Can be associated at the former hemilaminectomy when multiple sites are present. Fenestration: prophylactic procedure.. Very controversial subject. Often personal choice of the surgeon. Should be completely performed from T11-T12 to L3-L4. It is not a easy procedure. Aortic damage is possible. Some authors use this a s only treatment method. It is not a decompressive procedure. Some authors claim same reoccurrence statistics without it. Postoperative treatment: Postoperative attention should be devoted to: • Pain control and treatment • Continence management and treatment • Physiotherapy Possible complications refers to: • Gastrointestinal complications • Wound complications

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Diagnosis and treatment of hypothyroidism AD Rijnberk

Summary Hypothyroidism at young age in both dogs and cats is usually a congenital disorder, due to an enzyme deficiency that prevents synthesis of thyroid hormones. The diagnostic challenge in these rare disorders is the elucidation of the inborn error. In most adult dogs with hypothyroidism it is a primary thyroid disorder, whereby progression of an autoimmune process leads to lymphocytic infiltration and disappearance of thyroid tissue. The combination of a low thyroxine concentration and a high TSH concentration in plasma is diagnostic of primary hypothyroidism. However, in a number of cases the thyroxine concentration is low without a concomitantly elevated TSH concentration. In some cases a thyroid biopsy may be needed for a definite diagnosis. With appropriate substitution therapy the long-term prognosis is excellent.

Introduction In the dog and cat the thyroid glands are separate lobes lying beside the trachea from about the third to the eigthth tracheal ring. They are covered ventrally by the sternohyoid and sternothyroid muscles. Normal thyroid glands are not palpable. The basic functional unit of the thyroid is the follicle, a hollow sphere of cells, about 30-300 µm in diameter. The wall of the follicle is a single layer of thyroid epithelial cells. These follicular cells are cuboical when quiescent and columnar when active. The lumen is filled with a proteinaceous colloid that contains a large glycoprotein called thyroglobulin, within the sequence of which the thyroid hormones are synthesized and stored. Hormone synthesis and secretion. The main secretory hormonal product of the thyroid gland is L-thyroxine or 3,5,3’,5’-L-tetraiodothyronine (T4). The other thyroid hormone, 3,5,3’-L-triiodothyronine (T3), is secreted in much smaller quantities (about 20% of that of T4). Most of the circulating T3 is produced in peripheral tissues by outer ring deiodination of T4.Inner ring deiodination results in the metabolically inactive 3,3’,5’ triiodothyronine (reverse T3, rT3). Iodide, the main building block of the thyroid hormones, is actively transported (“trapped”) from the extracellular flu-

id into the thyroid follicular cells, resulting in thyroid/plasma-concentration ratios of around 25. Tissues other than the thyroid, such as gastric mucosa, salivary glands and choroid plexus, also have an active transport mechanism for iodide. In contrast to the thyroids, these tissues do not have the capacity for organic binding of iodide. All of these iodide-concentrating tissues are also capable of concentrating other structurally related monovalent anions such as thiocyanate (SCN–), perchlorate (ClO4–) and pertechnetate (TcO4–). However, unlike iodide, these ions are also not organically bound in the thyroid and hence their duration within the thyroid is short. This property together with its short physical half-life, makes the radioactive isotope of pertechnetate (99mTcO4–) a valuable radionuclide for imaging the thyroid by scintillation scanning. Once within the thyroid cell, inorganic iodide is rapidly oxidized by thyroid peroxidase in the presence of H2O2 into a reactive intermediate that is then incorporated into tyrosine residues of acceptor proteins, mainly thyroglobulin. These iodotyrosines (MIT and DIT) in thyroglobulin can combine to form iodothyronines. Both organic binding of iodide and coupling of iodotyrosines can be inhibited by thiourea compounds, which are used in the treatment of hyperthyroidism. The thyroglobulin is iodinated at the apical (follicular) border of the cell and is then brought into the colloid by exocytosis. For secretion, thyroglobulin is resorbed into the thyroid cell via pinocytosis of colloid droplets. Each colloid droplet is enclosed in a membrane derived from the apical border. This is combined with a lysosome and as the phagolysosome moves toward the basal aspect of the cell the droplet becomes smaller and more dense with progression of the hydrolysis of the thyroglobluin by the lysosomal proteases. Regulation of thyroid function. Thyrotropin or thyroidstimulating hormone (TSH), a glycoprotein secreted by the anterior lobe of the pituitary, promotes thyroid hypertrophy and hyperplasia, and stimulates the synthesis and secretion of thyroid hormones. This TSH secretion by the pituitary is inhibited primarily by T3, that is produced locally from T4 by Type II deiodinase (catalyzes deiodination exclusively at the 5’-position) and also by T3 derived from the pool of free T3. The setting of this T4/T3-TSH feedback loop is modulated by a hypothalamic tripeptide, TSH-releasing hormone (TRH), that stimulates TSH release, whereas somatostatin and possibly other neuropeptides inhibit TSH release.

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Hypothyroidism in young animals Early in life the presence of thyroid hormones is crucial for growth and development of all body tissues and particularly the skeleton1. Hence in addition to the signs of adult-onset hypothyroidism, disproportionate dwarfism may be a prominent sign of congenital or juvenile-onset hypothyroidism. Juvenile-onset hypothyroidism can be congenital or acquired. Among the causes of the latter is the classic iodine deficiency, which occurred in times when owners took too literally the notion that dogs and cats are carnivores. A diet consisting of meat alone is deficient in many respects and certainly in iodine. This entity is no longer seen in countries in which it is customary to feed manufactured diets, which are rather rich in iodine. Another, although also very rare, cause of acquired juvenile-onset hypothyroidism is lymphocytic thyroiditis. This is the common cause of primary hypothyroidism in the adult dog. Rarely the process of autoimmune destruction of the thyroid glands occurs during adolescence and as a consequence the animal may be slightly retarded in growth, in addition to developing the signs of hypothyroidism of the adult. Apart from the extremely rare condition of thyroid dysgenesis, congenital hypothyroidism may also occur, in both dogs and cats, because of an enzyme deficiency that prevents synthesis of thyroid hormones. Among these the defective peroxydase activity is not uncommon in kittens. Animals with this so-called organification defect concentrate iodide in the thyroid glands but have limited ability to use this iodide in thyroid hormone synthesis. The disorder appears to be heterogenous, for in some animals the defect is complete and no iodide peroxydase activity can be demonstrated, while in others it is partial. In the latter case the defect may be an abnormal localization of the enzyme within the thyroid cell. The clinical hallmark of these defects is the combination of goiter and hypothyroidism. The severity of both the goiter and the hypothyroidism may vary considerably and it may also be difficult to palpate a goiter in a very young animal. Diagnosis. The diagnosis of hypothyroidism can be made by measuring the concentration of circulating thyroxine. When a goiter is detected, stimulation with TSH is redundant, as the goiter is already evidence of increased endogenous TSH secretion. The diagnostic challenge is the elucidation of the defect in thyroid hormone synthesis that is causing the increased TSH secretion. This requires in vivo studies with radioiodine. In some cases there is rapid uptake of radioiodide by the thyroid but the iodide remains nonorganified, as is readily demonstrated by the precipitous discharge of the accumulated radioactivity from the thyroids when an ion that competes for uptake, such as perchlorate or thiocyanate, is given.2 Treatment. As in all forms of juvenile hypothyroidism except that caused by iodine deficiency, treatment consists of oral administration of thyroxine (see next section). This will lower the TSH secretion and as a result the goiter will shrink.

Hypothyroidism in adult animals Hypothyroidism is the clinical syndrome resulting from

deficient production of thyroid hormone. At adult age in approximately 95 % of cases it is a primary thyroid disorder. Only in 5 % or less of cases the disease is of (supra) pituitary origin, i.e., secondary hypothyroidism.

Primary hypothyroidism Pathogenesis. In the spontaneous form a progressive autoimmune process leads to lymphocytic infiltration and disappearance of thyroid tissue. Also the so-called idiopathic forms, in which there is thyroid atrophy without inflammatory infiltrate, are generally regarded as the end result of an autoimmune disorder. These immune-mediated destructions are slow processes. Clinical manifestations of hormone deficiency will become evident only after a considerable amount of tissue has been destroyed. Although rare, there may coexist another hormone deficiency syndrome such as diabetes mellitus3. These multiple autoimmune endocrine deficiencies are known as polyglandular failure syndromes. The combination of hypothyroidism and hypoadrenocorticism is known as Schmidtâ&#x20AC;&#x2122;s syndrome4. In dogs with hypothyroidism and dogs with lymphocytic thyroiditis with or without overt hypothyroidism, circulating antibodies to thyroglobulin (Tg), a second colloidal antigen and to a thyroid microsomal antigen have been identified. These autoantibodies and especially those against the microsomal fraction may initiate the complement cascade or antibody-dependent cell-mediated cytolysis resulting in further release of thyroid antigens. Although they may not be of great pathogenetic importance, autoantibodies against Tg may have some virtue as markers of autoimmune thyroiditis. Circulating antibodies to Tg have been detected in over 50 % of hypothyroid dogs. These Tg antibodies may also occasionally interfere with radioimmunoassays used to measure plasma concentrations of thyroid hormones, and especially T3. The occasional occurrence of T3 autoantibodies is due to antibodies recognizing a T3-containing epitope of Tg that is different from the epitopes involved in eliciting the predominant population of canine Tg-autoantibodies5,6. These rarely (< 1 % of samples sent to diagnostic laboratories) occurring T3 autoantibodies may cause falsely elevated or decreased (depending on the assay) values. T4-autoantibodies are encountered much less frequently than T3-autoantibodies; in routine diagnostic laboratories they are observed only once in several years. Apart from spontaneous hypothyroidism there is the iatrogenic form. This is especially seen in cats as a result of the treatment of hyperthyroidism, a condition frequently occurring in this species. The hypothyroidism may be the result of radioiodine therapy or bilateral thyroidectomy. Clinical manifestations. Acquired primary deficiency of thyroid hormone is a condition of young and middle-aged dogs (1-6 years). Dogs of larger breeds are more frequently affected than smaller dogs. The incidence is equally distributed between male and females. So far there is only one convincing description on the occurrence of spontaneous primary hypothyroidism in the adult cat7. The classical clinical picture of overt hypothyroidism in-

volves simultaneous manifestations from nearly all organ systems. However, even in severe cases symptoms from a single organ system (e.g. locomotor system) may dominate in such a way as to distract from the causative disease. Nevertheless, centrally in the syndrome usually there is the history of slowing of mental and physical activities. Most dogs with hypothyroidism have some degree of mental dullness, lethargy and disinterest in exercise. These signs are gradual in onset, often subtle and may not be recognized by the owner until after treatment has been started. Changes of hair and skin are also common observable signs. Differential diagnosis. As indicated above the presenting symptoms may vary widely and therefore the most common pitfall in the diagnosis of hypothyroidism is undoubtedly to overlook the possibility that the presented problem(s) could be due to hypothyroidism. For example, it is not uncommon that dogs with hypothyroidism are presented in specialty areas such as cardiopulmonology (lethargy misinterpreted as decrease in exercise tolerance) or orthopedics (locomotor disturbance). With regard to the most common problem, lethargy, the disease may be mistaken for metabolic (hepatoencephalophathy) or neurologic (encephalitis, hydrocephalus) cerebrocortical disease. As far as the atrophy of skin and adnexa is concerned, conditions such as estrogen excess, hyperadrenocorticism and growth hormone deficiency may also be considered. Diagnosis. In man a low T4 level in plasma combined with a high concentration of TSH establishes the diagnosis of primary hypothyroidism. This approach has been impossible in the dog until recently, as a valid canine-specific assay for TSH was not available. Therefore the diagnosis of hypothyroidism is still strongly based upon measurements of T4 concentrations in plasma. As a measure of thyroid function T4 has to be preferred over T3, as T4 is only produced from the thyroid gland. T3 concentrations in plasma are largely derived from peripheral conversion and may remain within normal limits in moderate hypothyroidism and may be low in many non-thyroidal diseases. In addition the T3 measurements are more often than T4 measurements subject to artifactuallly high or low results due to autoantibodies. However, there are also many factors that can affect basal T4 concentrations in euthyroid dogs, often leading to a false lowering and consequently a false positive diagnosis of hypothyroidism. Of these factors, concurrent illness and drugs (glucocorticoids, antiepileptics and analgesics) are the most relevant. Drugs such as glucocorticoids have multiple effects on peripheral T4 and T3 transfer, distribution and metabolism8. These effects include altered T4 binding to plasma carrier proteins, resulting in altered free fraction levels of T4. Probably due to the multiple character of these drug- and disease-induced effects, measurements of free T4 concentrations in dogs have not provided improvement of the diagnostic accurary above that of measurements of total T48. Thus, where available, the TSH-stimulation test continues to be a conclusive test for the diagnosis of primary hypothyroidism. The test will distinguish depression of basal T4 concentrations due to drugs and illness from advanced primary hypothyroidism, but not from secondary hypothyroidism and early stages of primary hypothyroidism. Here

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scanning with 99mTcO4-, radioiodine-uptake studies and/or thyroid biopsy may provide the final diagnosis. Now in many countries bTSH is no longer available the TSH-stimulation test is disappearing from the diagnostic scene. It has been tried to replace this test by a stimulation test with the supra-pituitary stimulant TRH. However, the rise in plasma T4 concentrations in healthy control dogs is insufficient to allow any discrimination.10 The recently introduced immunoassays for the measurment of canine TSH are an important step forward. In cases of (experimentally induced) primary hypothyroidism the expected combination of a low plasma T4 concentration and a high TSH concentration has been found.11,12 However, in a number of cases of primary hypothyroidism the T4 concentration is low without a concomitantly elevated TSH concentration, whereas also in euthyroid dogs elevated circulating TSH concentrations can be found.13,14,15 The lack of response of endogenous TSH to TRH stimulation may become a useful adjunct for the diagnosis of canine hypothyroidism.15,16,17 When still in doubt about the definite diagnosis minor surgery and thyroid biopsy usually will give a definite answer. It is worth pursuing until a definite diagnosis has been established because the decision for (life-long!) substitutution therapy should be on solid ground. Treatment. Although T3 is the metabolically active thyroid hormone, it is not the supplement of choice. A primary advantage of providing the “prohormone” T4 is that the body is given the opportunity to regulate the amount of T3 generated by normal physiologic mechanisms. In fact appropriate T4 therapy results in normal levels of both T4 and T3. Both T4-production rates and parenteral L-T4 replacement doses required to maintain euthyroidism are around 5 µg per kg body weight per day. However, when T4 is administered orally the bioavailability is low and variable, due to incomplete and variable gastrointestinal absorption. Oral supplementation with synthetic L-thyroxine is started at a dose rate of 10 µg/kg twice daily. After two months a control examination is carried out. When blood is collected at 10-12 h after the last dose the T4 level in plasma should be ≥ 20 nmol/l. If not, the dose should be adjusted. Because of the individual variation in intestinal absorption of T4 further control examinations and adjustments may be needed.18 With increasing experience also the lowering of the circulating TSH concentrations may turn out to be a useful variable for establishing the replacement dose of thyroxine.19 Prognosis. Hypothyroidism is one of the most gratifying diseases to treat, because of the ease and completeness with which it responds to treatment. With appropriate treatment and follow-up examinations (every half year) all of the alterations associated with hypothyroidism are reversible. The long-term prognosis is excellent.

Secondary hypothyroidism In secondary or central hypothyroidism the thyroids are not primarily affected but deprived of stimulation by TSH. On histological examination there are no losses of follicles but rather characteristics of inactivity. The condition is rare compared to primary thyroid failure. The spontaneous forms

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in adult animals usually result from a tumor of the pituitary or adjacent regions. Central hypothyroidism may also result from surgical removal of pituitary tumors, whereby there is of course also the possibility that it was present initially.20 Clinical manifestations. The clinical picture is similar to that of primary hypothyroidism, although generally less pronounced. There may be lethargy and some alopecia, but the tendency to thickening of the skin is less pronounced. Often there is accompanying impairment in the secretion of other pituitary hormones such as growth hormone and gonadotrophins. Not uncommonly, the lesion causing low TSH secretion is a hormone-secreting tumor (e.g., ACTH). The symptoms and signs that arise from such a pituitary tumor may precede, accompany, and even obscure the manifestations of pituitary failure. In the example of an ACTH-secreting tumor the central hypothyroidism may only become manifest when the associated hyperadrenocorticism has been cured. Diagnosis. Suspicion of central hypothyroidism should arise in case of low plasma concentrations of both T4 and TSH. This is with the condition that in all likelihood the low T4 concentration is not caused by illness or drugs. Apart from thyroid function, diagnostic evaluation should include (1) the secretion of other pituitary hormones21 and (2) the pathomorphology of the pituitary and adjacent areas by diagnostic imaging. Treatment. Treatment with L-thyroxine can be the same as in primary hypothyroidism. In addition, hypofunction of other endocrine glands resulting from pituitary hormone deficiencies should be corrected. Prognosis. In the spontaneous forms the prospects are completely dependent upon the course of the causitive lesion in the hypothalamus-pituitary area. In the iatrogenic form, i.e., following total hypophysectomy, supplementation with thyroxine (and glucocorticoids!) may enable the animal to live a healthy life for several years.

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References 18. 1.

Saunders MH, Jezyk PK, (1991), The radiographic appearance of canine congenital hypothyroidism: Skeletal changes with delayed treatment. Vet Radiol 32:171-177. Sjollema BE, den Hartog MT, de Vijlder JJM, van Dijk JE, Rijnberk A, (1991), Congenital hypothyroidism in two cats due to defective organification: data suggesting loosely anchored thyroperoxidase. Acta Endocr 125:435-440. Eigenmann JE, Van der Haage MH, Rijnberk A, (1984), Polyendocrinopathy in two canine littermates: Simultaneous occurrence of carbohydrate intolerance and hypothyroidism. J Am Anim Hosp Ass 20:143-148.

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Kooistra HS, Rijnberk A, van den Ingh ThSGAM, (1995), Polyglandular deficiency syndrome in a Boxer dog: thyroid hormone and glucorticoid deficiency. Vet Quart 17:59-63. Young DW, Haines DM, Kemppainen RJ, (1991), The relationship between autoantibodies to triiodothyronine (T3) and thyroglobulin (Tg) in the dog. Autoimmunity 9:41-46. Gaschen F, Thompson J, Beale K, Keisling K, (1993), Recognition of triiodothyronine-containing epitopes in canine thyroglobulin by circulating thyroglobulin autoantibodies. Am J Vet Res 54:244-247. Rand JS, Levine J, Best SJ, Parker W, (1993), Spontaneous adult-onset hypothyroidism in a cat. J Vet Int Med 7:272-276. Kaptein EM, Moore GE, Ferguson DC, Hoenig M, (1992), Effects of prednisone on thyroxine and 3,53’-triiodothyronine metabolism in normal dogs. Endocrinology 130:1669-1679. Nelson RW, Ihle SL, Feldman EC, Bottoms GD, (1991), Serum free thyroxine concentration in healthy dogs, dogs with hypothyroidism, and euthyroid dogs with concurrent illness. J Am Vet Med Ass 198:1401-1407. Frank LA, (1996), Comparison of thyrotropin-releasing hormone (TRH) to thyrotropin (TSH) stimulation for evaluating thyroid function in dogs. J Am Anim Hosp Ass 32:481-487. Williams DA, Scott-Moncrieff JC, Bruner J, Sustarcic D, PanosianSahakian N, Unver E, Said El Shami A, (1996), Validation of an immunoassay for canine thyroid-stimulating hormone and changes in serum concentration following induction of hypothyroidism in dogs. J Am Vet Vet Med Ass 209:1730-1732. Rushig S, Kraft W, (1996), Determination of canine thyroid stimulating hormone (cTSH) in blood serum of dogs and its reaction to the TRH stimulation test. Tierärztl. Prax 24:479-483. Melian C, Peterson ME, Nichols CE, (1997), Evaluation of free T4 and endogenous TSH as diagnostic tests for hypothyroidism in dogs. J Vet Int Med 11:120 (ACVIM Abstract 68). Dixon RM, Graham PA, Harvie J, Mooney C, (1997), Comparison of endogenous serum thyrotropin (cTSH) concentrations with bovine TSH response test. Results in euthyroid and hypothyroid dogs. J Vet Int Med 11:121 (ACVIM Abstract 69). Hoppen HO, Lohmann P, Schlote S, Günzel-Apel AR, Müller-König A, Grünau B, Hämmerling R, Leidingern K, Morisse B, Nolte I, (1997), Die Messung von caninem TSH zur Diagnostik der Hypothyreose des Hundes. Prakt Tierarzt 78:13-17. Hoenig M, Ferguson DC, (1997), Comparison of TRH-stimulated thyrotropin (cTSH) to TRH- and TSH-stimulated T4 in euthyroid, hypothyroid, and sick dogs. J Vet Int Med 11:121 (ACVIM Abstract 71) Scott-Moncrieff JC, Nelson RW, (1997), Response of serum canine thyrtropin (cTSH) to stimulation by thyrotropin releasing hormone (TRH) in euthyroid dogs, hypothyroid dogs, and euthyroid dogs with concurrent disease. J Vet Int Med 11:121 (ACVIM Abstract 70). Rijnberk A, (1996), Clinical Endocrinology of Dogs and Cats. Kluwer Academic Publishers, Dordrecht/Boston, 43-48. Ferguson DC, Hoenig M, (1997), Re-examination of dosage regimens for l-thyroxine (T4) in the dog: Bioavailability and persistence of TSH suppression. J Vet Int Med 11:121 (ACVIM Abstract 72). Meij BP, Mol JA, Bevers MM, Rijnberk A, (1997), Residual pituitary function after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism. J Endocrinol 155:531-539. Meij BP, Mol JA, van den Ingh TSGAM, Bevers MM, Hazewinkel HAW, Rijnberk A, (1997), Assessment of pituitary function after transsphenoidal hypophysectomy in beagle dogs. Domest Anim Endocrinol 14:81-97.

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Diagnosis and treatment of hyperadrenocorticism AD Rijnberk

Summary The diagnosis of hyperadrenocorticism can be made according to two principles: (1) to test the integrity of the feedback system, and (2) to measure cortisol production. In the first approach the sensitivity of the pituitary-adrenocortical system to suppression is tested by administering dexamethasone in a dose that discriminates between healthy animals and animals with hyperadrenocorticism, that is the low-dose dexamethasone suppression test (LDDST). In the second approach an integrated reflection of the corticoid production is obtained by measuring urinary corticoids (largely cortisol) in relation to the creatinine concentration, known as the urinary corticoid/creatinine ratio (UCCR). Pituitary-dependent hyperadrenocorticism and hyperadrenocorticism due to adrenocortical tumor can be distinguished with the highdose dexamethasone suppression test (HDDST), in which either plasma cortisol levels or UCCRs can be used. The latter has the advantage of combining both the diagnosis and the differential diagnosis in one test procedure.. Also for the treatment of pituitary-dependent hyperadrenocorticism two principles can be followed: (1) elimination of the stimulus for the augmented production of cortisol, i.e., the pituitary lesion causing excessive ACTH secretion, and (2) elimination of the glucocorticoid excess. In the first approach hypophysectomy is the best option, but it requires a team of (super)specialists (neurosurgeon, endocrinologist, radiologist and pathologist), whereby the skill and the experience of the neurosurgeon are crucial. The glucocorticoid excess can be eliminated by bilateral adrenalectomy or by adrenocorticlysis with o,pâ&#x20AC;&#x2122;-DDD.

Introduction Synthesis and release of glucocorticoids (and androgens) by the two inner zones of the adrenal cortex is almost exclusively controlled by the pituitary hormone ACTH. The production of aldosterone in the outer zone (zona glomerulosa) is regulated by the volume and potassium status of the organism by a complex, multifactorial and almost exclusively extrapituitary control system, the renin-angiotensin system. Glucocorticoid and especially cortisol secretion is directly dependent on the plasma concentration of ACTH or corticotropin. Chemically ACTH is a single-chain peptide comprising 39 amino acid residues. In the anterior lobe (AL) it

is synthesized from a well-characterized precursor molecule pro-opiomelanocortin (POMC), which also gives rise to a number of other peptides that are co-released with ACTH. In dogs and cats the pars intermedia (PI) contains two cell types that also can synthesize POMC. One cell type is similar to the corticotropic cells of the anterior lobe. In the other cell type ACTH is cleaved into ACTH1-14 (precursor of MSH) and corticotropin-like intermediate-lobe peptide. ACTH secretion by the anterior pituitary is regulated by the hypothalamus and central nervous system via neurotransmitters that cause the release of hypophysiotropic hormones such as corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP). In this neuroendocrine control four mechanisms can be distinguished: (1) episodic secretion and possible diurnal rhythm of ACTH, (2) response to stress, (3) feedback inhibition by cortisol, and (4) immunological factors. Central nervous system events regulate both the number and magnitude of ACTH and -MSH bursts. The ACTH bursts range in the dog from 6 to 12 per 24-h period1 and the -MSH bursts from 1 to 11 per 24 h2. ACTH and cortisol are secreted within minutes following the onset of stresses such as surgery and hypoglycemia. Stress responses originate in the central nervous system and cause an increased release of the hypothalamic hypophysiotropic hormones such as CRH and AVP. These stress responses are reduced or totally abolished by prior high-dose glucocorticoid administration and also less pronounced in spontaneous hyperadrenocorticism3. Dogs and cats differ considerably in their responses to stress. In dogs several emotional or neurogenic stresses do not result in stimulation of ACTH secretion or MSH secretion.4 In cats, on the other hand, mild stresses such as handling and intradermal skin testing cause impressive increases in the plasma concentrations of cortisol, ACTH and -MSH. In contrast to dogs, cats appear to have a more actively secreting pars intermedia that is strongly responsive to stress5.

Adrenocortical hyperfunction; Cushingâ&#x20AC;&#x2122;s syndrome Hyperadrenocorticism is defined as the complex of physical and biochemical changes that is the result of chronic glucocorticoid excess, whatever its cause. Apart from the exogenous form of the disease due to glucocorticoid therapy, there are two endogenous forms in both the dog and the cat:

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(1) ACTH-dependent, and (2) ACTH-independent. In the ACTH-dependent form there is chronic ACTH hypersecretion, resulting primarily in hypersecretion of cortisol and in hyperplasia of the two inner zones of the adrenal cortices. In this form, which accounts for about 85% of cases, the ACTH excess originates form the pituitary; an ectopic or paraneoplastic ACTH syndrome has not been recognized in dogs and cats so far. Thus for these two species the name for this category can be more specific: pituitary-dependent hyperadrenocorticism. ACTH-independent hyperadrenocorticism is due to autonomous glucocorticoid-secreting adrenocortical adenomas or carcinomas and comprises about 15% of cases. The simultaneous occurrence of both pituitary-dependent hyperadrenocorticism and autonomously hyperfunctioning adrenocortical tumor has been described.6

Pituitary-dependent hyperadrenocorticism There is increasing evidence that the ACTH excess is the result of a process of tumorigenesis, that may be a multi-step process requiring more than one mutation in the protooncogenes involved in hormone production and/or cell proliferation. An inherited aberration may be the earliest step7. The process does not seem to be dependent upon continuous hypothalamic stimulation8. In about one-fourth to one-fifth of cases an adenoma in the PI is found, but tumors in both lobes may also occur9. This is of clinical interest not only because the PI tumors tend to be larger than the AL tumors9, but also because of the specific hypothalamic control of hormone synthesis in the PI. The PI is under direct neural control. This is principally a tonic dopaminergic inhibition, which suppresses the expression of glucocorticoid receptors. This explains why cases of pituitary-dependent hyperadrenocorticism of PI origin are resistant to suppression by dexamethasone10. However, this is not an absolute difference from AL lesions, as pituitary lesions causing hyperadrenocorticism may not maintain the regulation characteristics of the lobe of origin. There does not seem to exist a dichotomy in the suppressive effect of dexamethasone, but rather a sliding scale. The degree of insensitivity to glucocorticoid feedback is correlated with the size of pituitary corticotrophic adenomas.11 Clinical manifestations. Many of the signs and symtoms can be related to the actions of glucocorticoids, that is, increased gluconeogenesis and lipogenesis at the expense of protein. In dogs the cardinal physical features are centripetal obesity and atrophy of muscles and skin with adnexa. In addition polyuria and polyphagia are often dominating features. In dogs the polyuria is known to be due to both impaired osmoregulation of vasopressin release and interference of the glucocorticoid excess with the action of vasopressin. In cats the situation is somewhat different from that in the dog. The cutaneous manifestations are initially less pronounced than in the dog. Furthermore glucocorticoid excess gives rise less readily to polyuria/polydipsia in this species than in dogs, and it may become obvious only when diabetes mellitus develops. Cats seem to be much more susceptible than dogs to the diabetogenic effects of glucocorticoids. In the vast majority of the described cases of feline hyperadrenocorticism the disease was associated with diabetes mel-

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litus and the suspicion of hyperadrenocorticism has often arisen specifically because of insulin resistance encountered in the treatment of diabetes mellitus. Only about 10% of dogs with hyperadrenocorticism develop overt diabetes mellitus. Among the routine laboratory data a consistent finding (in dogs only!) is an elevation of the plasma concentration of alkaline phosphatase (AP)13. This is due to the induction of an isoenzyme which has greater stability at 65 oC than other AP-isoenzymes and is therefore easily measured by a routine laboratory procedure. It is also noteworthy that in the majority of dogs with hyperadrenocorticism decreased T4 concentrations are found, which seems to be a consequence of altered transport, distribution, and metabolism of T4, rather than hyposecretion. Diagnosis. There are two ways to make the diagnosis: (1) to test the integrity of the feedback system, and (2) to measure urinary corticoid excretion. In the first approach the sensitivity of the pituitaryadrencortical system to suppression is tested by administering a synthetic glucocorticoid in a dose that discriminates between healthy animals and animals with hyperadrenocorticism. A potent glucocorticoid such as dexamethasone is used in order that the administered compound may be given in such small amounts as not to contribute significantly to the steroids to be analyzed. In this so-called dexamethasone screening test or low-dose dexamethasone suppression test (LDDST), 0.01 mg dexamethasone per kg body weight is administered intravenously in the morning. Blood for cortisol measurement is collected 8 h after dexamethasone administration. In healthy animals the plasma cortisol concentrations are still depressed at this time, whereas in animals with hyperadrenocorticism they have remained high or may have escaped from initial suppression. This LDDST is increasingly replaced by the second approach, i.e., the measurement of urinary corticoids. In this way an integrated reflection of the corticoid production is obtained, thereby adjusting for fluctuations in plasma levels. The urinary corticoids (largely cortisol) are measured by radioimmunoassay and related to the creatinine concentration, thus providing the urinary corticoid/creatinine ratio (UCCR). This test requires little time from the veterinarian, is not invasive (no blood collection), has a high diagnostic accuracy and easily allows follow-up examination for the purpose of documenting remission and recurrence.14,15 In addition the test procedure has the advantage of combining a test for basal adrenocortical function and a dynamic test for differential diagnosis (see below). The test can be used in both dogs and cats, albeit in cats with higher reference values than in dogs.16 Once the diagnosis of hyperadrenocorticism has been made it is necessary to distinguish between pituitary-dependent hyperadrenocorticism and hyperadrenocorticism due to adrenocortical tumor. Despite a decreased sensitivity to suppression by glucocorticoids, the ACTH secretion of most animals with pituitary-dependent hyperadrenocorticism can be suppressed with a 10-fold higher dose of dexamethasone, resulting in a decreased cortisol secretion. The autonomous hypersecretion by adrenocortical tumors will not be influenced by the high dose of dexamethasone. Two procedures are used, one employing plasma cortisol as a reflection of

adrenocortical secretion and the other urinary corticoid/creatinine ratios. In both, a greater than 50% decline from baseline values is regarded as diagnostic for pituitary-dependent hyperadrenocorticism.17 When suppression is less than 50%, the hyperadrenocorticism may be due to either an adrencortical tumor or a pituitary ACTH excess that is extremely resistant to dexamethasone suppression.18 For the differentiation between these two forms, measurements of endogenous ACTH are necessary. In the great majority of the dogs with adrenocortical tumor the basal ACTH values are completely suppressed. In the rare situation of questionable ACTH values, which for example might be due to the simultaneous occurrence of both entities6, further studies are required. These may include a CRH-stimulation test17 and visualization of the adrenal glands and the pituitary. It may also be helpful to measure plasma concentrations of -MSH. High values may be found especially in cases of intermediate lobe tumors, which tend to be dexamethasone resistant and rather large (see also above). Once the biochemical work-up indicates the presence of pituitary-dependent hyperadrenocorticism, the pituitary is visualized if possible. This visualization is imperative in institutions where hypophysectomy or pituitary irradiation are options for treatment. If this is not the case then visualization still gives insight into the prognosis. Treatment. The treatment of pituitary-dependent hyperadrenocorticism should be directed at the elimination of the stimulus for the augmented production of cortisol, i.e., the pituitary lesion causing the excessive ACTH secretion. Particularly because there is increasing evidence that these lesions are of primary pituitary origin (see above) and not the result of increased hypothalamic stimulation8, hypophysectomy is being revisited19. Visualization techniques have become available that enable presurgical insight into the size and expansion of the lesion. This in combination with improved surgical and anesthetic techniques now permits removal of rather large tumors. Also because in this approach the causative lesion is removed, this may become the method of choice in dogs and cats, as it is in man. The animals need lifelong replacement therapy with thyroxine and cortisone. In addition there may be transient diabetes insipidus, requiring treatment for some time. Other approaches are directed at the elimination of the glucocorticoid excess, either by bilateral adrenalectomy or by chemotherapy. With total adrenalectomy the cure is 100% and the prognosis with glucocorticoid and mineralocorticoid replacement is good, unless the expansion of the pituitary lesion gives rise to neurologic signs. Details on the peri- and postoperative medication are given in section. Probably because of the effectiveness and relative convenience of chemotherapy with o,p’-DDD, bilateral adrenalectomy is hardly used in dogs. As o,p’-DDD in cats does not give satisfactory results, in this species bilateral adrenalectomy has been used most often to treat pituitary-dependent hyperadrenocorticism. It is often successful but from the experience with the few cats that have been operated it has been concluded that long-term prognosis is guarded20. As in dogs, hypophysectomy may become a more attractive approach. Currently the most common form of treatment of pituitary-dependent hyperadrenocorticism in the dog is still the

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administration of the adrenolytic drug o,p’-DDD (Lysodren®, Bristol Laboratories). Many schedules aim at the selective destruction of the adrenal cortices, i.e., the destruction of the zona fasciculata and zona reticularis, while sparing the zona glomerulosa. However, in 5-6% of the dogs the zona glomerulosa is destroyed to such an extent that iatrogenic hypoadrenocorticism occurs21 In more than half of cases there are one or more relapses of hyperadrenocorticism during treatment21. In order to circumvent these complications a treatment schedule has been introduced that is aimed at the complete destruction of the adrenal cortices and substitution therapy for the induced adrenocortical insufficiency22: - 50 to 75 mg o,p’-DDD/kg per day is given for 25 days. This daily dose should be divided into three or four portions and administered with food. - On the third day, supplementations begins: Cortisone, 2 mg/kg per day Fludrocortisone, 0.0125 mg/kg per day Sodium chloride, 0.1 g/kg per day All doses are divided into at least two administrations. After 25-30 days, a follow-up examination is made. The cortisone dose is reduced to 0.5-1.0 mg/kg per day. Fludrocortisone and/or salt are adjusted according to the results of measurements of Na and K in plasma. Owner compliance is imperative for good results; written instructions for owners should be provided.23 During the first month the owner is requested to report by telephone at least once a week and as often as questions or problems arise. The owner is also instructed very clearly to stop o.p’-DDD administration when partial or complete inappetance develops, but with equal emphasis, to continue adrenocortical hormone substitution. If this measure is taken, the owner should also contact the veterinarian, who may increase the cortisone substitution temporarily. When a reduction in appetite is neglected and the o,p’-DDD treatment is continued the dog may start to vomit, refuse substitution therapy, and develop a hypoadrenocorticoid crisis. However, with good instructions this is rare and usually the o,p’-DDD administration can be resumed after a few days without further problems. As compared with treatment schedules that aim at the selective destruction of the two inner zones of the adrenal cortex, while trying to spare the zona glomerulosa21, the above described schedule has the advantage that the disease is stopped completely soon after initiation of the treatment and is not merely suppressed. In addition, lifelong substitution therapy is provided for the resulting primary hypoadrenocorticism and hence there is less risk of sudden, unexpected adrenocortical insufficiency. Finally, concurrent diabetes mellitus is more easily managed.24 Despite this drastic treatment schedule, recurrences do occur in about 30% of cases within one year. The owner may call because the animal’s appetite and water intake have increased. Omitting the cortisone substitution may ameliorate the signs temporarily, but the possible recurrence should be investiged by asking the owner to send urine specimens for measurements of corticoid/creatinine ratios. Two morning urine samples are collected at an interval of 4 to 5 days, each time omitting the cortisone and fludrocortisone administration on the preceding evening. Ratios exceeding the upper

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limit of the reference range indicate glucocorticoid excess, and o,p’-DDD therapy is then started for another 25 days, followed by once weekly administration of o,p’-DDD for 8 weeks. Substitution therapy and follow-up examinations are carried out as in the first course. In the rare case of a second recurrence, this procedure is repeated and the weekly o,p’DDD dose is continued for half a year. Another therapeutic option, although an expensive one, could be the inhibition of adrenocortical steroidogenesis by ketoconazole, a synthetic imidazole analogue used as a broad-spectrum antifungal agent. The major limitations in using ketoconazole in dogs are (1) the need for continuing twice daily administration, (2) the expense, and (3) the failure of some dogs to respond. In cats the results have been unpredictable and variable. Finally, two treatment options should be mentioned that so far have been used infrequently. First there is radiation therapy for pituitary macroadenomas. This may lead to some decrease in the tumor mass and peritumoral edema, but concurrent adrenocortical suppression treatment is needed. Probably still based upon the the abandoned concept of a hypothalamic origin of the disease the neuropharmacological approach has been reintroduced recently with the monoamine-oxidase inhibitor selegiline. This drug is not effective in ameliorating signs such as pu/pd and does not affect cortisol secretion.25

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ful removal of the tumor will result in complete recovery without the need for continuing medication. Because of the atrophy of the contralateral adrenal, due to the longstanding glucocorticoid excess, glucocorticoid substitution is needed initially. At the time of anesthesia, when intravenous fluid administration is started, 5 mg hydrocortisone or 1 mg prednisone per kg body weight is added to the first bottle and this amount is administered over a period of 6 h. Subsequently 0.5 mg hydrocortisone/kg is administered at 6 h intervals until oral medication is possible. This will consist of 1 mg cortisone/kg body weight of twice daily, which is gradually decreased and then stopped 6-8 weeks after surgery6. Dogs with irresectable tumor or recurrence of disease after adrenalectomy can often be treated successfully with o,p’-DDD, thereby initially employing the same schedule as for pituitary-dependent hyperadrenocorticism (see above). After 25 days of daily administrations of 50-75 mg o,p’DDD/kg, this chemotherapy is continued for at least three months by once weekly administrations of the same daily dose.23 This approach often leads to complete and permanent cure of the hyperadrenocorticism, and ultrasonographic examinations may reveal that the size of the tumor has decreased considerably. Even lung metastases may disappear, although it may also happen that this tumor dissemination cannot be affected.

References Hyperadrenocorticism due to adrenocortical tumors Adrenocortical tumors causing hyperadrenocorticism occur in both the dog and the cat Most are unilateral solitary lesions. The left and the right adrenal glands are affected about equally. Bilateral tumors occur in about one out of 10 cases6,26. Histological types range from small well-encapsulated adenomas to large carcinomas with liver and lung metastases. However, it should be noted that miscroscopic examination of a seemingly benign looking tumor may reveal expansion of tumor tissue into vessels6. Diagnostic imaging. Ultrasonography is the first choice for the visualization of adrenal glands. The technique allows good estimates of the size of the tumor and may reveal information about its expansion. In individual cases it may be difficult to distinguish between macronodular hyperplasia and adrenocortical tumor. In these instances additional visualization with CT may be needed, and especially in these cases the observations should be interpreted in conjunction with the results of the biochemical studies, i.e., basal plasma ACTH concentrations and if necessary extended by a CRH test.21 Once the presence of an adrenocortical tumor has been established, the possibility of distant metastases should be considered. During the abdominal ultrasonography for the identification of the adrenals also the liver can also be investigated for metastases. In cases of suspicion of liver metastases an ultrasound guided biopsy can be performed to test this this supposition. In addition thoracic radiographs should be made. Treatment. When the preoperative investigations have revealed that it is likely that there is a resectable unilateral tumor, it should be treated by surgery, because the success-

10.

Kemppainen RJ, Sartin JL, (1984), Evidence for episodic but not circadian activity in plasma concentrations of adrenocorticotrophin, cortisol and thyroxine in dogs. J Endocr 1984;103:219-226. Kooistra HS, Greven SH, Mol JA, Rijnberk A, (1997), Pulsatile secretion of -MSH and the differential effects of dexamethasone and haloperidol on the secretion of -MSH and ACTH in dogs. J Endocrinol 152:113-121. Meijer JC, de Bruijne JJ, Rijnberk A, Croughs RJM, (1978), Biochemical characterization of pituitary-dependent hyperadrenocorticism in the dog. J Endocr 1978;77:111-118. Kemppainen RJ, Sartin JL, (1987), Differential regulation of peptide release by the canine pars distalis and pars intermedia. Front Horm Res 17:18-27. Willemse T, Vroom MW, Mol JA, Rijnberk A, (1993), Changes in plasma cortisol, corticotropin, and -melanocyte-stimulating hormone concentrations in cats before and after physical restraint and intradermal testing. Am J Vet Res 54:69-72. Van Sluijs FJ, Sjollema BE, Voorhout G, van den Ingh TSGAM, Rijnberk A, (1995), Results of adrenalectomy in 36 dogs with hyperadrenocorticism caused by adrenocortical tumour. Vet Quart 17:113116. Scholten-Sloof BE, Knol BW, Rijnberk A, Mol JA, Middleton DJ, Ubbink G, (1992), Pituitary-dependent hyperadrenocorticism in a family of Dandie Dinmont terriers. J Endocr 135:535-542. Van Wijk P, Rijnberk A, Croughs RJM, Voorhout G, Sprang EPM, Mol JA, (1992), Corticotropin-releasing hormone and adrenocorticotropic hormone concentrations in cerebrospinal fluid of dogs with pituitarydependent hyperadrenocorticism. Endocrinology 131:2659-2662. Peterson ME, Orth DN, Halmi NS, Zielinski AC, Davis DR, Chavez FT, Drucker WD, (1986). Plasma immunoreactive proopiomelanocortin peptides and cortisol in normal dogs and dogs with Addison’s disease and Cushing’s syndrome: Basal concentrations. Endocrinology 119:720-730. Orth DN, Peterson ME, Drucker WD, (1988), Plasma immunoreactive proopiomelanocortin peptides and cortisol in normal dogs and dogs with Cushing’s syndrome: Diurnal rhythm and responses to various stimuli. Endocrinology 122:1250-1262.

11.

12.

13.

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17.

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Kooistra SH, Voorhout G, Mol JA, Rijnberk A, (1997), Correlation between impairment of glucocorticoid feedback and the size of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism. J Endocrinol 152:387-394. Biewenga WJ, Rijnberk A, Mol JA, (1991), Osmoregulation of systemic vasopressin release during long-term glucocorticoid excess: A study in dogs with hyperadrenocorticism. Acta Endocr 124:583-588. Teske E, Rothuizen J, de Bruijne JJ, Rijnberk A, (1989), Corticosteroid-induced alkaline phosphatase isoenzyme in the diagnosis of canine hypercorticism. Vet Rec 125:12-14. Meij BP, Mol JA, Bevers MM, Rijnberk A, (1997), Residual pituitary function after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism. J Endocrinol 155:531-539. Guptill L, Scott-Moncrieff JC, Bottoms G, Glickman L, Johnson M, Glickman N, Nelson R, Bertoy E, (1997), Use of the urine cortisol:creatinine ratio to monitor treatment response in dogs with pituitary-dependent hyperadreancorticism. J Am Vet Med Ass 210:1158-1161. Goossens MMC, Meyer HP, Voorhout G, Sprang EPM, (1995), Urinary excretion of glucocorticoids in the diagnosis of hyperadrenocorticism in cats. Domest Anim Endocrinol 12:355-362. Galac S, Kooistra HS, Teske E, Rijnberk A, (1997), Urinary corticoid/creatinine ratios in the differentiation between pituitary-dependent hyperadrenocorticism and hyperadrenocorticism due to adrenocorticial tumour in the dog. Vet Quart 19:17-20. Van Wijk PA, Rijnberk A, Croughs RJM, Wolfswinkel J, Selman PJ, Mol JA, (1994). Responsiveness to corticotropin-releasing hormone

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19.

20.

21.

22.

23. 24.

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and vasopressin in canine Cushing’s syndrome. Eur J Endocrinol 130:410-416. Meij BP, Voorhout G, van den Ingh TSGAM, Hazewinkel HAW, van’t Verlaat JW, (1997), Transsphenoidal hypophysectomy in beagle dogs: Evaluation of a microsurgical technique. Vet Surg 26:295-309. Duesberg CA, Nelson RW, Feldman EC, Vaden SL, Scott-Moncrieff CR, (1995), Adrenalectomy for treatment of hyperadrenocorticism in cats: 10 cases (1988-1992). J Am Vet Med Ass 207:1066-1070. Kintzer PP, Peterson ME. Mitotane (o,p’-DDD) treatment of 200 dogs with pituitary-dependent hyperadrenocorticism, (1991), J Vet Int Med 5:182-190. Rijnberk A, Belshaw BE. O,p’-DDD treatment of canine hyperadrenocorticism: an alternative protocol. In: Kirk RW, Bonagura JD, eds. Current Veterinary Therapy XI. Philadelphia: WB Saunders 1992:345-349. Rijnberk A, (1996), Clinical Endocrinology of Dogs and Cats. Kluwer Academic Publishers, Dordrecht/Boston, 61-88. Den Hertog E, Braakman JCA, Teske E, Kooistra HS, Rijnberk A, (1997), Treatment of pituitary-dependent hyperadrenocorticism in the dog by non-selective adrenocorticolysis with o,p’-DDD. Vet Quart 19:S17. Steffen T, Hörauf, Reusch C, (1997), Selegiline HCl (L-Deprenyl) for treatment of canine pituitary-dependent hyperadrenocorticism. J Vet Int Med 11:122 (ACVIM Abstract 74). Ford SL, Feldman EC, Nelson RW,(1993), Hyperadrenocorticism caused by bilateral adrenocortical neoplasia in dogs: Four cases (1983-1988). J Am Vet Med Ass 202:789-792.

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Supraventricular tachycardia in the dog Karsten Schober

Summary Supraventricular tachycardia (SVT) is a common rhythm disturbance in dogs. It is almost always a rapid, narrow complex tachycardia. SVT may be a complication of cardiac disease but may also occur in normal hearts. Reentry, altered automaticity, or triggered activity have been elucidated as the underlying electropathophysiologic mechanisms of SVT. The different types of SVT may be distinguished according to onset and cessation, duration, P wave configuration, regularity, ventricular rate, response to vagal maneuvers and antiarrhythmic drug therapy. However, the surface electrocardiogram alone may be inadequate for the complete differentiation of a specific mechanism. Sinus tachycardia and atrial fibrillation are the most important types of SVT in dogs. Owing to the high heart rates, SVT may lead to clinical signs such as weakness, tachypnea, syncope, systolic and diastolic cardiac failure, and death. Management aims at termination of acute episodes of SVT, convertion into sinus rhythm and prevention of recurrence. Precordial thumps, vagal maneuvers, and antiarrhythmics may be tried. In dogs with heart disease and SVT (particularly atrial fibrillation, atrial flutter, or atrial tachycardia), reduction of ventricular response rate is the primary therapeutic goal. Digitalis glycosides, beta-adrenergic blocking agents, and calcium antagonists are most often to be used. However, restoration of sinus rhythm is highly improbable.

Supraventricular tachycardia (SVT) is a reletively common rhythm disturbance in the dog.1,2 It should be considered in any patient with extremely rapid, narrow QRS tachycardia.3-6 However, SVT with bundle branch block

(Fig. 1) as well as ventricular pre-excitation may lead to wide QRS complexes.7 The P waves may be buried within the ST-T complex and be virtually invisible. This is termed a wide QRS supraventricular tachycardia. Ventricular tachycardia with narrow QRS complexes may also occur but this is a very rare condition (arrhythmogenic substrate is ventricular but located very close to the AV node) and accounts for less than 1 % of narrow complex tachycardias in humans.4 SVT may be classified according to their site of origin and the underlying mechanism.8,9 Functional or anatomical reentry, altered automaticity and, less frequently, triggered activity (delayed after depolarizations) have been elucidated as the fundamental mechanisms of SVT (Tab. 1).3,6,8-10 The surface electrocardiogram alone may be inadequate for the differentiation of a specific mechanism,6,9,10 however, an understanding of electrophysiology will better enable us to categorize and manage these arrhythmias. SVT may be further subdivided according to their duration into sustained (> 30 s) or nonsustained.3,7 However, a working definition of 10 or more consecutive beats to characterize sustained SVT seems to be more practical.3 According to onset and offset, SVT may be paroxysmal (sudden onset and cessation) or nonparoxysmal (gradual acceleration and deceleration). Paroxysmal SVT is suggestive of reentry whereas nonparoxysmal SVT usually characterizes automatic rhythms.8 Automatic supraventricular tachycardia develops within the sinus node or the atrial or junctional myocardium. Altered automaticity, particularly increased spontaneous depolarization rates may occur in response to catecholamine stimulation, ischemia, infection, electrolyte disturbances, enlarged atria, myocardial fibrosis and digitalis intoxication.8,9 Typically, a warm-up phenomenon characterizes automatic rhythms,11 i.e. the heart rate gradually accelerates

Figure 1 - Atrial fibrillation with left bundle branch block pattern (160 beats/min) in an 11 years old male giant snauzer with DCM. Paper speed, 50 mm/s; 5 mm = 1 mV.

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DVM, Med Vet Department of Small Animal Medicine (Head: Prof. Dr. G. Oechtering) Faculty of Veterinary Medicine, University of Leipzig - Germany

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Table 1. Classification of supraventricular tachycardia according to their site of origin and mechanism4,6,8 delayed after abnormal reentry depolarizations automaticity sinus tachycardia atrial tachycardia - paroxysmal - permanent atrial flutter atrial fibrillation AV nodal reentrant tachycardia junctional tachycardia AV reentry tachycardia (WPW)

(+)

–

+++

+++ (+) +++ +++ +++ – +++

(+) – – – – (+) –

– +++ – – – +++ –

WPW, Wolff-Parkinson-White syndrome; AV, atrioventricular; +++, common mechanism; (+), rare or questionable mechanism

and decelerates. Automatic rhythms are usually not as rapid as reentrant rhythms. Sinus tachycardia is the most common type of benign SVT seen in dogs (Fig 2). Fear, pain, hypovolemia, hypotension, shock, hyperthermia, anemia, thyreotoxicosis, treatment with atropine or catecholamines may lead to excess sympathetic stimulation which is the driving force for this arrhythmia.10 Normal P waves on ECG which are sometimes hidden in the previous QRS-T complex, a regular rhythm and heart rates up to 300/min are typical ECG features. Treatment is usually directed towards the correction of the underlying, often non-cardiac problem. Vagal maneuvers do little to slow down the heart rate.10 The temporary use of ß-blockers may be indicated. Atrial tachycardia arises from abnormally increased automaticity or reentry within the atrial myocardium.5 Automatic atrial tachycardia is nonparoxysmal and not as rapid as reentrant rhythms. Typically, discrete P waves are seen on ECG, although they are different in configuration compared

to sinus P waves. P-R interval and the ratio between P waves and QRS complexes depend on the site of origin in the atrium, the rate of impulse formation, and atrioventricular (AV) nodal transmission characteristics.8 Atrioventricular block can occur and may confirm the suspicion of primary atrial tachycardia.5 Atrial automatic tachycardia is often very resistant and nonresponsive to treatment; vagal maneuvers, drugs, overdrive pacing or electrical cardioversion rarely abolish the arrhythmia.5,8 It is usually observed in patients with myocardial disease but little is known about the initiating events.6 The persistant nature of the tachycardia and the inability to control the ventricular rate may virtually result in dilated (tachycardia induced) cardiomyopathy.6,8,12 Atrial reentrant tachycardia occurs less commonly (Fig. 3). This arrhythmia is a regular, very rapid (180-500 beats/min) and paroxysmal tachycardia that is rather responsive to antiarrhythmic therapy. Class Ia agents, digitalis or βblockers can be used to control the arrhythmia.10 About 20 % of paroxysmal atrial tachycardias in people is assumed to base on triggered activity resulting from delayed after depolarization.13 Automatic junctional tachycardia arises from in or near the His bundle/AV junctional tissue, occurs nonparoxysmally and may be regular or irregular, depending on autonomic tone.9 Negative P waves preceding the QRS complex may be seen as well as P waves occuring within the QRS complex. It may coexist with atrial fibrillation (AF) and may result in regular ventricular response despite AF.10,14 Reentrant supraventricular tachycardia may develop within the sinus node, the atrial myocardium and the AV nodal tissue (functional reentry) or between the atria and the ventricles via accessory pathways (anatomical reentry). Reentry is thought to be the most common cause of supraventricular tachydysrhythmias. Requirements for reentry include: 1) an available circuit (two pathways), 2) an area of slow conduction, 3) an area of unequal refractoriness (functional unidirectional block), and almost always 4) an

Figure 2 - Sinus tachycardia (195 beats/min) in a 5 years old male Pyrenean mountain dog. P-waves are fused with the preceeding T-wave (12th to 19th QRSTcomplex). Paper speed, 25 mm/s; 10 mm = 1 mV).

Figure 3 - Paroxysmal atrial reentrant tachycardia (480 beats/min) in a 9 years old female German shorthaired pointer. Paper speed, 50 mm/s; 10 mm = 1 mV.

Table 2. Drugs commonly used in the management of supraventricular tachycardia in dogs1,8,9,24,38 Drug

Route

Adenosine Amiodarone Ajmaline Atenolol Quinidine sulfate Diltiazem Endrophonium chloride Esmolol Flecainid Metildigoxin

IV PO IV PO IV PO IV PO IV

0.05-0.30 mg/kg (fastest bolus) 2 mg/kg q 8 h 0.5-1.5 mg/kg (bolus) 0.2-1.0 mg/kg q 24 h 2-10 mg/kg (slow bolus) 10-20 mg/kg q 6-8 h 0.10-0.25 mg/kg (slow bolus) 0.5-2.0 mg/kg q 8-12 h 0.15 mg/kg mg (slow bolus)

0.25-0.50 mg/kg (bolus) or 0.1-0.2 mg/kg (constant infusion) 1 mg/kg (bolus) 0.01-0.02 mg/kg (divided into 4 aliquots, each given hourly) 0.005-0.010 mg/kg q 12 h (or 0.22 mg/m2 BSA) 0.2-1.0 mg/kg q 12-24 h 6-8 (-25) mg/kg (very slow bolus) 10-20 (-40) mg/kg q 6-8 h 0.02- 0.10 mg/kg (very slow bolus) 0.25-1.0 mg/kg q 8 h 1-2 mg/kg (bolus) 0.008 mg/kg/min (constant infusion) 1-5 mg/kg q 8 h 0.5-2.0 mg/kg q 8-12 h 0.05-0.10 mg/kg every 10-30 min to effect (slow bolusus, do not exceed 0.20 mg/kg), 0.002-0.010 mg/kg/min (constant infusion) 0.5-2.0 (-5.0) mg/kg q 8 h

IV IV PO

Metoprolol Procainamide

Propafenone

PO IV PO IV PO IV

Sotalol Verapamil

PO PO IV

Propranolol

PO BSA, body surface area

General Dose Schedule

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excitable gap within the circuit.10,15-17 When the circuit is tiny, such as within the AV node, it is termed micro-reentry. When the circiut traverses a longer path, the term macroreentry is used.10 Of all sustained supraventricular tachycardias, atrial fibrillation (AF) is by far the most common and most important. It is usually not difficult to diagnose AF from the surface electrocardiogram. Typically, the ECG shows rapid, irregular atrial activity in absence of P waves and rapid irregularly irregular ventricular response (Fig. 4 and 5). Exceptions can be found in dogs with concurrent AV nodal conduction disease or junctional tachycardia, where the ventricular response may be regular in rhythm.10,14 Atrial fibrillation commonly accompanies other disorders such as mitral valve disease, congenital heart defects, congestive heart failure, hypertrophic cardiomyopathy, or hyperthyroidism,17 most often associated with extremely large left atria. Toxins, autonomic dysbalance, trauma, anesthesia, or other tachycardias may also induce AF.14,17,18 Atrial fibrillation with a normal ventricular response rate in the absence of known structural heart disease is well described in men14,17,19 and dogs20,21 and is termed “lone atrial fibrillation”. AF may be paroxysmal, persistent (conversion into sinus rhythm possible) or permanent („incessant“; conversion into sinus rhythm impossible).16 The latter one is the most common type of AF in dogs. The electrophysiologic basis of atrial fibrillation has been ascribed primarily to the multiple wavelet hypothesis.22,23 The wavelet theory is based on continuous multiple intra-atrial reentry. Interlacing wavelets are able to reexcite areas that have been activated by other wavelets. There is a continuous changing pattern of excitation with AF, with 4 to 6 simultaneous reentrant wavelets necessary to maintain atrial fibrillation.17,23 Leading circle reentry may be responsible for multiple wavelets, but an excitable gap has recently been demonstrated in one type of AF.17 However, limited information is available on the pathological, electrophysio-

Figure 4 - Atrial fibrillation (230 beats/min) in a 12 years old male dachshound with mitral valve endocardiosis and ruptured chordae tendineae. Paper speed, 50 mm/s; 10 mm = 1 mV.

Figure 5. Atrial fibrillation (210 beats/min) in a 4 years old male Doberman pinscher with dilated cardiomyopathy. Paper speed, 25 mm/s; 5 mm = 1 mV.

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logical and initiating mechanisms of AF.12,17 Over the past few years it became obvious that atrial electrophysiological remodeling and regional electrical heterogeneity may be the electrophysiologic basis for the development of AF. A heart that is electrophysiologically homogeneous probably cannot fibrillate.17 Multiple profibrillatory events can contribute to the development of electrical heterogeneity and thus atrial fibrillation:6,15,17 A. autonomic effects B. atrial stretch C. a single discharging focus D. atrial remodeling. Autonomic effects. Vagal stimulation has been shown to cause unequal shortening of refractoriness in the atria and thus creates electrophysiologic heterogeneity in experimental dogs.24 Elevated catecholamine and angiotensin II levels produce structural changes in the myocardium (hypertrophy, collagen accumulation, fibrosis) which might facilitate the onset of AF by directly modifying electrophysiologic atrial properties.25 Paroxysmal atrial fibrillation may be vagally initiated (“vagally-sensitive type”) or catecholamine-induced (“catecholamine-sensitive type”) in otherwise normal, healthy athletes.8,26 Atrial stretch. Increased atrial stretch, a common feature in dogs with volume overloaded left atria, prolongs atrial refractoriness. This increase in refractoriness occured heterogeneously as shown in dogs with acute atrial distension. Thin areas of the atria were more stretched than thick areas resulting in heterogeneous prolongation of refractoriness and increasing the dispersion of atrial effective refractory period resulting in more easily inducable AF.6,27 Focal atrial fibrillation. A single rapidly discharging focus, similar to a pacemaker, as a cause of AF has been shown in humans.28 Rapid atrial activation may lead to fragmentation of excitation, electrical heterogeneity and thus atrial fibrillation. Atrial remodeling. Rapid atrial activation as shown in dogs12 causes time-dependent nonuniform electrophysiological remodeling of the atrial myocardium. Effective refractory period decreases as well as conduction velocity and wavelength, which, along with increased regional heterogeneity and vulnerability, provide a substrate for AF.9,12 Thus, fast heart rates created by supraventricular tachycardia leads to electrophysiological remodeling that favours its own maintenance (“AF begets AF”).12,29 A critical mass of myocardium seems to be necessary to maintain AF.23 The larger the heart the easier it is to sustain

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atrial fibrillation.10 However, recent data suggest that sustained AF may also occur spontaneously in very small animals such as chickens.30 Atrial flutter is a relatively rare form of SVT in dogs. It is different from AF and is most likely based on a single macro-reentrant circuit of activation with an excitable gap located in the right atrium, while the left atrium behaves as a bystander not incorporated in the circuit.3,15 It may present as brief paroxysms or as a sustained event. The classical sawtooth pattern of atrial activity (undulating F waves) is the ECG hallmark of this tachyarrhythmia. AV conduction is usually less than 1:1, often 3:1 or 4:1 and thus appears to be more regular.8,10 Atrial flutter can be paced terminated in contrast to AF.9 Sinus nodal reentry is a rare condition in dogs. The pathway of reentry is confined within the sinus node or between the sinus nodal and the surrounding atrial tissue. The arrhythmia starts paroxysmal (in contrast to sinus tachycardia) and shows P waves that are very similar to sinus P waves.9 Increases in vagal tone or antiarrhythmic drugs may interrupt the reentry. AV nodal reentrant tachycardia is a common cause of SVT in people.6,8 The reentrant circuit is composed of two pathways within the AV node (“dual AV node”): antegrade conduction occurs in functionally differentiated fibers with slow conduction and a short refractory period (slow α-pathway), and retrograde conduction occurs in fibers with rapid conduction and a long refractory period (fast β-pathway).10,11 Atypical AV nodal reentrant tachycardia is assumed to use the two pathways in the opposite direction.26 The paroxysmal tachycardia is regular with normal QRS complexes on surface ECG and is initiated by a premature impulse (Fig. 6).6,8,26 The negative P waves are either completely hidden in the QRS complex or distorting the terminal portion of QRS. Increased vagal tone or drugs that slow AV conduction or increase effective refractory period may terminate the arrhythmia.5,6,8-10 Atrioventricular reentrant tachycardia (synonyms: bypass-tract reentrant tachycardia, circus movement tachycardia, reciprocating tachycardia) is well recognized in young human patients4-6 but is less common in the dog.2,31,32 It represents a macro-reentry because the reentrant circuit is large involving the AV node, the His-Purkinje system, ventricular and atrial myocardium, and the bypass tract (the bundle of Kent, James fibers, or Mahaim fibers).10,31 The bypass-tract, an embryonic muscular remnant, may be very short (some millimeters in length) and extremely thin (hair-sized in di-

Figure 6 - AV nodal reentrant tachycardia (480 beats/min) in a 11 years old male dachshound with syncope but without echocardiographically detectable organic heart disease. Paper speed, 50 mm/s; 5 mm = 1 mV.

ameter).3,16 In man, 60 to 70% of AV pathways are left sided.26 AV reentrant tachycardia may be orthodromic or antidromic.6,9 Ventricular pre-excitation occurs when the impulse from the SA node bypasses the AV node through the accessory pathway to the ventricles. As impulse conduction in the bypass tract is faster than in the AV node, the impulse conducted through the accessory pathway stimulates a portion of the ventricles prematurely with the rest of the ventricles being activated in the normal sequence through the AV node. The Wolff-Parkinson-White syndrome consists of ventricular pre-excitation with episodes of paroxysmal SVT (Fig. 7). When the accessory AV connection conducts antegrade during sinus rhythm, ventricular pre-excitation is manifested by the presence of delta waves, short PR interval and prolonged QRS duration on surface ECG (Fig. 8). A concealed bypass tract (which has only ventriculo-atrial conduction) is inapparent on the ECG during normal sinus rhythm.2,9,31,32 SVT can be induced by premature atrial or ventricular beats31,32 and is often very fast (> 300 beats/min). Usually, QRS complexes are narrow (except antidromic impulse conduction) and retrograde P waves are to be seen within the ST segment.6,26 Unfortunately, P waves are often difficult to discern, especially with very rapid heart rates.31 Medical therapy aims at slowing AV conduction or at increasing refractoriness of the accessory pathway to ameliorate the arrhythmia.9,10,31

Management Supraventricular tachyarrhythmias are important when they result in clinical signs, when they lead to further deterioration of heart function or when they may be a marker or indicator of patients at risk for collapse or sudden death. Clinical signs resulting from tachycardias may include tachypnea,

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worsening or development of congestive heart failure, weakness, reluctance to exercise, collapse, and syncope. Atrial fibrillation is by far the most relevant type of SVT in dogs. Dilated cardiomyopathy, severe chronic valvular disease, or congenital malformations (patent ductus arteriosus, mitral valve dysplasia) usually account for AF in dogs. Rapid ventricular rates during AF increase myocardial oxygen consumption, decrease diastolic filling and thus, result in myocardial ischemia, stiffness and arrhythmia, reduce cardiac output, leading to hypotension and congestive heart failure.14,33 AF also causes myocardial electrophysiological remodeling that itself maintains AF and may lead to tachycardia-induced cardiomyopathy.6,17 Treatment of AF depends on the stability of the patient and the underlying problem. Lone atrial fibrillation in giant breed dogs with slow ventricular response rate (< 120 beats/min at home) should not necessarily be treated.21 Sustained or suddenly observed AF with a fast ventricular response but without structural heart disease may be converted to sinus rhythm pharmacologically using class Ia (procainamide, quinidine), Ic (propafenone), II (esmolol, metoprolol), or III (amiodarone, sotalol, dofetilide) drugs14,20,33-35 or treating the initiating problem. Antiarrhythmic agents change the refractory period, conduction velocity, or wavelength.9 Thump on chest can be tried but rarely restores sinus rhythm (Fig. 9). The primary goal in the management of AF (or atrial flutter) in dogs with heart disease is to reduce ventricular response rate, unload the heart and to correct neurohumoral activation.6,9 The optimal heart rate in experimental dogs with AF has been reported to be approximately 130 to 145 beats/min but this is rarely to be reached.36 The drug of choice in animals with ventricular myocardial failure is digitalis although response to digoxin is often unpredictable. It has positive inotropic action, prolongs AV refractoriness, and decreases AV conduction.10,14 Digoxin shows ventricular

Figure 7 - Supraventricular tachycardia with WPW syndrome (334 beats/min) in a 2 years old male Siberian husky dog with recurrent episodes of weakness. Note the retrograde P-waves in the ST-segment. Paper speed, 50 mm/s; 5 mm = 1 mV.

Figure 8. Ventricular pre-excitation and sinus rhythm (100 beats/min) in a 2 years old male Siberian husky dog with Wolff-Parkinson-White syndrome. Deltawaves are to be seen before onset of the R-wave. Paper speed, 50 mm/s; 5 mm = 1 mV.

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Figure 9. Conversion of atrial fibrillation (300 beats/min) into sinus rhythm (150 beats/min) following precordial thump (applied at the 7th QRS complex on ECG) in a 3 years old female Great Dane with fever and increased sympathetic activity. Paper speed, 50 mm/s; 10 mm = 1 mV.

response predominantly by augmenting vagal tone,6,9,14,33 therefore, digoxin is relatively ineffective in situations where sympathetic drive predominates, causing failure to control ventricular rates with excitement or exercise.6,9,33 Hence, additional drugs may be required, if the rate control is not satisfactory, eg. calcium channel blockers or β-blockers. As the latter are negative inotrops, careful monitoring during therapy is necessary.14 In dogs with preserved systolic function, calcium antagonists, β-blockers, or propafenone may be used without digitalis for rate control. Diuretics and angiotensin converting enzyme inhibitors are beneficial in decreasing preload and thus left atrial size and profibrillary myocardial stretch.6 Radiofrequency catheter ablation of the AV node, direct current cardioversion, implantable atrial defibrillators, or biatrial pacing have been suggested to interrupt AF and prevent recurrences of atrial fibrillation in humans.14,17 However, such sophisticated therapeutic means are still under investigation and not routinely available for veterinary use.37 WPW-syndrome. Asymptomatic ventricular pre-excitation or infrequent, non-life-threatening and self-terminating episodes of SVT do not require treatment. In sustained symptomatic SVT with heart rates often above 300/min therapeutic intervention is mandatory. In these cases, SVT is a life-threatening rhythm disturbance.38 Acute treatment aims at the termination of the tachycardia whereas long-term treatment aims at prevention of recurrences. Initial management of SVT, irrespective of mechanism, should start quickly and follow a logical progression: 1) “Vagal maneuvers”. Reflex vagal maneuvers (gentle bilateral ocular pressure, carotid sinus massage, facial emersion in ice-water, external application of abdominal pressure) increases parasympathetic nervous (vagal) input that may transiently impair AV conduction to the point of second degree AV block resulting in abrupt termination of bypass tract tachycardia.5,6,31 Emetics such as apomorphine may also abolish the tachycardia via increases in vagal tone.31 2) Mechanical termination. Precordial thumps in fast tachyarrhythmias should initially always be tried although abolition of the tachycardia mechanically is often not very successful.31 3) Pharmacological cardioversion. Calcium channel blocking agents such as verapamil or diltiazem slow conduction and prolong the refractory period of the AV node.31 Bypass tract refractoriness may be shortened. Beta-blockers such as esmolol or atenolol have the same effect on the AV node beside its antisympathetic activity.10 Adenosine, an ul-

trashort-acting endogenous nucleoside (plasma half-life about 1.5 seconds), slows AV conduction, increases AV nodal refractoriness, is negative inotrop, and has antiadrenergic actions.6,39 It should be given as a rapid bolus dose followed by a saline flush.39 Adenosine may terminate the vast majority of junctional tachycardias and re-entrant tachycardias involving the AV node within seconds.39 Edrophonium is a transient cholinesterase inhibitor, that produces a response similar to vagal maneuvers.6 Procainamide and quinidine lengthen the refractory period of the accessory pathway.31 Propafenone increases conduction time of the accessory pathway and the AV node and can be used acutely and long-term.31 Digitalis glycosides depress AV nodal conduction but may shorten refractory period of the bypass tract. As the conduction via the accessory pathway may be favoured with digitalis, verapamil, or adenosine, administration of these drugs is usually avoided in humans with WPWsyndrome and atrial fibrillation because of the risk of rapid ventricular response and subsequent ventricular fibrillation4,5,31 4. Transesophageal stimulation. 5. Direct current cardioversion. Long-term management of WPW-syndrome can be accomplished by slowing conduction or prolonging refractoriness in either arm of the reentrant circuit. To the author´s experience, procainamide, β-blockers, and propafenone may be used successfully. Curative radiofrequency ablation of bypass tracts is the ultimate in management strategies in people3,4 and has also been reported in dogs.2,32

References 1. 2.

3. 4.

Bonagura JB, (1989), Atrial arrhythmias, In: Kirk RW (ed), Current Veterinary Therapy X, WB Saunders, Philadelphia, 271-278. Atkins CE, Kanter R, Wright K et al., (1995), Orthodromic reciprocating tachycardia and heart failure in a dog with a concealed posteroseptal accessory pathway, J Vet Int Med, 9:43-49. Campbell RWF, (1996), Supraventricular tachycardia. Occasional nuisance or frequent to treat?, Eur Heart J, 17:21-25. Grimm W, Menz V, Hoffmann J et al., (1996), Elektrokardiographische Differentialdiagnose tachykarder Rhythmusstörungen. Teil I: Tachykardien mit schmalem QRS-Komplex, Herz/Kreisl, 28:109-117. Paul T, Pfammatter JP, (1994), Supraventrikuläre Tachykardien im Säuglings- und Kindesalter. Diagnostik und Therapie, Monatsschr Kinderheilkd, 142:774-780. Van Den Berg, MP, Tuinenburg AE, Crijns, HJGM et al., (1997), Heart failure and atrial fibrillation: current concepts and controversies, Heart, 77:309-313.

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Grimm W, Menz V, Hoffmann J et al., (1996), Elektrokardiographische Differentialdiagnose tachykarder RhythmusstĂśrungen. Teil II: Tachykardien mit breitem QRS-Komplex, Herz/Kreisl, 28:157-163. Wellens HJJ, (1996), The value of the ECG in the diagnosis of supraventricular tachycardias, Eur Heart J, 17 (Suppl C):10-20. Moise SN, (1992), Mechanisms of supraventricular arrhythmias, Proc 10th ACVIM Forum, San Diego, 605-607. Lunney J, Ettinger SJ, (1995), Cardiac arrhythmias, In: Ettinger SJ, Feldman EC (eds), Textbook of Veterinary Internal Medicine, 4th ed, WB Saunders, Philadelphia: 959-995. Zipes DP, (1988), Specific arrhythmias: diagnosis and treatment, In: Braunwald E (ed), Heart Disease. A Textbook of Cardiovascular Medicine, 4th ed, WB Saunders, Philadelphia: 658-716. Gaspo R, Bosch RF, Talajic M et al., (1997), Functional mechanisms underlying tachycardia-induced atrial fibrillation in a chronic dog model, Circulation, 96:4027-4035. Rosen MR, (1988), The links between basic and clinical cardiac electrophysiology, Circulation, 77:251-263. Baer M, Goldschlager N, (1995), Atrial fibrillation: an update on new management strategies, Geriatrics, 50:22-29. Mary-Rabine L, Mahaux V, Waleffe A et al., (1997), Atrial flutter: historical backround, J Cardiovasc Electrophysiol, 8:353-358. Campbell RWF, (1997), personal communication. Zipes DP, (1997), Atrial fibrillation: from cell to bedside, J Cardiovasc Electrophysiol, 8: 927-938. Russell LC, Rush EJ, (1995), Cardiac arrhythmias in systemic disease, In: Bonagura JD (ed), KirkÂ´s Current Veterinary Therapy XII, WB Saunders, Philadelphia, 161-175. Kopecky SL, Gersh BJ, McGoon MD et al., (1987), The natural history of lone atrial fibrillation. A population-based study over three decades, N Engl J Med, 317:669-674. Edwards NJ, (1993), Atrial fibrillation rate control in three groups of patients, Proc 11th ACVIM Forum, Washington DC, 408-410. Harpster NK, (1994), Cardiac arrhythmias in the Irish Wolfhoud: preliminary study, Proc 12th Forum ACVIM, San Francisco, 319-321. Moe GK, (1962), On the multiple wavelet hypothesis of atrial fibrillation, Arch Int Pharmacodyn Ther, 140:183-188. Allessie MA, (1995), Reentrant mechanisms underlying atrial fibrillation, In: Zipes DP, Jalife J (eds), Cardiac Electrophysiology: From Cell to beside, WB Saunders, Philadelphia, 562-566. Zipes DP, Mihalick MJ, Robbins FT, (1974), Effects of selective vagal stellate ganglion stimulation on atrial refractoriness, Cardiovasc

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Res, 8:647-655. Borzak S, Goldstein S, Sabbah HN, (1993), Hemodynamic and neurohumoral predictors of the development of atrial fibrillation in dogs with chronic heart failure, Circulation (Suppl I), 88:18. Josephson ME, Schibgilla VH, (1996), Athletes and arrhythmias: clinical consideration and perspectives, Eur Heart J, 17:498-509. Satoh T, Zipes DP, (1996), Unequal atrial stretch in dogs increases dispersion of refractoriness conductive to developing atrial fibrillation, J Cardiovasc Electrophysiol, 7:833-842. Haissaguerre M, Marcus FI, Fischer B et al., (1994), Radiofrequency catheter ablation in unusual mechanism of atrial fibrillation: report of three cases, J Cardiovasc Electrophysiol, 5:743-751. Wijffels MC, Kirchhoff CJ, Dorland R et al., (1995), Atrial fibrillation begets atrial fibrillation: a study in awake chronically instrumented goats, Circulation, 92:1554-1568. Mukai S, Machida N, Nishimura M et al., (1996), Electrocardiographic observation on spontaneously occuring arrhythmias in chickens, J Vet Med Sci, 58:953-961. Atkins CE, (1994), Supraventricular tachycardia associated with atypical accessory pathways in dogs, Proc 12th ACVIM Forum, San Francisco, 325-327. Scherlag BJ, Wang X, Nakagawa H et al., (1993), Radiofrequency ablation of a concealed accessory pathway as treatment for incessant supraventricular tachycardia in a dog, J Am Vet Med Assoc, 203:1147-1153. Riley RD, Pritchett ELC, (1997), Pharmacologic management of atrial fibrillation, J Cardiovasc Electrophysiol, 8:818-829. Stroobandt R, Stiels B, Hoebrechts R et al., (1997), Propafenone for conversion and prophylaxis of atrial fibrillation, Am J Cardiol, 79:418-422. Falk HR, Pollak A, Singh SN et al., (1997), Intravenous dofetilide, a class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter, J Am Coll Cardiol, 29:385-390. Hamlin RL, (1995), What is the best heart rate for a dog in atrial fibrillation?, Proc 13th ACVIM Forum, Lake Buena Vista, 1072-1074. Wright KN, Bright JM, Cox JW et al., (1996), Transcatheter modification of the atrioventricular node in dogs, using radiofrequency energy, Am J Vet Res, 57:229-235. Keene B, (1991), Emergency management of cardiac arrhythmias, Proc 9th ACVIM Forum, New Orleans, 13-15. Oates JA, Wood AJJ, (1991), Adenosine and supraventricular tachycardia, N Engl J Med, 325:1621-1629.

