42a edizione Scivac Rimini by E.V. Soc. Cons. a r.l.

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CURRICULUM VITAE DEI RELATORI

DAVID S. BILLER DVM, Dipl ACVR David Biller si è laureato nel 1980 presso la Auburn University. Dopo un anno di internship presso il New Haven Hospital for Veterinary Medicine nel Connecticut e tre anni come membro dello staff del South Shore Veterinary Associates nel Massachussets, ha completato un residency in radiologia presso l’Ohio State University. In seguito si è trasferito per un periodo presso l’Università del Wisconsin-Madison con incarichi di insegnamento e ricerca. Nel 1991 è ritornato all’Ohio State University come radiologo. Attualmente il Dottor Biller è professore associato nel Dipartimento di Scienze Cliniche ed è Responsabile del reparto di radiologia presso il College of Veterinary Medicine dell’Università del Kansas. L’attività clinica che maggiormente interessa il Dottor Biller è la diagnosi con ultrasuoni su piccoli e grandi animali. Le sue ricerche più significative riguardano l’uso degli ultrasuoni nelle diagnosi e nella valutazione delle malattie spontanee negli animali, oltre che lo studio del rene policistico nei gatti. David Biller è Diplomato dal 1987 all’American College of Veterinary Radiology.

DAWN BOOTHE DVM, MS, PhD, Dipl ACVIM, Dipl ACVCP Laureata alla Texas A&M University nel 1980. Ha completato un programma di Internship presso la Auburn University. È poi ritornata alla Texas A&M University dove ha ottenuto un MS in Fisiologia Veterinaria, un PhD ed un Fellowship in Farmacologia Clinica e dove ha completato un programma di Residency in Medicina Interna. Si è quindi diplomata ACVIM (Medicina Interna) e ACVCP (Farmacologia Clinica). Nel 1990 è entrata nel corpo docente della Texas A&M University come Associate Professor nel Dipartimento di Fisiologia e Farmacologia Veterinaria. Ricopre inoltre il ruolo di Direttore del Laboratorio di Farmacologia Clinica e svolge attività clinica presso il Teaching Hospital della facoltà. La sua attività di ricerca è concentrata sui dosaggi farmacologici nei piccoli animali, in modo particolare per quanto riguarda gli anticonvulsivanti e gli antimicrobici. È membro del Comitato Scientifico del Journal of American Veterinary Research e della Morris Animal Foundation ed è Presidente del North American Veterinary Nutraceuticals Council. È autrice del nuovo testo scientifico “Small Animal Clinical Pharmacology and Therapeutics” che verrà pubblicato quest’anno.

DEA BONELLO Med Vet, Dipl EVDC Si laurea nel 1989 alla Facoltà di Medicina Veterinaria di Torino. Si specializza nel 1997 in Radiologia Veterinaria e nello stesso anno inizia il Dottorato di Ricerca in Medicina Interna presso la Facoltà di Medicina Veterinaria di Torino. Dal 1989 si dedica all’odontostomatologia veterinaria ed in questo settore svolge attività di consulenza per i piccoli ed i grossi animali. Dal 1996 si reca ogni anno, a scopo di aggiornamento, presso l’Università di Davis, California. Dal 1998 Diplomata dell’European College of Veterinary Dentistry. Relatore a numerosi congressi in Italia ed all’estero e autore di pubblicazioni inerenti l’odontostomatologia veterinaria e comparata. Dal 1998 è Segretario dell’EVDC e Coordinatore del Gruppo di Studio di Odontostomatologia della SCIVAC.

MICHELE BORGARELLI Med Vet, Dipl ECVIM-CA (Card) Si è laureato presso l’Università di Torino nel 1989 con una tesi di fisiologia. Dal 1990 si occupa di cardiologia e di ecografia nei piccoli animali. Da allora ha seguito numerosi periodi di aggiornamento in Italia e all’estero. È stato professore a contratto in ecocardiografia per gli anni 1996-97, 1998-99 e 2000-01 presso la Facoltà di Medicina Veterinaria di Torino. Nel 1999 si è diplomato al College Europeo di Medicina Interna (Cardiologia). Ha tenuto numerosi seminari scientifici e corsi di perfezionamento su argomenti riguardanti la cardiologia e l’ecografia internistica nei piccoli animali ed ha presentato i risultati dei suoi esperimenti ed esperienze clini-

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che in congressi nazionali ed internazionali. È segretario e tesoriere della Società Europea di Cardiologia Veterinaria. È autore di numerose pubblicazioni di cardiologia ed ecografia internistica su riviste nazionali ed internazionali. Attualmente collabora come Dottorando di ricerca con la Facoltà di Medicina Veterinaria di Torino in programmi di ricerca sulla miocardiopatia dilatativa nel cane.

CLAUDIO BUSSADORI Med Vet, Dipl ECVIM-CA (Card) Nato a Milano il 24/6/56. Laureato in medicina veterinaria il 23/3/82 presso la Facoltà di Milano. Diplomato dell’European College of Internal Medicine ECVIM in medicina interna e cardiologia. Professore a contratto in cardiologia presso la facoltà di Medicina Veterinaria. Attualmente collabora in programmi di ricerca cardiologica con la Facoltà di Medicina Veterinaria di Parma, la Facoltà di Medicina Veterinaria di Torino, la Divisione di Cardiologia dell’ospedale Maggiore di Milano, l’Istituto di Anatomia Patologica della Facoltà di Medicina di Milano. Inoltre ha svolto e svolge il ruolo di Study dierctor in vari trial clinici multicentrici di cardiologia. Coordinatore del gruppo di studio di cardiologia SCIVAC. Presidente dell’E.S.V.C. - European Society of Veterinary Cardiology. Membro dell’International Small Animal Cardiac Healt Council. Vice presidente dell’ECVIM-CA European College of Veterinary Internal Medicine-Companion Animals. Autore di 90 pubblicazioni italiane e straniere inerenti la cardiologia veterinaria.

MARCO CALDIN Med Vet Laureato a Bologna con una tesi in “Diagnostica Strumentale nella Cardiologia dei Piccoli Animali”. Ha rivestito il ruolo di coordinatore del gruppo di studio SCIVAC di “Diagnostica per immagini” negli anni 1988/89 e 1990. Ha partecipato come relatore a vari Congressi, Corsi e Seminari. Professore Incaricato alla Facoltà di Veterinaria di Pisa per l’Anno Accademico 1994-1995 e per la facoltà di Padova per l’Anno 19961997. Attualmente è coordinatore del gruppo di studio SCIVAC di medicina interna. Il Dott. Marco Caldin eserci-

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ta come libero professionista a Padova presso la Clinica Veterinaria San Marco.

DAVID CHIAVEGATO Med Vet Laureato nel 1984 alla Facoltà di Medicina Veterinaria di Bologna. Si occupa di cardiologia e diagnostica ecografia da circa 7 anni. È relatore ed istruttore ai corsi di “Cardiologia” e di “Ecografia” ed attuale coordinatore del Gruppo di studio di “Diagnostica per immagini” della SCIVAC. Lavora a Padova come libero professionista dove svolge prevalentemente attività di referenza in cardiologia ed ecografia addominale. Principali interessi sono rivolti allo studio dell’ipertensione polmonare ed alla diagnostica ecocardiografica.

FABRICE CLERFEUILLE, Med Vet Med Vet, MBA Medico veterinario, libero professionista dal 1989 al 1996. Possiede 2 MBA ed un Dottorato in Gestione. È attualmente professore di Marketing all’Università di Nantes e professore a contratto di Practice management presso 3 Scuole Veterinarie. Egli detiene inoltre il ruolo di manager di una delle più grandi cliniche veterinarie di Nantes. Past President del gruppo di management della CNVSPA è attualmente presidente della società europea di management veterinaria (EGVPM)

MICHAEL DAVIDSON DVM, Dipl ACVO Michael Davidson è Professore di oftalmologia presso la North Carolina State University. È Diplomato all’American College of Veterinary Ophthalmologists di cui è anche President-Elect. È membro del Comitato Scientifico del Journal of Veterinary Ophthalmology. È autore o co-autore di oltre 75 lavori scientifici, 60 estratti scientifici e 10 capitoli di libri. Le sue ricerche e interessi includono la ch i ru rgia del cristallino, la retinoscopia, il trattamento delle p at o l ogie oculari con laser, la toxoplasmosi oculare,

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le malattie infettive dell’occhio e l’opacificazione capsulare posteriore.

ha esercitato la libera professione per quasi dieci anni in cliniche private della California.

GINO D’AGNOLO Med Vet

ANTONIO FERRETTI Med Vet, Dipl ECVS

STEPHEN DIBARTOLA DVM, Dipl ACVIM Di Bartola si è laureato all’Università di Davis, California nel 1976. Ha completato un internship in medicina e chirurgia presso la Cornell University di Ithaca nel 1977 e un residency in medicina per piccoli animali presso l’Ohio State University nel 1979. È stato Assistan Professor di medicina presso la University of Illinois dal 1979 al 1981, anno in cui è ritornato all’Ohio State University come Assistant Professor. Nel 1985 è stato nominato Associate Professor e nel 1988 Professor. È autore del testo Fluid Therapy in Small Animal Practice di cui è stata pubblicata la seconda edizione nel marzo 2000. Il Dottor Di Bartola è attualmente coeditor-in-chief del Journal of Veterinary Internal Medicine. I suoi interessi clinici includono le malattie renali e le alterazioni dei fluidi, dell’equilibrio acido-base e degli elettroliti. Le sue aree di ricerca comprendono l’amiloidosi sistemica reattiva, l’amiloidosi ereditaria del gatto abissino e il rene policistico nel gatto persiano. Di Bartola è Diplomato all’American College of Veterinary Internal Medicine.

BERNARD F. FELDMAN DVM, PhD, Dipl ACVIM Bernard F. Feldman è Professore di Ematologia Clinica Veterinaria e Biochimica Clinica e Direttore del Laboratorio del Virginia Maryland Regional College of Veterinary Medicine. È Responsabile Editoriale (Editor-in Chief) della quinta edizione dello Schalm’s Veterinary Hematology, finito di pubblicare nell’agosto 2000. È autore o co-autore di altri tre importanti testi di ematologia, nonché di oltre 300 tra articoli scientifici e capitoli di libri. È Past President dell’American Society for Veterinary Clinical Pathology. È stato Professore di Patologia Clinica all’Università della California a Davis. Prima di ritornare all’attività accademica in Università

Antonio Ferretti è nato a Cortina d’Ampezzo nel 1948. Dopo quattro anni di Ingegneria Meccanica è passato alla Facoltà di Medicina Veterinaria di Milano laureandosi nel 1979 con tesi di argomento chirurgico. Si è dedicato fin dall’inizio della attività professionale al settore chirurgico sviluppando in particolar modo la Chirurgia Ortopedica e Traumatologica. Nel 1982 ha iniziato lo studio del Metodo Ilizarov e, nell’anno seguente, la sua applicazione clinica. Nel 1988 e nel 1991 ha trascorso un periodo di approfondimento presso il Prof. G.A. Ilizarov, all’Istituto Ortopedico Traumatologico della città di Kurgan (Siberia). Nel 1993 ha conseguito il Diploma dell’European College of Veterinary Surgeons. Svolge l’attività libero professionale esclusivamente nel campo ortopedico nella propria clinica a Legnano (MI).

RICHARD B. FORD DVM, MS, Dipl ACVIM Richard Ford è Professore di medicina presso la North Carolina State University. Dopo la laurea conseguita presso l’Ohio State University, Richard Ford ha svolto per tre anni la libera professione su piccoli animali e cavalli in Giappone. Successivamente ha completato un residency in medicina interna presso la Michigan State University. In seguito si è trasferito presso la Purdue University e nel 1982 presso la North Carolina State University. Gli interessi clinici del Dotto Ford sono le malattie infettive degli animali da compagnia, i vaccini e le vaccinazioni. È autore-editore di tre libri scientifici tra cui Handbook of Veterinary Procedures and Emergency Treatment attualmente pubblicato nella settima edizione. È membro del Feline Vaccination Advisory Panel e co-autore del Feline Vaccination Guidelines. È Past Presidente della North American Veterinary Conference di cui continua a svolgere un ruolo nel comitato scientifico.

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THERESA W. FOSSUM DVM, MS, PhD, Dipl ACVS Theresa Fossum è Professore e Responsabile di Chirurgia all’Università A&M del Texas. Nel 1982 ha conseguito la laurea in Medicina Veterinaria presso il Washington State University College. Dopo aver completato un internship presso l’ospedale veterinario di Santa Cruz, ha iniziato nel 1983 una residency in chirurgia all’Ohio State University. Nel 1987 ha ottenuto il Diploma dell’American College of Veterinari Surgeons (ACVS), collaborando con l’Università A&M del Texas nello stesso anno. Nel 1992 ha concluso un PhD in Microbiologia Veterinaria. I principali campi di interesse della Dottoressa Fossum sono le malattie dei sistemi respiratorio e cardiovascolare. È editrice del Small Animal Surgery, un testo di chirurgia pubblicato da Harcourt Brace Publishing Co (precedentemente Mosby Publishing Co.). È, inoltre, autrice di numerosi articoli sul chilotorace e su altre malattie respiratorie. Ha ricevuto il Wiley Distinguished Professor of Veterinary Medicine Award e, nel 1988, il Carl J. Norden Distinguished Teacher Award presso l’Università A&M del Texas.

CECILIA GORREL BsC, MA, Vet MB, DDS, MRCVS Hon FAVD, Dipl EVDC Cecilia Gorrel è Dottore in Chirurgia Dentale, in Patologia Orale e in Chirurgia Veterinaria. Si occupa di ricerca nel campo delle malattie orali dei cani e dei gatti. Gestisce, inoltre, uno studio dentistico veterinario e una clinica di chirurgia orale nel Regno Unito. È Diplomata dell’European Veterinary Dental College, di cui ricopre attualmente la carica di Presidente. È membro onorario dell’Academy of Veterinary Dentistry. La Dottoressa Gorrel è lettrice e tutor ai corsi riguardanti la chirurgia orale e le materie dentistiche veterinarie, sia nel Regno Unito che all’estero. Ha scritto numerosi articoli ed è autrice o co-autrice di numerosi libri.

MASSIMO GUALTIERI Med Vet Il Prof. Massimo Gualtieri si è laureato presso la Fa-

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coltà di Medicina Veterinaria di Milano nel 1983 dopo un periodo di 3 anni trascorso, in qualità di “allievo interno”, presso l’Istituto di Clinica Chirurgica. Nel 1992 ottiene la nomina a Ricercatore in ruolo presso l’Istituto di Clinica Chirurgica e Radiologia Veterinaria dell’Università di Milano. Dal 1995 è docente presso la Scuola di Specializzazione in Patologia e Clinica degli animali d’affezione della Facoltà di Medicina Veterinaria di Milano. Dal 1996 è docente per il Corso di Medicina Operatoria che ha in affidamento presso la Facoltà di Medicina Veterinaria di Milano dove attualmente è anche docente del corso di Chirurgia Endoscopica. Dal 1992 è docente al “Centro de Cirurgia de Minima Invasion” presso la Facoltà di Caceres (Spagna) per il “Corso Internazionale Teorico-Pratico di Endoscopia nei Piccoli Annimali” e dove, dal 1997, è direttore e organizzatore del “Corso Teorico-Pratico di Endoscopia Flessibile nei piccoli Animali” per Veterinari italiani. Attualmente è anche Direttore del Corso di Perfezionamento in Endoscopia Veterinaria presso la Facoltà di Medicina Veterinaria di Milano. Dal 1996 è Direttore Scientifico e fondatore della rivista internazionale The European Journal of Compartative Gastroenterology. Dal 1998 è Presidente della European Society of Compartative Gastroenterology (ESCG) della quale è inoltre membro fondatore (1993); è inoltre membro della New York Academy of Sciences, European Society of Veterinary Surgery (ESVS), Società Italiana di Chirurgia Veterinaria. Il Dott. Massimo Gualtieri è autore e coautore di più di 80 pubblicazioni su riviste italiane ed estere comprese le comunicazioni congressuali e videocassette.

TIMOTHY HACKETT DVM, MS, Dipl ACVECC Tim Hackett ha conseguito la laurea presso l’Università del Colorado nel 1989. Dopo aver completato un internship presso il West Los Angeles Veterinary Medical Group, si è occupato di medicina d’emergenza nella California del Nord, ritornando in seguito presso l’Università del Colorado per un master ed un residency in medicina d’urgenza e terapia intensiva. Diplomato nel 1994 presso l’American College of Veterinary Emergency and Critical Care, il Dottor Hackett ha operato, dal 1994 al 1996, presso il pronto soccorso del VCA West Los Angeles Animal Hospital. Dal 1996 è assistente alla cattedra di Terapia intensiva/Medicina d’urgenza all’University Veterinary Teaching Hospital del Colorado.

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I suoi interessi includono le malattie cardiopolmonari, la tossicologia e i traumi. Èstato relatore su tematiche relative alla Medicina d’urgenza negli Stati Uniti, in Europa e in Australia.

EDWARD J. HALL MA, Vet MB, PhD, DipECVIM-CA, MRCVS Laureato alla Cambridge University nel 1979. dopo aver frequentato un Internship e un Residency in Medicina Interna nei Piccoli Animali a Philadelphia, ha intrapreso una Scholarship di Ricerca in gastroenterologia presso l’Università di Liverpool. Ha conseguito un PhD nel 1988 e nel 1991 un dottorato di ricerca, quindi ha ottenuto incarichi di insegnamento in patologia veterinaria all’Università di Liverpool. Nel 1995 si è trasferito all’Università di Bristol dove ha ottenuto incarichi di insegnamento in medicina interna nei piccoli animali e nel 1999 è stato promosso a Senior Lecturer. Ha pubblicato numerosi lavori di gastroenterologia nel cane ed è stato co-autore del capitolo sull’intestino tenue dell’ultima edizione dell’Ettinger ed è stato coeditore del Manuale BSAVA Canine and Feline Gastroenterology. La sua ricerca clinica riguarda soprattutto le enteropatie canine.

tanti ricerche riguardano la fisiopatologia e la terapia delle malattie del cuore.

PHILIPPE R. HENNET DVM, Dipl AVDC, Dipl EVDC Philippe R. Hennet si è laureato nel 1988 presso l’Ecole Vétérinaire di Tolosa, in Francia, dove ha completato anche un internship in chirurgia dei piccoli animali. Dal 1987 al 1989 si è occupato di un progetto di ricerca sull’endodonzia nei cani in collaborazione con la Toulouse Dental School. Dal 1990 al 1992 ha operato come ricercatore in odontostomatologia alla scuola Veterinaria dell’Università di Pennsylvania, a Philadelphia. Attualmente lavora a Parigi come referente specialista in problematiche orali, dentali e nasali. È consulente dentistico presso l’Alfort Veterinary School di Parigi. È consulente scientifico per alcune ditte e per progetti di ricerca. Ha ricoperto l’incarico di Presidente dell’associazione dentistica veterinaria (GEROS / CNVSPA). È Presidente della European Veterinary Dental Society (EVDS) e vice Presidente dell’European Veterinary Dental College (EVDC). È Diplomato dal 1993 presso l’American Veterinary Dental College (AVDC), e dal 1998 presso l’European Veterinary Dental College (EVDC). È autore di molte pubblicazioni su tematiche cliniche e di ricerca ed ha collaborato alla stesura di capitoli in diversi libri sia in lingua francese che inglese.