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Therapeutic considerations in dogs with dilated cardiomyopathy Karsten Schober

Summary

Etiology

Dilated cardiomyopathy (DCM) is a primary heart muscle disease of unknown etiology characterized by gradual ventricular dilation, loss of contractility and often symptoms of congestive heart failure. It occurs predominantly in middle aged, male large breed dogs. Despite the development of new treatment strategies it remains an important cause of morbidity and mortality in dogs. Long-term prognosis depends on disease stage and breed but is, in general, poor. The primary goals of management in dogs with DCM are stabilization of the patient, improvement of quality of life and prolongation of survival. Inotropic support (digitalis glycosides, sympathicomimetics, phosphodiesterase F-III inhibitors, calcium sensitizers), pre- and afterload reduction (diuretics, vasodilators), heart rate control (beta-adrenergic blocking agents, calcium antagonists) and arrhythmia suppression (class I, II, and III antiarrhythmics) are the basic principles of management. Supportive therapy (rest, oxygen supply, chest or abdominal draining, low salt diet, exercise regimen, carnitine, taurine, or coenzyme Q10 supplementation) are complemental to drug therapy. Dynamic cardiomyoplasty, growth hormone administration, and immunosuppressive drug therapy are still under investigation.

The causes of idiopathic DCM in dogs are still unknown. Evidence suggests that DCM represents end stage myocardial failure resulting from a variety of disorders. Investigations into the pathogenesis of the disease have focused on four basic mechanisms: (1) familial and genetic factors, (2) viral myocarditis and other cytotoxic insults, (3) immune mediated abnormalities, and (4) metabolic, energetic, and contractile abnormalities.11-16 It is likely that more than one primary disease processes can induce the same functional and morphologic abnormalities that are clinically recognized in DCM.

Idiopathic dilated cardiomyopathy (DCM) is a primary heart muscle disease of unknown etiology, characterized by left ventricular or biventricular dilation and impaired systolic function.1,2 The disease is reportedly the second most common cause of congestive heart failure in the dog3 and, despite the development of new treatment strategies, it remains an important cause of morbidity and mortality in dogs as well as humans. Idiopathic DCM is a condition usually affecting large breed dogs between one and five years of age and is common in males.4 DCM seems to be a term that rather represents different syndromes in different breeds or even individuals within one breed than a uniform disease entity. The natural history of the disease is not well established and differs in certain breeds, the clinical signs vary, the disease progression may be different as well as the response to treatment. Specific cardiomyopathies in Doberman pinscher dogs,5,6 boxer dogs,7 Dalmatians,8 English cocker spaniels,9 and Irish Wolfhound dogs10 have been described. To the authors experience, giant snauzers may also develop a special type of DCM.

Pathophysiology Impaired systolic ventricular function is the primary pathophysiologic abnormality in most dogs with DCM. Reduced stroke volume may result in signs of low cardiac output manifested as weakness, syncope, exercise intolerance, or cardiogenic shock. Compensatory mechanisms are activated early in the course of the disease that attempt to normalize cardiac output and maintain arterial blood pressure. The neurohormonal compensatory changes in heart failure include increases in sympathetic nervous tone, activation of the renin-angiotensin-aldosterone system (RAAS), and the release of vasopressin and other vasoactive peptides (endothelins, atrial and brain natriuretic peptides, neuropeptide Y, gamma2-melanocyte-stimulating hormone, dopamine, prostaglandins, endogenous opioids)17 or cytokines.15 The long-term consequences are increased pre- and afterload, myocyte injury,18 muscular, vascular and interstitial ventricular remodelling19 and, therefore, further aggravation of heart failure.13 Diastolic function may also be abnormal in dogs with DCM.20 In a small subset of human patients, diastolic dysfunction may occur before onset of systolic disturbance.21 Markers of diastolic abnormality correlate strongly with congestive symptoms as pulmonary edema, pleural effusion, ascites, or cachexia. Other factors contributing to further deterioration of ventricular performance include valvular insufficiency secondary to atrial and ventricular dilation and dysrhythmias such as atrial fibrillation or ventricular ectopy.20

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Clinical diagnosis Dilated cardiomyopathy is a progressive disease, usually characterized by a subclinical, occult stage that lasts for months or even years (asymptomatic DCM) and the stage of overt cardiac failure (symptomatic DCM). The spectrum of clinical signs exhibited by dogs with DCM is similar in all breeds but considerable differences between various breeds in the frequency and severity of these signs and the outcome may be observed.2,20,22 Occult DCM has been described predominantly in Doberman pinschers,3,23 boxer dogs7,24 and Irish Wolfhounds.10,20 Ventricular or supraventricular arrhythmias may be observed frequently in these dogs despite normal echocardiographic systolic indices. Some of the dogs eventually develop heart failure, some die suddenly.20,23 Physical examination. In dogs with clinical signs of DCM, forward failure results in tissue hypoperfusion and is seen as weakness, lethargy, exercise intolerance, syncope, anorexia, pale mucous membranes, and hypothermia. Backward failure leads to tachypnoea, dyspnoea, jugular distension, ascites, muscle wasting and peripheral edema. Cardiac auscultation may reveal muffled heart sounds, pulmonary crackles, soft and often variable regurgitant systolic murmurs, arrhythmias, and gallop sounds. Weak arterial pulses, pulse deficit, and pulsus alternans also indicate myocardial failure.2,20,22,25 Biochemical analysis. Clinical pathologic changes in dogs with DCM may be as follows: prerenal azotemia, hepatic enzyme elevations, mild metabolic acidosis, mild hypoproteinemia, hyperkalemia or hyponatremia. Serum thyroid concentrations are often depressed.20 Serum markers of myocardial cell injury like cardiac troponin I concentrations or the MB bands of creatinine kinase are elevated in most dogs with DCM.18 Electrocardiography. High amplitude or widened QRS complexes, widened P waves, and ST segment coving may be discovered. Small R wave amplitudes occur in pleural or pericardial effusions. Of greater clinical importance is the high prevalence of cardiac dysrhythmias in dogs with DCM. Atrial fibrillation or atrial tachycardia, ventricular premature depolarizations, and ventricular tachycardia are common whereas conduction disturbances may be observed less frequently.20,22 Holter ECG monitoring (24-hour ambulatory ECG) is a very useful method to detect ventricular arrhythmias in dogs with occult DCM.23,24,26 Radiography. Cardiac silhouette enlargement (due to cardiomegaly or pericardial effusion), left atrial enlargement, pulmonary venous congestion, alveolar and interstitial edema, pleural effusion, distended caudal vena cava, hepatosplenomegaly, or ascites may be evident in congestive heart failure.19,20 Echocardiography. This method has become the â&#x20AC;&#x153;gold standardâ&#x20AC;? used to document and quantify myocardial dysfunction and to exclude other causes of heart disease. Atrial and ventricular dilation, ventricular hypokinesis, asymmetric chamber contraction, decreased mitral valve excursion, mitral or tricuspid valve regurgitation, decreased cardiac output, pseudonormal or restrictive flow patterns of ventricular filling, prolonged or shortened ventricular isovolumic relaxation interval, and pericardial effusion may be observed

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in dogs with DCM.10,20,27 Angiography and endomyocardial biopsy are invasive diagnostic methods that are restricted in its use to research and referral centres.

Management The prognosis for survival in dogs with DCM is, in general, poor. However, prognosis in the individual case is difficult to predict.12,27 Death results from worsening cardiac failure or malignant arrhythmia. The ideal in any treatment regimen is to identify the etiology of the disease so specific therapy can be instituted. As the cause of idiopathic DCM is unknown, specific therapy is not possible.2 Management rather than therapy is aimed at the consequences of DCM like congestive heart failure or dysrhythmias but not at the primary cause.11,12 Unfortunately, there is no single therapeutic regimen that can be instituted for each patient with DCM. Every dog has existing and evolving individual requirements according to the nature and severity of clinical signs. Managing asymptomatic patients differs from that of symptomatic dogs, and therapy of acute congestive cardiomyopathy differs from long-term treatment of DCM. Therefore, the therapeutic plan must be tailored to each patient and its individual needs.2,11,28,29 The primary goals of management in dogs with DCM are to stabilize the patient, to improve the quality of life, and to prolong survival. Cure is highly improbable. Inotropic support, preload and afterload reduction, improvement of peripheral tissue perfusion, arrhythmia control, and inhibition of further myocardial remodelling are the aims of therapeutic intervention. Drugs, currently used to manage dogs with DCM, include positive inotrop agents, diuretics, angiotensin-converting enzyme (ACE) inhibitors, vasodilators, and antiarrhythmics including beta-adrenergic receptor blocking agents and calcium channel antagonists (Tab. 1).12,20,29 Supportive therapy (rest, oxygen supply, chest or abdominal draining, diet, salt restriction, and exercise regimen) are complemental to drug therapy. More sophisticated treatment strategies include dynamic cardiomyoplasty, dual chamber pacing, counter-pulsation (augmentation of diastolic function), or heart transplantation but these are not routinely available for veterinary use.

Positive inotrops Inotropic support is the backbone of therapy.2,12,20 Digitalis is indicated in dogs with DCM and signs of heart failure or supraventricular rhythm disturbances.12,20 Digoxin was shown in humans to improve exercise capacity and to decrease signs and symptoms of heart failure.2,30,31 It increases the amount of calcium binding by the intracellular structures thus acts as a positiv inotrop. Digoxin may also be effective for slowing the ventricular rate in patients with supraventricular tachyarrhythmias, reduces systemic vascular resistance, decreases myocardial oxygen consumption, and improves diastolic function.30,32,33 In recent years, evidence in man has emerged that digoxin additionally has a

Table 1. Drugs commonly used in the management of canine DCM Drug

Route

Atenolol

Bumetanide Carnitine Diltiazem Dobutamine

PO PO PO IV

Dopamine

Enalapril Esmolol Furosemide Furosemide Hydralazine Metildigoxin Metoprolol

PO IV IV/SC PO PO PO PO

Nitroglycerin

TransC

Nitroprusside

Pimobendan Propranolol

PO PO

Spironolactone Taurine

PO PO

General Dose Schedule 6.25-12.50 mg/dog q 24 h (start very low) 0.025-0.100 mg/kg q 12 h 50 mg/kg q 8 h 0.50-1.25 mg/kg q 8 h (start low) 2.5-10.0 µg/kg/min constant infusion (24-72 h) 2.0-7.0 µg/kg/min constant infusion (24-72 h) 0.5 mg/kg q 12-24 h 0.25-0.50 mg/kg (single dose) 2.0-4.0 mg/kg bolus, q 6-12 h 1.0-4.0 mg/kg q 8-24 h 0.2-0.5 (-1.0) mg/kg q 12 h 0.005-0.010 mg/kg q 12 h (do not exceed 0.25 mg BID) 0.05-1.00 mg/kg q 12-24 h (start very low) 2.5-10.0 mg/24-h patch: 12 h on/12 h off 2.0-10.0 µg/kg/min constant infusion (monitoring!) 0.25 mg/kg q 12 h (not licenced yet) 0.05-1.00 mg/kg q 8 h (start very low) 2.5 mg/kg q 12 h 250-500 mg/dog q 8-12 h

variety of positive effects on neuroendocrine activation: (1) reduction of sympathetic tone, (2) increase of parasympathetic activity, (3) normalization of impaired baroreceptor mediated mechanisms with partly restoration of the impaired circadian pattern of heart rate variability, and (4) decrease in serum norepinephrine concentration and plasma renin activity.30,32,34 The action of digitalis is dose-dependent. Low doses primarily exert neurohumoral and autonomic effects, whereas higher doses mainly have hemodynamic action. The inotropic effect appeared to be greater among patients with lower contractility and more severe heart failure. However, in asymptomatic patients or patients with milder stages of DCM and sinus rhythm, digoxin in long-term was beneficial as well.32,34,35 In contrast to studies with other positive inotrops in people, Digoxin was shown to have a neutral effect on total mortality.36 At lower doses, the number of side effects, particularly serious arrhythmias, will decrease. In most patients, slow oral digitalization is adequate.16,18 Loading doses should be avoided. Larger breed dogs (in particular Doberman pinschers) tend to tolerate less digoxin, and the lower end of the dosage scale should be employed. Care should be taken when giving the drug intravenously. Digitalis may cause peripheral and coronary vasoconstriction and malignant arrhythmias.35 Administration of digoxin intravenously should, if necessary, be performed as follows:37 The total dose (0.01-0.02 mg/kg of BW) is divided into 4 aliquots to be administered at hourly intervals by slow (over 10-15 min) IV injection. Digitalis may aggravate the clinical

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condition in the setting of cardiogenic shock and, therefore, dobutamine or dopamine should initially be used instead.30 Sympathicomimetics. Both catecholamines, Dopamine and Dobutamine, provide potent inotropic strength to the failing myocardium. Dobutamine is a synthetic agent with selective β1-activity, mild β2- and dose dependent α-adrenergic effects. It is the preferred positive inotrop for the initial treatment of severe systolic dysfunction associated with cardiogenic shock. At low doses (2-8 µg/kg/min), it increases cardiac output and decreases systemic vascular resistance much more than digitalis. Its use is limited to intravenous constant infusion (24 to 72 h). The effective as well as the toxic dose of dobutamine in dogs may be very individual. Careful cardiac monitoring is, therefore, imperative as higher doses may cause vasoconstriction and severe tachyarrhythmias. If arrhythmias develop or heart rate elevates (> 20%), the infusion should be temporarily halted. The ßblocking agent esmolol may additionally be used to antagonize the arrhythmogenic effect of dobutamine. In humans38 as well as in dogs with DCM (particularly in Doberman pinschers; own experience) short periods of infusion have been associated with long-term (several weeks) improvement in cardiac performance. Dopamine is a endogenous precursor of norepinephrine and has dose dependent effects as well. At low doses (1-3 µg/kg/min), it activates dopaminergic receptors and causes selective peripheral vasodilation. At moderate doses (3-7 µg/kg/min), ß-receptor activation results in positive inotropic effect. At higher doses (7-10 µg/kg/min), predominantly αadrenergic stimulation leads to peripheral vasoconstriction and positive chronotropy.39,40 Dopamine is indicated to support cardiac function and blood pressure in cardiogenic shock and to support renal function in oliguric or anuric states. A newer class of positive inotropic agents, the selective phosphodiesterase F-III inhibitors (Amrinone, Milrinone, or Enoximone), is currently under investigation regarding its suitability for clinical use in patients with DCM. Pimobendan exerts its positiv inotropic effects partially by sensitization of contractile proteins to intracellular calcium. It also causes venous and arterial vasodilation and positive lusitropy. It may increase exercise duration and quality of life in humans with moderate to severe heart failure41,42 but was shown to increase mortality.42 Studies in dogs are rare but promising.43,44,45 Pimobendan (beside standard therapy) did not affect mortality in Cocker spaniels with DCM (n=10) but improved quality of life and survival in Doberman pinschers with DCM (280 days in the pimobendan group vs. 72 days in the placebo group) in a double-blind placebo controlled study.43

Diuretics Furosemide, a loop diuretic, is generally considered in dogs with congestive heart failure. It decreases preload and retention of sodium and water. It is an effective diuretic, is rarely truely toxic, is cheap, and easily manipulated to effect. Intravenous administration will rapidly reduce systemic venous pressure thus preload. The potential to cause electrolyte disturbances in dogs is low. Administered long-term at ap-

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propriate doses, it may decrease cardiac output, may cause prerenal azotemia, and may early activate the RAAS.46 Furosemide can be used in combination with thiazides or spironolactone (an aldosterone antagonist) particularly in refractory cases of fluid accumulation.2,11,12,17,20,22 Bumetanide, another loop diuretic, may technically be more potent and seems to offer advantage in a small number of patients resistant to furosemide, but is more expensive.

Vasodilators Controlled clinical trials have shown that dogs with DCM treated with diuretics and digoxin benefit from additional use of ACE inhibitors.47,48 Enalapril, Ramipril, Quinapril, or Benazepril inhibit the conversion of angiotensin I to II, which is a potent vasoconstrictor. They reduce aldosterone and ADH release, decrease the degradation of vasodilating kinins, reduce myocardial remodelling and sympathetic tone. Clinically, ACE-inhibitors improve exercise tolerance, breathing, appetite, stage of heart failure, and survival in dogs with DCM. The incidence of side effects is low: hypotention, renal failure, hyperkalemia, and gastrointestinal signs have been described predominantly at higher doses.20,47-49 Care should always be taken in using ACE inhibitors in compensated renal disease. As activation of the RAAS occurs early in the course of DCM asymptomatic patients may benefit from early ACE inhibition.2 Nitrates (glycerol trinitrate, isosorbide dinitrate, sodium nitroprusside) are often used in dogs with acute pulmonary edema in conjunction with standard therapy. Nitroglycerine is purely a venodilator. Tolerance develops rapidly in dogs. Sodium nitroprusside is an ultrashort acting arteriolar and venodilator mainly used in life-threatening left heart failure and pulmonary edema. Because of its potency to cause severe hypotention, arterial and venous blood pressure should be monitored during continuous intravenous infusion.20,49 The use of direct-acting arterial vasodilators, such as hydralazine, may be useful adjunct therapy for dogs with persistant signs of heart failure despite treatment with digoxin, furosemide, and ACE inhibitors. Combination therapy with nitrates is an acceptable alternative as well. Hydralazine may activate neurohormonal reflexes resulting in tachycardia, sodium and water retention, hypotention, and alimentary disturbances.12,20,49 Beside dopamine, ibupamine, an orally active dopamine analogue that causes vasodilation, diuresis, and natriuresis has investigationally been described in man as additional drug for congestive heart failure.50,51 Data on the use of ibopamine in dogs are currently not yet available.

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antisympathetic, and antidysrhythmic effects. Myocardial oxygen consumption is reduced. Therapy for congestive heart failure with β-blockers in humans has always been controversial since their beneficial effects were reported firstly 23 years ago52. As therapies for heart failure have shifted away from the simple correction of hemodynamic abnormalities and have moved toward the long-term correction of excessive neurohormonal activation, the importance of drugs like ACE inhibitors or β-blockers has gained increasing interest. Because of the dose-dependent negative inotropic action of β-blockers, therapy must be initiated at very low doses after initiation of standard therapy and stabilization of the patient, and then titrated slowly (in weekly intervals). Improvement of ventricular function does not occur until one month of therapy.48,49,52-56 Beta-blockers may cause acute detrimental hemodynamic and clinical effects in patients with severe heart failure and should, therefore, be avoided in critically ill patients. Nonetheless, β-blockers may improve symptoms, exercise capacity, left ventricular ejection fraction and may prolong life in patients with less severe heart failure as shown in people.49

Antiarrhythmics The use of antiarrhythmic drugs like procainamide, quinidine, mexiletine, or tocainide in dogs with ventricular arrhythmias secondary to DCM is controversial. There is no evidence that any antiarrhythmic drug but beta-blockers reduce the risk of sudden death and prolong life in people. Moreover, some antiarrhythmic drugs (in particular class I agents) may increase mortality in patients with heart failure.57 All antidysrhythmics have profound negative inotropic and proarrhythmogenic effects and should exclusively be used in life-threatening ventricular rhythm disturbances. Carnitine, Taurine, or Coenzyme Q10 supplementation may be helpful in a subset of patients with DCM.12 Immunosuppressive drugs or growth hormone administration were tried in humans, however, effects were rather poor.

References 1. 2.

3. 4. 5.

Beta-adrenergic blocing drugs Beta-blockers (propranolol, atenolol, metoprolol) or βblockers with additional α-blockings properties (carvedilol) and calcium channel antagonists (diltiazem) are used in dogs with DCM and atrial fibrillation when digoxin has failed to adequately control the heart rate. Beta blockers have negative inotropic, negative dromotropic, neagtive chronotropic,

6. 7. 8.

Report of the WHO/ISFC task force on the definition and classification of cardiomyopathies, (1980), Br Heart J, 44: 672-673. Wynne J, Braunwald E, (1997), The cardiomyopathies and myocarditides, In: Braunwald E (ed), Heart Disease, a Textbook of Cardiovascular Medicine, 5th ed, WB Saunders, Philadelphia, 14041463. O’Grady MR, Horne R, (1995), Occult dilated cardiomyopathy in the Doberman pinscher, Proc 13th ACVIM Forum, 1072-1074. Lombard CW, (1984), Echocardiographic and clinical signs of canine dilated cardiomyopathy, J Small Anim Pract, 25: 59-70. Calvert CA, Chapmann WL Jr, Toal RL, (1982), Congestive Cardiomyopathy in Doberman pinscher dogs, J Am Vet Med Assoc, 181: 598-602. Koch J, Jensen AL, Fredholm M et al., (1997), Juvenile dilated cardiomyopathy in Doberman pinscher, Proc WSAVA Congress, 273. Harpster NK, (1983), Boxer cardiomyopathy, In: Kirk RW (ed), Current Veterinary Therapy VIII, WB Saunders, Philadelphia, 329-337. Freeman LM, Michel KE, Brown DJ et al., (1996), Idiopathic dilated cardiomyopathy in Dalmatians: Nine cases, J Am Vet Med Assoc, 9: 1592-1596. Staaden RV, (1981), Cardiomyopathy in English cocker spaniels, J Am Vet Med Assoc, 178: 1289-1292.

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trial: A stimulus for further research, Am Heart J, 134: 3-10 The Digitalis Investigation Group, (1997), The effect of Digoxin on mortality and morbidity in patients with heart failure, N Engl J Med, 336: 525-533. Beardow AW, (1995), Emergency management and critical care, In: Miller MS, Tilley LP (eds), Manual of Canine and Feline Cardiology, 2nd ed, WB Saunders, Philadelphia, 447-468. Liang CS, Sherman LG, Loherty JV et al., (1984), Sustained improvement of cardiac function in patients with congestive heart failure after short-term infusion of dobutamine, Circulation, 69: 113-119. Anyukhovsky EP, Guo SD, Danilo P et al., (1997), Responses to norepinephrine of normal and „ischemic“ canine Purkinje fibers are consistent with activation of different a1-receptor subtypes, J Cardiovasc Electrophysiol, 8: 658-666. MacIntire DG, (1995), The practical use of constant-rate infusions, In: Bonagura JD (ed), Kirks current veterinary therapy XII, WB Saunders, Philadelphia: 184-188. Kobo SH, Gollub S, Bourge R et al., (1992), Beneficial effects of Pimobendan on exercise tolerance and quality of life in patients with heart failure: Results of a multicenter trail, Circulation, 85: 942-949. The Pimobendan in congestive heart failure (PICO) investigators, (1996), Effect of Pimobendan on exercise capacity in patients with heart failure: main results from Pimobendan in congestive heart failure (PICO) trial, Heart, 76: 223-231. Luis Funtes V, Kleemann R, Justus C, French A, Schober K, Corcoran B, (1998), The effect of the novel inodilator Pimobendan on heart failure status in Cocker spaniels and Dobermans with idiopathic dilated cardiomyopathy, Proc 12th BSAVA congress, in press. Le Bobinec G, (1993), The place of inodilators in the treatment of congestive heart failure (CHF): Clinical trial of Pimobendan in dogs, Proc 11th ACVIM Forum, 550-552. Bruyere D, (1994), Clinical trial of Pimobendan: A new inotropic/vasodilator drug, Proc 4th ESVIM Congress, 168-169. Bayliss J, Nonorell M, Canepa-Anson R et al., (1987), Untreated heart failure: clinical and neuroendocrine effect introducing diuretics, Br Heart J, 57: 17-22. The COVE study group, (1995), Controlled clinical evaluation of enalapril in dogs with heart failure: Results of the COoperative Veterinary Enalapril study group, J Vet Int Med, 9: 243-252. The IMPROVE study group, (1995), Acute and short-term hemodynamic, echocardiographic, and clinical effects of enalapril maleate in dogs with naturally acquired heart failure: Results of the Invasive Multicenter PROspective Veterinary evaluation of Enalapril study, J Vet Int Med, 9: 234-242. Darke PGG, Long KJ, Luis Fuentes V et al., (1995), Cardiac therapy, Edinburgh, University press, 13-30. Dohmen HJM, Dunselman PHJM, Poole-Wilson PA, (1997), Comparison of captopril and ibopamine in mild to moderate heart failure, Heart, 78: 285-290. Andrews R, Charlesworth A, Evans A et al., (1997), A double-blind, cross-over comparison of the effects of a loop diuretic and dopamine receptor agonist as first line therapy in patients with congestive heart failure, Eur Heart J, 18: 852-857. Waagstein F, Hjalmarson A, Vamauskas E et al., (1975), Effect of chronic beta-adrenergic receptor blockade in congestive cardiomyopathy, Br Heart J, 13: 1022-1036. Just H, (1996), Pathophysiologic targets for beta-blocker therapy in congestive heart failure, Eur Heart J, 17 (Suppl B): 2-7. Hampton JR, (1996), Beta-blockers in heart failure - the evidence from clinical trials, Eur Heart J, 17 (Suppl B): 17-20. Eichhorn EJ, Bristow MR, (1997), Practical guidelines for initiation of beta-adrenergic blockade in patients with chronic heart failure, Am J Cardiol, 79: 794-798. Slatton ML, Eichhorn EJ, (1996), b-Blocker therapy for heart failure, Curr Opinion Cardiol, 11: 263-268. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators, (1989), Effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction, N Engl J Med, 321: 406-412.

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Nutrition and nutritional diseases of pet birds Peter W. Scott

Summary The diversity of species and the lack of detailed understanding of the requirements of most species of captive birds has lead to a progression by trial and error. While the vast majority of captive birds are fed “semi-natural” diets, so called complete diets have also been developed. Much of the data supporting these is held “in house” but many of these diets perform well, whether they supply the nutritional needs of birds is one aspect of the debate, the other major aspect is their apparent failure to cater for the behavioural aspects of feeding. Practical diets and nutritional deficiencies will be reviewed.

Wild birds, like wild mammals, eat to meet their normal energy requirement. Obesity would be a dangerous condition in the wild for many birds. Captive birds however may become obese. This may be simply due to overeating because of greater availability of food or it may be a behavioural problem to relieve boredom, or finally it may be due to a physiological drive to attempt to balance other nutrients which may be deficient in the captive diet. If the ratio of energy to protein is correct, and the amino acid profile and mineral and vitamin levels are suitable, birds do not generally become obese. Such “well fed” birds look good, with good plumage, good disease resistance, and spend a reasonable part of the day in normal feeding activities, hopefully preparing for breeding. Consideration given to providing the right foods to provide the essential nutrients is vital in any captive breeding project. Deficiencies occur when birds are fed a restricted diet; they then often develop “fads” and further restrict their own diet. Pet psittacines are often kept indoors and denied access to natural light; this causes vitamin D3 deficiency, unless additional dietary vitamin D3 is provided. The basic diet types of many of the commonly kept species are summarised in Table 1. Table 2 gives some information on the nutrient balance of various dietary items. The two tables can be use together for improving a diet.

PRACTICAL DIETS FOR BIRDS Formulating these cannot be an exact science, as much of the necessary data is not available. There are various obser-

vations relating to particular species. Many psittacines, such as macaws and cockatiels, perform well on approximately 20% protein for growth; macaws seem to require a higher fat level than cockatiels. Quite low levels of protein seem to be sufficient to maintain body weight in adult cockatiels.

Diets for larger parrots Complete pelleted diets There are several of these now available in the Europe, (eg. Hagen, Pretty Bird, Roudybush, Kaytee). Most are well researched products which appear nutritionally adequate, they are certainly better on a purely nutritional level than many of the pure seed diets fed to pet parrots. Many birds eat nothing but seed simply because it is more convenient for the owner. For these birds, when owner convenience is a major factor, there is sound justification for converting them to pelleted diets. A pelleted diet will almost always be better than the purely seed diet fed to many pet parrots. Experience suggests that seeds are used mainly because many owners think that is what parrots eat, because pet shops sell it to them. The main problem seems to be one of education. Some recommend that they be supplemented with restricted amounts of fresh food. It is important to realise that “complete diets” are not usually formulated as “part diets”, if they are designed as complete diets this is how they should be used, adding fresh foods unbalances them. The major disadvantages with pelleted diets appear to be cost (which is balanced by convenience), that they appear to perform not as well as a balanced natural diet, and perhaps the most important disadvantage that they are eaten too quickly - they totally ignore the birds relatively high intelligence and inquisitive nature.

“Natural diets” Commonly used “natural” diets used by aviculturists are often along the lines of: • One third: Carrots, apples, beetroot in equal amounts. • One third: Soya beans, chick peas, field/garden peas, maize, maple peas. • One third: Pearl barley (hulled), whole sunflower, wheat.

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Msc, BVSc, FRCVS RCVS Specialist in “Zoo & Wildlife Medicine” and “Fish Health & Production” Zoo & Aquatic Veterinary Group, Winchester - United Kingdom

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Table 1. Summary of dietary requirements of commonly kept psittacines Main groups

Commonly kept species

Notes on diet

Australian Parakeets

Budgerigar.

Small seeds, eg. hemp, canary seed, millet.

Cockatiel.

As budgerigars plus some larger seeds. Fruit, especially apples, pears, orange, grapes. Groats, wheat, lettuce, carrot, chickweed. Sprouted pulses.

Kakariki

Sunflower seed, larger parrot mix (sunflower, safflower, pumpkin seeds etc). Look out for selective feeding.

Lovebirds

Large seeds, small nuts, berries, apple and carrot. Green foods are popular. Soft fruits.

Ring necked parrots

Moustache parakeets, Slaty-headed parakeets, Alexandrines, Indian Ringnecks.

Large seeds, small nuts, berries, apple and carrot. Green foods are popular. Soft fruits.

Cockatoos

Moluccan, Goffin and the various sulphur crested cockatoos.

Large seeds (roseate cockatoos are prone to obesity so with these it is often better to use small seeds). Fruit, greens, soaked pulses. Provide wood to “strip”.

Conures

Sun conures, Green cheeked and maroon bellied conures.

Mixed seeds; enjoy fruit; like to bathe in large water bowls.

Brush tongued parrots

Lorikeets. These have a long extensible tongue which is covered in papillae to collect pollen. They often crush flowers and lick nectar.

Nectar, pollen, soft food, seeds, berries. Commercial lory diets

Macaws

Scarlet, Blue and Gold, Greenwing (Red and Green), Dwarf macaws such as Hahns, Severe and Illigers.

Large seeds, nuts in moderation, small pine nuts for “interest”. Enjoy soft fruit.

Amazons & Pionus

Amazons eg. Blue fronted, red lored, yellow headed, Cuban, Pionus eg. Blue headed, Dusky

Large seeds, nuts in moderation, small pine nuts for “interest”. Mixed pulses, fruit & vegetables. Enjoy soft fruit.

Eclectus

Vosmaeri.

As amazons, but with more fruit.

African Greys

Congo and Silver Greys, Timneh Greys.

As amazons taking particular care to keep the diet balanced, avoiding fads. In particular avoid exclusively sunflower seed diets.

Non-nutritional “food” items are very important. Cockatoos like to strip wood - any fruit branches are suitable provided that they have not been sprayed with garden chemicals. It is sensible to give them a good scrub with an antibacterial cleanser such as Ark-Klens (Vetark) to avoid introduction of infection from wild birds. Hide dog chews can be drilled and hung from chains etc.

• Plus

Plus sprinkling of small high quality pine nuts in the afternoon/evening. Plus an appropriate vitamin/mineral supplement such as Avimix (Vetark). The legumes and grains are soaked overnight to allow some germination. The pearl barley does not sprout but soaking loosens the hulls which then can be washed off. Sunflower does seem to show some activity. During the summer, sprouted components are best fed in the mornings when the temperatures are cool; this avoids rapid spoilage. In practical terms a bird eating to a particular energy intake ingests more protein, and has a better calcium:phosphorus ratio when fed the aviculturists diet than the seed (high protein/high energy) diet. As an additional benefit it is

also taking in a wider range of micronutrients. Appropriate vitamin/mineral supplementation is still valuable.

Handrearing mixes This is an area where ready made diets have become extremely useful. There are a number of diets available (Aviplus, Pretty Bird, Hagen) which all appear to perform well. The person carrying out the handfeeding can greatly influence performance, but changing diets can still cause problems. It is not unusual for an experienced handrearer using a home-made blend to experience serious problems when changing to a prepared diet. This is not a poor reflection on

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Dietary classes

Typical ingredients

Comments

Small seeds

Hemp, millet, canary seed. Millet sprays when birds have reduced appetite, or when young are fledging.

Lower fat and higher carbohydrate than the larger seeds.

Large seeds

Sunflower, safflower, pumpkin. Grains - wheat, oats, buckwheat, groats.

Cereals are fairly low in protein (corn and wheat have 9 - 10%, oats and barley contain 11 - 12%) but have a high energy value due to their starch stores. Vitamins A, D3, B6, and B12 are quite low or absent, corn is the only grain which contributes towards vitamin A requirements. Cereals are also low in calcium, and their phosphorus is mainly in the form of phytate. These mixtures are of very variable quality, some being extremely poor. Seeds need to be looked at carefully for fungal growth; “webby” seeds need to be avoided. Aspergillus flavus can grow on such food and can produce aflatoxin which may cause chronic hepatitis and other problems. Oil seeds need to be rationed; birds develop fads and often will eat nothing but sunflower seed.

Nuts

Brazil nuts are generally popular with Fed in moderation, tiny pine nuts are ideal therapy, birds enjoy macaws. Most parrots enjoy pine nuts, spending time opening them for the high fat taste, but actually from the giant Chinese ones to the tiny ones. get relatively little nutritionally from them. Batches of nuts should be checked by opening a few prior to using them. Harvesting followed by storage while damp encourages fungal growth. Peanuts in shell often harbour Aspergillus, these are best avoided.

Fruit

Apples are popular with most psittacines; soft fruit from berries to grapes are also usually well received, as is pomegranate.

Must be fresh, or it won’t be eaten and if left will encourage growth of Aspergillus. In general the fruit isn’t eaten, it is squeezed to release pulp and juice. Orange is enjoyed and orange juice can be used to flavour new foods or medicines.

Vegetables

Any fresh vegetables can be given. Grated carrots, sweetcorn and celery are popular.

Frozen mixed veg is a very useful standby. Beetroot is enjoyed but will stain the faeces red.

Sprouted and soaked pulses

Various beans such as haricot, soya, mung, black eyed and maple, chick peas and green peas, and lentils.

Legumes (peas, beans, and pulses) are concentrate feeds with protein levels in the range 22 - 31%, fat level in the 1 - 6% range, and carbohydrate 58 - 68%. Oilseeds may have even higher protein levels, such as soybeans at 43%; they can be up to 55% fat. Soybeans are also the best balanced in terms of amino acids. Sprouting is a very important way of improving palateability and digestibility. Nutritional value improves a little.

Animal protein

Cooked bones, such as chicken or lamb.

These are always enjoyed, but the fatty remnants should be removed or high blood cholesterol levels and atherosclerosis may result.

the diet. Changes to handrearing diets should only be made very cautiously. A general analysis of 18 - 20% protein and 5% fat seems to be acceptable and produces good results.

Nectar feeding parrots In the wild, psittacines consuming nectar take in fairly large amounts of pollen. There is evidence, however, than much of this passes through the psittacine gut undigested. Some digestion occurs in the nestling bird, and in adults overnight. Some species may be better than other at digest-

ing pollen. Pollen is a rich source of protein, typically 15 20% protein, 20 - 35% carbohydrates and 1 - 3% oils. Nectar consists mainly of sugar (depending on the source 13 60%, with most approximately 35%), with trace amounts of organic acids, oils, dextrin, protein, and enzymes. The main sugars are sucrose, fructose, and glucose.

Processing/Treatment of food Sprouting of legumes and pulses raises the digestibility of the components. Some of the fairly indigestible carbohy-

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Table 2. Information on dietary items

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drate, such as starch, is converted into more digestible dextrins etc, and even into proteins as the sprout grows. The vitamin levels also rise slightly, especially vitamin C, although not enough to be relied on as a major source. Sprouting also makes the seeds of legumes safer, by reducing some of the toxic or anti-nutritive factors present in them; soybeans, for instance, contain a trypsin inhibitor which reduces the digestion of proteins. The act of soaking also makes it easier for birds to break up the seed for digestion. Water used for sprouting/soaking of seeds should be changed every couple of hours as some of the nutrients will enter solution and encourage bacterial growth. For the same reason seeds should be well rinsed and drained before feeding.

Converting “Seed Junkies” • Estimate the amount of seed normally eaten in a day and give half of it; monitor the bird’s condition whilst trying the following: “weed” the mixture, changing the balance of seeds away from sunflower seed. • Use a top quality mix. The hulled blends available, such as Ultra Mix and Tidy Mix, are ideal. Importantly, they are fresh and palatable and can be top dressed with vitamins using a little peanut oil or orange juice. • Use “non-threatening” forms of food. Shredded carrot is less suspicious to a bird than a whole one! • Try introducing new items in amongst the seed. • Sprout seeds and pulses - they taste much better. • Introduce a soft-food, baby cereal, fruit pulp, or proprietary mixes (CeDE or EMP). Again, this will give a vehicle for vitamins. • Consider interval feeding. Instead of leaving food in the cage all day try introducing meal times; 30 - 60 minutes access three times a day. • Move the cage; place new food items such as corn on the cob close to favourite toys. • “Monkey see, Monkey do”. Birds will often take and investigate titbits which they see the owner eating. Being able to see other birds eating a better diet may also help. • Change the photoperiod. The natural photoperiod for many birds is 12 hours light, 12 hours dark. In captivity this is extended in the home by early risers and late night television. Covering the cage from 9pm till 9am can change a birds behaviour and sometimes help with establishing new feeding patterns. • Consider hospitalisation, or boarding out. A new regime may be more acceptable under new management where everything else is new. Remember - owners have starved birds to death trying to change their diet!

NUTRITIONAL DISEASE Protein and Essential Amino Acid (EAA) Deficiency Protein required for growth is limited by the availability of the various essential amino acids. To obtain sufficient

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amounts of the limiting amino acids, the bird on a poor diet is forced to overeat and then eliminate the excess nitrogen. Protein levels in excess of that which can be used, are broken down as an energy source and may result in obesity, or gout due to the formation of urates. The pathogenesis of gout is not clear, water deprivation and nephrosis, even very short term may make a considerable difference. Although birds can manage on low protein levels, this does not apply to periods of special need. When birds are producing eggs, a low protein diet will stop production and also can inhibit new feather growth. Choline, lysine and tyrosine deficiency all lead to colour abnormalities. Methionine deficiency has been linked with stress lines in feathers. Lysine levels are low in seeds, therefore purely seed-fed birds often develop poor feathering. The requirement for lysine is estimated at between 1 - 2% (high percentage of a low protein diet). Poor matrices within the bones are another result of protein or amino acid deficiencies. EAA deficiencies in general will lead to fatty liver problems. These are compounded due to the high fat diets often fed.

Vitamin A deficiency This is the most common vitamin deficiency seen in parrots. The pathogenesis includes squamous metaplasia of the epithelial surfaces of the oropharynx, renal tubules, reproductive tract, and air sacs. Poor condition or chronic upper respiratory problems are the commonest presenting signs, although nephrosis is also linked to the renal tubule changes. Feather colour changes, hyperkeratosis of the feet, and general poor feathering are also involved. The efficiency of the conversion of ß-carotene (in the fruit or vegetables) into vitamin A is uncertain in psittacines, but it is likely that due to the overabundance of carotenes in their normal diet, conversion is not particularly efficient. The relatively high requirement of vitamin A by psittacines may be met by ß-carotene in fresh vegetables, carrot, cornon-the-cob, iceberg lettuce, green beans, celery, apricots, oranges, papaya etc. Supplementation is generally required, ACE-High or Avimix (Vetark). This is particularly important once signs of deficiency have been seen.

Metabolic Bone Disease (Calcium and Vitamin D3 problems) Calcium deficiency in adult birds can result in: • acute hypocalcaemic “fits” (especially African Greys) • the production of soft shelled eggs • egg–binding due to poor muscular function • a cessation in breeding. Conversion into vitamin D3 requires exposure to sunlight. It may be this factor which is most important in deficiencies seen in captive birds. African Greys, in particular in breeding establishments, are normally bred indoors and often spend most of their time in the nestbox, perhaps only coming out for food. Birds kept indoors need regular supplementation, particularly breeding birds. Nutrobal (Vetark) provides an appropriate balance of calcium and vitamin D3.

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Vitamin E deficiency Deficiency of vitamin E may come about through rancidity. Commonly fed seed mixes may contain seeds stored far too long, in which levels of vitamin E have fallen and fats have become somewhat rancid. Signs of disease (especially myopathies) are particularly seen in birds which are also deficient in selenium or sulphur-containing amino acids. Supplementation of these poor diets is essential, eg. ACE-High (Vetark). Vitamin E also has an important part in disease resistance.

Fat and essential fatty acids Fat related problems, often associated with vitamin E deficiency, are common among pet birds. These are often the result simply of overeating on a high calorie, low quality diet. In birds the liver is very active in lipogenesis. Linoleic and arachidonic acids are essential: when they are lacking, a fatty liver can develop due to impaired fat metabolism. Any hepatic pathology which inhibits proper fat metabolism may also lead to fatty liver. Diets high in saturated fats can lead to atherosclerosis and fatty liver syndrome, and are usually linked with a hypercholesterolaemia. Excessive amounts of cheese or too frequent titbits of lamb bones have both been seen to lead to these problems.

B Vitamin deficiencies The high fat diets of pet psittacines are normally low in B vitamins. Deficiency syndromes are poorly understood but poor growth, general unthriftiness and poor feathering

are major features. They may be quite important. Classic single B vitamin deficiencies are associated with: • Thiamine (B1) - opisthotonus, fits. • Riboflavin (B2) - curled toes, dry skin, poor feather pigmentation, fatty livers. • Pyridoxine (B6) - perosis, jerky movements, convulsions. • Pantothenic acid - dermatitis around eyes and mouth, wiry down, ataxia. • Biotin - brittle feathers, swollen feet, ataxia, chondrodysplasia, fatty liver. • Folic acid - poor feathering, white or brittle feathers, beak deformities. • Choline - perosis.

Vitamin C deficiency Any form of stress, or physical, nutritional, toxic or infectious disease tends to deplete endogenous stores of vitamin C. Supplementation produces positive effects on egg quality so even though a specific deficiency syndrome is not reported in psittacines there is good reason for including vitamin C in general supplements, especially those used when birds are under stress. ACE-High (Vetark) is particularly useful in this regard.

References BAUCK, L. (1995) Nutritional problems in pet birds. In. Seminars in Avian and Exotic Pet Medicine. 4, (1). BRUE, R.N. (1994). Nutrition. in Ritchie, B.W., HARRISON, G.J. & HARRISON, L.R. eds. Avian Medicine. Principles and Application. Wingers Publishing. CLUBB, S. (1997). Us eof psittacine handrearing formulas. Basic Day Proceedings of the 4th Conference of the European Committee of the Association of Avian Veterinarians. EAAV,1997. London. HAGEN, M. (1992) Nutritional observations, hand-feeding formulas, and digestion in exotic birds. In. Seminars in Avian and Exotic Pet Medicine. 1, (1). ROUDYBUSH, T.E. (1997) Nutrition. In: Avian Medicine and Surgery. (Eds R.B.Altman, S.L.Clubb, G.M.Dorrestein & K.E.Quesenberry. W.B.Saunders, Philadelphia. SMITH, J.M. & ROUDYBUSH, T.E. (1997) Nutritional Disorders. In: Avian Medicine and Surgery. (Eds R.B.Altman, S.L.Clubb, G.M.Dorrestein & K.E.Quesenberry. W.B.Saunders, Philadelphia. SCOTT, P.W. (1996) Nutrition of Psittacines. BSAVA Manual of Psittacines. Pub. British Small Animal Veterinary Association.

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In African Greys it is often also necessary to supplement using calcium lactate in drinking water. Marginal hypocalcaemic birds may show clinical disease during or following medication with oxytetracycline on other binding agents. Hypervitaminosis D3 has been reported in several species in the USA, macaws appear particularly featured. Cases are generally associated with over-supplementation of already supplemented commercial diets.

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Avian skin disease: your worst nightmare Peter W. Scott Msc, BVSc, FRCVS RCVS Specialist in “Zoo & Wildlife Medicine” and “Fish Health & Production” Zoo & Aquatic Veterinary Group, Winchester - United Kingdom

Summary

stratum corneum

Avian skin disease presents many problems for the veterinarian. Causes will usually have a nutritional component, often a behavioural component or possibly an untreatable viral component. Reaching a diagnosis can be complex, and attempting treatment an be frustrating, correcting nutritional diseases takes months, the new plumage must appear before any improvement is seen (this may take a year). Topical treatments are generally not appropriate because birds preen them off. Behavioural changes are extremely difficult to implement due to poor client compliance.

Clinical anatomy Birds have a thinner, more delicate skin than mammals, it may be almost transparent. There is an epidermis, dermis and subcutis. The dermis is very thin with few blood vessels and contains the feather follicles and their supportive muscles which run to adjacent body prominences. Skin haemorrhage is rare. Bird skin has virtually no glands other than the holocrine glands of the external ear canal and the uropygial gland, however the whole skin surface of the bird can be regarded as a gland - it is lipogenic. The uropygial gland is a large bilobed gland situated dorsally at the base of the tail, it is common in birds, all

s. intermedium s. basale basal membrane dermis

psittacines except amazon parrots (Amazona spp) have one, it is most developed in aquatic species and absent in ratites. The gland produced a lipoid sebaceous material which the bird spreads over its feathers when preening. Perhaps surprisingly the uropygial gland produces less than 10% of the plumage sebum, the rest comes from the skin itself. At the time of breeding many birds show a thickened dermis - the brood patch, this is much more vascular and may bleed if injured, breeding birds will often pluck a patch over this area. the subcutis is mainly loose connective tissue with fat. Hormone control of feather growth is not fully understood, in some species oestrogens retard feather growth, in others they promote it, generally testosterone has little effect and thyroxine initiates growth. Birds cannot rear and moult at the same time, generally they moult before or after a rise in sex steroids. Once adult plumage is developed most birds moult once a year, usually after breeding. In most species this occurs in waves through the feather tracts so that the bird is not made flightless, although many water birds and flamingos do become flightless.

Feathers Feathers are of epidermal origin growing around a feather follicle from the dermis, they grow in distinct feather tracts and in several types depending on their location in the body. Feathers are held in place in the “mature” telogen phase at least partially by tension of the non-striated feather muscles between follicles.

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s. transitivum

Avian dermatoses almost all have a nutritional component since the majority of parrots are fed incorrectly or inappropriately, the clinician must review the diet of the bird looking both at the nutritional content and the recreational aspects of actually eating it. Many dermatoses have a behavioural component since we are often keeping pet psittacines in situations which are abnormal, flock/social birds taken from the wild and bred even a dozen generations in captivity (which would be unusual) are not domesticated. The majority of pet parrots are less than two generations from the wild. Their instincts are those of wild birds and social influences such as flock structure, companionship, mutual preening, time spent foraging for food and avoidance of potential predators all have parallels in captivity. This paper will review the various causes of avian dermatoses highlighting common ones and discussing practical techniques for diagnosis and treatment.

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distal barbule hamuli rachis

barb

proximal barbule

hypopenna

The primary remiges (wing feathers) arise from the manus, and the secondaries from the ulna. They are linked by the interremigeal ligament which has some smooth muscle components, and the primaries in particular firmly attached to bone. The tail feathers (remiges) are paired, most birds have 6 pairs. Contour • Flight • Body (includes the coverts which cover the bases of the flight feathers) • Semiplumes - especially waterbirds Others • Down - especially chicks, not in ratites, pigeons, and passerines • Powder down - especially cockatoos, cockatiels & african greys • Hypopennae - very large in ratites • Filoplumes - not found in ratites • Bristles

• lice are common and said to be rarely a problem, many birds carry a “load” with no problems they do appear to be linked with untidy feathers in a number of birds, especially recent imports • mites are common eg. Cnemidocoptes in scaly leg/face Dermanyssus gallinae the red mite does occur • Myialges nudus (mange mite) in Brotogeris - canarywinged parrakeet, mainly the head affected Fungal • fungal causes are not common, but Aspergillus is seen Viral • Psittacine Beak & Feather Disease (PBFD) - Psittacine circovirus. This is a major problem and has spread from its “natural hosts” the Australian parrots and parakeets to cause serious disease in a wide range of psittacines including amazons, african greys and macaws. This probably responsible for most cases of “French moult” • polyomavirus / papovavirus. Like PBFD this is not uncommon, its natural host seems to be the budgerigar where it causes Budgerigar Fledgling Disease and in some countries appears to be the major cause of “French moult” • avian poxvirus - papules or proliferative masses, secondary infections are common • herpes virus in psittacines, proliferative lesion Bacterial not common • Staphylococcal pyodermas • pododermatitis especially canaries, raptors nestling psittacines • pansystemic infections sometimes manifest as skin conditions

Non-infectious semiplume

flight feather

filoplume bristle vane

down feather

rachis scapus distal umbilicus calamus proximal umbilicus

Disease Infectious Parasitic • roundworms, tapeworms, • giardia is reported as a cause of pruritis, especially cockatiels,

Genetic / Congenital • little or no feather growth • deformities eg. straw feather, chrysanthemums • feather cysts • beak deformities • wing-web dermatitis in lovebirds • amazon mutilation syndrome - dorsal surface of the feet • preening though instinctive appears to also require an element to be taught, hand-reared birds may simply do it badly Nutritional Poor diets will lead to poor feathering, to have a new healthy plumage it is vital that the diet is corrected. There is little point addressing behavioural factors or pathogens in a bird being fed poorly. Low protein diets will generally adversely affect new feather production, a sudden improvement in protein level using cooked rabbit or chicken or egg foods may often trigger a moult. Vitamin supplementation is important with natural diets. • choline, lysine & tyrosine deficiency all lead to colour abnormalities. Lysine deficiency in seed diets. Lysine in legumes is often high, making up for the relatively low levels in seeds/cereals. The cereals on the other hand tend to pro-

vide good levels of the sulphur-containing amino acids methionine and cystine which are low in the legumes. • Vitamin A deficiency in psittacines is the common vitamin deficiency - poor condition and chronic upper respiratory problems are the main signs, although nephrosis is also linked due to renal tubule changes. Feather colour changes, hyperkeratosis of the feet and general poor feathering are also involved. The relatively high levels of vitamin A needed by psittacines may be met by ß-carotene in fresh vegetables, carrot, corn-on-thecob, iceberg lettuce, green beans, celery, apricots, oranges, papaya etc. Supplementation with ACE-High or AVIMIX (Vetark) is recommended • folic acid - poor feathering, white or brittle feathers • pantothenic acid - dermatitis around eyes and mouth, wiry down • biotin - brittle feathers • faults through illness like “stress lines” Hormonal • age- brown hypertrophy of the cere in female budgies • sexual brood patch - it is suggested that sexually related plucking is often in the clavicular region or the tops of the wings, certainly cockatoos may extend the brood patch. oBald male canaries need testosterone! • thyroid hypothyrodism in amazons, poor moult & feather regrowth Environmental • Toxic “stress lines” - also following hormone use? Exposure to cigarette smoke, or nicotine on owners hands • Psychological separation anxiety in handreared birds very common, encouraging results with use of “anxiolytics” such as haloperidol, or naltrexone • Aggression wounds beak injuries lost toes • wire damage - to the tails of wire hangers • frost bite • post wing clip, especially if done badly Neoplastic • lipomas, xanthomas • fibrosarcomas • haemangiomas & haemangiosarcomas • basal cell tumours & squamous cell carcinoma • adenomas of the uropygial gland Allergic / Hypersensitivity • cockatiels & macaws in USA

Diagnostic approach to feather picking • Discuss the diet Correct it as appropriate, seed is completely unbalanced in most cases. Balance seed with soaked/spouted pulses, introduce fruit and vegetables - grated is often more palatable and less threatening/abnormal in appearance. Use supplements, it

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is impossible to provide the variety available in nature. Complete diets are available and may be better than some made diets, compensation for lack of non-nutritional stimulation of a natural diet may be necessary. • Give the bird a full clinical examination • Check birds skin for parasites • Biochemistry looking especially for indications of hepatopathy • Haematology, serology as appropriate • Check faecal sample for parasites as appropriate • PCR tests for PBFD / Polyomavirus - not actually chewers but look similar, also PCR faeces for Chlamydiosis • Feather follicle cytology - should be sterile • Biopsy infectious causes bacterial / fungal dermatitis / folliculitis PBFD allergy endocrine disorders neoplasia • Treatment will be based on the diagnosis reached but may include: specific treatment of infections - antiparasiticides, antibiotics behavioural modification anxiolytics Patience - some birds may take 2 years to moult damaged feathers, few will look better quickly. • At worst PBFD or Polyomavirus may warrant euthanasia.

Behavioural modification for feather pickers • Provide the largest cage that the room and wallet will accommodate, this allows room to move and also allows you to create different areas. • Move the cage around, presenting a different view from time to time, presenting a busy view when the bird is to be left stimulates a curious bird. The majority of birds benefit from being part of the family. Most parrots are social birds and do not enjoy isolation. • Allow a good rest period, many birds require the cage to be covered at night, this helps establish a routine. At least 12 hours dark is important, for birds which are seriously plucking starting out with 16 hours dark is useful then gradually extending the daylight to a 12/12 regime. • Spray the bird regularly, a fine mist from small house plant spray is ideal, birds will spend time cleaning and drying feathers rather than pulling them out. This simulates the regular natural rainfall which most parrots are exposed to in the wild. • Spend more time with the bird, talk to it more often, eat with it and give it food/titbits, take it from room to room. • Leave a radio, tape, or TV on when you are out. Some birds will chatter away, dance, or generally be stimulated.

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• Create a theme park in the cage, acrylic toys, hide, fruit tree (eg apple) branches from the garden, swings, bells etc all provide recreation. Some birds are used to spending all day foraging for food, to have all meals provided ad lib inside a small cage is extremely boring and leaves a lot of free time for vices. • Provide “nibbles” such as carrots, broccoli and other vegetables. Small pine nuts given as a titbit are good, birds spend ages trying to open them. • Consider a training program, there are good videos available to help and in some countries specialists who can advise you. • Review the diet and ensure that you provide a balanced diet which encourages healthy feather growth, old unmoulted feathers in a poor skin are itchy and encourage feather pecking. Sometimes increasing the protein level will induce a moult. Use appropriate supplements such as ACE-High or AVIMIX (Vetark).

References & reading list Cooper, J.E.,& Harrison, G.J. (1994). Dermatology in Ritchie, B.W., HARRISON, G.J. & HARRISON, L.R. eds. Avian Medicine. Principles and Application. Wingers Publishing. FLAMMER, K. (1991). Diseases of the Integument of Cage & Aviary Birds. in Avian Medicine. TG Hungerford. Refresher Course for Veterinarians. Post Graduate Committee in Veterinary Science, University of Sydney. 431-442. HILLYER, E., QUESENBERRY, K.E., & BAER, K. (1989). Basic Avian Dermatology. Proceedings of the Annual Conference of the Association of Avian Veterinarians. Seattle. 101-121. KING, A.S., & McLelland, J. (1984). Birds, their structure and function. 2nd ed. Baillière Tindall, London. Latimer, K.S., Rakich, P.M., Niagro, F.D., Ritchie, B.W., Steffens, W.L.,

Campagnoli, R.P., Pesti, D., and Lukert, P.D. (1991) An updated review of Psittacine Beak and Feather Disease. J.Assoc. Avian Vet. 5, (4) 202-206. MADILL, D.N. (1991). Feather problems & bald birds. in Avian Medicine. TG Hungerford. Refresher Course for Veterinarians. Post Graduate Committee in Veterinary Science, University of Sydney. 87-92. Niagro, F.D., Ritchie, B.W., Latimer, K.S., Lukert, P.D., Steffens, W.L., and Pesti, D.: Polymerase chain reaction detection of PBFD virus and BFD virus in suspect birds. In Proceedings of the Annual Conference of the Association of Avian Veterinarians. Phoenix: 25-37, 1990. Perry RA. Gill, J, & Cross, GM. 1991. Disorders of the Avian Integument. in Pet Avian Medicine. Veterinary Clinics of North America 21, (6) 1307-1328. REAVILL, D.R. (1996) Ed. Dermatology. in. Seminars in Avian and Exotic Pet Medicine. 4, (4). Ritchie, B.W., Niagro, F.D., Latimer, K.S., DAVIS, R.B., Pesti, D., and Lukert, P.D. (1991) Avian polyomavirus: An Overview. J.Assoc. Avian Vet. 5, (3)147-153. Ritchie, B.W., Niagro, F.D., Latimer, K.S., DAVIS, R.B., Vernot, J., Pesti, D., Campagnoli, R.P. and Lukert, P.D. (1991) Polyomavirus Infections in adult psittacine birds. J.Assoc. Avian Vet. 5, (4) 202-206. ROSSKOPF, W. & WOERPEL,R. 1996. Feather-picking and therapy of skin and feather disorders. In Diseases of Cage and Aviary Birds. 3rd ed. Editors ROSSKOPF, W. & WOERPEL,R. Williams & Wilkins. Baltimore. SCOTT, P.W. (1993) DNA Technology: Practical applications for the avian veterinarian. in Proceedings of the 1993 European Conference on Avian Medicine & Surgery. Utrecht, Netherlands. European Committee of the Association of Avian Veterinarians. 178-190. SCOTT, P.W. (1994). Psittacine Polyomavirus in Britain. Veterinary Record. Aug 13. SCOTT, P.W. (1996) Nutrition of Psittacines. BSAVA Manual of Psittacines. Publ. British Small Animal Veterinary Association. Pearman, R.I.C. & Hardy, J.A. (1985). Integument. in Form and Function in Birds. Vol 3. eds KING, A.S. & McLelland, J. Academic Press. London. 1-56. WILSON, L. 1996. Non-Medical Approach to the Behavioural Feather Plucker. In Proceedings of the Annual Conference of the Association of Avian Veterinarians. Tampa: 3-9, 1996.

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Anaesthesia and surgery of pet fish Peter W. Scott Msc, BVSc, FRCVS RCVS Specialist in “Zoo & Wildlife Medicine” and “Fish Health & Production” Zoo & Aquatic Veterinary Group, Winchester - United Kingdom

Summary

Kidney Spleen

Dorsal fin

Swimbladder

MAIN PROGRAMME

Fish are an uncommon animal presented to the veterinarian, anaesthesia is a simple technique which makes certain aspects of examination and treatment much more straightforward. Fish as diverse as koi carp, goldfish, sharks and marine puffer fish all respond to the same basic approach. Surgical techniques will be discussed, including removal of external neoplasms, radiosurgery, and intra-abdominal surgery.

Gonad

Operculum Heart Gill arches

Anal fin Gall bladder

Pectoral fins

Pelvic fin

Liver

Anaesthesia of fish is a sometimes joked about topic. Sadly it is one which many koi keepers have adopted, almost as a routine, yet which many veterinarians haven’t even considered. It can provide a very useful way of obtaining samples, scrapings or biopsies, or even tackling serious surgery. Much becomes possible if the veterinarian is prepared to undertake anaesthesia.

Artery Gill lamella

Vein

Water flow

ONE GILL ARCH ONEGILL FILAMENT

Anatomy In general fish anaesthetics are administered via the water in which the fish is swimming, the drug enters and leaves the fish via the respiratory surfaces of the gills (eg. gaseous anaesthesia in birds and mammals). In just the same way that a bird or mammal is assessed prior to anaesthesia this should be done with the fish. Compromised gills (not uncommonly affected with degrees of hyperplasia) may mean that uptake and elimination are slowed, increasing the risk, especially of deep anaesthesia.

marking or tagging surgery/debridement eg. removal of neoplasms long distance transportation handling of - valuable fish dangerous fish particularly large fish The needs of these various tasks are different so care must be taken with all applications. The transition between stages of anaesthesia can be very rapid so great care is needed.

Reasons for anaesthesia Handling of fish, in or out of the water, is physically difficult and not without risk to the fish, and in some circumstances to the handler. Anaesthetics are useful in making any necessary handling procedures as “non-stressful” as possible. There are a variety of reasons why anaesthesia may be required: handling broodstock for stripping, blood sampling, treatment etc vaccination by injection

Responses The individual response of a fish to an anaesthetic and its transition between the various stages is dependent on a number of factors:species: gill area to body weight ratio size and weight: metabolic rate lipid content: season, sex, maturity, diet condition disease

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Levels of anaesthesia

STAGE

PLANE

SIGNS/INDICATORS

Light sedation

slight loss of reactivity

Deep sedation

total loss of reactivity except to strong pressure, equilibrium normal

Partial loss of equilibrium

erratic swimming, increased opercular rate

Total loss of equilibrium

reactivity only to deep pressure stimuli

Loss of reflex activity

total loss of reactivity, very shallow opercular movements

Medullary collapse

gasping followed by cessation of opercular movements

The transition between these stages is dependent on several factors, particularly dose used, species and activity. Stages 2/3 are often ideal for simple procedures, when the head and tail of the fish can be wrapped struggling is minimised. The aim is generally to maintain the fish at the level of minimal activity which can be considered sedation rather than anaesthesia. In general use a low level of anaesthetic until you are confident. Fish react differently, trout will be very agitated and very active then suddenly roll over, carp will often tend to settle quietly and unless you are observant may overdose. When possible keep the fish moving using your hands or a net, this way you can judge its depth of anaesthesia. My own preference is not to use gloves, except for venomous species some other veterinary surgeons always use surgical gloves which they claim do less injury to the fish skin than human hands.

Benzocaine Benzocaine is probably the cheapest of the available anaesthetics and it seems to work just as well as MS222 without the pH caused by that compound. Unfortunately it is not very water soluble. A stock solution can be made up in acetone or methanol (40g per litre). This can be kept at least 3 months in a dark bottle (necessary to prevent the formation of toxic compounds). stock solution per 2 gall (9 litres) gentle handling 25ppm 5.5ml deeper surgical anaesthesia 50ppm 11ml The figures above should be considered guidelines for providing a safe sedation in an acceptable period of a few minutes; experience will allow higher doses to be used for more rapid effect. When this is done, however, great care should be taken, as fish can easily be overdosed and irreversible medullary collapse may occur. All anaesthetics carry a degree of risk. Benzocaine is not licensed. There is considerable interspecies variation and one should always err on the side of caution. Relatively sedate species such as carp are slower to succumb than trout, and can become very deeply anaesthetised without the operator always appreciating it.

Phenoxyethanol This has been used at a concentration of 0.1-0.5 ml/litre (100-500 mg/litre) as an anaesthetic. It also has bactericidal effects and may therefore be of some use when handling broodstock in reducing surface contamination. As an antibacterial it has been sold for aquarium use for over 40 years. There is an increased safety margin at lower temperatures since the lower doses can be used. The lower level (0.1 ml/litre) is reported useful for prolonged sedation. At a concentration of 1 ml/litre (1000 mg/litre) it gives rapid anaesthesia and fish must be removed quickly when anaesthetised or they will die. Care needs to be taken when advising its use. It is reported to elute toxins from activated carbon in filters.

MS222 (Tricaine methylsulphonate, Sandoz)

Specific surgery

At present MS222 is the only anaesthetic licensed in the United Kingdom for fish, it also has the benefit of being water-soluble. Depth of anaesthesia needs to be watched carefully and the fish removed when the desired plane is reached. Its disadvantage is that it causes pH changes and may cause irritation. MS222 is fat soluble so there may be some residual depression in large adult fish with well developed fat.

TYPE

COMMENTS

Arterial cannulation

Normal dose: 1:10,000 solution ie. 1g/10 litres ie. 100ppm for anaesthesia 1:20,000 1g /20 litres ie. 50 ppm for tranquillising 1:50,000 1g/30 litres ie. 33ppm for transport

Laparotomy

Experimental procedure in salmonids cannulating the dorsal aorta via the roof of the mouth This has been carried out in sharks to obtain biopsies for diagnostics. Insufflation is generally necessary Gonadectomy has been carried out, both experimentally and for behavioural control. Usually a ventral midline approach but indi-

Laparoscopy

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from Stoskopf (1993)

Preparing for surgery There are a few “points” to consider when planning surgery: • have the client bring the fish in a manageable container of water, another container of the same amount of water should be available for recovery. For koi carp plastic dustbins are often ideal! • starve the fish pre-operatively if possible for 12 hours. This avoids any potential regurgitation which in a small container may damage the gills. • unless you have set up a recycling system, plan to complete the surgery quickly • use the lowest level of anaesthesia consistent with the surgery • ensure that wherever possible you research the anatomy of the species, if you can’t then take extra care! There are over 20,000 species of fish which might be kept in private or public aquaria and anatomy varies considerably. • most fish surgery will be performed with the fish out of water positioned on a suitable surface which presents the fish in the chosen fashion • fish skin is not “mobile”, repairing skin deficits post-operatively following tumour removal will be difficult/impossible • cryosurgery works well with skin neoplasia • electrosurgery using the Ellman Surgitron has proved highly effective in larger fish • tissue adhesives or superglue have been used successfully for skin closure and for waterproofing sites. • antibiotic injections at the time of surgery avoid the need for stressful repeat anaesthetics or restraint • polyglycolic acid sutures have been used successfully for

wound closure, care must be taken to knot the sutures securely, especially in seawater which seems to loosen them, steel wire has been used in sharks as have other standard non-resorbable sutures • Good surgical loupes are useful for work with small ornamental fish Prolonged anaesthesia presents problems beyond the scope of this paper but which are covered by Brown (1994) and Stoskopf (1994).

Resuscitation Fish are normally placed into a container of the same water which they were kept in and moved gently to encourage a flow of water across the gills, a finger placed ventrally just behind the lower jaw will keep the mouth open. It is worthwhile when planning to anaesthetise a fish to have the client bring a container with the fish in water and another spare container with enough water to transport the fish home. With large fish a pump recycling tank water through the gills can be useful, and (where appropriate) a diver can assist the fish in early attempts at swimming on recovery.

Euthanasia of fish Humane anaesthesia is possible by administering a gross overdose of anaesthetic and leaving the fish in the water for a longer period. It is possible to sedate the fish using a water soluble anaesthetic and even then use the intravenous approach to administer barbiturates.

References BROWN, L. (1992). Restraint, Handling and anaesthesia. In. Manual of Ornamental Fish. Ed. R.L.Butcher. British Small Animal Veterinary Association, Cheltenham. BROWN, L. (1994). Anaesthesia and Restraint. In: Fish Medicine. Ed M.K.Stoskopf. W.B.Saunders Co, Philadelphia. SCOTT, P.W. (1992). Clinical examination of fish. In. Manual of Ornamental Fish. Ed. R.L.Butcher. British Small Animal Veterinary Association, Cheltenham. SCOTT, P.W. (1992). Therapeutics. In. Manual of Ornamental Fish. Ed. R.L.Butcher. British Small Animal Veterinary Association, Cheltenham. STOSKOPF, M.K. (1994). Surgery. In: Fish Medicine. Ed M.K.Stoskopf. W.B.Saunders Co, Philadelphia.

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Ulcer debridement

vidual species anatomy may alter this. Tumour removal may be possible. Be aware that in cyprinids the abdominal organs are all adherent and may make such an intervention unlikely to succeed. Routine, allows thorough cleansing, potential to pack with barrier cream. Remove material which may act as foreign body and then allow epithelialisation.

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Management of peritonitis - Current update Daniel D. Smeak

Summary Peritonitis is a complex disease condition that results in many pathophysiologic alterations affecting multiple organ systems. Surgeons must possess a thorough understanding of the pathophysiology of this disease so that effective treatment can be made. Treatment should be directed at eliminating the cause of peritonitis and preventing the resulting pathophysiologic responses. Peritoneal injury triggers many physiologic responses that are intended to control the peritoneal irritant. Although these responses are beneficial initially to the patient, as they progress they often have deleterious effects. The purpose of this seminar in review current information about treatment of peritonitis in small animals.

these lymphatics into the thoracic duct. The peritoneum functions as a by-directional barrier to the diffusion of water and low molecular weight substances.

Peritoneal fluid Peritoneal fluid is constantly produced and reabsorbed. It provides lubrication for the movement of abdominal organs within the peritoneal cavity. Although the peritoneal fluid has minimal antibacterial properties, it does contain fibronectin â&#x20AC;&#x201D; a bacterial opsonizing protein. Fibrinogen is not present, so normal peritoneal fluid will not clot.

Particulate matter and microbial absorption Introduction Peritonitis is a complex disease condition that results in many pathophysiologic alterations affecting multiple organ systems. Surgeons must possess a thorough understanding of the pathophysiology of this disease so that effective treatment can be made. Treatment should be directed at eliminating the cause of peritonitis and preventing the resulting pathophysiologic responses. Peritoneal injury triggers many physiologic responses that are intended to control the peritoneal irritant. Although these responses are beneficial initially to the patient, as they progress they often have deleterious effects. The purpose of this seminar in review current information about treatment of peritonitis in small animals.

Peritoneal physiology Peritoneal cavity The peritoneal cavity is the largest preformed extravascular space in the body. It is lined by a single surface layer of mesothelial cells. On the visceral surface of the diaphragm special lymphatic vessels are present under the mesothelial membrane. Small spaces between mesothelial cells called stomata function as channels for lymphatic drainage from the peritoneal cavity. Contraction and relaxation of the diaphragm results in influx and emptying of

Particulate matter in the peritoneal cavity is absorbed through the diaphragmatic lymphatic channels that drain via several series of lymph nodes and empty into the thoracic duct. Particles such as bacteria are rapidly absorbed from the peritoneal cavity. Red blood cells are also rapidly cleared from the peritoneal cavity.

Intra-peritoneal circulation Intra-peritoneal fluid and particulate matter move along a definite path in dogs. There is a general movement of fluid in a cranial direction towards the diaphragm. The intraperitoneal circulation of a contaminate appears to be influenced by diaphragmatic movement, gravity, and the site of origin of the contaminate. A contaminate originating from the cranial portion of the peritoneal cavity is dispersed throughout the peritoneum within 15 minutes, while a caudal intra-peritoneal contaminate requires almost an hour for complete dispersion. Increasing the viscosity of the contaminate will also reduce its rate of dispersion.

Peritoneal injury and healing The peritoneal mesothelium is easily damaged and will undergo permanent damage after minimal exposure to air or saline. Regeneration of this mesothelial lining occurs rapid-

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DVM, Dipl ACVS Professor, Head of Small Animal Surgery The Ohio State University, College of Veterinary Medicine,Columbus, Ohio - USA

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ly. Within hours of injury, the defect is covered with round cells originating from circulating mesothelial cells within the peritoneal fluid. Peritoneal defects will heal at the same rate regardless of the size of the original defect. Certain injuries to the peritoneum result in formation of adhesions. When the mesothelial lining is damaged, normal release of plasminogen activator by the mesothelial cells is inhibited, so plasmin is not available to break down fibrin. Fibrin then persists and provides a framework for fibroblasts and deposits of collagen that leads to fibrous adhesion formation. The reason for formation of adhesions following some injuries and not of others is unclear, but it is thought to be related to tissue injury and serosal anoxia, and the presence of foreign material. The presence of foreign material within the peritoneal cavity is a consistent cause of adhesions. Peritoneum responds to foreign material as it does to ischemic tissue; inflammation, granulation tissue formation, and finally adhesion formation. The intensity or strength of the inflammatory action and the amount of adhesions produced is dependent on the stimulant. Adhesion inflammation may be controlled by reducing the initial injury, preventing coagulation of fibrinous exudate, dissolving coagulated fibrin, and counteracting the fibroblast proliferation. Proper surgical technique including prevention of tissue damage, meticulous hemostasis, careful suture placement, and complete removal of foreign debris will help reduce subsequent adhesion formation.

Pathophysiology of peritonitis Peritonitis, or inflammation of the peritoneum, is induced by a contaminate or irritating agent. Peritonitis can be classified as primary or secondary, acute or chronic, localized or generalized, and aseptic or septic. Primary peritonitis (such as feline infectious peritonitis) in animals is much less common then secondary peritonitis. Secondary peritonitis usually results from a prior disease or an acute lesion causing contamination of the peritoneal cavity. Contamination may be septic or aseptic; however, aseptic or chemically-induced peritonitis usually progresses to septic peritonitis. Peritoneal contamination results in an inflammatory response characterized by influx of protein rich fluid and white blood cells into the peritoneal cavity. The protein rich fluid is thought to dilute the contaminate while the cells are important for phagocytic and bactericidal activity. Compliment and other immune agents also enter the peritoneal cavity and aid in this activity. Bacteria and other particles are cleared rapidly from the peritoneal cavity via the diaphragmatic lymphatics. Fibrinous adhesions isolate the contaminate initially and seal small perforations in hollow organs. The omentum is important in assisting the isolation of bacteria and sealing of perforations. Inflammation around the intestine induces an ileus condition which is thought to be mediated by the sympathetic nervous system. This state of paralysis of the intestines helps to localize the contamination by slowing the intra-peritoneal circulation reducing direct spread from the leakage area. Peritoneal irritation also causes increased rigidity of the abdominal musculature which inhibits respiratory movements and subsequently reduces intra-peritoneal circulation. Initially these responses to conta-

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mination are helpful to the host, but they may progress to have harmful affects. Rapid lymphatic clearance of bacteria may induce septicemia and the exudation of protein rich fluid and cells can induce hypovolemia and hypoproteinemia. Excessive intra-peritoneal fluid will exceed the lymphatic resorptive capacity and allow bacteria to remain in the cavity and eventually proliferate. The oxygen tension in the fluid is reduced and this inhibits neutrophil activity and promotes proliferation of anaerobes. Bacteria suspended in fluid are not readily phagocytized since neutrophils function best on a fixed surface. Fibrinous adhesions occlude diaphragmatic lymphatics and protect bacteria from white blood cells and humoral agents. The protected areas then form abscesses and become organized into fibrinous adhesions that obstruct or strangulate organs after weeks of disease. Ileus causes sequestration of large amounts of fluid within the bowel and exacerbates the hypovolemia. Bacteria proliferate as the bowel continues to distend and this potentiates the effects of endotoxin and septic shock. Cardiovascular alterations reflect the hypovolemia and endotoxic shock. Eventually from hypovolemia and endotoxic shock, visceral blood supply is reduced, metabolic acidosis ensues, and tissue hypoxia results. An increased metabolic rate and massive protein loss in the peritoneal cavity results in an overwhelming catabolic state of the patient with peritonitis. Reduced kidney profusion can cause insufficiency that reduces clearance of toxic by-products of metabolism and inflammation. Acute renal failure may result. Disseminated intravascular coagulopathy (DIC) may occur with septic peritonitis. Blood sludging within the microvasculature secondary to peripheral vasoconstriction and hemoconcentration predisposes the peritonitis patient to DIC.

Chemical peritonitis Chemical peritonitis is the result of the presence of a non-septic irritating substance within the peritoneal cavity. The degree of inflammation depends on the chemical contaminate. Contamination by bile will produce intense peritoneal irritation. The presence of bacteria in the peritoneal cavity with bile markedly increases the severity of the disease. Bile salts have an enhancing effect on bacterial proliferation, and they also reduce the activity of neutrophils. Bile also lyses red blood cells and this releases hemoglobin which has an enhancing effect on bacterial proliferation. Gastric juices and pancreatic secretions are more irritating than bile and cause immediate cellular damage. Intra-peritoneal urine may or may not be contaminated with bacteria initially, depending on the status of the urinary tract before the injury. Although urine peritonitis can produce profound uremia subsequent to the absorption of urinary constituents across the peritoneum, urine causes a relatively minor irritating response from the cavity provided heavy bacterial contamination is not present. When combined with the contents of bile, bariumâ&#x20AC;&#x2122;s toxic effect is greater than either contaminate alone. Morbidity and mortality of peritonitis induced by barium has been related to the volume of barium into the peritoneal cavity. Water soluble contrast agents are less toxic but are still associated with a high morbidity with

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Management of peritonitis The role of the surgeon (Hosgood) Diagnosis Peritonitis should be suspected in patients that develop abdominal pain and or distension, fever, and leukocytosis following abdominal surgery or trauma. Depending on the severity, leukocytosis may be characterized by neutrophilia with a left shift, or leukopenia. Hypoproteinemia is common and this occurs due to the exudation of large amounts of protein rich fluid into the peritoneal cavity. Blood glucose levels may be increased, decreased, or normal but extremely high or low levels are associated with high mortality rates. Abdominal radiographs are usually characterized as a ground-glass appearance with lack of contrast of serosal surfaces which suggests free intra-peritoneal fluid. Free intraperitoneal gas may be present if rupture of a hollow viscus has occurred. Ileus may be evident by the presence of dilated gas-filled loops of bowel. The most useful aid in reaching a definite diagnosis of peritonitis is cytologic examination of intra-peritoneal fluid. Abdominocentesis can be performed with a 20-gauge 1 1/2” needle. The accuracy of diagnosis can be increased dramatically with diagnostic peritoneal lavage (Kolata). With this technique, saline is infused into the peritoneal cavity, and the cavity is “washed” or allowed to circulate with the cavity. The fluid is then collected by gravity flow and analyzed cytologically and chemically. Fluid findings that are indications for exploratory celiotomy include: high white blood cell count (degenerative neutrophils), presence of bacteria, vegetable or meat fibers suggestive of bowel perforation, increased creatinine levels or increased bilirubin levels.

Treatment Treatment of peritonitis is based on four important principles: 1. Patient stabilization 2. Treatment of infection 3. Correction of the cause of peritonitis 4. Abdominal drainage

Patient stabilization Patients with generalized peritonitis are usually hypovolemic due to the exudation of large volumes of fluid into the peritoneal cavity. Adequate fluid therapy is very important and a balanced electrolyte solution should be administered at a rate sufficient to replace the patient’s blood volume (90 ml per kilogram body weight in one hour). Although fluid therapy is the most important element in the treatment of shock, corticosteroid administration may also be indicated. The beneficial effects of corticosteroids include preservation of vascular and lysosomal membranes, positive cardiac inotropic affect, dilation of pre-capillary sphincters, increased regional blood flow, prevention of bowel mucosa ischemia, and reduction of adhesion formation. I prefer to use a rapidly acting glucocorticoid; prednisolone sodium succinate administered intravenously. Administration of a cyclo-oxygenase inhibitor such as flunixin meglumine is also beneficial to the peritonitis patient in endotoxic shock. Flunixin administration (1.0 mg/kg, IV) has also been shown to block production of damaging prostaglandins which may contribute to multiple organ failure.

Infection treatment Systemic antibody therapy should be initiated as soon as the diagnosis of peritonitis is made. A broad spectrum antibiotic combination should be given initially until microbial culture and susceptibility results are known. Antibiotics selected should be effective against gram-positive and gramnegative aerobic bacteria and anaerobic bacteria. Although some controversy exists over the use of bacteriostatic versus bactericidal antibiotics, only the bactericidal antibiotics have shown efficacy in the treatment of septic shock. Most recommended antibiotic regiments have been a combination of an aminoglycoside (for its gram negative aerobic activity), a penicillin (for their gram positive aerobic and anaerobic activity), and either clindamycin or metronidazole (for their broader spectrum anaerobic activity). In more recent years, development of new antibiotics such as the third generation cephalosporins and new synthetic penicillins have been shown to be as successful as multiple antibiotic regimens in acute, uncomplicated peritonitis. A new group of antibiotics that may have some application in the prolonged treatment of peritonitis is the quinolones. The quinolones such as enrofloxin or trade name, Baytril, are broad spectrum bactericidal drugs that have good gram negative and gram positive aerobic activity and are particularly effective against Pseudomonas spp. These drugs however, have poor activity

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concurrent bacterial contamination. Powders and other foreign surgical material particles such as lint, will induce a severe inflammatory reaction. Talc has been replaced as a glove powder by corn or rice starch which are less irritating. Blood itself causes minimal irritation of the peritoneum and is completely absorbed from the peritoneal cavity, often within one day. Residual peritoneal blood enhances bacterial proliferation and also this blood contains fibrin which may occlude diaphragmatic lymphatics and enhance formation of fibrous adhesions. These adhesions block lymphatic clearance of bacteria and isolate bacteria. Severity of peritonitis from gastrointestinal leakage is related to the site of the leakage and the type of bacterial contamination from the site. Mixed bacterial populations are present in the GI tract, but the quantity of bacteria and the prevalence of anaerobic species increase distally in the GI tract. Higher bacterial numbers seen in the distal GI tract increase mortality if leakage occurs. Initially, aerobic bacteria proliferate rapidly in septic peritonitis. As the peritonitis progresses, bacterial synergism between aerobic and anaerobic species is evident. Gram-negative aerobes particularly E coli are responsible for early mortality while the anaerobes such as Bacteroides fragilis predominate in the later stages.

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against anaerobes and should, therefore, be used in combination with clindamycin or metronidazole for adequate spectrum of antimicrobial activity. Some surgeons advocate intra-peritoneal administration of antibiotics for treatment of peritonitis. Remember, most antibiotics reach therapeutic concentrations in the peritoneal fluid following systemic administration. It is generally recommended that intra-peritoneal administration of antibiotics is not necessary if appropriate systemic antibiotic therapy is administered.

Determination and correction of the cause of peritonitis In small animals, peritonitis is usually a surgical disease. Most cases of peritonitis are secondary to inciting problem and exploratory celiotomy is indicated to determine and correct the cause of the problem. At the time of the exploratory surgery the extent of the peritoneal contamination should be reduced by peritoneal debridement and irrigation, and peritoneal drainage should be established. Specimens should be taken for aerobic and anaerobic cultures.

Peritoneal debridement Peritoneal debridement reduces intra-peritoneal bacterial numbers by removing bacteria sequestered in fibrinous material and by removing exudate, blood clots, and necrotic tissue that enhance bacterial growth. Adhesions act as barriers to fluid and antibiotic penetration and should be broken down. During peritoneal debridement and breakdown of adhesions there is a potential risk of spreading infection throughout the peritoneal cavity and creating more damage to the peritoneal mesothelium; however, this presents as less of a clinical problem than the potential for abscess formation. Remember to control hemorrhage during adhesion breakdown because intra-peritoneal blood will enhance bacterial growth. Debridement should be complete as possible; however, in patients with chronic abscess formation or fibrinous peritonitis complete debridement may be impossible. In critical patients with extensive adhesion formation, less aggressive debridement in conjunction with thorough peritoneal irrigation may be indicated initially. Repeat debridement can be performed after the patientâ&#x20AC;&#x2122;s condition has improved.

Intra-peritoneal irrigation Following peritoneal debridement, irrigation should be performed to aid in the removal of bacteria and particles that enhance bacterial proliferation. Irrigation is most effective if used within hours of contamination before fibrin traps bacteria. Irrigate the peritoneal cavity with warm, sterile normal saline solution until the fluid suctioned from the cavity is clear. Remove as much of the irrigation fluid as possible because residual intra-peritoneal fluid enhances bacterial proliferation and reduces neutrophil function. Even though irrigation could spread infection to adjacent areas, copious irri-

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gation and complete removal of intra-peritoneal fluid is considered much more important. The need for antiseptic or antibiotic additions to the irrigation fluid is generally not thought to be necessary. Antiseptics such as povidone-iodine are potent inhibitors of neutrophil function and may actually damage peritoneal surfaces and exacerbate sepsis. The addition of antibiotics to the irrigation fluid will initially deliver higher antibiotic levels to the peritoneal cavity but systemic administration is required for maintenance of adequate levels in the serum and intra-peritoneal fluid. We currently recommend intra-operative irrigation with warm, sterile normal saline in conjunction with systemic antibiotic administration. Administration of heparin systemically or in the irrigation fluid can prevent drain occlusion and adhesion formation. Clinical studies have not proven the efficacy of this therapy. Heparinization may be contraindicated in the early stages of peritonitis because it may limit the hosts ability to isolate the infection by reducing and limiting adhesion formation.

Peritoneal drainage (Greenfield) After debridement and irrigation of the peritoneal cavity, peritoneal drainage should be established with either an intra-peritoneal drain or open peritoneal drainage.

Intra-peritoneal drains Intra-peritoneal drains are usually indicated to drain localized fluid collections such as abscesses. One of the major problems with intra-peritoneal drains is that they are rapidly encased by omentum and this reduces drain function as early as several hours after placement. The sump-Penrose drain appears to be several times more efficient than closed or passive penrose drainage of the peritoneal cavity. The sump drain consists of a double lumen tube in which the second lumen serves as an external airvent to break the intra-peritoneal vacuum. The drain can act passively or be connected to a continuous suction vent. A triple lumen sump drain can be constructed easily from a modified Foley catheter and a fenestrated Penrose drain. A 22 French Foley catheter is modified by removing the bulb and the bulb injection port. The intra-peritoneal portion of the catheter is fenestrated and the entire Foley catheter is inserted into a fenestrated halfinch Penrose drain. The penrose drain is sutured at each end of the Foley catheter with two sutures of non-absorbable material. The sump-Penrose drain is placed into the peritoneal cavity and exited through a dependent portion of the abdominal wall. All intra-peritoneal drains should be kept covered by a sterile bandage to help prevent contamination of the drain and allow monitoring of the amount and character of the drainage. Bandages should be changed several times daily depending on the amount of drainage. Remember that drainage will not cease completely even if the peritoneal infection has resolved, since the presence of a drain will incite the production of up to 50-100 mls of fluid per day. In my experience, most intra-peritoneal sump-penrose drains can be removed 4-8 days postoperatively. The most common complication associated with drains is an ascending infec-

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tion. This problem can be minimized by maintaining a sterile absorbent bandage over the exposed portion of the drain until removal. The complications associated with these drains include incomplete drainage, intestinal or omental herniation at the drain exit site, and retraction of the drain into the peritoneal cavity. Inadvertent removal of the drain by the patient can be reduced by bandaging the drain exit site, and placement of an Elizabethan collar on the patient.

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excessive discomfort even during bandage changes. They move around freely and return to food and water consumption during the period of treatment. Most common clinical complications reported with open peritoneal drainage include hypoproteinemia, hypoalbuminemia, and nosocomial infections of the peritoneal cavity.

Open peritoneal drainage Open peritoneal drainage means that the whole peritoneal cavity is left as an open wound. This method of peritoneal drainage has been shown to result in more rapid and complete drainage of intra-peritoneal radiographic contrast medium than sump-penrose drainage in normal dogs. Open drainage technique allows easy abdominal re-exploration with repeated peritoneal debridement which is beneficial particularly in open peritoneal drainage of pancreatic abscesses. The technique requires thorough surgical exploration, debridement, and exploration of the peritoneal cavity first. The linea alba is sutured the full length of the incision in a loose simple continuous pattern with a monofilament nonabsorbable suture such as polypropylene or nylon. A gap of approximately 2 to 2.5 cm is left between the edges of the linea alba. Subcutaneous tissue and skin are not closed and a sterile absorbent bandage is placed over the incision. When attempting opem drainage of the abdomen in male dogs, the portion of the abdominal incision at the prepuce is closed primarily in three layers. Only the cranial portion of the abdominal incision is loosely approximated. The open portion of the incision is planned in the most dependent portion of the abdomen to promote drainage. Sterile absorbent dressings are placed over the incision using aseptic technique to prevent contamination. Some surgeons have found that gas sterilized disposable infant diapers are convenient and a practical bandage material for open abdominal incisions. A nonadherent contact layer such as petrolatum impregnated gauze is used to prevent visceral adhesions to the bandage. I prefer to use sterile laparotomy sponges as the second layer with a sterile diaper placed over the sponges when fluid drainage is excessive. In the male dog an indwelling urinary catheter may be necessary to prevent urine soilage of the bandage. Change bandages aseptically when fluid material strikes through the bandage. Bandage changes are normally performed without sedation of the standing patient. If the patient appears painful or resistant to bandage changes, a low dose narcotic analgesic can be used. If the abdominal drainage appears purulent or the patient shows signs of sepsis, the abdomen is easily re-explored. The abdomen is closed once drainage is minimal and serosanguineous in nature, and the patients condition has improved. This usually takes at least three to five days in my experience. The open abdomen treatment potentially allows drainage from the whole peritoneal cavity and this provides an unfavorable environment for anaerobic bacteria. It also provides an easy access for re-exploration and assessment of the intra-abdominal problem. Clinical experience has shown that dogs and cats tolerate this treatment well and do not appear to be in

The selection of the drainage method to be used in the peritonitis patient should be based on the severity of peritonitis, the source and degree of peritoneal contamination, and the experience of the surgeon. In the patient with mild chemical peritonitis (such as that occuring secondary to urinary bladder rupture in the absence of urinary tract infection), post-operative peritoneal drainage may be unnecessary. Management of these patients requires correction of the cause of peritonitis together with thorough intra-operative peritoneal irrigation with warm, sterile saline. Patients with localized peritonitis such as that occuring secondary to a prostatic abscess or patients with generalized peritonitis of mild severity should be managed surgically by correction of the cause of peritonitis, intra-operative irrigation, with or without placement of an intra-peritoneal sump drain. Patients with severe generalized peritonitis or extensive contamination of peritoneal cavity should have open peritoneal drainage. Abdominal closure can be performed usually within a week. Open peritoneal drainage is more labor intensive and more costly than sump- penrose drainage and this may limit its application to patients with severe generalized peritonitis.

Post-operative peritoneal lavage Some surgeons recommend the use of post-operative peritoneal lavage in patients with generalized peritonitis; however, clinical results with this method of treatment are inconclusive. Lavage aids in continual mechanical removal of bacteria and substances that enhance bacterial proliferation. The fluid movement is reported to reduce adhesion formation however, small areas of localized fluid accumulations have been reported in human patients after four to five days of vigorous lavage. Lavage also has been reported to slow the speed of peritoneal healing possibly because of the mechanical disruption of the wound or removal of free-floating macrophages.

Post-operative care and supportive therapy Mangement of ileus Ileus is a pathophysiological response to peritonitis. Treatment of ileus has obvious beneficial effects of decompression of the bowel to reduce intra-abdominal pressure which will in turn enhance respiration, and venous return from the abdomen. Physical closure of the abdomen is easier and return

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Selection of drainage method (Donner)

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of appetite is promoted which is important in the catabolic patient. Decompression of the stomach can be performed with the use of nasogastric tubes or, alternately, a jejunostomy tube can be placed at the time of celiotomy. This will allow bowel decompression as well as enteral nutrition. The correction of electrolyte imbalance, particularly hypokalemia, is important for return of gastrointestinal function.

Nutritional support Nutritional support has in the past been often overlooked, but it is an important component in the management of the peritonitis patient. The septic patient has a metabolic rate up to four times above normal and is catabolic. Surgery further increases the patientâ&#x20AC;&#x2122;s energy expenditure. Anorexia which is common in the peritonitis patient also contributes to the negative nitrogen balance. This malnutrition results in the impaired cell mediated and humoral immunity, increased suseptibility to infection, delayed wound healing, and increased incidence of wound dehiscence. Enteral hyperalimentation has been used successfully in the dog; however, the technique is expensive and requires intensive patient monitoring. Enteral hyperalimentation is the preferred route of nutritional support in the small animal patient if the bowel is functional. Liquid food products can be administered by oral-gastric tube, nasogastric tube, pharyngostomy, gastrostomy, or jejunal tube feeding. Feeding methods should use

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as much of the patientâ&#x20AC;&#x2122;s functional gastrointestinal tract as possible. A variety of diets can be used for enteral hyperalimentation but my preference is to use gruelled canned dog food mixed with water or liquid nutritional supplement.

Complications and prognosis Peritonitis is a complex disease condition. It may be associated with many potentially life-threatening complications. End stage septic shock is the usual cause of death. Based on reports on mortality from septic peritonitis, up to 70% of dogs will eventually die from complications related to the condition. With early diagnosis, aggressive supportive therapy, effective peritoneal drainage, and appropriate antibiotic therapy, the prognosis may be improved.

References Hosgood G, Salisbury S, (1988), Generalized peritonitis in dogs: 50 cases (1975-1986). J Am Vet Med Assoc, 193:1448-1450. Kolata R (1976) Diagnostic abdominal paracentesis and lavage: Experimental and clinical evaluations in the dog. J Am Vet Med Assoc, 168:697-699. Greenfield C, Washaw R, (1987), Open peritoneal drainage for treatment of the contaminated peritoneal cavity and septic peritonitis in dogs and cats: 24 cases (1980-1986). J Am Vet Med Assoc, 191:100-105. Donner G, Ellison G, (1986), The use and misuse of abdominal drains in small animal surgery. Compend Contin Educ Pract Vet, 8:705-712.

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Clinical update: gastric dilatation-volvulus in dogs Daniel D. Smeak

Summary Major advances have been made in the medical and surgical management of gastric dilatation-volvulus syndrome (GDV) in the dog in the past 10 to 15 years. Hypovolemic shock, ventricular arrhythmias, and sepsis related to gastric wall necrosis are common problems associated with this disease syndrome. The morbidity and mortality from these complications have dramatically decreased because of improved clinical awareness, new anesthetic regimens, the advent of new surgical techniques, improved perioperative management, and a better understanding of the pathophysiology of this syndrome. The purpose of this seminar is to update practitioners to these recent advances and to review current treatment recommendations.

Introduction Major advances have been made in the medical and surgical management of gastric dilatation-volvulus syndrome (GDV) in the dog in the past 10 to 15 years. Hypovolemic shock, ventricular arrhythmias, and sepsis related to gastric wall necrosis are common problems associated with this disease syndrome. The morbidity and mortality from these problems have dramatically decreased because of improved clinical awareness, new anesthetic regimens, the advent of new surgical techniques, improved perioperative management, and a better understanding of the pathophysiology of this syndrome. The purpose of this seminar is to update practitioners to these recent advances and to review current treatment recommendations.

tial studies showed that gastrin concentrations are increased in dogs afflicted with GDV. However, the cause and effect of increased gastrin concentrations have not been explained. Recent studies have shown that gastrin levels in dogs that have had GDV surgically corrected are not different that of clinically normal dogs. Plasma concentrations do not increase in clinically normal dogs in response to inflation of an intragastric balloon. Therefore, the role of gastrin in this disease remains unproven.

Myoelectric dysfunction It has been difficult to determine if changes in myoelectric activity seen in dogs after GDV correction actually are the cause of the initiating problem or are secondary to the event. It appears that surgical manipulation alone disrupts activity as much or more than experimental creation of GDV. Clinical use of percutaneous electrogastrography may be required to determine the role of myoelectric abnormalities in GDV and any changes induced by gastropexy.

Esophageal motility Abnormal esophageal motility has been documented in dogs with recurrent GDV. In this study aerophagia was seen mainly when primary esophageal peristalsis failed to transport a food bolus into the stomach. In many cases the ingestion of air elicited secondary peristaltic waves that were strong enough to transport esophageal contents to the stomach.

Dietary factors Proposed etiologic mechanisms (Hosgood) Gastrin Gastrin has a trophic effect on gastric mucosa, and it has been proposed that gastrin could play a role in the development of GDV by causing delayed gastric emptying secondary to pyloric obstruction and hypertrophy. Also, increased gastrin concentrations could directly delay gastric emptying and could increase gastroesophageal sphincter pressure, thereby inducing esophageal spasm, initiating aerophagia, and decreasing the possibility of vomiting. Ini-

Diet and feeding have long been implicated in the etiopathogenesis of GDV. Dogs fed a commercial diet once daily instead of three times have higher gastrin levels and more stomach distention. It was proposed that once daily feeding of a commercial dog food could predispose to GDV by causing a heavy, chronically distended stomach that could easily undergo volvulus. More recent studies have failed to show any difference in gastric motility in dogs that had distended stomachs from dietary manipulations and those that did not. Gastric emptying times did not vary between clinically normal dogs and dogs previously fed diets

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DVM, Dipl ACVS Professor, Head of Small Animal Surgery The Ohio State University, College of Veterinary Medicine,Columbus, Ohio - USA

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of various volumes, some of which caused massive gastric distention. Gastric emptying times in dogs that have had surgical correction are not different from clinically normal dogs when liquid test meals are used. Despite these findings, feeding small, frequent meals may still be prudent in dogs of predisposed breeds.

Predisposing factors (Glickman) A study conducted of 101 dogs that had acute episodes of GDV were compared to the same number of dogs that had no GDV history. Control dogs were matched individually to case dogs by breed or size and age. Predisposing factors that significantly increased a dogâ&#x20AC;&#x2122;s risk for GDV were male gender, being underweight, eating one meal daily, eating rapidly, and a fearful temperment. The only factor that appeared to precipitate an acute episode of GDV was stress. Perhaps stress precipitates GDV by changing hormone levels which regulate gastric function and motility.

Pyloric surgery - Is it necessary? Pyloromyotomy and pyloroplasty have been routinely performed during GDV correction at some institutions despite the absence of evidence that delayed gastric emptying or pyloric lesions are causal factors in the disease. Gastric emptying in dogs that previously had GDV without pyloric surgery was no different than clinically normal dogs in one study. In addition, the long-term outcome for dogs that underwent surgical treatment for GDV and pyloroplasty was not different from that for dogs that underwent surgical treatment without pyloric surgery. The rate of complications, however, was higher in dogs undergoing pyloric surgery. Complications observed included: vomiting, cardiac arrhythmias, and death. Pyloric surgeries such as the pyloromyotomy and plasty do not significantly alter gastric emptying time and may, in fact, prolong this time. The relationship between outflow diameter and gastric emptying is still uncertain. These findings strongly suggest that pyloric surgery is contraindicated unless a pyloric lesion causing outflow obstruction is demonstrated. Inclusion of pyloric surgical techniques with the surgical protocol for treatment of GDV may have contributed to the high postoperative complication and mortality rates reported in earlier studies.

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tropexy techniques became popular and reported complication rates were dramatically reduced. Recurrence of GDV ranges between three and 6% with these new techniques. A rapid gastropexy technique method has been recently developed to prevent recurrence of GDV (Meyer-Lindenberg et al). It involves including the seromuscular layer of the pyloric antrum in the closure of the cranial portion of the linea alba. Seven percent of 84 dogs treated with this method had gastric dilatation without volvulus within six months of surgery. None of the dogs had GDV recur. In comparison, 76% had recurrence of GDV after orogastric intubation and gastric decompression alone. This technique is quick but has the obvious disadvantage of creating difficulties during subsequent laparotomy. It appears that a properly performed right-sided gastropexy is critical for reducing the risk of recurrent GDV. The tube gastrostomy technique is associated with more complications but I still prefer this technique if stomach resection is required. This permits a small tube to be placed down the foley catheter and into the intestine to bypass an atonic stomach during early postoperative feeding. The focus in surgery currently is the development of less invasive methods of gastropexy. Recently, a study was performed to evaluate right-sided percutaneous endoscopic gastrostomy as a method for creation of permanent gastropexy. The percutaneous method resulted in inferior adhesion formation when compared to incisional gastropexy (Waschak). Since assessment of gastric wall and splenic viability is important for prognosis and treatment decisions, early exploratory laparotomy remains the preferred approach. Percutaneous methods may have value for prophylactic gastropexy.

Adjunct treatment modalities update (Hosgood) Lipid peroxidation inhibitors Use of a lipid peroxidation inhibitor could prevent death in dogs with experimentally induced GDV. Lipid peroxidation activity in the small intestine and colon, pancreas, and liver was significantly reduced after correction of GDV (after reperfusion) in dogs treated with an inhibitor than in dogs treated with saline. The results of using these drugs in clinical trials have not yet been published.

Prostaglandin inhibitors Gastropexy techniques update Until the mid 1980â&#x20AC;&#x2122;s, tube gastrostomy was the gastropexy technique of choice. The recurrence rate following tube gastrostomy for treatment of GDV is from five to 11%. Complications such as leakage around the tube exit site from the stomach, cellulitis around the tube exit site in the skin, premature tube removal, and permanent stoma development caused mortality in up to 30% of cases so treated. Surgical techniques that do not require an opening in the stomach and an external tube were developed after these complications were reported. Circumcostal gastropexy and belt loop gas-

Plasma endotoxin concentration is high in dogs with experimentally induced GDV. Plasma concentration of prostacyclin, a prostaglandin produced when cyclooxygenase acts on arachidonic acid released from lipid cell membranes, also is elevated suggesting that the increase in prostacyclin concentration may be a result of endotoxin-induced cell damage. Administration of flunixin meglumine, a NSAID with antiprostaglandin activity, after GDV did not result in appreciable improvement in hemodynamics but plasma concentrations of prostacyclin did not increase further. It is now accepted that endotoxemia plays a critical role in pathologic

alternations associated with GDV and that flunixin administration after the onset of GDV may prevent further rise in plasma prostacyclin and, therefore, attenuate the effects of endotoxemia.

Hypertonic saline solution Intravenous administration of hypertonic saline (7% NaCl) solution in 6% dextran (5 ml/kg body weight infused over five minutes) followed by 0.9% NaCl solution (60 ml/kg/hr) has been demonstrated to be superior to IV administration of normal saline solution alone for initial treatment of shock associated with experimentally induced GDV. The addition of dextran appears to sustain the effects of hypertonic saline solution, compared with the short-term effects of hypertonic saline solution alone. Slowing fluid administration in dogs receiving normal saline solution resulted in deterioration in hemodynamic values in dogs receiving normal saline alone; hemodynamic values of dogs receiving hypertonic saline in dextran followed by normal saline were maintained.

Brief clinical report updates Dogs that require gastric wall resection at the time of correction of GDV have a high complication and mortality rate. Of 30 dogs with GDV that required partial gastrectomy, 90% developed complications and over 50% died. Although unavoidable, if partial gastrectomy is required, the prognosis for survival after surgery is poor. Another study showed that coagulation abnormalities develop in most dogs with GDV and may contribute to the high mortality rate associated with the disease. Mesenteric volvulus may occur with GDV and this carries a grave prognosis. A syndrome characterized by intermittent mild bloating, vomiting, regurgitation, and excessive borborygmi has been documented recently. Radiographically, a displaced pyloric antrum is seen with or without mild gastric distention. Delayed gastric emptying is not a factor in this syndrome. My experience with the chronic form of GDV is good. A right-sided gastropexy resolves the clinical signs in most dogs. If spontaneous pneumoperitoneum is seen after surgical treatment of GDV, splenic infarction, or gastric perforation should be considered. Recurrent gastric dilatation after GDV correction has been attributed to displacement (kinking) of the pyloric antrum causing partial obstruction. If delayed gastric emptying can be demonstrated, correction of the kink often eliminates further dilatation.

Current treatment recommendations Although exceptions do occur, I believe there is a direct correlation between mortality and duration of GDV. Improved client education regarding clinical signs and the importance of early emergency treatment, especially to owners and breeders of predisposed breeds, cannot be overemphasized.

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I prefer to perform exploration and gastropexy in any large or giant breed dog presenting with â&#x20AC;&#x153;bloatâ&#x20AC;?, regardless of whether there is radiographic evidence of volvulus. This opinion is based on 1) the high recurrence rates of dogs that do not receive prophylactic gastropexy; 2) dogs may spontaneously resolve their volvulus alone or after emergency decompression and lavage; 3) clinical experience with dogs that were not operated because of marked clinical improvement after temporary stabilization and normal post-decompression radiographs, and subsequently died followed by unexpected gastric rupture. In addition, it does not make sense to delay resuscitation and decompression by taking radiographs to confirm the diagnosis of GDV unless the dog is stable. When possible, early exploratory laparotomy for ongoing gastric necrosis and prophylactic gastropexy should be performed after clinical stabilization and before the high incidence period of ventricular dysrhythmias. If decompression is not possible, emergency laparotomy is recommended. Surgery may be delayed until fluid, electrolyte and acid-base status is improved provided decompression is possible. Recent experimental studies indicate that 360 degree gastric volvulus does alter gastric blood flow in decompressed patients. Although most cases of GDV are usually not malpositioned 360 degrees and the effects of lesser degrees of volvulus are not known, decreased perfusion to sections of the malpositioned stomach may be present despite decompression. Ventricular arrhythmias commonly have a delayed onset (75% occur with 12-36 hours of presentation). Early surgical intervention often allows anesthesia and surgery to be performed well before the onset of dysrhythmias (Whitney).

Treatment outline for acute GDV Priority #1 Treatment of hypovolemia, and decompression A minimum of two large bore catheters in the cephalic or jugular vein are placed; hypertonic saline (7% NaCl) solution in 6% dextran (5 ml/kg body weight infused over five minutes) followed by 0.9% NaCl solution (60 ml/kg/hr) is administered. Pressure bag systems are helpful in increasing the delivery rate of administration. Do not place catheters in the saphenous veins- venous return is reduced due to the dilated stomach obstructing caudal vena cava flow. Sedate the unruly patient with Ketamine and Valium or Oxymorphone to pass the stomach tube. Tape the mouth closed over a roll of tape to help prevent tube chewing and fighting. Premeasure a pre-lubricated large-bore orogastric tube to the level of the last rib and insert until resistance is met or until the measured spot is reached. If you meet resistance, try blowing in the tube while rotating it 180 degrees. When this is unsuccessful, trocar (use 16 - 18 gauge needle) the most tympanic area of the abdomen (usually right side just caudal to costal arch; away from the spleen) and remove as much gastric pressure as possible. This maneuver usually unlocks the cardia area and allows the stomach tube to pass without difficulty. Remember easy tube passage does not mean that the patient does not have volvulus. Priority #2 Treat for endotoxic shock Intravenous corticosteroids and antibiotics are indicated.

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I administer 20 mg/kg of prednisolone sodium succinate and Kefzol (20 mg/kg) after the intravenous line is placed. A single IV dose of flunixin meglumine (0.5 mg/kg) may be given if the hemodynamic status of the patient remains unstable despite adequate volume replacement. Priority #3 Confirmation of gastric volvulus; rule out other disease A right lateral view has been shown to be the most helpful in determining gastric malposition. A thorough radiographic examination should be routinely employed to rule out gastric perforation, other causes of aerophagia such as obstruction, intestinal volvulus, and respiratory disease, especially in smaller breeds or those with peculiar histories. Submit a cell blood count and serum chemistry profile to evaluate for concurrent disease. Priority #4 Ensure patient is stable as possible About 50% of all dogs presenting with GDV have arrhythmias. Treatment with lidocaine is initiated when strings of VPCs, multifocal VPCs, rapid unfocal VPCs with poor cardiac output are present. Ensure that hemodynamic status of patient is stable. Continuously monitor for arrhythmias throughout perioperative period. Be sure the magnesium and potassium concentrations are adequate since deficiencies of these electrolytes in particular will reduce the effectiveness of lidocaine treatment of arrhythmias. Priority #5 Anesthetize patient carefully Arrhythmogenic drugs such as the ultrashort barbituates and hypotensive agents such as Acepromazine are avoided. Induce anesthesia with Oxymorphone/Diazepam, Diazepam/ketamine combinations, or mask with Isofluorane. Nitrous oxide is contraindicated. Assist ventilation especially if the stomach has not been fully evacuated. Priority #6 Reposition stomach, assess stomach and spleen viability Decompress the stomach if it remains distended. Pass an orogastric tube or use a needle to trocar the stomach. Reach toward the esophageal hiatus and grasp the pylorus. Move the fundus caudally and pull the pylorus toward the right side. Untwist the spleen unless it is necrotic or the hilus is thrombosed. After the stomach and spleen are repositioned they should be assessed for viability. The viable spleen will become smaller and return to a more normal color within minutes of repositioning. If the spleen is grossly necrotic or thrombosed, perform splenectomy without fully untwisting the hilus. Occasionally the short gastric vessels become avulsed and may require ligation to stop hemorrhage. Observe the fundic area for signs of gastric necrosis. There are no reliable ways to determine gastric wall viability; serosal coloration and wall texture are used most. Give the stomach wall 5-10 minutes after repositioning before making a final judgement about viability. Larger grey-green, purple, or black areas with a thin or torn appearance should be resected. Approximately 10% of all GDVs require partial stomach wall resection. About 30-60% of patients that require partial gastrectomy will die after surgery. Therefore, the stomach viability should be assessed carefully; aggressive resection of questionable areas is not warranted and may increase the mortality rate needlessly. If perforation and peritonitis are present, a grave prognosis is given to the owners before proceeding. I prefer to use the partial invagination technique

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rather than resection for questionable areas of stomach wall. The TA autostapling devise or conventional suture techniques are used to resect necrotic areas. Priority #7 Perform a permanent right-sided gastropexy The tube gastrostomy technique is usually preferred in cases requiring gastric wall resection. Continuous decompression and enteral nutritional support can be offered with this technique. A pyloric outflow surgery is not performed unless abnormalities are found. The ideal gastropexy technique is simple and quick to perform, permanently adheres the stomach to the abdominal wall in an anatomic position to prevent recurrence, does not interfere with gastric emptying, has minimal complications, and require minimal postoperative care. The belt-loop gastropexy and circumcostal gastropexy are the most practiced techniques in the United States. To achieve a permanent adhesion, both the abdominal wall and stomach must not have a serosal covering, and raw muscle surfaces must be in contact until wound strength is adequate. Priority #8 Carefully monitor the patient for complications postoperatively Most postoperative mortality occurs within the first four days. The two most common problems resulting in death include 1) peritonitis, sepsis and shock associated with gastric wall necrosis and 2) cardiac dysrhythmias. Persistent vomiting, anorexia, fever, or depression following surgery should signal to the clinician that an underlying problem exists. Aspiration pneumonia is occasionally seen after surgery following orogastric intubation. Signs of shock or sepsis in the early postoperative period may be the result of cardiac dysrhythmias or stomach necrosis. Since pneumoperitoneum is present after laparotomy, free air in the peritoneal space on abdominal films does not necessarily indicate gastric leakage. If gastric perforation is suspected, abdominocentesis and cytologic evaluation or contrast gastrogram studies usually confirm the diagnosis. Constant ECG monitoring and treatment of severe arrhythmias are essential.

Postoperative Management Goals 1. Maintain normal fluid, electrolyte, and acid-base status after surgery. Aggressive intravenous fluid administration is continued after surgery. Watch for hypokalemia, the most common electrolyte abnormality seen after GDV surgery. I prefer to supplement of maintenance fluids with 20 mEq/L of potassium chloride during the first few days after surgery until normal appetite is observed. 2. Monitor for ventricular arrhythmias; treat with lidocaine if focal VPCs occur greater than 15/min., rapid multifocal VPCS or runs of ventricular tachycardia are present. Intravenous 2% lidocaine is given as a bolus up to three times at a minimum of 15 min between injections. A constant rate infusion of lidocaine is begun (50-70 ug/kg/min). I prefer to â&#x20AC;&#x153;piggybackâ&#x20AC;? intramuscular procainamide (15 mg/kg QID) at the onset of constant lidocaine infusion. Gradual withdrawal of the lidocaine infusion over the next 24 hours and continued procainamide administration is easier to maintain after surgery since not drip rates need to be monitored. Watch for signs of lido-

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Treatment of recurrent gastric distention Following gastropexy, or â&#x20AC;&#x153;Chronic Bloatersâ&#x20AC;? Priority #1 Differentiate simple dilation from recurrent volvulus Special radiographic studies may be indicated if the right lateral and ventro-dorsal view do not reveal a problem. Priority #2 Evaluate for gastric emptying problem Perform upper GI series and fluoroscopic studies to evaluate gastric emptying times. If the gastropexy site is intact, use of motility modifiers such as metoclopramide (0.4

mg/kg, TID) and multiple feedings may be beneficial. When gastric emptying is delayed and medical therapy is unsuccessful, surgical exploratory is performed to rule out underlying pyloric abnormalities. If kinking is seen at the previous gastropexy site, remove the original adhesion area and reperform a gastropexy in a more functional area. In my experience, problems with kinking of the pylorus following gastropexy is usually due to creating a gastropexy more toward the body of the stomach rather than the pylorus.

References Hosgood G,(1994), Gastric dilatation-volvulus in dogs. J Am Vet Med Assoc, 204:1742-1747. Glickman L, Glickman N, Schellenberg D, Simpson K, Lantz G, (1997), Multiple risk factors for the gastric dilatation-volvulus syndrome in dogs: a practitioner/owner case control study. J Am Anim Hosp Assoc, 33:197-204. Meyer-Lindenberg A, Harder A, Fehr M, Luerssen D, Brunnberg L, (1993), Treatment of gastric dilatation-volvulus and a repid method for prevention of relapse in dogs: 134 cases (1988-1991). J Am Vet Med Assoc, 203:1303-1307. Waschak M, Payne J, Pope E, Jones B, Wagner-Mann C, (1997), Evaluation of percutaneous gastropexy as a technique for permanent gastropexy. Vet Surg, 26:235-241. Whitney W, (1989), Complications associated with the medical and surgical management of gastric dilatation-volvulus in the dog. Prob Vet Med, 1:268-280.

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caine toxicity such as seizures, depression, and vomiting. 3. Observe for gastric dilatation after surgery; monitor for persistent vomiting. Postoperative vomiting is usually self-limiting, provided the patient is not fed in the early postoperative period. Decreased gastric motility is common after surgery and may result in gastric distention and vomiting. The use of a motility stimulant such as metoclopramide (10 mg IM, TID) may be beneficial. Another cause of postoperative vomiting is reflux esophagitis. H-2 blockers such as Ranitidine, or Cimetadine is recommended for suspected esophagitis or gastric ulceration from mucosal sloughing.

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Treatment of feline otitis media and inflammatory polyps Feline sinusitis: surgical management Daniel D. Smeak

Summary Middle ear infections and chronic sinusitis are common disease conditions affecting cats. These conditions are initiated by a variety of causes. A thorough diagnostic workup is critical since successful therapy depends upon elimination of the cause of the problem and identification of predisposing factors. This seminar will outline a diagnostic plan for these diseases to help practitioners identify causal disorders. Indications for medical and surgical treatment, and detailed surgical techniques will be discussed.

Polyps that grow into the nasopharynx cause upper respiratory signs such as sneezing, nasal discharge, and, in late stages, dysphagia.

Etiopathogenesis

Otitis media is an inflammation within the middle ear structures, which include the tympanic membrane, tympanic cavity, auditory tube, ossicles, and tympanic nerve (a small branch of the facial nerve). Otitis media is thought to occur most often as a sequela to otitis externa in dogs (up to 50% of dogs with chronic otitis externa have concurrent otitis media). Another route of infection of the middle ear is through the auditory tube. Cats are thought to commonly develop otitis media through this route as a sequela to upper respiratory disease. Although otitis media can be caused by trauma, foreign bodies, neoplasms, parasites, and bacterial invasion, many cats presented with middle ear disease have inflammatory polyps. The purpose of this seminar is to review middle ear disease in cats with focus on the surgical treatment of inflammatory polyps and bacterial otitis media.

Although the etiology of inflammatory polyps remains a mystery, there is some suggestion that they may be congenital or secondary to viral or bacterial infections. A congenital etiology has been proposed because inflammatory polyps occur predominately in young cats and also because they have been seen in sibling kittens and in kittens from the same cattery (Stanton). A viral etiology is suspected because feline calicivirus has been recovered from the nasopharynx in two cats and the polyp from another cat (Parker). Whether otitis media is a primary or secondary factor in the etiopathogenesis of nasopharygeal polyps is unknown. Obstruction of the auditory tube causes negative pressure within the tympanic cavity. The negative pressure gradient causes vessel transudation and serous otitis media. Potential causes of auditory tube obstruction include inflammation of the tubal mucosa (viral, bacterial, or allergic reaction), anatomical structural abnormalities, and obstructive masses (such as nasopharyngeal polyps). The structure of the narrow eustachian tube is a factor in development of otitis media in infants and young children (Fireman). This relationship has not been proven in cats. As a general rule, polyps occur mostly in young cats, otitis media in middle-aged cats, and neoplasia in old cats.

Feline inflammatory polyps

Diagnosis

Inflammatory polyps or nasopharyngeal polyps may originate from the pharyngeal mucosa or auditory tube, but, in the authorâ&#x20AC;&#x2122;s experience and others, most arise from the middle ear region (Pope, Kapatkin). These slowly growing benign fibrous polypoid masses are composed of myxomatous to dense fibrous connective tissue covered by epithelium. They have been reported to extend externally out the external ear canal or through the auditory tube into the nasopharynx (Faulkner). Depending on the route of growth, clinical signs vary. External ear extension results in clinical signs of otitis externa such as otic discharge and head tilt.

A diagnosis of inflammatory polyp is based on otoscopic, radiographic, and histologic information. Heavy sedation or anesthesia is necessary in most cases to thoroughly examine the external ear canal, tympanic membrane, and nasopharynx. Remove debris in the external ear canal by lavage with warm saline solution. Avoid antiseptic agents for lavage if possible because most have been incriminated in causing inner ear damage if the tympanic membrane is ruptured. Swabs of the debris can be obtained prior to cleaning if culture or cytology is indicated. Once the debris is cleared from the canal, look to see if the tympanic membrane is per-

Introduction

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DVM, Dipl ACVS Professor, Head of Small Animal Surgery The Ohio State University, College of Veterinary Medicine,Columbus, Ohio - USA

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forated, or bulging, cloudy, or discolored if it is intact. These changes are consistent with otitis media. Polyps extending into the ear canal appear smooth, pedunculated, and pink. Multilobulated masses that bleed when manipulated should be biopsied since these characteristics suggest another disease process such as ceruminous adenocarcinoma. Try to determine whether the mass appears to originate in the middle ear or external ear canal. Retract the soft palate forward to explore the eustachian tube openings. Generally, when clinical signs occur from nasopharyngeal polyps, the masses are easily seen once the palate has been pulled forward. The ear and pharynx should be viewed since polyps occasionally extend in both directions. Failure to determine the full extent of the disease will result in a poor surgical outcome. Oblique lateral, open-mouth, and ventrodorsal views of the skull are recommended for adequate evaluation of the tympanic bullae; general anesthesia is required to obtain good quality films. Oblique lateral and open-mouth views are particularly useful for evaluating the air-filled tympanic cavity. Softtissue density within the cavity suggests either fluid or a mass within the middle ear. In chronic otitis media, the tympanic bulla become thickened and sclerotic. Destruction of the bulla may be observed with severe infection or neoplasia. Thickness of the bullae bone is noted by the surgeon to determine the extent of the surgical approach and the instruments needed to expose the tympanic cavity. Positive radiographic findings are highly sensitive in the diagnosis of otitis media, but negative findings do not rule it out. Nasopharyngeal polyps can be seen best on lateral skull radiographs. The normally air-filled nasopharynx is obscured by a soft-tissue dense mass.

Treatment The recommended treatment for long-standing otitis media, or for removal of inflammatory polyps regardless of where they extend, is ventral bulla osteotomy. Acute otitis media can be treated with antibiotics with or without myringotomy (Shell). More than 50% of polyps removed by traction-avulsion recur within one year. Some surgeons recommend traction when there is no evidence of otitis media on skull films, while the author and others (Kapatkin) strongly recommend that the bulla should be explored in all cats with middle ear polyps. The author has consistently found remnants within the tympanic cavity after polyps have been removed by traction just prior to bulla exploration.

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4. A paramedian skin incision is made from the angle of the mandible to the hyoid apparatus on the affected side. Avoid the linguofacial vein at the caudal aspect of the incision. 5. The bulla is located by blunt dissection between the digastric and hyoglossal muscles in a rostral and medial direction. The hypoglossal nerve can be seen on the medial side of the hyoglossal muscle. The digastric muscle and, the more dorsal located, external carotid artery are lateral to the bulla. 6. A periosteal elevator is used to remove the soft tissues from the ventral surface of the bulla. The bulla is penetrated with a 1/8â&#x20AC;? Steinmann pin and the opening is enlarged with a Lempert rongeur. Alternately, when the bulla is very thick, an air-drill can be used to burr-away the bone. 7. Appropriate culture samples are taken (be sure to submit a sample specifically for Mycoplasma culture also) and the ventral compartment of the bulla is inspected. A small amount of clear serous fluid is normal. An incomplete septum of the bulla divides the aforementioned area from the dorsal compartment. This septum is opened with the Steinman pin and enlarged with rongeurs. The base of the polyp should become visible when the septum is removed. While traction is placed on the polyp, a small curette is used to dislodge the base of the polyp stalk. The remainder of the abnormal tissue and material within the bulla is removed with gentle curettage and irrigation with sterile saline (submit tissue for culture and sensitivity, and biopsy). With primary bacterial otitis media, a rim of granulation tissue is seen lining the pus-filled inner tympanic cavity. This tissue is gently teased out with elevators and curettes. 8. A Penrose drain is sutured to the periosteum surrounding the bulla and is exited through the ventral skin incision. The tubing is secured to the skin with suture. The skin incision is partially sutured closed on the rostral and caudal borders. Be sure to scope the ear and nasopharynx after surgery to ensure that all polyp tissue has been removed.

Postoperative care An Elizabethan collar is placed immediately following surgery. Drains are usually removed by 3-5 days, when wound discharge is minimal. Appropriate antibiotics are given for a minimum of 21 days. The external ear is lavaged and cleaned as needed.

Technique-ventral bulla osteotomy (Ader)

Complications

1. The cat is placed in dorsal recumbency after being intubated and maintained with gas anesthesia. 2. The head and neck is extended and the ventral neck area is prepared for aseptic surgery. 3. The tympanic bulla is located caudomedial to the muscular process of the mandible and rostromedial to the tympanohyoid bone. The ventral wall of the bulla can be palpated externally in most cats.

Complications associated with ventral bulla osteotomy include damage to the hypoglossal nerve, auditory ossicles, oculo-sympathetic trunk, boney labyrinth of the inner ear, facial nerve, and vascular structures in the region. Over 80% of cats undergoing this procedure will have Hornerâ&#x20AC;&#x2122;s syndrome; most resolve within one month (Kapatkin). Iatrogenic inner ear damage may be permanent. Most cats with polyps or bacterial otitis media will have long-term resolution.

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References

Patient evaluation

Ader P, Boothe H, (1979), Ventral bulla osteotomy in the cat. J Am Anim Hosp Assoc 15: 757-762. Pope E, (1990), Feline inflammatory polyps. Friskies Veterinary J, Sept/Oct, 18-20. Kapatkin A, Matthieson D, Noone K, Church E, Scavelli T, Patnaik A, (1990), Results of surgery and long-term follow-up in 31 cats with nasopharyngeal polyps. J Am Anim Hosp Assoc 26: 387-392. Faulkner J, Budsberg S, (1990), Results of ventral bulla osteotomy for treatment of middle ear polyps in cats. J Am Anim Hosp Assoc 26: 496-499. Stanton M, Wheaton L, Render J, Blevins W, (1985), Pharyngeal polyps in two feline siblings. J Am Vet Med Assoc 186: 1311-1313. Parker N, Binnington A, (1985), Nasopharyngeal polyps in cats: three case reports and a review of the literature. J Am Anim Hosp Assoc 21: 473-478. Fireman P, (1985), Eustachian tube obstruction and allergy: a role in otitis media with effusion? J Allergy Clin Immunol, 76: 137-140. Shell L, (1995), Otitis media and interna. WB Saunders Co., Philadelphia, 1128-1132.

A thorough history is important especially with cats affected with chronic nasal disease. Direct your attention toward the vaccination and environmental history since viral rhinitis is much more common in catteries, immunocompromised cats and multi-cat households. Sneezing and nasal discharge are the most common primary presenting complaints. Gagging may be noticed if discharge drains into the nasopharynx or a nasopharyngeal mass is present. Dysphagia and severe gagging are commonly reported complaints from owners of cats with nasopharyngeal polyps (nasal discharge is also commonly present in these cats). Owners should be questioned about the presence of gastrointestinal signs, because occasionally ingesta enters the caudal nasal passage and results in rhinitis. Duration and progression of signs, medications and response to these treatments should be noted. Characterize the volume and character of the nasal discharge and whether it is bilateral or unilateral, acute or chronic. Mucoid discharge is usually present if the condition is chronic, serous discharge is seem with more acute disorders. Hemorrhage may be seen with trauma, coagulopathies, hypertension, erosive or invasive disease, or with severe prolonged sneezing induced by any cause. Food or water from the nares usually indicates communication of the nasal and oral cavities. Unilateral nasal disease is more typical of nasal foreign body, tumor, oronasal fistula, or tooth root abscess. Physical examination of the cat with nasal disease should include thorough examination of the oral and nasal cavities and a complete examination of the remaining body systems to rule out underlying systemic disease. Dyspnea if present, more often is from lower versus upper respiratory conditions in the cat. Palpate the nose to detect defects or swellings. Facial deformity and lymphadenopathy is most often seen with fungal diseases and neoplasia. Inspect the oral cavity for oronasal fistulae or severe dental disease. Oral or corneal ulcers are seen more often with calicivirus than herpesvirus infections. Nasal ulceration or mass in the nostril may be associated with Cryptococcus or neoplasia. A bulging soft palate could signal the presence of a nasopharyngeal polyp. Facial symmetry and nostril patency should be noted. Examine the eyes for discharge or exophthalmia. Fundic examination may provide evidence of systemic disease associated with Cryptococcus, coronavirus, or Toxoplasma. Otic examination may reveal signs consistent with otitis media. Hornerâ&#x20AC;&#x2122;s syndrome may be associated with otitis media.

Feline Rhinitis/Sinusitis: surgical management Introduction Evaluation of a feline patient with rhinitis and nasal discharge may be a frustrating situation for the veterinarian. Although the relative frequency of various causes of rhinitis/sinusitis varies in dogs and cats, many of the same etiologies that cause rhinitis in dogs are seen in cats (see Table-Van Pelt). Due to the high incidence of viral induced upper respiratory infections in the cat population, the diagnostic workup for cats with nasal discharge often is focused on these etiologies. The anatomic structure of the nasal cavity and sinuses in cats is different than dogs, and this may at least partially explain why viral induced upper airway infections become chronic unresponsive sinusitis conditions. The purpose of this seminar is to review the pathogenesis, diagnostic approach, and treatment of surgical disorders related to feline rhinitis/sinusitis.

Anatomy and physiology Significant differences are found when the turbinate and sinus anatomy is compared in the dog and cat. The attachments of the ventral and dorsal turbinate bones are more widely separated from each other in the cat than the dog, and the turbinated portion of the ethmoid is more extensive. The cat lacks the maxillary recess that is part of the paranasal sinus system in the dog. This recess is believed by some to be one of the regions of early nasal cancer growth in the dog. The nasal cavity can only respond in a limited number of ways, regardless of the cause, so the patients history and clinical signs are often similar (Van Pelt). The nasal lining is limited to glandular hyperactivity in response to many different stimuli. As glandular secretions become stagnant, secondary bacterial infection occurs. Therefore most chronic processes involving the nasal and sinus regions have a bacterial infection component.

Diagnostic workup Perform a diagnostic workup to rule out nonsurgical disorders. When the diagnosis of a chronic nasal discharge is not possible with the regimen below, surgical exploration is warranted. Other tests may be obtained depending on the individual case (see Table). Diagnostic workup History and physical examination CBC, Serum chemistry profile, Felv & FIV tests Nasal cytology, culture, india ink preparation Skull radiography, including frontal sinus views Rhinoscopy and retroflexed nasopharyngeal scoping

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Surgical Procedures (Nasal exploratory, sinus drainage, turbinectomy, intranasal mass excision, nasopharyngeal polyp excision) Cats with chronic sinusitis are candidates for surgery if medical therapy does not control the clinical signs. Owners must understand that if the chronic sinusitis is due to recurrent herpesvirus infection, surgery is attempted to help CONTROL the secondary bacterial infection by providing drainage and removal of necrotic turbinates. Surgery should not be considered curative since many cats are improved but most require intermittent treatment throughout their lives.

Dorsal nasal exploratory A dorsal midline skin incision is made through the periosteum to bone from the top of the sinus to just behind the nasal cartilage. A Steinman pin is introduced just off-midline at the medial canthus level. The bone is removed over the sinus or nasal cavities depending on the extent of the disease and the need for exposure. Take samples of the abnormal tissue for bacterial and/or fungal culture, and histopathology. Remove abnormal tissue and be sure to excise enough obstructing ethmoturbinates to allow drainage of the frontal sinuses. Fenestrated 8 French feeding tubes are introduced into both frontal sinuses and the fenestrated portion is passed to the affected area. Hemorrhage is controlled with gauze stripping. Periosteum is closed in a simple continuous pattern to form an airtight seal. Skin closure is routine. Fix irrigation tubes to the skin exit sites. An Elizabethan collar is worn by the patient until suture and tube removal. Antibiotics at recommended systemic dosages (based on the intraoperative culture and susceptibility results) are used for at least 4 to 6 weeks. Bacteria commonly isolated from affected cats include staphylococci, streptococci, coliforms, and Pasteurella (Cape). Clavulenic acid/amoxicillin or cephalosporin antibiotics are recommended for empirical therapy. Irrigation tubes are flushed with 5 ml of antibiotic solution (at systemic dosages). I prefer to use Tris EDTA solution with aminoglycosides to irrigate sinuses of cats with

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resistent Gram negative bacteria. Fat obliteration of the frontal sinuses is considered if persistent signs of infection occur despite appropriate drainage (Anderson). In a series of six cats with idiopathic rhinosinusitis treated with this procedure, improvement was seen in all cats. About 65% of cats treated this way had long-term resolution of sneezing and purulent nasal discharge without long-term medical therapy.

Staphylotomy The cat is positioned in dorsal recumbency and the endotracheal tube is checked to be sure there is no evidence of air leakage. A mouth-gag is used to keep the mandible extended and provide exposure to the caudal pharyngeal area. If the nasopharyngeal polyp is obstructing the airway, grasp the mass with a towel forceps or Allis tissue forceps and pull it out. If the mass cannot be grasped intubate the patient first and perform a staphylotomy. A midline incision is made in the soft palate from the hard palate junction to about 0.5 cm from the caudal aspect of the palate. Preserving this edge reduces the risk of breakdown of the palate incision closure. Remove the mass and close the incision in two layers; nasal mucosa and oral mucosal sides. Perform a ventral bulla osteotomy to remove remnants of the polyp within the tympanic cavity.

References Van Pelt D, Lappin M, (1994), Pathogenesis and treatment of feline rhinitis. Vet Clin N Am [Small Anim Prac] 24: 807-823. Cape L, (1992), Feline idiopathic chronic rhinosinusitis: A retrospective study of 30 cases. J Am Anim Hosp Assoc 28:149155. Bradley R, (1984), Selected oral, pharyngeal, and upper respiratory conditions in the cat. Oral tumors, nasopharyngeal and middle ear polyps, and chronic rhinitis and sinusitis. Vet Clin N Am [Small Anim Prac] 14: 1173-1184. Anderson G, (1987), The treatment of chronic sinusitis in six cats by ethmoid conchal curettage and autogenous fat graft sinus ablation. Vet Surg 16: 131-134.

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Dental emergencies Frank Verstraete

Summary Emergencies occur in all fields of dentistry and have traditionally been classified as emergencies in periodontics, endodontics, orthodontics, oral medicine and maxillofacial surgery. Alternatively, dental emergencies may be classified according to clinical syndromes, an approach which will be followed in this paper. The most commonly encountered dental emergencies in small animal clinical practice include the puppy with the abnormal bite, the loose tooth, acute oral pain, the fractured tooth, the suspected tooth abscess and maxillofacial trauma.

THE PUPPY WITH THE ABNORMAL BITE Persistent deciduous teeth The exfoliation of deciduous teeth may be delayed (for a variety of reasons) and, in the extreme form, deciduous teeth may persist after the eruption of the permanent teeth. This is most commonly seen with the canines and incisors, especially in toy breeds. In most cases the permanent tooth develops normally, although the time and direction of eruption are influenced by the persistent deciduous tooth. Permanent incisors erupt immediately caudal to the persistent deciduous incisors. Persistent deciduous canines cause linguoversion of the erupting mandibular canines, and facial deviation of the maxillary canines. Furthermore, persistent deciduous teeth alter the gingival contour, which results in plaque and débris accumulating between the deciduous and permanent teeth.

“Rostral (anterior) crossbite” The terms “rostral crossbite” and “anterior crossbite” are commonly used for a malocclusion whereby the normal incisor relationship is reversed while the rest of the occlusion is normal. This usually involves all six incisors but can be more limited. In most cases a palatoversion of the maxillary incisors in present. When a crossbite is evident in the deciduous dentition, or when there is reason to anticipate that a crossbite will be present in the permanent dentition, the early extraction of the deciduous maxillary incisors is indicated. This is called inter-

ceptive orthodontics and is performed at 6 - 8 weeks. Similarly, the deciduous mandibular incisors can be removed if there is an indication that an overshot dentition may develop. The extraction does not stimulate jaw growth but just removes a potential mechanical barrier to normal development.

Linguoversion of the mandibular canines This syndrome is commonly also referred to as base-narrow canines. In this condition the mandibular canines stand in a more upright position than normal, thereby impinging on the gingiva between the maxillary third incisor and maxillary canine, or even the palatal mucosa. This is usually a dental malocclusion caused by a delayed exfoliation of the deciduous mandibular canines. The condition should be differentiated from an underdeveloped mandible (mandibular micrognathia), which is a skeletal malocclusion; the condition is characterized by a mandible that is too narrow and too short. The condition may also result in the mandibular canines traumatizing the soft tissues of the maxilla. Deciduous canines traumatizing the soft tissues of the maxilla should be removed as a matter of urgency, not only because of the associated pain and discomfort, but also to remove a potential mechanical barrier to normal development.

Wry bite Wry bite is a descriptive term used for a variety of malocclusion syndromes characterized by asymmetry of the head. These are skeletal malocclusions of genetic or traumatic origin. Severe maxillofacial trauma in puppies with disruption of the periosteum is a common cause of skeletal malocclusion, which often times is very difficult if not impossible to correct. As a general rule, maxillofacial trauma in puppies should be treated as conservatively as possible in order to avoid further trauma to the periosteum.

THE LOOSE TOOTH Increased mobility of teeth is most commonly caused by advanced periodontitis, associated with extensive loss of attachment. Occasionally, cases presenting with increased tooth mobility have an underlying neoplastic etiology.

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Med Vet, DVM, Dipl AVDC University of California, Davis - USA

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Acutely increased mobility, however, generally is associated with periodontal trauma. The following injuries to the periodontal tissues have been recognized: • Concussion • Subluxation • Intrusive luxation • Extrusive luxation • Lateral luxation • Exarticulation (or avulsion) Concussion and subluxation are very discrete injuries to the periodontal ligament that are rarely diagnosed in veterinary dentistry. Malocclusion and excessive orthodontic forces also result in this type of periodontal trauma. An intrusive luxation occurs when the tooth is forced into its alveolus. This is virtually only possible in the maxilla where a tooth can be pushed into the nasal cavity. In an extrusive luxation the tooth has loosened and come slightly out of the alveolus. The injury causing the tooth to come out completely is called an exarticulation (also often referred to as an avulsion). The most common type of periodontal trauma is a lateral luxation. This is a displacement of a tooth in a direction other than axially and is accompanied by comminution or fracture of the alveolar socket. Most cases of severe periodontal trauma are associated with disruption of the pulpal blood supply at the apex, resulting in pulpal necrosis. Luxated and exarticulated teeth can be repositioned and splinted. The prognosis is guarded because of the high incidence of root resorption. The success of reimplantation depends on the length of time the tooth has been out of the alveolus, the status of development of the apex and the viability of the periodontal ligament on the root surface.

ACUTE ORAL PAIN Acute oral pain may be due to a variety of conditions. An in depth discussion of these is beyond the scope of this lecture. In general, acute stomatitis is relatively uncommon, but acute exacerbations of chronic stomatitis, e.g. in the cat, are often seen. The immediate considerations in the management of these cases is pain and food intake. Hospitalizing and feeding these patients by means of a nasogastric, pharyngostomy or PEG tube for the first few days may be indicated. A patient should not be discharged until it can feed itself. The therapeutic plan may further include the following: • steroidal or non-steroidal anti-inflammatory agents • appropriate antibiotics • antiseptic oral rinses (e.g. chlorhexidine 0.05%) or gels • toothbrushing, if tolerated • dietary measures

THE FRACTURED TOOTH Classification Dental fractures are common in the dog and cat. The following classification, derived from the World Health Organization classification of dental fractures in man, has been proposed:

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Classification of dental fractures Enamel infraction or fracture

A chip fracture or crack of the enamel only

Uncomplicated crown fracture A fracture involving enamel and dentine, but not exposing the pulp Complicated crown fracture

A fracture involving enamel and dentine, and exposing the pulp

Uncomplicated crown-root fracture

A fracture involving enamel, dentine and cementum, but not exposing the pulp

Complicated crown-root fracture

A fracture involving enamel, dentine and cementum, and exposing the pulp

Root fracture

A fracture involving dentine, cementum and the pulp

Pathophysiology Enamel fractures and uncomplicated crown fractures are of little clinical importance in small animals. The dog is largely resistant to caries. The exposed dentine is initially sensitive, but this disappears after sclerosis of the dentinal tubules and formation of tertiary dentine in the pulp chamber. Dentine is somewhat rougher than enamel and thus facilitates plaque and calculus accumulation. Sharp fracture edges may cause soft tissue trauma and can be rounded-off if necessary. Crown-root fractures involve the periodontal ligament and may lead to periodontitis because of the altered gingival contour. A small fracture fragment and the overlying unsupported gingiva can be removed to restore a physiological contour. Many deep crown-root fractures lead to an irreversible periodontitis and are an indication for extraction. Complicated fractures cause pulp exposure. The pathophysiology associated with pulp exposure and subsequent pulp necrosis and periapical pathology will be described later. Root fractures of traumatic origin are occasionally seen; iatrogenic fractures are also common. A root tip left behind may become covered by bone and gingiva in the absence of infection. Alternatively pulp necrosis may take place and lead to sequestration. Pathological root fractures are common in the cat because of external odontoclastic resorption lesions associated with periodontitis. In most root fractures the coronal fragment is lost; however, traumatic root fracture with retention of the coronal fragment may occur. Clinical signs may include increased mobility and crown discolouration. The diagnosis is confirmed radiologically. The prognosis for the tooth depends on the level of the fracture: fractures in the coronal third of the root will not heal. Fractures further apically can heal by means of a dentino-cemental callus, a fibrous union or a fibro-osseous union.

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THE SUSPECTED TOOTH ABSCESS

Lip lacerations

A so-called tooth abscess usually refers to a periapical abscess or a periodontal abscess. A periodontal abscess is relatively rare. This condition may occur if pus accumulates in a deep periodontal pocket with a relatively healthy and tight gingival margin. Periapical pathology is more common. A wide variety of conditions may cause pulpitis, pulp necrosis and associated periapical pathology. One of the most common conditions is direct pulp exposure due to a complicated tooth fracture. Complicated dental fractures cause pulp exposure. Haemorrhage occurs and an acute pulpitis ensues which is very painful. Soon thereafter, bacterial invasion and obliteration of the blood vessels cause pulp necrosis. Blood vessel obliteration occurs because the narrow root canal does not allow for the swelling associated with an inflammatory reaction. A plug of desiccated débris forms at the coronal opening of the pulp chamber. At this stage the condition is no longer painful (because the nerve is necrotic) and it can go unnoticed for a considerable period of time. The end result of acute pulpitis is generally pulp necrosis. The combination of necrotic pulp and (a usually anaerobic) bacterial infection spreading through the apical delta gives rise to periapical pathology. Acute periapical periodontitis and abscessation appear to occur infrequently in animals. This condition is very painful and facial soft tissue swelling is evident. More commonly, a periapical granuloma develops. A periapical granuloma may remain quiescent for a considerable period of time. This lesion has the potential however, to give rise to a periapical abscess and associated severe pain and swelling. The acute flare-up of pain and swelling associated with chronic and thus far asymptomatic pulp necrosis and periapical pathology, is also known as a phoenix abscess. Periapical abscessation may also result in osteomyelitis of the surrounding jaw bone. In the dog and cat, a complicated fracture of the maxillary fourth premolar causes the occurrence of a typical syndrome. After the formation of the periapical granuloma, a sinus tract forms and breaks open ventral to the medial canthus of the eye. Whether this sinus tract involves the maxillary recess needs further investigation. Haematogenous pulpitis and complicated fractures involving other teeth in the region can cause the same syndrome. Sinus tracts originating from periapical granulomas involving other teeth may open into the nasal cavity and can cause a chronic nasal discharge, or they may break out in the oral cavity. A periapical granuloma is visible on radiograph as a well-circumscribed round radiolucent area, while a periapical abscess is poorly circumscribed. A periapical cyst is very radiolucent, wellcircumscribed and often has a mineralized lining. A very low-grade chronic response may give rise to an increase in periapical bone density, known as condensing osteitis.

Lip lacerations are commonly seen. Primary closure or early delayed primary closure, combined with careful débridement, is indicated. Closure is effected in two or three layers. The suture material of choice is fine atraumatic monofilament nylon or polypropylene for the skin, and synthetic absorbable material for the deeper layers and mucous membrane. An irregular defect may be converted to a wedge-shaped defect to facilitate a more aesthetic closure, especially a smooth mucocutaneous line. More involved techniques utilizing mucosa and skin flaps have been described for correcting extensive lip defects.

MAXILLOFACIAL TRAUMA Maxillofacial trauma in small animals commonly arises as a result of road traffic accidents or fighting. In some parts of the world gunshot wounds involving the head are also seen relatively frequently.

Avulsion of the lower lip is a common condition in the dog and cat, caused by a degloving injury. Bone exposure occurs and there is usually not enough soft tissue left on the mandible to allow conventional wound closure. After cleaning and débridement the soft tissue flap should be replaced and kept in contact with the bone using large horizontal mattress suture which are passed around the canine or incisor teeth. These are tied fairly loosely, avoiding further compromising the blood supply to the tissue flap, whilst still achieving approximation of the tissues. If the entire mandible is denuded more elaborate fixation techniques should be used.

Trauma to the tongue Trauma to the tongue is occasionally seen in small animals. Lingual trauma includes bite wounds, sharp penetrating foreign bodies, electric burns and elastic foreign bodies trapped at the root of the tongue. Lacerations are managed by primary closure or early delayed primary closure. In all instances the maximum amount of tongue tissue should be preserved. Healing is rapid because of the abundant blood supply.

MANDIBULAR FRACTURES Initial management The patient should be fully examined in accordance with accepted clinical practice regarding trauma cases. A mandibular fracture is usually an obvious lesion; a potential pitfall exists in that other less obvious but equally serious problems may go unnoticed. The pathophysiology of trauma to the head and its anaesthetic implications should be borne in mind when planning surgical repair of mandibular fractures. The diagnosis of a fracture of the mandible can usually be made by inspection and palpation. The ventral borders of both mandibles should be gently palpated for asymmetry and discontinuity. Some patients will permit gentle opening of the mouth. As most fractures are open to the oral cavity, the discontinuity in the dental row, gingival laceration and

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Avulsion of the lower lip

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even the fracture line are usually easily visible. The nature and extent of the fracture can be further assessed by gentle palpation once the patient is under anaesthesia prior to surgical treatment. Radiological examination is indicated to visualize the fracture site and to diagnose concomitant dental trauma. This should be done when the patient is anaesthetized and care should be taken to avoid causing additional soft tissue trauma. Fracture of the mandible is a most painful condition because of the inherent sensitivity of facial tissues in general; in addition, concurrent trauma to the mandibular alveolar nerve in the mandibular canal makes the condition particularly painful. The mandible is, contrary to many other bones in the body, a bone which can hardly be spared when traumatized; drinking, eating, swallowing and panting cause continuous movement at the fracture site. To lessen the patientâ&#x20AC;&#x2122;s discomfort and to prevent further damage to the soft tissues, the fracture should be temporarily reduced and immobilized as soon as possible. Gross reduction can be obtained by gentle palpation using the occlusion of the canine teeth as a guide. A simple tape muzzle is then applied to maintain reduction.

Principles The management of fractures of the mandible body should be aimed at the restoration of normal occlusion. It is therefore imperative that the occlusion is inspected and used to guide the surgical repair of mandibular fractures. Malalignment of the fracture fragments leads to malocclusion, which is of great clinical importance. Malocclusion with faulty interdigitation of teeth leads to abrasion of the teeth involved, periodontal trauma and loss of function, preventing normal mastication. The mandible is subject to continuous movement under

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normal circumstances and the rapid restoration of this function is an important goal in the management of mandibular fractures. Most mandible fractures in the dog are open to the oral cavity and inevitably contaminated. Removing devitalized tissue will enhance healing and may to a large extent prevent later complications. The surgical dĂŠbridement of soft tissues is usually limited to trimming irregular and frayed edges of the torn gingiva and oral mucosa. The dĂŠbridement of oral soft tissues should be very conservative as their blood supply and healing capacity are excellent. Small, loose pieces of bone should be removed if they do not contribute to the stability of the repaired fracture. If they are retained, it is important to preserve their soft tissue attachments and to ensure that they are rigidly fixed. In the presence of infection these small, loose pieces of bone may cause sequestration and necessitate subsequent surgical exploration and removal. It is common for an alveolus to be involved in the fracture line. If the tooth involved is luxated, it should be removed. If there is still enough healthy periodontal attachment, evidenced by the fact that the tooth is non-mobile, retention of the tooth is usually indicated as it will contribute to the stability of the fracture fixation. The presence of a tooth in the fracture line increases the incidence of infectious complications; however, the immediate removal of the tooth cannot reverse these effects. If a tooth involved in the fracture line is retained, it should be carefully monitored subsequently for any evidence of periodontal or endodontal pathology; appropriate treatment should be instituted as soon as either is recognized.

Key words Dental emergencies, emergency treatment, dentistry, dog, cat.

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An update on feline dentistry Frank Verstraete

Summary In addition to the dental diseases that affect all species, the oral pathology of cats includes some unique conditions. The pathogenesis of feline odontoclastic resorption lesions and oral inflammatory diseases, chronic gingivo-stomatitis in particular, is poorly understood. These diseases cause considerable pain and discomfort to the patient and the therapeutic options are limited.

ANATOMY The incisors in the cat are very small single-rooted teeth; their size increases from the first to the third incisor. The maxillary third incisor has a triangular cross-section and its apex is situated adjacent to the nasal cavity. The roots of the mandibular incisors are mesiodistally flattened. The canines are the largest teeth. The apex of the mandibular canine tooth is located lingual to the mental foramen. Only a thin bone plate is present between the root of the maxillary canine and the nasal cavity. The premolars in the cat are reduced in number and the numbering system may be confusing. The first premolar seen on the maxilla is actually the second premolar, a very small tooth which is usually single-rooted; double or two fused roots are occasionally seen. The next premolar is the third premolar; this tooth is usually two-rooted but a small third root on the palatal aspect is occasionally present. The large maxillary fourth premolar is similar to the dog, except that the distal root is considerably larger than the two mesial roots. Only two premolars are present on the mandible, namely the third and fourth. The mandibular first molar has two similar, large and sharp cusps. The mesial root of the mandibular first molar and, to a lesser extent, the third and fourth premolars lie in close proximity to the mandibular canal. The cat has one very small and largely non-functional two-rooted molar on the maxilla, placed transversely, distal and palatal to the fourth premolar.

MALOCCLUSION IN THE CAT Malocclusion in the cat used to be extremely rare. This can largely be attributed to the fact that a cat has a very pre-

cise centric anisognathic occlusion, allowing very little deviation from the normal. Recently however, the incidence of malocclusion in the cat has increased and this has been associated with the selective breeding of cats with more extreme skull types (e.g. Persian). The most common abnormality seen is a syndrome characterized by the presence of the mandibular canine tooth on the outside of the upper lip when the mouth is closed; usually only one tooth is involved. This occurs in extremely flatnosed brachycephalic breeds. This skeletal malocclusion is characterized by head asymmetry (wry bite) and exaggerated brachycephalism. The canine tooth rubbing against the upper lip causes the clinical problem.

PERIODONTAL DISEASE IN THE CAT Pathophysiology Periodontal disease in the cat is characterized by a number of unique features, compared to other species. Typical periodontal disease associated with plaque and calculus, similar to that found in other species, also occurs in the cat. In addition, inflammatory diseases of infectious origin would appear to play an important role in the pathogenesis of periodontal disease in the cat. Periodontal disease in the cat is also often associated with the occurrence of external odontoclastic resorption lesions. The nature of this association, if any, is unclear. The radiological signs of periodontitis in the cat may include expansion of the buccal bone plate overlying the canine teeth, which is not seen in other species.

Maintenance of oral health Daily toothbrushing is currently the best way to prevent periodontal disease. In order to be helpful, toothbrushing must be performed every day. Patient and owner compliance with toothbrushing is very limited in the cat. If daily brushing is not feasible, a few options are available. Treats coated with hexametaphosphate have been shown to reduce calculus accumulation on teeth by sequestering calcium in dogs. Similar products may be developed for cats. It should be noted that these products were shown to reduce calculus, not plaque. Cats may enjoy CET Forte Chews, made

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from freeze-dried fish. Be aware that the edible products may add a significant amount of calories to the pet’s diet, and regular feedings should be decreased to avoid obesity. Hill’s t/d diet is available for cats and can have a substantial effect on plaque and calculus accumulation. In cats t/d reduced plaque by 42% and calculus by 47% compared to Purina Cat Chow. Both diets were shown to be more effective than once weekly toothbrushing in reducing plaque and calculus. Chlorhexidine is a commonly utilized oral antiseptic rinse. Chlorhexidine gluconate is preferred to the diacetate form due to its higher residual activity and decreased tissue irritation. Chlorhexidine is an effective and non-irritating antiseptic at a concentration of 0.05%; higher concentrations, such as 0.12-0.20% used in most commercial preparations, may be irritating for cats. Alcohol-containing solutions should be avoided.

EXTERNAL AND INTERNAL ODONTOCLASTIC RESORPTION LESIONS

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Clinical presentation External and internal odontoclastic resorption lesions can be difficult to evaluate, both clinically and radiologically. Externally, lesions may be seen as the localized absence of dental substance. The lesions are usually filled with granulation tissue. The severity of the concomitant gingivitis is variable. Lesions can be diagnosed using a dental explorer. The lesions are usually very painful and even under anesthesia, jaw chattering often occurs when probing external FORL. Clinical examination alone tends to underestimate the incidence and severity of FORL compared to radiographic examination. Survey radiographs are indicated if there is any clinical suspicion of FORL, and for diagnosing internal odontoclastic resorption lesions. Lesions are visible as sharply defined radiolucent areas, externally most often at the cemento-enamel junction, and internally around the root canal or pulp chamber. The extent of FORL varies from superficial to deep; pulp involvement may occur in the latter. In an attempt at classification the following stages were proposed:

Classification of feline odontoclastic Resorption lesions

Pathophysiology Periodontitis in the cat is characterized by the occurrence of feline odontoclastic resorption lesions (FORL). The lesions mainly occur at or below the cemento-enamel junction, usually on the buccal aspect, on the mesial and distal edges or at the furcation; lesions may also develop further apically on the periodontal ligament. The exact pathogenesis of FORL has not been determined, but they are not carious lesions. Internal odontoclastic resorption lesions result from inflammation within the pulp. The lesions appear to occur most commonly in the canine teeth and may lead to disruption of all organized root structure. The etiology of odontoclastic resorption lesions is unclear. A local immune response and the release of biochemical components (e.g. cytokines) which attract odontoclasts offer a plausible explanation. An abnormal local and systemic calcium metabolism, e.g. a calcium-poor diet, may also play a role. Other dietary factors have not yet been identified, except that two studies showed that the acidic coating of dry cat food did not predispose the teeth to the development of FORL. Histopathologically, two stages are identifiable in the pathogenesis of FORL: an acute stage, with many odontoclasts on the surface of the excavated lacunae, and a reparative stage, with few odontoclasts on the dentinal surface and the deposition of bone-like or cementum-like material in the defects. External odontoclastic resorption lesions appear to be a recent phenomenon, with very few lesions found in skull collections dating prior to 1950. The current incidence in cats presented for veterinary or dental care can be as high as 67 %. The prevalence and number of affected teeth increase with increasing age. In most studies, the most commonly affected teeth were the maxillary fourth premolar and the mandibular premolars and molars.

Stage 1

Shallow cementum or enamel defects

Stage 2

Defects involving cementum or enamel, as well as dentin

Stage 3

Defects involving cementum or enamel, dentin and pulp

Stage 4

Severe loss of tooth structure, complete root resorption or root ankylosis

Treatment Properly performed periodontal treatment is indicated in all cases of external odontoclastic lesions associated with periodontitis. All the principles of periodontal treatment are applicable. In addition, particular attention should be paid to the dental examination in order to detect FORL. The treatment for these lesions remains highly controversial. Restoration using various materials such as glass-ionomer and fluoride treatment are currently practiced and advocated by some veterinary dentists. The rationale for the use of fluoride is to desensitize the exposed dentin and to strengthen the remaining tooth substance; this is extrapolated from the use of fluoride in man. There are no studies as to the effectiveness of this treatment in the cat. One author reported a 33 % success rate for glass-ionomer -restoration while others’ results were even more disappointing. Failure occurs as a result of progressive resorption alongside the restoration or new FORL. Restoration of subgingival lesions is technically very difficult even for experienced dentists. It may be scientifically more justifiable to treat very shallow lesions by subgingival curettage and root planing, and to extract teeth affected by deeper lesions. Extraction is

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ORAL INFLAMMATORY DISEASES “Feline stomatitis” Inflammatory conditions affecting the oral mucosa and gingiva of cats are commonly seen in practice. “Feline stomatitis” consists of a number of syndromes with a common presenting clinical symptom: inflammation of the gingiva and/or varying parts of the oral mucosa. This may result from abnormalities in local or systemic immunity. The pathways involved in regulation of the immune response are complex, and poorly understood in cats. Cats infected with the feline immunodeficiency virus (FIV) are commonly afflicted with severe periodontitis, gingivitis, and oral ulceration, suggesting that systemic and local immunity are vital to the maintenance of oral health. However, local immune responses may contribute to the development of feline lymphocytic-plasmacytic gingivitis-stomatitis complex, evidenced by the fact that affected cats often respond to immunosuppressive doses of corticosteroid.

Infectious agents in the oral cavity Many of the bacteria present in a normal feline oral cavity are pathogenic in other circumstances, such as Pasteurella multocida, the most common bacterium present in cat bite abscesses, but do not cause disease in a healthy mouth. Also, while non-resident bacteria may be present as secondary invaders following a primary insult, there are few instances of oral disease initiated by bacteria. Feline immunodeficiency virus (FIV) and feline calicivirus (FCV) are the most common infectious agents associated with oral inflammatory conditions in cats. These viruses may be shed in the saliva of infected cats, including asymptomatic carriers. Severe periodontal disease and gingivitis are commonly noted in FIV-infected cats, and chronic oral ulcerative conditions are also diagnosed in a higher percentage of FIV-infected cats than in non-infected cats. Feline calicivirus causes acute faucitis, and persistent oral carriage has been linked to chronic ulcerative-proliferative faucitis-stomatitis. Infection with feline herpesvirus (FHV) may result in ulcers of the tongue, palate, or nasal philtrum in addition to upper respiratory or ocular symptoms. Stress may precipi-

tate intermittent bouts of virus shedding into saliva and may lead to recurrent oral ulceration, though this has not been documented. The feline leukemia virus, though actively shed in saliva, is less often associated with oral disease than is FIV. Unlike FIV, a strong relationship between oral disease and infection with FeLV has not been demonstrated in clinical studies. However, FeLV-infected cats may have secondary oral infections as a result of generalized immunosuppression.