JENS HÄGGSTRÖM DVM, PhD, Dipl ECVIM-CA (Card) Jens Häggström ha conseguito la laurea nel 1990 presso la Facoltà Veterinaria dell’University of Agricultural Sciences di Uppsala, in Svezia. Successivamente ha svolto un periodo di praticandato, per ritornare ad Uppsala nel 1991 per motivi di studio riguardanti la cardiologia veterinaria. Nel 1996 il Dottor Häggström ha conseguito un PhD con una tesi riguardante la degenerazioni mixomatosi della valvola mitrale. Attualmente è Professore Associato alla Facoltà Veterinaria di Uppsala ed insegna fisiologia veterinario e cardiologia clinica. È autore di circa 30 articoli su riviste distribuite a livello internazionale e co-autore del capitolo sulla degenerazione mixomatosi della valvola mitrale nell’edizione del 2000 dell’Ettinger Textbook of Internal Medicine (cardiologia). I suoi interessi clinici e le sue più impor-

THOMAS KERN DVM, Dipl ACVO Tom Kern si è laureato nel 1975 presso l’Università del Missouri. Dal 1975 al 1976 ha seguito un programma di internship presso l’Università della Georgia e in seguito un residency in oftalmologia presso la Cornell University fino al 1979. Dal 1980 è Diplomato all’American College of Veterinary Ophthalmologists di cui è stato Presidente dal 1989 al 1990. I suoi interessi di ricerca comprendono l’oftalmologia degli animali da laboratorio e la farmacologia oculare.

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GEORGE LUBAS Med Vet, Dipl ECVIM-CA (Med Int) George Lubas si é laureato presso l’Università di Pisa nel 1975, dove ha anche conseguito la specializzazione in “Malattie dei Piccoli Animali” nel 1977. Dal 1979 Assistente Ordinario presso la Cattedra di Clinica Medica. Dal 1983 al 1997 Professore Associato di “Ematologia Clinica Comparata” quindi dal 1998 a tutt’oggi di Propedeutica Medica nel corso di Studi in Medicina Veterinaria dell’Università di Pisa. Dal 1985 a tutt’oggi Professore Incaricato di “Genetica” nella Scuola di Specializzazione in “Patologia e Clinica degli Animali d’Affezione” presso l’Università di Pisa. Dal 1999 é diplomato del Collegio Europeo di Medicina Interna per gli Animali da Compagnia, specialità Medicina Interna (Dipl. ECVIM - CA). È autore e coautore di oltre 170 pubblicazioni inerenti l’immunoematologia e l’ematologia clinica del cane, gatto, cavallo e bovino. Ha tenuto oltre 70 tra Conferenze, Seminari e Corsi di aggiornamento sulle medesime tematiche ai medici veterinari che si dedicano ai piccoli animali ed equini.

CARLO MARIA MORTELLARO Med Vet Nato Rivolta D’Adda, il 5 Febbraio 1950, si è laureato in Medicina Veterinaria presso la Facoltà di Medicina Veterinaria dell’Università degli Studi di Milano il 29 Marzo 1974. È stato professore di Anestesiologia Veterinaria presso la stessa Università dal 1976 al 1979. Dal 1980 al 1992 ha ricoperto il ruolo di Professore Associato di Patologia Chirurgica Veterinaria e Podologia, e nel 1993 è stato nominato Professore Ordinario di Patologia Chirurgica Veterinaria, ruolo che tuttora ricopre. I suoi principali interessi scientifici sono rappresentati dalle patologie di orecchio, naso e gola nel cane e nel gatto, lesioni del cavo orale, endoscopia delle vie aeree superiori ed infine patologie della regione anale e circumanale (da un estremo all’altro del corpo senza transitare in mezzo) In questi ultimi anni un interesse particolare è stato rivolto alle patologie osteo-articolari distrofico-displastiche (nota la sua avversione per le forme “carenziali”) del cane e del gatto. Si è dedicato inoltre, sin dagli inizi della sua carriera, allo studio delle lesioni digitali del bovino, tematica che non ha mai abbandonato anche perché qualche “sciagurato” farmer olandese ha legato

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il suo nome ad una diffusissima lesione della cute digitale delle vacche da latte: la cosiddetta “Mortellaro’s Disease”. Cose più serie: è presidente in carica dell’IVENTA (International Veterinary Ear Nose and Throat Association) membro dell’International Committee for Foot Disorders in Ruminants, socio della SIB (Società Italiana di Buiatria) della SICV (Società Italiana di Chirurgia Veterinaria) della SISVET (Società Italiana delle Scienze Veterinarie) della FIMUA (Federazione Italiana di Micologia Umana ed Animale). È inoltre socio onorario dell’AIVPA (Associazione Italiana Veterinari per Piccoli Animali) e della SCIVAC (Società Culturale Italiana Veterinari per Animali da Compagnia). È infine socio affiliato dell’“American Animal Hospital Association” (AAHA), dell’“International Elbow Working Group” (IEWG), dell’“European Society of Veterinary Orthopaedics and Traumatology” (ESVOT) dell’“European Society of Veterinary Surgery” (ESVS) e della “Veterinary Cancer Society” (VCS). È referee scientifico del Gruppo di Studio di Ortopedia della SCIVAC. È autore-coautore di 160 pubblicazioni ed infine coautore del testo “Le lesioni digitali del bovino” in collaborazione con Renato Cheli e Flaminio Addis. È stato relatore in numerosi congressi e seminari di aggiornamento post-universitario in Italia ed all’Estero. È sposato con Vanda (che non è medico veterinario) ma non ha figli. Non possiede cani né gatti ma… solo camelie (japonica, sasanqua, reticulata, higo etc) ed agrumi (citrus limon, c.paradisi, c.myrtifolia, c.sinensis, c.mitis, c.medica ect.) Il suo sogno… avere un “Giardino delle Esperidi”. È micologo dilettante, ha raccolto Aspergilli (fumigatus, terreus, niger), Criptococchi, Rinosporidii, ma soprattutto appassionato ed esperto micofago. Oltre al regno vegetale c’è il mondo degli orologi che lo affascina… ma solo Breitling. Talvolta suona. P.S. Attualmente l’amore per le camelie non è più corrisposto…

GREGORY K. OGILVIE DVM, Dipomate ACVIM Greg è full professor, oncologo clinico e internista presso la Comparative Oncology Unit della Colorado State University, dove lavora come oncologo e insegna l’importanza del legame uomo-animale. Dopo la laurea conseguita presso la Colorado State University ha lavorato come libero professionista nel Connecticut prima di completare un residency in medicina interna, cardiologia ed oncologia presso la Tufts University/Angell Memorial Animal Hospital. Come membro del corpo

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docente della University of Illinois, Greg è stato coinvolto nel programma sul rapporto uomo-animale. È Diplomato all’American College of Veterinary Internal Medicine. È autore di un libro tradotto anche in francese e giapponese e di oltre 160 articoli scientifici. Ha ricevuto numerosi premi e riconoscimenti tra cui: List of Outstanding Teachers, University of Illinois 19841988; Norden Distinguished Teacher Award 1987 e 1988; Arnold O. Beckman Research Award; Beecham Research Award; Purina Small Animal Research Award; Scheidy Memorial Research Award e American Veterinary Medical Association/American Kennel Club Award. Greg Ogilvie è stato relatore in tutto il mondo. È istruttore certificato di sci e gli piaccione le immersioni e la bicicletta. Ha una figlia di 12 anni di nome Torrie.

MASSIMO OLIVIERI Med Vet Laureato in Medicina Veterinaria presso l’Università di Milano nel 1988. Dal 1986 al 1988 frequenta la Clinica Chirurgica della Facoltà di Medicina Veterinaria di Milano. Dal 1988 al 1993 ha lavorato con il Dr. G. Romanelli. Nel 1991, con altri veterinari, ha aperto la “Clinica Malpensa” dove si occupa di chirurgia dei tessuti molli (torace e addome), di ortopedia e di artroscopia. Ha frequentato vari stage all’estero (Ohio, Francia, Colorado). Dal 1997 ha iniziato il suo residence program per l’ECVS presso il Dr. A. Vezzoni. È relatore e istruttore in vari corsi SCIVAC di chirurgia e ortopedia. È il nuovo coordinatore del gruppo di ortopedia insieme al Dr. E. Baroni e al Dr. G. Rovesti.

ROBERT R. PADDLEFORD DVM, Dipl ACVA, Dipl ACVEEC Bob Paddleford attualmente è Professore e Direttore del servizio di anestesia del Department of Small Animal Clinical Sciences presso il College of Veterinary Medicine dell’Università del Tennessee a Knoxville. Stati Uniti. Laureato nel 1970 presso l’Università del Missouri. Quindi ha seguito un programma di internship presso l’Università della California a Davis, seguito da un programma di residency all’Università del Missouri. Nel 1973 si è diplomato all’American College of Veterinary Anesthesiologists, di cui ha ricoperto gli incari-

chi di Executive Secretary negli anni 1982-1992 e Presidente in 1994. Dal 1973 al 1976 è stato Assistant Professor presso il College of Veterinary Medicine dell’Università del Missouri. Dal 1976 lavora presso l’Università del Tennessee. È Charter Diplomate dell’American College of Veterinary Emergency and Critical Care. Ha pubblicato oltre 50 lavori scientifici, 14 capitoli di libri e un testo completo di anestesia. Ha presentato relazioni in oltre 250 congressi tra Stati Uniti, Canada, Europa e Giappone. Ha ricevuto diversi premi tra cui il Norden Distinguished Teaching Award, l’Outstanding Clinician Award e l’Educator of the Year Award (due volte).

MASSIMO PETAZZONI Med Vet Laureato nel 1997 in Medicina Veterinaria all’Università di Milano. Dal 1996 è titolare di una borsa di studio erogata da Hill’s per una ricerca sulle patologie scheletriche del cane nel periodo dell’accrescimento i cui risultati sono stati presentati ai meetings dell’International Elbow Working Group nel 1998 a Bologna, nel 2000 ad Amsterdam ed al congresso nazionale SCIVAC 2000. Dal 1998 svolge l’attività di libero professionista occupandosi esclusivamente di ortopedia e traumatologia canina e felina. È coautore della monografia “L’artrosi nel cane” edita da SCIVAC (1999). Ha collaborato alla traduzione italiana della terza edizione americana del libro “Ortopedia e trattamento delle fratture dei piccoli animali” - Piermattei, Flo È stato relatore ai Seminari Regionali SCIVAC Lombardia 1997, Sicilia 1998 e Liguria 1999 sulle “Patologie scheletriche della crescita nel cane e correlazioni nutrizionali”. È socio della SCIVAC, dell’European Society of Veterinary Orthopaedics and Traumatology, dell’International Elbow Working Group, dell’ASAMI, Associazione per lo Studio e l’Applicazione delle Metodiche di Ilizarov e socio affiliato dell’American Animal Hospital Association. È iscritto al Gruppo di Studio di Ortopedia Veterinaria SCIVAC.

VIVIEN ROLFE BSc (Hons), PhD Vivien Rolfe è laureata in Fisiologia presso la Sheffield University ed ha ottenuto un PhD sul meccanismo patogenetico della diarrea da trasporto causata da Escherichia coli.

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È stata relatrice in scienze biomediche presso la Greenwich University. È stata ricercatrice presso l’unità di gastroenterologia del Great Ormond Street Hospital for Sick Children di Londra, svolgendo principalmente indagini sulle malattie infiammatorie dell’intestino. Attualmente è manager del centro di gastroenterologia del Waltham Centre for Pet Nutrition, dove è impegnata principalmente nello studio della fisiologia dell’apparato digerente del cane e del gatto.

GIORGIO ROMANELLI Med Vet, Dipl ECVS Laureato alla Facoltà di Vete-rinaria di Milano nel 1981. Conseguita la laurea ha lavorato ad un programma di Chirurgia sperimentale sul trapianto di cuore nei maiali e di pancreas nei cani. Lavora a Milano come libero professionista. Si occupa principalmente di Chirurgia Generale ed Ortopedica e di Oncologia Clinica e Chirurgica. Diplomato dal luglio 1993 all’European College of Veterinary Surgeons. Autore del video SCIVAC sulla fissazione ossea esterna. Ha ricoperto dal 1993 al 1995 la carica di Presidente SCIVAC. Oltre che della SCIVAC è membro di AAHA, BSAVA, ECVS, AOI, SINVET, ESVN, Veterinary Cancer Society.

ROBERTO SANTILLI Med Vet, Dipl ECVIM-CA (Card) Laureato presso la Facoltà di Medicina Veterinaria di Milano nel 1990. Si è diplomato all’European College of Veterinary Internal Medicine - Companion Animals (Specialty of Cardiology) nel 1999. Lavora presso la Clinica Veterinaria Malpensa in Samarate Varese). È stato professore a contratto in cardiologia felina per l’anno 1997-1998 presso la Scuola di Specializzazione in Patologia e Clinica degli animali d’affezione dell’Università degli Studi di Milano. Dal 1992 al 1998 ha svolto programmi di aggiornamento in cardiologia ed ecografia addominale presso la North Carolina State University, l’Ohio State University, University of California, Cornell University e Missouri State University. È istruttore ai corsi S.C.I.V.A.C. di cardiologia, ed ecografia addominale. È autore di numerose pubblicazioni di cardiologia ed ecografia addominale su riviste nazionali ed internazionali. Il suo principale settore di ricerca sono le cardiomiopatie e l’ipertensione arteriosa del gatto.

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ALDO VEZZONI Med Vet, Dipl ECVS Laureato nel 1975 presso la facoltà di Veterinaria dell’Università di Milano, ha ottenuto il titolo di Specialista in Medicina dei Piccoli Animali nel 1978 presso la stessa facoltà. Dal 1976 lavora a Cremona come libero professionista nella propria clinica veterinaria. Si è Diplomato al College Europeo di Chirurgia a Cambridge nel 1993. Ha tenuto diverse relazioni sia in Italia che all’estero su temi riguardanti la filariosi canina, l’ortopedia, la chirurgia e l’odontostomatologia. Autore di numerosi articoli scientifici sulla filariosi e sulla chirurgia e ortopedia nei piccoli animali. Autore e co-autore di un testo sulla filariosi canina e del prontuario SCIVAC, è stato anche curatore di numerose edizioni italiane di testi stranieri. Dal 1994 è membro del Comitato Centrale FNOVI di cui riveste dal 1997 la carica di Segretario. Dallo stesso anno è anche Presidente dell’Ordine dei Veterinari di Cremona.

MICHAEL WILLARD DVM, MS, Dipl ACVIM Michael Willard è Professore di medicina per piccoli animali presso la Texas A&M University dove lavora come gastroenterologo ed endoscopista dal 1988. È Diplomato all’American College of Veterinary Internal Medicine ed è Past- President della Comparative Gastroenterology Society. Ha pubblicato oltre 50 articoli scientifici e oltre 50 capitoli di libri. I suoi interessi clinici comprendono il vomito cronico, la diarrea, le ulcere gastriche, l’esofagite, le enteropatie proteino-disperdenti e l’endoscopia.

ANDREA ZATELLI Med Vet

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ESTRATTI DELLE RELAZIONI

Gli estratti sono elencati in ordine alfabetico secondo il cognome del relatore. Le relazioni di uno stesso autore sono elencate secondo lâ&#x20AC;&#x2122;ordine cronologico di presentazione.

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Imaging of the oncologic patient Diagnostica per immagini nel paziente oncologico

David Biller DVM, Dipl ACVR - Kansas State University - Manhattan, Kansas, USA

Neoplasia almost always alters the normal spatial relationships of tissues and organs and therefore diagnostic imaging is critical not only for the diagnosis of cancer but also for staging patients and for following response to therapy. At present the most frequently used imaging modalities for the diagnosis of cancer are conventional radiographs and ultrasound but the use of magnetic resonance imaging (MRI), computerized tomography (CT), and nuclear medicine (Nuc Med) are increasing in availablitity and usage. Even with these advances it is necessary to emphasize that the clinician still is not able to make a tissue diagnosis based on the image and that relevant clinical information as well as cytology or histopathology are necessary to make a definitive diagnosis. The use of ultrasound, CT, MRI, and Nuc Med have not replaced conventional diagnostic radiographs but they serve to complement them. These newer imaging modalities have made assessing tumor margins, evaluating for metastasis, and determining the degree of invasiveness more reliable. These techniques are quite expensive but at the same time lend more information to the diagnosis, staging extent of tumor burden, and degree of invasion. In the long run this may decrease cost and patient suffering. They may also aid in narrowing the list of differentials and prevent unnecessary surgery. The newer imaging modalities will also help to guide deep needle aspirations or biopsies, as well as planning open biopsies and surgical resections. Conventional diagnostic radiographs still remains a valuable diagnostic tool in the practice of veterinary oncology. Availability and cost are a major advantage to the use of conventional radiographs. Radiographs provide good spatial resolution but have poor contrast discrimination between normal and neoplastic soft tissues. Invasiveness and tissue architecture cannot be assessed. One advantage to the use of conventional radiographs is their ability to cover a large area such as the abdomen or thorax in 2 images (lateral and VD/DV). They can provide information regarding the size, shape, margination, opacity, position, and organ displacement easier than other imaging modalities. Conventional radiographs are a good screening procedure and guide to further diagnostic procedures and ima ging modalities. Improved ultrasound technology and increased clinical applications for ultrasound have made ultrasound an important imaging modality for the diagnosis, and evaluation of therapeutic response in the veterinary cancer patient. The af-

fordable cost and availability of ultrasound equipment has resulted in a tremendous increase in the use of ultrasound in veterinary practice. Ultrasound excels as an imaging modality when discrimination of cystic versus solid masses is neccessary, when evaluation of a body cavity filled with fluid (abdominal or pleural effusion) is necessary, when knowledge of internal architecture of an abdominal organ is needed, or when guidance of fine needle aspiration or tissue core biopsy is to be done . Computed tomography is the production of tomographic images (cross sectional slice images) using x-rays and computers. With CT scanning the recorded tissue densities have the same significance as the film densities on conventional radiographs. Computed tomography compared to conventional radiographs has excellent contrast discrimination and the ability to separate deep structures without the superimposition of overlying tissues (visualize brain without the inconvience of the surrounding skull). Soft tissues must be significantly altered by disease before changes can be visualized with conventional radiographs, with CT changes can be appreciated earlier and more accurately. Magnetic resonance imaging can be easily obtained in any plane (axial, sagittal, and coronal). The contrast between different soft tissues is superior to all other imaging modalities. Standard MRI scans also take a relatively long time (minutes rather than the seconds required in a CT) therefore body, respiratory, cardiac, intestinal motion are a potential problem. General anesthesia is required and monitoring of patients can be difficult depending on the type of MRI unit utilized.