Feline lymphocytic-plasmacytic gingivitis-stomatitis complex The use of the non-specific term “stomatitis” suggests a single clinical presentation and a single cause, and should therefore be avoided. It is preferred to define lesions according to duration (acute or chronic), severity (mild, moderate, severe), physical characteristics (i.e., erythematous, edematous, ulcerative, proliferative, suppurative, fibrinous, vesicular, haemorrhagic), and location (gingivitis, buccal mucositis, faucitis, pharyngitis, glossitis, palatitis). The following clinical “syndromes” are commonly identified: (1) acute “marginal” gingivitis: inflammation mainly affecting the free gingiva, clinically evident as a red line, occurring most commonly in young cats. (2) Severe gingivitis with stomatitis: grossly obvious gingivitis extending across the mucogingival junction. (3) Severe stomatitis with gingivitis: severe inflammation of the glossopalatine folds (fauces), gingivitis present but less obvious. (4) Severe oropharyngitis (faucitis): severe inflammation of the caudal oral cavity and oropharynx, with ulceration or granulation. Affected cats may exhibit halitosis, ptyalism, dysphagia, pawing at the mouth, poor grooming, and weight loss. Lesions may be localized (e.g. to the marginal gingiva, fauces, or buccal mucosa), or generalized. Tissues may appear hyperaemic, edematous, proliferative, or ulcerated. Regardless of initiating cause, histopathology of these lesions often reveals deep infiltrates of lymphocytes, plasma cells, and monocytes, suggestive of chronic antigenic stimulation and resulting in the use of the term “lymphocytic-plasmacytic stomatitis”. A superficial layer of neutrophils is often present as well, indicative of ulceration and secondary infection. It is often difficult or impossible to identify the cause of these inflammatory lesions. Contributing factors may include infection with feline calicivirus (FCV), feline herpesvirus (FHV), feline immunodeficiency virus (FIV), and feline leukemia virus (FeLV). Purebred cats, especially Abyssinians, Siamese, Persians, Himalayans, and Burmese, may be predisposed. Periodontal disease and odontoclastic resorptive lesions are often present concomitantly. A complete diagnostic database should consist of a detailed history, thorough physical examination, dental examination (under anaesthesia if necessary), complete blood count, serum

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complicated by root resorption, which make the teeth prone to iatrogenic root fractures. Leaving fractured root tips behind was found to be acceptable in one recent study but is thought by others to perpetuate the problem. External odontoclastic resorption lesions in the reparative stage may result in ankylosis when located apical to the cemento-enamel junction. This makes an extraction procedure considerably more difficult. Asymptomatic ankylosis by itself is not an indication for extraction. Early internal odontoclastic resorption lesions can be treated endodontically. However, the lesions typically seen in the cat are usually advanced and are treated by extraction.

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biochemistry profile, urinalysis, systemic viral serology and local viral isolation, oral radiography, and histopathology of affected areas. Hyperglobulinemia is a common biochemical abnormality identified in cats with chronic gingivitis-stomatitis complex. Systemic diseases may present with primary oral signs and must be ruled out prior to initiating therapy. Uraemia is a common cause of painful oral ulcers in cats with renal failure. Although auto-immune diseases are less common in cats than in dogs, it is important to consider them when a feline patient presents with oral ulceration. Medical therapy has had limited success in the treatment of these conditions. Long-acting injectable corticosteroid (methylprednisolone acetate) is given every four to eight weeks and may result in significant improvement. However, benefits may be transient, and adverse side effects may occur (iatrogenic hyperadrenocorticism or diabetes mellitus). Orally administered corticosteroids (prednisone, prednisolone) are more difficult to administer but may have fewer adverse side effects. Antibiotics are often administered concurrently with corticosteroid therapy. Amoxycillin-clavulanic acid has an excellent spectrum against oral pathogens. It is available in a liquid form to improve patient acceptance. Clindamycin has a narrower spectrum but is also commonly used in practice for oral diseases. Surgical therapy is, at this time, the most consistently successful therapeutic approach to these cases. Extraction of premolar and molar teeth resulted in substantial improvement in 80% of treated cases in a recently published study. Refractory cases may respond to extraction of the remaining canines and incisors. Supportive treatment, ensuring adequate nutrition and hydration, and pain management are extremely important in these cases.

EXODONTICS IN THE CAT Because of the small size of the roots, root tip elevators should be used as dental elevators in the cat. These instruments should however, be used with great care, as they are very sharp and the bone plate between the nasal and oral cavity is very thin. Oronasal fistula formation is a possible sequel to the overzealous use of these instruments. External odontoclastic resorption lesions make dental

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extraction in the cat particularly difficult because of the high risk of root fractures. Root fractures with retention of the apical fragment may result in persistent pain and complications such as osteomyelitis of the alveolar bone. Leaving root tips behind may be acceptable in certain circumstances: e.g. half-resorbed root tips deeply embedded in bone or anaesthetic-risk patients. Leaving fractured root tips behind, in the absence of periodontal and endodontic pathology, was found to be acceptable in one recent study. Root tip fragments can be loosened and lifted out using root tip elevators or root tip picks (e.g. Heidbrink # 13/14 or Davis # 11 root tip elevator). Good lighting, irrigation and suction are essential for good visibility. If necessary, a mucogingival flap can be created and an alveolotomy performed in order to get access to and obtain good visualization of a root fragment. Alternatively small root tips can be drilled out under constant irrigation (â&#x20AC;&#x153;pulverization, atomizationâ&#x20AC;?); however, this technique can result in considerable iatrogenic trauma and is not recommended.

Key words Dentistry, oral disease, oral pathology, feline odontoclastic resorption lesion, chronic stomatitis, cat.

References HARVEY CE (1991) Oral inflammatory diseases in cats. Journal of the American Animal Hospital Association 27:585-591. HARVEY CE (1995) Feline oral pathology, diagnosis and management. In: Manual of Small Animal Dentistry (Eds. DA Crossley & S Penman) 2nd edn. British Small Animal Veterinary Association, Cheltenham: 129-138. HENNET P (1997) Chronic gingivo-stomatitis in cats: long-term follow-up of 30 cases treated by dental extractions. Journal of Veterinary Dentistry 14(1):15-21. LYON KF (1992) Subgingival odontoclastic resorptive lesions. Veterinary Clinics of North America: Small Animal Practice. 22(6):1417-1432. OKUDA A, HARVEY CE (1992) Etiopathogenesis of feline dental resorption lesions. Veterinary Clinics of North America: Small Animal Practice. 22(6):1385-1432. PEDERSEN NC (1992) Inflammatory oral cavity diseases of the cat. Veterinary Clinics of North America: Small Animal Practice 22(6):13231345. REUBEL GH, HOFFMAN DE, PEDERSEN NC (1992) Acute and chronic faucitis of domestic cats. Veterinary Clinics of North America: Small Animal Practice 22(6):1347-1360.

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Radiology: enhanced visualization of dental problems Frank Verstraete

Summary Dental radiographic equipment is easy to use and the techniques easy to master. Dental radiographs form an essential part of a comprehensive oral examination and may be taken as part of a full-mouth survey or as indicated by the clinical findings. The radiological findings are a key element in diagnostic and therapeutic decision-making. Furthermore radiography is indispensable to assess the quality of endodontic treatment.

technique of choice but it is difficult to obtain due to the shape of the oral cavity. When it is not possible to place the film parallel to the tooth and perpendicular to the X-ray beam, the bisecting angle technique is used. The X-ray beam is directed perpendicular to the line that bisects the angle formed by the film and the long axis of the tooth. In doing so the image obtained is neither elongated nor foreshortened.

Radiographic technique The use of proper dental radiographic equipment, films and technique is strongly recommended. Although diagnostic radiographs of dental conditions can be made using conventional radiographic equipment, the inconvenience of having to transport a patient to a separate radiography room may be an important factor influencing the decision whether to take radiographs or not. The radiological signs of early periodontal or periapical disease are subtle and can be missed if the positioning, exposure and developing are not optimal. Two main techniques are in use in dental radiography: the paralleling technique and the bisecting angle technique. In the paralleling technique the long axis of the tooth is parallel to the film and perpendicular to the X-ray beam. This is the

Figure 1 - The paralleling technique (left) and the bisecting angle technique (right).

DOG

CAT

The following table summarizes a recommended system for standardizing radiographic positioning, views and technique, suitable for full-mouth radiographic evaluation in the dog and cat:

View

Position

Technique

View

Position

Technique

maxillary I and C (occlusal)

intra-oral

bisecting angle

maxillary I and C

intra-oral (occlusal)

bisecting angle

caudal maxilla: P4 - M2

intra-oral

bisecting angle

maxilla: P2 - M1

extra-oral

parallel

rostral maxilla: P1 - P3

intra-oral

bisecting angle

mandibular I and C

intra-oral (occlusal)

bisecting angle

mandibular I and C

intra-oral (occlusal)

bisecting angle

mandible: P3 - M1

intra-oral

parallel

caudal mandible: P4 - M3

intra-oral

parallel

rostral mandible: P1 - P4

intra-oral

parallel

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Additional intra-oral bisecting angle views for the evaluation of the canine teeth are occasionally indicated. Slightly oblique views of the caudal maxilla are indicated to visualize the two mesial roots of the maxillary fourth premolars separately.

Indications Dental radiographs form an essential part of a comprehensive oral examination and radiological findings are a key element in dental decision-making. Full-mouth radiographs may be taken when the patient is first presented for dental treatment. Full-mouth radiographs of small animal patients presented for dental treatment are not routinely taken in practice, mainly because it is considered cost-prohibitive, and because it is not established practice to do so. An alternative approach is to radiograph those areas where one expects to find pathology, based on the visual oral examination and periodontal probing. The indications for elective dental radiography can be summarized as follows: (1) clinical signs of periodontal or endodontic disease; (2) prior to extraction, and post-extraction, if there is any suspicion of root fracture; (3) before, during and after endodontic procedures; (4) clinical staging of oral tumours; (5) maxillofacial trauma (root fractures, maxillofacial fractures, TMJ-problems); and (6) diagnosis of missing teeth.

Systematic evaluation of dental radiographs The following system is recommended for evaluating dental radiographs: (1) Technical quality: Are the films diagnostic? Errors in exposure or processing? Elongation or foreshortening? All teeth included? All apices included? (2) Normal anatomy: Deciduous or permanent dentition? Any teeth missing? Unerupted teeth? Anatomical variations (root dilaceration, fused roots, supernumerary roots, etc.)? Examples of normal anatomical structures which should not be mistaken for pathological changes include: the mandibular canal, mental foramen, infraorbital foramen, palatine fissure. (3) Periodontal evaluation: Follow the outline of each tooth and examine the periodontal ligament space for uniformity (space between the lamina dura of the alveolus and the cementum). Evaluate the alveolar bone crest and the trabecular bone interproximally and in the root furcations. (4) Endodontic evaluation: Compare the diameter of the pulp chambers and root canals. Examine the periapical region of each tooth for uniformity of bone density. (5) Other conditions: Presence of metabolic bone disease, ankylosis/resorption, tumours, root fractures, etc.

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Radiological signs of common dental problems Radiology is of great practical value for the early diagnosis of missing teeth in prospective show dogs. This can already be done in 9-12 week-old puppies. The absence of permanent tooth buds underneath the deciduous teeth indicate that these teeth will be missing in the permanent dentition. Adult patients with missing teeth are occasionally presented for certification that the tooth loss is due to trauma or periodontitis, and not to hypodontia. This is only possible shortly after the tooth loss has occurred when the empty alveolus has not yet been replaced by bone, or if a root fragment is visible. Although the diagnosis of periodontitis is primarily a clinical diagnosis, radiology can be used to document and assess the extent of the lesions. Radiological signs of periodontitis may include: (1) rounding of the cemento-enamel junction; (2) widening of the periodontal space; (3) loss of integrity of the lamina dura; (4) osteolysis of the supporting bone; and (5) resorption of the alveolar crest. If the alveolar crest over a number of teeth has receded parallel to the level of the cemento-enamel junctions, the term horizontal bone loss is used. When the bone loss is irregular and the alveolar crest is no longer parallel to the cemento-enamel junctions, the condition is referred to as vertical bone loss; this condition is usually confined to one or two roots. Resorption of the alveolar crest at the furcation occurs with furcation involvement and is an important finding. Periodontitis in the cat is characterized by the occurrence of odontoclastic resorption lesions. These lesions present radiologically as radiolucent areas, most often at the cementoenamel junction. Radiographs are useful for determining the depth of the lesions and for demonstrating lesions in the furcation area. Pulpal pathology will usually be clinically evident because of obvious pulp exposure or crown discolouration. Radiology is used to prior to endodontic therapy (1) to assess the morphology of the pulp chamber and root canal, and (2) to determine the presence of periapical pathology. Furthermore radiology is indispensable to assess the quality of a root canal treatment. Periapical pathology starts as a periapical periodontitis, evidenced by a discrete widening of the periodontal space around the apex. Eventually a periapical granuloma or abscess forms which is seen as a round radiolucent area around the root tip. This is the lesion that may give rise to a dental sinus tract. The injuries to the periodontal tissues that have been recognized and that can be radiographically demonstrated, include: (1) concussion; (2) subluxation; (3) intrusive luxation; (4) extrusive luxation; (5) lateral luxation; and (6) exarticulation. Dental fractures are diagnosed on a clinical basis, but radiology is useful in determining the extent of the subgingival fracture line in crown-root fractures and the diagnosis of root fractures. The extent of the subgingival fracture line in crown-root fractures is clinically very important and can be assessed radiographically. A root fracture is a fracture involving dentine and cementum. Traumatic root fractures with the coronal fragment still in place are occasionally

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Radiology should be used if there is any indication that this complication might have taken place during the extraction procedure.

Key words Dental radiography, dental radiology, intra-oral radiography, intra-oral radiology, dog, cat.

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seen. Root fractures can occur in the cat as a result of extensive odontoclastic resorption lesions. Pre-extraction radiographs of teeth to be removed are indicated to confirm the diagnosis, to allow visualization of the root morphology and to ascertain the presence of root resorption or root ankylosis. Post-extraction radiographs are recommended to confirm that no root tips were left behind and to document possible alveolar bone injury due to the extraction procedure.

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Early diagnosis of canine hip dysplasia (CHD) Aldo Vezzoni Med Vet, Dipl ECVS Private Practitioner, Cremona - Italy

Canine Hip Dysplasia is an inherited, developmental condition that involves a lack of conformity between the femoral head and acetabulum and invariably leads to osteoarthritis.2 Laxity of the hip joint has been recognized as a constant feature of CHD and it appears to have an hereditary basis too.2,3 CHD, in contrast to a similar disease in human beings, cannot be diagnosed at birth as it develops during the growth phase as a consequence of several factors leading to joint laxity and incongruity like collagen disease, imbalance between hip adductor and abductor muscles, sloped orientation of the acetabular roof, overweight. 2,3 Hip dysplasia is a dynamic process and all the aspects of the disease depend on the time in which it is evaluated. Generally it is possible to separate acetabular hip dyplasia from femoral hip dysplasia, both leading to hip laxity and joint degeneration.7 Most cases of CHD involve acetabular hip dysplasia which is characterized by excessive slope of the dorsal rim of the acetabulum and its secondary osteoarthritic changes.7 This excessive slope could be caused during growth by an insufficient magnitude or incorrect direction of forces pushing the femoral head into the developing acetabulum which becomes shallow.7 During weight bearing the femoral head is laterally deviated by the inclined plane of the sloped dorsal acetabular rim stretching the joint capsule which becomes inflammed and causing microfractures of the cartilagineous labium. Femoral hip dysplasia is characterized by abnormalities in the femoral neck length, inclination and anteversion which lead to uneven loading of the articular surfaces, joint incongruency and joint capsule stretching.5,7 Clinical signs of CHD can be seen as early as at 5 to 6 months of age in severe cases or in the mature age according to the physical activity and to the degree of degenerative joint disease developed.2,7 In dogs the disease can be detected radiographically when they are between 4 and 8 months old although in some individuals the disease is not evident radiographically until they are 12 to 24 months old2,7,12 Combining a physical orthopaedic evaluation and a dynamic radiographic study it is possible to anticipate the diagnosis of CHD in every susceptible dog at the age of 6 months which is very useful for dog selection in controlled breeding programs; it is also a good opportunity to assess the patient for future hip problems according to the ownerâ&#x20AC;&#x2122;s expectations for performance and to provide the possible more appropriate conservative or surgical treatments.

Physical orthopaedic hip evaluation at 6 months Gait observation The dog is observed from behind while walking, looking at the distance between the hind paws; in the base normal walking the paws are touching the ground perpendicularly to the hips, while the dysplastic dog walks passing from base narrow to base wide.7 With base wide the hips are reduced by the active contraction of the abductor and rotators muscles and the dog must walk base wide to maintain the hips reduced, particularly when climbing stairs or before jumping, but with their fatigue the hips reluxates causing the dog to walk base narrow.7 When walking base narrow the dog is showing discomfort and to reduce it the dog loads more the front legs and flexes the back. While running, the dysplastic dog needs to distribute the hind loading on both legs simoultaneously for better comfort and thereafter the hind feet are placed close and are used toghether, with a â&#x20AC;&#x153;bunny hoppingâ&#x20AC;? gait.7 The stand test is performed to evaluate the ability of the dog to stand on its hind legs only and to ascertain the possibility of the hip joints to fully extend in loading position without pain; the normal dog has no difficulty to stand in an erect position while its owner is holding its front legs; the dysplastic dog will refuse this position or will stand up with discomfort keeping the back and hips in flexion and staying away with the pelvis, as the standing position is stressing the inflammed and streched joint capsule.7 Physical examination without anaesthesia The physical examination should demonstrate pain in the hip joint and that lameness is caused by hip problems. Passive movements of the hind legs that would stretch the hip joint capsule will elicit a positive response from the patient when inflammation is present; with repeated tearing of the joint capsule when the femoral head subluxates during weight bearing, inflammation and synovitis will develop. To stress the joint capsule the hip is abducted, externally rotated, and extended simultaneously.7 Negative response from the patient is indifference, while positive response is pain and discomfort manifested by vocalization or aggressive behaviour. The same type of reactions can be elicited by testing the hip for subluxation pushing the proximal femur laterally and the ilium medially.7

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Physical examination with anaesthesia In the anesthetized dog it is possible to evaluate the stability of the femoral head in the acetabulum, the amount of joint laxity and the features of head subluxation if present. When the joint is stable it is possible to perform passive movements in full range without causing any feeling of subluxation. When joint laxity is present, the femoral head is allowed to translate dorsally with axial compression and hip abduction will cause the Ortolani sign, a characteristic “clunk” caused by the femoral head returning into the acetabulum, while hip adduction will cause the Barlow sign created by the femoral head slipping out of the acetabulum.4,7 It is possible to measure and evaluate the angles at which subluxation and reduction occur to obtain reference values. The dog is positioned in dorsal recumbency, with the pelvis parallel to the table and the sagittal plane being vertical; the stifle of the leg being examined is brought in vertical position without hip flexion and extension.4,7 Then slight axial femoral compression will cause hip subluxation if joint laxity is present and the operator will notice a positive Barlow sign feeling the femoral head slipping outside the acetabulum for a certain amount proportional to the amount of joint laxity.4,7 The hip is then abducted slowly until the femoral head returns into the acetabulum, and the characteristic “clunk” is perceived producing the Ortolani sign; the inclination of the femur relative to the sagittal plane when the reduction occurs is measured as the angle of reduction (AR).4,7 The hip is then slowly adducted until the femoral head begins to subluxate

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producing the Barlow sign; the inclination of the femur relative to the sagittal plane when the subluxation occurs is measured as the angle of subluxation (AS).4,7 The AS has a negative value if subluxation occurs when the distal femur is medial to the sagittal plane, and positive value if subluxation occurs when the distal femur is lateral to the sagittal plane These measurements are repeated until consistent results are obtained. The same procedure is followed in the other hip. Two angles, AR/AS, are measured and recorded for each hip. To measure these angles it is possible to use a standard arthrogoniometer or the Canine Eletronic Goniometer designed by Slocum for this purpose.7 The AR is indicative of joint capsule laxity: the greater the laxity, more the femoral head subluxates, higher the AR.7 Higher the AR, greater the “clunk” that is perceived, greater the stretching of the capsule. In normal hips, without any joint laxity, the AR is not detectable, as it isn’t in cronic hip dysplasia with thickened joint capsule. In tolerable joint laxity as it is present in several dogs that will not develop hip dysplasia, the AR range between 10° to 25°. AR higher than 25° is indicative of excessive joint laxity that could lead to degenerative joint disease. The AS is indicative of the dorsal acetabular rim (DAR) slope and of acetabular filling: the DAR slope is the inclination of the weight bearing dorsal part of the acetabulum.7 It should be almost perpendicular to the direction of the weight bearing forces to be perfectly functional; in normal dogs the slope is no more than 7.5° from a line perpendicular to the long axis of the pelvis.7 If the DAR slope is more than 7.5° it will act as an inclined plane dividing the loading forces in two components, one vertical against the acetabular roof and one lateral stretching the joint capsule. Higher the DAR slope, higher the AS at which the femoral head can translate laterally to rest in the joint capsule. Acetabular filling by osteophytes and thickened round ligament also cause an increase of the AS.7 In normal dogs, without any joint laxity, the AS is not detectable. In tolerable joint laxity the AS should have a negative to 5° positive value. DAR slope between 8° to 10° and AS between 5° and 10° are predictive of light hip dysplasia. DAR slope higher than 10° and AS higher than 10° are predictive of moderate to severe hip dysplasia. In some normal puppies undergoing rapid growth between 4 and 6 months of age, the adductor muscle mass overpowers the abductor muscles and the axial femoral force is directed lateral to the DAR, against the joint capsule which stretches and became lax.7 As a result of this temporary muscular imbalance the AR is increased as it is the radiographic measurable joint laxity, while the DAR slope is normal and the AS is 0° or negative. Such joints can be lax without being pathologic and without any arthrotic changes and if not damaged by excessive exercise during the growing time will appear normal at 12-18 months of age.7

Static and dynamic radiographic hip study at 6 months Using orthogonal views, lateral, ventrodorsal and anteroposterior, a three dimensional study of the hip can be done to evaluate the bone morphology of both pelvis and femur; using a distraction device to push the femoral heads apart, a

dynamic evaluation of joint laxity is performed. Because correct positioning and muscle relaxation are essential to run this study, the dog is anesthetized. Standard ventrodorsal view. To evaluate the joint congruity the pelvis positioning should be simmetric and the femurs should be parallel, well extended and inward rotated to have the patella in the center of the femoral troclea. The center of the femoral heads should be medial to the dorsal acetabular rim indicating at least 50% coverage.8 Any tilting of the pelvis would alter the percentage of head appearing covered by the acetabulum. The congruency between the craniolateral acetabular rim and the femoral head is evaluated to identify any flattening or cranial curvature of the craniolateral acetabular rim.8 The Norberg angle should be at least 105째. In this position any valgus or varus deviation of the femoral neck is recognized, according the femoral positioning is correct. Any sign of osteoarthritis is identified examining the craniolateral acetabular rim, the dorsal acetabular rim, the femoral head and neck. Standard frog view. In this position the femurs are flexed and slightly abducted and the femoral heads are pushed in the acetabula. In a normal joint the articular rim should be uniform and thin; any filling of the acetabular fossa caused by a permanently displaced femoral head or hypertrophied teres ligament will widen the articular rim.8 In this position the first osteophyte formation can be seen on the femoral neck as a spur between the head and the greater trochanter. Lateral view. This position is useful to evaluate the lumbo-sacral joint to differentiate other problems like diskospondilitis, spondilarthosis, cauda equina compression, OCD of the sacral proximal endplate; it is also useful to evaluate the femoral neck anteversion. Dorsal Acetabular Rim view (DAR). Described by B.Slocum in 1990 this radiographic view is the most informative to evaluate the integrity and the slope of the dorsal acetabular rim. 6 The dog is placed in sternal recumbency with the hind legs pulled cranially to rest along the thorax. 6,8 A circumferential belt holds the stifles against the torso and 10 cm elevation of the hocks provides hamstring tension that causes enough rotation of the pelvis to allow the x-ray beam to pass through its longitudinal axis.6,8 With this view it is possible to see and evaluate the weight bearing portion of the acetabulum in cross section. In normal

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dogs the lateral aspect of the DAR is pointed and its slope is no more than 7.5째 from a line perpendicular to the long axis of the pelvis.8 The femoral head is well seated in the acetabulum and is well covered by the DAR. In the dysplastic dog the slope of the DAR is increased to 20째 or more and its lateral aspect is rounded to blunted, the femoral head moves dorsally and laterally along the inclined plane of the sloped DAR and osteophyte formation can be seen on the lateral aspect of DAR and filling the acetabulum.8 Distraction view. Several Authors suggested the usefulness of stress radiographs of the hip to evaluate the joint laxity, but G.Smith and colleagues at the University of Pennsilvania in 1990 described an improved method both to distract the joint and to calculate its laxity. 12 With this distraction technique the hip is held in neutral position to avoid the twisting of joint capsule that would limit the distraction effect; to calculate the joint laxity he described the distraction index (DI) which is calculated by dividing the measured distance between the femoral head center and acetabular center by the radius of the femoral head.12 This yields a unitless variable that ranges from 0 to approximately 1.12 A hip having an index of 0 is tightly compressed in its congruent position, and a hip having an index of 1 has little to no acetabular coverage of the femoral head (ie, joint luxation). 12 A DI of 0.30 is considered to be the dividing line between normal hips and hips predisposed to hip dysplasia.2,12,13 Some dogs with a DI greater than 0.3 could not develop hip dysplasia if the joint laxity is caused by a muscular imbalance between the abductors and adductors only and it is not dependant by an excessive slope

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of DAR.2,8 Some dogs with hip dysplasia have a DI less than 0.3 because capsular fibrosis, following the inflammatory arthritis, limits femoral head luxation. In a study conducted by R. Badertscher at the University of Georgia in 1977 using the half-axial position to improve the radiographic visualization of subluxation in canine hip dysplasia, results similar to the ones described later by G.Smith were found.1 As this procedure was simplest and quicker providing reliable results, we adopted his method since 1994, only improving the device used to distract the hips. The dog is positioned ventrodorsally with the femurs at approximately 45° to the table top and the tibiae parallel to the plane of the table surface.1 A teflon table-device 2 cm thick, 5 to 12 cm width and 50 cm long, with a S shape to better adapt to the pubis area, with an hinged base to keep it in contact and parallel to the table was placed on the ventral surface of the pelvis; applying pressure to the medial aspects of the proximal femurs through the hand held tibiae resulted in the fulcrum subluxating the femoral heads from the acatabula.1 To compensate for the superimposed muscle mass an increase of 10 KvP was necessary for adequate tissue penetration.1 In our experience the 45° of hip flexion doesn’t cause hip joint capsule twisting in such an extent to limit the complete hip distraction that is obtained with the hip in neutral position, as consistent results were obtained in the same dogs with both positions.

Dog selection in controlled breeding programmes With the physical orthopaedic evaluation and the radiographic findings at 6 months of age it is possible to detect an already established CHD and to advise the breeder not to

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select that dog. But the most important result is to predict the probability that a dog without clinical signs and without radiographic evidence of CHD in the standard ventrodorsal view at 6 months of age would have normal or dysplastic hip joint at 1 year of age and later. The key points to predict the evolution of an apparently normal hip joint at 6 months of age are the evaluation of the reduction and subluxation angles measured in the anesthetized dog, the distraction index measured in the distracted ventrodorsal radiographic view and the slope of the DAR view. - In all breeds, if the reduction and subluxation angles are not detectable, the DI is < 0.3 and the DAR is < 7.5° the probability that the dog will not develop hip dysplasia is very high. - In all breeds, if the reduction angle (AR) is < 20°, the subluxation angle (AS) is < 5°, the DI is between 0.3 and 0.4 and the DAR slope is 8° to 10° the probability that the dog will develop borderline or light hip dysplasia is high. - In all breeds, if the reduction angle (AR) is > 20°, the subluxation angle (AS) is > 5°, the DI is between 0.3 and 0.7 and the DAR slope is > 10° the probability that the dog will develop moderate to severe hip dysplasia is high. - In rapid growth breeds if the reduction angle (AR) is up to 30°, the subluxation angle (AS) is up to 5°, the DI is between 0.3 and 0.6 and the DAR slope is < 7.5° (normal) the probability that the dog will not develop hip dysplasia is good, but that dog needs a strict nutrition and exercise control.

Treatment planning When hip dyplasia is diagnosed at an early age it is possible to alter the progression of the disease with appropriate treatments, before osteoarthrosis prevents successful results. The window of opportunity to correct the developing hip dysplasia by surgical treatments is limited and it is lost if cartilage damage, dorsal acetabular rim microfractures and acetabular filling occurs.7 Under these circumstances the attending veterinarian that underestimates the problem would loose the opportunity to have the dog treated and his hip salvaged before arthrosis will develop.7 Particularly when the expectations by the owner on the functional aptitude of the dog are high it is essential to consider and to advise a prophylactic treatment. The surgical options that are available to correct or to limit the developing hip dysplasia in the growing dog are: - triple pelvic osteotomy; the acetabular segment of the ilium is outward rotated along its longitudinal axis to increase the coverage of the femoral head and hip joint congruity. The technique described by Slocum is the most reliable;10 this surgical treatment is indicated in dogs 5 to 12 months old, with no or minimal signs of osteoarthosis, joint subluxation, AR between 20° and 40°, AS between 10° and 20°, DAR slope between 10° and 30°.7 The degree of acetabular rotation, i.e. the degree of torsion of the canine pelvic ostotomy plate (CPOP), is determined according to the DAR slope, avoiding excessive correction that would limit the abduction of the leg.7 After correction the DAR slope shoul be 0°. With proper indication, the most successful degree of cor-

rection is 20°; with this correction there is no impingement between the dorsal acetabular rim and the femoral neck. The maximum possible correction without excessively altering the relationship between the femoral neck and the dorsal acetabular rim is 30°. When subluxation is still possible after a 20° or 30° correction, then a femoral neck lenghtening procedure in adjunct should be performed.7,9

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mation of the proximal femur with anteversion and valgus deviation of the femoral neck, being the DAR slope normal.5 In the mature dog, when the degenerative joint disease has already established, beside the conservative treatment with NSAID drugs, weight and exercise control, the surgical options that are available are: - total hip replacement; both the acetabulum and the femoral head are substituted with implants to allow a free and painless joint motion. Several techniques are used in dogs, with cemented and not-cemented prosthesis, with excellent functional results reported. - head and neck ostectomy; the femoral head and neck are excised to eliminate the contact between the bone surfaces of the diseased joint components and to allow formation of a fibrous pseudoarthrosis with a synovial membrane. This technique is considered a salvage procedure14 with limited functional results and it could be indicated when other techniques are not possible and when functional demand is limited.

References - femoral neck lenghtening the femoral neck length is increased by a diverging osteotomy of the proximal femoral methaphysis, to increase the proximal femoral lever arm and the medially directed force produced by the internal and external hip rotators muscles; this procedure is aimed at eliminating the amount of joint laxity evidenced by the distraction index in the stressed radiographic view. This technique was described by Slocum and it is indicated as a sole procedure in dogs with excessive joint laxity (DI between 30° and 70°) and a DAR slope less than 10°, in dogs with a short femoral neck like Akita, Chow and several molossoid breeds;9 it is also indicated in adjunct to triple pelvic osteotomy when an excessive joint laxity is evidenced by the DI (between 40° and 75°) to allow the application of a lesser degree of acetabular torsion; this avoids the necessity of overrotatong the acetabular segment in patients with excessive joint capsule laxity.7,9 - dorsal rim acetabuloplasty; the dorsal acetabular rim is increased by a bone graft harvested from the ilium wings with a bone guage and applied between the joint capsule and the deep gluteal muscle, activating the osteointegration of the graft by drilling several holes in the dorsal acetabular rim. This technique was described by Slocum and it is indicated in severly subluxated and arthosic hips, when the TPO is no more indicated, with DI up to 1.0, AS up to 20°-30°, DAR slope between 20° and 40°, acetabular filling, ostephytes on the dorsolateral acetabular rim and on the femoral neck, and cartilage eburneation.11 - intertrochanteric ostectomy: the direction of the femoral neck is modified from valgus to varus and from anteversion to normoversion with and intertrochanteric osteotomy and the removal of a wedge of bone. This technique was described by Prieur and it is indicated in dogs with hip joint subluxation caused by a malfor-

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Badertscher RR: The half-axial position: improved radiographic visualization of subluxation in canine hip dysplasia, MS Thesys, Athens, Georgia, 1977. Lust G: An overview of the pathogenesis of canine hip dysplasia, J Am Vet Med Ass 210- 10:1443, 1997. Madsen JS: The joint capsule and joint laxity in dogs with hip dysplasia. J Am Vet Med Ass 210- 10:1463, 1997. Piermattei DL, Flo GL: Brinker, Piermattei, and Flo’s Handbook of Small Animal Orthopedics and Fracture Repair, Philadelphia, 1997, WB Saunders, 441. Prieur WD: Intertrochanteric Osteotomy. In Bojrab MJ, Ellison GW, Slocum B, editors: Current Techniques in Small Animal Surgery, Philadelphia, 1998, WB Saunders, pp 1165-1168. Slocum B, Devine TM: Dorsal acetabular rim radiographic view for the evaluation of the canine hip. J Am An Hosp Assoc 26:289, 1990. Slocum B & Devine Slocum T: Hip: Diagnostic Tests. In Bojrab MJ, Ellison GW, Slocum B, editors: Current Techniques in Small Animal Surgery, Philadelphia, 1998, WB Saunders, pp 1127-1145. Slocum B & Devine Slocum T: Radiographic Characteristics of Hip Dysplasia. In Bojrab MJ, Ellison GW, Slocum B, editors: Current Techniques in Small Animal Surgery, Philadelphia, 1998, WB Saunders, pp 1145-1151. Slocum B & Devine Slocum T: Femoral Neck Lengthening. In Bojrab MJ, Ellison GW, Slocum B, editors: Current Techniques in Small Animal Surgery, Philadelphia, 1998, WB Saunders, pp 1154-1159 Slocum B & Devine Slocum T: Pelvic Osteotomy. In Bojrab MJ, Ellison GW, Slocum B, editors: Current Techniques in Small Animal Surgery, Philadelphia, 1998, WB Saunders, pp 1159-1165. Slocum B & Devine Slocum T: DARthroplasty. In Bojrab MJ, Ellison GW, Slocum B, editors: Current Techniques in Small Animal Surgery, Philadelphia, 1998, WB Saunders, pp 1168-1170. Smith GK, Biery DN, Gregor TP: New concepts of coxofemoral joint stability and the development of a clinical stress-radiographic method for quantitating hip joint laxity in the dog. J Am Vet Med Ass 196:5970, 1990. Smith GK, Gregor TP, Rhodes WH, et al.: Coxofemoral joint laxity from distraction radiography and its contemporaneous and prospective correlation with laxity, subjective score, and evidence for degenerative joint disease from conventional hip-extended radiography in dogs. Am J Vet Res 54:1021, 1993. Vasseur PB: Femoral Head and Neck Ostectomy. In Bojrab MJ, Ellison GW, Slocum B, editors: Current Techniques in Small Animal Surgery, Philadelphia, 1998, WB Saunders, pp 1170-1175.

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New material and new implants in bone internal fixation Tubular external fixator, Pc-Fix, Maxillofacial mini plate

C. Von Werthern DVM, Dipl ECVS Veterinar-Chirurgische Klinik der Universitat Zurich - Switzerland

Four new implants for internal fracture fixation are presented. All implants except the external fixator are developed by the AO Davos, Switzerland. These implants were applied on the cats and dogs at the small animal surgery department of the University of Zurich. The PC-fix (point contact) is a new bone plate, which has only point contact with the bone and is fixed with monocortical selftapping screws. The 3,5 mm plate has used for fracture fixation of 47 long bone fractures in dogs. The plate is easy to apply and reduces operation time. Compared to a dynamic compression plate bone healing time is reduced to 38% and fracture healing is superior. The tubular external fixator has been developed for fracture fixation of distal extremities in humans. This fixator was applied to 28 fractures of small animals less than 5 kg body weight. Advantages compared to other external fixator systems is its low weight and price and the possibility of placing several Kirschner wires in very close proximity to each other. A special indication was therefore distal radius /ulnar fractures in toy breed dogs. A mini titanium maxillofacial plate, smaller than the AO mini plate, was used for fixation of mandibular fractures in cats and phalangeal fractures in cats and dogs. With the cutable mini plate and the selftapping 1 mm screws osteosynthesis of smallest bone fragments is now possible. A human titanium arthrodesis plate is introduced. It has been used for panarthrodesis of the carpus and the tarsus with dorsal application in dogs. It is a LC-DC plate with a special design that allows insertion of 2,7 mm screws at the distal end and 3,5 mm screws at the proximal end. The special developed profile of the plate is reinforced at the stress site over the joint.

erated with this new bone plate and were retrospectively investigated.

Material and methods The PC-fix is a bone plate which has only a point contact with the bone (Fig. 1). This is achieved by a special design of the contact area of the plate with the bone. Multiple arches leave space under the plate for vascularity and callus formation during fracture healing. The PC-fix is fixed to the bone with monocortical screws. Special screws with a conical head which locks into a complementary hole of the plate are used (Fig.1). Deformation of the holes is avoided during contouring using a hole to hole bending. The screws are selftapping and there is only one standard lenght. In contrast to a dynamic compression plate (DCP) these screws can only be inserted in a predeterminated 90o angle to the axis of the plate. The fixed angle between the screw and the plate adds stability to the plate-bone unit. Because external fixator have the same mechanical principle, the PC-fix can be regarded as an internal fixator. At the small animal surgery department of the University of Zurich the 3.5 mm PC-fix was applied to 47 long bone fractures in dogs. Median weight of the dogs was 28.4 kg bodyweight, the average age was 38 months. The 47 longbone diaphyseal fractures were classified as transvers (n = 11), oblique (n = 21), spiral (n = 5) and mildly comminuted (n = 4) or severly comminuted (n = 4). Two revisions had been treated with

1. The PC-fix Introduction The name PC-fix stands for point contact internal fixator and is a new bone plate for fracture fixation. It has been developed by the AO Davos, Switzerland (TEPIC et al., 1997). At the small animal surgery department of the University of Z端rich 47 dogs with long bone fractures have been op-

Figure 1 - Design of the PC-fix plate.

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a PC-fix (1 malunion, 1 osteomyelitis). 18 patients had open fractures. An average plate length of 10 holes with an average screw number of 6 screws were used. While in the beginning of this study the PC-Fix was used only in neutralisation function, during the last 18 months we applied the PC-fix also in higher comminuted fractures with buttress function. This was achieved by means of double bone plating (n = 5).

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2. Tubular external fixator (F.E.S.S.A.): Application in small dogs and cats1 The tubular external fixator was designed by the french military for temporary and permanent fixation of fractures of the extremities in humans. At the small animal surgery department of the University of Zurich we applied the tubular external fixator especially in the fracture stabilisation of dogs less than 5 kg body weight and cats (REICHLER et al., 1997).

Results Material and methods All fractures except three healed without complications. Two fracture fixation collapsed due pull out of the screws. One fracture repair collaps because the plate broke. Time of implant removal was on average 3.5 months.

Discussion Atraumatic soft tissues handling in fracture treatment is a basic principle for biological osteosynthesis. Healing of a fractured bone relies on the soft tissue surrounding the fracture which initiates callus formation. Internal fixation of the fracture should add as little soft tissue damage as possible to achieve an umcomplicated and fast bone healing. The design of the new PC-fix plate is based on this concept. The plate is layed only with point contact on the periost of the bone. This leaves space under the plate for vascularity and callus formation. The PC-fix is hold in place by the threads of the screws and the stable 900 angle determinated between the screws and the plate (Fig. 1). The screws do not press the plate on the bone, as in DC-plate application, which prevents the development of implant-related cortical necrosis under the plate. A complete different screw design allows beside monocortical application a smaller number of screws for fracture fixation (6 average). Selftapping screws reduce the operation time and the instrumental equipment. Monocortical application minimises damage to peri- and endosteal bloodsupply. This biological concept of the PC-fix resulted in a 38% shorter healing time (SAVOLDELLI, 1995) and a superior healing of fractured bone compared to conventional DCplate application (TEPIC, 1997). The PC-fix concept is promissing, but smaller plate sizes for application in cats and smaller dogs would be appreciable. Different shapes of PC-fix plates for fixation of metaphyseal and periarticular fractures could be developed. Longer screws for metaphyseal application are needed. The price of the implants should be reduced for their use in veterinary medicine.

References Tepic S, AR Remiger, K Morikawa, SM Perren (1997). Strength recovery in fractured sheep tibia treated with a plate or an internal fixator: an experimental study with two year follow up. J Ortho Trauma 11(1): 14 - 23. Savoldelli D, PM Montavon (1995). Clinical handling:small animals. Injury 26: 47 - 50.

The tubular external fixator (Fig. 2) consists of a stainless steel tube that is available in different sizes (6, 8, 10 mm diameter). Six and 8 mm tubes were applied. The tube has two axial aligned rows of predrilled holes perpendicular to each other (Fig. 2). One line of holes is for introduction of the Kirschner wires (K-wires), the holes perpendicular to these are threaded and provided with little screws for fixation of the K-wires. In the 6 mm tube K-wires of 2 mm or smaller diameter, in the 8 mm tube wires of 2,5 mm or smaller can be inserted. Only threaded K-wires were used and inserted by a low speed power drill.

Figure 2 - Tubular external fixator (FESSA).

The tubular external fixator has been applied to 6 toy breed dogs with distal radius-/ulna fractures and 20 cats with various fractures. All patients were less than 5 kg body weight. The average weight of the dogs was 2,7 kg and that of the cats 3,2 kg.

COVELY-SMV, Z.I. Lyon-Nord, 69730 Genay, France.

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Eleven out of 20 fractures in cats were open fractures, most of them severely comminuted. All fractures were reduced closed or with a minimal approach to the fracture site. In all cases a Typ I unilateral, uniplanar configuration was applied.

Fracture healing was radiologically diagnosed after an average time of 93 days with a range of 21 to 201 days. Out of 28 fractures fixed with the tubular external fixator 26 healed. One dog was euthanasied for unrelated reasons, a cat was treated conservatively after premature removal of the fixator and relaps of the fracture. Minor complications as pin tract infection or breakage of K-wires were seen but did not interfere with the fracture healing.

Discussion Fracture fixation with an external fixateur is a optimal way to perform a “biologic osteosynthesis”. Compared to bone plating, there is no implant present at the fracture site and the fracture can be reduced either in closed fashion or with a mini approach. Additional soft tissue trauma is therefore reduced. Fracture fixation with the tubular external fixator is easier as with other systems. Others have a connecting bar and several clamps for fixation of the K-wires. The steel tube of the tubular external fixateur is one functional unit that combines both the connecting bar and multiple clamps. Beside a simplifed application, its weight is only 14% of other systems (AO, Kirschner and Menard). The diameter of the K-wires used with the tubular fixator are equal or smaller than the diameter of the gliding holes. The diameter of the K-wires is therefore not determinated by the fixator system and can be adapted to the size of the bone. Distal metaphyseal radius-/ulna fractures of toy breed dogs were a special indication for the tubular external fixator. These type of fractures are often very close to the joint. Even using a AO-miniplate it is often difficult to place two proper screws in the distal part of the radius. With the tubular external fixator 4 K-wires can be placed on the same distance as 2 screw holes of a AO miniplate. This results in a better fracture stablity. Transarticular application is also possible by use of a connecting joint between 2 tubes. This allows stabilisation and optimal wound treatment of transarticular shearing injuries.

References Reichler IM, CJ von Werthern, PM Montavon (1997). Der tubuläre Fixateur externe (FESSA): Klinische Anwendung zur Frakturversorgung bei 6 Zwerghunden und 20 Katzen. Kleintierpraxis 42: 407 - 419.

Figure 3 - Application of the tubular external fixator to a distal tibia.

Craniofacial adaptation plate (Compact 1,0)2 A craniofacial titanium miniplate system (Compact 1,0) was developed by the AO, Switzerland for fixation of craniofacial fractures in humans (PREIN und RAHN, 1998). At the small animal surgery department of the University of Zurich the adaptation plate of the Compact 1,0 has been successfully used for fixation of manibular fractures in cats, metacarpal and metatarsal fractures in cats and phalangeal fractures in small dogs. 12 cases were treated with this plate.

Material and methods For economical reasons we put together a partial Compact 1,0 craniofacial set which is listed below: A craniofacial titanium adaption plate (34 holes, thickness 0.7 mm, length 100 mm). Selftapping screws (core diameter 0.7 mm, outer diameter 1.0 mm, length of 6 or 8 mm). Emergency screws (core diameter 0.9 mm, outer diameter 1.2 mm, length 6 or 8 mm). Special screwdriver, two 0.7 mm drills, the handpice of the screwdriver and the drill were the ones of the AO mini set.

Figure 4 - Mini maxillo facial titanium plate with one screw (1.0 Compact).

Synthes, Mathys Medizinal Technik AG, Bettlach Schweiz.

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During the last 6 months 12 cases had been operated with the titanium craniofacial plates in our small animal surgery department. The patients were 6 cats with mandibuar fractures, 2 cats with metatarsal fractures, 1 cat with metacarpal fractures and 1 dog with multiple phalangeal fractures. Furthermore 2 avulsion fractures were fixed with single screws of the Compact 1,0 system: One avulsion of the short part of the medial collateral ligament in a cat, one avulsion of the collateral ligament of a phalangeal joint in a dog. Ten cases accomplished fracture healing. The follow up of the other patients is not yet completed.

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been started at our departement to evaluate its application for carpal- and tarsalarthrodesis in dogs. Preliminary results are very promising.

Material and methods This 9 holes straight titanium plate is basically a LC-DC plate. The plate has a distal and a proximal end. The four screw holes at the distal end are assigned for 2,7 mm screws. Those of the proximal end have a larger diameter for the use of 3,5 mm screws. The profile of the plate becomes progressively smaller from the middle to the distal end of the plate. Two tarsal panarthrodesis and one carpal panarthrodesis using dorsal plating have so far been performed in dogs weigthing 28 - 33,5 kg.

Results Till deadline of this abstract only one tarsal arthrodesis has been radiologically diagnosed as fused 3 months after the operation.The other two showed uncomplicated fast fusion of the joint.

Figure 5 - Fracture fixation with the miniplate between vertical and horizontal ramus of the mandibula of a cat.

Discussion Fracture treatment in cats and small dogs can be challenging regarding the relation between the size of the bones and available implants. Most of smaller bone fractures can be repaired with the AO mini instrument and implant set (MONTAVON et al., 1988). Especially in cats and toy breed dogs some of the bone fragments are too small for the AO mini implants. They can now be stabilized with the AO mini craniofacial plate system. Successful application in mandibular and phalangeal fractures have been accomplished.

References Montavon PM, OE Pohler, ML Olmstead, KL Wendelburg (1988). The mini instrument and implant set and its clinical application. VCOT 1: 44-51. Prein J, BA Rahn (1998). Scientific and technical bachground. In: Manual of internal fixation in the cranio-facial skeleton. Editor: J. Prein, Springer Verlag; 1-50.

Carpal- and tarsal-arthrodesis titanium plate3

Introduction A special titanium plate for wrist arthrodesis in humans has been developed by the AO, Switzerland. A study has

Synthes, Mathys Medizinal Technik AG, Bettlach/Schweiz

Figure 6 - Pantarsal arthrodesis in a dog with the titanium arthrodesis plate.

Discussion This implant has an advantageous design for panarthrodesis of carpal and tarsal joints in dogs. The LC-DC principle provides a fast bone healing. The major complication in conventional panarthrodesis is a fracture at the distal screw hole. Using screws with smaller diameter, as possible with this plate, reduces this risk. The tappered profile at the distal end also reduces the probability of suture dehiscence. Price of this plate should be adjusted by the AO for veterinary use. A steel version from an an American company is now available in two different sizes (2.7 mm screws and 2.0 mm screws, 3.5 mm screws and 2.7 mm).These are less expensive.

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Patellar luxation: techniques for optimal reestablishment of the articular biomechanics Cranialization of the tuberositas of patellar luxations in dogs and cats

C. Von Werthern

Summary A new surgical technique had been developed for the correction of patellar luxation in small animals. This technique combines the conventional transposition of the tuberositas tibiae with its additional cranialisation. A broad oblique performed osteotomy of the tuberositas tibiae allows its deplacement in cranial direction. This results in a quicker healing, a reduction of the retropatellar pressure and therefore an earlier use of the operated limb postoperatively.

Introduction Patellar luxation is often observed in small breed dogs, but can also be diagnosed in larger breeds. Medial patellar luxation predominate in every breed and size of dogs. Lateral patellar luxation are uncommon however more often seen in large breed dogs. To classify the severity of a patellar luxation a grading system from grad I - IV (PUTNAM, 1968) is used. In grad I and II luxations the patella is located in the trochlear groove but can be manually dislodged. In grad I luxations the patella repositions back spontaneously, whereas in grad II luxationthis has to be supported manually. Grad III and IV luxations are permanently luxated, whereas grad IV luxated patellar can not be brought back into the normal position. The standard surgical technique to correct a patealla luxation is a sulcoplasty of the trochlea femoris combined with transposition of the tuberositas tibiae. With the conventional technique the osteotomised fragment of the tuberositas tibae is very small. It will is transposed and fixed with a K-wire slightly caudally to its original position. This results in an increased retropatellar pressure (Fig. 1). By performing a different osteotomy of the tuberositas tibiae (Fig. 2) it can be transposed medially or laterally and in a more cranial position. This results in a reduced retropatellar pressure and the patient uses its leg sooner postoperatively. The technique was applied to over 50 cats and dogs with all different grades of patella luxation.

dorsal recumbency at the end of the operation table. The leg is draped proximally and the tarsus is left undraped for better intraoperative manipulation. A lateral and medial arthrotomy to the stifle is performed before the tuberositas tibiae is osteomised. To achieve a cranialisation effect of the tuberositas tibae and the straight patella ligament, a vertical cut must be performed slightly oblique (Fig. 2). It is directed to the distal end of the tuberositas tibiae. The cranial aspect of the medial meniscus and the sulcus extensorius should be visualized in order to prevent damage. The short distal osteotomy is then performed horizontally (Fig. 2).

Figure 1 - Schematic diagramm of retropatellar pressure: a) normal position, b) cranialisation, c) caudalisation of the tuberositas tibiae. R represents the resulting pressure between patella and femur.

Material and methods The affected leg is aseptically prepared for surgery from the thight distal to the tarsus. The patient is positioned in

Figure 2 - Direction of the osteomies for correction of a medial patellar luxation.

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Next the tuberositas tibiae is flipped dorsally and a wedge osteotomy (SLOCUM, 1982) of the trochlear femoris is performed with a saw. In dogs younger than 5 months the trochlea femoris in deepened with a chondroplasty (FLO, 1969). The joint is inspected for cranial cruciate rupture. The tuberositas tibae is now transposed medial or lateral and in a more cranial position and fixed with a K-wire. The transposed position is acceptable, if the patella does not luxate when the leg is rotated externally or internally with the stifle extended and the tarsus flexed. If you are satisfied with the result, the tension band wire is completed with an additional K-wire and a cerclage wire. Soft tissue techniques can be applied if there is still a trend for a patellar luxation. These can be the imbrication of fascia lata, the release of the fascia on the opposite side or a partial myotomie of a severly contracted part of the quadriceps muscle.

Results Four cats and 16 dogs operated with this technique have been retrospectively evaluated in our department (Koch, 1997). Fifteen cases showed a medial, 5 a lateral patellar luxation. Fifteen months after surgery 63% were free of lamness and 27% intermittent lame. Radiologicaly diagnosed

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slow progression of arthrosis did not correlate with clinical findings. All owners except one were satisfied with the results of surgery.

Discussion The cranialisation of the tuberositas tibiae for treatment of patellar luxation is a safe and easy surgical technique. The broad osteotomy provides a fast bone healing. The postoperatively reduced retropatellar pressure allows an early use of the limb. It has been successfully applied to all degrees of patellar luxation in dogs and cats.

References Putnam R. W.(1968):Patellar luxation in the dog. MS Thesis, University of Guelph, Ontario. Koch D. A., P.M. Montavon (1997): Klinsche Erfahrungen bei der Therapie der Patellaluxation des Kleintieres mittels Sulkoplastie und seitlicher und kranialer Versetzung der Tuberositas tibiae. Schweizer. Arch. Tierheil. 139, 259 - 264. Slocum B., D. Slocum, T. Devine (1982): Wedge recession for treatment of recurrent luxation of the patella. Clin. Orthop. 164, 48. Flo G. L. (1969): Surgical correction of a deficient trochlear groove in dogs with severe congenital patellar luxations utilizing a cartilage flap and subchondral grooving. MS Thesis, Michigan State University, East Lansing, Michigan.

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Identification of lesions the spine Simon J. Wheeler BVSc, PhD, MRCVS Dipl ECVN, RCVS Specialist in Veterinary Neurology The Royal Veterinary College, University of London - United Kingdom

The clinical syndromes seen in animals with spinal disease are generally well recognised. It is usually apparent if an animal has spinal disease, either from the history or the physical findings. Lesion localisation depends on the performance and interpretation of the neurological examination, and the use of appropriate ancillary tests. Only then can a realistic differential diagnosis be determined, and appropriate therapy considered.

The clinical syndromes seen in animals with spinal disease are generally well recognized. It is usually apparent if an animal has spinal disease, either from the history or the physical findings. Less obvious circumstances where spinal disease should be suspected include non-specific pain and lameness that is not orthopaedic in origin. Taking a history and making a full clinical examination are prerequisites to a more detailed neurological examination. The history taken from the owner will often assist in reaching a provisional diagnosis. Items of particular note are any history of trauma; whether the condition is progressive, static or episodic; other episodes of disease; the vaccination status; current or previous episodes of pain and the patientâ&#x20AC;&#x2122;s urinary status. A general physical examination should be performed on all animals where spinal disease could be present. If there has been trauma or if anaesthesia is contemplated, evidence of other concurrent problems must be determined. Also, some patients where spinal disease is suspected are in fact suffering from problems of other systems. It is not unusual for orthopaedic disorders to mimic neurological conditions. Careful clinical examination should identify such problems. Particular note should be made of joint pain or enlargement as these are present in many dogs misdiagnosed as having neurological disorders. The presence of any spinal pain or deformity also should be noted. The quality of the femoral pulse must be determined, particularly in acutely paralysed cats.

the animal upright in the first instance and later placed in lateral recumbency.

Assess attitude, posture and gait Watch the patient as it relaxes in the examination room. Let it move to the best of its ability, unless it has an acute spinal injury where movement should be restricted. Note the degree of function, the gait and general demeanor. In cats, this part of the examination is particularly important as later parts may be difficult to perform. It is useful to listen to dogs as they walk on a hard surface; if conscious proprioceptive deficits are present, the examiner may hear the claws scuff.

Determine the locomotor status The animal is encouraged to move, except where an acute spinal injury has occurred or if there is severe pain. Dogs that appear paraplegic at rest may show some voluntary movement if supported by a sling or by the tail. Unilateral weaknesses may be revealed by hopping, hemistanding and hemiwalking tests. Assess muscle strength, if the dog is able to stand, by pressing down on the shoulders and hips. The patient may then be classified according to its locomotor status, for example, paraplegic, hemiparetic, etc.

Assess conscious proprioception This is evaluated in the standing animal by the paw position test. Animals with deficits of conscious proprioception that can walk often wear the dorsum of the claws abnormally; this can be appreciated on examination.

Palpate the abdomen Examination The neurological examination is carried out with the aim of determining the location of the spinal lesion. The neurological examination described here is readily performed with

Determine the degree of bladder filling and the ease with which urine is expressed by palpating the abdomen. Urinary incontinence is often a feature of spinal disorders, and some assessment of urinary function should be gleaned from the history.

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Panniculus reflex

Muscle palpation

This is tested by pinching the skin along the dorsal surface of the trunk with fine forceps and observing the twitch of the cutaneous trunci muscle on both the ipsilateral and, to a lesser extent, the contralateral side. The arrangement of the reflex is illustrated in.

Muscle atrophy is assessed by observing and palpating muscle masses. This is best assessed in muscles with a definite bony border, such as the cranial tibial, infraspinatus and supraspinatus muscles in the limbs, and the temporal muscles of the head. Muscle tone is evaluated by gently flexing and extending the joints. In a normal animal, there is a degree of resistance to such manipulation. Care must be taken in interpreting findings in excitable or fractious animals, or where painful orthopaedic conditions exist, as an incorrect impression of increased tone may be gained. Increased tone in the forelimbs is seen in the Schiff-Sherrington sign.

Palpate the spine Determine the presence of spinal hyperaesthesia by palpating the vertebral column and evaluating the patients response. This is an important step in the examination.

Cranial nerve examination Even though abnormal cranial nerve findings may not be expected in spinal disorders, it is good practice to perform such an examination. Some animals with multifocal neurological diseases present as apparent spinal cases. Also, it adds little time to the routine clinical examination to examine the cranial nerves. Particular note should be made of the presence of Horner’s syndrome (ptosis, miosis, enophthalmos and third eyelid protrusion), which occurs because of interference with the sympathetic nerve supply to the eye originating in the T1-T3 spinal cord segment. This may be a feature of spinal disease if the cervical or cranial thoracic cord segments, or nerve roots are involved. An ophthalmoscopic examination also should be carried out in a complete neurological examination. The patient is then placed in lateral recumbency, and each limb evaluated with the aim of placing it into one of the following categories: • NORMAL • LOWER MOTOR NEURON TYPE ABNORMALITY • UPPER MOTOR NEURON TYPE ABNORMALITY Some explanation of the functional anatomy is required to appreciate the difference between the types of deficit (See above). The effect of lesions on the LMN and UMN systems can be considered in terms of motor function, muscle atrophy, muscle tone and local reflexes. The clinical signs that allow differentiation between UMN and LMN abnormalities are summarized in Table. Lower motor neuron deficits are characterized by flaccid paralysis; severe (neurogenic) muscle atrophy; reduced muscle tone; and reflex loss. Upper motor neuron deficits show paresis or paralysis; mild (disuse) muscle atrophy; normal or increased muscle tone and intact or hyperactive reflexes. There are some variations in mild cases, but from the neurological examination, it should be possible to categorize each limb as being “normal”, “UMN”, or “LMN” type abnormality. Motor function has been evaluated previously. With the animal in lateral recumbency, the examination proceeds as follows.

Reflex testing There are a number of local spinal reflexes available for examination, but it is usual to evaluate the patellar reflex and the flexor (withdrawal) reflexes. Other reflexes such as the triceps, biceps, cranial tibial, and extensor carpi radialis may be tested. However, they are found inconsistently in normal animals, and their main significance is in finding hyperactive responses in UMN disorders.

Localization On the basis of the findings, it is possible to identify the location of the lesion in the cord. Functionally, the cord may be divided into four regions. • A BRAIN - C5 • B C6 - T1/2 BRACHIAL OUTFLOW • C T2/3 - L3 • D L4 - S3 LUMBOSACRAL OUTFLOW For clinical purposes, areas A and C, the cervical and thoracolumbar cord, may be considered as UMN carrying areas. Part of the LMN lies within the spinal cord; thus, lesions in certain areas of the cord will produce LMN signs in the limbs. Area B of the cord provides the LMN to the forelimbs and area D the LMN to the hindlimbs, bladder and perineum. Lesions in the various areas will produce different combinations or neurological signs. • Lesions in the cervical cord (A) produce UMN signs in the fore and/or hindlimbs. • Lesions of the brachial outflow segments (B) produce LMN deficits in the forelimbs and UMN signs in the hindlimbs. However, asymmetrical lesions in this area may produce LMN signs in one forelimb only, with UMN signs in both the hindlimbs and the other forelimb. • Lesions in the thoracolumbar cord produce UMN signs in the hindlimbs only, with normal forelimbs (although the Schiff-Sherrington sign may be present). • Lesions in the lumbosacral outflow segments (D) produce LMN signs in the hindlimbs, tail and perineum, but the forelimbs are normal. There are variations possible, for example, in some Dobermans with caudal cervical spondylomyelopathy,

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Assessing the severity or extent of the lesion Assessing the severity of a lesion plays a major part in the diagnostic procedure. In certain patients, the severity of the lesion has as much bearing on the prognosis as the aetiology; if a poor prognosis is suggested, further investigations may be deemed unnecessary. In general, patients with spinal disease showing LMN deficits have a worse prognosis for a return to function than cases showing UMN deficits, because of destruction of the cell body in LMN spinal cord diseases. Patients with major LMN deficits have a poor prognosis for return of that particular function, although associated UMN signs may recover. In UMN injuries, the rate of onset, the duration and the degree of the spinal cord damage all have a bearing on the clinical signs. The degree of dysfunction can be graded from mild ataxia, through paresis, to paralysis (or -plegia) with loss of deep pain perception. The degree of severity of signs is based on two anatomical features. These are the position in the spinal cord where the tracts lie that carry the respective function, and the size of the fibbers transmitting that function. Superficial tracts are more susceptible to damage, and larger myelinated fibbers are more easily damaged than small nonmyelinated fibbers. Conscious proprioception loss, which is the one of the earliest neurological deficits seen in mild spinal cord damage, is transmitted by large myelinated fibbers in superficial tracts. Deep pain sensation is transmitted throughout a large area of the cord in small, nonmyelinated fibbers. Thus, by inference, loss of this function indicates a major degree of cord damage. The prognosis worsens with the increasing neurological deficit, which reflects increasing degrees of spinal cord damage. The prognosis for patients without deep pain sensation is poor, especially if the situation has been so for over 48 hours. Animals that have lost deep pain sensation following trauma carry a poor prognosis whatever the duration of the signs. In patients with similar deficits, the prognosis is dependent on the aetiology. For example, a dachshund with paraparesis may be suffering either from a thoracolumbar disc protrusion or possibly a spinal tumour. Clearly the prognosis

for such cases would differ greatly. The further course of action and some assessment of the prognosis depends on the information gained from the neurological examination. It must be remembered that the radiological appearance of the spine bears no direct relationship to the neurological status, and the neurological findings must be considered when assessing the prognosis. Once the location of the lesion has been established, a list of likely differential diagnoses can be made. Many components go into making this list, including breed and age of the patient, history, presenting signs, progression, physical and neurological findings. Ancillary diagnostic aids are employed to provide the diagnosis.

DIAGNOSTIC AIDS Routine laboratory evaluations Serum biochemistry and haematology are unlikely to provide definitive diagnostic information, but they have an important role to play in the diagnostic process. Certain metabolic disorders will effect the nervous system, and the value of these tests is in identifying or ruling out such conditions. Also, they have an important role in evaluating the general health of the animal. In selected circumstances, the evaluation of blood parameters will be virtually diagnostic, for example, where creatine kinase (CK) concentrations are raised in myopathy or bile acid concentrations elevated in hepatic dysfunction.

Cerebrospinal fluid Cerebrospinal fluid (CSF) analysis plays a significant role in the investigation of nervous system diseases and forms a part of the diagnostic protocol in many cases. Cerebrospinal fluid is collected routinely from the cisterna magna, a straightforward procedure in the majority of dogs. While the technique is safe in experienced hands, practice on cadavers is recommended prior to attempting collection in clinical cases to allow the clinician to become familiar with the procedure. Cerebrospinal fluid collection is indicated in a number of situations: • Where there is evidence on the neurological examination of a structural brain lesion except in suspicion of raised intracranial pressure. • In spinal cord diseases, where the diagnosis is not apparent by other means, particularly radiology. As the radiological investigation of spinal diseases often involves myelography, CSF should be collected before contrast media is injected. • In multifocal neurological diseases. • Where signs of generalized peripheral polyneuropathy are present, as such signs may be due to nerve root diseases. • In dogs with epilepsy, where seizures are proving difficult to control with adequate anticonvulsant therapy or where there are neurological signs indicating the presence of a focal lesion.

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UMN signs in the hindlimbs predominate even though the lesion is in the cervical cord. The possibility of a thoracolumbar lesion in such patients should not be overlooked. The type of urinary incontinence also indicates the site of the lesion. The LMN to the bladder are in the sacral segments. Lesions of these segments produce a LMN incontinence with a flaccid, easily expressed bladder. Lesions cranial to the sacral segments produce an UMN incontinence where the bladder is full and difficult to express. On the basis of the neurological examination, the location of the lesion can be identified to a particular area of spinal cord. It must be remembered that the cord segments are not all located anatomically within the vertebra of the same name; This is especially so in the lumbar region. This is important when the actual anatomical location of the lesion is being considered.

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Collection of CSF requires general anaesthesia, thus the major contraindication to CSF collection is any situation where general anaesthesia is not considered safe. Performance of a spinal tap, either at the cisterna magna or lumbar cistern, is dangerous where there is raised intracranial pressure. There is a tendency for the brain to herniate where increased intracranial pressure exists and the procedure should not be performed. The methods of collection and laboratory evaluation of CSF are covered elsewhere (Further Reading).

Serology

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and has a role in other areas, for example, in evaluating the tympanic bullae. Plain films are not particularly useful in the evaluation of brain lesions, other than those that involve the nasal cavity or the skull. Myelography is required for the full evaluation of many spinal lesions. Other contrast techniques such as epidurography or discography may be useful in selected cases.

Computed tomography and magnetic resonance imaging

The evaluation of blood and CSF for viral antibodies has some application in canine neurology. It is most useful in attempting to confirm a diagnosis of viral infection of the central nervous system.

The diagnosis of brain lesions has been transformed by the use of central nervous system imaging. While the equipment required for computed tomography is limited in availability, its use is becoming more widespread in veterinary medicine.

Microbiology

Electrodiagnostic testing

It can be difficult to culture organisms from the CSF even in the face of fulminating infections, but attempts should be made to isolate pathogens and determine antibiotic sensitivity in such cases. Failure to obtain a positive result does not eliminate the possibility of CNS infection being present. Blood cultures are useful in dogs with discospondylitis.

The various electrodiagnostic procedures, which are used in dogs, are limited in their availability due to the requirement for expensive equipment. The indications for performance of the various techniques and the findings have been reviewed (Further Reading). It is important to remember that none of these methods is a substitute for thorough neurological evaluation, and the information that they provide only enhances the clinical data. Electromyography and nerve conduction studies are most useful in peripheral neuropathies and some spinal diseases.

Radiology Radiology is the major diagnostic tool utilized in neurology, particularly in the identification of spinal and brain lesions. The subject of neuroradiology is ever expanding as new technology is employed. The reader is directed to other sources for information regarding technique and interpretation (Further reading). There are certain particular points regarding radiology that warrant emphasis. Plain radiography will provide the diagnosis in the majority of spinal disorders

Further reading Wheeler SJ (Ed). Manual of Small Animal Neurology, 2nd edn, BSAVA Publications, Cheltenham, UK. 1995. Wheeler, SJ & Sharp, NJH. Small Animal Spinal Disorders: Diahnosis and Surgery. Mosby, London 1994.

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Seizure: diagnosis and management Simon J. Wheeler

Summary

DIAGNOSIS IN EPILEPSY

Seizures are a frequently encountered clinical sign in canine medicine. The diagnosis and management of the underlying disease process and the control of the clinical signs are of prime importance. Most dogs with seizures are suffering from idiopathic epilepsy, but there is no specific test fro this condition and the diagnosis can only be reached by eliminating other causes. Appropriate therapy can bring good results in many patients.

The presentation of a dog with a history of recurrent seizures requires a painstaking approach from the clinician. The fundamental elements of the process are taking a careful history, performing a thorough clinical examination, including laboratory evaluations of blood and urine, and a complete neurological examination. The aim in any case is to reach a diagnosis both in terms of the neurological localization and the underlying pathological process. It is a significant mistake to assume that all dogs with recurrent seizures are idiopathic epileptics. In fact, it is not particularly difficult to rule out physical causes of seizures in most dogs by the judicious use of laboratory tests and the performance of a careful neurological examination. A sensible approach in a case is to attempt to rule out structural brain disease by the neurological examination and extracranial causes by the laboratory evaluations. The breed and age of the patient may have a bearing on the origin of the presenting problem. Idiopathic epilepsy usually commences in dogs between six months and five years old. The occurrence of a first seizure in a dog outside this age range should alert the clinician to the possibility of other diseases being present. Certain breeds are predisposed to idiopathic epilepsy and in some others an inherited pattern is evident. Similarly, the brachycephalic breeds are relatively more frequently affected by brain tumours than other types of dogs. Other conditions that may cause seizures also may have breed associations, for example, pug encephalitis. In cats, idiopathic epilepsy is less common than in dogs. Seizures in cats are more likely to be the result of structural brain disease. In considering the history, the owner should be questioned carefully with regard to the nature of the episodes. It may be evident that some other body system is involved. It should be possible to determine whether the seizures match the typical pattern: The prodromal phase where there is abnormal behaviour for a period of hours or more prior to the episode. Many owners recognize this phenomenon. The aura which is usually a very short period of behavioral alteration immediately prior to the episode. The ictus or fit, which usually consists of typical rhythmic movements of the limbs, salivation, chewing, defaecation and urination. This usually lasts for one to two minutes. The post ictus where the dog again shows a period of altered behaviour lasting a number of hours.

Seizures are a frequently encountered clinical sign in canine medicine. The diagnosis and management of the underlying disease process and the control of the clinical signs are of prime importance. A seizure is the physical manifestation of a paroxysmal electrical disturbance within the brain. It is important to recognize that a seizure is not a disease entity in itself. Rather, it is a clinical sign generally indicative of cerebral dysfunction. The state of recurrent seizures is termed epilepsy, but similarly this is not a specific disease condition. The most frequently encountered situation in which the clinician will see a dog with seizures is in idiopathic epilepsy. Where recurrent seizures become continuous seizures, status epilepticus exists. The clinician may be presented with a dog in status epilepticus, or may see an epileptic dog have a seizure. More frequently, the owners will report a perceived seizure-like episode although no abnormalities will be evident on evaluation of the patient. Causes of seizures may be classified as being intracranial or extracranial in origin. Intracranial causes are further subdivided into those where a structural lesion is identified, for example, encephalitis, tumour or traumatic injury, and those where no such lesion is present, that is, idiopathic epilepsy. Extracranial causes of seizures include toxicity, hepatic encephalopathy, hypoglycaemia or other metabolic derangement.

Classification of causes of seizures Intracranial

{

Structural lesion No lesion - idiopathic

Extracranial

{

Toxic (“Extra-dog”) Metabolic (“Intra-dog”)

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Not all seizures follow this typical pattern and any deviation from it should be noted. The owner should be questioned whether there are any consistent features of the seizure, particularly if any part of the body shows abnormal activity as a precursor to the ictus, for example, muzzle twitching or single limb movement. Such signs are strongly suggestive of the presence of a focal origin of the seizure, which indicates structural disease. The neurological examination must be meticulous with particular emphasis on cranial nerve function and conscious proprioception. Neurological deficits that persist in the interictal period are indicative of a focal lesion being present, although the absence of any neurological abnormalities does not rule out the possibility of structural brain disease being present. A very small proportion of dogs with brain tumours will have a normal interictal examination on first presentation. However, the disease usually progresses, leading to abnormal findings on subsequent evaluations. Caution must be exercised in the interpretation of a neurological examination performed during the postictal phase, as the findings are likely to be most unreliable. Transient deficits may be present the day after a seizure in some dogs. Following the neurological examination, all cases should have a full blood and urine evaluation. This will help to identify any extracranial causes of the seizures. The collection of cerebrospinal fluid (CSF) probably should be restricted to cases where structural brain disease is suspected, although here some discretion should be exercised if increased intracranial pressure could be present. Also, CSF should be collected where seizures are not controlled by anticonvulsant medication at normal therapeutic concentrations.

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ease, the acute crisis being triggered by some additional insult, for example, anaesthesia. Hepatic encephalopathy results when blood is diverted past the intrahepatic circulation via either an acquired or congenital portosystemic shunt. The diagnosis is based on laboratory evaluations, particularly the blood ammonia concentration and the sulphobromophthalein (BSP) test, and radiography. Hypoglycaemia may cause seizures and may be seen in a number of circumstances. Liver disease, sepsis and insulin overdose may cause a decline in blood glucose, but the most common cause is the presence of an insulin-secreting pancreatic tumour (insulinoma). The brain depends on a continuous supply of glucose for normal function as energy stores are severely limited. Various clinical signs may be seen associated with hypoglycaemia, particularly seizures, weakness, depression, disorientation, visual disturbances and ataxia. The signs are of a distinctly episodic nature. The diagnosis is based on demonstrating low fasting blood glucose concentrations, and the presence of clinical signs related to these low glucose concentrations that are relieved by glucose administration. The measurement of blood insulin, with calculation of the glucose:insulin ratio and the glucagon tolerance test also are useful. If an insulinoma is suspected, exploratory laparotomy and excision of the mass is indicated. Surgical removal of the tumour may provide relief from signs for a number of years. Various electrolyte disturbances also may cause seizures, for example, hypocalcaemia.

Intracranial structural disorders Causes of seizures Extracranial disorders Toxic insults and metabolic derangements are the most frequent extracranial causes of seizures. Many toxins cause seizures, for example, ethylene glycol, various insecticides and herbicides. The identification of a toxic origin depends largely on historical information and other physical manifestations of the toxicity, for example, gastrointestinal upset. Laboratory evaluations may be useful in some circumstances. Whilst dogs of any age may be poisoned, puppies seem particularly prone. Treatment is aimed at removing and neutralizing the poison, and controlling the seizures. Hepatic encephalopathy is the primary metabolic disturbance causing neurological signs. The signs are often episodic in nature, although the overall clinical impression is of a forebrain disorder. The clinical signs include abnormal behaviour, disorientation, head pressing, seizures, ataxia and collapse. The episodes may be related to feeding and affected dogs may be in poor body condition. The neurological disturbance arises due to the presence of toxins in the circulation, which are normally cleared by the liver. Occasional cases of hepatic coma will be seen where there is a relatively acute picture of profound neurological deterioration. This usually occurs in dogs where there is underlying hepatic dis-

It is highly unusual for seizures to be the lone manifestation of structural brain disease. In virtually all cases persistent interictal neurological deficits will be present, although these may be relatively subtle. In forebrain tumours the neurological deficits may be restricted to mild deficits of conscious proprioception in the hindlimbs or a relative loss of facial sensation. In cases of inflammatory CNS disease, there often will be spinal hyperaesthesia or multifocal neurological deficits. Also, retinal lesions may be evident on fundoscopic examination. Various intracranial disease processes may lead to signs of forebrain dysfunction in dogs. The most important are neoplasia, inflammation and trauma. Less common causes are degenerative conditions, for example, the lysosomal storage diseases. Hydrocephalus is often implicated in causing forebrain signs, but this is unusual. Investigation of such cases may reveal an inflammatory process that underlies the hydrocephalus.

Neoplasia Tumours involving the brain may be primary or secondary, the latter being either metastatic or locally invasive, for example nasal adenocarcinoma. Confirmation of the diagnosis depends largely on the use of computed tomography. The collection of CSF samples is somewhat

hazardous where there is raised intracranial pressure - a situation often encountered where a tumour is present - due to the potential for brain herniation. Also, whilst abnormal CSF findings correlate well with the presence of parenchymal CNS disease, they are relatively nonspecific and rarely solely diagnostic. Brain tumours have a primary effect on the nervous system by infiltrating and compressing neural structures. Also, they have secondary effects, oedema and herniation, due to the response of the brain to the presence of the tumour. The secondary effects can be dramatic and account for the acute signs seen in some cases as well as the early response to treatment that also may occur. Brain tumours have long been considered to be candidates only for symptomatic therapy, and until recently there has been relatively little consideration of more aggressive treatment in the veterinary literature. However, many centres now are adopting a more radical approach, employing combinations of chemotherapy, surgery and radiotherapy. Treatment of the animal with a brain tumour has two aims. First, to control the potentially life-threatening situation caused by raised intracranial pressure and seizures, and secondly, the removal or reduction in size of the tumour mass. The prognosis for dogs with brain tumours is variable and depends on a number of factors. These include the tumour type and location, the severity of the secondary effects and the neurological status of the animal at presentation. Animals which have severe secondary effects that result in brain herniation carry a grim prognosis. This contrasts with those cases with mild neurological deficits that have a readily accessible tumour, which may be treated with a reasonable expectation of a good recovery. Following surgical removal and radiation therapy, some cases may live for several years.

Inflammatory brain diseases Inflammatory disease of the CNS are prevalent in the dog and various aetiological agent are incriminated. The clinical signs are variable, dependent on the parts of the nervous system involved. The presence of multifocal signs is strongly suggestive of inflammatory disease being present, particularly where hyperaesthesia is a feature. The predominant clinical signs vary; there may be forebrain signs with depression and seizures or cervical signs may be present, particularly hyperaesthesia. Confirmation of a diagnosis of inflammatory CNS disease may be problematical. Cerebrospinal fluid evaluation is the most useful test, although this may be normal between bouts of what often is a episodic disease course. Electroencephalography and CT scanning also may be useful. Canine distemper virus infection of the CNS is an important cause of neurological disease in dogs. Seizures are a frequent finding and are often of the â&#x20AC;&#x2DC;chewing-gumâ&#x20AC;&#x2122; type, suggestive of involvement of the temporal cortex. The other common sign is myoclonus where there are rhythmic, involuntary contractions of muscles. The prognosis for dogs with canine distemper virus infections is poor. Acute forms of the disease are terminal in many cases. The persistent neurological deficits seen in chronic encephalitis, particularly

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seizures and myoclonus, may be tolerated for some time, although recovery does not occur. Rabies causes various neurological signs, including behavioural changes in the early stages, pupillary dilation, hyperaesthesia, photophobia, disorientation, incoordination, seizures and paralysis. The possibility of rabies infection being present must be considered in any dog with obscure neurological signs and the course of action is well defined. Toxoplasma gondii infection may cause neurological signs in dogs, most often spastic paralysis, ataxia and seizures. Puppies are usually affected, although milder forms of the disease may be seen in adult dogs. Steroid responsive meningitis is relatively prevalent in dogs. Clinical signs suggestive of cervical spinal disease often predominate, although depression and seizures feature. The condition occurs in young dogs, often less than 2 years old. Similar clinical signs are caused by a vasculitis of the CNS. Specific syndromes have been recognised in the Bernese mountain dog and the beagle, with other breeds occasionally affected. The prognosis for this condition is guarded, despite some early response to treatment. Granulomatous meningoencephalitis or reticulosis is a frequent cause of multifocal CNS signs in dogs. Small and toy breeds primarily are affected and the condition is most often seen in dogs of 3 - 7 years old. The most common syndromes are suggestive of cerebral, brain stem or vestibular involvement. Certain features such a seizures, blindness, ataxia and cranial nerve deficits may be seen in isolation and spinal cord involvement occurs. The course is usually chronic, but some dogs show a relatively rapid decline. Treatment with corticosteroids may lead to a temporary remission, although the long term prognosis is poor. Pug encephalitis, a syndrome similar to granulomatous meningoencephalitis has been recognised in the pug breed. Signs of forebrain involvement predominate although brain-stem signs also occur. Typically, cases show seizures, behavioural change, particularly aggression, circling and depression. Traumatic injury to the skull has the potential to cause neurological damage either in association with or independent of skull fractures. Road accidents are the most common inciting injury in dogs, although kicks or falls may be implicated. Trauma may lead to seizures in the acute phase following the injury. Alternatively, the dog may recover from the acute episode, but seizures may occur several months later.

Idiopathic epilepsy If the dog fits into the expected age range, and no cause for the seizures and no persistent neurological deficits are identified, the working diagnosis of idiopathic epilepsy is established. When to commence anticonvulsant therapy is a matter of some controversy. Certainly, any dog which has more than one seizure every three months, or which experiences clusters of seizures, should be treated. Seizures themselves precipitate more episodes via the mechanism of kindling. Thus, it may be argued that all cases that suffer more than one seizure should be treated.

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The anticonvulsant of choice in the dog is phenobarbitone (2mg/kg per os, b.i.d.). After 10 days, the serum phenobarbitone concentration must be checked to ensure that it is within the therapeutic range of 15-45 µg/ml. If it falls outwith this range, the dose is adjusted accordingly. It is usual to aim for a serum concentration of 25-35 µg/ml in the first instance. The serum concentrations should be monitored periodically as alterations in drug metabolism occur with time and the dogs response to a particular concentration will change. Should the dog fail to be controlled, the phenobarbitone concentration should be checked and the dose increased to take it to the upper part of the therapeutic range, or even above. Such therapy will control approximately 60-75% of canine epileptics to an adequate degree. The prognosis for the remainder is less good, as other anticonvulsant drugs alone do not offer increased rates of control. Primidone is the most frequently used alternative, but very few dogs that have not been controlled by a therapeutic dose of phenobarbitone will benefit from primidone, and it carries a significant risk of liver toxicity. Thus, there is little merit in the use of primidone in dogs either as the first choice anticonvulsant or as a subsequent adjunct to phenobarbitone. Dogs which fail to response to phenobarbitone therapy alone may be given another drug in combination. Phenytoin (which, due to its short half life is not suitable as a primary anticonvulsant), valproic acid and chlorazepam all have been tried although the clinical efficacy of any of these drugs is unproven in dogs. These combinations also carry a significant risk of hepatotoxicity, and thus should be avoided. Recently, potassium bromide has reappeared as an adjunct anticonvulsant in dogs. Its use in combination with phenobarbitone reduces seizure frequency in some dogs that are resistant to phenobarbitone alone. The recommended dose is 30-40 mg/kg given once daily. The half-life of KBr is prolonged in dogs and it takes approximately four months to reach a steady serum concentration. The therapeutic range is 700-2300 mg/l. Owner education is an important aspect of the management of the idiopathic epileptic dog. Careful noting of the frequency of occurrence and severity of the seizures will enable the clinician to discuss reasonable expectations for the therapy and document the response. “Control” in idiopathic epilepsy is often defined as being the doubling of the interictal period, that is, halving the frequency of seizures, and eliminating clusters. This target should be defined for the owner early in the discussions of the case, as over-ambitious expectations are a common cause of owner dissatisfaction. The importance of regular drug administration must be emphasised to the owner. An abrupt cessation of therapy may lead to a precipitation of status epilepticus. Where control is not achieved, repeated neurological evaluations should be made. If there is any suspicion of a structural brain lesion being present, further investigative procedures such as computed tomography scanning and CSF collection should be performed. Attempts to wean dogs off therapy may be made if there have been no seizures for a number of years, although this process must be extremely gradual.

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Management of status epilepticus The presentation of a dog in status epilepticus is an emergency and the priority is to arrest the seizures rather than to determine the aetiological diagnosis. This is best achieved by the use of intravenous diazepam, which may be given in relatively large doses (up to 1mg/kg i/v). If this fails to control the situation, the use of phenobarbitone (2mg/kg i/v) or pentobarbitone (4-20mg/kg i/v) is indicated. The patency of the airway should be ensured, if necessary by inserting an endotracheal tube. Hypoxia due to seizure activity and compromise of the airway will lead to cytotoxic brain oedema and possibly raised intracranial pressure. Blood should be collected for haematology and biochemistry and the serum glucose concentration determined. Intravenous fluids and dextrose, if appropriate, are administered. If the cause of the seizures is believed to be toxic, the source should be removed. Seizure control via parenteral agents should continue until oral medication can be administered. Only when the seizures are controlled and the postictal phase has passed can any meaningful neurological evaluation be made.

Further reading BIRCHARD, S.J. (1984) Surgical management of portosystemic shunts in dogs and cats. Comp. Cont. Ed. Pract. Vet., 6, 795. BUNCH, S.E., CASTLEMAN, W.L., BALDWIN, B.H., HORNBUCKLE, W.E. & TENNANT, B.C. (1985) Effects of long term primidone and phenytoin administration on canine hepatic function and morphology Am J Vet Res 4-6, 105. CHRISMAN, C.L. (1980) Postoperative results and complications of insulinomas in dogs. J Am Anim Hosp Assn, 16, 677. CUDDON, P.A. & SMITH-MAXIE, L. (1984) Retciulosis of the central nervous system in the dog. Compendium on Continuinq Education, 6, 223. DRAZNER, F.H. (1983) Hepatic encephalopathy in the dog. In Current Veterinary Therapy VIII (ed R.W. Kirk) W.B. Saunders Co., Philadelphia. FARNBACH, G.C. (1984) Serum concentrations and efficacy of phenytoin, phenobarbitone and primidone in canine epilepsy. JAVMA 184, 1117. FREY, H.-H. & LOSCHER, W. (1985) Pharmokinetics of anti-epileptic drugs in the dog: a review J vet Pharmacol Therap 8, 219. JOHNSON, C.A., ARMSTRONG, P.J. & HAUPTMAN, J.G. (1987) Congenital portosystemic shunts in dogs: 46 cases (1979-1986). JAVMA 191, 1478-1483. LECOUTUER, R.A. (1995) Seizures and Epilepsy. In Manual of Small Animal Neurology, 2nd edn. (Ed. S.J. Wheeler) BSAVA Publications, 95. MERIC, S.M. (1988) Canine meningitis. J. Vet. Int. Med., 2, 2635. OLIVER, J.E., HOERLEIN, B.F. & MAYHEW, I.G., eds. (1987) Veterinary Neurology. W.B.Saunders Co., Philadelphia. SCHWARTZ-PORSCHE, D (1992) Management of refractory seizures. In Current Veterinary Therapy Xi (eds R.W. Kirk & J. D Bonagura) W.B. Saunders Co., Philadelphia. SKERRITT, G.C. (1988) Canine epilepsy In Practice 10 (1), 27. TURREL, J.M., FIKE, J.R., LeCOUTEUR, R.A. & HIGGINS, R.A. (1986) Computed tomographic characteristics of primary brain tumours in 50 dogs. JAVMA 188, 851. WHEELER, S.J. (1990) Seizures in dogs: Diagnosis and managment. Vet International 1, 2.

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Cervical disc disease Simon J. Wheeler

Summary Cervical disc disease is a frequent disorder of dogs. Most animals present with neck pain or mild neurological deficits. Other conditions should be considered in differential diagnosis, particularly in young dogs. In view of the high number of patients with significant cord compression, many consider surgical therapy to be the treatment of choice.

creasing caudally. The C6/7 disc is rarely affected, with the exception of Dobermans and other large breeds as part of caudal cervical spondylomyelopathy. The C7/T1 disc occasionally herniates. It may be possible to determine the approximate location of the lesion in the cervical spine by identifying the site of most pain on palpation.

DIAGNOSIS Cervical disc disease is a frequent disorder of dogs. Small breeds, particularly those with chondrodystrophoid characteristics, are commonly affected, but the condition can occur in any dog. Dachshunds, Beagles, Poodles, Spaniels, Shih Tzus, Pekinese and Chihuahuas are most often affected. Dobermans suffer from cervical disc disease as part of the syndrome of caudal cervical spondylomyelopathy. Most patients are two years old or more, with a mean of six years. Disc disease is so rare in dogs less than one year old that other conditions must be considered first, for example, inflammatory CNS disease, atlantoaxial subluxation or discospondylitis. There is no sex predilection. (Denny 1978; Dallman, Palettas & Bojrab 1992)

CLINICAL SIGNS The predominant clinical sign is severe neck pain, which may be acute or chronic. Often this is unremitting and unresponsive to medication. This is one of very few conditions that causes dogs to scream spontaneously. Affected dogs may be reluctant to eat unless the food is raised off the floor. When examining the patient, it is usually not necessary to flex and extend the neck to demonstrate pain. Generally, it is adequate to palpate the spine and muscles of the neck where the tension and pain are evident. Neurological deficits related to cervical spinal cord compression may be seen; paresis or lameness in a thoracic limb is the most frequent. However, any signs related to cervical spinal cord compression can be seen, including hemiparesis and tetraparesis. Nerve â&#x20AC;&#x153;root signatureâ&#x20AC;? (pain apparent on palpation or traction of the limb) is another frequent finding. Disc herniation follows degeneration of the disc. Most occurrences are Hansen Type I extrusions. Hansen Type II protrusions do occur, generally in larger breed dogs. The C2/3 disc is the most frequently involved, with the incidence de-

Radiography The diagnosis is based on the clinical signs described above. Confirmation is by radiographic demonstration of narrowing of the intervertebral space and dorsal displacement of mineralised disc material.

Myelography Myelography is required if the diagnosis is not apparent on survey films or if there are multiple discs potentially involved. In some lateral or intraforaminal extrusions, lateral and ventrodorsal projections of the myelogram may be normal; oblique views may reveal the offending disc. They are also useful in locating on which side an asymmetrical extrusion lies.

CSF analysis Analysis of CSF is useful to eliminate inflammatory disease. Results of CSF analysis may be abnormal in disc disease, but elevations of protein and cells are usually mild (Thomson, Kornegay & Stevens 1989). The differential diagnosis of cervical disc disease is given below. Be particularly cautious in diagnosing cervical disc disease in dogs less than 2 years old or in aged animals.

DIFFERENTIAL DIAGNOSIS OF CERVICAL DISC DISEASE Young dogs with neck pain Atlantoaxial subluxation Inflammatory CNS disease

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Discospondylitis Congenital disorders Trauma Neoplasia Dogs without neck pain Ischaemic myelopathy (generally large breeds) Neoplasia (intramedullary) Adult dogs with neck pain Atlantoaxial subluxation Discospondylitis Neoplasia Trauma Inflammatory CNS disease

TREATMENT OPTIONS Treatment may be non-surgical or surgical.

Non-surgical treatment This entails cage rest and use of anti-inflammatory medications. It is appropriate to try this course with any patient, unless marked neurological deficits are present. Generally, NSAIDs are used. Diazepam or methocarbamol may also be of benefit. Catastrophic worsening of the neurological status with medical treatment, which is often seen in thoracolumbar disc disease, is rare in cervical discs. Neck pain in cervical disc disease seems to be less responsive to non-surgical treatment than does pain from thoracolumbar disc disease. Progression of signs or lack of response in one or two weeks indicate treatment failure. A dog that is responding well to non-surgical treatment should be kept rested for at least two weeks after clinical signs have resolved. Recurrence of clinical signs after non-surgical treatment occurs in 36 per cent of patients (Russell & Griffiths 1968).

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SURGERY Fenestration It is usual to fenestrate the discs from C2/3 to C5/6 as a routine. C6/7 is fenestrated if there is evidence of disease. Some surgeons have questioned the value and desirability of such widespread fenestration (Fingeroth 1989), but others believe it is useful in treatment and prophylaxis. Some dogs will experience very rapid improve-ment following fenestration, and some dogs with profound neurological disabilities recover after this procedure. A well-executed fenestration should prevent further herniation of disc material into the vertebral canal.

Ventral decompression Accurate identification of the disc involved is necessary before performing a ventral slot. Removal of the disc material from the vertebral canal provides the most rapid resolution of clinical signs. The best method of performing a ventral slot is by using powered instruments (Swaim 1974). It is possible to perform the operation using a trephine and rongeurs, but this is a poor alternative. Fenestration is a useful prophylactic procedure and can be performed on the other cervical discs at the time of the decompression (Russell & Griffiths 1968).

Hemilaminectomy Hemilaminectomy via a dorsolateral approach is indicated in a few patients. If there is a markedly asymmetrical myelographic compression, there may be some doubt about the diagnosis. Intraforaminal extrusions occur occasionally, and these are best approached in this way (Felts & Prata 1983).

Surgical treatment Indications for surgical treatment are: • Failure of non-surgical treatment. • Marked neurological deficits. • Progressive neurological deficits. • Unremitting pain. Ventral fenestration or ventral decompression (“ventral slot”) are the most frequently performed procedures. Rare cases may require dorsal laminectomy or hemilaminectomy. The choice between ventral fenestration and decompression must be made on an individual patient basis. There are advantages and disadvantages to both procedures. General indications for ventral decompression are: • Presence of neurological deficits. • Myelographic evidence of spinal cord compression. • Failure of fenestration. Clinicians who routinely perform myelography find that most cervical disc patients come into one of the first two categories. Current opinion is that ventral decompression is the optimal method of treatment.

COMPLICATIONS The ventral surgical approach should have few complications if proper care is exercised. It is possible to damage vital structures, particularly the recurrent laryngeal nerve. Spinal cord damage during fenestration can occur if the intervertebral space is explored recklessly. Neurological deterioration after fenestration may occur, probably where incorrect fenestration technique leads to disc material being forced into the vertebral canal (Tomlinson 1985). Ventral decompression is more prone to complications than fenestration. Inaccurate identification of the disc involved, either on radiographs or at surgery, is a mistake. Haemorrhage can be problematical at various stages. Concurrent use of aspirin or the presence of coagulopathy (particularly VW disease in Dobermanns) increases the danger of severe haemorrhage. One study reported death in 3 of 50 dogs undergoing ventral decompression for cervical disc herniation (Clark 1986). One of the dogs died following uncontrollable haemorrhage from the venous plexus. The other two dogs experi-

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PROGNOSIS The prognosis for dogs with cervical disc herniations is generally good. Non-surgically treated dogs may have a prolonged convalescent period (several weeks to months) and have an approximately 36 per cent chance of recurrence of signs (Russell 1968).

Fenestration Following fenestration, recovery times vary. Denny (1978) reported that 11 of 12 dogs with neck pain recovered, although 30 per cent of these took an average of two weeks for pain to subside. Of dogs with mild neurological deficits (thoracic limb paresis), 12 of 17 (70 per cent) recovered in an average of 3.6 weeks (maximum 8 weeks). Of those with severe deficits (hemiparesis, tetraparesis, or tetraplegia), 6 of 10 (60 per cent) recovered in an average of 6 weeks.

Decompression The results of ventral decompression have also been analysed in a series of 54 patients (Seim & Prata 1982). In dogs with neck pain and root signature (n=33), all dogs were normal or improved within 48 hours of surgery, and all were normal at 12 months after surgery. In dogs with moderate deficits, but still able to walk (n=14), 12 were improved at 48

hours and all were normal at 12 months. Interestingly, two of these dogs were worse (more severe pain or worse neurological status, or both) at 48 hours. Of dogs that were unable to walk before surgery (n=7), 6 were improved at 48 hours and 6 were normal at 12 months, the remaining dog having some residual deficits but being able to walk and free of pain. In a comparison of dogs with cervical disc disease that were able to walk prior to surgery, ventral decompression provided superior results to fenestration in all neurological parameters. Dogs recovered more rapidly and recovery rates were higher following ventral decompression. Surgical complications was fewer in fenestration (Fry et al. 1991). Thus, ventral decompression carries a more favourable prognosis, both in terms of rate of recovery and time of convalescence. It is on this basis that we recommend ventral decompression for most dogs with cervical disc herniations.

CERVICAL DISC DISEASE IN CATS Disc herniation is quite common in cats, particularly in the cervical region, but clinical signs related to these lesions are rare (Heavner 1971; Littlewood, Herrtage & Palmer 1984; Wheeler, Clayton Jones & Wright 1985). Type II protrusions are more frequent than Type I extrusions (King & Smith 1960). Diagnosis and treatment are as discussed above.

References Clark, D.M. (1986) An analysis of intraoperative and early postoperative mortality associated with cervical spinal decompressive surgery in the dog. Journal of the American Animal Hospital Association 22, 739-744. Dallman, M.J., Palettas, P. & Bojrab, M.J. (1992) Characteristics of dogs admitted for treatment of cervical intervertebral disc disease: 105 cases. Journal of the American Veterinary Medical Association 200, 2009-2011. Denny, H.R. (1978) The surgical treatment of cervical disc disease in the dog: a review of 40 cases. Journal of Small Animal Practice 19, 251297. Felts, J.F. & Prata, R.G. (1983) Cervical disc disease in the dog: intraforaminal and lateral extrusions. Journal of the American Animal Hospital Association 19, 755-760. Fingeroth, J.M. (1989) Fenestration: Pros and Cons. Problems in Veterinary Medicine 1(3), 445-466. Fry, T.R., Johnson, A.L., Hungerford, L. & Toombs, J. (1991) Surgical treatment of cervical disc herniations in ambulatory dogs. Progress in Veterinary Neurology 2, 165-173. Heavner, J.E. (1971) Intervertebral disc syndrome in the cat. Journal of the American Veterinary Medical Association 159, 425-427. King, A.S. & Smith, R.N. (1960) Disc protrusions in the cat: distribution of dorsal protrusions along the vertebral column. Veterinary Record 72, 335-337. Littlewood, J.D., Herrtage, M.E. & Palmer, A.C. (1984) Intervertebral disc protrusion in a cat. Journal of Small Animal Practice 25, 119-127. Russell. S.W. & Griffiths, R.C. (1968) Recurrence of cervical disc syndrome in surgically and conservatively treated dogs. Journal of the American Veterinary Medical Association 153, 1412-1416. Seim, H.B. & Prata, R.G. (1982) Ventral decompression for the treatment of cervical disk disease in the dog: a review of 54 cases. Journal of the American Animal Hospital Association 18, 233-240. Stauffer, J-L, Gleed, R.D., Short, C.E., Erb, H.N. & Schukken, Y.H. (1988) Cardiac arrhythmias during anaesthesia for cervical decompression in the dog. American Journal of Veterinary Research 49, 1143-1146. Swaim, S.F. (1974) Ventral decompression of the cervical spinal cord in the

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enced acute bradycardia and hypotension and died during the surgery. It is suggested that a syndrome of â&#x20AC;&#x153;acute sympathetic blockadeâ&#x20AC;? was responsible for these deaths. Anaesthetic complications are also seen following surgery for cervical disc disease (Stauffer et al. 1988). Arrhythmias (bradycardia and ventricular premature contractions) were seen in 31% of dogs; these were 2.5 times more common in cervical disc surgery than thoracolumbar disc surgery. Two of 48 dogs died following cervical disc surgery in this study. Neurological worsening occurs in some patients following ventral decompression. Extensive spinal cord manipulation may account for this, but it is not always clear why deterioration occurs, particularly in dogs with Type II disc protrusions. Fortunately, this situation usually improves. Vertebral instability may result if the slot is made too wide, leading to subluxation and possible nerve root compression. This will lead to marked deterioration in the condition of the patient. If this does occur, the lesion should be managed by distraction and fixation, as for a traumatic fracture or subluxation. Infection of the intervertebral space (discospondylitis) can occur following either procedure if strict asepsis is not observed. Swelling or oedema may be seen in the ventral neck. Care with haemostasis and wound closure helps to avoid this. Use of drains may be occasionally necessary. Persistent neck pain occurs in many dogs that undergo fenestration, and may take up to a month to resolve. Following ventral decompression, neck pain usually resolves within a few days.

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438 dog. Journal of the American Veterinary Medical Association 164, 491-495. Tomlinson, J. (1985) Tetraparesis following cervical disk fenestration in two dogs. Journal of the American Veterinary Medical Association 187, 76-77.

4th European FECAVA SCIVAC Congress Thomson, C.E., Kornegay, J.N. & Stevens, J.B. (1989) Canine intervertebral disc disease: Changes in the cerebrospinal fluid. Journal of Small Animal Practice 30, 685-688. Wheeler, S.J., Clayton Jones, D.G. & Wright, J.A. (1985) Myelography in the cat. Journal of Small Animal Practice 26, 143-152.

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Treatment of caudal cervical spondylomyelopathy (Wobbler’s syndrome) Simon J. Wheeler

Summary The decision on the best way to treat each patient with caudal cervical spondylomyelopathy (CCSM) is based on the presenting history, neurological status, radiological findings, and the owners expectations and their ability to undertake any necessary aftercare. Most dogs that show neurological deficits are surgical candidates. Many aspects of surgery make this a difficult problem to deal with, and patients tend to have concurrent diseases. The surgical procedures are difficult and challenging, and the prognosis can be uncertain.

The decision on the best way to treat each patient with caudal cervical spondylomyelopathy (CCSM) is based on the presenting history, neurological status, radiological findings, and the owners expectations and their ability to undertake any necessary aftercare. Most dogs that show neurological deficits are surgical candidates, but consideration will be given here to non-surgical treatment.

The main factor governing the choice of surgical procedure is the appearance of the spinal cord on myelography, particularly the traction view. Many lesions, when evaluated by traction, show a combination of both static and dynamic compression. A judgement must then be made as to which is the major component. All of the surgical techniques are technically challenging.

Operative considerations Because some dogs with CCSM deteriorate postoperatively for obscure reasons, methylprednisolone given prior to dorsal or ventral decompression may be useful. It should also be remembered that prolonged excessive extension of the neck during surgery is undesirable. In addition, overzealous retraction of soft tissues during a ventral approach to the neck can damage any of the nerves in the cervical region. This can induce arrhythmia, Horner’s syndrome, or laryngeal paralysis, and retraction may also exacerbate bleeding from the internal vertebral venous plexus (“vertebral sinuses”) by compressing the jugular veins.

NON-SURGICAL TREATMENT Ventral decompression Dogs that develop mild neurological deficits following minor trauma may respond favourably to non-surgical treatment. However, surgery should be considered as most dogs will undergo a slow but steady deterioration (Denny, Gibbs & Gaskell 1977). As surgery is elective for the majority of dogs with CCSM, a two to four week course of severe exercise reduction and use of a chest harness can usually be justified.

SURGERY A large number of different surgical techniques have been proposed for CCSM, with many of the authors claiming a 70 to 80 per cent success rate. The way to obtain the best overall results is to consider three basic types of surgery and to perform these for certain, relatively well defined indications. The three types of surgery are: • Ventral decompression. • Vertebral distraction/fusion. • Dorsal decompression.

Ventral decompression (“ventral slot”) is indicated primarily for the relief of static ventral lesions such as herniated disc material, although some surgeons also use it for dynamic lesions. In CCSM it may be complicated by ventral osteophytosis or a misshapen C7 vertebra. Access to the C6/7 site may be restricted, but this problem is minimized by taking particular care with patient positioning. In general, ventral decompression can only be considered to have been completed satisfactorily when the dura is clearly visible in the depths of the slot. In CCSM, it is uncommon to identify an obvious mass of herniated disc material as seen with a classic type I disc extrusion in a chondrodystrophoid dog. Rather, the compression often appears to be comprised of fibres of the anulus fibrosus infiltrated by degenerate nuclear material. To promote vertebral fusion at the surgical site, cancellous bone may be packed around the slot. Cancellous bone enhances fusion, which usually occurs within eight weeks. Without grafting, osseous fusion is delayed and occurs in only about 50% of dogs, with the others presumably un-

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dergoing fibrous union. Thus some range of motion may be preserved by not using a graft. This could be advantageous in a dog where only one of two adjacent lesions is operated on with this technique, to try and lessen the potential for the domino effect (Chambers et al. 1982; VanGundy 1988, 1989).

Vertebral distraction and fusion The primary indication for distraction and fusion is the presence of a dynamic component to the spinal cord compression. This can affect either the dorsal, the ventral, or both aspects of the vertebral canal. Distraction has been attempted in the past using a number of different techniques, but the two methods described here are by use of metal implants and bone cement, and a screw and washer technique. An advantage of both of these distraction methods is that they often provide rapid relief of cervical hyperaesthesia, probably because of decompression of nerve roots at the distracted interspace. Both techniques have the potential for implant failure, which can be catastrophic (Ellison, Seim & Clemmons 1988; Bruecker, Seim & Blass 1989; McKee et al. 1990). Other methods have been described, for example the use of harrington rods (Walker 1989).

Metal implant and bone cement method In the metal implant and bone cement technique, the cement renders revision of a surgical failure difficult, and also raises the risk of implant infection. The dog should receive an intravenous intraoperative antibiotic effective against staphylococci (such as cephazolin 20 mg/kg, repeated every 1 to 2 hours during surgery). Despite potential disadvantages, metal implant and bone cement distraction is a well tested technique with good long term follow up results. The metal implants can either be Steinmann pins or bone screws, but neither are suitable for distraction at more than one interspace (Ellison et al. 1988; VanGundy 1988).

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treated (McKee et al. 1990). The use of bone screws without washers may also reduce instability and so relieve dynamic spinal cord compression (Denny et al. 1977). It often results in fusion and can also be used at multiple sites. The screw and washer technique is preferable because the washer shares the load of distraction, which should lower the risk of implant failure and enhance fusion. Ventral fusion performed in horses with “Wobbler syndrome”, an equivalent condition to CCSM in dogs, can cause new bone around the articular processes to regress (Grant et al. 1985). Similarly, ventral fusion in dogs might also relieve compression caused by dorsally located osteophytes, especially as ligamentum flavum has been shown to atrophy in dogs following fusion (Bruecker, Seim & Blass 1989; McKee et al. 1990). Using a ventral approach in these patients may avoid the morbidity problems sometimes associated with dorsal laminectomy in dogs.

Dorsal decompression This technique would seem to be the logical treatment for dogs with multiple sites of vertebral canal stenosis, and for those with osteophytes in the region of the dorsal articular processes. It also provides an option in dogs with ventral lesions at two or more intervertebral spaces. Long term results of dorsal laminectomy appear to be favourable (Lyman & Seim 1991), but several authors have reported significant postoperative morbidity and deterioration in neurological status (Trotter et al. 1976; DeLahunta 1983; Trotter 1985; Walker et al. 1985). In a survey of perioperative mortality associated with cervical decompressive surgery, dorsal laminectomy was associated with three times the mortality rate of ventral decompression (Clark 1986). Another potential complication is constrictive fibrosis at the surgical site by so called “laminectomy membranes”. Dorsal decompression should not cause the domino effect, as the vertebrae do not usually fuse together. Fusion can be encouraged, if necessary, by screwing and then bone grafting the dorsal articular processes.

Screw and washer The screw and washer technique will probably benefit from further modification to overcome its main problem of vertebral endplate resorption, with subsequent collapse of the distracted interspace. The collapse appears to be caused by suboptimal washer design, so that all of the force resulting from distraction is concentrated on relatively small areas of contact between the endplate and washer. However, the temporary stability provided by the implants seems to allow fusion to occur. This provides long term relief of spinal cord compression, despite the subsequent collapse of the distracted site. The reported results are very good. A major advantage is that, unlike metal implant and cement distraction, the screw and washer technique can be applied to more than one site. The surgeon can therefore be more aggressive in dealing with a dog that has two adjacent lesions, one of which could go on to cause a domino problem in the future if not

Ventral fenestration Fenestration is not a suitable treatment for adult dogs with CCSM. It has been proposed as an effective treatment for young Dobermanns with this condition, although others have reported mixed results (Mason 1979; Lincoln & Pettit 1985).

Dogs with multiple lesions Between 15 and 50 per cent of Dobermanns present with compression at both C5/6 and C6/7 intervertebral spaces (Bruecker, Seim & Withrow 1989; McKee, Lavelle & Mason 1989). Dogs with more than one lesion may be treated in one of several ways:

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PROGNOSIS The seriousness of this condition is illustrated by the fact that a quarter of dogs with CCSM in one series were euthanatized within six weeks of surgery for neurological problems (Seim 1986). Dogs with more than one lesion generally have a worse prognosis than dogs with single lesions, and dogs with chronic tetraparesis have a very guarded prognosis. In contrast, dogs with a sudden onset of tetraparesis often respond well to surgery if treated promptly. Most severely tetraparetic dogs that are going to recover will do so within six weeks (Trotter 1985). A useful general estimate of the likely outcome in this condition has been provided by Seim (1986). For dogs with single lesions, about 80 per cent of those that are walking prior to surgery will have a favourable outcome. However, but only about 40 per cent of those that cannot walk will recover. These success rates are some 20 per cent lower for dogs with two lesions. It is hoped that careful tailoring of the surgical procedure to the type of lesion may be able to improve on these figures.

References Bruecker, K.A., Seim, H.B. & Blass, C.E. (1989). Caudal cervical spondylomyelopathy: Decompression by linear traction and stabilization with Steinmann pins and polymethylmethacrylate. Journal of the American Animal Hospital Association 25, 677-683. Chambers, J.N., Oliver, J.E. & Bjorling, D.E. (1986). Update on ventral decompression for caudal cervical disk herniation in Dobermann pinschers. Journal of the American Animal Hospital Association 22, 775-778. Clark, D.M. (1986). An analysis of intraoperative and early postoperative mortality associated with cervical spinal decompressive surgery in the dog. Journal of the American Animal Hospital Association 22, 739-744. DeLahunta, A. (1983) Veterinary Neuroanatomy and Clinical Neurology, 2nd edn. W.B. Saunders Co., Philadelphia, p204 Denny, H.R., Gibbs, C. & Gaskell, C.J. (1977). Cervical spondylopathy in the dog - a review of thirty-five cases. Journal of Small Animal Practice 18, 117-132. Ellison, G.W., Seim, H.B. & Clemmons, R.M. (1988). Distracted cervical spinal fusion for management of caudal cervical spondylomyelopathy in large-breed dogs. Journal of the American Veterinary Medical Association 193, 447-453. Grant, B.D., Hoskinson, J.J., Barbee, D.D., Gavin, P.R., Sande, R.D. & Bayly, W.M. (1985). Ventral stabilization for decompression of caudal cervical spinal cord compression in the horse. Proceedings of the 31st Annual Convention of the American Association of Equine Practitioners. pp75-103. Lincoln, J.D. & Pettit, G.D. (1985). Evaluation of fenestration for treatment of degenerative disc disease in the caudal cervical region of large dogs. Veterinary Surgery 14, 240-246. Lyman, R. & Seim, H.B. (1991). Viewpoint: Wobbler syndrome. Progress in Veterinary Neurology, 2, 143-150. Mason, T.A. (1979) Cervical vertebral instability (wobbler syndrome) in the dog. Veterinary Record 104, 142-145. McKee, W.M., Lavelle, R.B. & Mason, T.A. (1989). Vertebral stabilisation for cervical spondylopathy using a screw and washer technique. Journal of Small Animal Practice 30, 337-342. Seim, H.B. (1986). Caudocervical spondylomyelopathy. Proceedings of the 14th Annual Veterinary Surgical Forum. pp.72-78. Trotter, E.J., deLahunta, A., Geary, J.C. & Brasmer, T.H. (1976). Caudal cervical vertebral malformation-malarticulation in Great Danes and Dobermann pinschers. Journal of the American Veterinary Medical Association 168, 917-930. Trotter, E.J. (1985). Canine wobbler syndrome. In Textbook of Small Animal Orthopaedics. (Eds. C. D. Newton & D. M. Nunamaker). J.B. Lippincott Co., Philadelphia. pp.765-790. Van Gundy, T.E. (1988) Disc-associated wobbler syndrome in the Dobermann pinscher. Veterinary Clinics of North America, Small Animal Practice 18, 667-696. Van Gundy, T.E. (1989). Canine wobbler syndrome. Part II. Treatment. Compendium on Continuing Education for the Practicing Veterinarian 11, 269-284. Walker, T.L. (1989) Use of Harrington rods in caudal cervical spondylomyelopathy. In Current Techniques in Small Animal Surgery (Ed. M. J. Bojrab). Lea & Febiger, Philadelphia, 584-586.

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• Perform surgery at both sites. This increases the overall complication rate, and is contraindicated for the metal implant and bone cement technique of distraction because of the high risk of implant failure. Screw and washer distraction can be used on two adjacent lesions without increasing the complication rate. • Try to determine which lesion is more significant, perhaps with the help of an extension view during myelography, and then correct this lesion in isolation. Correcting the worst lesion might be successful with ventral decompression, but distraction at only one site may well exacerbate the adjacent lesion (domino effect), and should be undertaken with great circumspection. If only one of two lesions is corrected, dogs that deteriorate or do not respond after surgery should undergo repeat myelography within seven days. • Perform a continuous dorsal decompression over both sites. This approach avoids the risk of a domino lesion, but can cause significant morbidity.

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Surgery of the spine Simon J. Wheeler

Summary Surgical treatment is required for many diseases of the spine in dogs and cats. The surgeon must possess basic surgical skills, and must be familiar with the special techniques and instrumentation required for neurosurgery. Diseases best treated by surgical means include disc herniation, atlantoaxial subluxation, trauma, lumbosacral disease, neoplasia and Wobbler syndrome. The presence of neural structures complicates the surgical procedures and surgeons must be fully aware of these structures when performing surgery. It is the author’s view that neurosurgery is best performed by persons specifically trained in this regard, and not be considered an extension of orthopaedic surgery.

Ventral fenestration or ventral decompression (“ventral slot”) are the most frequently performed procedures. The choice between ventral fenestration and decompression is made on an individual patient basis. There are advantages and disadvantages to both procedure. General indications for ventral decompression are: • Presence of neurological deficits. • Myelographic evidence of spinal cord compression. • Failure of fenestration. Clinicians who routinely perform myelography find that most cervical disc patients come into one of the first two categories. Current opinion is that ventral decompression is the optimal method of treatment.

Thoracolumbar disc herniation Surgical treatment is required for many diseases of the spine in dogs and cats. The surgeon must possess basic surgical skills, and must be familiar with the special techniques and instrumentation required for neurosurgery. Further details of the techniques are found in Small Animal Spinal Disorders: Diagnosis and Surgery, by S. J. Wheeler & N. J. H. Sharp, Mosby-Wolfe, London.

INTERVERTEBRAL DISC DISEASE Intervertebral disc disease is a frequent disorder of dogs (but is rarely a cause of clinical signs in cats). Most clinicians are familiar with the diagnosis of the condition, but there is some confusion about the most appropriate methods of treatment. While there is some controversy regarding certain regimes, particularly involving unconventional methods, there is a large amount of data in the veterinary literature concerning the disease. Analysis of these data allows certain guidelines to be drawn, which can be used in selecting the most appropriate method of treatment for individual patients.

Cervical Disc Herniation Indications for surgical treatment are: • Failure of non-surgical treatment • Marked neurological deficits • Progressive neurological deficits • Unremitting pain.

Hemilaminectomy is the treatment of choice for most dogs with neurological deficits of grade 2 or more. Decompression should be performed as soon as possible after the onset of neurological signs, especially for dogs with severe deficits. This is crucial in animals with depressed or absent deep pain sensation. Those with grade 5 neurological deficits should be regarded as emergencies, requiring surgery within 24 hours to have the best chance for a successful outcome. Reasonable results can still be obtained if surgery is performed within 48 hours, but after three days the results are dismal. The rate of recovery is also faster after hemilaminectomy than after the other two methods of treatment, and there is less likelihood of any residual neurological deficits after surgical decompression of the spinal cord. Specific recommendations for hemilaminectomy include: • Grade 5 lesions of less than 48 hours duration. • Deterioration or lack of response to other types of therapy. • Recurrence after previous treatment. • Myelographic evidence of spinal cord compression. • Presence of LMN deficits. Hemilaminectomy without fenestration can result in a recurrence rate as high as 27 per cent, so concomitant disc fenestration is recommended. The ideal treatment for disc herniation is to combine decompression of the spinal cord with fenestration of all high risk discs (T11/12 to L4/5 inclusive). This would require considerable dissection if undertaken from a dorsolateral approach, and so a compromise is usually reached entailing fenestration of the affected disc and the one on either side (where possible including T12/13, T13/L1 and L1/2).

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BVSc, PhD, MRCVS Dipl ECVN, RCVS Specialist in Veterinary Neurology The Royal Veterinary College, University of London - United Kingdom

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External and middle ear surgery Richard A.S. White

Summary This lecture looks at the common causes of external ear diseases in both the dog and the cat and emphasises the role of medical management in the first instance. The indications for surgical intervention are reviewed, the various techniques for external ear surgery are explained and some of the common causes of failure are presented. The aetiology of middle ear problems in the dog differs considerably to that in the cat and the disease is compared in the two species. Middle ear surgery in the dog is predominantly the result of extension from external ear disease and can often be managed medically. Failing which total ear canal ablation with bulla curettage or lateral osteotomy of the bulla is indicated and for the dog carries an excellent prognosis. In the cat, middle ear disease is more likely to result from ascending infection or neoplastic disease. Ventral bulla osteotomy is more frequently practiced for the cat and the prognosis tends to be more guared because of neoplastic disease. This presentation will cover all of the common surgical procedures for external and middle ear disease.

Introduction The ear is composed of structures at three levels - the outer, middle and inner ear. Most surgically-related conditions are a consequence of disease that involves the outer ear which is formed around the auricular and scutiform cartilages most distally. The auricular cartilage is subdivided into several components (scapha, helix, anthelix, tragus, antitragus) and forms the pinna dorsally and the cone-shaped vertical canal below. Below the auricular cartilage the horizontal component of the external ear is formed by the annular cartilage which is attached to the external auditory prominence.

Aetiologies of ear disease The concept of initiating, predisposing and perpetuating aetiologies has been applied to ear disease for more than decade and has provided a useful basis for analysing the causes of otitis externa. Initiating causes: include such causes as foreign bodies

and parasites which are capable of promoting a response even within the normal ear. Particularly important in this category are generalised dermatoses since the ear is simply a specialised part of the skin are a frequent underlying cause of otitis externa. Predisposing causes: these can add the the problem without actually being responsible for starting it. The conformational anomalies of the Spaniel ear is good example of such a cause. The shape of the ear reduces the efficiency of the normal ventilatory system and whilst this rarely, if ever, actually causes the original problem it will exacerbate the inflammatory changes once established. Perpetuating causes: this category includes the presence of micro-organisms such as bacteria and yeasts which are capable of prolonging and maintaining the disease process once an inflammatory change is under way. Once again, they are unlikely to initiate the problem in the first instance.

Diagnosis When investigating the chronic ear patient to identify the underlying aetiology the clinician should always try to consider the patient as a whole and not the ears in isolation. It should always be borne in mind that the ears are simply part of the integument - albeit a very specialised part. The external meatus provides the most frictional, most humid and most enclosed dermal environment possible (others include the interdigital spaces, the groin and the axillae). Initial inspection should take note of the condition of the pinna, the external auditory meatus and the tympanic membrane by means of otoscopy, microbiology. Where disease involving the middle ear is supected myringotomy may be complemented with radiography although this imaging technique is useful only in advanced cases. Modern scanning techniques (CT, MRI) are far more sensitive in determining if disease exists within the middle ear chamber.. More sophisticated electrodiagnostic techniques such as brain stem auditory evoked potential should be reserved for investigation of inner ear disease.

Medical management Where specific initiating causes can be directly identified (eg: parasites) appropriate therapy can be instigated. In

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many instances, however, it may not be possible to identify a specific initiator and treatment follows an empirical path using cerumen-dissolving agents, anti-inflammatories and topical antibiotic therapy to manage symptoms rather than causes. Often with less than satisfactory results. In very high proportion of chronic otitis externa cases the initiating aetiology will be found to be associated with a dermatosis and it is not surprising that the ears will be the first indicators of skin disease. Identification and management of an underlying dermatological problem should therefore be a primary aim when investigating and managing the chronic ear.

THE EAR - SURGERY FOR CHRONIC OTITIS Introduction The value of surgical intervention to improve ventilation / drainage in the management of chronic ear disease has long been recognised. More than 150 years ago cutting off the pinna was recommended for dogs that suffered with otitis externa. Improving the ventilation of the outer ear by incising the lateral wall of the vertical canal was described in 1853 whilst this concept was later improved by removing a section of cartilage from the lateral wall to prevent the opening from closing over. The lateral wall resection procedure which later include a ventrally reflected ‘drainage board’ was described in the 1930’s and provides the basis for the widely practised lateral wall resection. More recent innovations include the total ear canal ablation which has revolutionised the management of the “end stage” ear.

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the circumferenceis removed in a strip which is folded ventrally. The incisions are continued as far ventrally as the scutiform cartilage (horizontal canal opening). The reflected cartilage is anchored in position with simple interrupted monofilament sutures. The edges of the skin are sutured in a similar pattern to the remaining portion of the vertical canal. Any excess reflected tragus is amputated.

Prognosis Despite the widespread use of the LWR for otitis externa there is no doubt that this procedure alone does not provide a complete solution to all chronic ear diseases. Some reviews have indicated that as many as 40% of LWR’s end in failure or continuing ear disease. The reasons for LWR failure include: poor surgical technique, poor patient selection, failure to control the underlying cause of the otitis externa (usually a dermatological problem) and unremiting middle ear disease.

Vertical canal ablation Several other surgical procedures have been developed in an effort to resolve the nonresponsive cases including vertical canal ablation (VCA) designed to remove the entire vertical canal to manage irreversible changes which are not amenable to LWR. VCA was later modified to include a ventral drainage board.

Indications Lateral wall resection Indications LWR is indicated where improved ventilation and / or drainage will reduce for the need for repeated medical management of persistent otitis externa. Removal of the auricular cartilage will in some cases also minimise the opportunity for frictional dermatoses. It cannot be stressed strongly enough that many persistent cases of otitis externa are the result of an underlying dermatological problem and attention should be paid to this aspect of the problem before surgical management is considered.

Technique The patient is positioned in lateral recumbency and two parallel incisions made over the vertical canal from the auditory meatus as far as the level of the horizontal canal. This strip of skin is reflected dorsally but usually left attached to the dorsal aspect of the tragus. The auricular cartilage is dissected free of the overlying muscle on its lateral aspect. Any blood vessels are ligated or dealt with using diathermy. Two vertical incisions are made through the tragus (ie: lateral aspect of the vertical canal) such that approximately 40% of

VCA is indicated in the management of diseases of the external ear which are confined to the vertical canal - ie: the horizontal canal is normal and unaffected by the disease. In fact this is a rather unusual situation. In most instances of external ear disease the changes are not limited solely to the vertical canal in which case total ear canal ablation may be a more suitable alternative.

Technique The approach is similar to that for LWR however, the whole circumference of the vertical canal is dissected free of the surrounding soft tissues. The auricular cartilage is amputated from the base of the scapha to the level of the horizontal canal. A portion of the tragus is preserved to create a ‘drainage board’ as for LWR below the opening to the horizontal canal. The resulting dead space above the canal is closed.

Total ear canal ablation The need for a procedure to deal with changes that involved the entire aural canal (ie: vertical and horizontal) was perceived by Youatt as early as 1871 but received little at-

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Indications 1. Chronic proliferative changes in the ear canal. 2. Complete ear canal stenosis / para-aural abscessation. 3. Unremiting middle ear disease. 4. Neoplastic disease of the ear canal or bulla. Most of the dogs requiring this type of surgery will have undergone prolonged treatment previously and many will have had unsuccessful surgical interventions. The most frequently presented breeds include Spaniels, German Shepherds, Labradors and Old English Sheepdogs. Often the ear disease represents the â&#x20AC;&#x153;tip of a dermatological icebergâ&#x20AC;? and ablation may be considered as a salvage procedure in such cases.

Technique The procedure includes the following steps: Mobilisation of the canal by incising around the opening of the vertical canal and then bluntly dissecting the auricular muscles away from the ear canal until the lateral aspect of the bulla is reached. The facial nerve emerging from the stylomastoid foramen and running ventrally to the canal is isolated and retracted from the field of dissection. The ear canal is amputated at the OEAP. The integumental residue lining the OEAP and bulla is carefully stripped away until a clean boney surface is left. In some cases of extensive middle ear disease lateral bulla osteotomy may be performed to improve access to the tympanic cavity. The lateral aspect of the bulla is removed with rongeurs and debris within the bulla gently irrigated away. The soft tissues are closed over the

bulla placing taking care to minimise the potential for dead space.If indicated, a Penrose drain is placed from the bulla medial to the parotid salivary gland and exiting ventrally.The skin is closed in T or inverted L shape.

Complications A number of complications of TECA (LBO) have been reported including facial nerve injury - neuropraxia - paralysis, wound dehiscion, haemorrhage from the retroglenoid vein, vestibular signs and chronic sinus tract development. Some early reports indicated levels of complication of 80+%. However with careful dissection the incidence of serious complications should be less than 10%.

Prognosis With care the procedure can be extremely sucessful in resolving the most recalcitrant of chronic ear diseases and greater than 90% success rates have been reported.

General management of ear surgeries Whatever the surgical procedure contemplated there are several important general principles that can be applied: Surgical asepsis: it is extremely difficult if not impossible to ensure that the surgical site can be prepared to a surgically-aseptic standard. Rather than pursue endless lavage of the external ear it is probably preferrable to accept that aural surgery is a contaminated procedure. Hence, there is a strong rationale for perioperative antibiotic therapy. The postoperative stategy for ongoing therapy should be determined once the degree of surgical contamination has been assessed. Analgesia: surgery involving the ear is frequently a painful procedure and consideration should always be given to appropriate (often opioid analgesia) in cobination with extended non-sterodial anti-inflammatory therapy. Self trauma: because ear surgery may be uncomfortable there is a high risk of self trauma and premature wound disruption. Bandages should be avoided since there is a possibility of airway obstruction and suitable collars should be used to protect the wounds.

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tention until this century. Initially workers advocated removal of the auricular and annular cartilages up to the osseous external auditory prominence (OEAP). This failed to resolve any middle ear disease andresulted in an integumental residue being left in the bulla and sinus tracts frequently developed subsequently. Other procedures included the ventral approach to the bulla for the management of middle ear disease. The classical ventral approach did not meet with consistent success and long term relief of the infection. Most recently the concept of total ear canal ablation has been combined with lateral bulla osteotomy [TECA / LBO].

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Guided transcutaneous fine needle biopsy (FNB) in abdominal and pelvic disorders Mario Caniatti Med Vet, Istituto di Anatomia Patologica Veterinaria e Patologia Aviare, Università di Milano - Italy

Skill and experience with the technique are important owing to the fact that cellular material is a prerequisite for diagnosis. A minimum amount of gel should be used during ultrasound-guided FNB because it can contaminate the sample and cause cytological artifacts. At least two ot three smears should be collected. Unsuitable specimens are commonly caused by the failure to reach the lesion (obese patient, deep seated lesion, single and small-sized lesion...), or because of the firmness of the lesion (e.g. inflammatory fibrotic reaction, well differentiated spindle-cell tumors, desmoplastic epithelial tumors...). Hence, the operator must become familiar with the macroscopic appearance of an adequate cellular slide. A rapid microscopic assessment of the sample can also be attained using Romanowsky-type fast stains (e.g.: Hemacolor®, DiffQuik®, DipStat®...). If the cellularity of the sample appears too scanty for cytodiagnosis, the procedure should be immediately repeated.

Necrosis, hemorrhage or inflammation that may accompany malignancy, can cause false negative diagnosis of tumors in spite of good quality specimens. In these cases, multiple aspirations can help to make the right diagnosis. Based on the above mentioned causes of inadequacy or false negative specimens, the rate of false negative aspirate may vary, and an open biopsy via laparotomy may be necessary for definitve diagnosis. Impression smears or FNB can be made during surgery, although in this istance an incisional or excisional biopsy should be always preferred. The pitfalls in cytomorphologic interpretation, which in a percentage of neoplastic lesions can cause negative or “suspicious” reports of FNB, can be avoided with increased practical experience of cytopathologists. The increasing use of the sonographic guidance should help in this task. The main purposes of FNB of abdominal and pelvic organs are: 1) Identification of space-occupying lesions (benign-malignant; primary-metastatic) 2) Staging cancer 3) Treating benign cystic lesions. FNA biopsy can be therapeutic in cases of benign cystic lesions, which are often completely collapsed by aspiration. In these cases, both diagnosis and treatment are ensured by the aspiration. 4) Evaluation of diffuse disorders of the liver, spleen and prostate. In some cases of inflammatory process or metabolic disorder, particularly in liver pathology, histologic specimens are best suitable for accurate diagnosis The main contraindication to transcutaneous abdominal and pelvic FNB are: 1) Uncorrectable bleeding disorder 2) Lack of a safe biopsy path to the target (e.g. through a large vessel such as the aorta or the vena cava). Occasionally it is not possible to avoid passing a thin-gauge needle (21to 22- gauge) through a variety of viscera such as the bowel loops, stomac, liver; however it does not appear that this procedure increases the risk of infection or hemorrhage. In fact we should consider that the size of the needle is smaller than surgical sutures used in these organs.

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Clinical signs associated with abdominal, pelvic and retroperitoneal disorders are often vague and related to the location, type and size of the lesion. In some cases (e.g neoplasia, infection...), extra-abdominal abnormalities such as periferal lymphadenopathy can help to reach the diagnosis, while in many other instances only a bioptic procedure can lead to a definitve diagnosis. Fine needle biopsy (FNB) is a well established diagnostic method, which has expanded in recent years to include sampling of organs and masses in virtually any body site, whether superficial or deep, palpable or nonpalpable. The success of FNB is in part due to percutaneous needle biopsy under sonographic guidance, which has emerged as one of the most important recent advance in veterinary diagnostic imaging. It gives the opportunity to assess and biopsy deep seated organs and tissues without the need of surgery and at a very low cost. FNB can be obtained by conventional fine needle aspiration technique (FNA) or by nonaspiration technique termed “cytopuncture” or “fine needle capillary” (FNC) sampling. In human beings, some reports indicate FNA superior to FNC, some reports indicate FNC superior to FNA and some others indicate that there are no differences, suggesting that the technique of FNB (aspiration/nonaspiration) employed for cytodiagnosis can be left to the personal preference of the operator.

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Fine needle-track seeding of neoplasia is considered a very rare complication (1 out of 20.000 patients in a study in human beings) Many neoplastic (primary or metastatic) and non-neoplastic (inflammatory or degenerative) conditions of the abdomen can cause effusion. Cancer is a common cause of effusion, although not all the patients with abdominal cancer develop effusion and not all the effusions in patients with cancer are caused by cancer. It is very easy to collect abdominal fluid, much easier and safe than collect an adequate specimen from an abdominal mass. Therefore, the patient with an abdominal disorder should be thoroughly examined to identify an even mild effusion that must be sampled and cytologically examined. In this way, many inflammatory and neoplastic conditions can be diagnosed and useful information for prognosis and treatment can be recorded. We must be aware that cytology can not replace histopathologic examination, although, very often, a good cyto-

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logic sample can help to determine the inflammatory or neoplastic nature of the lesion. Inflammatory lesions can be subclassified as neutrophilic, eosinophilic, macrophagic, lymphocytic or mixed (e.g. mixed neutrophilic-macrophagic), and a specific etiology can often be determined. Neoplasia can be classified by cytology as epithelial, spindle-cell (mostly mesenchymal) and round-cell tumor. Based on these criteria, most tumors can be easily classified or sublclassified (e.g lymphomas), while others do not exhibit enough characteristics to be classified by cell type. Based on â&#x20AC;&#x153;criteria of malignancyâ&#x20AC;?, tumors can be defined as benign or malignant, although some malignant tumors show little criteria of malignancy. False positive diagnosis of neoplasia must be avoided by cytology, therefore extreme caution should be used in making a cytological diagnosis of neoplasia in cases where the smear is characterized by a mixed population of inflammatory and non-inflammatory (reactive or neoplastic) cells.

Ways to approach to selected abdominal diseases Roberto A. Santilli Med Vet, Private Practitioner, Samarate, Varese - Italy

Introduction Percutaneous ultrasound-guided biopsy have a particular importance in the diagnostic work-up of abdominal diseases. Ultrasound permits to discover the abdominal organ with disease particularly when focal lesions are present due to the difference in acoustic impedance. Ultrasound does not permit to exclude diseases with diffuse infiltration of abdominal organs that could appear with normal echotexture. Ultrasound has a very low specificity in the differentiation of inflammatory vs. neoplastic processes, and in the evaluation of malignancy of a particular neoplasm. Percutaneous biopsy include fine needle aspiration biopsy (21 - 22 gauge) for citological examination, and tissue core biopsy with tru-cut of 18 gauge, for histological examination. Contraindications for biopsy include coagulation disorders, hypoalbuminemia, and ascitis, although human reports demonstrated no increases in complications with peritoneal fluid. Different opinions exist as for the local tumour seeding secondary to percutaneous biopsy. A human medicine study demonstrated, on a sample of 800 biopsy in 19 years, no local tumour seeding following percutaneous biopsy; another

study showed malignant cells in peritoneal lavage fluid in 75% of patients with pancreatic adenocarcinoma that underwent a pre-surgical percutaneous biopsy, while only in 19% of patients with the same disease that did not underwent the biopsy. S.J. Withrow has some reserves about local tumour seeding and he does suggest to perform percutaneous biopsy only for abdominal mass in which citological diagnosis will permit a palliative treatment, if surgery is an option he suggests to obtain post-surgical histological samples. Complications during percutaneous biopsy include minor parenchimal haemorrhages, major cavitary of retroperitoneal haemorrhages, and biliary peritonitis or death. The incidence of these complication varies between 0% for fine needle aspiration and 2,7-5,6% for core biopsy. Fine needle aspiration technique is less expensive, easier, quicker with less complications than tissue core biopsy one. Fine needle citological samples can be obtain throughout aspiration or infissione with spine needle or special needle prepared for ultrasound-guided biopsy. Tissue core needle biopsy is performed throughout tru-cut set on a biopsy device (Biopty, Pro-mag or disposable), these devices permit an automated and pre-set shot which reduces parenchimal damages. Tissue core samples are about 1 cm long with a diameter of 2 mm. They must be prepared de-

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pending on the type of histological examination in 10% buffered formalin for light microscopy, 2% buffered glutaraldehyde for ultra-structural electron microscopy and with Michelâ&#x20AC;&#x2122;s fixative for immunocytochemistry or immunofluorescence. It is particularly important to include a coltural examination both for aerobes and anaerobes if a septic process is suspected. The choice between the two types of biopsy depend on the organ, and on the disease suspected. Tissue core biopsy are indicated in liver, kidney, prostate, linfonodes or mediastinal diseases; fine needle biopsy is indicated in spleen, pancreas, lung, prostate and liver diseases. Citological examination of the kidney is rarely diagnostic. Accuracy of percutaneous biopsy is about 84% for fine needle technique, while about 97% for tissue core with some variations depending on the organ.

the inability to follow the needle tip since the beginning, so it is suggested to expertise operators. Needle guided technique is easier particularly for inexpert because it permit the visualisation of the tip all during its course, and therefore it limits complications. Following biopsy the underlining area must be carefully scanned for 10 minutes and 4 - 6 hours later to look for minor or major haemorrhages. If haemorrhages occur compressive bandage, transfusion or reparative laparatomy are indicated. A remote possibility of biliary peritonitis does exist, particularly after liver biopsy in patients with cholangitis or post-hepatic icterus, in case of gallbladder or major biliary tract perforations. Clinical signs of biliary peritonitis include vomiting, icterus and abdominal pain 24 to 36 hours post-biopsy. Treatment of biliary peritonitis is surgical peritoneal lavage.

Technique

Personal experience

Before any tissue-core biopsy the coagulation profile, the packed cells volume and total solids must be obtained from the patient. The latter two parameters must be repeated 4 to 6 hours later to evaluate haemorrhage occurrence. Sedation is rarely needed during fine needle aspiration technique, while it is always indicate during tissue-core biopsy to prevent movements of the animal during the procedure that could cause laceration of the organ. Anesthesiological protocols more utilised both for cats and dogs include the association of diazepam (0,5 mg/kg) and ketamine chloridrate (10 mg/kg) I.V. The animal must be shaved and scrub with alcohol and betadine, a complete ultrasound examination must be repeated before the biopsy particularly to find the right area for the sampling, avoiding vascolarized areas and vital structures. Focal lesions apart, liver biopsy must be done at the left subcostal region, kidney biopsy at the cortical zone of caudal pole of the left kidney. There are two way to perform ultrasound-guided percutaneous biopsy: free hand and with needle guided. With the former the operator has free movement with less risks of laceration of the tissues, he can obtain different angle between the transducers and the needle to better visualised the tip (45Â° angle). The major problem with this technique is often

During 1996 and 1997 the author performed 59 tissue core biopsy (28 liver, 12 kidney, 7 prostate, 4 digiunal linfonodes, 1 uterus, 6 mediastinal mass) and 172 fine needle biopsy (78 liver, 31 abdominal nodes, 24 spleen, 17 prostate, 12 stomach or small intestine, and 10 kidney) Accuracy of citological diagnosis with fine needle biopsy was 77%, while histological diagnosis with tissue core 96%. Complications with fine needle aspiration were around 0,58% with one case of biliary peritonitis in a suppurative cholangitis resolved with immediate peritoneal lavage. The incidence of complications during tissue core biopsy was around 3,38% with one case of major retroperitoneal haemorrhages resolved with compressive bandage and transfusion and one case of bladder haemorrhage self-limiting.

Conclusions Ultrasound-guided percutaneous biopsy is an important diagnostic tool, its use and performing by expertise operators permit to limit complications and to obtain diagnostic samples both for citological and histological examination that allow to establish a correct treatment and to formulate a precise prognosis.

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Intramedullary interlocking nailing: a new technique in small animal orthopedics Daniele Cotto Med Vet, Private Practitioner, Torino - Italy

Gian Luca Rovesti

Summary Intramedullary interlocking nailing expanded for a terrific extent the indications for classic intramedullary nailing. In the past few decades different kinds of nails were developed for human orthopedic surgery, whereas the systems available for veterinary orthopedics are few and they need further experimental and clinical trials. The common feature of all these nails is to be locked in the medullary canal. The most common interlocking technique is to put screws through some holes in the nail perpendicular to its longer axis. When the interlocking is performed both proximally and distally to the fracture site it is referred to as static, whereas if it is done only on one side of the fracture it is referred to as dynamic. The technical modalities of application differ if an open or closed osteosynthesis is to be performed. The more demanding procedure of the technique is getting the distal holes with the screws. Tolerance of the implant is usually excellent and the results are very encouraging, even if in our experience healing times are longer than those commonly seen with external fixation techniques on average. It is possible to allow free weightbearing very early in the course of recovery, preferably in case of static interlocking, also if the osseous callus is still immature. Complications are grouped in intraoperative, postoperative and late. Among the operative ones the most frequent is the missing of the distal holes in the nail by the screws, and among the postoperative the most severe is the development of a nonunion. Complications related to the removal of the implant are negligible.

Intramedullary nailing was one of the first techniques used in both human and veterinary orthopedics.1 From the mechanical point of view the intramedullary nail is the device of choice for fixation of tubular bones, because it is coaxial with the bone, and the axis of loading of the nail and of the bone is the same.2-4 On a bone segment can be exerted bending, torsion, compression and distraction forces. A

cylindrically shaped nail can counterbalance only bending forces that are exerted on a fracture.5 In an attempt to counteract rotational forces, Kuntscher introduced a nail with a clover-leaf cross-section and a longitudinal slot, so that it could exert a strong friction on the inner cortex by means of a spring effect. An other technique suggested to neutralize torsional forces is the stack pinning.6,7 None of these techniques, however, can counterbalance axial compression and distraction forces. For this reason the selection of the fractures amenable with these techniques was limited to those not comminuted, transverse or short oblique of the shaft, so that their anatomical features could hinder the fracture collapse and the eventual proximal extrusion of the nail.8 Intramedullary interlocking nailing effectively solved these problems, extending the selection of cases in which intramedullary nails may be used.9 Many different interlocking nails have been developed in the past few decades in human orthopedics5,9 and they all have the common feature to be interlocked in the medullary canal, even when they differ for shape and technical modalities of application. The most common device used for interlocking is a screw positioned through a hole in the nail perpendicular to its longer axis. This can be done in two different ways: if the nail is locked both proximally and distally to the fracture site this is referred to as a static lock, whereas when is locked only proximally or distally is referred to as a dynamic lock. In the first configuration the forces exerted on the fracture are completely bypassed by the nail, while in the dynamic configuration an axial shearing along the major axis of the bone is allowed. The interfragmentary compression obtained with the dynamic locking can be intended as a mean to stabilize a fracture already quite stable, for example a transverse one, or be used to accelerate the maturation of the osseous callus when, coming from a static lock, this is dynamized by removing the screws, proximally or distally, once a primary bony callus is present.5 Intramedullary locking nailing may be performed with reamed or unreamed nails. Reaming has been proposed with the aim to adapt to the maximum degree the diameter of the medullary canal with the one of the nail,

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increasing in this way the contact surface, and to use nails of bigger size. Furthermore, some authors have emphasized the role of the reaming products as osteoinductive material, even if the procedure was heavily debated when first suggested.5 As a matter of fact, however, reaming is very harmful for the endosteal vascularization that, as shown by Rhinelander in his studies, supplies the medullary canal and at least the 2/3 of the cortex.10 If the physiological responses to the fracture are impaired by the medullary vascular damage the outcome may be a non-union. Some authors disagree with this hypothesis, and they suggest that the periosteal vascular system is more important, and it can supply the tissues formerly supported by the medullary vascularization.11 Unreamed unlocked nails, for example the Ender or Rush ones, and some unreamed locked nails used in human orthopedics have not been widely used in veterinary orthopedics. Only the Kirschner and Steinman pins used for the stack pinning technique have been applied in veterinary orthopedics. The intramedullary locked nail proposed by dr. Dueland12 has a full round section, and is not intended to fill completely the medullary canal with the purpose not to severely damage the medullary vascularization. Reaming may be done by means of rigid reamers if the fracture is surgically exposed, or it must be done by means of cannulated flexible reamers if the surgery is going to be performed without opening the fracture site. In this latter case the image intensifier is also needed. These requirements make this modality of nailing applicable in only few veterinary institutions. For closed nailing a preliminary reduction of the fracture by means of a transcheletal traction technique is required. Once the correct alignement of the bone segments is obtained, the guide wire is inserted until it bypasses the fracture area (Fig. 1) and then seated in the distal portion of the distal bone segment. Next the cannulated flexible reamers are inserted in the medullary canal following the guide wire (Fig. 2), starting with the smallest diameter and then increasing the diameter of the reamer of 0,5 mm until the desired size. Our protocol is to stop at that reamer that first reams the inner cortex, and to use a nail whose diameter is 0,5 to 1 mm smaller. Manual reamers are available, but it is better to use the motorized ones, at 300 to 600 rpm based on the bone characteristics. When the reamer bypasses the fracture site it is better to push it along the guide wire without reaming, to avoid both damaging the soft tissues and spreading apart the bony fragments when present. The guide wire has a distal olive that hinder the reamer to escape distally, avoiding in this way unplanned perforations; furthermore, it is useful in retrieving reamers broken in the medullary canal. It is very important its use during closed osteosynthesis, because it keeps the reamer along the longer axis of the bone without damaging the cortex. Using an open technique and rigid reamers is simpler, because usually reaming of the bone segments is performed starting from the fracture site and can be visually checked, even if it is easier to damage the cortex during the procedure. Unreamed nails are inserted directly or with a previous directional drilling. They have a point to proceed in the cancellous bone, and they are usually inserted by means of rotation movements or by hammering. Once the nail has been inserted in the medullary canal and the axis of the bone has been checked, locking is done

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next. Conceptually the interlocking may be performed in a static or dynamic way, as already told. Static interlocking is usually performed in unstable fractures, for example comminuted, long oblique, fragmented or with loss of substance. Static interlocking produces a great stability at the fracture site, and allows the maintaining of the bone segment length even when its anatomical reconstruction has not been done. Dynamic interlocking is performed only proximally or distally to the fracture site. Usually the interlocking is done on the smaller bone fragment, and is used when the fracture is quite stable, for example the transverse or short oblique without comminution and the impacted ones. In the absence of specific technical reasons, in our experience is preferable to interlock the nail proximally, to avoid it may slightly protrude from the hole of insertion causing seroma formation and local pain. It is possible to convert a static interlocking in a dynamic one when the local conditions of the fracture are ready to allow more loading. The positioning of the screws for interlocking is one of the most difficult parts of the technique. The proximal interlocking is usually the simpler to perform, because the proximal holes of the nail are closer to the targeting device, and therefore the drilling and the insertion of the screws are quite easily performed. For the distal screws the problems are many more. During the insertion of the nail in the medullary canal, in fact, the nail is subjected to bending and torsion forces that make the finding of the holes with an external targeting device very difficult, because it was set on a not deformed nail. This problem is bigger in human5 than in veterinary orthopedic, because the length of veterinary nails is much shorter, and for this reason the mistakes in targeting are less likely. Nevertheless, a system capable to get the distal holes with a percentage close to the 100% of attempts has not been proposed to date. Now the distal interlocking is feasible with different techniques. In human orthopedics is available the Brooker-Wills nail, that gains distal fixation by means of two flanges that are extruded from the nail. Quite commonly targeting devices applied on the image intensifier are used; when the hole in the nail is seen perfectly round through the targeting device, it is possible to drill and put the screw through it.5 Two techniques used both in human and in veterinary orthopedics are the free hand positioning of the screws and the use of external targeting devices to be connected with the nail. The free hand positioning needs the use of the image intensifier, and is done by positioning the limb of the patient so that the hole in the nail is seen perfectly round, that means the X-ray beam and the hole have the same axis (Fig. 3). A drill bit or a Kirschner wire are moved on a plane parallel to that of the limb until their point is seen at the center of the hole, and then the drill bit or the wire are tilted so that they are positioned perpendicular to the limb, without moving the point. If the point has not been translated during the maneuver the hole should be centered. Once the drill bit is removed, a self-tapping screw is inserted (Fig. 4). An other option is using a cannulated screw, that can be advanced along the Kirschner wire positioned through the hole and then removed after the screw is tightened. Now many efforts are put in developing an external targeting device that does not require the use of an image intensifier. If such a device could be developed, it would have the double

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result to reduce the X-ray exposition of the operating room personnel and to allow a bigger diffusion of the technique in veterinary medicine, because the availability of an image intensifier is not common in veterinary institutions. Our experience has been done mostly with an adjustable targeting device proposed by dr. Cotto, which is connected to an in-

tramedullary nail with section similar to the Kuntscher nail (Fig. 5). Once secured the nail to the targeting device, the centering bushings are set to get the holes in the nail, and they are fastened in that position. The nail is disconnected from the targeting device and inserted in the medullary canal by means of the handler that can be hammered, and then the

Figure 1 – Intraoperative image of the guide wire while it is pushed through the fracture site in the distal bone segment.

Figure 2 – Intraoperative image of a flexible cannulated reamer while it is advanced along the guide wire in the medullary canal.

Figure 3 – Intraoperative image of the distal holes in the nail. When they are seen perfectly round this means that the radiographic beam and the holes are on the same axis.

Figure 4 – Intraoperative image of the screws inserted through the distal holes in the nail.

Figure 5 – The targeting device proposed by dr. Cotto.

Figure 6 – The targeting device derived from the Grosse & Kempf system by dr. Rovesti.

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Figure 7 â&#x20AC;&#x201C; X-ray film showing a screw that broke the near cortex and went inside the medullary canal, seating directly on the nail.

Figure 8 â&#x20AC;&#x201C; X-ray film showing a non-union whose development was attributed to an excessive reaming of the medullary canal and to the use of a too big nail.

handler is removed and the targeting device is connected to the nail again. The bushings are now the guides for getting the holes. This targeting device can be used for nails customized for a specific patient, creating new holes in the nail and setting the bushings to get the new holes. The first experiences are encouraging, but more experimental and clinical work are needed to make the procedure more precise and repeatable. An other system is available in veterinary medicine, adapted from the Huckstep human nail for veterinary use by dr. Dueland, with an external targeting device with a series of holes. I used a personal system, derived from the human Grosse & Kempf one, with an handler can be hammered for insertion of the nail and targeting device specific for each size of nail (Fig. 6). These systems have good results but they do not have solved the problem of positioning the distal screws easily to date. In the postoperative period the patient is allowed full weightbearing, but with a restricted physical activity. In our experience the fracture healing took longer times if compared with external fixation techniques. Tolerance of the implant is usually excellent and the patient can have a quite normal life before the complete healing is achieved. Once a primary bone callus is present, if the interlocking was static it can be changed in dynamic to further stimulate the fracture healing. The nail may be removed when a complete healing has been achieved as judged radiographycally. In our expe-

rience the removal has been done between 4 and 14 months after the surgery. The removal of the nail is usually uneventful. For the procedure to be done correctly it is necessary an extractor; it should be performed cautiously, to avoid iatrogenic fractures. Complications can be classified as surgical, postsurgical or relating to the recovery period, and late or relating to the extraction of the implants. The most frequent surgical complication is the missing of the distal holes by the screws.13 As already anticipated, this is one of the major drawbacks for the application of the technique. If bent tibial nails are used, particular attention should be paid not to damage the posterior cortex, particularly when using rigid reamers. The damage to the posterior tibial cortex can cause a iatrogenic metaphyseal proximal fracture or a more severe lesion of the popliteal vessels.5 A surgical problem that has consequences on the removal of the nail is the breaking of the near cortex when the screw is tightened, so that it is anchored only on the far cortex and the screw head sits on the nail inside the medullary canal (Fig. 7). In the postsurgical period the most severe complication we had was a nonunion (Fig. 8). The cause of this problem has been attributed to the excessive reaming of the medullary canal and the use of a nail of too big size, with potential damage to the endosteal and medullary vascularization. In this case has been used a different technique. If a delayed consolidation is present with a static interlocking the dynamization of the con-

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References 1. 2. 3. 4. 5.

6. 7.

9. 10. 11. 12.

13.

Brinker WO, Hohn RB, Prieur WD et al., (1983), Manual of internal fixation in small animals, Springer-Verlag, Berlin, 5. Roe SC, (1995), Biomechanics of interlocking nail fixation., Am Coll Vet Surg Sympos, Chicago, IL, 280-281. Tarr RR, Wiss DA, (1986), The mechanics and biology of intramedullary fracture fixation, Clin Orthop Rel Res, 212: 10-17. Kinast C, Freigg R, Perren SM, (1990), Biomechanics of the interlocking nail, Arch Orthop Trauma Surg, 109: 197-204. Fontanesi G, Costa P, Giancecchi F, (1991), Inchiodamento endomidollare bloccato dellâ&#x20AC;&#x2122;arto inferiore, Aulo Gaggi, Bologna, 37-38, 1319, 5, 35, 45-47, 107-110. Kagan KG, (983), Multiple intramedullary pin fixation of the femur of dogs and cats, J Am Vet Med Assoc, 182: 1251-5. Vasseur PB, Paul HA, Crumley L, (1984), Evaluation of fixation devices for prevention of rotation in transverse fractures of the canine femoral shaft: an in vitro study, Am J Vet Res, 45: 1504-7. Brinker WO, Piermattei DL, Flo GL, (1990), Handbook of small animal orthopedics and fracture treatment, 2nd ed., W.B. Saunders Company, Philadelphia, 29. Court-Brown CM, (1991), An atlas of closed nailing of the tibia and femur, Martin Dunitz Ltd, London, 11-12, 1-7. Rhinelander FW, (1968), The normal microcirculation of diaphyseal cortex and its response to fracture, J Bone Joint Surg, 50(4): 784-800. Strachan RK, McCarthy I, Fleming R et al., (1990), The role of the tibial nutrient artery, J Bone Joint Surg, 72-B: 391-4. Dueland RT, Berglund L, Vanderby R et al., (1996), Structural properties of interlocking nails, canine femora, and femur-interlocking nail constructs, Vet Surg, 25: 386-396. Durall I, Diaz MC, Morales I, (1994), Interlocking nail stabilization of humeral fractures. Initial experience in seven clinical cases, Vet Comp Orthop Trauma, 7: 3-8.

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figuration is usually enough to accelerate the callus formation. Infections were not a problem in our experience. The dynamization of the nail gave some problem when performed proximally, because even a slightly protrusion of the nail through the insertion hole may result in seroma formation and local pain. For this reason dynamization was done almost exclusively distally, except for specific technical reasons. In the late complications we found the difficult finding of the heads of the screws because covered by fibrous tissue. If the head of the screw broke the near cortex during the surgery, when it is to be removed is necessary to drill the cortex, to find the screw inside the medullary canal and then to remove it. A minor problem was the presence of fibrous or osseous tissue in the proximal part of the nail, so that it is not possible to introduce the extractor. This tissue is usually easily removable, and this problem could be solved by positioning a plug on the top of nail when its insertion is completed. Iatrogenic fractures are reported as consequences of brutal maneuvers during the extraction of the nail. We did not see any complication following the removal of the implants.

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Leukemias in the dog C. Guillermo Couto

Summary Leukemias are malignant hemolymphatic neoplasms that originate in the bone marrow. Although they are not as common as lymphomas, they should be recognized clinically. This lecture will discuss the diagnostic and therapeutic approach to acute and chronic leukemias in dogs.

Epidemiology and classification Leukemias are malignant neoplasms that originate from hematopoietic precursor cells in the bone marrow. These cells have the inability to undergo terminal differentiation, thus self-replicating as a clone of usually immature (and nonfunctional) cells. The neoplastic cells may or may not appear in peripheral circulation, thus the confusing terms aleukemic or subleukemic leukemia are used when neoplastic cells proliferate within the bone marrow but are absent or scarce in circulation. Leukemias can be classified philogenetically according to the cell line they originate from into two broad categories: myeloid (or nonlymphoid) and lymphoid. The term myeloproliferative disease or disorder has also been used to refer to myeloid leukemias. According to their clinical course and the cytologic features of the leukemic cell population, leukemias can be classified as acute or chronic. Acute leukemias are characterized by an aggressive biologic behavior (i.e., death ensues shortly after diagnosis if untreated) and by the presence of immature (blast) cells in bone marrow and/or blood; chronic leukemias have a protracted, often indolent course, and the predominant cell is a well-differentiated, late precursor (i.e., lymphocyte in chronic lymphocytic leukemia and neutrophil in chronic myelogenous leukemia). In dogs, chronic myelogenous leukemia (CML) can undergo blast transformation (blast crisis), during which stage the disease behaves as an acute leukemia and is usually refractory to therapy. Blast crises do not appear to occur in dogs or cats with chronic lymphocytic leukemia (CLL). Acute leukemias may be difficult to classify morphologically based on evaluation of Giemsa- or Wright’s-stained blood or bone marrow smears as myeloid or lymphoid because poorly differentiated blasts look similar under light microscopy. In veterinary medicine, cytochemical stains are used routinely in several diagnostic laboratories to establish whether the blasts are lymphoid or myeloid, and also to sub-

classify myeloid leukemias as described below (i.e., myeloid vs. monocytic vs. myelomonocytic). These cytochemical stains reveal the presence of different enzymes in the cytoplasm of the blasts, which aid in establishing their origin. A classification scheme for acute leukemia in people was devised by a group of French, American, and British investigators (the FAB scheme) based on the morphologic features of the cells in blood and bone marrow Giemsa-stained smears. So far, this scheme has no prognostic or therapeutic implications in cats or dogs; thus it is not discussed. In the dog, leukemias represent less than 10% of all hemolymphatic neoplasms and are therefore considered to be rare. In our hospital, the leukemia-to-lymphoma ratio is approximately 1:5 to 1:7. This ratio is artificially high, since most dogs with lymphoma are usually treated by the local veterinarians, whereas most dogs with leukemia are referred for treatment. Most leukemias in dogs are considered to be “spontaneous”, although radiation exposure and viral particles have been identified as possible etiologic factors in dogs with this disease.