PULMONARY Conventional radiographs represent the most valuable and cost effective examination for primary screening of neoplasia of the thorax. Radiographs should be taken in all patients suspected of having cancer and during treatment periods to monitor response to therapy. Taking three views of the thorax (right and left laterals as well as DV or VD) should act to increase sensitivity for finding lesions. Pulmonary neoplastic lesions can be divided into several categories: 1) solitary or multiple well defined nodules or masses, 2) solitary or multiple ill defined nodules or masses,

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3) amorphous ill defined alveolar opacities, 4) diffuse miliary (micronodular) interstitial opacities, 5) diffuse interstitial opacities, and 6) diffuse and lobar alveolar opacities. Solitary nodules with either well or ill defined borders are the most characteristic findings of primary pulmonary neoplasia. Cavitation is occasional present within primary or metastatic pulmonary nodules or masses. Primary lung tumors are most commonly found in the caudal lung lobes (right greater than left). Metastatic disease from non-lung cancer is much more common than primary lung cancer in the dog and cat. Pulmonary metastasis can be divided into several types. Less commonly pulmonary metastases are represented by solitary, cavitary or noncavitary interstitial masses (> 4 cm diameter), interstitial nodules (2 - 4 cm diameter), or interstitial miliary masses(< 2 cm diameter). The most common radiographic appearance of pulmonary metastasis is multiple well circumscribed non-cavitary pulmonary masses, nodules, or miliary masses. Computed tomography by virtue of its cross sectional display of anatomy, and superior contrast and anatomic resolution can differentiate pulmonary lesions from overlying normal superimposed structures. CT is clearly superior to conventional radiography in demonstrating the extent of the primary lesion, invasion of the hilum or mediastinum, body wall or pleural space involvement, and the presence of enlarged lymph nodes. Iodinated intravenous contrast can help to distinguish between vascular and nonvascular abnormalities. The most sensitive modality at present time in the diagnosis and staging of pulmonary metastatic disease is CT.

SKELETAL A diagnosis of skeletal neoplasia can often be supported on conventional radiographs. Bone scintigraphy may be used to screen for additional lesions , or to evaluate the extent of lesions diagnosed radiographically. MRI and CT are not used to obtain a diagnosis but rather to supply additional information about location and extent of the tumor. Definitive diagnosis is made based on biopsy and histopathology. It is impossible to make a definitive diagnosis of neoplasia versus an infectious or benign bone lesion by radiographic means alone. By integrating signalment, history, physical and laboratory examination along with the radiographic changes a prioritized differential diagnosis can be made with a high degree of accuracy. Radiographic changes may include: adjacent soft tissue swelling, aggressive radiographic changes (poorly demarcated long transition zone between normal and abnormal bone, cortical lysis,periosteal reaction - amorphous or sunburst, and a pathologic fracture. Primary bone tumors usually begin in the metaphysis and extend into the epiphysis and diaphysis secondarily. Uncommonly they may cross joints or invade adjacent bones, but this usually occurs late in the disease. Multifocal areas of increased medullary opacity (bone infarction) within the medullary cavity may be seen. Magnetic resonance provides a highly sensitive means to document or exclude pathology. MRI is superior to all other imaging modalities for delineating the margins of a tumor with respect to adjacent normal tissues.

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CENTRAL NERVOUS SYSTEM Evaluation of the brain and spinal cord is one of the few places where conventional radiography is of little value unless there is adjacent bone involvement. It provides little information other than location of lesion. Computed tomography provides diagnostic information for many brain and spinal lesions. Two scan series are usually performed with CT, the first one being a survey and the second one after intravenous iodinated contrast injection. Intravascular contrast agents usually enhance masses, demonstrate vascular alterations and areas of disruption of the blood brain barrier. Certain canine brain tumors may have distinguishing features on CT images based on location and pattern of contrast enhancement. Magnetic resonance imaging is the technique of choice for imaging brain and spinal cord neoplasia. MRI is ideally suited for imaging of intracranial neoplasia because of its inherent property of producing excellent contrast between normal and abnormal tissue. Intravenous Gadodiamide contrast may also be valuable to show blood brain barrier disruption.

ADRENAL Radiographic changes of the adrenal are detectable if the adrenal tumor is large or mineralized. Large unilateral adrenal masses may displace the kidney or other adjacent abdominal organs providing additional evidence of adrenomegaly. Mineralization of adrenals can occur with neoplasia as well as nonneoplastic adrenals. Other changes that might be radiographically apparent with a adrenocortical tumor are large blunted pulmonary arteries secondary to pulmonary thromboembolism and pulmonary interstitial mineralization. If tumor invasion of the caudal vena cava is suspected a nonselective venogram can be diagnostic . Adrenal ultrasound is very sensitive for the diagnosis of adrenal neoplasia. The one problem is that nodular hyperplasia may mimic the appearance of an adrenal adenoma. Although adenomas are usually unilateral and may not disrupt or disrupt the architecture far less that do malignant tumors. Adenomas (nodular hyperplasia) may appear as hyperechoic foci within a normal size and shaped adrenal. Tumors may appear hypoechoic or have a mixed echogenicity. Invasion of the caudal vena cava may be detected. Diagnosis of an adrenal mass with ultrasound is not diagnostic for tumor type. The liver, abdominal lymph nodes, and adjacent structures can be evaluated for invasion and metastasis.

NASAL There are basically 4 different radiographic patterns of change that occur in the nasal passages. These are; 1) increased soft tissue opacity (focal or diffuse) overlying a normal conchal pattern, 2) increased soft tissue opacity (focal or diffuse) overlying areas of conchal destruction, 3) areas of conchal destruction without accompanying increase in soft tissue opacity, and 4) a combination of the above patterns. These patterns rather than indicating an etiology reflect a

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level of aggressiveness and duration. Most nasal neoplasia originate from the level of the ethmoid conchae and cribiform plate. Disruption of the nasal and vomer bone (boney nasal septum) can be seen. Large areas of the cartilaginous nasal septum may be destroyed and not be evident radiographically other than a bilateral increase in soft tissue opacity. Because radiographic changes are nonspecific definitive diagnosis should be based on nasal flushes and cytologic studies, biopsies, and culture. Computed tomography is superior to conventional radiography for demonstrating changes associated with nasal neoplasia in dogs. This superiority is because of the higher contrast resolution and ability to obtain an image in the third dimension, which minimized superimposition of overlying structures. Several CT findings are strongly correlated with a diagnosis of neoplasia. These include; patchy areas of increased opacity within soft tissue, destruction of all or part of the ethmoid bone, abnormal soft tissue in the retrobulbar space, destruction of the lateral maxilla, destruction of the nasal bone or the rostral dorsal maxilla, and hyperostosis of the lateral maxilla. CT is more helpful in differentiating fluid versus masses in the frontal sinuses. Because the extent of nasal neoplasia can be more accurately determined with CT. It is recommended if surgery or radiation therapy are to be used as treatment modalities. Magnetic resonance imaging appears superior to CT for detection of cribiform plate involvement and provides better anatomic detail of the tumor and secondary pathology.

ABDOMINAL Conventional abdominal radiographs are still an excellent screening technique for suspected abdominal neoplasia. Radiographic differentiation of abdominal masses depends on a good working knowledge of normal radiographic anatomy. An abdominal mass that is palpated is not always visualized on survey radiographs directly, but indirectly may demonstrate displacement of bowel or other abdominal organs. Conventional radiographs help to guide the diagnostic

workup as well as determine the use of other imaging modalities. Before resorting to contrast radiography to enhance visualization of a poorly demarcated mass one should consider positional or compression radiography. Positional radiography may consist simply of obtaining the opposite lateral, a DV or an oblique. Positional radiography may also include horizontal beam projections with erect and decubitus patient positioning. Compression radiography creates anatomic separation of adjacent abdominal structures. This may help define the appearance of the mass as well as the organ of origin. Ultrasound is an excellent follow-up to radiographs as it can define the organ of origin, internal architecture, and evaluate the rest of the abdomen for metastasis. This includes other abdominal organs as well as lymph nodes. Abdominal effusion which may be present with cancer (carcinomatosis) usually doesn't hamper but even enhance ultrasounds ability to diagnose neoplasia. Ultrasound is also very helpful in the guidance for FNA and biopsy. CT also provides excellent abdominal detail, but cost and the necessity of general anesthesia limits its current use.

BIOPSY TECHNIQUES Biopsy techniques can be used with fluoroscopy (thorax), ultrasound (anywhere ultrasound can provide information), or computed tomography (anywhere). At present they are use most often performed blindly or with ultrasound guidance. If many instances neoplasia is just part of the differential diagnosis and a definitive diagnosis is necessary for prognosis and accurate treatment. Percutaneous ultrasound guided fine needle aspiration and tissue core biopsy are minimally invasive and cost effective techniques for obtaining diagnosis. Risks that should be considered include: neoplastic dissemination, infection, and hemorrhage. Ultrasound guided tissue sampling have yielded few risks and even fewer life threatening risks. Benefit versus risk dictates that these high yield low risk procedures provide helpful information necessary for the diagnosis and treatment of cancer in veterinary patients.

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Autosomal dominant polycystic kidney disease in persian and persian related cats Diagnosi e riconoscimento precoce del rene policistico nel gatto

David Biller DVM, Dipl ACVR - Kansas State University - Manhattan, Kansas, USA

Polycystic kidney disease (PKD) is an inherited disease in Persian and Persian related cats. Polycystic kidney disease is not a new disease. This disease has been present and reported sporadically in the veterinary literature for approximately 30 years. Over the last 10 years however it has been characterized as a slowly progressive irreversible inherited renal disease. The inheritance in Persian and Persian related cats is as an autosomal dominant gene. Autosomal dominant polycystic kidney disease is a late onset renal disease that causes enlarged kidneys with renal dysfunction occurring at 7 years of age on average. Multiple cysts are present bilaterally from birth, and slowly grow in size causing the kidney to enlarge and eventually reducing the kidneys function. Ultimately this can result in renal failure. Cysts may vary in size from less than 1 mm to greater than 1 cm in size, with older animals having larger and more numerous cysts. Clinical signs are nonspecific and include depression, anorexia or reduced appetite, polyuria, polydypsia, and weight loss. These are similar to signs of chronic renal failure of any etiology. Cysts have been documented in other organs in addition to the kidney including the liver and uterus. Due to the slow progression of the disease, not all cats with PKD will develop clinical renal disease and death. The rate of growth of renal cysts is quite variable, with growth rate varying between kidneys in the same cat, between affected parents and offspring, between siblings and between genetic lines. Polycystic kidney disease (PKD) has been defined as a structural disorder in which an appreciable portion of the normal renal parenchyma is replaced by cysts. Two forms of PKD have been described in people, autosomal dominant (ADPKD) previously referred to as Adult PKD and autosomal recessive (ARPKD) and in the past referred to as Infantile PKD. These two forms differ in inheritance, clinical manifestations, morphological features, and clinical outcome. ARPKD is uniformly lethal at a relatively young age. Autosomal dominant PKD in people is inherited as a simple autosomal dominant trait with a very high penetrance (approaching 100%). Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited diseases and is certainly the most common inherited renal disease in people. It affects 1 in 400 to 1 in 1000 people (400,000 - 600,000) in the United States, and accounts for 10% of end stage renal disease.

Human autosomal dominant polycystic kidney disease (ADPKD) is a slowly progressive irreversible renal disease that progresses to renal failure over years in people. It is characterized by development and growth of cysts in both kidneys and frequently in the liver. The disease has a variable time of clinical onset and development of renal failure. The reasons for the wide variability in time of onset of end-stage renal disease are not known. The kidneys may become enlarged and contain hundreds of fluid-filled cysts of widely differing sizes. Enlargement of cysts with compression of normal renal parenchyma may be a central factor in the pathogenesis of renal failure. Neither physical examination nor routine laboratory data are sufficient to establish or exclude a definitive diagnosis of ADPKD early in the course of the disease. Consequently, imaging (ultrasound) is required to establish a definitive diagnosis. Feline polycystic kidney disease has been described in the veterinary literature in 8 mature cats ranging in age from 3 to 10 years. Of these cats, one was male, 6 were female, and in one the gender was unavailable. Four were Persian cats and 7 had bilateral renal involvement. The clinical signs in these cats were similar to those observed in cats with chronic progressive renal failure and included: lethargy, anorexia, vomiting, polydipsia, polyuria, and weight loss. In retrospective studies of feline chronic renal disease, PKD was the primary lesion found in 2 (2.7%) of 74 cats evaluated in Ohio and in 12 (18%) of 68 cats studied in Minnesota. In addition, PKD was reported as a cause of renal failure among cats selected for renal transplantation.

GENETICS A 6-year-old female Persian cat was seen for hematuria, polydipsia, and polyuria. Examination revealed palpably enlarged kidneys. Serum creatinine was 2.6 mg/dl (normal 0.7-1.8 mg/dl) and serum urea nitrogen was 69 mg/dl (normal 15-33 mg/dl). Ultrasound examination revealed multiple bilateral renal cysts with only a small amount of residual parenchymal mass. The cat died 2.5 months later. Necropsy revealed bilaterally enlarged kidneys with visible cysts of 0.5 to 1.0 cm diameter. No other organs contained cystic lesions. Two repeat breedings of this queen and an unrelated, un-

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affected (based on sonographic examination) male Persian cat produced 5 kittens. Ultrasonography was performed on the 4 available offspring revealing 3 affected cats

Breeding Possibilities with PKD Cats Unaffected cat = xx Heterozygous affected cat = Xx Homozygous affected cat = XX Unaffected

Unaffected

50% Affected

100% Affected Heterozygous Affected

75% Affected

Utilizing the two male offspring of our 6-year-old female PKD positive Persian cat a colony of cats with PKD was established. These two males were bred to unaffected, unrelated PKD negative cats. Affected offspring were detected by ultrasound as early as 7 weeks of age. Absence of cysts on ultrasound examination at 6 months of age was correlated with absence of PKD at necropsy. Both males and females were affected and, of progeny from affected X unaffected crosses, 42% were affected and 58% were unaffected. In affected X affected crosses, 73% of progeny were affected and 27% were unaffected. These results are compatible with autosomal dominant inheritance of this trait.

PATHOGENESIS No single hypothesis completely explains the development of PKD in people. Consequently, multifactorial explanations have been advanced. One theory suggests that hyperplastic epithelial cells develop into polyps that cause partial obstruction and subsequent dilatation of the tubules . A second theory suggests a defective tubular basement membrane creating a weak wall and secondary dilatation, and some believe that both factors may be operative. Cysts resulting fron non-union of portions of the nephron have not yet been excluded in cats, although this has not been shown to be true in other species.

PATHOLOGY Grossly ADPKD in cats is characterized by cysts throughout the kidney involving only a small percentage of nephrons. Cysts increase in size with age. Histologically the

site of origin of the cysts in variable. Ultrastructural features of cyst morphology, although not characteristic of specific nephron segments, are markedly variable. Cysts arise in different segments of the nephron and, as has been previously suggested in other species, dedifferentiate during cystogenesis with loss of characteristic features. Rare foci of proliferating cyst epithelial cells are found. These foci have been implicated as a cause of cyst development by causing obstruction and dilatation of ducts or tubules into cysts. There is an increased epithelial proliferation rate in some cysts in young cats, up to 30 times the proliferation rate of unaffected cortical tubular epithelium. Increased proliferation is intermittent, occurs early in the course of cystogenesis, and ceases once a cyst becomes established. The increasing size of established cysts may be due to other mechanisms. Hepatic lesions are common in cats with ADPKD. Hepatic cysts in the cats in our study were uncommon (< 10% of affected cats). This may be related to the young age of the cats, because the occurrence of hepatic cysts in people increases with age. There was a high frequency of hepatobiliary hyperplasia, similar to congenital hepatic fibrosis, in affected cats. Approximately 30-60% of people with ADPKD have liver cysts. The incidence of cysts increases with age to approximately 75% prevalence at > 60 years of age. People with ADPKD also may have cysts in the pancreas, uterus, as well as increased prevalence of cerebral aneurysms (10-30%), and colon diverticuli. Certain families with ADPKD have a greater susceptibility for intracranial aneurysms. Valvular dysplasia also has been documented in people with ADPKD. These valves undergo myxomatous degeneration and most often involve the aortic and mitral valves. Some Persian cats with ADPKD have liver cysts (no studies for percent involvement with liver cysts has been done to date) and one cat observed by the author had lymphatic dilatation and cyst formation in the uterus. Cats with ADPKD may die of renal failure before they develop polycystic liver disease. In people, polycystic liver disease (PLD) develops approximately one decade post development of polycystic kidney disease (PKD). People with PKD survive longer than affected cats as a result of renal transplantation and dialysis.

IMAGING Neither physical findings nor routine laboratory data are sufficient to establish or exclude a definitive diagnosis of PKD early in the course of disease. Therefore, diagnosis of PKD early in life requires imaging. Early identification of PKD is beneficial because it would allow early recognition and treatment of animals with chronic renal failure. It would also allow the identification of asymptomatic affected cats before they are bred. In Persian cats, PKD is inherited as an autosomal dominant trait. Thus, if a PKD positive animal is bred, 50 % of the offspring will develop PKD. Polycystic kidney disease typically has late onset,and affected cats may live many years before developing clinical signs. Early screening followed by neutering of all affected cats could potentially eliminate this disease from the at-risk population.

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Renal cysts in cats with PKD have been reported to be bilateral with one exception. The diagnosis of PKD may be difficult in its early stages because of variable severity. With minimal disease, the kidneys are normal in size, and their surfaces are smooth. As the size and number of cysts increase, the kidneys enlarge, but normal renal contour often is maintained. In more advanced disease, the cysts may project beyond the normal renal surface, causing it to become irregular. The renal collecting system may appear distorted grossly. Renal involvement is variably asymmetrical because of the progressive nature of the disease and the likelihood that only a small proportion of the nephrons is affected. With advanced disease, the renal parenchyma is almost completely replaced by numerous cysts.

DIAGNOSTIC RADIOGRAPHY Depending upon the age of the cat and extent of disease, the survey abdominal radiographs of cats with PKD can be unremarkable. As the disease progresses with age, symmetrical or asymmetrical renomegaly is apparent. Often it is not possible to identify the entire renal outline on radiographs, and renomegaly may only be appreciated by identifying displacement of perirenal structures. Initially, the enlarged kidneys may have smooth contours. With further progression, the margins of the kidney become more irregular or bosselated. Differential diagnoses for radiographically-evident renomegaly in cats should include hydronephrosis, granulomatous nephritis due to FIP (Feline Infectious Peritonitis), lymphoma, perinephric pseudocysts (fluid surrounding the kidneys), and PKD.

EXCRETORY UROGRAPHY Early in the course of the disease, the kidneys may appear enlarged. Their contour usually is smooth and the renal collecting system is normal. The nephrogram may appear mottled due to the presence of multiple small cysts, but no well-demarcated radiolucent areas are visualized. As the disease progresses, the contour may become irregular and the renal pelvis and diverticula may become distorted. In the later stages of the disease, the nephrogram is characterized by numerous, sharply-marginated radiolucent areas throughout the renal parenchyma.

ULTRASOUND Ultrasonography is a sensitive and noninvasive ima ging technique for the diagnosis of renal cysts. Its accuracy and reliability however are dependent on the experience of the individuals performing and interpreting the examination. The sonographic characteristics of renal cysts include: 1) a spherical outline; 2) sharply marginated, smooth walls; 3) no internal echoes; and, 4) the presence of through-transmission (acoustic enhancement posterior to the lesion consistent with the size of the lesion). Through transmission may not be observed in cysts that are small.

Very early in the course of the disease (as early as 6-8 weeks of age), the renal parenchyma may appear normal with the exception of one to several small (1-2 mm) cysts. Variation in the size of the cysts is common. The central renal sinus echoes may be distorted by larger cysts later in the course of the disease. Highly echogenic interfaces with posterior shadowing that r epresent calcification may be present in the cyst wall. Septa commonly are found in cysts. Polycystic kidney disease is most easily diagnosed using ultrasound. We recommend using a high frequency transducer (7 MHz or higher) to better visualize smaller cysts allowing diagnosis of this disease earlier in life. PKD has been diagnosed as early as 4 weeks of age using ultrasound. With the proper equipment and experience this disease can be diagnosed with appr oximately 95% accuracy after 10 months of age. The older the cat, the larger the cysts allowing easier detection. All affected cats must have at least one parent that is affected (autosomal dominant trait).

TREATMENT No specific therapy for PKD currently is available. Treatment of renal failure resulting from PKD is similar to that of chronic renal failure of any etiology and should be directed at slowing the progression and reversing the consequences of renal failure. This includes moderate dietary protein restriction with the use of high biologic value protein (Feline k/d Prescription Diet), fresh water available at all times, the use of phosphate binders, and treatment of anemia as necessary. No diet or regimen of phosphate restriction has been studied as to its effects on cystogenesis or on preservation of renal function or renal histology. There are three main complications of PKD in people: infection, hemorrhage, and hypertension. Renal interstitium or solitary cysts may be infected. In pyelonephritis, the urine may contain white blood cells (WBC),WBC casts, or bacteria. In contrast, infection of a cyst may result in no clinical signs other than fever. The use of nuclear medicine (gallium, indium-labeled WBC, or Technetium-labeled WBC) may be helpful. These techniques are only available at referral institutions, and the diagnosis usually is based on failure to respond to antibiotics and lack of appropriate changes in the urine. Ultrasound may be helpful, but identification of a single infected cyst can be difficult or impossible. Infection must be treated with appropriate antibiotics, but in people it has been shown that not all antibiotics can permeate cyst walls. In people, lipophilic antibiotics seem to have the best cyst penetration. In people, cyst puncture studies have shown therapeutic concentrations in cysts for trimethoprim-sulfamethoxazole, chloramphenicol and ciprofloxacin. Hemorrhage in people usually occurs in kidneys with cysts that are very large or in large kidneys. Hematuria also may occur after trauma or strenuous exercise. Usually, hematuria is self-limiting. In people, hypertension appears to adversely affect prognosis. Large cysts may compress renal vessels. Reduction in cyst size potentially results in decreased systemic blood pressure, improved prognosis, and decreased pain. This can be acheived by cyst aspiration and sclerosis of the cyst wall.

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Sclerosis of renal cysts has been achieved in people by injection of 90% isopropyl alcohol into the cysts. Surgical deroofing of the cyst also may be helpful. Studies in cats demonstrating changes in systemic blood pressure, reduction in pain, improvement in renal function, or increased survival time following cyst decompression and or sclerosis are lacking. The author has safely performed ultrasound-guided cyst sclerosis with 90% isopropyl alcohol, but its effect on survival was questionable.

GENETIC COUNSELLING The Persian cat with PKD should be considered to have an inherited disease. If offspring or relatives are available for study, these animals should be examined by ultrasound. Owners should be informed that this is a heritable disease and that, if the animal is bred, 50 % of the offspring will be affected. It is important to emphasize to an owner that this is a late onset disease, the cat may live many years before demonstrating clinical disease, and breeding of affected cats has great potential to produce PKD-affected offspring.

ELIMINATION OF POLYCYSTIC KIDNEY DISEASE FROM PERSIAN AND PERSIAN RELATED BREEDS The Persian cat with PKD should be considered to have an inherited disease. If offspring or relatives are available for study, these animals should be examined by ultrasound. Owners should be informed that this is a heritable disease and that, if the animal is bred, 50 % of the offspring will be affected. It is important to emphasize to an owner that this is a late onset disease, the cat may live many years before demonstrating clinical disease, and breeding of affected cats has great potential to produce PKD-affected offspring. Our definition for polycystic kidney disease is multiple cysts in both kidneys. We may have to alter this definition for ultrasound because we have recognized mature Persian cats ultrasonographically with a single cyst or multiple cysts in one kidney. These cats may have more cysts but the cysts could be smaller than the resolution ability of the equipment used. We suspect these cats are positive although they do not meet the above definition. We have recognized at least one cat with a single cyst that has produced positive offspring. Re nal cysts in the general cat population are uncommon. A study is now being undertaken to evaluate non-Persian or Persian related cats that are renal healthy and determine the percentage of these cats that have cyst(s) within their kidneys. This may help us determine the significance of a single cyst or cysts in one or two of the kidneys of a Persian or Persian related cat. If a cat is found positive for cysts with ultrasound it’s parents, siblings, and offspring should be checked. The quickest way to eliminate this heritable problem is to neuter or spay these individuals to remove them from the breeding population. If one of these individuals is an extremely valuable cat within the cattery then an alternative to consider is to breed that cat to a PKD negative cat and try to maintain the positive genetic traits that the breeder has

42° Congresso Nazionale SCIVAC

worked so hard for, while eliminating the PKD gene through its offspring. It is important that breeders and veterinarians work together to recognize PKD, and develop PKD free breeding programs. This will improve the genetic health of the Persian and Persian related cat breeds. Research to develop a DNA test or probe is now underway for PKD, but may take 3-5 years to develop. During that period of time the use of ultrasound which is noninvasive and highly accurate may help identify affected cats and reduce the incidence in the Persian population. At present approximately 4000 Persian cats in the United States have been scanned with ultrasound and of these 4000 cats 37% have tested positive for polycystic kidney disease.

Web Sites & Links for Feline ADPKD http://w1.155.telia.com/~u15508574 or http://welcome.to/felinepkd = The Feline PKD Home Page, English site http://w1.155.telia.com/~u15508574/svenska.ind.html = The Feline PKD Home Page, Swedish site http://home.swipnet.se/sequoyahs/pkdbanne.htm = PKD banners for web sites http://cfacats.com/pkd> = Available Scanning Clinics (Maintained by Gene Wright) http://www.indyweb.net/~lucky/Stats.html = PKD Statistics Summary, world wide reports Maintained by Barbara Brush http://www.cfainc.org/health/pkd.html = Article, the CFA Almanac http://209.85.57.248/pkd.htm = the CFA Midwest Region, PKD clinic page http://www.best.com/~lynxpt/ = the Feline CRF Information Center http://www.netcat.org/pkd.html = Article, by Colleen Power http://members.aol.com/simbakui/pkd.html = Article, by Tracy A. Smith http://www.perigee.net/~pojo/pkd.htm = "The PKD-Thing", seen by Joni Young http://w1.155.telia.com/~u15508637/index.sophie.htm = In Loving Memory of Sophie, by Eileene Ault http://www.erinet.com/lebordo/PKD/pkdfaq.html = The Feline PKD FAQ. Answers to Frequently Asked Questions About Polycystic Kidney Disease in Cats Put together by Paul Russell http://www.fen.baynet.de/~ba2156/pkd-klinik.html = A list of clinics organised to scan for PKD in Germany http://w1.155.telia.com/~u15508574/clinics.htm = A list of clinics/hospitals that perform PKD scannings in Sweden http://www.fen.baynet.de/~ba2156/pkd-breedlist.html = Persian PKD Tested Referral Breedlist http://home.telia.no/pkd = Norwegian Feline PKD Home Page http://www.uio.no/~margareh/perserveng.html = Persian Friends, Norway http://disc.server.com/Indices/56803.html = Site for PKD-discussions in Swedish

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Full name of the cat, according to the r egistration papers: Breed:

Registry:

Date of birth:

Age at the examination:

Color:

Sex:

Eye color:

Registration number: Identification number (micro chip):

Name, complete address and phone number of the owner: Date of examination: Left kidney:

Positive

Transducer ( MHz): Negative

Right kidney:

Positive

Number of cysts:

Size of the largest cyst present:

PKD-status for this cat (positive or negative): Comments/recommendations from the veterinarian or radiologist doing the examination: Name, complete address and phone number of the veterinarian or radiologist :

Signature of the veterinarian/radiologist: The certificate form can be ordered through - E-mail to: thiers.sequoyahs@swipnet.se

Negative

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Imaging of canine osteoarthrosis: past, present and future Diagnostica per immagini: ieri, oggi e domani

David Biller DVM, Dipl ACVR - Kansas State University - Manhattan, Kansas, USA

Osteoarthrosis typically is a slowly progressive, degenerative condition that most frequently involves the highly moveable, or diarthrodial joints. The terms degenerative joint disease and osteoarthritis have also been used to described this condition as synonyms. Osteoarthrosis has been estimated to effect as much as 20% of the canine population over one year of age. The etiology of osteoarthrosis can be difficult to determine as it is usually secondary to some type of trauma. This includes an abnormal force on a normal joint or a normal force on an abnormal joint.

PATHOLOGY OF OSTEOARTHROISIS Changes associated with osteoarthrosis typically involve all joint tissues, including the joint capsule, subchondral bone, ligaments, and muscle. The pathologic changes consist essentially of: 1. erosion of portions of the articular cartilage, 2. sclerosis of and various other changes in the bone underlying the damaged cartilage, 3. grinding down of exposed subchondral bone, 4. a formation of bony overgrowths at the margins of the articular cartilages (osteophytes), and in some places, 5. shifting of bone cartilage border, resulting in bumpiness of the articular surface. The alterations in the synovial membrane are ordinarily very slight in comparison with those in the cartilage and bone of the joint ends. It is especially likely to show hypertrophy where it reflects off the bone. Osteophytes are a characteristic abnormality of osteoarthrosis. They develop in areas of the joint that are subject to low stress. They are usually marginal (peripheral) although they may become apparent at other locations within or around the joint. They appear as characteristic bony outgrowths. Marginal osteophytes appear as new bone around the edges of joints. They develop initially in the periarticular regions covered by the synovial membrane. Osteophytes may also occur in the central (central osteophytes) areas of the joints, where remnants of articular cartilage still exist. On radiographs these osteophytes can be misinterpreted as evidence of intraarticular, loose osseous bodies. Periosteal and synovial osteophytes may develop from the periosteum or synovium membrane and termed buttressing. Osteophyte formation can develop at the site of bony attachment of the joint

capsule or adjacent ligament or tendon insertion and have been termed enthesophytes. Joint space narrowing has been a well accepted indicator of articular cartilage degeneration in people. The assessment of joint space narrowing is considered more accurate on weight bearing radiographs. This radiographic change has limited use for evaluating the joint in the dogs.

IMAGING The selection of the appropriate diagnostic imaging study is determined by the anatomic structure to be evaluated, and the type of information sought. With the advent of newer imaging modalities, both anatomic and functional information about the musculoskeletal system can be determined with increasing diagnostic accuracy and anatomic resolution. Survey and contrast radiography, though replaced in some areas by newer imaging modalities, continued to be readily available, cost effective, and accurate tools in the evaluation of joint disease. It is recommended that survey radiographs proceed any special imaging study. The range of imaging technologies available to the veterinary practice and referral centers has increased considerably in recent years. The aim of imaging an affected joint is to document the signs of degenerative change in the joint and also to demonstrate the cause of the abnormal joint mechanics that may have initiated the degenerative changes. Changes that can result in secondary osteoarthrosis include direct damage to cartilage, causes of joint instability, and any conditions subjecting the joint to abnormal directional forces. Trauma, whether overt or chronic and low grade in nature is the main local factor that may induce osteoarthrosis. The net effect of these changes is to hasten the loss of cartilage loss. Characteristics of osteoarthrosis that may be identified by imaging techniques include: 1. degenerative features, including articular cartilage loss/joint space narrowing, subchondral cysts, loose bodies, meniscle degeneration/tears, ligamentous laxity/tears, angular deformity; 2. reparative features, including marginal osteophytes and subchondral sclerosis; and 3. inflammatory features including joint effusion and bursal extension.

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DIAGNOSTIC RADIOLOGY Conventional radiographs are most commonly utilized to establish the diagnosis of osteoarthrosis, to determine the severity and extent of disease, to monitor progression of the disease, and to select appropriate candidates and therapies. Survey radiography has been the main stay of assessment of osteoarthrosis. Plain film radiographic findings of osteoarthrosis include a symmetric joint space narrowing, osteophytosis, subchondral sclerosis and bone cysts. Weaknesses in plain film radiography of osteoarthrosis include heavy reliance of osteophyte formation, and sensitivity to early changes in articular cartilage, and poor discrimination of periarticular structures. Furthermore, soft tissue structures, including synovium, ligaments, and muscular tissue, which are commonly involved with osteoarthrosis are inadequately imaged on plain film radiography. Survey radiography is an excellent method for imaging bone and joints but is a poor method for ima ging specific soft tissue structures. The subchondral bone plate appears radiographically as a thin, radiopaque strip parallel to and adjacent to the joint space. The subchondral bone surfaces and the articular margins should be well defined and clearly distinguishable from the homogenous, trabecular bone pattern of the rest of the epiphysis. The periarticular areas, where ligaments and tendons attach, should have relatively smooth cortical outlines. The joint space appears as a radiolucent area between adjacent subchondral bone plate surfaces. It should be noted that joints are almost always evaluated in a small animal patient that is not weight bearing. Therefore, to evaluate the joint space as a uniform width is very difficult.

ARTHROGRAPHY Arthrography consists of placing aqueous iodinated contrast material intra-articularly and recording the images. This provides information on intra-articular structures. Arthrogram can be used to evaluate articular cartilage, the joint capsule, and joint mice or free osseous or cartilage bodies. Cartilage fissuring and fragmentation such as what occurs with osteochondritis dessicans are best demonstrated with positive contrast arthrography and are identified with contrast material infiltrates beneath the articular cartilage. Synovial proliferation may take the form of thick, irregular synovial outline or a small mass lesion within the joint capsule.

COMPUTED TOMOGRAPHY Computed tomography provides excellent contrast resolution and has the advantage of allowing cross-sectional display of the anatomic region. This eliminates superimposition of tissues allowing the clinicians to better visualize osseous structures which are difficult to assess with comventional radiography. Computed tomography represents a digital reconstruction of the cross-sectional anatomy of an object. It is able to define soft tissue and bony alterations that are undetectable with conventional radiographs because of excellent contrast resolution, cross-sectional display, and its abil-

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ity to measure specific attenuation values. The elimination of superimposed structures thereby decreasing the complexity of the image is a further advantage and the more complex the anatomy of the joint the more likely that it is additional information will be provided by this technique. CT may play and important role in detecting nonuniform joint space narrowing. In osteoarthrosis loose bodies may result from pieces of articular cartilage that become detached and float freely within the joint. These can be demonstrated on CT arthrography. CT in a axial plane can allow detection of very small osteophytes. Subchondral sclerosis is another feature of osteoarthrosis, generally seen after loss of articular cartilage. Subtle new bone formation and bone lysis are better identified on CT scanning images when compared with conventional radiography because of their better physical density discrimination, the ability to manipulate the grey scale of the digital image and the elimination of overlying structures.

MAGNETIC RESONANCE IMAGING Magnetic resonance imaging is capable of directly visualizing all components of the joints simultaneously and can detect a wide variety of joint abnormalities. One of the primary advantages of MR is its ability to acquire images in any desired anatomic plane. Magnetic resonance imaging is characterized by great inherent contrast, excellent spacial resolution, and exquisite anatomic display. MR imaging reliability shows the whole spectrum of osteoarthrosis and its changes much more accurately and earlier in time. MRI requires the patient lie motionless for at least several minutes, and therefore general anesthesia is usually required in veterinary patients. One of the most promising applications of MRI is the early detection of articular cartilage destruction. Its main indications are to visualize cartilage structures and to establish diagnosis. It can demonstrate diffuse cartilage thinning and even small focal cartilage defects can be detected. Thickened trabecula produced by excessive stress and subchondral lesion are also an early finding in osteoarthrosis that can be noted the magnetic resonance imaging. Small subchondral cysts can also be visualized. One of the most characteristic features of osteoarthrosis on imaging studies is joint space narrowing that is nonuniform, due to uneven loss of articular cartilage. MRI is excellent at revealing loss of articular cartilage. Ulceration and cartilage loss can also be demonstrated early and clearly with MRI. MRI allows the detection of small subchondral cysts no visualized on conventional radiographs. In osteoarthrosis loose bodies may result from pieces of articular cartilage that become detached and float freely within the joint. These can be shown on MRI, as there is often an accompanying joint effusion. MRI has proven to be extremely accurate in the diagnosis of meniscle tears. MRI clearly demonstrates ligamentous abnormalities clearly and accurately.

ULTRASOUND Ultrasound is particularly useful in evaluating tendons and bursa around joints. Sonography has been used to evaluate ar-

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ticular cartilage including detection of focal lesions and measurements of cartilage thickness. Due to limitations such as its inability to look beyond a bony margin restricted assessibility and only a small part of the cartilage surface can be visualized.

SKELETAL SCINTIGRAPHY Bone scanning or skeletal scintigraphy is a sensitive method of detecting abnormalities in the bones and joints often before radiographic abnormalities can be seen. It offers high sensitivity for detecting early disease, and the ease of evaluation of the entire skeleton or region, making it an ideal tool for screening cases of obscure or acult lameness. Scintigraphy also offers and easily quantified method for determining the activity of a bone lesion, thus allowing assessment of the significance of radiographically identified lesions of questionable activity, and monitoring of lesions and responsive therapy.