Acute leukemias In the dog, acute myeloid leukemias are more common than acute lymphoid leukemias, representing approximately three fourths of the cases of acute leukemia. It should be remembered, however, that morphologically (i.e., by evaluation of a Wright’s- or Giemsa- stained blood or bone marrow smear) most acute leukemias are initially classified as lymphoid. After performing cytochemical staining of the smears, approximately one third to one half of them are reclassified as myeloid. Approximately half of the dogs with myeloid leukemia have myelomonocytic differentiation when cytochemical stains are used. The clinical signs and physical examination findings in dogs with acute leukemia are usually vague and nonspecific. Briefly, most owners seek veterinary care when their dogs develop lethargy, anorexia, persistent or recurrent fever, weight loss, shifting limb lameness, and other nonspecific signs; neurologic signs occur occasionally. Splenomegaly, hepatomegaly, pallor, fever, and mild generalized lymphadenopathy are commonly detected during routine physical examination. The spleen in these dogs is usually markedly enlarged, and it has a smooth surface on palpation. Careful inspection of the mucous membranes in dogs

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with acute leukemia often reveals petechiae and/or ecchymoses in addition to pallor; icterus may also be detected if marked leukemic infiltration of the liver or hemolysis is present. The generalized lymphadenopathy in dogs with acute leukemia is usually mild, in contrast with dogs with lymphoma, in which the lymph nodes are massively enlarged. Also, the majority of dogs with leukemia display constitutional signs (i.e., they are clinically ill), whereas over half of the dogs with lymphoma are asymptomatic. The treatment of dogs with acute leukemias is usually unrewarding. Most dogs with these diseases respond poorly to therapy, and prolonged remissions are rarely obtained. Treatment failure is usually because of one or more of the following factors: 1. Failure to induce remission (more common in AML than in ALL) 2. Failure to maintain remission 3. Presence or development of organ failure resulting from leukemic cell infiltration does not allow for the use of aggressive combination chemotherapy (i.e., because of enhanced toxicity) 4. Development of fatal sepsis and/or bleeding caused by already existing or treatment-induced cytopenias Prolonged remissions in dogs with AMLs treated with chemotherapy are extremely rare. In most dogs with AML remissions are rarely observed. If they do so, the remission is usually extremely short-lived, and survivals rarely exceed 3 months. Also, over half of the dogs die during induction because of overwhelming sepsis or bleeding. The supportive treatment required in these patients (e.g., chemotherapeutic agents, blood component therapy, intensive care monitoring) is financially unacceptable to most owners (the cost of treatment for a 70-pound dog with acute leukemia ranges from $1500 to $3000 for the first month of treatment), and the emotional strain placed on the owner is also quite high. Therefore, the owners should be aware of all these facts before deciding to treat their dogs with chemotherapy. In dogs with ALL, the prognosis may be better; however, responses to treatment and survival times are considerably lower than in dogs with lymphoma. The remission rates in dogs with ALL are approximately 20% to 40%, in contrast with those in lymphomas, in which they approach 90%; survival times are also shorter than those in dogs with lymphoma, averaging 1 to 3 months, when appropriate chemotherapy protocols are used. Untreated dogs usually live less than 2 weeks.

Chronic leukemias In dogs, CLL is more common than CML; the latter is a poorly characterized entity. In our hospital, we evaluate approximately 6 to 8 dogs with CLL a year, whereas we evaluate approximately one dog with CML every 3 to 5 years. Chronic lymphocytic leukemia is one of the most commonly diagnosed leukemias in most diagnostic referral laboratories. As with their acute counterparts, clinical signs in dogs with CLL or CML are vague and nonspecific; however, a chronic history of vague clinical signs precedes the diagno-

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sis of chronic leukemia in approximately half of the dogs. A large number of cases of chronic leukemia are diagnosed incidentally during routine physical examination and laboratory evaluation (i.e., dogs are asymptomatic). Clinical signs are present in approximately half of the dogs with CLL and include lethargy, anorexia, vomiting, polyuria/polydipsia, detection of enlarged lymph nodes by the owners, intermittent lameness, intermittent diarrhea and/or vomiting, and weight loss. Physical examination findings in these dogs include mild generalized lymphadenopathy, splenomegaly, hepatomegaly, pallor, and pyrexia. The clinical signs and physical examination findings in dogs with CML appear to be similar to those of dogs with CLL. A terminal event in dogs with CLL is the development of a diffuse large cell lymphoma termed Richterâ&#x20AC;&#x2122;s syndrome, characterized by massive generalized lymphadenopathy and hepatosplenomegaly. Once this multicentric lymphoma develops, chemotherapy-induced long- lasting remissions are difficult to obtain, and survival times are short. Blast crisis, characterized by the appearance of immature blast cells in blood and bone marrow, occurs in humans and dogs with CML months to years after the initial diagnosis. In humans, these blasts are either myeloid or lymphoid; the origin of the blast cell in dogs with blast crises has not been determined. Five of 11 dogs with CML reported in the literature for which sufficient clinical and hematologic information is available developed blast crises. Blast crises do not appear to occur in dogs with CLL. The clinician usually faces the dilemma of whether or not to treat a dog with chronic leukemia. If the dog is symptomatic, or has organomegaly or concurrent hematologic abnormalities, treatment with an alkylator (with or without corticosteroids) is indicated. If paraneoplastic syndromes (i.e., immune hemolysis or thrombocytopenia, monoclonal gammopathies) are absent, we recommend using single-agent chlorambucil (LeukeranÂŽ) at a dose of 20 mg/m2 PO once every 2 weeks. If paraneoplastic syndromes are present, the addition of corticosteroids (prednisone, 50 to 75 mg/m2 PO sid for 1 week; then 25 mg/m2 PO qod) may be beneficial. Because the growth fraction of neoplastic lymphocytes in CLL appears to be low, a delayed response to therapy is common. In a high proportion of dogs with CLL treated with chlorambucil or chlorambucil/prednisone, resolution of the hematologic and physical examination abnormalities may take over 1 month (and as long as 6 months). This is in contrast to dogs with lymphoma and acute leukemias, in which remission is usually induced in 2 to 7 days. The survival times of dogs with CLL are quite long. Indeed, even without treatment, survival times of over 2 years are common. Over two thirds of the dogs with CLL treated with chlorambucil (with or without prednisone) in our clinic have survived in excess of 2 years. Most dogs with CLL do not die from leukemia-related causes, but rather from other geriatric disorders. Treatment of dogs with CML using hydroxyurea may result in prolonged remission, provided blast crisis does not occur. However, the prognosis does not appear to be as good as for dogs with CLL (i.e., survivals of 4 to 15 months with treatment). Treatment of blast crises is usually unrewarding.

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Extranodal lymphomas C. Guillermo Couto DVM, Dipl ACVIM, Department of Veterinary Clinical Sciences, College of Veterinary Medicine The Ohio State University - Columbus - USA

Extranodal lymphomas are relatively common in both dogs and cats. In the former they occur in the alimentary tract, skin, and other areas, while in cats they are common in the alimentary tract, upper respiratory system, and central nervous system. This lecture will discuss the clinical recognition and treatment of this neoplasm.

Epidemiology Lymphoma (malignant lymphoma, lymphosarcoma [LSA]) is defined as a lymphoid malignancy that originates from solid organs (e.g., lymph nodes, liver, spleen). This differentiates lymphomas from lymphoid leukemias, which originate in the bone marrow. Previous reports document that approximately 70% of cats with lymphoma are feline leukemia virus (FeLV)-positive. The prevalence of viremia in cats with lymphoma varies with the anatomic form of presentation (see below); but, in general, young cats with lymphoma are FeLV-positive, whereas older cats are negative. Over the past few years, the prevalence of FeLV infection in cats with lymphoma in our clinic appears to be decreasing. The role of feline immunodeficiency virus (FIV) in the pathogenesis of feline lymphoma is still unclear, although it has been documented that FIV-positive cats appear to have a higher risk of developing lymphoma. In dogs, lymphomas are considered to be multifactorial in nature, since no single etiologic agent has been identified. However, a genetic component is evident, since the prevalence of this neoplasm is high in certain blood lines. There is also a distinct breed predisposition for lymphoma in dogs, with some breeds such as Boxer, Basset Hound, Rottweiler, Cocker Spaniel, St. Bernard, Scottish Terrier, Airedale Terrier, English Bulldog, and Golden Retriever being at high risk; the breeds most commonly affected in our clinic are Golden Retrievers, Cocker Spaniels, and Rottweilers. The age of presentation in cats with lymphoma is bimodal, with the first peak occuring at approximately 2 years of age and the second one at approximately 10 to 12 years of age. The first peak is composed mainly of FeLV-positive cats, whereas the second one includes predominantly FeLVnegative cats. The mean age of presentation of lymphoma in FeLV-positive cats is 3 years, whereas in FeLV-negative cats

it is 7 to 8 years. As discussed previously, the prevalence of lymphomas in FeLV-positive cats appears to be decreasing. In contrast, most dogs with lymphoma are middle-age or older (6 to 12 years of age).

Clinical features The clinical signs and physical examination findings in cats and dogs with extranodal lymphomas are extremely variable and depend on the location of the mass(es). In general, the clinical signs are the results of compression or displacement of normal parenchymal cells in the affected organ (e.g., azotemia in renal lymphoma, variable neurologic signs in central nervous system [CNS] lymphoma). Common extranodal forms in dogs include cutaneous and ocular, and in cats they include nasopharyngeal, ocular, renal, and neural. Cutaneous lymphoma is one of the most common extranodal forms of presentation in dogs, representing the most common extranodal form of this neoplasm in dogs in our clinic, but it is rare in cats. Clinical signs and lesions are extremely variable, and they can mimic any primary or secondary skin lesion. Dogs with mycosis fungoides (an epidermotropic T-cell lymphoma) usually present with a chronic history of alopecia, desquamation, pruritus, and erythema, eventually leading to plaque and tumor formation. Mucocutaneous and mucosal lesions are relatively common, and generalized lymph node involvement may be absent on first presentation. A characteristic lesion in dogs with this form of lymphoma is a circular, raised, erythematous, donut-shaped, dermoepidermal mass that contains normal skin in the center of the lesion. Most of the cases of cutaneous lymphomas in cats reported in the literature were in cats with negative FeLV status. Renal lymphoma is relatively common in cats, but rare in dogs. Cats with this anatomic form are presented for evaluation of vague clinical signs, usually secondary to chronic renal failure. Physical examination reveals an emaciated cat that is usually anemic and has large, irregular, and firm kidneys; both kidneys are commonly affected. There is a purported association between renal and CNS lymphoma in cats, to the point that some clinicians recommend using drugs that achieve high CNS concentrations (i.e., cytosine arabinoside) in cats with renal involvement in attempts to prevent secondary CNS dissemination. In our clinic, this association has not been recognized.

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Summary

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Table 1: Chemotherapy protocols for dogs and cats with extranodal lymphomas 1) Induction of remission: • COAP protocol1: - cyclophosphamide (Cytoxan®) 50 mg/m2 BSA, PO, 4 days a week (or every other day); in cats, cyclophosphamide is used at 200300 mg/m2, PO, every 3 weeks to decrease prevalence of anorexia. - vincristine (Oncovin®) 0.5 mg/m2 BSA, IV, once a week - cytosine arabinoside (Cytosar-U®) 100 mg/m2 BSA/day, IV drip or SQ, for only 2 days in cats and 4 days in dogs - prednisone 50 mg/m2 BSA, PO, sid for a week; then 20 mg/m2 BSA PO, every other day 2) Intensification: DOGS: • l-asparaginase (Elspar®) 10,000-20,000 IU/m2 BSA, SQ (one dose) or • vincristine (Oncovin®) 0.5-0.75 mg/m2, IV, every 1 to 2 weeks CATS: • doxorubicin (Adriamycin®) 25 mg/m2, IV, every 3 weeks or • mitoxantrone (Novantrone®) 4-6 mg/m2, IV, every 3 weeks 3) Maintenance2: • LMP protocol: - chlorambucil (Leukeran®) 20 mg/m2 BSA, PO, every other week - methotrexate (Methotrexate®) 2.5 mg/m2 BSA, PO, 2 to 3 times per week - prednisone 20 mg/m2, PO, every other day • COAP protocol: - use as above every other week for 6 treatments, then every third week for additonal 6 treatments, and try to maintain the patient on one treatment every 4th week. MAINTENANCE THERAPY IS CONTINUED UNTIL THE TUMOR RELAPSES 4) Rescue: DOGS: - D-MAC protocol (14-day cycle) - dexamethasone 0.5 mg/lb, PO or SQ on days 1 and 8 - actinomycin D (Cosmegen®) 0.75 mg/m2, IV push on day 1 - cytosine arabinoside (Cytosar®) 200 -300 mg/m2, IV drip over 4 hours OR SQ, on day 1 - melphalan (Alkeran®) 20 mg/m2, PO, on day 8* - AC protocol (21 day cycle) - doxorubicin (Adriamycin®) 30 mg/m2 BSA IV, day 1 - cyclophosphamide (Cytoxan®) 100-150 mg/m2, PO, days 15 and 16 - ADIC protocol (cycle is repeated every 21 days) - doxorubicin (Adriamycin®) 30 mg/m2 BSA, IV, on day 1 - dacarbazine (DTIC®) 700-1,000 mg/m2 BSA, IV infusion (over 6-8 hours), on day 1 - CHOP protocol (21 day cycle) - cyclophosphamide (Cytoxan®) 100-150 mg/m2, IV, on day 1 - doxorubicin (Adriamycin®) 30 mg/m2, IV, on day 1 - vincristine (Oncovin®) 0.75 mg/m2, IV, on days 8 and 15 - prednisone 20-25 mg/m2, PO, every other day CATS: - MiC protocol (21 day cycle) - mitoxantrone (Novantrone®) 4-6 mg/m2, IV drip over 4-6 hours on day 1 - cyclophosphamide (Cytoxan®) 200-300 mg/m2, PO, day 15 or 16 - AC protocol (21 day cycle) -doxorubicin (Adriamycin®) 25 mg/m2, IV, on day 1 -cyclophosphamide (Cytoxan®) 200-300 mg/m2, PO, day 15 or 16 - MiCA protocol (21 day cycle) - mitoxantrone (Novantrone®) 4-5 mg/m2, IV drip over 4-6 hours on day 1 - cyclophosphamide (Cytoxan®) 200-300 mg/m2, PO, day 15 or 16 - cytosine arabinoside (Cytosar-u®) 200 mg/m2, IV drip over 4-6 hours (MIXED IN THE SAME BAG WITH MITOXANTRONE) on day 1 - CHOP protocol (21 day cycle) -cyclophosphamide (Cytoxan®) 200-300 mg/m2, IV, on day 10 -doxorubicin (Adriamycin®) 20-25 mg/m2, IV, on day 1 -vincristine (Oncovin®) 0.5 mg/m2, IV, on days 8 and 15 -prednisone 20-25 mg/m2, PO, every other day 1

Use for 6 to 10 weeks, then use LMP. Use until relapse occurs; then go to “rescue”. * After 6 doses, substitute Leukeran (20 mg/m2, PO, q/2 weeks) for Alkeran 2

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Diagnosis Before instituting therapy, a confirmatory cytologic or histopathologic diagnosis should be obtained. In addition, a minimum data base consisting of a CBC, serum biochemistry profile, and urinalysis should be obtained if the owners are contemplating treatment. In most cats and dogs with multicentric, superficial extranodal, mediastinal, or alimentary lymphoma, a diagnosis can easily be obtained by fine-needle aspiration cytology of the affected organ(s) or lymph node(s). Lymphomas are characterized by the prevalence of a monomorphic population of immature round lymphoid cells, with prominent nucleoli. In our practice, lymphomas can be diagnosed cytologically in approximately 90% of dogs and 70% to 75% of cats

evaluated (i.e., usually in only 10% of the dogs and 25% to 30% of the cats is histopathologic evaluation of a surgically excised lymph node necessary to establish a diagnosis). Until conclusive evidence that the histopathologic classification of canine and feline lymphomas offers prognostic information, the surgical removal of a lymph node or extranodal mass for histopathologic evaluation in a patient with a cytologic diagnosis of lymphoma is not indicated. Obtaining a cytologic diagnosis rather than a histopathologic diagnosis from an excisional lymph node biopsy also offers two major benefits: it is associated with minimal or no morbidity, and it is financially acceptable to most owners.

Treatment The treatment of cats and dogs with lymphoma is divided into several phases or strategies: induction of remission, intensification, maintenance, and reinduction of remission or â&#x20AC;&#x153;rescueâ&#x20AC;? (Table 1). Immediately after diagnosis, a relatively aggressive multiple agent chemotherapy protocol (COAP) is used to induce remission; during this phase, which lasts 6 to 8 weeks, the patients are evaluated by a veterinarian weekly, at which time they receive an intravenous injection of an antimitotic agent (vincristine) in addition to undergoing a routine physical examination (with or without a CBC). If at the end of this phase the patient is considered to be in complete remission (CR) (i.e., complete disappearance of all neoplastic masses), the maintenance phase is initiated. During the maintenance phase, a multiple agent chemotherapy protocol consisting of three drugs (LMP) administered orally is used, so that the patient requires less intensive monitoring (once every 6 to 8 weeks). This phase continues until the tumor relapses (i.e., is out of remission), at which time the reinduction phase begins. This phase is similar to the induction phase, in that intensive treatments are used. Once remission is obtained, the patient is placed again on a maintenance protocol that is usually a modification of the original maintenance protocols (at OSU we typically use the LMP protocol, but we substitute Cytosar for the methotrexate, at a dose of 200-300 mg/m2, SQ, every other week). If at the end of the induction phase the patient is not in CR, intensification with L-asparaginase is recommended before initiating the maintenance phase. In addition to the chemotherapeutic approach discussed in this section, a variety of protocols have been used successfully in the treatment of cats and dogs with lymphoma.

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Ocular lymphoma occurs both in cats and dogs, but is apparently more common in the former. In dogs ocular involvement appears to be commonly associated with the multicentric form, whereas in cats both primary and secondary ocular involvement are commonly recognized. A variety of signs and lesions may be present in these patients, including photophobia, blepharospasm, epiphora, hyphema, hypopyon, ocular masses, third eyelid infiltration, anterior uveitis, chorioretinal involvement, and retinal detachment. Nasopharyngeal lymphoma is relatively common in cats but is extremely rare in dogs. Clinical signs are similar to those of cats with any upper respiratory disorder and include sneezing, unilateral or bilateral nasal discharge (from mucopurulent to frankly hemorrhagic), stertorous breathing, exophthalmus, and facial deformity; this is one of the most common forms of presentation of extranodal lymphoma in cats in our clinic. Cats and dogs with neural lymphoma are presented with a variety of neurologic signs. Although CNS signs are more common, peripheral nerve involvement may occur (predominantly in cats). Three forms of presentation are clinically recognized, including solitary epidural lymphoma, neuropil (intracranial or intraspinal) lymphoma (also referred to as true CNS lymphoma), and peripheral nerve lymphoma. Neurologic signs are usually multifocal, although solitary intracranial or spinal involvement also occurs. Neural lymphomas can be primary (e.g., epidural lymphoma), or they may be secondary to the multicentric form; as discussed, secondary CNS lymphoma may be common in cats with the renal form.

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Follicular dysplasias Luis Ferrer

Dysplasia: a confusing term

Common clinicopathologic features

Dysplasia originates from the greek words dys (bad) and plassein (to give form). In medicine, initially was used to describe abnormalities in the development, growth or tissue differentiation and may be this is the most correct definition. We still use the word with this sense in “renal dysplasia”, “retinal dysplasia” or “hip dysplasia”. However, in 1949, Papanicolau used dysplasia in medical lenguage with another aception: to define pre-malignant lesions or lesions of borderline malignancy: “cervical dysplasia” or “epithelial dysplasia”. Furthermore, the term dysplasia have a few more minor aceptions, restricted to some scientific fields. In consequence, some authors have suggested that the term is empty of meaning and it is useless. The term is very unprecise1 and should be avoided. For those authors, the term “prostatic dysplasia” is so vague that it is equivalent to “disease of the prostate”, only seems more technical, more precise. It is true that dysplasia is a confusing and abused terminology. The problem is their substitution in the several meanings that this word has accumulated. Dunstan has suggested to substitute, in dermatopathology, the term dysplasia by dystrophy. However, dystrophy is also very difficult to define and in pathology textbooks and dictionaries is used with different meanings. Before a broad consensus is reached, I will continue using the term follicular dysplasia. In veterinary dermatology the term is used to define a group of diseases of hair follicles, with a strong genetic basis but usually not congenital, in which there is abnormal development of hair follicles of non-neoplastic and non- inflammatory origin, which leads to abnormal follicular architecture. Although the list of diseases included in this group changes from one author to the other, a few diseases are almost always included: • colour dilution alopecia, black hair follicular dysplasia and other dysplasias related to the pigmentary system. • Follicular dysplasia of portuguese water dog and other curly coated dogs (spanish water dog, irish water spaniel, ...). • Cyclic dysplasia of Boxers, Airedale Terriers and Staffordshire Terriers (also called cyclic flank dysplasia). • Melanoderma and alopecia of Yorkshire Terriers.

1) Strong breed predilection (reflecting the genetic background). 2) Affect young to middle aged animals (usually between 6 months and 4 years). 3) Clinically, the affected dogs present symmetric alopecia, with typical regional distribution (trunk, pinnae, flanks,...). Alopecic areas usually develop hyperpigmentation. There is not pruritus and the general condition of the patients is otherwise good. Seborrhoea and bacterial folliculitis are also common in the alopecic areas. 4) The diagnosis based on examination of skin biopsies. Histologically the hair follicles are abnormally or incompletely formed. 5) There is no effective treatment.

Colour dilution alopecia and related follicular dysplasias Cause and pathogenesis: unknown. Several hypothesis have been proposed. Some authors think that these diseases are conquence of a defect in the transfer of melanine from melanocytes to keratinocytes. Other dermatologists2 think that the key defect is an abnormal degradation of melanosomes, may be due to abnormal calcium metabolism. For either reason, there is an abnormal accumulation of stage III and IV melanosomes inside keratinocytes and hair cortex cells. Later, these melanosomes rupture and leak melanine, which is toxic to epithelial cells. The genetic basis is partially known. The locus D, probably together with others, regulates the dilution of the hair colour. The alelle “d”, recessive, leads to the diluted colour. In consequence, d/d dogs have a blue-gray coat. However, not all blue-gray animals develop alopecia and an alopecia of identical clinicopathologic charcteristics have been identified in brown-black dogs. The alopecia/follicular dysplasia may be is the consequence of another gen, that is most prevalent between diluted animals or the effects of this gen are more evident on dogs of diluted coat. Presentation: blue or gray dogs, males or females without distinction. Any breed or cross. Very common in Doberman Pinschers, Yorkshire Terriers and Great Danes. The disease usually begins between the 6th and 9th month of life. In less diluted animals the alopecia begins later, between the

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Med Vet, Dipl ECVS Private Practitioner, Cremona - Italy

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2nd and 3rd year. Beco and coworkers3 have described an early development of the disease in Teckels (before the third month). Clinical signs: symmetric alopecia that usually begins on the dorse of the patient and progressively extends to all diluted areas. In early stages, occasionally, the disease waxe and wane (hairs regrow), but the alopecia with time become permanent. At 2-3 years of age diluted dogs (blue or gray) are usually completely alopecic (in all diluted areas). Desquamation and folliculitis are common in the alopecic areas. In black dogs (black and brown) a very similar disease has beeen described.4 However, in these animals the alopecia begins after the second year of life and is less severe. Complete truncal hair loss has not been recognized. May be these animals are recessive for the gen that causes the alopecia or in non-diluted dogs the efects of the gen expression are less severe. The so-called black hair follicular dysplasia -the alopecic change only affects black hairs- is considered to be also a related disease. Dysplasia, because it is cyclic (reversible). Clinical signs: the disease is more common in Boxers, Bulldogs, Airedale Terriers and Staffordshire Terriers, but can be diagnosed in any breed. Males and females are equally affected. Most animals are older than 2 years and the lesions appear predominantly in spring and autumn. Characteristic signs consist in well-demarcated (“geometric”) alopecic and hyperpigmented areas located in both flanks. The alopecia persist for a few months and then, usually, the. Mild pigmentary incontinence is also common in early stages. Later, hair follicles present dysplastic forms and follicular keratosis. Inside hair follicles appear clumps of melanine. In chronic stages hair follicles appear in telogen, dilated, filled with melanine and keratine. Pigmentary incontinence around hair follicles is very prominent. Suppurative folliculitis is common. Treatment: there is no known treatment. Some authors have suggested that retinoids can be useful to stop the development of alopecia but in our experience this treatment is uneffective. If necessary, topical therapy has to be used to control seborrhoea and folliculitis.

Follicular dysplasia of portuguese water dog and other curly coated dogs Cause: unknown. Probable genetic origin. The authors that have investigated the disease5 think that there are abnormality in the pigmentary system and in the hair matrix cells. Clinical signs: the disease affects, probably, all curly coated breeds although it has been described in portuguese water dogs, spanish water dogs and irish water spaniels. Both males and females are equally affected. The clinical signs appear between the first and the fifth year of life and consist in symmetric alopecic areas that affect the trunk, posterior limbs and periocular areas. The hair is brittle, dull. In some patients the hair loss is permanent and in other patients waxes and wanes. Diagnosis: histologic. Hair follicles appear dysplastic, filled with melanine and detritus. Perifollicular pigmentary incontinence is prominent. There is apoptosis of ker-

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atinocytes of the hair sheaths and vacuolization of cells of the inner root sheath. Treatment: there is no effective treatment.

Cyclic dysplasia of Boxers, Airedale terriers and Staffordshire Terriers (also called cyclic flank dysplasia and cyclic flank alopecia) Cause: Unknown. Hormonal imbalances has been discarded.6 May be the alopecia is related to abnormal responses to photoperiod. Many authors consider that this entity should not be considered a dysplasia, because it is cyclic (reversible). Clinical signs: the disease is more common in Boxers, Bulldogs, Airedale Terriers and Staffordshire Terriers, but can be diagnosed in any breed. Males and females are equally affected. Most animals are older than 2 years and the lesions appear predominantly in spring and autumn. Characteristic signs consist in well-demarcated (“geometric”) alopecic and hyperpigmented areas located in both flanks. The alopecia persist for a few months and then, usually, the hair grows again. General condition is good and there is no pruritus. Diagnosis: clinical picture is very suggestive. However, deffinitive diagnosis is based on skin biopsy. In early stages, hair follicles appear in telogen, moderately dilated and with dysplastic images. Dysplastic follicles usually have an octopus-appearence. Sebaceous glands are melanized. Treatment: Paradis has treated some patients with melatonine. Prognosis is unpredictable in any given patient.

Alopecia and meloderma of Yorkshire Terriers Cause: unknown. Genetic basis suspected (only YT affected, high prevalence in certain families and breederds). Clinical signs: Yorkshire Terriers, males and females, between 6 months and 3-4 years are affected. Typical changes are alopecia and hyperpigmentation over the bridge of the nose, on the pinnae and occasionally tail and feet. Affected skin is smooth and shiny. There is no pruritus. Diagnosis: skin biopsies revealed hyperkeratosis, and telogenic, moderately dysplastic hair follicles. Treatment: no effective treatment for these entity has been described.

References 1. 2. 3.

4. 5.

King DF, (1992), Dysplasia. An abused and confusing terminology, Am J Dermatopatol, 14: 454-461. Roperto F, Cerundolo R, Restucci et al., (1995), Colour diluton alopecia (CDA) in ten Yorkshire Terriers, Vet Derm, 6: 171-178. Beco L, Fontaine J, Gross TL et al., (1996), Colour dilution alopecia in seven dachshunds. A clinical study and the heredity, microscopical and ultrastructural aspects of the disease, Vet Derm, 7: 91-97. Miller WH, (1990), Folllicular dysplasia in adult black and red Doberman pinschers, Vet Dermatol, 1: 181-186. Miller WH, Scott DW, (1995), Follicular dysplasia of the portuguese

water dog, Vet Derm, 6: 67-74. Curtis CF, Lloyd DH, Evans H, (1995), An investigation of the reproductive and growth hormone status of dogs affected by cyclical (seasonal) flank alopecia at both maximu and minimum photoperiod, Proceedings of the 12th Annual Congresss of the ESVD, pp 230, Barcelona. Miller M, Dunstan R (1993), Seasonal flank alopecia in Boxers and Airedale Terriers: 24 cases (1985-1992), J Am Vet Med Assoc, 203: 1567-1572.

469 8.

9. 10. 11.

Paradis M, (1995) Hereditary skin diseases in dogs and cats: selected topics, Proceedings of the 12th Annual Congress of the ESVD, pp 138-139. Carlotti DN, (1993), A propos de alopecies auriculaires. Point Veterinaire, 25: 8-12. Lampiris D, (1985), Skin condition in Yorkshire Terriers, Canine Pract, 12:29. Lampiris D, (1985), Skin condition in Yorkshire Terriers, Canine Pract, 12:29.

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Fracture, nonunion and deformity treatment with the Ilizarov Method Antonio Ferretti

The Ilizarov apparatus is a circular type, three-dimensional fixator characterized by wires which can be driven through the bone in all directions, fixed to the rings at 360째. The only limitation is the anatomy, with certain positions which have to be avoided to prevent neurovascular damage or tenomuscular interference which may lead to motory function failure or alteration. The possibility of inserting wires at an angle, possibly at 90째, opposing wires with stoppers or threaded pins make the Ilizarov apparatus incredibly stable against shear and rotational forces.

Fracture treatment It is for these reasons that the Ilizarov system is perfectly indicated for fracture and nonunion treatment. Furthermore, the possibility of correcting bone segment positioning via wire or ring movement makes the closed reduction of fractures, as well as fracture site compression and distraction, possible. The ideal assembly, which produces the highest degree of stability, is the one with four levels of fixation: a proximal block with two rings and a distal block with two rings (Fig. 1a). The proximal and the distal rings have to be as far as possible from the fracture site; the middle rings as close as possible to the fracture site. This is clearly not always possible. Figure 1b shows the assembly which is necessary when dealing with an extensive diaphyseal comminuted fracture: in this case the apparatus has a support function. The assembly in Figure 1c is not correct for fracture or nonunion treatment while it may be used, even if it is not the ideal solution, for bone lengthening. The stability of the apparatus is increased by the tenomuscular elements and by the regenerated tissue subject to distraction tension. The assembly in Figure 1d is surely not correct because of its instability. Both the rings of the proximal block and the rings of the distal block are too close to the fracture site and are consequently unable to contrast a long lever arm. To stabilize metaphyseal fracture sites it may be necessary to extend the apparatus to the contiguous bone segment (Fig. 2a-b). If this is not possible the metaphysis is to be fixed with two levels of fixation (Fig. 3): at least two wires on the ring and the third wire on supports or with threaded pins as in Figure 4b.

The use of threaded pins in the proximall portion of some segments (femur, humerus, tibia, radius-ulna) proved itself an extremely valid solution enabling the stable fixation of segments which cannot be surrounded by the apparatus (proximal humerus and femur) (Fig. 4a) or when the wires have to be positioned at an angle inferior to 60째 (proximal tibia and radius). The use of threaded pins in the proximal tibia resulted extremely valid while problems have arisen in the proximal radius, due to the limited thickness of the bone. A hybrid assembly (wires and threaded pins) may easily be used in the distal radius and tibia. If in the distal stump of a short radius or tibia two levels of fixation cannot be used (two rings with 4 wires or one ring with 2 wires and a third wire on supports) an extremely stable fixation may be achieved using two wires and a threaded pin, thus avoiding the need of having to extend the apparatus to the metacarpus or metatarsus (Fig. 4b). The stability of the construct and the closed surgical technique usually enables fracture healing in extremely brief periods of time: 30-45 days. This is also dependent on the extent of the vascular damage, the degree of contamination of open fractures and the age (puppy or adult).

Nonunion treatment The Ilizarov transosseous osteosynthesis technique may be used extensively in small animal long bone nonunion treatment. The correct therapeutical approach makes it first necessary to analyse and classify the nonunions: clinical presentation: stiff, mobile radiographic presentation: hypertrophic, normotrophic, atrophic biological presentation: aseptic, septic. The apparatus has to be assembled so as to guarantee the maximum stability. Goal of the approach is to re-establish (directly or subsequently) bone continuity. That being said, nonunion treatment is as follows: closed synthesis: the method is usually non invasive, open synthesis: nonunion site opening is necessary to - remove foreign bodies (metal implants)

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Med Vet, Dipl ECVS Private Practitioner, Cremona - Italy

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Figure 1 - Different assembly confgurations of the Ilizarov apparatus.

- bring together stumps with a minimal contact surface - sequestrectomy - resection of necrotic or septic stump ends. In consideration of the already limited viability of atrophic nonunion tissue any invasive intervention has to be as limited and as precise as possible. In small animals the nonunion osteosynthesis techniques more commonly being used are: - distraction monofocal osteosynthesis: indicated in the treatment of hypertrophic, aseptic, stiff nonunions with sure stump viability; - compression monofocal osteosynthesis: indicated in all cases of nonunions (including the hypertrophic, for which a simple stabilization would be enough), while it is absolutely indispensable in the treatment of atrophic nonunions; - compression and subsequent distraction monofocal osteosynthesis: it may be used for normotrophic or atrophic nonunions in which the compression has led to an improved trophism of the nonunion site. - Distraction and subsequent compression bifocal osteosynthesis, also defined as transportation or internal lengthening osteosynthesis: it may be used for atrophic nonunions with spontaneous loss of substance or following the surgical resection of necrotic or septic bone.

a Figure 2 - Frame extension to the carpus and tarsus.

In the case of transportation or internal lengthening the distraction should be of 1/4 mm every 6 hours, the same as for lengthenings, however in all other cases of nonunion site distraction it is necessary to go down to 1/4 mm every 12 hours or even every 24 hours. This until the appearance of a lively and abundant regenerated tissue. At this point the distraction can continue with a faster pace. Nonunion consolidation takes place in times varying between 50 and 90 days.

Limb deformity treatment Causes of limb deformity in the dog are various. In the growing animal they may depen d on metabolic disorders or on traumas affecting the growth cartilage; the radio-ulnar segment is the most affected. In both mature animals and puppies the deformity may present itself as a stiff nonunion, a malunion or joint stiffness. Deformity analysis The deformity may be simple, if it has a single plane of deviation, or complex if the deviation is on more planes. Taking the curved radius as an example there are three

b Figure 3 - Metaphyseal fixation with wires.

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Figure 4a - Proximal fixation of tibia and femur with half-pins.

Figure 4b - Distal metaphyseal fixation of radius and tibia with wires and half-pins.

Figure 7 - Hinges application in a complex deformity.

planes of deviation: valgism, forward curvature and external rotation. The first two may be assessed radiographically, while the external rotation is to be assessed on the patient. A careful analysis of the deformity helps to plan the procedure and to carefully pre-assemble the apparatus. The intervention is thus easier and faster.

b a

Figure 5 - Positioning of the rings: the rings have to be perpendicular to the bone on both a) the frontal plane and b) on the lateral plane.

Assembly of the apparatus The apparatus is pre-assembled using x-rays as reference. The ring and half ring diameter is selected according to the patientâ&#x20AC;&#x2122;s size: it has to be greater (by at least 2 cm per side) than the maximum diameter of the segment to be treated. Taking the radius and the tibia as an example the dimension which determines the diameter of the assembly is the

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Figure 6 - Construction of hinges.

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Figure 8 - The type of correction depends on the positioning of the hinges: a) in correspondence with the apex of the convexity; b) beyond me apex of the deformity; c) in an intermediate position between the convex and concave apex of the deformity.

one of the proximal third of the bone. The rings have to be perpendicular to the longitudinal axis of the bone segment. To apply the rings correctly it is therefore fundamental to recognize the various planes of deviation. In a deformity with both valgism and forward curvature the rings have to be perpendicular to the bone on both the frontal plane (valgism) and on the lateral plane (forward curvature). The rings are consequently set in an oblique position, downward anteriorly and medially (Fig. 5). It is not always necessary to correct all the deformities present. In a deformity with a serious valgism and a slight forward curvature it may be for example better to treat the first and not the second, clearly only if this should not lead to functional disorders. Hinge positioning The hinges are the mechanical elements which enable the dynamic correction of the deformity (Fig. 6). It is thanks to the invention of the â&#x20AC;&#x153;hingesâ&#x20AC;? that Ilizarov transformed a circular external fixator into a real bio-apparatus capable, via distraction and compression, of progressively altering the shape of a bone segment. Hinges - They have to be positioned at the same level of the deformity with their axis exactly perpendicular to the plane of deformity (Fig. 7). If the deformity is characterized by more deviations (as in the case of the curved radius), the plane of deformity is not exactly frontal or lateral but is instead an oblique plane resulting from the combination of the two deviation planes. Taking the curved radius as an example the plane is oblique in a postero-anterior and lateral-medial direction with a tendency to being closer to the plane of the more serious deviation; or exactly in-between if the two deviations are of equal importance. - They may be positioned in correspondence with the apex of the convexity (Fig. 8a): by progressively distracting the opposite side a wedge shaped space is obtained which will then be filled by regenerated bone (Fig. 9). - If the correction of the axis together with a bone lengthening are desired, the hinges have to be positioned be-

yond the apex of the deformity and the amount of lengthening is proportional to the distance between the hinge axis and the apex of the deformity (Fig. 8b). - If they are instead set in an intermediate position between the convex and concave apex of the deformity this determines the distraction of the concave part and the compression of the convex part (Fig. 8c). Site of the deformity The site of deformity does not always correspond to the part which is visually deformed. To establish the exact site it is necessary to trace the axes of the segment. Their point of intersection corresponds to the real point of deformity, the point where the hinges have to be positioned with the possible variations presented in Figure 8 a, b, c. Figure 10 explains this concept in greater detail: in a the position of the stumps is presented. In b the point of intersection of the segmentâ&#x20AC;&#x2122;s axes enables to identify the real site of the deformity. The hinges are positioned in correspondence with such point (Fig. 10c). In Figure 10d the axis is perfectly correct; while in Figure 10e the hinges have been positioned in correnspondence with the apex of the malunion area. This enables to correct the angle however a lateral shift of the stumps remains. Distraction The correction requires that the cortical bone distraction on the concave side of the deformity is of 1 mm per day (Fig.

Figure 9 - Radiographic appearance of 23 days regenerate.

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Figure 10 - Deformity site in a case of malconsolidation: a) position of the stumps. b) The point of intersection of the segament axis enables to identify the real site of the deformity. c) The hinges are positioned in corrispondence with such point. d) The axis has been perfectly corrected. e) The hinges have been positioned in corrispondence with the apex of the malunion area. This enables to correct the angle however a lateral shift of the stump remains.

Figura 11 - Calculation of the distraction rate.

radiographic appearance of a viable regenerated tissue. Should this take place the usual 1/4 mm every 6 hour distraction may be resumed. Fixation The fixation period following deformity correction (meaning lengthening) is necessary to enable the consolidation of the regenerated tissue and is proportional to the extent of the lengthening. For example: a 3 cm lengthening of a dog radius-ulna requires about 30 days of fixation. Before removing the apparatus it is however necessary to confirm the degree of consolidation with an x-ray examination.

References Aaron A, Eilert R: Results of the Wagner and Ilizarov methods of limblengthening. J Bone Joint Surg Am 78:20-9, 1996 Aronson J, Johnson E, Harp J: Local bone transportation for treatment of intercalary defects by the Ilizarov technique. Biomechanical and clinical considerations. Clin Orthop p 71-9 1989 Breur GJ, Zerbe CA, Slocombe RF, et al.: Clinical, radiographic, pathologic, and genetic features of osteochondrodysplasia in Scottish deerhounds. J Am Vet Med Assoc 195:606-612, 1989 Catagni MA, Malzev V, Kirienko A: Correction of angular deformities, in Bianchi Maiocchi A (ed): Advances in Ilizarov apparatus assembly. Milan, Italy, Medicalplastic, 1994, pp 98-112 Delloye C, Delefortrie G, Coutelier L, et al.: Bone regenerate formation in cortical bone during distraction lengthening. An experimental study. Clin Orthop 250:34-42, 1990 Elkins AD, Morandi M, Zembo M: Distraction osteogenesis in the dog using the Ilizarov external ring fixator. J Am Anim Hosp Assoc 29:419426, 1993 Ferretti A: The application of the Ilizarov technique to veterinary medicine, in Bianchi Maiocchi A, J Aronson (eds): Operative principles of Ilizarov. Baltimore, Williams & Wilkins, 1991, pp 563-565, 570 Ferretti A: Small bone fixator, in Bianchi Maiocchi A (ed): Advances in Ilizarov apparatus assembly. Milan, Italy, Medicalplastic srl, 1994, pp 134-139 Fleming B, Paley D, Kristiansen T, et al.: A biomechanical analysis of the Ilizarov external fixator. Clin Orthop 241:95-105, 1989 Frierson M, Ibrahim K, Boles M, et al.: Distraction osteogenesis. A comparison of corticotomy techniques. Clin Orthop 301:19-24, 1994 Ilizarov GA: The tension-stress effect on the genesis and growth of tissues.

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11A). To achieve this it is necessary to measure (Fig. 11B) (both on x-rays and on the patient) the distance between the hinge axis and the distraction rod (C) and between the hinge axis and the cortical bone on the concave side of the deformity (B). The C:B ratio gives the daily rod distraction which generates a 1 mm bone distraction per day. These measurements are obviously approximate since both radiographic and patient measurements are also approximate. To verify if the amount of distraction is sufficient a radiographic examination is carried out after 7 days. If a corticotomy or an osteotomy have been carried out, meaning in all cases of deformity or malunion, the bone distraction rate has to be of 1/4 mm every 6 hours (after a 3-7 day waiting period depending on the damage produced). In the case of hypertrophic stiff nonunions the bone is not discontinued and is instead directly distracted with the goal of both correcting the deformity and of inducing, via the distraction tension, the consolidation of the hypertrophic nonunion site. In this case the distraction rate has to be slower, for example 1/4 mm every 12 hours, continuing until the

476 Part I. The influence of stability of fixation and soft-tissue preservation. Clin Orthop 238:249-281, 1989 Juan J, Prat J, Vera P, et al.: Biomechanical consequences of callus development in Hoffmann, Wagner, Orthofix and Ilizarov external fixators. J Biomech 25:995-1006, 1992 Latte Y: A specific vet Ilizarov apparatus for the treatment of fractures, delayed union, non union and mal union. Proc Vet Orthop Soc 1991, p 51 (abstr) Latte Y: Studies of 63 cases treated by Ilizarov apparatus: indications, results, complications. Proc Vet Orthop Soc 1993, p 12 (abstr) Latte Y: Application de la méthode d’Ilizarov en chirurgie orthopédique vétérinaire. Prat Méd Chir Anim Comp 29:545-570, 1994 Marcellin-Little DJ, Ferretti A, Roe SC, DeYoung DJ. Hinged Ilizarov external fixation for correction of radial deformities in dogs. Vet Surg 1997, 26:5, 439 Marcellin-Little DJ, Ferretti A, Roe SC, DeYoung DJ. Hinged circular external skeletal fixation for correction of radial deformities. ACVS Meeting, Orlando, Florida,1997/ ECVS Meeting, Versailles, France, 1997 Marcellin-Little DJ, Ferretti A, Roe SC, et al.: Hinged Ilizarov fixation for correction of antebrachial deformities. Vet Surg 27:in press, 1998 Orbay J, Frankel V, Finkle J, et al.: Canine leg lengthening by the Ilizarov technique. A biomechanical, radiologic, and morphologic study. Clin Orthop 1992, p 265-73

4th European FECAVA SCIVAC Congress Paley D: The principles of deformity correction by the Ilizarov technique: technical aspects. Techniques Orthop 4:15-29, 1989 Paley D, Catagni MA, Argnani F, et al.: Ilizarov treatment of tibial nonunions with bone loss. Clin Orthop 241:146-165, 1989 Paley D: Problems, obstacles, and complications of limb lengthening by the Ilizarov technique. Clin Orthop 250:81-104, 1990 Paley D, Fleming B, Catagni M, et al.: Mechanical evaluation of external fixators used in limb lengthening. Clin Orthop 1990, p 50-7 Stoffelen D, Lammens J, Fabry G: Resection of a periosteal osteosarcoma and reconstruction using the Ilizarov technique of segmental transport. J Hand Surg [Br] 18:144-6, 1993 Tetsworth K, Krome J, Paley D: Lengthening and deformity correction of the upper extremity by the Ilizarov technique. Orthop Clin North Am 22:689-713, 1991 Tetsworth KD, Paley D: Accuracy of correction of complex lower-extremity deformities by the Ilizarov method. Clin Orthop 301:10210, 1994 Waanders NA, Herzenberg JE: The theoretical application of inclined hinges with the Ilizarov external fixator for simultaneous angulation and rotation correction. Bull Hosp Jt Dis 52:27-35, 1992 Zembo MM, Elkins D, Morandi M, et al.: Radiographic analysis of regenerate bone formation following tibial distraction osteosynthesis by the method of Ilizarov with a circular external fixator in a canine model. Trans Orthop Res Soc 1990, 15: p 120 (abstr)

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Lymphnode cytology: normal, inflammatory and neoplastic aspects Corinne Fournel-Fleury Laboratoire d’Immunopathologie-Hématologie-Cytologie, Ecole Vétérinaire de Lyon - France

Cytology allows in most cases, the differential diagnosis between reactive and neoplastic lymphadenopathy. The different reactive lymphadenopathies may be classified in hyperplasias (plasma cells, follicular, immunoblastic, T-cells and mixed hyperplasias), adenitis (neutrophilic, granulomatous and eosinophilic) and mixed patterns. Neoplastic lymphadenopathies fall into two categories: the primary tumors of the lymph node i.e. malignant lymphomas and the metastatic lymphadenopathies. The main cancers which metastasize to the lymph node are mast cell tumors, carcinomas and malignant melanomas and, occasionally, sarcomas (in particular hemangiosarcomas). Three main difficulties exist for the diagnosis of metastatic lymphadenopathy: extensive necrosis, massive lymph node infiltration and micrometastasis. Malignant lymphomas can be recognized in most cases by cytology. They can be classified on the bases of morphological criteria which are closely related, in our experience, with their immunophenotype. Either in the B-cell or in the Tcell lineage, one can distinguish low-grade lymphomas, mainly constituted of small differentiated cells and highgrade “blastic” lymphomas. However, the determination of the immunophenotype necessitates immunological labellings which are used, either on cytological preparations or on tissue sections. The main difficulties for differential diagnoses between hyperplasias and malignant lymphomas are encountered for small-cell lymphomas, mixed lymphomas and lymphomas at early stages. In doubtful cases, the cytological examination provides the best arguments for a rapid lymph node excision and histological examination.

Lymph node fine needle aspiration cytology is justified: - in any case of a lymphadenopathy which constitutes a major clinical sign and particularly in all cases of generalized lymph node enlargement; - in any case of a persistent lymphadenopathy even moderate or isolated, whose origin is not apparent. Cytology allows in most cases: - the differential diagnosis between reactive and neoplastic lymphadenopathy; - furthermore, in many cases, the diagnosis or the presomption of the underlying disease. However, a histological examination of the lymph node

is indispensable in any instance where the diagnosis cannot be established with certainty by cytological examination alone.

Normal lymph node cytology To understand lymph node cytology and so, the possibilities and limits of cytological diagnosis, it is important to understand: - the histology of the normal lymph node; - the normal cellular composition of the different lymph node areas on a morphological and phenotypical point of view; - the successive stages of the lymphoid differentiation. On tissue section, the normal lymph node is organized in: - a dense cortical area - and medullary cords centred on the hilus. The cortical area is itself separated into: - a superficial cortex in which are located the follicles with the germinal centers; - a deep cortical area which goes from the interfollicular region to the medullary cords. The cellular composition of those different lymph node areas is constituted by lymphoid cells and non lymphoid accessory cells - The two categories of lymphoid cells are: • B-cells which produce antibodies via plasma-cells. They are located in the superficial cortex and the medullary cords which constitute B-cell areas • T-cells which regulate the humoral response (helpers or suppressors) or are effector cells (particularly the cytotoxic cells). They are located in the paracortex = T-cell area. - The three categories of non-lymphoid accessory cells of the immune response, are: • antigen presentating cells: follicular dendritic cells for B-cells and interdigitating cells for T-cells; • histiocyte-macrophages; • inflammatory cells, which appear only in reactive conditions. Cell identification is based on size, nuclear and cytoplasmic criteria: - cell size, established from the size of the nucleus in comparison with the size of two red blood cells;

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Summary

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- nuclear shape and chromatin; - nucleoli: number, size and location; - cytoplasm, size and colour.

So, the expected effect of an Ag stimulation is an increase of the number of blast cells and plasma cells in the lymph node! It is now easy to understand that:

The different B cells are: - Small B lymphocytes (mainly in the superficial cortex and primary follicles) - Centrofollicular cells in germinal centers of follicles - B immunoblasts (follicles and interfollicular regions) - Plasma cells (in the medullary cords) - An original macronucleolated medium-sized cell (MMC), particular to the canine species, in perifollicular marginal zones. Follicular B cells are also identified by their grouping with follicular dendritic cells which are recognized by their highly elongated, sinuous and pink cytoplasm. By contrast, the T-cell lineage is restricted to two categories of cells: - small T-lymphocytes, - T-immunoblasts, Small T-lymphocytes are very similar to their B-cell counterpart, except some nuclear irregularities and sometimes a more extended pale cytoplasm which may argue for their T-cell origin. T-immunoblasts, are quite similar to the B-immunoblasts but their cytoplasm may be paler than that of B-immunoblasts. So, regarding the common pale cytoplasm of T cells, clear cells, either in reactive lymph node or in lymphomas, may suggest a T-cell origin. Finally, T-cell areas are identified by the presence of their particular antigen-presentating cells named interdigitating cells characterized by their twisted nucleus and their abundant pale, poorly-outlined cytoplasm which stands out against the dense mass of surrounding small lymphocytes. At last, macrophages and inflammatory cells can be observed in the lymph node, and they are, more numerous, of course, in inflammatory conditions. The lymphoid differentiation scheme, established by Lennert for humans, can probably be applied, in the main outlines, to dog and cat. In this scheme, the successive stages of B and T cell differentiation would be the following: For the T-cell lineage: After Ag stimulation, small T lymphocyte (T1) gives rise to a T immunoblast and then to small lymphocytes (T2), regulator, effector of the cellular immune response or memory cells. For the B-cell lineage: After Ag stimulation, small B lymphocyte (B1) gives rise to a plasma cell via a B immunoblast or enters the follicle for amplification of the immune response and gives rise to a centroblast and then centrocytes and small B lymphocytes (B2), memory cells.

- Normal lymph node cytology is characterized by: • an heterogeneous lymphoid population • a large predominance of small mature lymphocytes (Bor T- cells) • less than 5% of blast cells (centroblasts and immunoblasts) • up to 5% of plasma cells. - Cytology bases the identification of the different reactive lymphadenopathies on the incidence of the different cell populations but also on their possible groupings.

REACTIVE LYMPHADENOPATHIES One can distinguish: - predominant lymphoid reactions (= hyperplasias), under Ag stimulation - and predominant inflammatory reactions (= adenitis). Reactive hyperplasias are characterized by: -an heterogeneous lymphoid population because of the mixing of the different cell populations involved in the normal differentiation scheme - an increasing number of blasts cells even if small lymphocytes remain predominant - a high number of plasma cells. However they can be classified on the basis of the predominant increasing cell population in: - Plasma cell - Follicular (centroblastic) - Immunoblastic hyperplasias. T-cell, and - mixed

}

* Plasma cell hyperplasia: -indicates a strong, local or systemic, antigenic stimulation - is very common in veterinary dermatology - is particularly suggestive of Leishmaniasis and other chronic dysglobulinemia in case of multiple adenopathies. * Follicular hyperplasia: -is suggested by an association of centroblasts, centrocytes, follicular dendritic cells, macrophages (with tingible bodies), numerous mitoses in dense packed cell agregates - is mainly encountered in feline retrovirus related persistent lymphadenopathies. * Immunoblastic hyperplasia - is characterized by an increasing number of immunoblasts, more numerous than the centroblasts - is a rare condition which suggests mainly a viral infection

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Adenitis are partial infiltrations of the lymph node by inflammatory cells. They consist of: - neutrophilic, acute or subacute - granulomatous (chronic) adenitis - eosinophilic - mixed

}

* The classification of neutrophilic adenitis is based on cell morphology: - The presence of degenerative changes (light staining of the nucleus, effacement of cytoplasmic outline...) is characteristic of acute suppurative adenitis and suggests sepsis. In our experience, it is a very rare event in canine and feline medicine. - On the other hand, the presence of neutrophils without degenerative changes is common in subacute non septic adenitis, mainly encountered in mixed inflammatory processes (especially associated with chronic skin diseases). * Granulomatous adenitis - is recognized on the basis of an increased number of histiocytes and macrophages - suggests a chronic process and especially a chronic bacterial or fungal infection, Leishmaniasis or mycobacterial infection if epithelioid cells are present - Finally, benign multicentric histiocytosis is a rare multicentric involvement of the skin and the lymph nodes of the young dog by histiocyte population, that may be classified like a particular granulomatous adenitis. * Eosinophilic adenitis - is easy to recognize due to the numerous eosinophils and frequently mast cells. - is a common feature in chronic skin disease associated with hypersensitivity. - is especially massive in feline eosinophilic granuloma complex.

• eosinophils • MMC - Leishmaniasis, if are encountered together: • plasma cell • epithelioid cells • MMC

Neoplastic lymphadenopathies They fall into two categories: - The primary tumors of the lymph node: the malignant lymphomas - The secondary invasions of the lymph node: the metastatic lymphadenopathies

METASTATIC LYMPHADENOPATHIES The main non-hematopoietic cancers with a predilection for lymphoid tissue are the carcinomas, mast cell tumors and malignant melanomas. Occasionally, certain sarcomas, and in particular hemangiosarcomas, may follow the lymphatic route. Furthermore, with certain malignant, non-lymphoid hemopathies, such as acute myeloid leukemias (AML) and malignant histiocytosis, there may be a secondary invasion of the lymph node.

General principles of diagnosis on the basis of a lymph node smear The results given by a lymph node smear depend on the following factors, in order of importance: - its technical quality; - the degree of invasion of the lymph node; - the degree of morphological difference between the tumor cells and the residual lymph node cell population; - the possibility of carrying out, in parallel, a cytological examination of the primary tumor, which considerably facilitates the identification of the same cells in the lymph node smear.

Metastatic, non-hematopoietic cancers * In fact, mixed patterns are more commonly encountered in reactive lymph node cytology. Among these mixed patterns, three are highly suggestive of a particular aetiology:

Malignant mast cell tumors

- Chronic skin disease lymphadenopathies grouping together: • various inflammatory cells • hemosiderin or melanin-laden macrophages • numerous plasma cells

In dogs, essentially, grade II and grade III mast cell tumors frequently metastasize to the lymph node. The diagnosis is mainly based on: - the massive involvement - and the abnormal morphology of the neoplastic cell in mast cell tumors.

- Systemic lupus erythematosus, suggested on lymph node smear by the grouping of: • numerous plasma cells

A particular difficulty exists in the differential diagnosis between adenitis and metastasis due to the possible massive invasion by the mast cell and eosinophils in the cat, in the

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* T-cell hyperplasia is different from other reactive patterns because of the predominance of an homogeneous small lymphocyte population. - It can be recognized by the presence of numerous interdigitating cells and sometimes of pale immunoblasts. It is mainly associated with chronic dermatitis (like in human medicine).

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Eosinophilic Granuloma complex, but also in the dog in case of hypersensitivity.

Carcinomas These metastasize, most frequently, in the form of voluminous emboli which preserve their organization in the form of characteristic juxtaposed epithelial cell clusters within the lymph node. The cells, which are often large, and with strong cytological criteria of malignancy, stand out in the middle of the residual lymph node cell population, which is often dispersed and mixed with a large population of inflammatory cells. A misdiagnosis between granulomatous adenitis and metastatic carcinoma must be avoided especially when epithelioid cells are very numerous. But the histiocytic appearance of this population, its frequent association with neutrophils and the absence of malignancy criteria are the basis of the diagnosis of reactive granulomatous adenitis.

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a residual lymph node population. Hemangiosarcomas, in particular, give highly hemorrhagic lymph node smears, in which a few cells, or groups of cells, are dispersed. These are cytologically very malignant, and for the most part, distinctly spindle-shaped, what suggests a mesenchymal origin.

Malignant metastatic non-lymphoid hemopathies Acute myeloid leukemias (AML) All AML’s can invade lymph nodes secondarily. It is the recognition of an often partial invasion of the lymph nodes by poorly-differentiated blast cells, with, occasionally, some rare, characteristic granules against a background of a reactive lymphoid cell population, which, associated with the result of the blood smear and the bone marrow smear, corroborates the diagnosis.

Malignant histiocytosis Malignant melanomas A diagnosis of metastatic invasion of the lymph node by a malignant melanoma may be very easy, or very difficult. It is very easy in case of: - lymphadenopathy associated with a pigmented oral or digital tumor - a massive invasion by cells with, frequently, abnormal nuclei, and characteristic, fine, blackish, dispersed cytoplasmic melanin granules. It is more difficult in: - the early detection (which is also the most useful) of rare, dispersed cells in a dense lymph node smear. - malignant amelanotic melanomas, which are often highly atypical, and suggest a metastatic lymphadenopathy of undifferentiated cancer as the only diagnosis. - when micrometastases appear against the background of an inflammatory lymph node with numerous melanophages and granules of melanin dispersed in the smear background. So, it is important: - to perform a careful examination of the smears which can allow the vizualisation of a single malignant cell which contains some granules of melanin. - to use the Fontana’s stain which can also be a valuable aid to the revelation of melanin granules. The identification of authentic melanophages is always of real diagnostic value in an oncological context, since, by concentrating melanin granules, they serve as a means to identify weakly-pigmented melanomas.

Sarcomas In comparison with the tumors mentioned previously, sarcomas rarely metastasize to the lymph node. When they do so, it is often in a massive fashion and with very aggressive tumors, it is sometimes very difficult to detect

This rare tumor invades lymph nodes and numerous other soft tissue sites (notably the lungs and pleura), and, especially, the hematopoietic bone marrow. The diagnosis is supported by the following histiocytic characteristics: - the finely reticulated appearance of the chromatin and - weakly basophilic cytoplasm, with imprecise outlines and cytophagocytosis capacities. As in the previous cases, the lymph node smear is no more than a complementary element in the diagnosis.

Finally, three main difficulties remain in the diagnosis of metastatic lymphadenopaties 1) The existence of extensive necrosis in all samples, without any possible characterization of underlying cells which poses in itself the problem of a neoplastic necrosis and often indicates the absolute necessity of doing a control biopsy. 2) The massive lymph node infiltration without any residual lymphoid population. 3) The possible existence of micrometastasis.

MALIGNANT LYMPHOMAS Classifications Malignant lymphomas are characterized by the progressive invasion of the lymph node by a neoplastic “cell clone” that has been more or less arrested at a certain stage of differentiation, destroying little by little the normal histological lymph node architecture. The classifications are based on the principle that lymphomatous cells represent the malignant equivalent of the different normal lymphoid cell types. In the dog the determination of the immunophenotype allows a classification of canine lymphomas according to the

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B-cell lymphomas Low-grade malignancy Small cell Lymphocytic Lymphoplasmocytic Prolymphocytic Centrocytic Centroblastic/centrocytic Macronucleolated medium-sized cell (MMC) High grade malignancy Centroblastic Monomorphic Polymorphic Immunoblastic Small cell, unclassifiable Burkitt-type Plasmacytoid Lymphoblastic T-cell lymphomas Low-grade malignancy Small cell Clear cell Prolymphocytic Pleomorphic small cell Mycosis fungoides High grade malignancy Pleomorphic, mixed, small and large cell Pleomorphic large cell Immunoblastic Small cell, unclassifiable, plasmacytoid Lymphoblastic According to their frequency, the most common types of NHL encountered in the dog are of the B-cell phenotype, mainly centroblastic polymorphic with a mixing of several cell components.

histological examination It is true that a cytological examination alone cannot confirm the follicular or diffuse architecture of a lymphoma, which requires histology. This is important for a prognosis, since follicular lymphomas are of lesser malignancy. The problem, however, remains minor with canine and feline lymphomas, given the low percentage of follicular lymphomas encountered In cytology, the diagnosis of the majority of lymphomas is easy on the basis of a blastic, monomorphous, homogeneous cell population without an associated plasma cell hyperplasia. This population replaces the reactive lymph node cell population, which is normally heterogeneous and rich in plasma cells. Cytologically speaking, the more massive the lymph node invasion is, and the more the lymphomatous cells differ from the cell populations that are normally dominant in the lymph node, the easier the diagnosis will be. However, the cytological diagnosis is difficult: - at the beginning of an invasion, or with an associated reactive lymphadenopathy (which is a frequent case when a lymph node smear is done on the mandibular lymph node that has been the site of repeated antigenic stimulation), - in small-cell lymphomas whose cells are similar to small normal lymphocytes, - in mixed lymphomas. The main difficulties remain among the small cell proliferations and the differential diagnosis must be established between: - T-cell hyperplasias and small cell lymphomas, - Plasma cell hyperplasias and immunocytomas or multiple myelomas which are two malignant lymphomas with plasmocytic differentiation. Among the blastic proliferations, the differential diagnosis will be made between: -blastic lymphomas and some marked follicular and / or immunoblastic hyperplasias.

General principles of the cytological characterization of lymphomas Cytological analysis of a lymph node smear or lymph node imprint gives an excellent identification of cell types, and distinguishes between variants that may escape notice at

- MMC lymphomas and marginal zone hyperplasias. In doubtful cases, a lymph node smear will settle the question of carrying out a rapid lymph node excision for a confirmatory histological examination.

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Updated Kiel classification. In this model the various types of canine lymphomas may be classified in:

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Inflammatory diseases of hair follicles Luca Mechelli Med Vet Institute of Veterinary Patology, University of Perugia - Italy

The primary task of the hair follicles is to produce hairs and this cyclic activity requires a complex structure. The knowledge of the microanatomy of the hair follicle provides the basis for the understanding of pathogenetic mechanisms occuring and to classify follicular inflammation/non-inflammation diseases.

The anagen hair follicle, extending from top to bottom, can be divided in three major anatomic regions: 1) the superficial segment, or infundibulum, which extends from ostium to the site insertion of the sebaceous gland duct, lined by an epithelium identical to epidermis; 2) the isthmus which extends from infundibulum to the insertion of the arrector pili muscle or, better, from the end of the follicular inner root sheath cornification to the beginning of it in the bulge region. The follicular outer sheath cells of this segment are small, differentiate and produce amorphous keratin (trichilemmal keratinization); 3) the inferior segment, which extends from the insertion of the arrector pili muscle to the base of the follicle. The inferior portion contains a spherical base known as the hair bulb. Inner and outer root sheath are present during the anagen phase in the inferior segment. Hair bulb with hair matrix surround dermal papilla. A hyaline basement membrane and fibrous tissue surround hair follicle (fibrous sheath).

Inflammatory diseases of the hair follicle The anatomical classification of folliculitis is based on the specific region of the hair follicle that is involved by inflammatory reaction and particular importance is placed upon whether there is invasion of the follicular lumen by inflammatory cells. A. PERIFOLLICULITIS This term, falled into disuse, is emploied to describe a perivascular inflammatory cells infiltration of the periadnexal vascular plexus without involment of the outer root sheath and no destruction of the basal cell layer of the hair follicle.

B. MURAL FOLLICULITIS The inflammatory response involves the outer root sheath of the hair follicle without invasion of the pilar canal. 1. Interface mural folliculitis The histological hallmarks are: a) sparse cell necrosis, mainly in the follicular basal layer and, less frequently, in stratum spinosum of the outer root sheath; b) diffuse hydropic change in the follicular basal layer; c) pigmentary incontinence, free in the dermis or phagocytosed by macrophages; d) diffuse infiltrates of inflammatory cells restricted to the middle and upper portions of the hair follicles. Examples: • erythema multiforme • lupus erythematosus • demodicosis • dermatomyositis • dermatophytosis (some manifestations) 2. Infiltrative mural folliculitis The inflammatory reaction involves the wall of the hair follicle mainly at and above the level of isthmus. Mononuclear cells, for the most part lymphocytes and histiocytes, are directed against antigens located into the outer sheath epithelium of the hair follicles. “Interface mural folliculitis” and “infiltrative mural folliculitis” are invariably connected, representing different phases of the same immunological reaction. Examples: • Canine and feline sebaceous adenitis • Feline idiopathic mural folliculitis • Idiopathic granulomatous folliculitis of dogs • Equine linear alopecia 3. Necrotizing mural folliculitis This lesion represent a particular form of mural folliculitis where the necrosis affects the wall of the follicle at and below isthmus. The cell infiltrate is predominantly eosinophilic and the lesions are the same as those described for “eosinophilic furunculosis”. Examples: • Canine eosinophilic furunculosis of the face • Feline mosquito bite hypersensitivity

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4. Pustular mural folliculitis The inflammatory process is characterized by pustules within the wall of the superficial hair follicle, usually at or above isthmus. The pustules contain neutrophils, rare eosinophils and acantolytic follicular epithelial cells. Examples: • Pemphigus erythematosus • Follicular pemphigus foliaceus. C. LUMINAL FOLLICULITIS This type represent the most common pattern of folliculitis. The inflammatory cells, usually neutrophils or eosinophils, migrate into the lumen of the hair follicle and gather in this side before releasing their inflammatory mediators. Evidently, all luminal folliculitis must be mural initially. Examples: • Bacterial or dermatophytic or parasitic folliculitis.

D. BULBITIS The lesion is characterized by cellular infiltrate that surrounds, invades and damages the inferior segment of the hair follicle, resulting in telogenization, follicular atrophy or dystrophic hair production. The infiltrate, often described as like a “swarm of bees” around the bulb, is primarily represented by T-lymphocytes (CD8 +) and handful of macrophages, Langerhans cells and neutrophils. Apoptotic cells in bulb and in outer root sheath of the inferior part of the hair follicle are a possible feature. Example: • Alopecia areata.

References Caswell, J.L., Yager, J.A., Ferrer, L., Weir, J.A.M. Canine demodicosis: a re-examination of the histopathologic lesions and description of the immuno-phenotype of infiltrating cells. Veterinary Dermatology, 1995, 6: 9-19. Dunstan, R.W. and Credille, K.M. The hair follicle and its diseases. Third Veterinary Dermatology Resident’s Pre-Congress Meeting ESVD / ECVD, Edimburgh, 11 September 1996. Fondati, A., Fabbrini, F. and Mechelli, L. Due casi di follicolite e foruncolosi eosinofilica facciale nel cane. Veterinaria 1997, 11(6): 99-103. Gross, T.L., Ihke, P.J., Walder, E.J. Veterinary Dermatopathology: a macroscopic and microscopic evaluation of canine and feline skin disease. St louis: C.V. Mosby, 1992. Gross, T.L., Stannard, A.A. and Yager, J.A. An anatomical classification of folliculitis, Veterinary Dermatology, 1997, 8:147-156. Mechelli, L. Patologie infiammatorie del follicolo pilifero del cane e del gatto - Atti del XV Convegno Nazionale Associazione Patologi Italiani Veterinari (A.P.I.V.), 1996. Olivry, T., Moore, P., Naydan, D. et al. Antifollicular cell-mediated and humoral immunity in canine alopecia areata. Veterinary Dermatology, 1996, 7: 67-69. Scott, D.W., Miller, W.H., Griffin, C.E. Bacterial skin diseases. Muller and Kirk’s Small Animal Dermatology, 5th edn. Philadelphia: W.B. Saunders Co., 1995. Stannard, A.A., Gross, T.L. Noninfectious folliculitis. Proceeding of the 11th Annual Congress of the European Society of Veterinary Dermatology, 1994; Bordeaux, France. Von Tscharner, C. Inflammatory diseases of the follicles. Third Workshop on Veterinary Dermatopathology (ESVD), 8-12 August 1995 - Royal Veterinary College, University of London, UK. Yager, J.A., Wilcock, B.P. Color Atlas and Text of Surgical Pathology of the Dog and Cat; Volume 1: Dermatopathology and Skin Tumors. London: Wolfe, 1994. Yager, J.A., Scott, D.W. The skin and appendages. In: Jubb, K.V.F., Kennedy, P.C., Palmer, N., eds. Pathology of Domestic Animals, Vol. 1, 4th edn. San Diego: Academic Press, 1993.

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Approach to the patient with upper airway obstructive diseases Richard A. White

Summary This interactive session gives the audience an opportunity to discuss the common problems encountered in small animal airway obstructive disease. The first session is dedicated to the management of the brachycephalic patient and deals with problems such as stenotic nares, overlarge soft palate, hypertrophied pharyngeal mucosa, everted tonsils, laryngeal collapse and the related conditions which exacerbate the obstructed brachycephalic dog. The second session deals with laryngeal dysfunction concentrating on the current opinions on the diagnosis of laryngeal paralysis and reviews the controversies which surround its management. Other less commonly encountered laryngeal diseases (polyps, tumours, trauma etc) will be discussed.

Brachycephalic obstructive disease Incidence Obstructive airway disease is commonly regarded as a problem of the brachycephalic breeds including Bulldogs, Pekingese, Pugs and to a lesser extent the less severely-affected breeds such as Mastiffs, Cavalier King Charles Spaniels. The syndrome has many separate features which contribute to the overall problem of airway obstruction and it is important to appreciate that some of these factors are primary, heritable and congenital as a consequence of deliberate conformational development whilst others are secondary and acquired as a consequence at a later stage in life. The early recognition and management of the primary features is important to limit the potential for the development of the more serious and possible fatal secondary changes. Clinical signs and evaluation The clinical features of airway obstruction are well established and range from stridorous breathing (pharyngeal turbulence) in mild cases to intermittent cyanosis and syncopal collapse. Other presenting signs may include noisy respiration, exercise intolerance, regurgitation and even dysphagia. The age of onset is variable and in some case may be in puppyhood in some cases whilst others only become

symptomatic as the secondary changes become more evident. Investigation should include auscultation of the entire upper respiratory area, thoracic radiography, ECG and inspection under general anaesthesia. Anaesthesia for investigation and airway surgery should always be undertaken with caution because of the difficulty of maintaining an airway during the period between induction and intubation and during the recovery period. Ideally, procedures should be planned during cooler weather or in environmentally-controlled circumstances. Intubation may be problematic due to the narrow size of the tracheal lumen and the obscured view of the larynx which may itself be narrowed. Stenotic nares The external nose of the brachycephalic dog is, in common with the remainder of the respiratory tract, considerably foreshortened and as a result the cartilaginous tissue of the lateral cartilages especially is broader and less rigid than is found in other breeds. The airway at the level of the nostril is in some dogs may be virtually obliterated and this problem may be exacerbated during the inspiratory phase during which the cartilage because of its lack of rigidity may be drawn into the nasal sinus. Although some authors have considered the problem of stenotic nares to be inconsequential there is no doubt that airway obstruction at this level is extremely important since in the normal animal the external nose and nasal sinus represents at least one third of the resistance to the flow of air. Research has shown that not only does narrowing of the nares contribute to airway obstruction it also causes significant turbulence in the nasopharyngeal region which may underlie pharyngeal weakness. Management is directed towards resection of the bulk of the lateral cartilage to increase the airflow and also towards stabilising the remaining tissue by anchoring laterally to the integument. Nasal sinuses Although there is little that can be considered in terms of management there is no doubt that the relatively narrow diameter of the brachycephalic nasal sinuses contributes significantly to the overall resistance to airflow patterns in the upper airway. There is evidence too in favour of the devel-

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B Vet Med, PhD, DSAS, DVR, FRCVS - Dipl ACVS , Dipl ECVS University of Cambridge - United Kingdom

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opment of the acquired secondary pharyngeal changes resulting from turbulent flow patterns resulting from the narrow nasal airway. Overlarge soft palate The brachycephalic soft palate is one of the major contributory features of upper airway obstruction. Although it is probably of normal dimensions for the mesocephalic dog of comparable weight its relative oversize in the compressed nasopharyneal space of the brachycephalic causes obstruction of both nasal and oral airways. In addition, more severely affected patients may be dysphagic and become syncopal whilst eating. Resection of the caudal aspect of the soft palate is considered the most practical option. The level of resection is important and generally should not be made cranial to the level of the tonsils because of the risk of nasopharyngeal reflux. In Bulldogs, however it is difficult to achieve over-resection. Although electrosurgical resection is practised by some surgeons removal with right-angled clamps followed by oversewing the pedicle with absorbable suture material is considered to be a safer option. Haemostatic control is crucial and even mild oozing at the site of surgery represents an unaceptable risk of postoperative airway obstruction. Relief immediately after surgery is often marked although this may deteriorate temporarily due to swelling at the surgical site and response to implanted suture material. Tonsilar hypertrophy Enlargement of the tonsils contributing to the obstruction of the airway is generally considered to be a secondary change. It may occur as a consequence of either: i) the conformation of the brachycephalic pharynx which tends to evert the tonsilar tissue from the fauces allowing them to constantly irritated or, ii) the chronically-reduced airway pressures in the pharynx which tend to induce collapse of the structures in the pharyngeal wall or, iii) both of these factors. Their relative contribution to airflow turbulence and obstruction is uncertain, however most consider their removal useful in improving airflow dynamics. The tonsils should be removed clamping the pedicle and oversewing this to control haemorrhage following sharp excision. Once again the value of electrocautery in this procedure is open to controvesry. Pharyngeal hypertrophy The precise mechanisms whereby the pharyngeal wall hypertrophies and weakens is not clear but it is thought that turbulent airflow patterns created by obstructed airways further cranially, chronic negative airway pressures and obesity are important contributing factors. The mucosa of the pharynx may become thrown up into redundant folds which due to their inherent weakness permit partial collapse of the pharyngeal diameter during the respiratory cycle. In severe cases these folds may even totally obliterate the airway (socalled aryepiglottic entrappment) precipitating severe syncopal episodes. Resection of redundant mucosa may be indicated although improving pharyngeal rigidity is a less attainable goal.

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Diseases of the larynx Anatomic structure The larynx is a semirigid fibroelastic cyclinder separating the upper and lower respiratory tracts, the structural basis of which are three major and two smaller hyaline cartilages. The larger cartilages include the spoon-shaped epiglottis positioned most rostrally, behind which are found the horseshoe-shaped thyroid cartilage and the circular cricoid cartilage. The thyroid and cricoid cartilages occupy fixed positions relative to each other by virtue of their firm attachment at the cricothyroid articulation although the thyroid is capable of some limited movement in a rostrodorsal plane. This â&#x20AC;&#x2DC;chassisâ&#x20AC;&#x2122; provides the rigid base necessary for movement of the other cartilages. The epiglottis hinges in a rostrocaudal plane about its base which is in contact with the thryoid cartilage. The smaller, paired arytenoid cartilages articulate with the cricoid cartilages on their medial aspect and are capable of a swinging lateromedial movement about the cricoarytenoid articulations. Interposed between the arytenoids and lying rostral to the lamina of the cricoid are the interarytenoid and the sesamoidean cartilages which bind the arytenoids to the dorsal aspect of the cricoid. The larynx is supported rostrally by its attachment to the hyoid apparatus - the thyrohyoid membrane and caudally by its attachment to the trachea. Two paired of ligaments are found within the lumen of the laryngeal cylinder - the vocal ligaments which extend from the vocal processes of the arytenoids to the ventral midline and the vestibular ligaments which extend from the cuneiform process to the ventral midline. The larynx is lined with a stratified mucosa, folds of which protrude into the lumen of the cylinder over these ligaments - these are, respectively, the vocal and vestibular folds. The resultant crypts formed between the two folds are the laryngeal ventricles. The ventricles are absent in feline species. The diamondshaped opening within the laryngeal lumen delineated by the arytenoids dorsally and the vocal folds ventrally is termed the rima glottidis and is the narrowest point separating the upper and lower airways. The diameter of the rima is determined by the position and length of the vocal folds which in turn are dependant on the position of the arytenoid cartilages and to a lesser extent on that of the thyroid cartilage. Dorsolateral movement of the arytenoids about their cricoid articulation pulls the vocal folds apart thereby widening the rima. Medial movement reduces the diamond-shape of the rima to a slit-like opening or completely closes it. Cranial to the rima is the wider opening of the larynx the aditus laryngis which is delineated by the corniculate processes of the arytenoids, the epiglottis and the aryepiglottic folds. The larynx has both extrinsic and intrinsic muscles. The extrinsic muscles function in concert with the hyoid apparatus to vary the position and angle of the larynx. The intrinsic muscles of the larynx are responsible for controlling glottic diameter and can be broadly divided into the constrictors and dilators, depending on their primary function. They contain Type I and II fibres providing both rapid and sustained contractile function. The majority of the intrinsic muscles are associated with glottic constriction (adduction) of the rima and include the cricothyroid, lateral crico-arytenoid,

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Laryngeal function The larynx performs a valve-like role at the junction of the upper and lower respiratory tracts and its major functions can be summarised as: 1. Protection of the lower respiratory tract from inhalation of debris, 2. Control of airway diameter during the respiratory cycle, 3. Phonation. Airway protection Prevention of aspiration is the result of a twofold reflex mechanism. Firstly, during the swallowing phase the epiglottis hinges abouts its base and is ‘flipped’ backwards over the aditus to direct the food upwards and over the larynx into the lateral food channels, thereby preventing aspiration. The epiglottis provides a tight seal at the level of the aryepiglottic fold and the whole process occurs in conjunction with rostral movement of the larynx and caudal movement of the tongue. Secondly, glottic protection is also provided by the intrinsic muscles of the larynx which adduct the vocal folds and arytenoid cartilages sealing off the rima tightly during swallowing. This may also occur in response to stimulation of the cranial laryngeal nerves by any food or liquid debris passing beyond the aditus. Control of airway diameter During the resting phase of the respiratory cycle the arytenoids and vocal folds lie in a passive or ‘neutral’ midline position such that the rima is a narrow slit. Contraction of the dorsal cricoarytenoid muscles during inspiration causes the arytenoids to rotate quickly in a dorsolateral direction dilating the rima to accommodate the inward flow of air. On expiration, the vocal folds move passively towards the midline slowing the outward air flow. During prolonged or

heavy exercise the rima may remain dilated during both the inspiratory and expiratory phases to minimise resistance to continued air flow. Phonation Barking or meowing is a glottic function and is the result of vibration of the vocal folds as air flows over them. The tone and pitch of the bark or meow are determined by the speed and amplititude of the vibrations which in turn are governed by air flow rate and the length of the vocal cords. Vocal fold characteristics are governed primarily by tone in the vocalis and cricothyroid muscles.