Scintigraphy is very sensitive but nonspecific method for assessing joint lesions. In evaluating a painful joint, comparison with the opposite side is helpful, as variations occur in the relative intensity of uptake in joints compared with that in surrounding bone and soft tissue. Scintigraphy may be a valuable diagnostic tool in the detection of early osteoarthrosis. It can demonstrate increased bone uptake of the radionuclei and can reveal the presence and extent of the disease. In the early stages of osteoarthrosis increased uptake is due to osteophyte production; in advanced stages it is related to subchondral ebernation; however scintrigraphic changes are nonspecific, this imaging modality is of use only as a screening method in diagnosing osteoarthrosis. The two main indications for ra d i o nu clei bone scanning as far as osteoarthrosis is concerned is to detect and evaluate the extent of articular involvement in various forms of joint disease and evaluate bone pain of any cause in the presence of normal radiographs.

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Imaging of the gastrointestinal tract: yesterday, today and tomorrow Cosa c’è di nuovo nella diagnostica per immagini dell’apparato gastroenterico

David Biller DVM, Dipl ACVR - Kansas State University - Manhattan, Kansas, USA

RADIOLOGY OF THE GASTROINTESTINAL TRACT With the advent and use of endoscopy the evaluation of the stomach, proximal small intestine (duodenum) and large intestine with contrast has decreased. The major use of radiographs with and without contrast for evaluation of the gastrointestinal tract is the diagnosis of ileus. Other uses in which radiographs are still useful include gastric position, foreign bodies, gastrointestinal wall integrity, infiltrative wall disease especially with severe or chronic disease because mild or acute disease may cause no changes other than histologic. Knowledge of the normal appearance and anatomy of the GI tract is very important otherwise it is difficult to recognize what is abnormal.

sured while compressed if exposure factors are in question. Failure to decrease technique will result in overexposure. Tranquilization may be helpful to aid in positioning, but is not required. Compression radiography can also be used in combination with contrast procedures of the gastrointestinal or upper and lower urinary tract. Cases for compression should be selected based on the area of interest and the size of the animal. The region of interest must be a compressible area. For example, this technique could not be used on structures underlying the rib cage. Cats and small to medium size dogs are more readily examined. This technique has been used on giant breeds with success. Compression can be used with any position, although lateral recumbency is most common.

POSITIONAL RADIOGRAPHY ABDOMINAL COMPRESSION RADIOGRAPHY Abdominal compression radiography is the use of a radiolucent device to compress an area of interest, thus decreasing subject thickness and allowing anatomic isolation of a structure. This technique provides for evaluation of the size, shape, location, and opacity of a specific organ, without the degree of superimposition of structures seen on survey radiographs. Indications include a suspected abnormality on survey abdominal radiographs, which is inconclusive due to superimposition of structures. Compression radiography of the abdomen provides additional information in cases, which helped with diagnosis, prognosis, and therapeutic options. The equipment necessary is minimal and consists of varying sizes of wooden or plastic (Lucite or Plexiglas) stirring spoons or paddles. Any rigid radiolucent material may be used. The size of the compression surface should be based on the area of interest. Ideally the compression surface should be 1.5 times the area of the target organ. The field size should be collimated to include only the region of interest. This will improve image quality and decrease personnel exposure by decreasing scatter radiation. It is important to recognize that compression of the animal will decrease the subject thickness, therefore exposure factors should be adjusted accordingly. A decrease in kVp by approximately 10% to 15% is usually adequate. The animal can be mea-

Radiography of the gastrointestinal tract is indicated in cases of foreign body ingestion, vomiting, regurgitation, abdominal pain, abdominal distention, weight loss, anorexia, and abnormal abdominal palpation. Standard survey abdominal radiographs include a ventrodorsal and either a left or right lateral recumbent view. The determination of which lateral radiograph is obtained is often personal preference. There are differences in the appearance of various organs, such as the kidneys, spleen, and gastrointestinal tract, between the right and left lateral recumbent radiograph. This varied appearance is particularly noticeable in the gastrointestinal tract, which is dependent on gas to provide contrast for visualization of the mucosal surface. Fluid and gastric contents are extremely mobile and tend to move to the dependent portion of the stomach during postural changes. Gas will rise to the non-dependent portion of the stomach. For example, in right lateral recumbency gas accumulates in the fundus, and in left lateral recumbency redistribution to the pyloric region occurs. Gas within the gastrointestinal tract serves as a negative contrast media. Specifically, the change in positioning of the animal for the opposite lateral abdominal radiographs will allow for the redistribution of gas already present in the stomach, small, and large intestines. The position of gas in the stomach changes in the following manner. If the animal is in left lateral recumbency gas will be present in the py-

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lorus if the stomach is in its normal location. Conversely, if the animal is in right lateral recumbency gas will be present in the fundus. It is important to realize that the amount of gas will have and effect on which portions of the stomach will contain gas. In a severely gas distended stomach, gas may be in all portions of the stomach on both lateral abdominal radiographs. Even in these situations the location of the pylorus can be determined. The right lateral recumbent radiograph is recommended in determining gastric dilatation from gastric dilatation with volvulus. Even in cases in which ileus is detected it is often helpful to gain additional information to help with surgical planning and prognosis. The fluid filled pylorus is an area, which can be misdiagnosed as a cranial abdominal mass when the right lateral recumbent radiograph is taken. When the left lateral abdominal radiograph is obtained the pylorus will be filled with gas. This technique may not always be useful if there is minimal air within the gastrointestinal tract. Air can be introduced via and orogastric tube and is especially useful in disorders of the stomach.

PARTIAL BARIUM ENEMA/PNEUMOCOLON A helpful technique in differentiating distended small intestine from large intestine is a partial barium enema. This technique also helps localize the colon in the abdomen.

PNEUMOGASTROGRAM Indications for the use of contrast in evaluation of the stomach include: 1) Suspicion of luminal or mural gastric masses. 2) Radiolucent gastric foreign bodies. 3) Hematemeisis. 4) Recur rent or non-responsive vomiting. 5) Gastric localization, identification, size, shape, and margination. 6) To evaluate motility. Preparation of the patient include survey radiographs which should always precede contrast studies. Survey radiographs allow evaluation for subsequent adjustment of technical exposure settings for the contrast study. The animal should be fasted 12 -24 hours before radiography. Cleansing enemas should be done the night prior and 2-3 hours before the procedure. Contrast procedures should always be individualized. If a patient has acute abdominal pain or there is a potential for time delay which may make a difference the enema and fasting should be overlooked. Many drugs affect motility and these drugs should be discontinued for an appropriate interval before any contrast study is done. Contrast agents include negative (room air) and positive (barium sulfate suspension which is micropulvarized). If perforation is suspected an organic iodinated solution like Iohexol should be used. Other equipment includes mouth gag and an orogastric tube. Gastrograms are most often used as part of an otherwise standard upper GI series (the small bowel evaluation follows the introduction of a positive contrast media). Technique includes dosage of barium of approximately 5 mls/lb that is administered via a gastric tube. Radiographs

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are routinely taken in right lateral and ventrodorsal but for complete and accurate evaluation of the stomach a DV and left lateral films may be taken. Films are taken immediately to evaluate the complete stomach, before it starts to empty.

ULTRASONOGRAPHY OF THE GASTROINTESTINAL TRACT Over the past 5 years, however, ultrasound has been applied successfully to the diagnosis of a number of gastrointestinal disorders. Fasting the animal prior to ultrasonography also improves the results of ultrasound examination. Complete ultrasonographic examination of the GI tract includes evaluation of wall thickness and layering, evaluation of luminal contents, and quantitation of peristaltic function. In the normal dog, the gastric wall is 3 to 5 mm thick when the stomach is moderately distended and may be slightly thicker when the stomach is not distended. Gastric rugae can be recognized in the fundus and body of the stomach, and their thickness also depends on the degree of gastric distension. The normal thickness of the small and large bowel wall is 2 to 3 mm when measured during bowel relaxation. Ultrasonography allows differentiation of the layers of the GI tract, which alternate in echogenicity. Under optimal conditions, five separate layers can be identified. Examination of the layers of the stomach and bowel may be helpful in determining the severity and location of pathologic processes of the GI tract. The ultrasonographic appearance of the gastrointestinal lumen depends on its contents. In a collapsed state the bowel lumen appears as a hyperechoic core ("mucosal stripe") surrounded by a hypoechoic halo of bowel wall. When fluid is present in the bowel lumen, an anechoic area is present between the walls of the bowel that appears tubular in long axis views, and circular in short axis views. Gas within the GI lumen causes a highly echogenic interface with distal acoustic shadowing.

GASTROINTESTINAL FOREIGN BODIES Ultrasonography has been useful in the identification of a number of different types of gastric and intestinal foreign bodies. The presence of a foreign body can also be suggested by ultrasonographic abnormalities in the surrounding gastrointestinal structures. The identification of bowel distension with fluid or gas may signify obstruction and should prompt a careful search for foreign material that may be causing the obstruction. Linear foreign objects are often associated with bowel wall thickening and plication, which can be identified on ultrasonographic examination.

INTUSSUSCEPTION Ultrasonography has aided in the diagnosis of intussusception of the intestine and stomach. In addition, we have observed cecal inversion in a dog and ileocolic intussusception in a cat, both of which were apparent ultrasonographi-

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cally. The sonographic appearance of an intussusception in a transverse plane has been described as a "target lesion" or as the "multiple concentric ring sign," reflecting the concentric layers of bowel wall within the intussuscepted segment. On longitudinal scan an intussusception has the appearance of a thickened segment of bowel with an excessive number of layers that alternate in echogenicity.

GASTROINTESTINAL NEOPLASIA The most common ultrasonographic features of gastrointestinal neoplasia are thickening of the stomach or bowel wall, loss of its normal layered appearance, and alterations in the contour of the mucosal and/or serosal surfaces. Changes associated with gastrointestinal neoplasia are most often focal but can also be diffuse, especially in the case of canine gastrointestinal lymphoma. Wall thickening is more

often asymmetric, but it may be symmetric. The loss of the normal layered appearance of the gastrointestinal wall reflects infiltration of neoplastic and inflammatory cells, necrosis, edema, and hemorrhage.

CHRONIC HYPERTROPHIC PYLORIC GASTROPATHY Ultrasonographic findings characteristic of chronic hypertrophic pyloric gastropathy (CHPG) include gastric distension and thickening of the pyloric wall. Examination of the pylorus in a transverse plane shows an evenly thick hypoechoic ring (representing the muscularis) surrounding the pyloric lumen. In six dogs with CHPG that were examined ultrasonographically the thickness of the pyloric wall was greater than 9 mm and the thickness of the muscular layer was greater than 4 mm.

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Gengivostomatite cronica del gatto (FCGS): una panoramica aggiornata delle attuali conoscenze Dea Bonello Med Vet, Dipl EVDC - Libero Professionista, Torino

La gengivostomatite cronica felina è una malattia molto comune del gatto, della quale ancora molto poco si sa dal punto di vista eziopatogenetico. Batteri (placca dentale), virus (FCV) e stati di immunodeficienza (FIV, FeLV) sono stati via via considerati agenti causali della malattia (Johnessee, Thompson, Cotter, Knowles, Harbour). Non esiste predilezione di razza o sesso, ed in un lavoro l’età media dei soggetti colpiti risulta essere di 7,1 anni (range da 4 mesi a 17 anni) (White). I sintomi clinici sono anoressia, difficoltà nella prensione o nella masticazione degli alimenti, alitosi, scialorrea e perdita di peso (White). Alla visita clinica si rilevano lesioni eritematose, ulcerative o proliferative delle gengive, degli archi glosso-palatini della lingua, della mucosa vestibolare, del palato duro, del faringe e delle labbra (White, Johnessee). Occasionalmente sono presenti anche parodontite, tartaro, lesioni odontoclastiche erosive (FORL) e linfoadenopatia regionale. Dal punto di vista istopatologico possiamo distinguere due tipi di stomatite cronica erosivo-ulcerativa: il primo caratterizzato da un denso infiltrato di linfociti e plasmacellule nella sottomucosa (Fig. 1) ed un secondo caratterizzato invece da una infiammazione cronica attiva (neutrofili) della mucosa e della sottomucosa (Fig. 2). Questi due quadri istopatologici possono coesistere nello stesso soggetto, e la sintomatologia in atto è spesso direttamente proporzionale alla gravità ed estensione del fatto infiammatorio cronico attivo. La patogenesi della gengivostomatite cronica felina è sconosciuta, e si pensa che possa essere la conseguenza di stati di immunodeficienza associati a fenomeni locali di ipersensibilità (o meglio iperergia) (Williams). Sono state evidenziate alterazioni significative di IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 (p35 &p40), IFN-gamma in campioni di tessuto prelevato dal cavo orale di gatti affetti da FCGS, ma non è stata evidenziata alcuna correlazione tra questi valori e la gravità delle lesioni (Harley). I trattamenti riportati in letteratura includono gli antibiotici, i corticosteroidi, il megestrolo acetato, i sali d’oro, il salicilato di sodio, la clorexidina, la detartrasi e l’estrazione completa o parziale dei denti (Johnessee, Thompson, White). L’utilizzo degli antinfiammatori steroidei per trattare la FCGS è estremamente comune, ma sconsigliato, ed in molti casi la terapia deve essere protratta per tutta la vita dell’ani-

Figura 1 - Flogosi linfoplasmacellulare.

Figura 1 - Flogosi mista.

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male. Questi farmaci purtroppo hanno numerosi effetti collaterali e spesso la loro efficacia decresce nel tempo, cosicchè sempre più alti dosaggi o sempre più brevi periodi di intervallo tra le somministrazioni sono necessari per garantire la remissione della sintomatologia acuta della FCGS. Analogo discorso è possibile fare per la somministrazione prolungata nel tempo di alte dosi di antibiotici, il cui scopo è quello di tenere sotto controllo la carica batterica patogena distribuita sulle mucose del cavo orale e sulla superficie dei denti. Proprio per evitare gli effetti collaterali di queste terapie farmacologiche, e nell’impossibilità di mantenere una corretta igiene orale nei soggetti affetti da FCGS, è stato proposto di estrarre tutti, o in parte (premolari e molari), i denti. Lo scopo di tale intervento, di per sé apparentemente molto aggressivo, è quello di impedire l’accumulo dei germi patogeni, che notoriamente proliferano all’interno dello spessore della placca dentale. I batteri della placca infatti migrando all’interno del solco gengivale, e di qui lungo lo spazio parodontale, si diffondono poi all’osso alveolare e ne provocano il riassorbimento. Per un formulare un corretto planning pre-oper atorio, e per una verifica post-chirurgica dei risultati, è indispensabile quindi l’ausilio della radiologia. Questo trattamento infatti ha dato e continua a dare ottimi risultati solo nel caso in cui i denti vengano estratti correttamente ed anche ogni singolo frammento di radice venga rimosso. Infatti in presenza di radici o frammenti di radici ritenuti nelle ossa mascellari persiste la flogosi cronica attiva, responsabile della sintomatologia acuta. Questo particolare fenomeno sembra essere, almeno apparentemente, in forte contrasto con la teoria che ritiene la placca batterica, depositata in grande quantità sulle corone dei denti, la principale causa della FCGS. Se non ci sono i denti infatti, ed è quindi almeno in parte inibito l’accumulo

42° Congresso Nazionale SCIVAC

di placca nel cavo orale, quale altro agente patogeno sostiene la sintomatologia della FCGS? In questa direzione si stanno oggi sviluppando nuove ricerche, volte ad indagare i diversi fenomeni infiammatori all’interno dell’osso alveolare, che verosimilmente alimentano anche la flogosi attiva a carico delle mucose del cavo orale (Bonello).

Bibliografia Hennet P, (1995) Trattamento delle stomatiti croniche del gatto, Summa 6:63-69. Harbour DA et al. (1991) Isolation of FCV and FHV from domestic cats 1980 to 1989. Vet Rec, Jan 26;128(4):77-80. Knowles JO, Gaskell RM,Gaskell CJ, Harvey CE,Lutz H,(1989) The prevalence of feline calicivirus, feline leukemia virus and antibodies to FIV in cats with chronic stomatitis, Vet Rec 124:336. Harley R et al., (1999) Cytokine mRNA expression in lesions in cats with chronic gingivostomatitis,. Clin diagn Lab Immunol Jul;6(4):471-8. Mallonnee DH, Harvey CE, Venner M,Hammond BF, (1988) Bacteriology of periodontal disease in the cat Arch Oral Biol 33:677-683. Pedersen NC, (1992) Inflammatory oral cavity diseases of the cat, Vet Clin North Am, Small Anim Pract, 22: 1323-1345. Poli G, Cocilovo A, (1996) Microbiologia e immunologia veterinaria, UTET, Torino, 799-825. Sims TJ, Moncla Bj, Page RC,(1990) Serum antibody response to antigens of oral gram-negative bacteria in cats with plasma cell gingivitis-stomatitis, J Dental Res 69:877-882. Ueno H, Hohdatsu T, Muramatsu Y, Koyama H, Morita C, (1996) Does coinfection of Bartonella henselae and FIV induce clinical disorders in cats?, Microbiol Immunol (9)40:617-620. Verstraete FJM, (1998) Update on feline dentistry, Atti del Congresso FECAVA,Bologna, Italy. White SD, Rosychuk RAW, Janik TA,Denerolle P,SchultheissP, (1992) Plasma cell stomatitis-pharyngitis in cats: 40 cases (1973-1991), J Am Vet Med Ass (200) 9:1377-1380.

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Sedazione con medetomidina: nuove possibilità Alessandro Bonioli Med Vet - Libero Professionista, Milano

Lorenzo Novello Med Vet - Libero Professionista, Padova

Marco Scandone Medico Chirurgo, Specialista in Anestesia, Rianimazione, Terapia Antalgica e Terapia Iperbarica

INTRODUZIONE E SCOPO DEL LAVORO La medetomidina è un farmaco alfa-agonista e in medicina veterinaria viene utilizzato prevalentemente come preanestetico e come analgesico sia da solo che in associazione ad altri farmaci. Essa possiede infatti una azione sedativa ed analgesica dose dipendente5,14,15, e permette di ridurre i dosaggi richiesti per l’induzione e il mantenimento dell’anestesia3,5,12. A differenza di altri farmaci della stessa categoria (clonidina, detomidina, xilazina) ha una elevata specificità per i recettori alfa 2 (alfa2/alfa1 ratio 1620)14,17, ed è una molecola racemica costituita da due stereoisomeri, la d-medetomidina (responsabile degli effetti analgesico e sedativo) e la l-medetomidina1,8,13. Come anche gli altri farmaci della stessa categoria non è però priva di effetti collaterali, anche clinicamente importanti, quali bradicardia, ipotensione, riduzione della frequenza respiratoria, cianosi, ipotermia, nausea, vomito, tremori muscolari5. L’effetto sedativo è dovuto alla sua azione a livello di “locus coeruleus” dove numerosi sono i neuroni noradrenergici. La stimolazione degli adrenocettori alfa2 iperpolarizza tali neuroni impedendo il passa ggio dello stimolo attraverso il cervello anteriore ed il sistema limbico 5. L’effetto analgesico è dovuto alla stimolazione dei recettori presenti a vari livelli delle vie del dolore, sia spinali che sopraspinali. Il meccanismo inibitorio coinvolto è sia presinaptico che postsinaptico 5. Gli effetti cardiovascolari sono da ricondurre alla stimolazione di recettori sia centrali che periferici. La stimolazione dei recettori a livello encefalico (tra cui il nucleo del tratto solitario, sede dell’attività autonoma)7 aumenta il tono vagale e diminuisce l’attività simpatica determinando bradicardia e ipotensione. Perifericamente la stimolazione presinaptica inibisce la liberazione di noradrenalina, riducendo il tono simpatico e contribuendo alla bradicardia, mentre l’azione postsinaptica sui recettori delle pareti arteriose e ve-

nose ha effetti vasopressori5. Proprio quest’ultima azione sarebbe responsabile dell’iniziale ipertensione, a cui segue ipotensione, descritta in letteratura5. A livello coronarico esplica un effetto vasocostrittivo13. Sia nel cane che nel gatto la riduzione della frequenza cardiaca indotta dal farmaco è stata stimata essere compresa tra il 20 e il 63%13,16. Gli effetti respiratori sono riconducibili ad una diminuzione della frequenza respiratoria senza significative diminuzioni della PO2.16 La cianosi, che si presenta nel 33% dei cani, si suppone sia dovuta alla lentezza del circolo che provoca una maggiore estrazione di ossigeno da parte dei tessuti con conseguente aumento della desaturazione venosa12. Provoca ipotermia per azione sull’ipotalamo9, e può dare nausea e vomito per azione diretta sul CRTZ (ChemoReceptor Trigger Zone)4. Si è ipotizzato che i tremori muscolari talvolta associati alla sua somministrazione possano essere dovuti ad ambienti rumorosi o ad animali particolarmente eccitabili6. Come preanestetico la medetomidina ha un’ottima azione sedativa, con riduzione dell’ansia e degli effetti neuroendocrini da essa determinati2,5, permettendo una notevole r iduzione dei dosaggi degli anestetici da utilizzare3,5,12. I dosaggi consigliati in letteratura per il cane variano da 10 a 40 mcgr/kg quando utilizzata in associazione ad altri farmaci14, ma possono arrivare fino a 180 mcgr/Kg quando utilizzata da sola5. Le vie di somministrazione normalmente utilizzate sono l’endovenosa e l’intramuscolare, entrambe in bolo, mentre la via sottocutanea è sconsigliata per la difficoltà di prevederne l’assorbimento e quindi l’effetto6. Sono stati anche proposti dei microdosaggi (1-2 mcgr/Kg)10 per via endovenosa in bolo senza che tuttavia la bibliografia ne abbia dimostrato l’efficacia. Durata e intensità degli effetti della medetomidina sono dose dipendenti, e può essere associata a qualsiasi tipo di ipnotico, analgesico e sedativo. Esiste una molecola antagonista, l’Atipamezolo, che ne reversa completamente l’azione.

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Scopo del lavoro e stato valutare se 2mcgr/kg di medetomidina somministrati per via endovenosa in infusione continua in 10 minuti sono in grado, nel cane, di determinare sedazione e diminuzione dell’ansia senza provocare effetti collaterali clinicamente significativi.

MATERIALI E METODI Abbiamo condotto uno studio multicentrico su 26 pazienti arruolati presso 8 strutture veterinarie: 1 Clinica con pronto soccorso 24 ore, 2 Cliniche con prevalente attività specialistica di referenza, 5 ambulatori. Sono rientrati nello studio 26 cani di diverse dimensioni, peso e razza, di età media 6 anni circa con un massimo di 12 anni ed un minimo di 3 mesi, divisi in 14 femmine (53%) di cui 2 sterilizzate, e in 12 maschi (47%) di cui 1 castrato, che dovevano essere sedati per essere sottoposti a procedure diagnostico-terapeutiche o ad anestesia per procedure diagnostiche o chirurgiche di vario tipo. Criterio di eleggibilità è stato l’assenza di controindicazioni assolute all’utilizzo della medetomidina quali bradicardia, ipotensione, insufficienza cardiaca grave scompensata, insufficienza respiratoria, probabile presenza di cibo nello stomaco, ipotermia. Sono rientrati nello studio pazienti che presentavano quali patologie concomitanti o pregresse: persistenza del dotto arterioso, stenosi aortica compensata, piastrinosi, calcificazioni epatiche, malattia di Von Willebrand, sindrome dilatazione-torsione gastrica, enterite linfoplasmacellulare, sindrome mitralica, obesità, soffio mitralico, filariosi cardiaca trattata. I pazienti sono stati classificati in base alla Classificazione di rischio della So cietà Americana di Anestesia (ASA) in ASA 1 (7), ASA 2 (8), ASA 3 (9), ASA 4 (2). Nessun paziente ha ricevuto farmaci nel periodo antecedente l’infusione in oggetto, fatta eccezione per quelli necessari per il controllo delle patologie concomitanti e/o pregresse.In tutti i pazienti è stato posizionato un catetere vascolare di dimensioni adatte in una vena periferica attraverso il quale sono stati somministrati 2mcgr/kg di Medetomidina, diluiti in soluzione glucosata al 5%, in infusione endovenosa costante in 10 minuti, utilizzando pompe infusionali a siringa (IVACP2000 e Vial Becton-Dickinson SE400Bm). In 23 soggetti dopo 15 minuti dall’inizio della stessa si è proceduto all’induzione dell’anestesia, utilizzando protocolli diversi in relazione alle necessità chirurgiche ed alle condizioni cliniche, e se ne è valutata la qualità. Prima della procedura in ogni paziente si sono r egistrati: frequenza cardiaca, frequenza respiratoria, colore delle mucose, tempo di riempimento capillare, volume del polso periferico, temperatura rettale e, quando possibile, pressione sistolica (Nihon Kodhen Lifescope 14, Nihon Kodhen Co., Tokio Japan e Doppler Franceschini con sonda da 8 MHz). La r egistrazione è stata ripetuta dopo 10 e dopo 15 minuti. In tutti i pazienti sono stati valutati e registrati sia il grado di agitazione e reattività prima dell’infusione che il grado di sedazione a 15 minuti dall’inizio dell’infusione. Le valutazioni sono state eseguite da personale medico estraneo allo studio che ha utilizzato due scale visive a punteggio modificate. È stata anche valutata la qualità dell’induzione, se ese-

42° Congresso Nazionale SCIVAC

guita, ed è stata segnalata l’eventuale comparsa di effetti collaterali e/o indesiderati. Bradicardia è stata considerata una frequenza cardiaca inferiore a 60 bpm, ipotermia una temperatura rettale inferiore ai 37°C, nausea il rimescolare della lingua e la scialorrea, vomito i tentativi di vomitare sia produttivi che non produttivi, ipotensione una pressione arteriosa sistolica inferiore a 100 mmHg o una diminuzione superiore al 30% del valore misurato a riposo.

RISULTATI Prima di iniziare l’infusione di medetomidina i pazienti sono stati valutati e quindi classificati, in base alla scala a punteggio modificata per la valutazione dell’agitazione, in tranquilli (1, pari al 4%), leggermente agitati (3, pari al 12%), moderatamente a gitati (10, pari al 38%), agitati (11, pari al 42%), molto agitati (1, pari al 4%). Dopo 15 minuti dall’inizio dell’infusione tutti i pazienti sono stati rivalutati utilizzando la scala a punteggio modificata per la valutazione della sedazione e ne è risultata: sedazione insufficiente in 3 pazienti (punteggio 2) pari al 12%; sedazione accettabile in 23 pazienti pari al 88%, dei quali 5 (19%) svegli (punteggio 3), 9 (34.5%) dormono ma sono reattivi (punteggio 4), 9 (34.5%) dormono e sono poco reattivi (punteggio 5). La frequenza cardiaca ha subito delle diminuzioni percentuali medie, a 10 minuti, del 26% (minima 0%, massima 57%). A 15 minuti la diminuzione media è stata del 29% (minima 2%, massima 60%). Solamente in 3 pazienti dopo 15 minuti (11% del campione) è risultata essere inferiore a 60 bpm. In 9 pazienti non è stato possibile valutare la frequenza respiratoria perché troppo agitati. Negli altri casi le diminuzioni percentuali medie sono state a 10 minuti del 25%(minima 0%, massima 51%) ed a 15 minuti del 31%(minima 0%, massima 47%). Il valore più basso è stato di 12 atti respiratori per minuto, riscontrato in due soggetti dopo 15 minuti. Il colore delle mucose non ha subito delle variazioni significative fatta eccezione per 5 casi nei quali, dopo l’inizio dell’infusione, la congestione iniziale è venuta meno con una normalizzazione del colore. Il tempo di riempimento capillare non ha subito sostanziali alterazioni tranne in 5 casi nei quali comunque il leggero aumento è rimasto nei limiti fisiologici (2”). Anche il volume del polso periferico non ha subito variazioni di rilievo: in 6 pazienti è addirittura migliorato rispetto alle condizioni iniziali, normalizzandosi. Quando è stato possibile misurare la pressione arteriosa sistolica sia prima dell’infusione che dopo 15 minuti dall’inizio della stessa (13 pazienti), abbiamo rilevato delle diminuzioni percentuali medie del 4% (minima 0%, massima 10%), e comunque solo in 1 paziente è scesa al di sotto dei 100 mmHg attestandosi sul valore di 90 mmHg. Negli altri 10 pazienti, in cui si è potuto misurare la pressione arteriosa sistolica solamente 15 minuti dopo l’inizio dell’infusione, non si sono registrati valori inferiori a 100 mm/Hg. Pertanto si è verificata ipotensione arteriosa solamente in 1 paziente su 23 (4%). In 3 pazienti non si è potuta misurare la pressione arteriosa né prima né dopo l’infusione di medetomidi-

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na. La temperatura non ha subito variazioni significative. Un paziente ha presentato nausea sotto forma di scialorrea,ed in due pazienti si sono osservati dei tremori prima dell’induzione dell’anestesia generale, induzione che è stata comunque rapida e dolce.

possa essere stata condizionata dalla eccessiva attività muscolare. In tutti i pazienti la buona azione sedativa ha sicuramente influenzato la rapidità e la dolcezza dell’induzione che sono state ottimali in tutti i casi in cui si sia provveduto ad un’anestesia generale.

DISCUSSIONE

CONCLUSIONI

La bradicardia, riscontrata in 3 pazienti, non è mai stata accompagnata da alterazioni emodinamiche clinicamente significative, come si è potuto dedurre anche dalla stabilità di tutti gli altri parametri da noi considerati. In un solo paziente è stata somministrata Atropina Solfato alla dose di 20mcgr/kg per via endovenosa senza che per altro si determinasse una remissione della sintomatologia. Le maggiori diminuzioni percentuali della frequenza cardiaca si sono riscontrate in pazienti in cui era presente una tachicardia iniziale dovuta ad eccitazione emotiva, e comunque i valori a 15 minuti si sono rivelati sempre (fatta eccezione per i 3 pazienti bradicardici) clinicamente accettabili. Questo fa pensare che tale decremento possa essere riconducile più ad un effetto sedativo ed ansiolitico sul paziente, piuttosto che ad un azione diretta del farmaco sul cronotropismo. La stessa considerazione può essere fatta per la frequenza respiratoria che ha segnato delle diminuzioni sostanziali soprattutto in quei pazienti che si presentavano fortemente eccitati prima dell’inizio dell’infusione. Il valore minimo è stato di 12 atti respiratori al minuto, valore per altro normale in un soggetto che dorme, e in nessun paziente si è riscontrata cianosi. Non si sono avute variazioni significative del volume del polso, del tempo di riempimento capillare, della temperatura e della pressione arteriosa sistolica, la quale solo in un caso è scesa al disotto dei 100 mmHg, attestandosi a 90 mmHg. In questo paziente l’ipotensione, non associata a bradicardia, si è risolta con la somministrazione di 40 ml/kg di soluzione cristalloide. Solamente un paziente ha presentato nausea, ma abbiamo poi saputo dal proprietario che prima della procedura era riuscito ad ingerire una piccolissima quantità di cibo e quindi lo stomaco non era vuoto. I nostri rilievi sembrano pertanto essere in accordo con quanto descritto in letteratura, e cioè che si assiste ad una diminuzione degli effetti collaterali indotti dal farmaco al diminuire dei dosaggi utilizzati. Inoltre la scarsità di effetti collaterali si può probabilmente attribuire alla particolare modalità di somministrazione che permette un controllo riflesso da parte dell’organismo delle eventuali modificazioni in atto. In due casi si sono manifestati tremori muscolari all’atto dell’induzione con pro p o fo l , che potrebbero anche essere imputabili all’azione dell’ipnotico. Di notevole interesse è stata la valutazione del grado di sedazione che si è dimostrato buono in 23 soggetti, senza che fosse evidente una consequenzialità tra situazione emotiva pre–trattamento e risposta alla medetomidina. Dei tre soggetti che hanno dimostrato sedazione insufficiente due erano particolarmente eccitati al momento della visita, per cui si può pensare che la farmacocinetica del farmaco

L’infusione endovenosa costante di 2 mcgr/kg di medetomidina in 10 minuti si è rivelata efficace nel garantire sedazione e diminuzione dell’ansia, senza per altro provocare bradicardia, ipotensione, ipotermia, nausea e vomito, reazioni indesiderate di comune riscontro quando si utilizzino farmaci alfa-2 agonisti. Alla luce dei risultati ottenuti, la metodica di somministrazione e il dosaggio da noi utilizzati sembrano garantire sicurezza anche in presenza di gravi patologie pregresse o concomitanti, patologie che di solito rendono la sedazione del paziente non esente da rischi. Riteniamo pertanto che la metodica vada ulteriormente sviluppata, possedendo a nostro avviso notevoli potenzialità applicative.

Ringraziamenti Gli autori ringraziano le dottoresse Maurella, FerreroMerlino e Vasconi per la collaborazione tecnica e la signorina Federica Ferro per la ricerca biblio grafica.

Parole chiave Cane, CONSTANT RATE INFUSION, medetomidina, SEDAZIONE.

Bibliografia 1.

4. 5.

7. 8.

ANSAH OB, et al,:Comparision of three doses of dexmedetomidine with medetomidine in cats following intramuscular administration. J. Vet. Pharm. Therap. 1998 21:380-7. BENSON GJ, et al,: Perioperative stress response in the dog: effect of pre-emptive administration of Medetomidine. Vet. Surg. 2000 29:85-91. BUFALARI A,et al,:Evaluation of selected cardiopulmonary and cerebral responses during Medetomidine, Propofol, and Halothane anesthesia for laparoscopy in dogs. Am. J. Vet. Res. 1997 58:1443-50. COLBY ED, et al,: Emetic action of xilazine on the chemoreceptor trigger zone for vomiting in cats. J. Vet. Pharm. Therap. 1981 4:93-6. CULLEN LK: Medetomidine sedation in dogs and cats: a review of its pharm a c o l ogy, a n t agonism an dose. Br. Vet. J. 1996 152:519-535. ENGLAND GCW & CLARKE KW,: The effect of route of administration upon the efficiency of Medetomidine. J. Ass. Vet. Anesth. 1989 16:32-4. HAYASHI Y & MAZE M.,: Alpha2 adrenoceptor agonist and anesthesia. Br. J. Anesth. 1993 71:108-18. KUUSELA E, et al,: Clinical effects and pharmacokinetics of Medetomodine and its anantiomers in dogs. J. Vet. Pharmacol. Therap. 2000 23:15-20. MACDONALD E, et al.,: Behavioural and neurochemical effects of Medetomidine, a novel veterinary sedative. Eu. J. Pharmac. 1988; 158:119-27.

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10. 11.

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PYPENDOP BH, et al,: Hemodynamic ef fects of Medetomidine in the dog: a dose titration study. Vet. Surg. 1998 27:612-22. REDONDO JI, et al,: Romifidine, Medetomidine or Xilazine Before Propofol-Halothane-N2O anesthesia in dogs. Can. J. Vet. Res. 1999 63:31-36. SAP R. & HELLEBREKERS LJ.:Medetomidine/Propofol anesthesia for gastroduodenal endoscopy in dog. J. Vet. Anesth. 1993 20:100-2. SCHMERLING WI; et al,: The effect of the stereoisomers of the alpha2-adrenergic agonist Medetomidineon systemic and coroary hemodynamics in conscious dogs. Anesthesiology 1991 75, 499-511 TRANQULLI WJ,BENSON JG:Advantage and guidelines for using

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Alpha-2 agonist as anesthetic adjiuvants. Vet. Clin. North Am. Small Anim. Pract. 1992 22:289-93. TYNER LC, et al,: Multicentric clinical comparison of sedative and analgesic effects of Medetomidine and Xilazine in dog. JAVMA 1997 211:1413-1417. VENUGOPALAN CS, et al,:Cardiopulmonary effects of Medetomidine in heathworm-infected and non-infected dogs. Am. J. Vet. Res. 1994; 55:1148-52. VIRTANEN R, et al.: Characterization of the selectivity, specificity and potency of Medetomidine as an alpha 2 –adrenoceptor agonist. Eur. J. Pharm. 1988 150, 9-14.