LARYNGEAL PARALYSIS Pathophysiology Laryngeal paralysis is the failure of arytenoid movement during the respiratory cycle. The absence of abducting function affecting one or both arytenoids during the inspiratory phase with consequent narrowing of the rima results in an increased resistance to air flow through the larynx. Air flow becomes turbulent both due to the increased resistance which necessitates a higher flow rate through the rima and to the movement of air over the fixed vocal fold(s). The concommittant reduction in intralaryngeal pressure may narrow the rima still further contributing to additional air flow resistance. This airway obstructive condition is encountered with some frequency in dogs and is occasionally seen in cats. Aetiology Paralysis of the vocal folds through failure of arytenoid function most often results from disease or damage to the innervation of the intrinsic muscles of the larynx. Much less frequently it may occur through disease involving the dorsal cricoarytenoid muscles themselves. Idiopathic laryngeal paralysis (ILP): by far the majority of dogs with laryngeal paralysis fall into this category. ILP has a marked predisposition for medium to large breeds which in the UK includes such breeds as Labrador retrievers, Afghan hounds, Irish setters, Pointers and some giant dogs. The male is affected two or three times more frequently than the female and the average age of the affected dog is usually greater than 10 years. The underlying cause of ILP still remains unclear. The suggestion that the condition may arise more frequently in hypothyroid dogs remains largely unsubstantiated. The condition has also been reported as part of a laryngeal paralysis-polyneuropathy (LPP) complex in which affected dogs manifest signs of a generalised neuropathy including motor deficits involving the rear limbs. Demyelination and remyelination and also axonal degeneration involving the intrinsic laryngeal and appendicular peripheral nerves has been recorded in these dogs. Congenital: laryngeal paralysis has been reported as an inherited congenital disease in the Bouvier des Flandres and the Siberian Husky. The disease is transmitted as autosomally dominant trait in the Bouvier affecting the male more frequently and may be unilateral or bilateral. Degenerative changes are found both peripherally in the laryngeal nerves

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transverse arytenoid ventricular and thyroarytenoid muscles. The latter of these being the most important in terms of constricting function. Only the dorsal cricoarytenoid muscle is concerned purely with dilation (abduction) of the rima. This muscle originates on the dorsal aspect of the cricoid cartilage and inserts on the muscular process of the arytenoid. Its contraction rotates the arytenoid laterally over the articulation with the cricoid. The larynx is innervated by the vagus via the cranial and caudal laryngeal nerves. The cranial laryngeal nerves are concerned primarily with sensory function and provide innervation to the mucosal lining of the larynx via their internal branches. The sole exception to the sensory function of the external branches is the motor innervation to the cricothyroid muscles. The caudal (recurrent) laryngeal nerves arise from the vagal branches at the thoracic inlet, the right looping behind the subclavian artery and the left behind the aorta before heading rostrally to lateral surface of the larynx. They provide motor innervation to all the intrinsic muscles of the larynx with the exception of the cricothryoid muscle. The vascular supply of the larynx originates from the external carotid artery via the cranial laryngeal artery. The cranial laryngeal vein drains to the external maxillary vein.

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and centrally in the nucleus ambiguus. Selective breeding has now significantly reduced the incidence of this condition in Europe. More recently, a LPP complex has been recorded in the Dalmatian affecting dogs under the age of 6 months and presenting as a diffuse, generalised polyneuropathy distinct from that found in the Bouvier and Husky. 5,6 Electromyographic abnormalities are present in laryngeal, facial, oesophageal and distal appendicular muscles and axonal degeneration is found affecting the laryngeal and appendicular nerves. A significant number of these dogs also have megaoesophagus. Most dogs with inherited laryngeal paralysis are presented as young pups and are rarely suitable for treatment. Traumatic: injuries to the neck or cranial thorax may bruise, or even sever the laryngeal innervation. Pharyngooesophageal trauma and â&#x20AC;&#x2DC;Big dog / little dogâ&#x20AC;&#x2122; confrontations resulting in crush injuries to the cervical region are probably the most important causes in this respect. Neoplastic: tumour infiltration of the caudal laryngeal nerve may disrupt normal conduction function. Amongst the more common tumours causing this presentation are malignancies of the thyroid gland and cranial mediastinal masses such as lymphomas and thymomas. Lymphomatous infiltration of the laryngeal nerve has also been recorded in the cat. Iatrogenic: any surgical intervention in the cervical region or rostral thorax which involves dissection of the caudal laryngeal nerves may result in their temporary dysfunction through neuropraxia or more seriously, in permanent paralysis. Although many surgeries may potentially result in this complication the most notable procedure in this category is reconstruction of the trachea which necessitates separation of the nerves from their tracheal course and may give rise to this complication. Cats: the aetiology of laryngeal paralysis in the cat is unknown although it has been recorded as part of a generalised neuropathy. Clinical presentation ILP typically has a prolonged and insidous onset and the clinical signs associated with it may predate presentation by months or even years. Inspiratory stridor is the major and consistent finding in all patients and results from the accelerated, turbulent air flow over the fixed vocal fold(s). Exercise intolerance occurs frequently although this sign is less obvious in some dogs which appear to tailor their exercise function to the reduction in their respiratory capacity. Severe cases will exhibit degrees of cyanosis and syncopy, possibly progressing to asphyxiation. These signs are frequently exacerbated by a warm environment and although dogs may present at any time of the year many are presented during the summer months. Excitement, car travel, anxiety and stress also tend to promote the signs. Dysphonia, or change in the character of the bark, is a very useful diagnostic pointer but is only found in approximately half of dogs with ILP. Dysphagia or cough whilst eating or drinking is occasionally encountered although aspiration leading to lower respiratory infection and coughing is probably less common than has previously been suggested. The symptoms of some patients may be exacerbated or

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precipitated by the presence of other coexisting respiratory disease, for instance, primary lung tumours. Many of the above features are also common to cases of laryngeal paralysis caused by non-idiopathic conditions. The consistent presenting sign in cats with laryngeal paralysis is a whistling inspiratory stridor. Diagnosis In many cases the presenting signalment may help the clinician to reach a presumptive diagnosis. A ten year old, male Labrador retriever with a prolonged history of exercise intolerance and stridorous breathing should raise a significant index of suspicion. Auscultation over the larynx even in the resting dog should allow detection of the earliest inspiratory stridor. This high-pitched, whistling respiratory noise should become more audible during exercise but care should be taken not to over-stress the patient and precipitate an obstructive crisis merely for the purposes of diagnosis. A complete physical examination should be performed in all cases and in cases of non-idiopathic paralysis a search should be made for possible causes (e.g.: thoracic mass). Thoracic radiographs should be taken at this stage to assess if any aspiration pneumonia is present which until satisfactorily resolved may temporarily preclude progression to the next diagnostic step. Laryngeal paralysis is a failure of dynamic function and hence a definitive diagnosis can only be made by observing this function or lack of it. In most instances this is done by means of laryngoscopy. In some dogs it may be possible to inspect laryngeal function under sedation but in most a light plane of anaesthesia is more satisfactory. A deep plane of anaesthesia will paralyse the intrinsic laryngeal muscles and remove all laryngeal movement preventing a meaningful assessment of function. Laryngoscopy is best performed, therefore either during induction of light anaesthesia or in the recovering patient as the laryngeal reflexes return. Arytenoid abduction is reduced or absent during the inspiratory phase in dogs with laryngeal paralysis. Most cases of ILP are affected bilaterally although it is common for one side to be more severely affected than the other and asymetric abduction may occur. Care should exercised when evaluating arytenoid movement since paralysed vocal folds often show paradoxical movement (i.e.: move apart passively due to the expiratory air flow). It is essential, therefore, that each phase of the respiratory cycle is identified preferrably by an assistant, whilst the larynx is observed. In some dogs the mucosa overlying the corniculate process of the paralysed arytenoid cartilage(s) is often hyperaemic due to the turbulent air flow over the mucosal surface. The use of ultrasonographic examination of the canine larynx has recently been described. Movement of the arytenoid and vocal folds during the respiratory cycle could be identified and this gives rise to the possibility of recognising laryngeal dysfunction using this technique. The non-invasive nature of ultrasonographic examination of the larynx coupled with the ability to perform it in unanaesthetised patients are attractive advantages of this approach. Respiratory function measurement techniques have been described in the investigation of laryngeal paralysis. The pa-

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LARYNGEAL EVERSION / COLLAPSE SYNDROME Pathophysiology Chronic respiratory diseases resulting in turbulent airflow and abnormal negative pressures in the lower respiratory tract or abnormal cartilage structure can initiate a progressive and degenerative sequence of events within the upper airway which eventually result in obstruction of the rima. In the early stages the mucosal lining of the larynx and pharynx become oedematous and chronically thickened. This process also involves the mucosa within the laryngeal ventricle and the saccules are consequently forced to evert into the ventral rima. As the condition progresses the laryngeal cartilages begin to loose their structural rigidity and collapse towards the midline. The leading and lateral edges of the epiglottis roll inward and the cartilage folds dorsally towards the glottic opening. The weaker regions of the arytenoids, including the cuneiform processes, collapse medially drawing the corniculate processes with them. The rima is progressively narrowed by these processes and in the final stages is completely occluded. The early changes involving the saccules and pharyngeal tissue are often reversible and may be resolved by prompt management of the underlying problem. Changes involving the cartilages are, however, more permanent and once clinically-evident laryngeal collapse is a difficult condition to manage. Aetiology Airway obstruction syndromes: the development of LECS is most often associated with concurrent upper airway obstruction syndrome. It is frequently encountered in the brachycephalic dogs in which the overlarge soft palate, stenotic nares and hypoplastic nasal sinuses are responsible for upper airway turbulence. It is unclear, however, if it is this airway turbulence during the inspiratory phaseor the presence of abnormally-weak laryngeal cartilages which are unable to resist deformation during the expiratory phase which allow the problem to develop. LECS may also be encountered as the sequel to other ostructive airway conditions such as tracheal collapse and hypoplasia. Congenital: laryngeal collapse is seen as an infrequent presentation in young English Bull Terriers during the first year of life. There is some indication that a congenital cartilaginous anomaly resulting in a weak, non-rigid larynx rather than airway may underlie the condition.

Clinical presentation Laryngeal obstruction due to collapse results in stridorous breathing and severely restricted exercise ability. In the brachycephalic dog the onset of these signs is insidious and often difficult to separate from those caused by the remainder of the obstructive airway syndrome. Ongoing exercise intolerance following surgical management of the overlarge soft palate and tonsils and the stenotic nostrils, however, should alert the clinician to the possibility of degenerative laryngeal changes. Diagnosis Dogs with laryngeal collapse have severely obstructive upper airway function. Auscultation directly over the larynx should enable the stridorous turbulence to be detected but in brachycephalic dogs it may be difficult to distinguish this from the accompanying stertor. Laryngeal inspection in mildly affected dogs will reveal the glistening pea-like, everted laryngeal saccules immediately in front of the vocal folds whilst in more advanced cases the rima will be obscured by the inverting epiglottis and arytenoids.

LARYNGEAL TRAUMA Pathophysiology/Aetiology Laryngeal trauma is uncommon in small animal species due to the relatively protected position of the larynx as compared with that of man or the larger species. External trauma may result from bite wounds, choke chain injuries and occasionally, crush injuries from road accidents. Compressive injuries such as these may fracture or dislocate the laryngeal cartilages and hyoid bones obstructing the airway. Additionally, there may be neurogenic damage particularly in the case of cervical bite wounds resulting in paralysis of the vocal folds. Damage directly to the laryngeal mucosa, epiglottis and arytenoids may be seen in stick penetration injuries. In the acute phase of laryngeal trauma the airway may be obstructed due to haemorrhage, oedema or dislocations and fractures of the cartilages. More long term complications include fibrosis of the cartilage articulations which prevent normal arytenoid function and glottic stenosis resulting from the development of intralaryngeal scar tissue. Clinical presentation Injuries involving the larynx are clinically evident due to the obstruction of the airway. Patients may have laboured respiratory patterns, stridor, cyanosis and asphyxiating syncope. Occasionally, there may be subcutaneous emphysema due to air leaking into the perilaryngeal tissues. Diagnosis Inspection of the cervical region may reveal obvious penetrating wounds or cervical swellings may be evident on palpation. Auscultation will reveal stridorous laryngeal sounds. Radiography may demonstrate hyoid fractures or variations in the normal relationship of the laryngeal cartilages. Air may be present in the perilaryngeal tissues. Laryngoscopy should be performed to assess the severity of the airway obstruction and detect the presence of paralysis.

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tientâ&#x20AC;&#x2122;s hypoxic (i.e.: low PaO2) status can be quantified by blood gas analysis. The abnormal air flow versus volume pattern can be identified by tidal breathing flow volume loop (TBFVL) studies. It is doubtful if these measurements add materially to the assessment of an individual clinical case which can be gained by careful auscultation and laryngoscopy but they do permit a more objective analysis of the problem for research purposes. Electromyography, nerve conduction velocity and histological studies have been used to demonstrate abnormalities in the laryngeal nerves and intrisic muscles.

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LARYNGEAL STENOSIS Pathophysiology/Aetiology Disease or injury involving the mucosal lining of the larynx may result in the development of either scar tissue or proliferating granulation tissue which narrows the glottic opening. Intralaryngeal surgical interventions are particularly implicated in the development of scar tissue and occasionally it may result from traumatic intubation of the larynx. A proliferating granulomatous form of laryngitis has been recorded as a cause of stenosis. Clinical presentation Dogs with laryngeal stenosis will have reduced exercise tolerance and stridorous breathing.

Diagnosis Auscultation over the laryngeal region may localise the source of the respiratory stridor but direct inspection under general anaesthesia is the only means of confirming the presence of the lesion. This should be undertaken with great care since the upper airway may be obstructed to a considerable degree by the tumour and prior preparation should be made to pass a narrow endotracheal tube or if necessary to perform tracheostomy intubation. Biopsy should also be performed with caution because of the risk of haemorrhage which may be aspirated. Radiography plays little role in the diagnosis of the primary tumour but a search for metastatic extension should be made.

Surgery for laryngeal paralysis Diagnosis Laryngeal auscultation will confirm the presence of stridor. Laryngoscopy will allow inspection of the scar or proliferating tissue within the rima. Surgically-induced lesions most often involve the vocal fold sites whereas granulomatous lesions may affect the arytenoid cartilages.

LARYNGEAL NEOPLASIA Epidemiology and incidence Tumours of the larynx are rare in the dog and cat but a variety of histological types have been reported including:

Benign: Malignant:

Dog oncocytoma chondroma squamous cell carcinoma adenocarcinoma chondrosarcoma osteosarcoma

Cat

lymphoma squamous cell carcinoma

Little is known of the epidemiology of tumours in this site although lymphoma seems to be common in the cat. There is no apparent breed predeliction but males may be at greater risk. Secondary tumours or local extension of other primary tumours, most notably thyroid carcinomas, are occasionally seen. Aetiology The aetiology of most laryngeal tumours is unclear. In man these tumours are frequently encountered and may be related to inhalation of the carcinogens associated with smoking. The oncocytoma in man it is derived from cells of epithelial origin found in glandular tissue in the head and neck region. Clinical presentation Symptoms are the result of upper airway obstruction and failure of laryngeal function such as is found in laryngeal paralysis. Early signs include respiratory stridor, exercise intolerance, dysphonia and hoarseness, dysphagia and cough. More advanced lesions cause serious respiratory obstruction with episodes of cyanosis and syncope.

Undoubtedly the most common indication for surgical intervention involving the larynx of small animals is the relief of laryngeal paralysis. Techniques for the managment of laryngeal paralysis are intended to enlarge the rima permanently and ameliorate the restricted air flow. It should be emphasised that a variety of surgical procedures have been described for the treatment of this condition since it was first recognised and there is ongoing controversy as to what are the most appropriate procedures. It is convenient to categorise these procedures according to whether or not the surgery disrupts the structures within the lumen of the larynx. Extralaryngeal procedures Procedures which dilate the rima without disrupting the laryngeal mucosa have significant advantages and in the author’s view are to be preferred. In particular, the following advantages are recognised: • Gaseous anaesthesia can be maintained by routine endotracheal intubation throughout the surgery. • The risk of aspiration during surgery and the postoperative period is minimal. • The requirement for postoperative care, notably temporary tracheostomy management, is substantially reduced. • The incidence of intralaryngeal scarring is extremely low. Arytenoid lateralisation Dilation of the rima by fixing the arytenoid(s) in abduction and attempting to mimic the function of the dorsal cricoarytenoid muscle has been described by various authors and is now a well established technique. The procedure may be performed with a variety of modifications and the following is a description of the basic technique. The unilateral procedure is performed with the patient in right lateral recumbency for a right-handed surgeon and vice-versa for the left. The neck is partially extended and supported on a pack. An incision is made at a point below the junction of the maxillary and linguofacial veins and the fibres of the panniculus muscle split. The dorsal wing of the thyroid cartilage is palpated through the overlying soft tissue which is dissected bluntly to expose the thyropharyngeus muscle. This muscle is transected horizontally or its fibres

split longitudinally to expose the dorsal wing of the thyroid cartilage. The thyroid cartilage can then be retracted laterally allowing the fascial tissue lying between the thyroid and the cricoid to be broken down. At this point the firm cricothyroid articulation may be disrupted if required. Selfretaining retractors are used to retract the dorsal aspect of the thyroid laterally and the sharp prominence of the muscular process of the arytenoid cartilage overlying the rostrodorsal aspect of the cricoid cartilage is located by digital palpation. The fibres of the dorsal cricoarytenoid muscle fan out from this to the dorsal midline of the cricoid and are carefully transected to allow access to the cricoarytenoid articulation below. In cases of idiopathic paralysis this muscle will be atrophied but in cases of acute onset paralysis (eg: trauma) the muscle remains substantial. It is very useful to leave part of the muscle attached to the muscular process to permit manipulation of the arytenoid during the procedure without tractioning the cartilage itself since it may prove to be friable in some cases. The arytenoid cartilage is now carefully separated with fine scissors from its underlying cricoarytenoid articulation without disrupting the laryngeal mucosa medially. The sesamoidean interarytenoid articulation is then cut which permits free movement of the cartilage. The arytenoid is now anchored in abduction by means of a suture prosthesis. A non-absorbable suture material is essential since this will be required to retain the abducted arytenoid permanently. Materials such as polypropylene or monofilament nylon are most suitable since stainless steel even when coated may tear through a more delicate cartilage. A swaged-on needle is used to introduce the suture through the thyroid cartilage immediately rostral to the caudal cornu. The needle is passed through the lateral aspect of the arytenoid emerging in the centre of its articular face and is then passed back through this surface from a more medial point. The mattress pattern is completed by passing the suture through the medial face of the thyroid cartilage in the region of, but not immediately adjacent to the original bite. The suture is now tied firmly but without overtensioning since this may cause it to ‘cheese wire’ through the cartilages. The degree of arytenoid abduction can be inspected at this stage by temporarily removing the endotracheal tube. The thyropharyngeus muscle is closed routinely with absorable sutures over the thyroid cartilage and the potential dead space overlying the larynx is obliterated by meticulous closure of the various layers of overlying soft tissues. If not previously inspected the larynx should be evaluated at this stage before the patient recovers consciousness to confirm that there is satisfactory dilation of the rima. Any blood which may have accumulated in the laryngeal lumen should the mucosa have been perforated during the procedure should also be removed by suction. Modifications of the above technique include the following: • Bilateral arytenoid lateralisation can be performed by repeating the above technique contralaterally with the patient in left-sided recumbency has been reported. This has been recommended for younger, working dogs in which there may be a need for more glottic dilation to accommodate their greater exercise requirements. Bilateral surgery is

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reported to be associated with a higher incidence of postoperative dysphagia and aspiration. • A ventral approach has been described with the patient positioned in dorsal recumbency to permit bilateral surgery. Access to each arytenoid is achieved by rotating the larynx laterally about its longitudinal axis and is restricted as compared with that achieved by the lateral approach. • Disarticulation of the cricothyroid junction is an optional step to allow further retraction of the thyroid cartilage and exposure of the cricoid and arytenoid cartilages. Some bleeding may occur from small vessels in the region of the articulation and it is important that this should be dealt with by careful diathermic cautery. Although omitting this step restricts access to the arytenoid cartilage it shortens the operative time somewhat and may result in a more stable base to which the lateralising prosthesis can be anchored. Bilateral disarticulation of the cricothyroid joint is reported to result in dorsoventral collapse of the rima. • Studies in post-mortem specimens suggest that sectioning the inter-arytenoid band with cricoarytenoid disarticulation allows greater dilation of the rima glottidis. The use of the cricoid rather than the thyroid cartilage for anchoring the prosthetic suture has been suggested as providing greater dilation of the rima. It should be emphasised, however, that neither of these assertions have been supported by clinical studies. Preoperative workup should include: • Routine haematological and biochemical investigations since almost all patients will be geriatric. • Thoracic radiographs to rule out co-existing pulmonary disease (e.g.: primary neoplastic masses, aspiration pneumonia). • Investigation of any dysphagic signs. Postoperative care should include: • A brief period of hospitalisation to permit observation of the patient for any signs of respiratory distress. In most cases this should be no more than 24 hours and patients should be discharged with instructions for limited exercise and permanent avoidance of collar use. • Perioperative antibiotic therapy since there is potential for minor disruption of the laryngeal mucosa and perforation of the airway mucosa. Antibiotic therapy may be extended postoperatively if any risk of aspiration is perceived. Complications of arytenoid lateralisation include: • Fragmentation of the arytenoid or thyroid may occcur during the procedure if either cartilage is handled too vigorously or the prosthetic suture is repeatedly placed through the cartilage. In the event of this complication the procedure should be repeated contralaterally. • Oedema may develop within the first 24-48 hours postoperatively in the perilaryngeal tissues causing obstruction of the rima and severe respiratory distress. Corticosteroids may be employed following a prolonged dissection to preempt this complication which may otherwise necessitate temporary tracheostomy intubation. The development of a seroma or haematoma is a similar possibility which may also necessitate airway by-pass in severe cases. • Prosthetic avulsion is occasionally encountered in the immediate postoperative period and is normally due to the inclusion of an inadequate cartilage ‘anchor’ within the suture. Much less commonly, it may be seen as a chronic de-

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velopment several weeks or even months after surgery. A repeat, contralateral procedure is a feasible solution in cases in which a unilateral procedure has been performed. • Aspiration is in theory at least, a complication of all procedures which leave the rima permanently dilated. Although this may appear as a potential problem after arytenoid lateralisation workers have reported no increase in the incidence of this problem after the unilateral procedure. There appears, however, to be more risk of dysphagia and aspiration following the bilateral surgery. Providing that the other glottic protection mechanisms (ie: epiglottic movement, lateral food channels) remain functional after surgery the risk of aspiration after unilateral procedures should be acceptably low. Prognosis The long term results of unilateral lateralisation for older dogs with ILP are very favourable indeed with rapid return to previous exercise function. In one long term study of the results of unilateral lateralization more than 90% of dogs were alive one year postoperatively and had little disernible stridor or excercise intolerance due to respiratory dysfunction. The technique can be applied to all sizes of dog and is also feasible in the cat. Laryngeal re-innervation Re-innervation of the larynx by both neuromuscular pedicle grafting and nerve anastomosis has been reported in dogs. Experimental studies with artificially-created laryngeal paralysis have shown that the dorsal cricoarytenoid m. can be re-innervated by transplanting a neuromuscular pedicle innervated by the first cervical nerve. Dogs regained abductor function over periods of 9-11 months. The sternothyroid m. was selected for the graft since it is: • not innervated by the recurrent laryngeal nerve, • an inspiratory muscle and therefore provides synchronous abduction of the rima, • has a nerve supply long enough to allow transplantation without undue tension on the graft. A number of practical problems complicate this otherwise encouraging approach. Firstly, re-innervation has only been demonstrated in recently-denervated (ie: nerve-sectioned) muscle and whilst this may be feasible for traumatic injuries of the laryngeal nerve it may not be effective in chronic neuropathies such as ILP. Secondly, re-innervation of the intrinsic laryngeal muscles is indiscriminate such that simultaneous contraction of both abductors and adductors (synkinesis) may occur resulting in uncoordinated movement of the arytenoids. Finally, the long interval between surgery and the clinical result represents an unacceptable delay in the management of the older dog with severe airway obstruction. Microsurgical repair of the caudal laryngeal nerve may be feasible in some instances but this only has application for traumatic lesions. Intralaryngeal procedures Procedures which necessitate surgery within the lumen of the larynx are characterised by a number of significant intra- and postoperative considerations. These include: • Endotracheal intubation is precluded during the proce-

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dure and hence maintenance of general anaesthesia dictates either placement of a temporary tracheostomy tube or the continuous infusion of an intravenous agent. • Blood or tissue debris from the surgical site may aspirated into the lower respiratory tract. The risk of aspiration during the procedure is further increased in the absence of endotracheal intubation. • The tracheostomy tube should be maintained in situ beyond the postoperative period to by-pass any upper airway obstruction resulting from intralaryngeal oedema. • The surgical disruption or removal of the laryngeal mucosa is intermittently associated intermittently with the incidence of intralaryngeal scarring or so-called ‘webbing’ which may severely stenose the airway at the level of the rima. All of the above considerations should be examined carefully before selecting any intralaryngeal procedure. It should be emphasised that a description of the intralaryngeal procedures is included here for the sake of completeness rather than the author’s confidence in their suitability or efficacy in the management of laryngeal paralysis. Partial laryngectomy Resection of the vocal folds or ventriculocordectomy is perhaps the oldest approach to creating a permanently-enlarged rima. Several options exist including resection of one or both folds, and combination of this with partial arytenoidectomy (ie: removal of part of one or both arytenoid cartilages). Following the induction of anaethesia a midcervical, transverse tracheotomy is performed to permit gaseous anaesthesia via an endotracheal tube or cuffed tracheostomy tube. Conventional laryngeal intubation with intermittent withdrawal of the endotracheal tube from the anaesthetised patient to allow access to the surgical site is an alternate, but less desirable option for maintenance of anaesthesia. The dog is positioned in sternal recumbency with the mouth held open by means of a gag. The rima is visualised by simultaneous rostral retraction of the soft palate and ventral depression of the tongue and epiglottis. Ventriculocordectomy This is performed by grasping the vocal fold with long dissecting forceps and tensing it rostrally. Begining at its attachment to the vocal process of the arytenoid the vocal fold and adjacent vocalis muscle are then resected using either fine Metzenbaum scissors or crocodile-action cup biting forceps the latter allowing for piecemeal removal of the fold. The procedure is repeated bilaterally. A small section of mucosa is left at the ventral commissure of the rima between the resected folds and is said to reduce the risk of postoperative intralaryngeal scarring. Partial arytenoidectomy Arytenoid resection is performed in conjunction with ventriculocordectomy as described above. Cup forceps are then used to resect additional arytenoid cartilage. Opinion is divided as to how much of the cartilage should be removed in order to achieve the desired improvement in airway function. Previously, it has been customary to remove corniculate, cuneiform and vocal processes but more recent reports

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Castellated laryngofissure Ventral bisection and separation of the thyroid cartilage has been described as an alternative concept for glottic dilation. The technique as originally described for the dog was a modification of a procedure for the management of cricoid collapse in humans and involved the creation of a series of step-like incisions through the base of the thyroid cartilage following tracheotomy intubation. The castellated thyroid projections allow the two halves of the cartilage to be abducted ventrally thereby dilating the rima. The basihyoid bone is then used to anchor the unstable thryoid fragments. This technique is combined with bilateral ventriculocordectomy and consequently has many of the problems associated with intralaryngeal manipulation. There is only one long term studies of the results of castellated laryngofissure. Modified castellated laryngofissure The subsequent modification of the castellated laryngofissure procedure to include bilateral arytenoid lateralization, underlined the unsatisfactory results achieved by the original procedure. There must be doubts too as to the ratio-

nale for the modified procedure since it is clear that arytenoid lateralisation alone is extremely successful in alleviating the signs of laryngeal paralysis and there are few reports of the clinical use of modified castellated laryngofissure.

SURGERY FOR LARYNGEAL COLLAPSE Conservative management In many dogs laryngeal eversion/collapse is a progressive process and hence early detection and management of the underlying disease is essential to limit the ultimate extent of the condition. Upper airway obstruction in brachycephalic dogs should be relieved at an early age by lateralising the nares, shortening the soft palate and resecting hyperplastic tonsils or redundant pharyngeal mucosal folds. This may relieve the turbulence and abnormal airway pressures sufficiently to permit remission of the earliest changes within the larynx (ie: mucosal oedema and eversion of the saccules) without additional management. For this reason it is essential that every effort should be made to correct the underlying pathology before any surgical intervention involving the larynx itself is undertaken. The judicious use of steroidal, anti-inflammatory drugs may be helpful in promoting resolution of the laryngeal changes after upper airway surgery. Resection of laryngeal saccules In cases where the laryngeal changes are limited to chronic eversion of the saccules which does not respond to conservative management resection of the everted tissue may be performed. The patient is prepared for surgery as for partial laryngectomy (see above) and positioned in sternal recumbency. The everted saccules are identified as small, red pea-like protrusions immediately behind the vocal folds and grasped with dissecting forceps. The saccules are resected through their base with fine scissors and haemorrhage is controlled by direct pressure over the site. As is the case for laryngectomy procedures the risk of postoperative aspiration may be reduced by temporary tracheostomy intubation. Partial laryngectomy Resection of the vocal folds and arytenoids has been used in the management of LECS. The long term results, however, are poor due to significant postoperative complications and the need for repeated surgeries to maintain the airway. Major intralaryngeal resection is therefore no longer recommended in the management of laryngeal collapse. Permanent tracheostomy Permanent tracheostomy is effective in the management of many advanced cases of laryngeal collapse since not only does it provide immediate upper airway by-pass but it also relieves the abnormal airway pressures responsible for the degenerative changes involving the larynx. Permanent tracheostomas should be managed by careful cleaning during the initial 2-3 weeks when tenacious tracheal secretions may tend to occlude the opening. Thereafter, once daily cleaning is sufficient to maintain its patency. Long term problems include skin fold obstruction and stenosis of the stoma.

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indicate that the incidence of postoperative complications, notably aspiration pneumonia, may be reduced by removal of only the corniculate process. The procedure is performed unilaterally and the decision as to which side should be operated is based on preoperative laryngoscopic examination in the case of unilateral paralysis. Haemorrhage after partial laryngectomy procedures is controlled by direct pressure using a small dental sponge on the excision sites. Any blood clots or mucus which accumulate in the airway should be meticulously suctioned following the completion of surgery. The tracheostomy tube is maintained postoperatively and periodically occluded over the next 48 hours to ascertain at what point it may be safely removed. Antibiotic therapy should be maintained for several days after surgery to reduce the risk of pneumonia resulting from the aspiration of any debris. Complications of partial laryngectomy include: • Aspiration pneumonia has been reported as a frequent and potentially fatal postoperative complication after vocal fold resection and partial arytenoidectomy. Recent reports suggest that bilateral vocal fold resection alone or alternatively, the use of an inflatable tracheostomy tube during surgery may result in a significant reduction in the incidence of this problem. • Glottic stenosis may be encountered as a longer term problem due to scarring ventrally of the site of the excised vocal folds. The so-called ‘webbing’ granulation tissue may prove difficult to manage and may recurr after resection. Other techniques include lining the site with mucosal flaps or the use of a ventral silicone stent to dilate the rima. Tapering doses of prednisolone following surgical resection has been reported as providing good results. • Oedema may develop within the larynx at the resection sites necessitating temporary tracheostomy. The perioperative use of dexamethasone sodium phosphate (0.25 - 1.0 mg/kg iv) or methylprednisolone sodium succinate (0.5 - 2.0 mg/kg iv) may reduce the incidence of this problem which otherwise prolongs the postoperative tracheostomy period.

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Tracheostomy must be regarded as a salvage procedure and the long term prognosis for dogs with advanced laryngeal collapse is very guarded. Techniques such as arytenoid lateralisation, designed to alleviate the signs of laryngeal paralysis by enlarging the rima are notoriously ineffective in the management of LECS since the rigid cartilage ‘chassis’ essential for the success of the procedure is no longer present. Surgery for laryngeal trauma Animals presented with airway obstruction due to laryngeal trauma frequently require prompt tracheostomy intubation to enable an airway to be maintained pending a more detailed evaluation of the larynx under general anaesthesia. Laryngeal trauma resulting from both compressive injuries and penetrating wounds are prone to perilaryngeal oedema and bruising. Early surgical intervention may exacerbate this and immediate management should, therefore, be limited to the control of any haemorrhage, debridement of non-viable tissue obstructing the airway and tracheostomy. In the case of penetrating wounds involving the perilaryngeal tissues provision should be made for drainage and the removal of any residual foreign material. Anti-inflammatory and antibiotic therapy should be maintained with upper airway bypass until the oedema resolves, normally 3-5 days, at which time mucosal tears can be further debrided and repaired. Dislocations of the arytenoid cartilages or hyoid bones should also be corrected where possible at this time. Laryngeal function may be more meaningfully evaluated at this point since laryngeal neuropraxia and paralysis are impossible to differentiate in the initial phases of the injury. In cases where laryngeal dysfunction is still evident it is more practical to assume permanent paralysis and perform lateralising surgery (see above) than to continue to manage the patient in the expectation of possible return of function. Injuries resulting fibrosis around the arytenoid cartilages may result in the development of glottic stenosis in the longer term and management of this condition by lateralisation may prove difficult. In such cases there may be little alternative but to consider an intralaryngeal intervention or permanent tracheostomy. Glottic stenosis due to intralaryngeal ‘webbing’ is a possible long term complication of trauma and may be managed as previously described. The prognosis is guarded for return to normal laryngeal function in such cases. Surgery for laryngeal neoplasia Few laryngeal tumours present as candidates for definitive surgical excision. The single exception to this is the oncocytoma which is usually found as a discrete mass underlying the laryngeal mucosa. The mass can often be removed by careful submucosal dissection from its position within the larynx where it obstructs the rima. Ventral laryngotomy Some benign tumours, and occasionally polyps, found within the larynx are less easily accessed via the rima and are better approached through a ventral laryngotomy wound. The patient is positioned in dorsal recumbency and the airway is maintained by either a narrow diameter endo-

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tracheal tube or temporary tracheostomy intubation during the procedure. An incision is made through the cricothyroid ligament and continued forward through the ventral ‘keel’ of the thyroid cartilage. The two halves of the cartilage are separated by means of retractors to permit access to the mass and other intralaryngeal structures. The thyroid is repaired with simple interrupted sutures in its ventral aspect taking care to achieve accurate apposition and stability. The cricothryoid membrane is repaired in a continuous pattern to ensure an airtight seal. Laryngectomy Malignant laryngeal tumours (carcinomas, adenocarcinomas etc) do not lend themselves to dissection from the larynx because of their tendency to local infiltration and their advanced stage at the time of detection. A variety of fanciful techniques for their management by partial laryngectomy have been described but are derived from human surgical literature and significantly, there are no long term reports of their successful application in small animals. Laryngectomy combined with permanent total tracheostomy is, in theory, an option. The dearth of reports of the long term results of its use in the management of canine tumours should probably be regarded as an indication of its lack of success and suitability. Experience with this procedure in 10 dogs with malignant laryngeal tumours shows that the complication rate is high and few dogs go on to enjoy a normal quality of life for periods of more than 3 months after the surgery. Megavoltage radiation therapy using twin oblique portals to spare the adjacent spinal tissue is commonly used in the treatment of laryngeal malignancy in man. There are no reports in the veterinary literature of the routine use of radiation in this mode although it is certainly a viable possibility. Cytotoxic therapy is indicated in the management of lymphoma of the larynx in the cat and may achieve dramatic resolution of the clinical signs. The value of chemotherapy for other histological types is unknown. The prognosis following surgical excision of the oncocytoma is guardedly good. It’s growth is normally slow and does not appear to metastasise although local recurrence over periods of many months or years is possible. Palliation of feline lymphomas is normally short-lived and the outlook for most malignant laryngeal tumours is poor. Since the overriding determinant is airway function euthanasia is often sought by owners at an early stage in the disease.

Tracheotomy and temporary tracheostomy Indications a) Bypass of upper airway obstructions (e.g. laryngeal injuries/obstruction tracheal trauma, nasomaxillary trauma electrical/chemical burns, neoplastic lesions, foreign bodies). A major indication in small animal practice is to facilitate anaesthesia during upper airway surgery. b) Ventilatory management: tracheostomy may be used as a means of maintaining prolonged postoperative mechanical ventilation.

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Technique Often the procedure is indicated as an emergency step and may be performed in the sedated animal using local anaesthesia only and some of the following comments may not apply. However, under elective circumstances the procedure should be performed as aseptically as possible under general anaesthesia. The dog is positioned in dorsal recumbency with the neck extended on packs. A standard ventral midline approach is made to the trachea through a small skin incision. The tracheotomy would should be located well away from the thoracic inlet and larynx alike so that it cannot be obstructed by normal flexion movements of the neck. The 5th-6th tracheal interspace is a suitable site and a variety of techniques may be used to open the trachea. Surgical techniques include: i) Transverse splitting of the annular ligament: allows for anatomic restoration once the tube is removed (65% of circumference cut). ii) Flap resection: resection of circular or rectangular flap allows for easy re-intubation and may be very useful where inexperienced help is available. The flap may be left hinged for replacement. iii) Longitudinal ring splitting: allows stenosis during the healing phase. Tracheostomy tube design Tubes may: - be made of nylon, PVC (or previously silver). - be cuffed for inflation and the addition of a cuff allows for a complete seal to prevent aspiration of debris and for the ability to use positive pressure ventilation. - have a removable obturator allows the easier introduction of the tube into the wound. - have a removable cannula to allow the inner sleeve to be removed for regular cleaning. Instrumentation For this procedure should include: - basic cut down pack - tubes with a range of sizes - suction (trap bottle) - good illumination - ideally ECG monitor

Immediate complications These are uncommon but may include: - apnoea - haemorrhage - tracheotomy misplaced - cardiac arrhythmiaâ&#x20AC;&#x2122;s Management - Cleaning: should be performed regularly. The frequency depends on the rate of secretion production. A removable cannula is very useful in this respect. - Position should be frequently inspected and cuff inflated if used. - Humidification: lack of humidity and air warming depresses cilial function and increases the viscosity of the secretions as well as predisposing infection. To counter this the animal can be placed in humidified cage or the tube should be flushed with 0.5 ml-5.0 saline every1-2 hours. - Suction: secretions should be removed regularly. - Wound: the tracheostomy wound is always contaminated and needs constant attention to reduce risk of aspiration. Short term complications There are 2 major and important complications during management: - tube dislodgement - tube obstruction Other complications can include: - subcutaneous emphysema (with pneumomediastinum, and possibly pneumothorax), - aspiration - infection Long-term complications - Subcutaneous emphysema can develop after the tube has been removed, - exhuberant granulation at site of tracheotomy, - tracheal stenosis, - tracheomalacia - tracheobronchial fistula Tube removal There is no hard and fast rule for when the tube should be removed but the obstructive problem should be resolved. Always check airway function by deflating cuff and obstructing tube temporarily.

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c) Access to the lower airway - the production of chronic tracheal debris (e.g. blood, mucus) may require repeated aspiration. Some foreign bodies may be removed from the trachea via this route.

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THORACOSCOPIC PERICARDIECTOMY FOR RECURRENT PERICARDIAL EFFUSION: CLINICAL EXPERIENCE IN TWO CASES F. Acocella Med Vet, F. Addis MedVet Istituto di Clinica Chirurgica Veterinaria, Facoltà di Medicina Veterinaria - Università degli Studi di Milano, Italy

Pericardiectomy is the surgical choice for recurrent effusive and constrictive pericardial disease. The traditional techniques need a thoracotomy or sternotomy with high morbidity. The thoracoscopic tecnique it seems to be a satisfactory technique, with high accuracy and low morbidity and short operating time only for recurrent effusive pericarditis. First case: German Sheperd dog, male, 8 years old with clinical, radiological and ecocardiografic signs of pericardial disease. The diagnosis was idiopatic pericarditis after pericardiocentesis. The surgical choice was decided after no results of multiple pericardiocentesis and conservative treatment. The dog was drained before induction of anaesthesia. No selective ventilation was established and the dog was positioned in a right lateral recumbence. The first trocar was positioned at the VI i.s. on the superior axillary line. This port was for the thoracoscope. The other two ancillary ports were positioned at the IV i.s. on the middle axillary line and at the VII i.s. along an intermediate line between the inferior and the middle axillary lines. The lung was displaced posteriorly and after visualization of the frenic nerve a subfrenic pericardial window was estabilished starting from the caudo-dorsal border of the pericardium. After a two years follow up the dog did not presented any clinical, radiological and ecocardiographic signs of pericardial disease. Second case: mix breed female dog, 9 years old with clinical signs of dispnea and ascites. After a clinical, RX, US and citological examination the diagnosis was effusive malignant pericardial disease. Video assisted partial pericardiectomy was performed with no complication. The istopathologic response was pericardial mesothelioma. The owner refused any cancer chemotherapy. The dog was killed after 6 months for multi organ failure.

LUTEOLYTIC PROPERTIES AND SIDE EFFECTS OF ALFAPROSTOL, A SYNTHETIC PROSTAGLANDIN F2 ALPHA ANALOG, IN THE BITCH: PRELIMINARY RESULTS S. Romagnoli DVM MS, S. Annarella DVM, I. Vannozzi DVM, R. Ballabio DVM* Dept of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, University of Pisa, Italy *Centralvet, Agrate Brianza, Milano, Italy

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Luteolytic properties and side effects of Alfaprostol (ALF), a synthetic analog of prostaglandin F2 alpha, were evaluated in the bitch. Side effects. Four anestrous bitches of different breeds and age were treated SC with 20 mcg/kg diluted 1:1 or 1:2 in saline. Side effects (increased respiratory frequency, decrease of 1°C of rectal temperature, occasional vomiting and diarrhea, some depression) were short lived, similar in degree to what reported for other PGF2a compunds in the bitch, and were not a cause of concern. Luteolytic properties. Three bitches in diestrous were treated SC with ALF diluted 1:2 with saline BID for 5 days starting on cytological diestrous day 11-12. Serum progesterone (assayed with RIA) was 35.2+13.7 ng/ml on day 1 (prior to onset of treatment), 0.6+0.5 ng/ml on day 5-6, 0.3+0.2 ng/ml on day 8 (N=2) and 0.0 ng/ml on day 15 (N=2). It is concluded that ALF can be used as a luteolytic agent to induce abortion in the bitch.

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PROTECTIVE EFFECT OF AN INSECTICIDAL SPRAY AGAINST PHLEBOTOMUS PERNICIOSUS, A VECTOR OF LEISHMANIASIS F. Ascher1 DVM, C. Alves-Pires2 DVM, C. Campos3 DVM, M.J. Capela2 DVM, P. Aguiar2 DVM Virbac S.A., 06511 Carros, France - 2Instituto de Higiene e Medicina Tropical, 1300 Lisboa, Portugal 3 Laboratoire Vétérinaire Départemental, R.E.S.F.I.Z., 06902 Sophia Antipolis, France

Phlebotomus perniciosus (P) is a primary vector of Leishmania sp. and the dog in addition to being the victim of the disease is the main reservoir in Europe. The objective of this study was to evaluate the effect of a long acting spray formulation containing an insect growth regulator (pyriproxyfen 0.02%) and a pyrethroid insecticide (permethrin 2%) on rabbits and dogs exposed to sandflies, with the purpose to prevent blood sucking and thus reduce Leishmania sp. transmission. Animals were allocated to two groups, either untreated control or treated (sprayed once with Duowin, Virbac S.A. at day 0). P were supplied from the Instituto de Higiene e Medicina Tropical of Lisboa in-house colony. Animals were exposed for 30 minutes to male and female unfed P under controlled conditions in mosquito cages (75% RH, 20 to 24°C, darkness). The P were removed from the cages 24 hours later and counted as dead or alive, fed or unfed. Three New Zealand rabbits were used to check the feasibility of the test, one of them as control. In the treated group only 2.1% P took an incomplete blood meal, half of them having died. In the control group, 43.1% P were fed and most of these were alive. Three treated (5 ml/kg BDW) and three untreated Beagle dogs were exposed respectively to a total of 572 and 556 female P at 1, 8 and 15 days post-treatment. P mortality was higher (p < 0.001) in the treated group with 60% vs 7% in the control group. Only 1% of the P took some blood (incomplete blood meals) in the treated group compared to the 18% fed P in the control group. It is noteworthy that all but one of the fed sandflies in the treated group died. P were killed by the treatment either before or after having taken a blood meal, preventing them from searching for another host. As the flying range of P is limited and dogs represent the main reservoir of infection, control measures could therefore be implemented by collectively spraying dogs with the aim to reduce disease incidence in highly infected areas. Where 10% of the dogs are infected and 4% of the P are vectors of protozoans, the percentage of new infections over one year could theoretically be reduced to 0.93% instead of being 6%. This epidemiological feature deserves to be tested in field conditions.

OESTRUS INDUCTION IN THE BITCH WITH AN ANALOGOUS OF GnRH S. Belluzzi Med Vet, D. Zambelli Med Vet, G. Mari Med Vet Veterinary Clinical Department, Obstetric Gynaecology Section, Bologna University, Italy The aim of this work was to check the real effectiveness of a LH-RH agonist to induce oestrus and ovulation in the bitch. In the man, the continuous administration of this drug is able to stop the testicular and ovarian production of steroids. The choice of this drug is due to its property (already tested on other species) to induce oestrus and ovulation, and also to the original depot formulation (the drug persist for 28 days) of small dimension which is easy and practical to administer. Ten bitches of different breeds were treated, anoestrus was defined on the basis of serum P4 < 1 ng/ml and the vaginal smear. The interval between the previous oestrus and the beginning of the treatment was 214.8±158.6 days (min. 95 max 510). The analogous used was goserelin acetate (Zoladex, I.C.I). The bitches up to 25 kg of body weight were treated with 1.8 mg. and bitches higher weights with 3.6 mg. of goserelin acetate by a single subcutaneous administration. The vaginal smears and serum concentration of E2 and P4 were carried out every other days after the implant. After a mean interval of 5.5 days clinical signs of proestrus took place clearly in six bitches while in a mild way in two of them and finally were absent in two bitches. The proestral peak of estradiol occurred in those six bitches after 8.3±3 days after the treatment and the mean values of E2 were 75.3±59.3 pg/ml (min. 37,3 max. 143.7), in the other subjects the values of E2 experienced discontinuous growths without reaching a real peak. Serum levels of P4 increased 10.3±2.3 days after the treatment. The cytological individuation of dioestrus allowed to identify the time of ovulation which was observed 12±0.5 days from the beginning of the proestrus. Four bitches (66.6%) was diagnosed pregnant by echography and then pupped normal litters. The two bitches which did not respond (absence of proestrus) to the treatment belonged to the German Shepherd breed and to the same breeding. A more careful check of the minimum quantities of product required will allow to the considerable cost of use.

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HISTOLOGICAL PARAMETERS OF PROGNOSIS IN MALIGNANT MAMMARY TUMOURS OF THE CAT C. Benazzi* DVM ECVP, M. Galeotti# DVM, G. Sarli DVM, P.S. Marcato* DVM ECVP Dip.to di Sanità Pubblica Veterinaria e Patologia animale*, Facoltà di Medicina Veterinaria - Bologna Dip.to Scienze Produzione Animale#, Facoltà di Agraria, Udine, Italy Mammary tumours are the most important after the skin tumours and lymphoid tumours in the cat, and have a high malignancy potential (up to 90%). This study shows the prognostic histological results obtained from 52 cats, which resulted M0 at mastectomy, followed up for two years. Among the histological parameters valued, the grade of invasion was the only one which resulted significant for the prognosis (P<0.05), while tubular differentiation showed to be not significant (P=0.34). As for the grade of invasion, significant survival differences were recorded between non-infiltrating and infiltrating tumours, and within these latter, between those with stromal invasion only and with intravascular emboli. In the subjects showing stromal invasion, the division into intracapsular and extracapsular stromal invasion was significantly associated with survival (P<0.05). In the cases with emboli in the lymph and/or blood vessels, useless was the division into “massive embolism” (s.c. inflammatory carcinoma, indicative of systemic micrometastases) and “occasional emboli” (P=0.22). The results obtained, analysed in terms of survival and/or post-surgery relapse, are presented as useful indicators of the need to support or not surgery with an additional therapy: mastectomy for the non-invasive tumours or for those with intracapsular stromal invasion; mastectomy eventually associated with an additional therapy for the tumours with extracapsular stromal invasion; additional therapy which is only a palliative for all the cases with “massive embolism” and for many of those with “occasional emboli”. In contrast to the inflammatory carcinoma of the woman, the ability to discriminate between these last two aspects (cases with diffuse probable micrometastases from those with the involvement of the regional lymph node only) by the histological exam of the tumour and surrounding tissue seems to be low.

EFFICACY OF A HIGH TITRE MLV AGAINST CDV IN PUPPIES WITH MATERNAL ANTIBODIES

Background. Trials carried out in the early eighties indicate that the percentage of puppies at 6 weeks of age that responded to the CDV component of Nobivac® Puppy DP was around 80%1. The average percentage of response to vaccination can differ between populations of puppies with different average maternal antibody levels, and these levels can change in time. A recent Swedish survey2 where the percentage of animals that responded to the CDV component of 4 different vaccines was evaluated demonstrated that not all vaccines were equally reliable. Two field studies were carried out to confirm the efficacy of the CDV component of Nobivac® Puppy DP that was found in earlier studies. Material and methods. The proportion of responders in both experiments was determined by calculating the percentage of animals that showed an increase in VN titre between serum samples taken before and 3 weeks after vaccination. In the first experiment 105 animals from 7 different breeds were included, 52 were vaccinated with Nobivac® Puppy DP, 53 served as unvaccinated controls. In the second experiment 63 animals from 6 different breeds were included, 32 were vaccinated with Nobivac® Puppy DP, 31 were vaccinated with a bivalent vaccine against CDV and CAV2a. Results. The percentage of animals that responded to vaccination in the first experiment was 83%. In the second experiment, 94% of the animals responded to the CDV component of Nobivac® Puppy DP, compared to 3% of the animals vaccinated with the bivalent vaccine. Conclusion. The results from both trials confirm that the CDV component of Nobivac® Puppy DP is suitable for vaccination of puppies at the age of 6 weeks. Literature 1) Chalmers W.S.K., and W. Baxendale, (1994), Vet. Record, 135, 349-353. 2) Olsen, P, Klingenborn, B, Bonnet, B, and A. Hekhammar, (1997), Proc. ACVIM forum, 15, 695. a) Canivax® CH, Merial

SHORT COMMUNICATIONS

J.G.H.E. Bergman DVM, G. Paul DVM PhD, R. Jaspers Intervet International B.V., P.O. Box 31, 5830 AA Boxmeer, the Netherlands

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ATYPICAL BEHAVIOR OF A NASOPHARYNGEAL POLYP CAUSING A VESTIBULAR SYNDROME IN A CAT X. Roura* DVM, M. Bernardini# Med Vet ECVN, D. Fondevila# DVM PhD, T. Peña# DVM PhD Veterinary Teaching Hospital*, and Department of Animal Production and Pathology#, Faculty of Veterinary Medicine, Universitat Autonoma de Barcelona, Spain Polyps of the bulla timpanica are a common cause of peripheral vestibular syndrome in cats. This syndrome is due to the compression of the vestibular structures in the inner ear by the mass. The polyps from the middle ear either growth down to the Eustachian tube into the nasopharynx or, less commonly they growth into the external ear canal. Surgical excision of the polyps is the treatment of choice in most cases. A two year old female european cat was presented at our hospital due to a chronic dyspnoic respiratory problem. The owner reported that the first signs of the disease, as sneezing and inspiration noises, appeared one year ago. The history was lacking of any symptoms related to ear and nervous diseases. At physical examination the cat was found in good general condition. A stertorous inspiratory breathing was the only clinical sign. Minimum data base was normal. Under general anesthesia, the exploration of the nasopharynx showed a 1,5 cm non ulcerated polypoid pink mass attached to the nasopharynx. No alterations were found during the examination of the external ear canal and tympanic membrane. Radiologic examination of the osseous bullae was negative. Differential diagnosis included polyps, neoplasias or granulomatous inflammation. A complete removal of the mass was performed. Post-anesthetic recovery was good and an antibiothic treatment was instituted. The histological results was an inflammatory polyp. Then, a steroid oral therapy was administered during three weeks. The cat showed no signs of the disease in the following four months. Then, a steroid non responsive inspiratory distress reappeared, followed after two weeks by a left head tilt. The reevaluation showed a regrowth of the mass in the nasopharynx, a growth of a mass in the external ear canal and radiological signs of thickening of the left bulla. The owner refused surgery and asked for euthanasia. Post mortem pathological findings were consistent of a polyp occuping the middle ear, Eustachian tube, part of the external ear canal and the nasopharinx. In conclusion, we believe that the growth of the polyp started in the nasopharinx up to the middle and external ear throught the Eustachian tube mainly because of the lack of signs of chronic otitis and the late occurrence of the neurologic syndrome.

PANCREATIC PSEUDOCYST ASSOCIATED WITH PANCREATIC ACINIC CELL CARCINOMA, CHRONIC PANCREATITIS AND MULTIFOCAL NECROTIZING STEATITIS IN A CAT A. Boari§ Med Vet, L. Della Salda* Med Vet, M. Cipone§ Med Vet, G. Gandini G.§ Med Vet, M. Joechler§ Med Vet, D.A. Williams° DVM MSc PhD G. Sarli DVM, P.S. Marcato DVM ECVP §Dip. Clinico Veterinario, *Dip. Sanità Pubblica Vet. e Patologia Animale, Università degli Studi di Bologna, Italy °Dept. of Small Animal Medicine and Surgery, Texas A&M University, USA The purpose of this study is to document clinical, laboratory, histopathological and ultrastructural findings of a rare case of pancreatic pseudocyst associated with pancreatic carcinoma, chronic pancreatitis and multifocal necrotizing steatitis in a cat. A 15-year-old neutered male siamese cat was referred for evaluation of vomiting and anorexia of 1 week of duration. In the last three years the cat had chronic intermittent vomiting. On physical examination, a mass was palpable in the middle-right cranial abdominal quadrant. Significant laboratory findings included leukocytosis with neutrophilic left shift (30.794 neutrophils/µl; reference range 3000-11000/µl), mild hyperamylasemia (1540 IU/l; reference range: 450-1400 IU/l), hyperglycemia (153 mg/dl; reference range: 70-130 mg/dl). The serum fTLI concentration was within normal range (48 ug/l; reference range: 17-49). Loss of detail throughout the entire abdomen mostly apparent in the cranial areas and just to the right of the midline associated with increased, irregular, soft tissue opacity caudal to the stomach was noted on survey radiographs. Ultrasonographically, in the region of right-pancreatic lobe, between the descending duodenum and right kidney, a well defined cist-like structure containing anechoic fluid and surrounded by hyperchoic tissue was identify. A cystic mass in the left lobe of the pancreas associated with severe saponification of mesenteric fat and mild serosanguineous peritoneal effusion were identified during an exploratory celiotomy. A fine-needle aspirate of the cyst yielded a very clear (water-like) fluid. The fluid amylase, lipase and fTLI were respectively 660 U/l, 6140 U/l and 80 ug/l. The mass was resected but the cat was euthanized per the owner’s request before recovery and necropsy was performed. Histopathologic examination revealed pancreatic pseudocyst associated with pancreatic acinic cell carcinoma, chronic pancreatitis and multifocal necrotizing steatitis.

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ELECTROCARDIOGRAPHIC FEATURES OF DEERHOUNDS A.R. Bodey, BSc, BVSc, PhD, MRCVS Centre for Small Animal Studies, Animal Health Trust, P.O. Box 5, Newmarket, Suffolk, CB8 8JH, United Kingdom Background. Electrocardiographic features differ from breed to breed in dogs on account of differences in chest shape and size, heart shape and size and spatial relationships between heart and chest. Method. Six lead electrocardiographs were recorded from 155 Deerhounds in right lateral recumbency using a Nihon Kohden Cardiofax ECG-6851. Dogs were considered to be normal by their owners at initial examination and ranged in age from 8 months to 13 years. Where possible examinations were repeated at 9 to 12 monthly intervals. In total 281 records were made. Results. Twenty dogs were electrocardiologically normal and among the normal dogs there was an wide range in heart rate, amplitude and durations of the various ECG features, and especially of mean electrical axis which often fell outside the previously described canine normal range (+40째 to +100째). Amplitudes of R waves often exceeded the previously described canine normal range. Dogs considered to be electrocardiologically abnormal (that is those with non sinus rhythm or extra complexes) were older and had higher heart rates than normal dogs. Most frequent electrocardiographic abnormalities were ventricular premature contractions, atrial fibrillation and atrial premature contractions. Conclusions. Electrocardiographic features of Deerhounds exhibit a large range in apparently normal animals and care must be taken when interpreting traces in the light of this. However, electrocardiographic abnormalities are often recorded in the absence of any clinical signs.

RADIOLOGY OF ORAL NON ODONTOGENIC TUMOURS IN THE DOG

Primitive tumours of the oral cavity of the dog are classified as benign tumours and malignant tumours. The malignant tumours account for approximately the 6% of all canine tumours, they are locally invasive and rarely metastasise. They are also classified as odontogenic tumours (arising from dental or periodontal tissues) and non-odontogenic tumours. The non-odontogenic tumours include the most common malignant oral neoplasm: squamous cell carcinoma, malignant melanoma, fibrosarcoma and osteosarcoma. Clinically, dogs affected by malignant oral tumours present symptoms that are common to many other oral pathologies, so to diagnose oral tumours it is mandatory to biopsy. The radiological characteristics of these lesions are also not specific, but it is possible to associate different images with different tumours types, and radiology is indispensable in determining their extension, aggressiveness and clinical stage. At least in the 60% of cases the primitive tumour invades the underlying bone, but often radiology underestimates the real grade of bone infiltration. This because bone lysis becomes evident radiographically when more than 40% of the compact bone has been already demineralized. Other imaging modalities, such as CT and RMI, give a better estimation of the tumour extension and a better idea of the tumour margins, but they have now a moderate or low availability in veterinary practice, and higher costs. Today, in veterinary medicine, radiology is probably the most useful imaging modality to study the behaviour of the non-odontogenic oral tumours, because of good quality of the informations obtained and the relatively low cost, if compared with other imaging techniques.

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D. Bonello, Med Vet Department of Animal Pathology, School of Veterinary Medicine, University of Turin, Italy

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EFFICACY OF INJECTABLE MARBOFLOXACIN IN THE TREATMENT OF LOWER URINARY TRACT INFECTIONS IN THE DOG C. Brovida* DVM, P. Gruet** DVM, M. Deinert*** DVM, E. Thomas** DVM *ANUBI Ospedale per Animali da Compagnia - Strada Genova 299/A - I-10027 Moncalieri - Italy **VETOQUINOL Research Centre - F-70204 Lure Cedex - France ***I. Med. Tierklinik - Veterinärstr. 13 - D-80539 München - Germany Background. Marbofloxacin is a third generation fluoroquinolone specifically developed for Veterinary Medicine and available for small animals as tablets in several European countries. Its massive elimination by renal route as the parent compound, its broad antimicrobial spectrum and excellent tolerance appear especially interesting characteristics. An ex-vivo study in dogs allowed to show the bactericidal activity of urine after 4 mg/kg-1 marbofloxacin dosage for at least 4 days on Staphylococcus intermedius and Escherichia coli. A new therapeutic dosage of 4 mg/kg-1 marbofloxacin, 3 subcutaneous (SC) injections at 4day intervals was thus selected and assessed in a previous comparative study, showing excellent efficacy and tolerance results. Aims. To confirm marbofloxacin injectable solution efficacy and safety in canine lower UTI. Methods. 55 dogs presenting clinical signs of lower UTI were included in France, Germany and Italy. The clinical diagnosis was confirmed by urine sampling taken by cystocentesis for complete urinalysis with bacteriology and antibiosusceptibility testing. The animals received then 3 SC injections at the dosage of 4 mg/kg-1 marbofloxacin, 4 days apart. Antimicrobials and anti-inflammatory drugs were forbidden but ancillary treatments could be undergone to treat the underlying disorders (Diabetes mellitus, Cushing’s disease, urolithiasis...). Dogs were clinically assessed on D0, D4, D8, D12 and D21 and urine sampled on D0, D12 and D21. Side effects were systematically sought at each visit. Results. Escherichia coli was the most frequently isolated pathogen, in 73.0% of the cases. Marbofloxacin provided 85.7% bacteriological cure rate and 77.3% clinical cure rate on D12. Few side effects were reported during the study but none led the investigator to stop the therapy. Conclusion. Marbofloxacin, used according to a new dosage regimen (3 SC injections at 4 mg/kg-1, 4 days apart), was shown to be a practical treatment for lower urinary tract infections in the dog, with both excellent efficacy and safety.

CLINICAL TRIAL OF PIMOBENDAN: A NEW INOTROPIC/VASODILATOR DRUG: LONG TERM SURVIVAL TIME STUDY: THE RESULTS D. Bruyère DVM Cardiology Department of Brussels Referal Center, Belgium Material. PIMOBENDAN (Boehringer UD-CG 115) Its mechanism of action is a phosphodiesterase inhibition (which increases the intracellular calcium disponibility) and an improvement of the sensitiveness of myofibrils for calcium. Protocol. 65 dogs with dilated cardiomyopathy (DCM) received Pimobendan 0.25 mg/kg BID. Some dogs with severe cardiomyopathy and atrial fibrillation received also digoxin. The heart failure treatment (vasodilators such Enalapril or Lisinopril and diuretics such Furosemide) was not interrupted. Results. NYHA class* and contractility (LVSF**) evolution.

Pimobendan Pimobendan + digoxin

Day 0 3.0/14% 4.0/10%

1 week 2.0/24% 2.4/23%

3-4 weeks 1.4/31% 1.6/31%

2 months 1.2/32% 1.5/30%

*New York Heart Association: (4 = severe, 1 = asymptomatic). **LVSF: Left ventricule shortening fraction. Long term study. From 1992 untill 1997. Breeds. 13 Labradors, 11 Dobermans, 10 Great Danes, 5 Cockers, 4 New Foundlands. Gender. 75% males. Age. 8 years (1-13 years). Median survival time of the dogs who died of cardiac disease: 7 months. (Exclusion of the deaths within the first month of treatment): 9 months. Median survival time of the surviving dogs or the dogs died of non cardiac diseases: 15 months (2 to 51 months).

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CARDIOPULMONARY RESPONSES IN NORMAL AND COMPROMISED DOGS DURING PROPOFOL ANAESTHESIA A. Bufalari* Med Vet PhD, C.E. Short** DVM MS PhD Dipl ACVA ECVA, R. Gialletti*** Med Vet, M. Pepe* Med Vet, R. Arcelli* Med Vet Institute of Surgery*, Faculty of Veterinary Medicine, University of Perugia; Dept. of Clinical Sciences**, Faculty of Veterinary Medicine, Cornell Univ., Ithaca, NY, USA; Faculty of Veterinary Medicine***, University of Camerino, Italy The purpose of this study was to determine the safety of propofol anaesthesia in cardiopulmonary compromised propofol anaesthetized dogs. Anaesthesia was maintained with propofol administered by infusion pump. The study was completed in adult dogs randomly selected to receive (a) 0.1 mg/kg IM acepromazine followed by propofol induction (4.4 mg/kg IV) and maintenance by infusion without cardiopulmonary compromise; (b) 0.1 mg/kg IM acepromazine followed by deliberate propofol overdose to cause respiratory depression; the final group (c) 0.1 mg/kg IM acepromazine, 4.4 mg/kg IV propofol with establishment of hypovolemic hypotension (20 ml/kg blood loss) during propofol anaesthetic maintenance. Blood pressure, heart rate, respiratory rate and arterial blood gas parameters remained in physiologic range in control group (a). In group b, fifty percent of dogs developed apnea (>60 sec.) to deliberate anaesthetic overdose and slight hypotension. Remaining dogs had significant respiratory depression as demonstrated by drop in oxygenation. All dogs responded well to oxygen administration with or without assisted breathing. Cardiopulmonary responses to deliberate haemorrhagic shock were evaluated during propofol anaesthesia along with the effects of fluid therapy, blood replacement and oxygen-enriched ventilation. Blood loss resulted in significant drop in mean arterial blood pressure (–30.1%). Oxygenation remained satisfactory. Propofol reduced the heart rate (-22.1%) during the hypovolemic state, blocking the normal sympathetic response to increase the heart rate, but did not interfere with pulmonary sympathetic compensatory mechanism to maintain a normal blood pH, O2 (+12.7%) and CO2 (-6.2%) level. Treatment of hypovolemia with fluid, blood and oxygen increased heart rate (+57.2%), mean arterial blood pressure (+81.5%) and PaO2 (+25.3%). The successful management of deliberate respiratory depression and hypotension during propofol anaesthesia in the groups of dogs by oxygenation or fluid therapy has been demonstrated safe and effective patient management during propofol anaesthesia.

INTEGRATION OF CLINICAL AND HISTOLOGICAL PARAMETERS FOR THE PROGNOSIS OF MAMMARY TUMOURS OF THE DOG AND CAT

Clinical parameters (dimension of the tumour (T) following the TNM system and lymph node involvement confirmed on histological basis) were singularly evaluated using survival analysis in 78 dogs and 31 cats, which were M0 at surgery, and followed up for 2 years. Each group determined according to T was then divided up into 3 levels of neoplastic infiltration as assessed on histological basis (non-infiltrating tumour, tumour with stromal invasion, tumour with emboli in the vessels). In the 3 groups (T1, T2, T3), both in the bitch and in queen, a significant survival difference was detected (P<0.05: T1vsT2 and T1vsT3 in the bitch, T1vsT3 in the queen); this difference was sligtly associated with survival in other comparisons (P=0.06 T2vsT3 in the queen; P=0.07 T1vsT2 in the bitch) with the only exception of T2vsT3 in the bitch (P=0.37). In both species lymph node involvement was significantly associated with prognosis (P<0.0001). Integration of T with grade of invasion: in the T1 group it did not offer additional prognostic information (P=0.37 in the queen; P=0.40 in the bitch); in the T2 group it evidenced a survival difference statistically significant between tumours with intravascular emboli and those non-infiltrating or with stromal invasion only (P<0.0001 in the bitch; P<0.05 in the queen); in the T3 group it maintained the same effect shown for T2 in the bitch (P<0.0001) but not in the queen (P=0.27). The information deriving from the integration of the neoplastic dimension and the grade of invasion would be important to define, in some T groups, 2 different risk classes: the one including the non-infiltrating tumours and those infiltrating with stromal invasion only, and the other including the cases with neoplastic emboli in vessels.

SHORT COMMUNICATIONS

O. Capitani* DVM, G. Sarli# DVM, C. Sassetti*, P.S. Marcato# DVM ECVP Dipartimento Clinico Veterinario*, Dipartimento di Sanità Pubblica Veterinaria e Patologia animale# Facoltà di Medicina Veterinaria - Bologna, Italy

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NEUROLOGICAL FINDINGS IN COCKER SPANIELS WITH FAMILIAL VITAMIN E DEFICIENCY AND RETINAL PIGMENT EPITHELIAL DYSTROPHY R. Cappello* DVM, G. McLellen* DVM, S. J. Wheeler* DVM, K. Chandler* DVM, C. Rusbridge* DVM, P. Lyabert* DVM, R. Elks* DVM, I.G. Mayhew# DVM, A.P. Bjornson§ DVM Departments of Small Animal Medicine* and of Veterinary Pathology§, The Royal Veterinary College Universitity of London, Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Medicine, University of Edinburg, Easter Busch Veterinary Centre# Background. Vitamin E deficiency has-been described in Cocker Spaniels suffering Retinal Pigment Epithelial Dystrophy (REPED). A spectrum of neurological disorders has been associated with chronic vitamin E deficiency in a range of species including man. Aim. To characterise the neurological and neuropathological changes in Cocker Spaniels with RPED and familial vitamin E deficiency. Methods. A full neurological examination was conducted on Cocker Spaniels which were diagnosed as suffering from RPED by the ophthalmology service of The Royal Veterinary College, University of London, between March 1996 and October 1997. In all cases plasma vitamin E deficiency was confirmed by High Performance Liquid Chromatography. In two cases electromyography (EMG) was performed and motor nerve conduction velocities (MNCV) measured. In 4 cases cerebrospinal fluid (CSF) examination and in 1 case magnetic resonance imaging were also performed. In 2 cases full post mortem examination including neuropathological examination was conducted. Results. The mean age at presentation was 4 years (range 2-7 years). Six dogs were female and 2 male. Three dog demonstrated severe ataxia affecting all four limbs, 2 dogs were ataxic in the pelvic limbs and 3 were normal. Proprioceptive deficits were noted in all four limbs in 2 dogs and in the pelvic limbs in 5 dogs. Four dogs manifested whole body tremor. EMG abnormalities were present in 3 dogs. MNCVs and amplitude were normal. MRI performed in one case was normal. CSF examination was normal in all 4 dogs in which it was performed. The neurohistopathological findings were similar in both dogs. Spinal cord neuronal fibre degeneration was recognised in most funiculi, being slightly more evident in the gracile, spinocerebellar and ventromedial tracts. In the medulla oblongata, the lateral cuneate nuclei revealed profound neuroaxonal dystrophy with spheroid formation, neouronal loss and astrogliosis. Conclusion. These clinical and neuropathological findings suggest that chronic vitamin E deficiency in Cocker Spaniels results in a proteiform neurological syndrome. These findings are similar to those associated with familial isolated vitamin E deficiency in man, and to those of equine degenerative myeloencephalopathy in which vitamin E deficiency has been described.

INCIDENCE OF ATOPIC DISEASES IN DOGS IN SLOVAKIA P. Chandoga, DVM, M. Kozák, Assoc Prof, DVM, PhD, J. Mojzˇisˇová, DVM, M. Tucˇková, Dipl Ing Department of Internal Diseases of Solipeds, Small Animals and Birds, University of Veterinary Medicine in Kosˇice, Slovakia Goals. To observe and evaluate anamnestic and clinical aspects at atopic disease in dogs. To judge the significance of allergendiagnostics for the evidence of environmental allergens at detection of atopy in dogs in the region of Kosˇice in Slovakia. Material and Methods. A basic set consisted of 65 patients with atopic symptoms of the disease. Dogs were examined at the 1st Internal Clinic of the University of Veterinary Medicine in Kosˇice during 1994-1997. Intradermal tests were performed using the Dutch allergens ARTU-BIOLOGICALS for diagnostics of atopy in dogs. Results. The highest incidence of atopy was found in German Shepherd dogs, then in crossbreds and Poodles. Atopic disease was recorded also in Slovak long-haired sheep dog. The first symptoms of allergy occurred between the 1st and 3rd year of life in 37 (56.9%) examined patients. The seasonal dependence of the diseases (spring-autumn) was observed in 30 (46.1%) cases. Besides pruritus with characteristic distribution of skin lesions, also disorders of gastrointestinal tract and paranal sacs were recorded. Of the seasonal allergens, the highest number of reactions (13.8%) was found on weed pollen, then grass pollen (4.6%) and tree pollen (3.1%). Of the non seasonal allergens, Dermatophagoides farinae (67.7%), Tyrophagus putrescentiae (55.4%), Acarus siro of (36.9%) and human epithelia (35.4%) ahowed the high number of reactions. Multisensitivity was observed in 78.5% cases. Conclusion. Atopic diseases with wide scale of allergens in dogs have been found to be frequent also in our conditions. Based upon our experiences at making diagnosis of atopy, it is necessary to map and to have at our disposal a complete set of environmental allergens for a certain geolocality.

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TERMINATION OF PREGNANCY IN THE BITCH BY VAGINAL ADMINISTRATION OF PGF2α M. Cinone* Res, G. Aiudi* DVM, M.E. Dell’Aquila* Tec Biol, A. Zarrilli # Ass Prof, R.L. Sciorsci* Res Inst. Biol. Reprod. & Obstetr. Dom. Anim.*, University of Bari, Italy Inst. Physiol. Vet.#, University of Bari, Italy The wide spreading of small animals and the birth control enlarged the requirements of pregnancy termination in the bitch. A suitable method to induce abortion is not available up to date and very toxic drugs, such as isochinolina, are currently commercialized. The aim of this work has been the definition of a pharmacological treatment useful to cause the abortion induction by means of PGF2α endovaginal administration. The experiment has been carried out on 10 bitches 2-7 years old and middle/large size (20-35 kg b.w.) which were between the 35°±5 day of the pregnancy. The pregnancy period was calculated on the basis of the first day of cytological diestrus. The pregnancy diagnosis was made by ecographical test. All bitches in healthy conditions were treated with endovaginal administration of syntetic PGF2α, luprostiol (Prosolvin-Intervet) every 24h up to abortion occurred. The dose was of 0.15 mg/kg b.w. adsorbed with a gel made of fumed silice and triacetin (Sigma). Blood levels of progesterone have been recorded by RIA. The abortion occurred after 4-5 days of treatment with the expulsion of fetuses and fetal membranes without complications. The subjects had mucoid losses after the first day of treatment. Blood losses were observed one day before the fetuses expulsion and continuing up to 3-4 days after the abortion. The side effects such as tachycardia, polypnoea, ipersalivation, contraction of the abdominal muscle with kyphosis, which were of low degree spontaneusly resolved 30’after the treatment. The subsquent clinical control did not show undesidered consequencies, indeed after 3-4 months the bitches presented natural fertile heat and two of them were coupled and became pregnant. The progesterone, after the second PGF2α administration, presented a fast fall and remained at basal levels till the abortion. The endovaginal administration in abortion induction allowed to use a very low dose of PGF2α and to reduce indesidered side effects.

A CASE OF CANINE CENTRAL DIABETES INSIPIDA CAUSED BY A CHROMOPHOBE CELL ADENOMA OF THE HYPOPHYSIS

Central diabetes insipidus (CDI) is a rare condition found in small animal practice. Idiopathic CDI is much more frequent than secondary CDI due to a neoplasm of the neurohypophysis or hypothalamus. The aim of this presentation is to make a differential diagnosis of a 6 year old male Boxer with polidipsia and polyuria without neurological signs. The first approach to this case was to differentiate the possible CDI from hyperadrenocorticism, diabetes mellitus and renal failure. This differential was based in clinical signs, history and results of blood and urine tests. Because the urine was hiposthenuric, the next step was to differentiate between central or nephrogenic diabetes insipidus and psicogenic polydipsia. After a water deprivation test, CDI was diagnosed. As the dog had no neurologic signs and the CSF was normal, a vasopressin treatment was recommended. In the next month the dog improved the polidipsia and polyuria, but subsequently showed some visual impairment and a lethargic state. A new neurologic examination revealed clinical signs compatible with a space-occupying lesion located in the cerebrum or diencephalon. CT scan showed a tumour over the hypophysis with a large oedema and deviation of the right cerebral ventricle. Three days later the dog became very ill and died. Histology and immunohistochemistry identified the tumour as a chromophobe cell adenoma of ACTH-secreting cells, originating from the pars distalis of the adenohypophysis. The differential diagnosis in these cases is complex; although the nature of the tumour ought to determine a clinical picture of Cushing’s disease, CDI was the presentation, probably due to compression of the hypophysis. CT scan is critical in arriving to a definite clinical diagnosis. Repeating the neurologic examination is probably the best method to rule out neurological involvement when it is impossible to use CT scan. The CSF sample was normal and, in this case, useless to assess the existence of the tumour.

SHORT COMMUNICATIONS

J.H.D. Correia*, DVM, PhD, A.J.A. Ferreira*, DVM, PhD, M.M.G.R.E. Niza*, DVM, PhD, J.M.J. Correia, DVM*, Mulas, J.M.#, DVM, PhD, M.L. Ferreira*, DVM, PhD *DEMOC, Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa, Portugal; #Dept. Anatomia y Anatomia Patologica Comparadas, Fac. Veterinaria, Universidade de Córdoba, Spain

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A CASE OF PRIMARY CILIAR DYSKINESIA IN A DOG D. De Lorenzi Med Vet Libero professionista, Forlimpopoli, Italy Although primary ciliary dyskinesia is an infrequent disease, it should be taken into account with young dogs suffering from recurrent rhinosinusitis, bronchitis and bronchial pneumonia. This disease is likely to be connected to a recessive autosomic gene causing ciliar asynchronism and consequently functional immobilization as well as very little or no mucociliar clearance activity. Thanks to electron microscopic ultrastructure tests of cilias, it is possible to evaluate which anomaly is affecting cilias and the percentage of cilias involved. A 5-month-old English Springer Spaniel, male, regularly vaccinated, has undergone a clinical examination, x-rays and bronchoscopic tests, because it had been underdeveloped, suffering from cough and occasional bilateral nose discharge with no response to previous antibiotic treatments, since the age of two months. No foreign body accidentally inhaled has been detected by the bronchoscopy. A bronchoalveolar lavage has been performed showing infectious neutrophilic exudate from which Pasteurella multocida and Staphilococcus intermedius have been isolated, but no Micoplasma sp. A 30-day antibiotic treatment based on the antibiogram has only ensured temporary results. Therefore the dog has subsequently undergone one more bronchoscopy even to take some fragments of the tracheobronchial and nose mucosa and carry out an ultrastructure evaluation of cilias. 300 ciliar structures from trachea, bronchi and nasal mucosa, almost half sectioned, have been examined. Ultrastructure modifications were apparent in 78% of them: loss of one or both central single tubes, partial absence of dineine arms, disarrangement of outer doublets, cilias accidentally arranged. The same test has been performed on a reference standard from an asymptomatic dog of the same race and age. Only 2.9% of cilias has shown a modified ultrastructure. As far as the author knows, this is the first case in Italy in which the assumed diagnosis has been confirmed by ultramicroscopical tests on the structures involved.