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Fans and rest of the world for the treatment of osteoarthritis FANS contro resto del mondo oppure FANS e resto del mondo (nutraceutici, condroprotettori ed altro)

Dawn Boothe DVM, MS, PhD, Dipl ACVIM, Dipl ACVCP - Texas A&M University Dept of Physiology and Pharmacology College Station, Texas, USA

INTRODUCTION: NSAID MECHANISM OF ACTION Nonsteroidal antinflammatory drugs (NSAIDs) are generally defined as drugs which target inflammation but are non-steroidal in structure. As a class, nonsteroidal antiinflammatory drugs are defined by their mechanism of action, inhibition of cycloxygenase. Recent advancements in the understanding of the relationship between NSAID pharmacologic effects and differences in their primary target, cyclooxygenase, has offered promise in the reduction of adverse side effects to these drugs. The discussion surrounding this promise requires an appreciation of the normal and abnormal actions of the prostaglandin end products, the ultimate target of NSAIDs, the specific mechanism of action of the NSAIDs and a focus on the cyclooxigenase enzymes. Cycloxygeanses catalyzes the metabolism of arachidonic acid, a fatty acid released from cell membranes by the action of phospholipase on cell membrane phospholipids. Stimuli such as chemical, mechanical or immune-mediated damage activate phospholipases and the subsequent release of the fatty acid. Conversion of arachidonic acid to prostaglandin endproducts occurs in two steps, at two different sites on the cyclooxygenase enzyme. Arachidonic acid is cyclized and oxidized to the endoperoxide PGG2 at the cyclooxygenase site of the enzyme; this product is then reduced to a second endoperoxide, PGH2 at the peroxidase site of the enzyme. Cycloxygenases are located in virtually all cells except mature red blood cells and PGs are thus ubiquitous throughout the body. Subsequent formation of prostaglandin endproducts from PGH2 depends on the presence of other enzymes. Prostaglandin endproducts include prostaglandin-like products thromboxane (TXA2), prostacycline (PGI2) and PGs of the E and F series. The role of PGs is complex but they often balance one another. Their pharmacologic effects are equally complex, and many of their actions result in relaxation (generally PGI and PGE) or contraction of smooth or vascular smooth muscle. Additionally, PGI2 inhibits and TXA2 stimulates platelet aggregation. PGs contribute to all five cardinal signs of inflammation by causing vasodilation and modulating the effects of other in-

flamamtory mediators. Among the prostglandins, PGE 2 is particularly effective as an inflammagen. PGs are formed in situ and are characterized by half-lives that are short (seconds); thus persistance of their effects requires persistent formation. Their role in the body could be summarized by describing them as protective, providing for normal homeostatic mecahnisms in most tissues. Thus, in all tissues, they are responsible for hemostasis; in the kidneys, for maintenance of renal blood flow in the presence of adverse conditions, in the gastrotintestinal tract, they minimize the adverse effects of hydrochyloric and bile acids, and they mediate all of the cardinal signs of inflammation. In the gastrointestinal tract, protective mechanisms are mediated by prostaglandin of the E series, and include inhibition of hydrochloric acid secretion, and increased bicarbonate and mucus secretion, epithelialization, and mucosal blood flow. Although PGs appear to have a limited role in renal homeostasis under basal conditions, their actions are critical in the presence of hypovolemia or hypotension. PGs of the E series (PGE 2) production in the glomeruli increases during these states. Antagonism of vasoconstrictive mediators such as norepinephrine, angiotensin II and vasopression results in vasodilation and redistribution of renal blood flow from the cortex to the medulla. Direct effects on the rental tubule stimulates sodium and water excretion and secretion of renin from the macula densa ((Hart 1987, Rose 1994). The result of these effects is to maintain renal blood flow and urine formation. In contrast to gastrointestinal effeccts, renoprotective effects of PGs become important only during states of hypotension. Nonsteroidal antiinflammatory drugs act to block the first step of prostaglandin synthesis by binding to and inhibiting cyclooxygenase conversion of arachidonic acid to PGG2 (Robinson, 1989). This action is both dose and drug dependent. The precise site at which cyclo-oxygenase is inhibited is not known. The planar form which characterizes these drugs is thought to facilitate NSAID binding to cyclooxygenase (Boynton et al. 1988; Higgins, 1985); the NSAID may physically block substrate binding or change conformation such that binding can not occur. Several investigators have shown that some drugs (eg, phenylbutazone and flunixin meglumine) also reduce formation of prostaglandin E2 in in-

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flammatory exudate at therapeutic doses (Lees et al. 1986). The major therapeutic and toxic effects of NSAIDs has been correlated extensively to their ability to inhibit prostaglandin synthesis (Robinson, 1989). Their potency as anti-inflammatory agents relates to their relative potency of inhibition of prostaglandin synthesis (Robinson, 1989) which in turn reflects their interaction with cycloxygenase. In the early 1990's, cyclooxygenase was recognized to reflect a family of enzymes. At least two forms of cycloxygenase were recognized. An inducible form was discovered following the stimulation of mononuclear phagocytic cells (mouse macrophage and human monocytes) by bacterial lipopolysaacchardes (Masferrer 1990, Fu 1990). COX-2 was initially discovered because of the negative effects of glucocorticoids (eg, dexamethasone) on COX-2 transcription (Crofford 1997). The inducible isoform of the enzyme was named cyclooxygenase 2 to disinguish it from cyclooxygenase I,a constituative form of the enzyme. The protein structure and enzymatic function of the two enzymes are very similar. Both are integral membrane proteins, but the active site of each sits within the membrane so that it is easily accessed by fatty acid substrates (eg, arachidonic acid). The active site of the enzyme is a channel; the channel appears to be more flexible for COX 2 compared to COX 1, suggesting a wider variety of substrates for this isoform (Crofford 1997). COX 1 is located in the endoplasmic reticulum, while COX 2 is localized to the endoplasmic reticulum and nuclear membrane. The enzymes may use different pools of substrate mobilized in response to different cellular stimuli (Crofford 1997). The measurement of thromboxane B2 synthesis from platelets, which constitutively express COX 1, following blood coagulation is a specific test for COX-1 activity. In response to endogenous thrombin formation (ie, clot formation) platelet COX-1 is maximally stimulated to produce thromboxane A2, which is converted to thromboxane B2 (Cryer 1998). The measurement of prostaglandin E2 production from monocytes and macrophages in whole blood following stimulation with lipopolysaccharide is a specific test for COX-2 activity. Twenty-four hours after incubation of whole blood with lipopolysaccharide, 95% to 99% of COX activity is COX-2 and prostaglandin E2 measured 24 hours after lipopolysaccharide stimulation is considered to almost exclusively reflect COX-2 activity. Does COX-1 versus COX-2 Selectivity Provide a Rationale Basis for NSAID Selection? This question might be answered best by providing evidence of selectivity regarding mechanisms of action and toxicity. Premise 1. Homeostatic PGs are derived primarily from COX-1. Support: Virtually all tissues express COX-1 under basal conditions (Crofford 1997). Subsequent studies revealed constitutive PGs mediated by COX 1 to be largely responsible for basal homeostatic mechanisms, although exceptions exist. Both isoforms of the enzyme are expressed constitutively in the central nervous system and, depending on the species, in selected areas of the kidney. In the gastrointestinal tract, PGE2 mediated by COX-1 is present in all areas of the gastrointestinal tract,and in selected areas, is expressed over 2 fold compared to COX-2 (Kargman 1996,

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Mizuno1997). In contrast, PGE mediated by COX-2 is induced in the presence of gastrointestinal ulceration or erosions. Indeed, COX-2 appears to be the isoform mediating repair of damaged tissues with expression being greatest within the first 10 days of damage. COX-2 appears to be responsible for homeostatic mechanisms in selected organs. It is constitutively expressed in the brain and the kidneys. In the brain, expression occurs in selected areas of the spinal cord, where it may be a key mediator of transmission of pain. Expression also increases in response to selected neuronal activity and after seizure activity. Species differences occur in COX-2 expression in the kidney, which occurs in the renal vasculature of the glomeruli, and in the smooth muscle and endothelium of the interlobular vessels. In dogs, COX-2 is consitutively expressed thick ascending loop of Henle and in the macula densa. COX-2 expression is increased by hypovolemia and by angiotensin-converting enzyme inhibitors such as captopril. In the reproductive tract, functions of COX-2 mediated PGs vary, but studies support that absence of COX-2 activity correlates with infertility in females. Conclusion: Although COX-1 PGs largely are responsible for homeostatic actions. COX-2 PGs have important roles in selected tissues (eg, kidney) and an important role in healing. The perioperative use of COX-2 selective drugs should be done cautiously. Premise 2. Inflammatory PGs are derived primarily from COX-2. In contrast to constitutive PGs, with some exceptions (eg, brain, kidney and reproductive tract) inducible PGs are largely limited to inflammatory responses and are expressed by endothelial and smooth muscle cells, chondrocytes, and inflammatory cells such as macrophages/monocytes, fibroblasts and synovial cells. In addition to bacterial lipopolysaccharide, COX 2 is expressed in response to cytokines (eg, selected interleukins, tumor necrosis factor) and growth factors (eg, platelet-derived, and epidermal). Selected anti-inflammatory mediators may decrease or suppress COX 2 expression (Smith 1998; Masferrer 1996). PGE2 responsible for inflammation is formed primarily by the actions of COX 2 (Seibert 1994). Studies have demonstrated that COX 2 expression increases in inflammatory joint diseases, particularly in synovial endothelial cells, whereas it is essentially non-detectable in normal, non-inflamed tissues. Additionally, studies with selective COX1 or COX 2 inhibitors support COX 2 as the primary enzyme producing inflammation-inducing PGs (Smith 1998). Although the preponderance of evidence supports the roll of COX-2 in mediating inflammation, some evidence exists that COX-2 also decreases the inflamamtory response. Interestingly, COX 2 expression is upregulated in selected carcinomas. Increased phenotypic changes in COX 2 has been interpreted in rat intestinal epithelial cells as an increase in tumorigenic potential. Increased COX-2 expression may be a common mechanism by which cellular phenotype is changed allowing unregulated proliferation. Although COX-2 derived PGs clearly play the dominant role in the generation of inflammation, COX-1 PGs have been found to be upregulated in a number of inflammatory models or syndromes, suggesting that inhibition of COX-1 may be necessary in some inflammatory conditions. Note that NSAIDs are characterized by anti-inflammatory actions

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other than those mediated by inhibition of PGs (eg, direct inhibition of neutrophil adhesion, uncoupling of oxidative phosphorylation, etc). Finally, although the focus of this discussion is the role of PGs in inflammation, many other mediators are responsible for an inflammatory response. Conclusion: Selective inhibition of COX-2 should only minimally (at most) decrease the efficacy of NSAIDs. Premise 3. The mechanism of NSAID toxicity is related to inhibition of COX-1 mediated PGS. The NSAIDs are recognized as a class of drugs to be potentially toxic. Among the toxicities, gastrointestinal ulceration is the most common in humans and animals. Although the mechanism of NSAID-induced gastrointestinal toxicity is not clear, NSAIDs as a class inhibit epithelialization and angiogenesis, two actions mediated by COX-1 PGE2 in the gastrointestinal tract (Levi 1990, Hudson 1995). Dogs have been described as being “exquisitively sensitive” to the gastrointestinal effects of NSAIDs and indeed appear to be more sensitive than human beings. A number of studies have attempted to document the clinical relevance of selective cyclooxygenase inhibition to the severity of NSAID induced gastrointestinal toxicity. Using a human whole blood assay, and a modified human whole blood assay, the effect of 40 NSAIDs on COX-1 and COX-2 concentrations was measured (Warner 1999). Additionally, the effects of specific COX-2 drugs (eg, celecoxib and rofecoxib) were studied. Based on this study, NSAIDs were classified into four groups, depending on the relative potencies (concentration necessary to inhibit 50% or 80% of the respective COX enzyme). Those groups that included NSAIDs relevant to veterinary medicine included: 1. Compounds that fully inhibited both COX 1 and COX 2 (ie, exhibited < 5 fold selectivity for COX 2) included (but were not limited to) in order of least preference for COX 2, fenop ro fe n , ampyrone, ibuprofen, n ap roxen, aspirin, indomethacin, ketoprofen, flurbiprofen and ketorolac. Others in this category (not ranked) include carprofen, diclofenac, mefenamic acid, naproxen, and sulindac sulphide. 2. Compounds that inhibited both COX 1 and COX 2 but with preferential activity (5 to 50 fold preference) for COX 2, included celexocib, etodolac, meloxicam and mimesulfide. However, the amount of drug necessary to inhibit 80% of the enzyme was often much greater than the amount necessary to inhibit 50% of the enzymes. Further, the amount of drug necessary to inhibit 80% of the enzyme often overlapped with concentrations that inhibited COX-1. Thus, tthese compounds have the potential, however, to fully inhibit COX-1 at concentrations that might be considered therapeutic. The third group included compounds (rofecoxib, and experimental drugs) that inhibited COX-2 with only weak activity against COX 1 (greater than 50 fold preference); one of these compounds (rofeoxcib) has recently been approved for use in human medicine as a COX 2 selective drug. The fourth group contained drugs that were weak inhibitors of both COX 1 and COX 2 and included 5-aminosalicylic acid, sodium salicylate, sulfasalazine, toamoxifen, ticlopidine and sulindac. A subsequent study measured COX-1 and COX-2 activity in whole blood samples collected from human volunteers receiving selected NSIADs. Results revealed marked vari-

ability in the inhibitory potency and selectivity of NSAIDs for COX-1 and COX-2 activity . Selected NSAIDs (eg, flurbiprofen, ibuprofen, ketoprofen, naproxen, aspirin) were inhibitory to both COX-1 and COX-2 with poor selectivity for COX-2; others were inhibitory to both COX-1 and COX-2, but with a 5 to 50 fold preference towards COX-2 (todolac, meloxicam, celexocib); or a greater than 50 fold preference for COX-2 (rofecoxib), and finally; some that had minimal effect on either COX-1 or COX-2 (5-aminoslicylic acid, paracemtamol, sulfasalazine). The inhibitory effects of NSAIDs on gastric prostaglandin E2 synthesis correlated with COX-1 inhibitory potency in blood and with COX-1 selectivity but not with COX-2 inhibitory potency. However, even those NSAIDs that appeared to be COX-2 selective had sufficient COX-1 activity to cause potent inhibitory effects on gastric prostaglandin E2 synthesis at concentrations achieved in vivo. Clearly, the risk of gastorintestinal toxicity exists even with relatively COX 2 selective drugs. The importance of species differences in interpreting these studies is exemplified by a similar study implemented by Ricketts and co-workers (1998) using using canine platelets and endotoxin – stimulated macrophage-like cells. They also studied the effects of various NSAIDs, basing comparison on a COX1:COX2 ratios. The ratios were:; carprofen: 129 for the racemic mixture, 181 for the S isomer and >4.19 for the R isomer; nimesulide: 38; meclofenamic acid: 15.4; tolfenamic acid: 15.0. meloxicam: 2.90; phenylbutazone > 2.64; flunixin meglumine: 0.635; etodolacc 0.517; aspirin: < 0.343; ketoprofen: 0.232. These numbers are more aligned with what appears to occur clinically, that is, carprofen and meloxicam as safer drugs compared to aspirin, ketoprofen and meleoxicam. However, this study also suggests that etodolac is less safe than phenylbutazone and even flunixin meglumine, a finding that contrasts with clinical use of these drugs. Despite this incongruency, these two studies, in two different species, offer guidance regarding the selection of NSAIDs to be used in veterinary medicine. Those that have a more favorable COX1:COX2 ratio do appear to be clinically safer in regards to minimizing the risk of NSAID-induced gastrointestinal ulceration. However, as pointed out by comparison of IC50 and IC80 concentrations, selectivity is often lost at higher concentrations, which are likely to occur at therapeutic doses. These two studies also point out the risks of using data that is collected using tissues from species other than the targeted species. Whereas the human data suggests that carprofen is non-selective in humans, the data in dogs notes just the opposite. Clearly these studies indicate that, although selectivity can be used as a basis for NSAID selection, information regarding COX-2 selectivity in one species can not be used as a basis for selectivity in another species. Conclusion: Although COX-1 mediated actions appear to be responsible for most NSAID GI toxicity, selectivity is lost at higher doses and selectivity apparently can not be extrapolated among species. Tests of selectivity are useful only as screening devices. Finally, clincians need to be aware of other mechanisms of NSAID toxicity not related to PGs (eg, hepatotoxicity). Evidence of Selective Safety of Currently Available Veterinary COX-1 Protective Drugs

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Currently, three veterinary drugs considered to be COX1 protective (preferred to COX-2 selective since none have been proven to be solely COX-2 selective) are available in the North America: carprofen (US, CA), etodolac (US) and meloxicam (CA). Two sources of data are available for consideration regarding the safety of these drugs. Pre-clinical data generated to support safety during the approval process is available on package inserts. Comparison of these data might offer some discrimination among the products regarding relative safety, although the data reflects overdosing (a situation that is not commonly clinically relevant). For carprofen, dogs received close to 6 times the recommended dose for a year with no evidence (gross or histologic) of GI damage; only mild gross GI damage was evident following two weeks of administration at 10 times the recommended dose. For Etodocal ÂŽ, at 5.3 times the reocmmended dose, 6 of 8 animals died with lesions in the gastrointestinal tract from 3 weeks to 9 months after therapy. For meloxicam, at 4 times the dose, no lesions were evident at 4 weeks into therapy. A post-market clinical trial offers insight into safety at doses that more appropriately reflect those likely to be used. Reimer and co worksers reported in JVIN (13:742, 1999) that carprofen and etodolac drugs, when compared to a placebo and buffered aspirin (each drug dosed at the recom mended label dose; aspriin at 15.6 mg/kg), had a score (based on endoscopic lesions) of 5 compared to a score of 25 for the placebo and aspirin groups when dosed for 28 days. Clearly, this data supports the relative safety of carprofen and etodolac compared to buffered aspirin, suggesting that these are the preferred NSAID products.