PRIMARY CUTANEOUS LYMPHOMATOID GRANULOMATOSIS IN A DOG M. Baldi° Med Vet, L. Della Salda* Med Vet, A. Boari# Med Vet, B. Passarini§ Med Vet *Dip. Sanità Pubblica Veterinaria e Patologia Animale, # Dipt. Clinico Veterinario, § Istituto di Clinica Dermatologica, Università degli Studi di Bologna, Italy ° Ist. di Patologia Speciale e Clinica Medica Veterinaria, Università degli Studi di Teramo, Italy The purpose of this report is to document clinical, histopathological and ultrastructural findings and therapeutical approach of a rare case of primary cutaneous lymphomatoid granulomatosis in a dog. A 5-year-old mixed breed male dog was referred for facial erythematous-erosive cutaneous plaques. Skin examinations were negative for cutaneous mites, bacteria and fungi. Cytological findings were compatible for a pyogranulomatous dermatitis. Two months after the initial visit the dog developed a severe erosive to ulcerative skin lesions associated with scaling and nodules over the head and left rear limb. Skin biopsies showed a pleocellular periadnexal and angio-invasive nodular to diffuse cell infiltration. Cell populations were mainly atypical large lymphohistiocytic cells, plasma cells and occasional neutrophils. Immunohistochemical examination (Antisera specific for T and B lymphoid markers used: CD3, CD4, CD8, CD21, MAC 387, and IgG, IgA, IgM) demonstrated an antigen expression referable to an atypical T-cell lymphoma. Ultrastructurally, the large lymphohistiocytic cells showed irregular cytoplasmic and nuclear contours, abundant heterochromatin and rough endoplasmic reticulum, some multivesicular bodies but no lysosomes. In the dermal endothelial cells several paracrystalline tubuloreticular structures were frequently observed. Based on the histopathological diagnosis of lymphomatoid granulomatosis, treatment was than started with a combination of prednisone and cyclophosphamide as proposed by Woods et al. (1984)1. Ciclophosfamide treatment was changed to chlorambucil (2 mg//m2/4 consecutive days/week os) when a sterile hemorrhagic cystitis recurred after about 1 year of ciclophosfamide therapy. Over the 16 month follow up, during which the dog was under clinical-laboratory control, skin lesions (alopecia, nodules and erythema) were still present on the face. References 1. British Journal of Dermatology 110, 619-625.

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MEDIAL APPROACH FOR TOTAL HIP REPLACEMENT IN DOGS. AN EXPERIMENTAL STUDY Z. Diószegi DVM, Z.S. Kendik DVM, J. Tóth DVM PhD, B. Fenyves DVM Department and Clinic of Surgery and Ophthalmology, University of Veterinary Science, Budapest, Hungary Background. Total Hip Replacement is a continuously developing procedure in canine orthopedic surgery. Aims. To experience the possibility of a new approach to the hip joint for Total Hip Replacement which provides better exposure of the acetabulum, has not negative effect on the gluteal muscle group, and has much better cosmetic appearance. Methods. In dorsal recumbency the origin of pectineus muscle, and the insertion of iliopsoas muscle is tenotomized. The adductor muscle is partly elevated from the femur, and the femoral head excision is completed. With abduction and caudal traction of the femur the acetabulum is widely exposed. To prepare the femur for the reaming of prosthetic stem the greater trochanter is lifted into the acetabulum and the leg is ad maximum abducted. From this point the procedure is similar to other cemented THR. Techniques finally the tenotomies are repaired and the wound is closed. Results. In the first case we did not repaired the pectineal miotomy, and so a medial luxation occurred. In two other cases the medial luxation was due to the improper placement of the acetabular component. One dog was exterminated intraoperatively due to the fracture of the greater trochanter. The remaining four cases were successful. Conclusion. We found it possible to do Total Hip Replacement via medial approach. The visibility of the acetabulum was better, the reaming was easier, but we had to learn the correct placement of the acetabular component in dorsal recumbency. Reaming of the femur was less convenient, even in cases with serious arthrosis with diminished angle of abduction. Avoiding the operative trauma of the gluteal muscle group, the possibility of lateral luxation is diminished. Last but not least for the pleasure of the owners in the future the hairclipping and the wound is hardly visible on a standing animal.

EFFICACY OF CIS:TRANS 25/75 MICROINCAPSULATED PERMETRINE IN THE THERAPY OF OTODECTIC MANGE IN THE DOG AND IN THE CAT

Objective. Clinical evaluation of the efficacy of a dermatologic acaricide cis:trans 25/75 0.3% water suspension permetrine (Zekout® ICF), in the treatment of otodectic mange in small animals. Material and methods. 20 animals (7 dogs and 13 cats) with otodectic mange (diagnosis obtained with otoscopic examination and/or microscopic examination of the exudate). When presented, none of the pets had been treated with injectable ivermectin (Ivomec®), parasitcides and corticosteroids (neither topic medication, nor ear canal medication used) in the previous 15 days. Every patient was submitted to general and dermatologic/otologic examination. All data concerning: presence of parasites and/or exudate in the ear canal, pruritus, erythema, and skin lesions, were recorded on day 0, 7, 14, 21, 31 on a special clinical record. All the subjects included in the study were submitted to the following therapy: A) ear canal detersion: a single application, only if the ear canal resulted obstructed with debris, of cerumene® and NaCl solution. B) dermatologic acaricide: application of the acaricide in the ear canal (3-4 drops), on the neck, on the back and on the base of the tail skin, every 7 days for 4 times (days: 0, 7, 14, 21). Criteria of selection for withdrawal in the therapeutical trial: no positive answer detected or worsening of the clinical signs, sudden signs of a drug reaction. The clinical evaluation of the efficacy of the acaricide used was detected by direct and mineral oil microscopic examination of the exudate (presence and number of parasites/eggs detected on 5 fields at 50x magnification) before the treatment (day 0), during the treatment (days: 7, 14, 21) and after 10 days since the end of the treatment (day 31). The efficacy was classified as: good (no parasites and/or eggs detected), moderate (presence of dead parasites and no eggs detected), no efficacy (presence of vital parasites and eggs detected). The clinical evaluation was done by detection of total absence of the following clinical signs, at the end and during the 10 days of therapeutical trial: 1) presence of pruritus and pain in the ear canal. 2) presence of erythema in the ear canal. 3) presence of exudate in the ear canal. The efficacy was classified as: good (no clinical signs detected) moderate to low (50% of clinical signs still detected), no efficacy (persistence of clinical signs detected). Results. In all the 20 cases presented a good efficacy of the microincapsulated permetrines has been detected. Nor parasites neither eggs has been found and clinical signs has not been detected too (two weeks since the first day of treatment). No side effects has been detected. Conclusions. According to the results obtained in this pilot study it is possible to state that 0.3% suspension of cis-trans 25/75 microincapsulated permetrine are effective in the treatment of otodectic mange in the dog and in the cat.

SHORT COMMUNICATIONS

F. Fabbrini DVM Clinica Veterinaria Papiniano 50 - 20123, Milano, Italy

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CASE REPORT OF ROCKY MOUNTAIN SPOTTED FEVER IN A DOG FROM NORT-EASTERN ITALY M. Caldin1 Med Vet, T. Furlanello1 Med Vet, G. Lubas2 Med Vet San Marco Private Veterinary Clinic, Padua, Italy; 2Veterinary Clinical Medicine Institute, University of Pisa, Italy

The Rocky Mountain Spotted Fever (RMSF) is a rickettsial disease caused by Rickettsia rickettsii. The disease is well known in North America, but it has been very rarely described in Europe, except in the recent years in Southern Italy. In April 1997, a referring veterinarian submitted to our Clinic a newfoundland female dog, 3 years old, with an history of febrile syndrome. The dog used to live in a large courtyard in a semi-urban area close to the city of Padua. At the clinical examination we found pyrexia (40.2 °C) and an obvious subcutaneous erythematous swelling, diffuse to the ventral area of the body. The main abnormalities in the blood works (including bile acids assay) were hypoalbuminemia (2.2 g/dl, normal 2.54.0) and a slight hyponatremia (139 mEq/L, normal 141-154). The coagulation profile was normal, except for a severe hypoantithrombinemia (79.3%, normal 100-148). The most obvious site of albumin and antithrombin loss was the subcutis and a diagnosis of vasculitis has been proposed. Since one of the most common cause of vasculitis is the acute infection by Rickettsia rickettsii, we tested the dog with a validated semiquantitative test. The serum titer for IgM was positive and comprised between 1:64 and 1:128. The titer for IgG was similarly beetwen 1:64 and 1:128. The serum titers for Ehrlichia canis and Borrelia burgdorferi were negative. At that point we suspected the RMSF, although no other diagnostic tests had been employed to support our thought. The dog has been treated with doxycycline (10 mg/kg q12h PO for 1 month). We experienced a very rapid clinical response to the treatment, although the hypoalbuminemia needed more than one month to recover. In summary, the clinical presentation (diffuse skin rush), the haemato-biochemistry findings (hypoalbuminemia, hyponatremia, no evidence of DIC) and the serum titer suggested us a diagnosis of RMSF. No informations were available about the source of the infection and the vector. Further researches are needed for redefining the epidemiology of RMSF, and european veterinarians need to be aware of the occurence of this infection, taking in account also the zoonotic importance of this tick-borne infection.

HISTOLOGICAL PARAMETERS OF PROGNOSIS IN MALIGNANT MAMMARY TUMOURS OF THE DOG M. Galeotti* DVM, C. Benazzi# DVM ECVP, G. Sarli# DVM, M. Montagnese* DVM, P.S. Marcato# DVM ECVP Dip.to Scienze Produzione Animale*, Fac. di Agraria, Udine, Italy Dip.to di Sanità Pubblica Veterinaria e Patologia Animale# - Fac. di Medicina Veterinaria - Bologna, Italy Mammary tumours are the most important tumours for their frequency in the dog, with a malignancy ranging from 40% to 60%. This study shows the prognostic histological results obtained from 107 dogs, which resulted M0 at mastectomy, followed up for two years. Among the histological parameters valued, the grade of invasion (P<0.0001) resulted significantly associated with prognosis while tubular differentiation (P<0.05) and myoepithelial proliferation (P=0.09) slightly associated with prognosis. As for the grade of invasion, significant survival differences were recorded between non-infiltrating and infiltrating tumours, and within these latter, between those with stromal invasion only and with intravascular emboli. In the subjects showing stromal invasion, the division into intracapsular and extracapsular stromal invasion was not important for the survival (P=0.35), but significantly associated with the cancer-free interval (P<0.01). In the cases with emboli in the lymph and/or blood vessels, the division into “massive embolism” (s.c. inflammatory carcinoma, indicative of systemic micrometastases) and “occasional emboli” (P=0.078) was useful. The results obtained, analysed in terms of survival and/or post-surgery relapse, are presented as useful indicators of the need to support or not surgery with an additional therapy: mastectomy eventually associated with an additional therapy for locally invasive tumours; mastectomy associated with an additional therapy for the tumours with “occasional emboli”; additional therapy which is only a palliative for all the cases with “massive embolism”, in which micrometastases are usually active. The loss of tubular differentiation and absence of myoepithelial proliferation do not seem important histological data, as the different survival times in these cases do not appear biologically important (1 month difference in the average value), even though they may influence the prognostic judgement and the therapeutic criteria to be followed.

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CORRELATION BETWEEN LEFT ATRIAL ENLARGEMENT, BODY WEIGHT AND ATRIAL FIBRILLATION IN THE DOG C. Guglielmini* Med Vet, V. Chetboul§ Med Vet, M. Pietra* Med Vet, J.L. Pouchelon§ Med Vet, M. Cipone* Med Vet Dip. Clinico Veterinario*, Università di Bologna, Italy Service Médécine§, E.N.V.A. Among the population of dogs referred for cardiovascular examinations during the period 1996-97, 164 subjects were selected with the criteria of cardiovascular diseases associated with left atrial enlargement (i.e. mitral valve endocardiosis, dilated cardiomyopathy, subaortic stenosis, patent ductus arteriosus and mitral valve dysplasia). An electrocardiographic (ECG) and echocardiographic, two-dimensional real-time and M-mode, examinations were conducted on all subjects. On the basis of ECG the dogs were divided in: Group A, 40 cases (24.4%) with atrial fibrillation (AF) and Group B, 124 cases (75.6%) without AF. The latter Group (B) was subdivided into Group C, 89 dogs (54.3%) which showed normal sinus rhythm (SR) and Group D, 35 dogs (21.3%) which showed other types of arrhythmia. The echocardiographic measurement of left atrial sistolic diameter (LA) and aortic diastolic diameter (Ao) were made and the LA/Ao ratio was calculated as an index of LA enlargement independent of body weight (BW). A statistical analysis (ANOVA) was carried out comparing the dogs of Group A with those of Group B and C according to the variables BW, LA and the LA/Ao ratio. A significant difference (p<0.001) was found between dogs of Group A and those of Group B and C for each of the considered variables. The predictive areas of developing an AF was subsequently calculated comparing to the maintenance of SR or the developing of other types of arrhythmia correlating the BW with the LA and the LA/Ao ratio. For the same degree of LA enlargement (expressed by the LA/Ao ratio) the probability of developing an AF increases in the same way of BW. Therefore AF is correlated to absolute LA enlargement rather than to its relative degree of enlargement, explaining the prevalence of this type of arrhythmia in giant dogs.

ATTEMPTS TO CURE FELINE LEUKEMIA VIRUS INFECTION WITH BIOLOGIC RESPONSE MODIFIER TREATMENT.

It caused a sensation when HÖRBER and MAYR (1991) published to be able to cure 80 to 100% feline leukemia virus- (FeLV) infected cats from viremia by using a biologic response modifier, because FeLV infection is still considered to account for most disease-related deaths in pet cats. Different treatment attempts with various drugs were performed in the past but none resulted in healing or complete virus elimination. HÖRBER and MAYR (1991) however, used the paramunity inducer PINDORF (Baypamun®, Bayer, Leverkusen) consisting of inactivated parapox ovis virus to cure FeLV infection. Since that time, Baypamun® is the most commonly used drug for treatment of FeLV infection in Germany. Two placebo-controlled double-blind trials were performed to determine the therapeutic efficacy of Baypamun® in naturally FeLV-infected cats under controlled conditions. In the first study, 120 cats were involved. Sixty cats were treated with Baypamun®, 60 with a placebo preparation of virus-free cell culture medium. Dosage and administration of the drug over a 7 week period were performed according to the instructions given by the company. Remission of viremia occurred in 12% and 7% of the cats treated with Baypamun® and placebo, respectively. This difference was not statistically significant. In the second study, 30 naturally infected cats were treated in a placebo-controlled double-blind trial. In complete, 20 clinical, laboratory, immunological, and virological parameters were examined, but no statistically significant differences could be demonstrated between Baypamun® and placebo application. Therefore, FeLV infection was not influenced by Baypamun® treatment. The importance of placebo-controlled studies to prevent uncritical misinterpretation was demonstrated.

SHORT COMMUNICATIONS

K. Hartmann* Priv-Doz Dr, A. Block* Dr, G. Ferk* Dr, A. Vollmar# Prof Dr, H. Lutz§ Prof Dr I. Medizinische Tierklinik*, Institut für Pharmakologie#, Ludwig-MaximiliansUniversität München, Germany, Veterinärmedizinisches Labor§ der Universität Zürich, Switzerland

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SAFETY TRIAL IN BITCHES WITH TABLETS CONTAINING OESTRIOL (INCURIN®) S. Hendriks DVM, B. Janszen DVM PhD Intervet International B.V., P.O. Box 31, 5830 AA Boxmeer, the Netherlands Background. Incurin® is indicated to treat bitches suffering from urinary incontinence due to sphincter mechanism incompetence. Because the active ingredient of Incurin ®, oestriol, is an oestrogen with a short receptor residence time, it shows only early oestrogenic effects. Experience in humans for over 30 years has shown that these early effects do not lead to toxicity. Results from clinical studies indicate that the effective dose is between 0.5 and 2 mg/animal, once daily or every other day. A safety trial in dogs was carried out to confirm the safety of oestriol when given up to 5 times the maximum clinical dose. Material and methods. Four groups of intact bitches were treated with 0 (n=5), 2 (n=4), 6 (n=4) or 10 (n=6) mg oestriol/animal for a period of 90 days. Clinical examinations were carried out at regular intervals, and blood samples were taken for haematology and blood biochemistry. Necropsy including histopathology of the bone marrow was performed after completion of the study. Results. All animals remained healthy during the study. Signs of oestrus were seen, mainly in the animals receiving the high doses. Haematology results and histopathology of the bone marrow indicated that bone marrow suppression did not occur. Conclusion. Incurin® is safe, even at 5 times the maximum clinical dose. This finding is in line with the results from clinical studies in which animals were treated up to 600 days without significant adverse reactions.

TREATMENT OF URINARY INCONTINENCE IN THE BITCH: CLINICAL TRIAL WITH TABLETS CONTAINING OESTRIOL (INCURIN®) S. Hendriks DVM, J.G.H.E. Bergman DVM, T. Nell DVM, P.H. van Laar, B. Janszen DVM PhD Intervet International B.V., P.O. Box 31, 5830 AA Boxmeer, the Netherlands Background. Sphincter mechanism incompetence (SMI) is an important cause of urinary incontinence (UI) in bitches. A clinical trial was performed with Incurin® (containing 1 mg oestriol/tablet) in bitches suffering from UI. Material and methods. One hundred and thirty-three (133) bitches with UI due to SMI were treated with Incurin ®. Of these bitches, 96% was spayed. The starting dose was 2.0 mg/animal once daily. In case of sufficient response after one week the dose was reduced to 1.0 mg and after two weeks to 0.5 mg/animal. In case of a response to either 0.5, 1.0, or 2.0 mg once daily, this dose was given once every two days. The total trial period was 42 days. Blood parameters were determined before and after treatment to monitor the influence of treatment on bone-marrow. Results. Response to treatment was seen in 83% of the bitches, 61% became continent and 22% improved. In 16% the condition was unchanged or worsened or treatment had been discontinued due to a lack of effect. The final effective dose varied from 0.25 to 3 Incurin® tablets per administration. In 65% of the cases tablets were given daily, in 35% on alternate days. The dose and the treatment frequency were not related to the weight of the animal. In 12 (9%) dogs, mainly at the 2 mg dose, signs of oestrus were reported. These signs disappeared after lowering the dose. In 12 dogs (9%) mild and transient side effects (vomiting, panting, short of breath) were reported. Treatment did not have any effect on haematological parameters. Conclusion. From the results of this clinical trial, it can be concluded that treatment with Incurin ® is efficacious and safe. No signs of bone marrow suppression were observed.

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CLINICAL EFFICACY OF THE NEW INODILATOR PIMOBENDAN, IN COMPARISON TO DIGOXIN FOR THE TREATMENT OF CONGESTIVE HEART FAILURE IN DOGS R. Kleemann* Med Vet, G. Le Bobinnec‡ DVM D ECVIM-CA, D. Bruyere# DVM, C. Justus* Med Vet, H. Schmidt* Med Vet Boehringer Ingelheim Vetmedica GmbH, Product Development, D-55216 Ingelheim, Germany* 5, Allee des Tanneurs, F-44000 Nantes, France‡, Theo Verbeecklaan 25, B-1070 Bruxelles, Belgium# Introduction. Pimobendan is a novel drug which is currently being developed for the treatment of congestive heart failure in dogs. Due to its dual mode of action calcium-sensitisation and inhibition of phosphodiesterase-III it exhibits positive inotropic as well as vasodilatory properties. Compounds with this combined mode of action are often referred to as inodilators. Aims. To assess the clinical efficacy of Pimobendan (0.4-0.6 mg/kg daily) in comparison to a standard digoxin treatment in dogs with congestive heart failure. Methods. A total of 109 dogs with congestive heart failure of which 60 dogs were treated with Pimobendan and 49 subjected to Digoxin were evaluated. Diagnosis was based on clinical examination, x-ray, ECG and echocardiography. The clinical assessment of heart insufficiency was based on the guide-lines of the New York Heart Association (NYHA-score 1-4). Follow up examinations were performed after approximately 7 and 28 days of treatment. Digoxin plasma levels were monitored to avoid Digoxin overdosing. The investigators had the option for a longer follow up. Results. Prior to initiation of therapy the mean NYHA-score was 3.5 for the Pimobendan and 3.4 for the Digoxin group. At the final examination it improved to 1.9 for the Pimobendan group but only to 2.6 in the Digoxin group. Overall 56 of 60 Pimobendan treated, but only 30 of 49 Digoxin treated animals improved their NYHA score during the study (p < 0.001). During the study significantly less side-effects were reported in the Pimobendan group (p < 0.05). During the optional follow up period (up to 524 days) sudden death occured in 20% of the Digoxin treated animals but only in 8% of the Pimobendan treated dogs. Conclusion. It is concluded that Pimobendan is superior to Digoxin for the treatment of congestive heart failure in dogs.

ˇ ANALYSIS OF MORBIDITY OF DOGS IN THE REGION OF THE CITY KOSICE, SLOVAKIA DURING 1995-1997 M. Kozák, DVM, PhD, Assoc Prof, M. Tucˇková Dipl Ing, P. Chandoga DVM Department of Internal Diseases of Solipeds, Small Animals and Birds, University of Veterinary Medicine in Kosˇice, Slovakia

SHORT COMMUNICATIONS

A great interest in breeding of small animals, above all, dogs emphasizes the health problem of these animals and their diseases. Modern veterinary medicine starts from preventive principles of active prevention of animal health. Goals. Clinical and scientific workers, teachers of veterinary universities have to know to which direction they should orientate their activity within preventive activity and consultation. Our work, evaluating the frequency of the disease incidence and analysis of morbidity in dogs at the Internal Clinic of the University of Veterinary Medicine in Kosˇice during 1995-1997, contribute to this. Methods. 28.600 case histories of examinations of the dogs affected with various diseases during three years were evaluated. Results. During three year observed period, there were 5 most numerous diagnoses: 1. Diseases of digestive (30,6%), 2. Diseases of skin and hair (29.6%), 3. Infectious diseases (10.25%), 4. Diseases of respiratory organs (8.2%), 5. Endoparasitoses (7.42%). As well, the seasonal dependence of dermal diseases and etiotrophic factors were evaluated. Conclusion. Our work indicates to the orientation in the practice of small animals. It analyses in detail morbidity of dogs within individual organ systems.

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EFFECT OF RECOMBINANT HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR ON HEMATOPOIESIS IN NEUTROPENIC CATS CAUSED BY DIFFERENT DISEASES M. Kuffer-Frank DVM, W. Kraft DVM Department of Veterinary Internal Medicine, Ludwig Maximilians University Munich I. Medizinische Tierklinik, Veterinärstr. 13, 80539 München, Germany Background. Colony stimulating factors are glycoproteins that regulate the proliferation and differentiation of hematopoetic progenitor cells. The recombinant human granulocyte stimulating factor (r-metHuG-CSF) filgrastim raises mainly the amount of neutrophile granulocytes in the blood (Cancer Res 1988; 48:5624-37). The use of r-metHug-CSF in cats has not been studied intensively. Fulton, et al., administered rhG-CSF to normal cats, demonstrating a significant increase in neutrophile counts (Exp Hematol 1991; 19:759-67). Aims. To evaluate the efficacy of r-metHuG-CSF in sick, neutropenic cats. Methods. 26 cats with severe neutropenia were treated with filgrastim during a two day trial period. WBC count, blood smears, PCV and the serumparameters AP, γ-GT, lactic dehydrogenase, cholesterin were monitored during the treatment period in all cats. Depending on the underlying disease process, the cats were divided into four groups for further evaluation: retrovirus infection (FIV, FeLV), cat flue, panleucopenia and bacterial infection. Results. A significant overall increase of neutrophile granulocytes was found. There was a more limited raise on monocytes and eosinophiles. Comparing the four groups, the group with retrovirus infected cats did not show an increase of neutrophile granulocytes, whereas the patients in the other groups showed a marked increase of this cell population. Conclusion. Therefore the clinical relevance of using r-metHuG-CSF in neutropenic cats appears beneficial. Filgrastim increases neutrophile granulocyte cell counts in neutropenic cats when neutropenia is caused by cat flue, panleucopenia and bacterial infection. No efficacy of filgrastim was found in the retrovirus group. Reasons therefore are possibly the obstruction of proliferation and differentiation by the virus itself or by cofactors.

COMPARATIVE STUDIES OF THE EFFICACY OF TWO LEUKAEMIA VIRUS VACCINES Hans Lutz DVM Clinical Laboratory - Dept of Internal Veterinary Medecine University of Zürich, Switzerland In a study conducted in 1997, we were interested in how well 2 different FeLV vaccines are able to protect against vigorous FeLV challenge infection. To this end, 45 cats were housed in 3 groups in 3 rooms of a special facility of the Dutch Institute for Animal Science and Health. Two veterinarians of our laboratory vaccinated the cats of group 1 with Fevaxyn FeLV + Dohycat Tetrafel (containing calici-, herpes-, parvovirus and chlamydia antigens, Solvay), of group 2 with Leucogen + Feligen (containing calici-, herpes-, parvovirus antigens, Virbac) and of the third group with a placebo (phosphat-buffered saline, PBS) under blinded conditions. Three weeks after the second vaccination, all 45 cats were challenged with 500 000 ffu of FeLV A Glasgow by intraperitoneal injection. The course of the infection was monitored by personnel and veterinarians ot the Institute who were not informed about which cats had received which vaccines. The parameters investigated included daily clinical observation, weekly clinical examination, weekly assays for p27 (by ELISA) and weekly quantification of anti p45 antibodies. Two months after challenge infection, the cats of groups 1 and 3 became depressed, showed reduced appetite, reduced weight gain and had enlarged palpable lymphnodes. With the exception of 1 cat where enlarged lymphnodes were palpated, all cats of group 2 were clinically normal, showed normal appetite and normal weight gains. The rate of viremia -the most important parameter to characterize protection- was 5 of 15 for the Leucogen group, 10 of 15 for the Fevaxyn group and 11 of 15 for the placebo group. It became clear that Leucogen was able to protect significantly (Fischer’s exact test, on-sided, p=0.0328) against viremia while the percentage of viremic cats in the Fevaxyn group was not distinct from that in the placebo group (p=1.0). In summary, Leucogen has not only be shown to be highly efficacious to protect cats against long-term FeLV challenge but also to be by far superior than other FeLV vaccines.

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COMPARATIVE DIAGNOSTIC IMAGING OF THE PELVIC CAVITY IN DOGS D. Malleczek - Dipl- Tzt Radiology Clinic, University of Veterinary Medicine, Vienna, Austria Purpose. The pelvic cavity is one of the hardest regions to examine, because of the surrounding pelvic bone. A number of dogs with lesions in the pelvic area were examined with different imaging methods. The purpose was to find the imaging method with the best diagnostic results. Materials and methods. Various cases with signs of obstipation and/or dysuria were referred to the Radiology Clinic. In most cases an undifferentiated mass was palpated rectally. The caudal abdomen and pelvic region were examined radiographically, sonographically, followed by computertomography. Surgery and/or a post mortem examination, including patho-histology, verified the diagnosis. Results. Lateral x-rays of the abdomen showed gross lesions in the pelvic region. A good indicator is a narrowing of the colon descendens in this area. The urinary bladder was often not distinguishable from the soft-tissue tumor mass. Exact localization of the mass was not possible. Lesions or masses near the apertura pelvis cranialis image well ultrasonographically. The colon descendens or surrounding bones may cause imaging artefacts. Lesions deeper inside the pelvic cavity are difficult to visualize with ultrasonography. CT-scans offer the best insight into the pelvic cavity. Bone structures, filled colon descendens, and superimposition do not interfere with axial scans deeper in the pelvic region. The size, origin, and localization of a mass or lesion can be imaged. The density of every tissue or mass can be measured in Houndsfield-units and allows for a more exact diagnosis. Conclusions. Computertomography is the imaging method with the highest diagnostic value for structures within the pelvic cavity. CT examinations should always be preceeded by a good radiographic and/or sonographic work-up.

EVALUATION OF THE LOCAL RELEASE OF CISPLATIN IN A RODENT MAMMARY CARCINOMA MODEL

The aim of this study was to determine the efficacy of cisplatin against local recurrence (LR) and metastatic spread (MT) when implanted in the tumor bed after marginal resection in a mammary carcinoma model. Ninety C3H-HeJ mice were injected with MTG-B (murine mammary tumor Gollin-B) tumor cells. Tumors were marginally (histologically incomplete) excised and the mice were randomly assigned to three treatment groups: 1 Cisplatin administred intraperitoneally (IP), 2 OPLA™ -Pt (biodegradable polymer containing cisplatin), and 3 no treatment (control). Fifteen mice (short-term group) chosen randomly from each of the three treatment groups were sacrificed 14 days after surgery and 30 (long-term group) were sacrificed 60 days after surgery. A complete necropsy was performed in each mouse. The results from the short term group were as follow. Group 1. Eight of 14 mice had LR. None had MT. Group 2. Ten of 14 mice showed evidence of LR. One had MT. Group 3. Thirteen of 15 mice had LR. One had MT. Results from the long term group were the following: Group 1. Ten mice of 14 had LR. Two had MT. Group 2. Five of 15 mice had LR. Two had MT. Group 3. Fifteen of 15 mice had LR. Ten had also MT. Results from long term group were more complete and interesting. Cisplatin and OPLA™ -Pt groups had significant advantages over controls in all variables measured (LR, MT, tumor score, survival time and delay to regrowth). OPLA™ -Pt had significant advantages over cisplatin in LR rate, tumor score, survival time and delay in regrowth.

SHORT COMMUNICATIONS

E. Morello* DVM, W. Dernell # DVM, MS, C. Kuntz # DVM, MS, P. Buracco* DVM, S. Withrow # DVM Department of Animal Pathology*, School of Veterinary Medicine of Torino, Italy Comparative Oncology Unit#, Department of Veterinary Clinical, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, USA

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RESULTS OF THE TREATMENT OF 56 CANINE ORAL TUMORS E. Morello* DVM, M. Martano# DVM, C. Dell’Acqua# DVM, P. Buracco* DVM From the Department of Animal Pathology*, School of Veterinary Medicine of Torino, Italy Private Practice# Oral tumors represent 6-7% of all malignancies in dogs. They can be either benign or malignant and can be localized everywhere in the mouth. A presurgical evaluation (clinical examination, X-rays, biopsy) is necessary to identify the tumor type and both clinical (TNM) and histological grading. Surgery is generally the first choice of treatment; in selected cases, neoadjuvant or adjuvant radiation therapy can be used. In this serie 56 dogs are presented (January 1989- November 1997). Nine had an acanthomatous epulis (AE), 5 an ameloblastoma (AM), 14 a malignant melanoma (MM), 10 a fibrosarcoma (FSA), 7 a squamous cell carcinoma (SCC), 5 an osteosarcoma (OSA), 1 a histiocytic lymphoma (LSA), 3 an undifferenziated sarcomas (US), 1 a chondroma rodens (CR), and 1 a matricial carcinoma (MC). Mandibulectomy and maxillectomy were performed respectively in 31 and 21 dogs. An “en bloc” resection (tongue, cheek, etc) was performed in 4 dogs. The survival at 1 and 2 years (with no recurrence and/or progression to metastasis) is respectively for dogs with AE 77.8% and 55.6%, with AM 100%, with MM 38.5% and 15.4%, with SCC 71.4% and 42.8% and with OSA 60% and 20%. For dogs with FSA the survival at 1 and 2 years is 40% while for those with US is 33%. The MC recurred after 89 days from surgery. The dog with CR is alive after 771 days from surgery. The LSA, despite chemotherapy, recurred after 84 days from surgery. In conclusion, radical surgery can be considered a valid option for the treatment of oral tumors in dogs. Cosmetic and functional results are encouraging.

GM1-GANGLIOSIDOSIS IN ALASKAN HUSKIES A. Moritz1 DVM, G. Müller2 DVM, A. Sewell3 DVM, W. Baumgärtner2 DVM Medizinische und Gerichtliche Veterinärklinik I1, Institut für Veterinär-Pathologie2, Justus-Liebig-Universität Giessen Zentrum der Kinderheilkunde3, Wolfgang-Goethe-Universität Frankfurt, Germany GM1-gangliosidosis was diagnosed in a breeding colony of Alaskan Huskies. Clinically, diseased animals exhibited proportional dwarfism and neurological dysfunction. Signs of nervous impairment, characterized by hyper- and dysmetria especially of the hind legs, intention tremor and nystagmus developed slowly and were most prominent between 4 to 7 months of age. In one female dog no skeletal abnormalities, in a male dog a prohibited enchondral ossification were noted radiographically. Blood parameters and CSF were normal, in urinanalysis typical oligosaccharides were found. Histological examination of the central nervous system revealed that the majority of neurons was enlarged, displayed a foamy cytoplasm, and were frequently filled with vacuoles that displaced the Nissl substance. Vacuoles were also present in various extracerebral cells including macrophages and circulating lymphocytes. Biochemical analysis of cultered primary skin fibroblasts and formalin-fixed splenic and spinal cord tissue revealed marked elevation of GM1-ganglioside, lack of β-galaktosidase activity and normal β-hexosaminidase activity in affected animals. Pedigree analysis indicated a transmission of the disease through an autosomal recessive pattern of inheritance.

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EVALUATION OF “VALTRAC” BIOFRAGMENTABLE ANASTOMOSIS RING ON THORACAL ESOPHAGUS IN THE DOG T. Kovács∗ MD, T. Németh# DVM, I. Köves∗ MD PhD, J. Tóth# DVM PhD Dept. of Surgery, National Institute of Oncology Budapest∗, Dept. and Clinic of Surgery and Ophthalmology, University of Veterinary Science Budapest#, Hungary The biofragmentable anastomosis ring (BAR) has been using as an alternative to hand-sutured or stapled anastomosis on intestinal tract in human surgery. Regarding its absorbable character, BAR provides with safe, atraumatic and sutureless anastomosis without remaining material. This technique has not been assessed so far in the thoracal esophagus in dogs. The main purpose of the study was to evaluate the “VALTRAC” BAR-created thoracal anastomosis (Daevis-Geck) in surgical, postoperative clinical and morphological-histological respect. Two groups of 3-3 experimental dogs were operated performing BAR anastomosis on the thoracal esophagus. Intraoperative features as surgical handling, expected complications and operation time were observed. During the follow-up period of 4 (Group I) and 14 (Group II) days, patients were fed with concentration diet through tube gastrostoma and were under continuous clinical supervision including the assessment of general state and respiratory signs. At the time of evaluation dogs underwent in vivo endoscopy and positive contrast esophagography. The anastomosis site was examined by in situ hyperbaric tensile strength measurement. Macroscopic as well as histological evaluation were also done. The surgical technique of BAR anastomosis was found easy to perform within a mean time of 13.6 minutes with no intraoperative difficulties. During the postoperative period neither general nor respiratory disorders were experienced excepting an episode of moderate pleural effusion in one dog of Group I. Either endoscopic or positive contrast esophagographic examination revealed no stricture or leakage in the anastomosis site. Strong adhaesions with the trachea and the pleura were found via necropsy. The mean tensile strength of the anastomosis was 80 mmHg in Group I and 192.5 mmHg in Group II. Histological evaluation revealed mild granulation tissue reaction in 2 dog of Group I and 1 dog of Group II, which did not lead to significant stricture. According to the results of the study, BAR can be a useful alternative surgical technique of thoracal esophagus anastomosis in dogs.

CLINICOPATHOLOGICAL FEATURES OF MULTIPLE CARTILAGINOUS EXOSTOSIS IN THREE LITTERMATE DOGS

Background. Multiple cartilaginous exostosis (MCE) is a rare benign proliferative cartilaginous and osseous disease characterized by knobby and protuberances involving endochondral bones during skeletal development. MCE have been occasionally reported in dog, and rarelly in horse and cat. In man, dog and cat, malignant transformation of MCE to chondrosarcoma or osteosarcoma has been described. An inherited origen, associated with an autosomal dominant gene, has been reported. Aims. To describe the clinicopathological aspects of MCE in three, 6 months-old, male, cross-breed littermate dogs and a comparative analysis with previous studies. Results. Exostosis were bilaterally symmetrical, involving in all cases the humerus, cubitus, radius and metacarpus in the forelimbs and femur, tibia, and perone of the hindlimbs. Metatarsus, pelvis bones, ribs, thoracic vertebrae and pennis bone were affected only in one of the three dogs. Radiographic analysis demonstrated exostoses in different stages of evolution, which arise from the methaphyseal and diaphyseal regions of long bones. In the three dogs premature closure of the distal cubital physis induced a poorly development of the radius, as well as secondary osteoarthosis of the elbow. Haemogram only revealed moderate hypercalcemia and mild increase of alkaline phosphatase. The urinalysis was normal. Gross pathology showed proliferative cartilaginous and osseous tissue lesions and areas of atrophy of normal cancellous bone. Microscopically, exostoses consisted on proliferative hialine cartilage tissue cap underlying spongous bone with variable degree of endochondral ossification. Conclusion. The symmetrical location and the similar stages of the lesions found in the three dogs resemble, more closely, some cases reported in human beings than that previously described in the dog.

SHORT COMMUNICATIONS

M. Novales* DVM PhD, J. Pérez** DVM PhD, E. Hernández* DVM, E. Mozos** DVM PhD Depts of Clinical Pathology* and Veterinary Pathology** - University of Córdoba, Spain

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SYSTEMIC RESPONSE OF BLOOD INFLOW OCCLUSION TO THE LIVER IN DOGS J. Pecˇar DVM, J. Butinar DVM MSc PhD, D. Podgornik DVM MSc, A. Selisˇkar DVM MSc Small Animal Clinic, Veterinary Faculty, University of Ljubljana, Slovenia Introduction. Liver surgery is relatively common in small animal medicine, including management of abdominal trauma or liver resection for other problems. Hepatic bleeding presents the problem sometimes difficult to manage. Portal triad clamping (PTC) which interrupts all the arterial and venous inflow to the liver is recognized and useful technique to arrest hepatic bleeding, well tolerated by human patients for up to 60 minutes. Clinical experiences and results of the study evaluating perihepatic packing suggest that dog may not resist the PTC for a period listed in veterinary literature, i.e. 15-20 minutes. A clinical trial was conducted to evaluate the systemic response and determine time of PTC, which is safe and useful when performed to control hepatic bleeding. Preliminary results are presented. Materials and methods. 5 beagle dogs were used in the clinical trial. Laparatomy was performed, lesser omentum opened and hepatoduodenal ligament (pedicle) encircled with a tape and PTC performed with Rummel tourniquet to occlude blood inflow to the liver. Blood pressures measurements and samples for blood gas analysis (arterial, mixed venous and portal) were taken and recorded before PTC, first and second minute after PTC and then in two minutes intervals. Mean arterial blood pressure (MAP) of 35-55 mmHg was considered as minimal safety margin to terminate the experiment and release the PTC. Results. Total blood inflow interruption (PTC), resulted in rapid deterioration of haemodynamics. The average duration of PTC was 5,25 (4-7) min. Values of MAP decreased from 128 (120-140) to 48,5 (38-56) mm Hg just prior of releasing PTC. ETCO2 values decreased from 5,65% (5,3-5,9) to 3,38% (2,9-3,8) before releasing PTC. Values of arterial, mixed venous and portal blood gas analyses reflect changes in haemodynamics. Conclusions. Preliminary results suggest that PTC is poorly tolerated in the dog, and therefore might be of limited value as a mean to minimize hepatic bleeding by establishing control of the major vascular structures.

SPINAL MENINGEAL CYSTS IN THREE DOGS: LONG TERM OUTCOMES EVALUATION AFTER THERAPY S. Romussi DVM PhD*, M. Digiancamillo DVM#, L. Carnevale DVM*, R. Lombardo DVM PhD*, F. Addis DVM Prof*, L. Leonardi DVM Prof# Istituto di Clinica Chirurgica Veterinaria*, Istituto di Radiologia Veterinaria# - Università degli Studi di Milano, Italy Introduction. Meningeal cystic dilation of the spinal cord represents an uncommon pathology with uncertain etiology and classification reported in dogs as rare isolated cases. The aim of the present work is to present three additional cases and to discuss the therapeutical results with a long term follow-up. Materials and Method. Three cases of meningeal cystic dilation were diagnosed at the Institutes of Veterinary Surgery & Veterinary Radiology - University of Milan from 1995 to 1997. All the patients underwent, after neurological examination, plain spinal radiographs and myelography under general anaesthesia. Cervical myelography was obtained in one case and lumbar myelography in the other two using a dymeric non ionic water-soluble contrast medium (300 mg/I/ml). Two dogs were submitted to dorsal laminectomy and complete cyst resection, the other patient underwent conservative treatment. The followup was based either on neurological examinations or telephone interviews. In one case M.R.I. was obtained during the followup period. Results and Conclusions. Case 1 (Surgical therapy) Pug, male 3 yrs. Two mos hystory of bilateral hind limb ataxia. Subarachnoid dilatation at T12-T13. Complete recovery 4 wks after surgery. Neurological worsening with similar initial clinical signs 20 mos. after therapy. Case 2 (Surgical therapy) Rottweiler male 5 yrs. Five mos hystory of fore and hind limb ataxia unresponsive to corticosteroid therapy. Subarachnoid dilatation at C5-C6. M.R.I. 32 wks. after surgery: no signs of local relapse. Significant improvement in neurological status following physical therapy. The dog was standing 6 wks. and walking 42 wks. after surgery. Case 3 (Conservative treatment) Rottweiler male 3.5 yrs. Weakness, hind an fore limbs ataxia, severe hip dysplasia. Unchanged clinical conditions 28 mos. after diagnosis. Despite the prognosis of meningeal cysts appears, according to the literature, to be favorable in case of surgical drainage, the long terms outcomes in case of cysts resection seems to indicate a more guarded final prognosis.

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TREATMENT OF FLEXION XONTRACTURE OF THE CARPUS WITH THE ILIZAROV TECHNIQUE: FOUR CASES G.L. Rovesti* Med Vet Dipl ECVS, A. Margini* Med Vet Ambulatorio Veterinario Associato “M. E. Miller”, Cavriago (Reggio Emilia), Italy Flexion contracture of the carpus is a severe disease with the unability to extend the carpus, actively and passively, as a common clinical feature, either in the awake patient and under general anesthesia. It’s equivalent to the Volkmann’s disease in man, and its pathophysiology is complex. The differentials to be considered are compartimental syndrome of the antebrachii, peripheric palsy of extensors muscles with predominance of flexors, primary rigidity or ankylosis of the radio-carpal joint, and sympatethic reflex dystrophy. The purpose of this study is to evaluate the technical feasibility, complications and results of this disease’s treatment using the Ilizarov’s technique. Four cases of flexion contracture of the carpus treated at the Ambulatorio Veterinario Associato “M. E. Miller”, Cavriago (Reggio Emilia), Italy, have been evaluated. In the first patient the contracture followed a proximal articular fracture of the ulna with tissue loss, treated with Ilizarov technique as well. In the second case it developed following some bandages, used to treat a procurvatus posture of the dog’s carpus when he was 2-3 months old. The third and fourth cases had no hystory about the problem, because both of them have been adopted from the present owners when the disease was already present. One of them had a functional radial nerve, whereas the other one was diagnosed to be affected by radial palsy. The treatment has been the same for all the patients, and was performed by means of a progressive extension of the carpus, using a frame with hinges centered on the rotation axis of the carpus and a threaded bar for traction on the cranial part of the device. The treatment lasted from 16 to 63 days, followed by 6 weeks of stabilization for patients with functional radial nerve or by a pancarpal arthrodesis for the one with radial palsy. All the patient could use the leg at the end of the treatment, even with some specific problem due to the presenting disease. The extension of the carpus to 20° has been a technical choise, because we believe that in patients with functional radial nerve this reduces the amount of contracture recurrence, whereas in those who will undergo arthrodesis it gives better posture of digits. We conclude that the Ilizarov technique has been useful in treating flexion contracture of the carpus.

CANINE LEPTOSPIROSIS, DO WE USE PROPER VACCINATION PROGRAMMES? D. Salgado DVM, R. Barrera DVM PhD, M.C. Mañé DVM PhD, C. Zaragoza DVM, S. Andrés DVM PhD, M. Benito DVM Dept. of Medicina y Sanidad Animal, Faculty of Veterinary, University of Extremadura, Spain

SHORT COMMUNICATIONS

It is usually considered that a proper immunization against Leptospira interrogans is achieved by 2-3 doses of vaccine (against serotypes canicola e icterohemorragiae), given at 3-4 weeks intervals and with booster injections each year to get a good IgG response. The aim of this study is confirm that the above mentioned statement is true. The vaccination programme of 246 dogs with leptospirosis, from the Veterinary Teaching Hospital of UEX (Spain) was studied. The animals were divided into 3 groups: I) Not vaccinated; II) Vaccinated in the last 6 months; III) Vaccinated in the last 6-12 months. Each group was divided in 4 subgroups according to age: < 6 months; 6-12 months; 1-6 years; > 6 years. The most remarkable results are: 42.68% of the affected animals belong to group III. Thus indicates that the yearly vaccination is not adequate. In fact, vaccinal immunity usually lasts at least 6-8 months. The percentage falls to 19.91% in group II. The data of the above mentioned groups, in relation with the total number of dogs sent to the referral center, show that the most affected population is that of dogs without vaccination (4.47%), followed by groups III (3.53%) and II (1.64%). The incidence of age in the groups with respect to the population studied, shows that in the non-vaccinated animals the risk increases with age, specially from 6 months. In group II there is a low incidence of the disease, decreasing with age. A higher incidence, although the same distribution, is observed in group III. Therefore, 3-4 doses of vaccine with 2-3 weeks intervals and booster injections each 6 months are recommended.

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DETECTION OF MICROMETASTASES IN LYMPH NODES IN MALIGNANT MAMMARY TUMOURS OF THE DOG G. Sarli DVM, P.S. Marcato DVM ECVP Dipartimento di SanitĂ Pubblica Veterinaria e Patologia Animale - FacoltĂ di Medicina Veterinaria - Bologna, Italy The histological evidence of neoplastic cells in mammary lymph nodes may be difficult in routine sections (stained with Hematoxylin-Eosin) when these cells do not appear in a large number, but only in microgroups or single cells. This study considers sections of regional lymph nodes (axillary or superficial inguinal) in cases of malignant mammary tumours of the the bitch at different histological stage: stage 0 (non infiltrating tumour) 20 cases; stage I (stromal invasion) 31 cases; stage II (presence of emboli in the lymph or blood vessels) 10 cases. All the cases were negative for metastasis in the regional lymph node with the routine staining method. Section of lymph node, formalin-fixed and paraffin-embedded, were used for immunohistochemical staining with a monoclonal antibody anti-cytokeratin-19. As positive control, for each case, a section of the corresponding mammary neoplasm was used. The immunohistochemical positivity to cytokeratin-19 was evidenced in the cytoplasm of both neoplastic cells of the primitive tumour and lymph node. The micrometastases in the lymph node were revealed prevalently in the subcapsular sinuses and rarely in the medullary ones. In no stage 0 malignant tumour micrometastases were present. These were evident in 7 cases out of 31 (22.5%) of the stage I malignant tumours and in 100% of the histological stage II neoplasms. The results obtained may be considered an estimation of the frequence that cases of mastectomy without regional lymphadenectomy have to mantain some cells which could give origin to a new neoplasm. The most interesting data concerns histological stage I, in which it could be possible to correct the gradation of invasion (from I to II for the presence of micrometastases) assessed on routine preparations.

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DIAGNOSIS OF GLOMERULOPATHY IN THE DOG: THE QUALITATIVE ASSESSMENT OF PROTEINURIA P. Scarpa Med Vet PhD, V. Corso Med Vet, O. Pozza Med Vet *Istituto di Patologia Speciale e Clinica Medica Veterinaria, Università degli Studi di Milano, Italy

SHORT COMMUNICATIONS

Introduction. Recently, the quantitative assessment (UP/UC) of proteinuria has aroused great interest in veterinary nefrology. On the contrary, in human medicine, the qualitative assessment and the concept of “marker” has been developed. The marker is a proteine that, detected in urine, is used to localise in an early time the seat and the severity of the renal lesion. The aim of this trial is to test the usefulness of the qualitative approach for a more complete diagnosis of glomerulopathy. Materials and methods. Urine samples from 15 proteinuric and suspected nephropatic dogs were collected. The physical-chemical properties and the sediments were analyzed. The quantitative assessment of proteinuria was performed by the UP/UP ratio. The qualitative assessment was made by: a) cellulose acetate electrophoresis previous samples concentration (densitometric reading); b) cellulose acetate electrophoresis followed by immunofixation and gold staining (visual interpretation). Immunofixation was performed using specific antibody in order to reveal the glomerular markers (anti dog -albumin and anti dog-IgG antibodies). Results. The cellulose acetate immunofixation resulted a valid method to discriminate the glomerular “selective” proteinuria (only albumin detected in urine) from the “unselective” form (both albumin and IgG detected). Data are summarized in table 1. Althought performed on a limited number of samples, the results show the limits of the quantitative index (UP/UC ratio), which is actually considered a good indicator of the glomerular function. As in human medicine, the lack of correlation between the amount of the proteinuria and its selectivity has been pointed out. A high proteinuria doesn’t necessarily correspond to wide bands of IgG, which instead could be detected in mild proteinuric samples with an UP/UC ratio just in the low side of the “doubt” range. Because of the different prognosis between the “selective” and “unselective” proteinurias and the possibility of achieving different therapies, further studies on the qualitative assessment of proteinuria should be necessary, in order to obtain better laboratory definitions of the different glomerular patterns.

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PERCUTANEOUS BALLOON VALVULOPLASTY IN DOGS WITH PULMONIC STENOSIS M. Schneider* Dr, I. Schneider* Med Vet, A. Steinberg* Med Vet, U. Wolf* Med Vet, K.-J. Hagel# Dr. PrivDoz., H. Neu* Dr. ADir. Innere Krankheiten der Kleintiere*, Medizinische und Gerichtliche Veterinärklinik I, Justus-Liebig Universität Gießen Pädiatrische Kardiologie#, Zentrum für Kinderheilkunde, University of Gießen, Germany The purpose of this study was to evaluate the immediate effects of balloon valvuloplasty (BV) of pulmonic stenosis in two different groups of dogs. Eigtheen dogs between 3 and 53 months of age (mean=13) and weighing between 3 and 33 kg (mean=15,8) were examined. In awake dogs one day before and one week after the BV continuous wave Doppler echocardiography (DE) was performed. Under general anesthesia, pressure was measured in the right ventricle and the pulmonary artery before and after the BV. Peak to peak pressure gradient was calculated. The pulmonic valve diameter (PVD) was measured in the right ventricular angiography. The balloon diameter was chosen equal to the PVD for group A (n=6) or 20-30% lager then the PVD for group B. The effect of the BV was significantly (p<0,05; p=0,012) different between both groups. In group A the peak pressure gradient change from an average value of 61 mmHg (sd=37) to 53 mmHg (sd=38) and the percentage of decreasing was not significant. In group B the peak to peak gradient decrease from an average value of 97 mmHg (sd=32) to 47 mmHg (sd=34). The percentage of decreasing amount to 51% (sd=26%) and was strongly singnificant (p<0,0001). The connection between peak to peak gradient before BV and percentage of decreasing was not significant. The rate of complication was nearly equal in both groups. Because of the better results with lager balloons we prefer this method for the future.

BONE DEFECTS IN DOGS TREATED BY A NEW TISSUE TRANSPLANTATION METHOD OF ADAPTIVE PERIOSTEAL CAMBIPLASTY N. Sesic* MD MSc, J.T. Triffitt# BSc PhD, M. Zobundzija & DMV PhD Prof, Z. Bacetic+ DMV MSc Dept. of Surgery*, University Hospital KBC Rebro, Zagreb, Croatia MRC Bone Research Laboratory#, Nuffield Orthopaedic Centre, University of Oxford, Oxford, UK Dept. of Anatomy, Histology and Embryology & Veterinary Faculty, University of Zagreb, Croatia Veterinarska Klinika Zoe+, Zagreb, Croatia A new operative procedure has been applied to traumatic bone injuries in dogs and compared with the use of autologous cancellous bone grafts (ACBG), which are currently considered the best materials for use in bone reconstructions. In this method, which is termed adaptive periosteal cambiplasty (APC), mechanical stimulation of periosteal bone yielded highly active osteogenic tissue which was used for autologous bone grafting in the skeletal defects. Faster healing of these defects by this mechanically-stimulated bone tissue transplant is based on highly increased cellularity and metabolic activity of this graft. Four weeks before transplantation, specially adapted conical screws were percutaneously applied to the healthy tibial bone shaft and this induced rapid production of new osteogenic tissue for grafting. The small induced injury to the tibia had no influence on the normal function and healing at this site was rapidly restored. Healing of the bone defects was assessed by scintigraphic, histomorphometric, densitometric and mechanical methods and the results of these investigations confirmed that autologous cambian bone derived by APC possessed greater osteoinductive activity than ACBG. Technecium scintigraphy indicated twice the osteogenic activity per unit mass and histomorphometry showed higher cellularity and osteoblast/osteoclast activity in the cambial graft compared with ACBG. By densitometry APC expressed in the healing defects at all phases after transplantation higher densities than the same bone defects treated with ACBG. In addition, there was a shorter time of immobilisation required and a more rapid healing without the appearance of delayed union. From these results it is concluded that the APC method is more efficient for curing bone defects in dogs than the use of ACBG.

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SIALADENITIS AND SALIVARY GLAND INFARCTION IN CATS AND DOGS M. Sozmen* DVM, P. Brown* BVMS PhD Dipl ECVP MRCVS, T. Whitbread** Bsc BVSc MRCVS Comparative Pathology Lab*, University of Bristol, School of Veterinary Science, Bristol BS18 7DU Abbey Veterinary Services**, 14 Oak Place, Newton Abbot, Devon, TQ12 2HW, United Kingdom The histochemical and immunohistochemical aspects of salivary gland necrosis and sialadenitis were studied. Salivary gland infarction is rare but most commonly affects the submandibular gland of dogs. The aetiology is largely speculative; it has been postulated that it results from inflammation because of constriction of the enlarged, inflamed gland within its fibrous capsule. A breed predisposition has also been suggested. The analogous disease in humans is termed necrotizing sialometaplasia; it has identical histological features but occurs mostly in the palate. It is a benign, self limiting ischaemic disorder of the salivary glands which has many clinical and histological features of neoplasia. Sialadenitis is a general term used to indicate inflammation within the parenchyma of the salivary gland and is the second most frequent pathologic change in dogs and cats. Males are more sensitive than females to salivary lesions, in both cats and dogs, and the submandibular gland was most frequently affected. The parotid gland was seldom affected and neither zygomatic nor sublingual glands were involved. Histochemical techniques applied included lectin histochemistry, immunochemistry of cytokeratins, a-SMA, S-100 protein and GFAP. Changes were detected in binding of lectins, CK14 and cytokeratin MNF116 in salivary gland infarction. Lectin histochemical changes were also detected in canine sialadenitis with DBA, PNA, SBA and TGP lectins; other lectin staining was unchanged. Loss of cytokeratin and CK14 expression by myoepithelial cells was a prominent finding in sialadenitis and salivary gland infarction, respectively.

SERUM BILE ACIDS AND FELINE TRYPSIN-LIKE IMMUNOREACTIVITY AFTER EXOGENOUS PANCREATIC STIMULATION WITH CERULETID IN NORMAL CATS

Objective. To assess the change of serum bile acids and feline trypsin-like immunoreactivity (fTLI) after stimulation of gall bladder contraction and pancreatic secretion with Ceruletid in normal cats. Design. Eleven normal cats received a single IM bolus of Ceruletid (0.3 µg/kg of body weight) together with 0.1 ml Lidocain 2%. Blood was collected at 0, 10, 20, 30, 40 and 50 minutes (min.). Serum bile acids were determined in 10 and fTLI in 11 cats. Procedure. Serum bile acid concentration was established by enzymatic measurement using Merckotest® (Merck) with the autoanalyser Cobas Mira (Hofmann La Roche) and the fTLI concentration was determined by radioimmunoassay. Results. The geometric mean of fasting serum bile acid concentration was x-g = 8.7 µmol/l (5.6 - 13.7). There was a significant increase in bile acid concentration after Ceruletid application (p< 0.01) with a maximum of x-g = 13.7 µmol/l (8.9 - 21.1) at 40 min. The arithmetic mean of fasting serum fTLI was x-g = 23.14 µg/l (± 4.12). There was a slight but significant rise in fTLI concentration after Ceruletid application (p<0.01) with two maximums of x-g = 26.02 (± 6.13) at 10 min. and x-g = 26.78 µg/l (± 6.72) at 30 min. after stimulation. Concentrations of fTLI at 10 and 30 min. have a statistically significant difference from the fasting fTLI value (p<0.01). Conclusion. In normal cats serum bile acids and fTLI concentrations rise significantly after IM administration of Ceruletid but remain within the reference ranges throughout the test. Whether the determination of postprandial bile acids in cats with suspected hepatic diseases can be replaced by the Ceruletid test needs to be investigated as well as the diagnostic value of the fTLI stimulation reaction in cats with suspected disorders of the exocrine pancreas.

SHORT COMMUNICATIONS

T. Spillmann* Med Vet, Ines Jacob* Med Vet, E.G. Grünbaum* Med Vet, K. Failing# Dr rer nat Dipl math, J.M. Steiner+ Med Vet, D.A. Williams+, MA, VetMB, PhD, MRCVS Department of Small Animal Internal Medicine*, Department of Biomathematics and Data Processing#, Justus-Liebig-University, Giessen, Germany College of Veterinary Medicine+, Texas A&M University, Texas, USA

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EXPLANATORY PRINCIPLES CONCERNING THE USE OF FULCRUM-LEVER IN TEETH EXTRACTION IN DOGS Paolo Squarzoni Med Vet Libero professionista, Molinella (BO), Italy The different techniques in dentals extractions often needs the aid of Bein’s lever restricted to the fragments of the single tooth using the neigh bours teeth as lever fulcrum we can induce the luxation of these ones. At the end of a personal study, the author after having misured all the teeth roots in different dogs cadavers (see the tablet enclosed), suggest that only some teeth can be used as fulcrum without being damaged. The author present different explanatory cases showing the possible techniques. COEFFICIENTS ESTABILISHED FOR BOTH ARCHES GIVING THE REFERENCE VALUE OF 1 TO THE SINGLE CANINE AREA

RECONSTRUCTION OF A LOWER CANINE IN A BOXER USING A RICHMOND’S CROWN Paolo Squarzoni Med Vet Libero professionista, Molinella (BO), Italy Dental rebuilding in human medicine has wide possibilities and techniques, independently on the number of therapeutical session. On the contrary, in veterinary medicine we must use simple and relatively cheap techniques that need only few anaesthesiological session. In this report the author will deal with the application of a Richmond’s crown (fusion between crown and pivot) in a boxer. The therapeutical schedule is based on two anaesthesiological sessions, excluding the cluttered test and the colour test normally used in human medicine. The case reported was treated in ’95 and, up to now, the reconstruction is still unaltered.

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EXTRACTION OF AN UPPER PARATOPIC CANINE TOOTH IN A DOG E. Stefanelli Med Vet Libero professionista, Ferrara, Italy A seven month old Pitbull was presented for the apparent absence of the upper left canine tooth. No abnormalities were reported about deciduous dentition. The clinical examination showed the presence of a crown, similar to that of a canine, palatally to the normally eruption site. Moreover, the absence of the lower right fourth premolar was reported. The x-ray examination confirmed the presence of a morphologically normal canine partially included in the maxillary bone. The apex was located in a topographically normal position while the root and a portion of the crown crossed the maxilla medio-distally, erupting almost in the middle of the palate. The absence of the lower right fourth premolar was confirmed. The dog was therefore put under general inhalant anaesthesia for the extraction of the paratopic canine, because the portion of palatal mucosa surrounding the palatally erupted crown was already inflamed and packed with food debris. The buccal mucosa was incised with a scalpel blade, proximal to the projection of the canine on the maxilla, from the root apex to the eruption site in the palate. A similar incision was made on the gingiva, from the upper left third incisor to the first premolar of the same side and two mucosal flaps, palatal and buccal, were elevated to expose the underlining maxillary bone. A high-speed handpiece with a surgical dental bur (size1557) was used to incise the bone deeply to the canine surface, following its mesial border, with a result of a deep fracture of the left maxilla. This solution was adopted, because it wouldn’t have been possible to carry out the standard technique for the upper canine extraction, given that the complete removal of all the bone on the buccal side of the canine would weakened severely the entire maxilla. The canine was entirely extracted with the combined action of an elevator inserted around the erupted crown to luxate the tooth and of a scalpel inserted into the bony incision to dilate the paratopic alveolus allowing for the canine passage. The buccal and palatal mucosal flaps were reconstructed with a single interrupted pattern with an absorbable suture (PDS® 3-0). The controls made 7, 15 days and 1 year later didn’t reveal any abnormality.

ADENOCARCINOMA OF A LABIAL MINOR SALIVARY GLAND IN A CAT D. Tontis1 DVM, F. Dakoronia2 DVM Laboratory of Pathology, Faculty of Veterinary Medicine, University of Thessaly, Karditsa, Greece 2 Small Animal Clinic, Athens, Greece

Neoplasms derived from salivary glands are uncommon in domestic animals. Particularly, minor (labial, bucal, palatine, lingual) salivary gland tumors are very rarely reported in veterinary literature. In this paper, after a brief review of feline primary and secondary neoplasms of the salivary glands (major and minor), compared to similar tumors in other animals and man, the clinical and histological features of a minor salivary gland adenocarcinoma in a 13-year-old, male, Siamese cat are described. The cat was referred because of a swollen and painfull lower lip, a decreasing appetite and excessive salivation, noticed by the owner. During clinical examination, a palpable, hyperaemic and slightly ulcerated, mass of 2.5 cm in diameter, was revealed between the left internal surface of the lower lip and gingiva. The mass was surgically excised and biopsied. Microscopic examination showed that the tumor was an adenocarcinoma of a labial minor mixed salivary gland, with negative surgical margins. Fine needle aspiration cytology of the regional lymph nodes, indicated that metastasis had not yet occured. The prognosis for long-term survival was guarded, since the only method of therapy was complete surgical excision of the cancer with no postoperative radiotherapy or chemotherapy. The recurrence of the tumor at the primary site, with metastasis to the regional lymph nodes, was noticed 14 months after surgery. This portended a poor prognosis, the animal was euthansized and no autopsy was performed upon the owner’s request.

SHORT COMMUNICATIONS

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ULTRASOUND MONITORING OF FETAL DEATH IN THE QUEEN: A CLINICAL CASE I. Vannozzi DVM, S. Romagnoli DVM MS, F. Camillo DVM Dept of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, University of Pisa, Italy A feline pregnancy of a 6 year old Persian queen was followed by ultrasound from day 18 after breeding every 3-4 days, using a Concept 2000 Dinamic Imaging ultrasound unit with a 5.0 MHz probe. On day 18 at least 3 embryonic vesicles were observed. Days of pregnancy and ultrasonographic parameters (embryonic-fetal vesicle diameter, roundness, homogeneity and presence of heart beat) are presented in the table. On day 33 lack of growth of fetal vesicular diameter, absence of fetal heart beat and alteration of roundness and homogeneity were observed. On day 43 absence of fetal image in one vesicle was observed. From day 45 on the queen was treated with bromocriptine (10 mcg/kg BID) to cause expulsion of uterine content, which occurred on day 48 when the queen expelled an empty vesicle and 3 dead fetuses. Microbiological and virological tests on aborted fetuses proved negative, while on necropsy all fetuses showed incomplete development of maxillary bones and presence of cleft palate, and one of them showed also lissencephaly. Although all ultrasonographic parameters became altered on the same day, loss of vesicular roundness and lack of growth of vesicular diameter were the most easily identifiable signs of fetal death. Ultrasound parameters vesicular diam.(mm) roundness homogeneity heart beat

18 10 + +

22 18 + +

26 20 + + +

Days of Pregnancy 29 28 + + +

33 25 -

37 25 -

43 26 -

Diameter of fetal vesicles, roundness, homogeneity (similarity among vesicular diameters) and presence of fetal heart beat in a feline pregnancy ending with fetal death and expulsion. Research performed with a grant from the University of Pisa (exâ&#x20AC;?60%)

PROLACTIN AND ANTIPROLACTINIC DRUGS IN DOGS AND CATS: RELATIVE EFFICACY AND MODE OF ACTION OF THE VETERINARY AVAILABLE DRUGS J. Verstegen DVM, K. Onclin DVM Department of Small Animal Reproduction, University of LiĂ¨ge, Belgium Prolactin nowadays appears to be one of the most important hormone regulating several different aspects of dogs and cats physiology. Prolactin has been demonstrated to play a major role in six different fields of physiology in all vertebrates: water and electrolyte balance, growth and development, endocrinology and metabolism, brain and behavior, reproduction, immunoregulation and protection. To study the role and importance of this hormone in dogs and cats, the characterization of the different drugs able to modify prolactin secretion is certainly really important. These drugs could be separated in drugs inhibiting prolactin secretion and drugs able to stimulate and increase prolactin production and liberation whose interest is particularly important in dogs and cats reproduction. Indeed, these drugs could then be utilized to inhibit pseudopregnancy, induce abortion, induce estrus and control anoestrus. Prolactin stimulating agents on the other being of interest in lactation stimulation in postpartum animals. In this study we have compared the relative efficacy on prolactin inhibition and the relative duration of action of the veterinary available prolactin inhibiting agents: bromocriptine, metergoline and cabergoline. Those effects were assessed by evaluating prolactin and progesterone secretion after the administration of the different inhibitors. From this study, it results that, at equipotent dosage, cabergoline and bromocriptine have the most important inhibiting effects of prolactin secretion and that only cabergoline is able after only one administration to inhibit prolactin secretion for more than 2 days. Metergoline only reduce prolactin levels at 50% of preadministration value and for only 1 to 10 hours, bromocriptine reduced Prl secretion to basal but for a maximum of 6 to 8 hours whereas cabergoline decreased prolactin secretion to basal after 8 to 12 hours and its effects is observed for more than 2 days. During the same study, the stimulating effects of several dopamine antagonists (Haloperidol, Metoclopramide and Tiapride) known to stimulate prolactin in other species were tested. Tiapride was demonstrated to be the most potent prolactin stimulator followed by metoclopramide and haldol.

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PRELIMINARY RESULTS ON THE USE OF CABERGOLINE, A PROLACTIN INHIBITOR, FOR THE CONTROL OF MAMMARY TUMORS IN THE BITCH BEFORE SURGERY J. Verstegen DVM, K. Onclin DVM Department of Small Animal Reproduction, University of Liège, Belgium Prolactin involvement in mammary tumors incidence and development in the bitch is still uncertain and questionable. Some studies have demonstrated that repeated pseudopregnancies are associated with an increased risk of mammary tumors whereas the effects of pregnancy and lactation was unclear. These two conditions are associated with an increase of plasma prolactin concentrations for several days or weeks. In clinical practice, it is often observed that bitches presented for mammary surgery show at the same time mammary enlargement due to pseudopregnancy. In this study, we investigated on more than 100 bitches with mammary tumors, the possible positive effect of cabergoline on mammary tissues before surgery. The animals were treated orally once daily for 5 days at the dosage of 5 µg/kg of cabergoline prior to surgery. The results of the histopathology after surgical resection were also recorded. From this study, 3 different situations were observed: 1) 57% of all bitches (83% of bitches with pseudopregnancy) displayed a significant reduction of the mammary enlargement thus allowing an easier surgical approach than that realised without anti-prolactinic pretreatment. The reduction of mammary swelling consented to have a clearer clinical picture of the tumour because of a better demarcation of the mass, enabling to detect some small size nodules that could not be observed before treatment with cabergoline. These nodules can be easily removed. 2) 10% of bitches had some small nodules prior to treatment that totally disappeared whilst some others (12%) with middle (between 1 to 3 cm) or larger size were observed to decrease after treatment. 3) The remaining bitches (21%) had some tumors among which all carcinomas and sarcomas and some benign tumors that did not show any changes due to the treatment. These preliminary results indicate the interests of anti-prolactinic treatments and possible usefulness of the use of cabergoline as an aid in mammary surgery. The possible beneficial effects of this treatment is clear in all cases when mammary hyperplasia and milk secretion is present mainly if associated to a reduction in size of some tumors before surgery. Potential interests are present to discreminate between benign and malign tumors, the malignant tumors clearly being not responsive to the treatment. These results clinically indicate possible implication of prolactin in mammary growth and tumoral development in bitches.

EFFICACY OF TERBINAFINE AGAINST DERMATOPHYTOSIS IN CATS AN OPEN RANDOMIZED BLIND-STUDY (PRELIMINARY RESULTS)

Terbinafine is a proven effective treatment for dermatophytosis, especially onychomycosis, in human medicine. The aim of the present study is to test the efficacy of terbinafine in treatment of dermatophytosis of cats. It is a randomized blind study with patients of the Internal Medicine Clinic I of the Veterinary University of Vienna. The control comparison consists of patients treated with griseofulvin, since for ethical and zoonotic reasons we could not administer placebo to infected animals. To enter the study, patients required a positive culture on a dermatophyte test medium, which proved a dermatophytosis. Two different dosages of terbinafine were chosen: 12.5 mg/kg BW and 25 mg/kg BW divided BID. The griseofulvin group was treated with 60 mg/kg BW daily also divided in two parts. We monitored CBC and for chemistry-profile ALT and GLDH and creatinine. Control examination, control culture and CBC were carried out every two weeks. After clinical recovery and a negative culture, we stopped treatment and 4 to 6 weeks later we set up a follow-up examination and a culture. So far we have completed treatment and follow-up of 7 cats, 3 persian and 4 european short hair cats. They were between 5 months and 12 years old (mean 2.7 years). Three cats were treated with 25 mg/kg/day, one with 12.5 mg/kg/day terbinafine and three with griseofulvin 60 mg/kg/day. The cats treated with terbinafine were cured (no clinical signs, negative culture) after 13 to 42 days (mean 24,3 days), the cats with griseofulvin-therapy were cured after 28 to 78 days (mean 61,3 days). The follow-ups showed, that two of the cats in the griseofulvin-group appeared culture-positive again. All others remained negative. There have been no clinical signs until weeks later. There were no severe alterations in the blood-values and the organ-screenings in any of the groups. In order to manage dermatophytosis safely in a short time of therapy, terbinafine seems to be an efficient drug to treat dermatophytosis in cats.

SHORT COMMUNICATIONS

B. Hofbauer Dipl Tzt*, R. Wagner Med Vet# I. Medizinische Klinik, Veterinärmedizinische Universität Wien#, Novartis Forschungsinstitut Wien*, Austria

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ESTRUS INDUCTION IN CAT WITH CABERGOLINA: PRELIMINARY STUDIES D. Zambelli Med Vet, S. Belluzzi Med Vet, G. Mari Med Vet Veterinary Clinical Department, Obstetric Gynaecology Section, Bologna University, Italy This paper presents the preliminary results obtained between May and August by administering Cabergolina to 5 cats, to induce estrus in subjects to be inseminated or to be synchronised. Before the start of the trial, a colpocytological examination and hormone dosing was performed to exclude subjects in a state of proestrus, estrus, pregnancy or pseudopregnancy. A total of 5 European cats, aged between 2 and 5 years, were orally administered 2,5 µg/die of Cabergolina for 8 days, and 3 cats (control), with similar characteristics, with the same volume of saline solution. All the subjects were kept in an unconditioned environment with a natural photoperiod. A colpocytological examination was made each day and a blood sample taken to measure progesterone (P4) and 17β estradiol (E2) levels. Colpocytology, initially revealed deep cells and numerous cell debris in all subjects. At start of proestrus, around 8 days after the start of the trial in the 5 cats treated, this exam revealed an increase in the intermediate and superficial cells. The mean concentration of E2 and P4 in the treated cats, showed initial values of 7.62±2.30 pg/ml and < 0.20 ng/ml as compared with 28.30±3.52 pg/ml and < 0.20 ng/ml on the 8th day. On the 9th-10th day, these subject showed external sign of estrus, keratinization of the superficial cells and mean E2 and P4 concentration of 37.52±5.48 pg/ml and < 0.20 ng/ml. The treated cats showed a considerable increase in the E2 concentration as compared with the controls, that showed no sign of estrus. The 5 treated cats were mated and the embryos recovered were 3,4,3,2 NS 2.

TREATMENT WITH FINASTERIDE IN DOGS WITH PROSTATIC PATHOLOGIES D. Zambelli Med Vet, S. Belluzzi Med Vet, G. Mari Med Vet Veterinary Clinical Department, Obstetric Gynaecology Section, Bologna University, Italy The aim of this work was to test the use of finasteride, combined with the specific therapy, to preserve the reproductive performances of subjects with benign prostatic hyperplasia (BPH), prostatitis (P) and prostatic absess (PA). Fifteen subjects with BP, six subjects with P and eight subjects with PA were treated for a period of seven months with finasteride (5 mg/day per os). In addition, subjects with P and PA received an antibiotic treatment for 30 days, while those with PA were subjected to omentalization. Before, during (after two month from the beginning) and after (one month from the suspension) the treatment with finasteride, the seminal fluid was valued and the following serous hormones were evaluated: testosterone (TST), dihydrotestosterone (DHT) and 17β estradiol (E2). In the three groups it was observed a clear drop in the mean values of DHT (pg/ml) before and during the therapy (BHP= 294.80 ± 75.1 Vs 105.20±60.1; P= 285.50±16.5 Vs 68.10±27.6; PA= 326.50±36.4 Vs 102.60±44.2). During the treatment, the mean concentrations of TST and E2 were nearly the same; in all the groups it was observed the disappearance of red blood cells, granulocytes, bacteria and degenerate spermatozoons present in the pre-treatment ejaculate according to the pathology. All the specific spermatic parameters showed no important variations before, during and after the treatment, in particularly for the group BHP, the percentage of motility was 73.5±21.5 Vs 72.7±21.3 Vs 71.5±23.1, and the percentage of normal acrosome was 73.8±15.3 Vs 73.4±15.4 Vs 75.2±13.8. Due to the pain present in the subjects of the groups P and PA it was not possible to obtain constant data on the pre-treatment ejaculated. During and after the therapy, the percentage of motility and the percentage of normal acrosome was: P= 66.3±15.5 Vs 66.3±18.9 and 47.3±35.6 Vs 44.8±37.8; PA= 77.56±13.9 Vs 75.6±12.9 and 80.8±15.5 Vs 80.4±14.5. Our findings shows that it is possible to preserve the reproductive performances of the subjects with these pathologies by replacing the orchiectomy with the therapy with finasteride, in a definitive or temporary way. During and after that therapy the libido was never lost and it was also possible to obtain good ejaculate and normal litters for what concerns number and morphology.

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Authors’ list click on the name for the abstract Acocella F. Annarella S. Ascher F. Aucoin D. Belluzzi S. Benazzi C. Bergman J.G.H.E. Bernardini M. Bjerkås E. Boari A. Bodey A.R. Bonello D. Brovida C. Brunetti L. Bruyère D. Bufalari A. Bussadori C. Caldin M. Caniatti M. Capitani O. Cappello R. Carlotti D.N. Chandoga P. Cinone M. Correia J.H.D. Cotto D. Couto C.G. Crosta L. De Lorenzi D. Della Salda L. Divers S.J.

Fabbrini F. Feldman B.F. Ferrer L. Ferretti A. Fournel-Fleury C. Furlanello T. Galeotti M. Guandalini A. Guglielmini C. Hartmann K. Hazewinkel H.A.W. Hendriks S. Heripret D. Jesus S.O.T.S. Kleemann R. Kozák M. Kuffer-Frank M. LeCouteur R.A. Lombard C.W. Lubas G. Lutz H. Malleczek D. Mechelli L. Meyer D. Michell A.R. Millefanti M. Montavon P.M. Morello E. Moritz A. Mosconi G. Németh T.

Niebauer G. Novales M. Pecˇar J. Peruccio C. Petersen-Jones S.M. Pizzirani S. Rijnberk A.D. Romussi S. Rovesti G.L. Salgado D. Sarli G. Scarpa P. Schneider M. Schober K. Scott P.W. Sesic N. Smeak D.D. Sozmen M. Spillmann T. Squarzoni P. Stefanelli E. Tontis D. Vannozzi I. Verstegen J. Verstraete F. Vezzoni A. Von Werthern C. Wagner R. Wheeler S.J. White R.A.S. Zambelli D.