MEDICAL MANAGEMENT OF OSTEOARTHRITIS Cartilage physiology and pathophysiology. Normal cartilage is avascular and tightly adhered to cortical bone. A load-bearing and gliding surface of the joint is formed such that a frictionless surface occurs throughout the range of motion of the joint. The fibrous capsule of the joint contains a layer of synovial cells which are very vascular and serve as a selective membrane precluding passage of molecules greater than 12,000 MW. Synovial fluid produced by the cells lubricates and nourishes cartilage. Hyaline cartilage contains a small number of chondrocytes which synthesize the matrix in which they are embedded. The matrix is comprised of collagen fibers interspersed in a well structure manner with proteoglycan (PGN) aggregates of varying molecular weights (MW). Proteoglycans are comprised of glycosaminoglycans encircling a core protein. The PGN complex in turn is bound (by a link protein) to hyaluronic acid. Chondroitin sulfate is the principle PGN of mature cartilage with other sulfates (keratin, dermaten, etc) making the remainder. Chondroitin sulfates are glycosaminoglycans composed of alternating sulfated recidues of a glucuronic acid and a galactosamine. Sources of chondroitin sulfate for commercial purposes include borine trachea, nasal septum and shark cartilage. Proteoglycans are large molecules which trap water, thus maintaining the gel-like consistency of cartilage and act as an elastic shock absorber. Chondro-

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cytes are very metabolically active, constantly breaking down and resynthesizing PGN and collagen. The substrates and energy for these activities are transported to, and waste material from the cartilage by a synovial "pump" mechanism. The initial insult leading to cartilage degeneration may vary (ie, injury, congenital malformation, chronic overload, age), but the sequence of events is similar. The changes occur well before clinical (including radiographic signs) are evident. The initial lesion in osteoarthritis occurs in cartilage. Chondromalacia (softening of the cartilage) occurs early in the course of disease. Collagen turnover markedly increases by the chondrocytes; reparation may not yield the appropriate (Type II) collagen. Ultimately, collagen loss may predominate. Species differences in the r epair of collagen are likely to exist. Proteoglycans are also lost as DJD progresses. Initially, PGN synthesis is markedly increased, but the normal ratios of high MW vs low MW PGNs may not be maintained. Eventually, PGN synthesis markedly decreases. Hyaluronic acid concentrations also decrease. The loss of cartilage matrix is mediated, in part, by proteolytic enzymes such as metalloproteases, including collagenases, stromelysin, and aggrecanase, and lysosomal enzymes released (stimulated by interleukin-I or TNF?) by synovial cells or chondrocytes. Interleukins a and 6, tumor necrosis factor and nitric oxide also act as cellular or molecular mediators. Mediators (eicosanoids, interleukin 1 and tumor necrosis factor) act to up-regulate catabolic enzymes of destruction while downregulating mediators which inhibit catabolic actions. The catabolic process of cartilage degradation worsens as these enzymes are released. Chondrocyte death may occur early in the process of DJD. Synovial cells phagocytize the products of degradation and initiate an (chemical) inflammatory process. Collagen is exposed; fissures develop in the cartilage. Local tissue degradation increases, leukocytes are activated, eventually leading to a viscous cycle of degradation and inflammation. As cartilage continues to bear weight, mechanical destruction and physiological changes continue. The damaged cartilage can not bear weight appropriately and subchondral bone is exposed to forces that normally would be dampened. Subchondral sclerosis occurs and apposing articular surfaces become eburnated. Cartilage homeostasis is interrupted, limiting access to fluid containing nutrients. Fluid released into the synovial joint may not be efficiently absorbed. In addition, mediators of inflammation are released by both chondrocytes and synovial cells. The joint becomes painful as a result. Microfractures and fissures allow synovial fluid to penetrate into the bone, with resulting subchondral cyst formation. The damaged cartilage attempts to repair the damage as it occurs by synthesizing new proteoglycan and collagen. Osteoarthritis probably occurs when the catabolic process overwhelms the repair process. The goal of drug therapy for DJD should be: 1. to control pain; 2. to increase mobility; 3. to prevent continued degradation of the joint; and 4. to provide support to reparative processes. In addition to drug therapy, dietary management (ie, weight control) and exercise control should be implemented and surgical options should be considered when appropriate. Disease Modifying Agents. A number of compounds are able to modify the progression of osteoarthritis, most com-

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monly due to support effects in the cartilage. These products help achieve the goals of preventing furher degradation and providing support for the reparative cartilage.Recent efforts in the treatment of osteoarthritis have focused on drugs which favorably shift the balance between degradation and synthesis of cartilage matrix. Polysulfated glycosaminoglycans. Polysulfated glycoaminoglycan (PSGAG; Adequan; Arteparon) is a polymeric chain of repeating units of hexosamine and hexuronic acid. Considered a hypersulfated compound, approximately 14% of the drug is sulfated. It is extracted and purified from bovine tracheal tissues. Normal cartilage matrix is composed of proteoglycan complexes, collagen and water. Side chains of glycosaminoglycans (keratin and chondroitin) are attached to the core protein of the proteoglycan molecule by a strand of hyaluronate. Water trapped in between these complexes accounts for the resiliency of cartilage. Polysulfated glycosaminoglycans closely mimic the proteoglycan complexes found in normal articular cartilage. Polysulfated glycoaminoglycans appear to be chondroprotective in both in vitro and in vivo models. In vivo models have included chemically and traumatically induced cartilage damage. Cartilage degradation is retarded in the presence of PSGAG. Although the mechanisms of these protective actions are not known, chondrocyte proliferation and matrix biosynthesis appear to be important. Collagen, proteoglycan and hyaluronic acid synthesis increases. In addition, proteolytic enzymes such as collagenase, leukocyte elastase, proteases and lysozomes are inhibited,although these actions are likely to be complex. Complement activity is also inhibited; the degree of inhibition appears to be related to the sulfate load of the chondroitin sulfate matrix. Polysulfated glycoaminoglycans appear to have no effect on the ability of interleukin 1 to stimulate metalloproteinase activity in cartilage. PSGAGs appear to prvent or decrease the development of hip dysplasia in dogs predisposed to the defect. Yet, results of clinical studies that document the favorable response to the use of PSGAG remain controversial. Deposition of PSGAG in normal and damaged cartilage has been demonstrated after parenteral administration in concentrations high enough to inhibit proteinase activity. Drug that is not retained in cartilage is excreted primarily by the kidneys with minimal degradation of the parent compound. Toxicity is limited in all species studied. In dogs, the LD50 is 1000 mg/kg. Heparin and PSGAG are chemically similar. Adverse effects related to the anticoagulant activity of PSGAG have been suggested. One study found coagulation times to be prolonged following adminsitration of high doses. The effect appears to last about 7 hours. This suggests that PSGAGs not be administered at the time surrounding a surgical procedure. Heparin-associated thrombocytopenia, a presumed immunologically-mediated decrease in circulating platelet numbers, has been reported in human patients receiving PSGAG. Adequan (5 mg/kg IM twice weekly) has recently been approved for use in dogs for the treatment of osteoarthritis. However, the drug might be considered in any situation in which the joint has been or will be (for example, elective surgery) injured. This includes trauma, elective surgical procedures, and arthritis associated with immune-mediated or infectious conditions. However, in horese, conditions with osteochondral defects repaired with more fibrous

than hyaline tissue, suggesting that PSGAG may not be indicated for these types of damages. PSGAGs should be considered in conjunction with NSAIDs both for their chondroprotective effects as well as with the intent to potentially discontinue the NSAID. Disease modifying agents including PSGAGs or its precursors (see Nutraceuticals, below) might also be considered as preventative therapy in animals that are likely to develop osteoarthritis for whatever reasons, including conformation problems. Use of these drugs prior to the development of clinical signs of osteoarthritis is likely to offset the time to the need of NSAIDs. In patients with osteoarthritis, the time to clinical response is likely to be directly related to the severity of disease. Treatment that is begun before the joint is markedly damaged is more likely to be successful. Care might be indicated in patients receiving aspirin and PSGAGs because of the potential for increased bleeding times. Nutraceutical Disease Modifying Agents. These products represent the newest therapy for treatment of DJD in dogs and cats. Most compounds (those which are likely to modify disease) contain glucosamine and chondroitin sulfates (extracted or synthesized) in various complex forms.These products undero no approval process. A large number of oral disease modifying agents are currently available for treatment of osteroarthritis. Note that no mechanism exist to assure quality control of the manufacture of these products. However, several products have been used by many veterinarians or pet owners with some evidence (subjective) of benefit. Examples include the mussel exract that may contain mucopolysaccharides/mixed glycosaminoglycans/chelating metals/etc found in Glyco-flex (components less certain) or synthesized glucosamine, chondroitin sulfates and manganes ascorbate) found in Cosequin (Nutramax Laboratories, Inc). Those products which contain various forms of glycosaminoglycans (aggregates form proteoglycans, the major consituent of cartilage matrix) such as glucosamines or chondroitin sulfates appear most promising based on studies that have supported their efficacy. Much of this work has been reported in horses although a large amount of literature supports the use of selected ingredients (especially glucosamine) in the treatment of OA. Presumably, as precursor nutrients, chondrotin sulfates and glucosamines will administered orally are extracted from the serum by chondrocytes and be used to synthesize proteoglycans. Ascorbic acid is a reducing agent for enzymes which form residues important for fibril formation and cross-linkage of collagen fibers for the articular cartilage, joint capsule, tendons, ligaments and bone. During periods in which cartilage degradation exceeds cartilage formation, the need for precursor molecules may exceed availability and the repair process is inhibited. The availability of orally administered compounds not only increases the efficiency of the ability of the chondrocytes to repair damaged cartilage as is evidenced by increased synthesis, but also leaves less opportunity for formation of inappropriate molecules. Orally supplemented precursors also may inhibit cartilage degradation. Glucosamines appear to modulate the inflammatory process, perhaps by scavenging oxygen radicals. Cartilage degradative enzymes are also inhibited. These products appear to be safe. Platelet function may change, but the clinical relevance

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of this finding is no obvious. Lethal doses can not be established in some animals (indicating the drugs are safe). Oral absorption (up to 70%) of chondroitin sulfate has been reported in a number of species administered radioactive materials. Bioavailability of glucosamine salts will vary, with the HCL salt being move bioavailable (87%) compared to the sulfate salts (47%); thus doses of sulfate salts should be higher.Both compounds appear to be taken up into the joint. Studies which have documented the ability of these compounds to modify disease are increasing. A number of studies have used rabbit models of surgically â&#x20AC;&#x201C; induced damaged. Controlled studies show clear histological and gross improvement in joints treated with a combination glucosamine-chondroitin product compared to placebo. Some evidence supports that the two components act synergistically. This in part reflects the difficulty encountered when studying disease modification of osteoarthritis. Studies intended to supported the use of these compounds are often hampered by inappropriate study design (lack of controls, etc), inappropriate models (sever synovial inflammation), failure to study response for a sufficiently long period, or inappropriate outcome measurements. Nonetheless, studies thus far have been supportive of efficacy and safety. This is supported by a survey study of veterinarians who have used the compound for treatment of a variety of orthopedic maladies. Most of the studies have focused on a single commercially available preparation (Cosequin) and it is not clear if the data can be extrapolated to similar products since the contents of these products often are not clear. These compounds might be considered as follow-up to patients that have responded to PSGAGs. However, as with injectable PSGAG agents - they should be considered in any condition in which joint damage is suspected or anticipated, including trauma, over use, surgery, or infections or immune-mediated causes. Combination therapy with various products (includ ing NSAIDs) (which can be chondestructive) should be considered. Dosing of these products might be based on Cosequin:500 mg glucosamine, and 400 mg chondrotin sulfate (chondroitin 4 preferred) per 25 lbs twice daily. Hyaluronic Acid. Hyaluronic acid is linear polydisaccharide (glucuronic acid combined with glucosamine) that is an essential component of synovial fluid where it is chemically linked to proteoglycans in articular cartilage. As such, it helps to form large, aggregating proteoglycans in articular cartilage. Its mode of action is not certain but it is assumed to function as a lubricant by increasing viscosity of synovial fluid. It may also act as an anti-iinflammatory. Studies in horses support its efficacy in treatment of ostoarthritis. Following intra-articular injection, the drug persists in joints for several days. The drug also has been given intravenously ; the half-life in horses is 96 hours, but the drug has not been studied iin dogs. Hyaluronic acid exists in variable molecular weights. High molecular with hyaluronic acid inhibits phagocytosis and lymphocyte migration and synovial permeability as well as stimulates HA synthesis. Prior treatment with glucocorticosteroids or bony changes limits response. Hyaluronic acid appearas to be very safe; side effects tend to be associated with administrtion of the drug. The drug has been used with variable success following intraarticular injection in horses and dogs. Pentosan Polysulfate. This product (PPS) is iso-

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lated from beechwood hemicellulose and synthetically modified by addiing sulfates to its repeating uints of xylanpyranoses. Thus, unlike previously described disease modifying agents, it is not derived from animal sources. Currently, it is not available in the US. In Europe, it is used to treat thrombosis and hyperlidemia, with application for treatment of osteoarthritis being only recent. It may improve subchondral and synovial membrane blood flow. In addition, it modulates cytokine actions, stimulates hyaluronic acid synthesis and maintains PSGAG content in joints. Its oral biovailability isnot as good as Cosequine, but it can be given orally. When administered IM(2 mg/kg once weekly) in a model of osteoarthritis in dogs, cartilage damage was significantly decreased. By 3 weeks. The drug appears to be safe, but like other PSGAG-like compounds, it appears to prolong clotting times, and may cause thrombocytopenia. Superoxide dismutase inhibits inflammation primarily by inactivating su peroxide radicals released during inflammation, although it may also prevent disruption of lysosomes. 3 Thus, its anti-inflammatory activity is somewhat limited compared to other anti-inflammatory agents. Because of its large chemical size, superoxide dismutase does not penetrate normal membranes; thus penetration to target tissues following intramuscular injection may be poor. The drug has been administered intraarticularly with equivocal effects. Side effects are uncommon. Clinical indications have been limited to soft tissue inflammation (horses) and in spondylitic syndromes or vertebral disk disease in the dog. Glucocorticoids Their use for the treatment of osteoarthritis is controversial. Opinions regarding their use in acute flair ups or trauma are consistently affirmative. However, long term use remains controversial. Glucocorticoids have variable and opposite effects on joint physiology, depending on the dose used. Low concentrations appear to be chondroprotective whereas higher concentrations are chondrodestructive. Much of the scientific evidence is based on in vitro studies or animal models (including dogs) which focus on human OA. Veterinary research has focused principally on the horse. The term "steroid arthropathy" was coined to refer to the destructive condition that occur in joints following multiple IA injections of glucocorticoids in human patients. Binding of glucocorticoid receptors on chondrocytes can inhibit chondrocyte growth or cause chondrocyte death. Hyaluronic acid production by canine synovial cells is decreased by glucocorticoids. In horses, a single IA injection reduces proteoglycan content. Weekly injections resulted in chondrocyte necrosis, reduced collagen and proteoglycan synthesis. In addition to the destructive damages induced by glucocorticoids on cartilage, indirect damage may occur due to failure to rest a damaged joint. Finally, glucocorticoids negatively impact subchondral bone by inhibition of osteoblastic activity. Despite these negative effects, there is little doubt among clinicians regarding the potential beneficial effects of glucocorticoids because of their anti-inflammatory and immunosuppressive actions. Controversy reflects lack of scientific knowledge in the specific species and what constitutes a physiologic dose. Using a canine model of OA, an oral dose of 0.2 to 0.25 mg/kg prednisone or an intraarticular dose of 5 mg/month triamcinolone hexacetonide significantly re-

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duced the incidence and severity of cartilage lesions and osteophyte formation. The choice of oral versus IA use of glucocorticoids can be influenced by preference for efficacy while reducing the likelihood of systemic side effects. These concerns may be counterbalanced by the risk of sepsis (which can probably be avoided by proper technique) and the potential need for chemical restraint. Systemic side effects are not likely to be completely avoided since glucocorticoids can reach systemic circulation after IA adminstration. Newer glucocorticoids characterized by increased antiinflammatory potency yet decreased negative effects on cartilage may resolve the controversy regarding the use of glucocorticoids in the treatment of OA. Until these drugs are available, or a "physiologic dose" has been established, the authors recommend reservation of glucocorticoids in the treatment of OA to the animal that has failed to respond

to chondroprotective agents, or nonsteroidal anti-inflammatories that are chondroprotective. Finally, if glucocorticoids are used, low doses (as noted above) should be administered and the simultaneous use of chondroprotective agents should be considered. The use of a pulse dose of 1 mg/kg/day has been recommended for treatment of acute musculoskeletal injuries, including animals with DJD that suffer an acute episode of pain or swelling following extensive exercise. Long term therapy with glucocorticoids should be reserved for joint conditions associated with (non-infectious) inflammation (eg, immune-mediated disorders). In such cases, routine procedures are recommended for long term therapy (ie, once daily dosing; alternate day therapy; minimum effective dose; tapering dose as opposed to rapid withdrawal). Glucocorticoids should not be combined with aspirin or other NSAIDs.

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Pharmacological differences between dogs and cats When applying in cats what you have learnt in dogs can become dangerous Differenze farmacologiche tra il cane e il gatto Quando può diventare pericoloso applicare nel gatto ciò che abbiamo imparato sul cane

Dawn Boothe DVM, MS, PhD, Dipl ACVIM, Dipl ACVCP - Texas A&M University Dept of Physiology and Pharmacology College Station, Texas, USA

Defining adverse reactions Adverse drug reactions, categorized as type A or B, include any undesired or unintended effect of drug treatment. Type A ("augmented") reactions are exaggerated, but otherwise normal and expected pharmacological (or toxic) responses to a drug. The adverse response may be a secondary response (e.g. bronchospasms induced by the nonselective beta antagonist propranolol), rather than the primary and intended pharmacological effect of the drug (e.g. negative chronotropy induced by propranolol), or it may be a toxic response (e.g., acetaminophen-induced methemoglobinemia) to the drug. Failure to generate an expected therapeutic response might also be a type A reaction. Although differences in receptor type, density or specificity may cause some adverse reactions in the cat, most type A reactions reflect differences in drug disposition which lead to different (usually elevated) plasma drug concentrations. Acetaminophen toxicity is an example of a type A adverse reactions in cats which results from differences in disposition (metabolism) and differences in hemoglobin structure. Type A reactions are dose-dependent, and, if adequate patient information is available, frequently predictable and avoidable. The incidence of type A reactions can usually be avoided by controlling plasma drug concentrations so that they remain within the therapeutic range, thus avoiding subtherapeutic or toxic concentrations. A number of adverse reactions to drugs which have been reported in cats can probably be attributed to type A reactions. In contrast to type A reactions,type B ("bizarre") adverse reactions are unexpected, aberrant responses which are unrelated to the drug's pharmacological effect. They are not dose-dependent and are unpredictable. They are more likely to reflect differences in drug-target tissues, genetic differences or drug allergies. Type B reactions are unpredictable, and, unlike type A adverse reactions, they are difficult to avoid.1 Descriptions of type B reactions are limited in the cat. Examples include mast cell degranulation (a non-allergic reaction) by cationic drugs such as radiocontrast material; amphotericin B; doxorubicin; and solubilizers or carriers

of drugs. Pretesting the cat with a small dose prior to treatment can help detect and thus offset some of these type B reactions. Other examples of type B reactions in cats include drug fever (eg, tetracyclines, caparsolate; because the lung is the shock organ in the cat, pulmonary edema (eg, caparsolate, plasma) and others. Adverse drug reactions in cats are discussed in more detail in the manuscript entitled Adverse Drug Reactions in Cats in this same proceedings.

Principles of drug disposition Dose-Response Relationship. Pharmacological responses to a drug (type A reactions) are usually linearly related to the plasma drug concentration. Thus tissue drug concentrations, which tend to parallel plasma drug concentrations, are usually the ultimate determinants of the magnitude of a response to a drug, whether it be a primary, secondary or toxic response. Generally, drug concentration-response relationships are the same for most species. The goal of drug therapy is to administer a dose that will maintain peak (maximal) and trough (minimal) plasma drug concentrations within therapeutic ranges, yet below toxic levels. Plasma peak and trough drug concentrations following administration of a drug according to a specific dosing regimen are determined by drug disposition. Determinants of Drug Disposition. The determinants of drug disposition include absorption from the site of administration (most commonly the gastrointestinal tract) into systemic circulation, distribution from circulating blood to body tissues, and metabolism and/or excretion from the body.4,5 The extent to which each of these factors determines the disposition of a particular drug is determined by the chemistry of the drug (ie, its lipid or water solubility, molecular size and pka) as well as various local environmental conditions. For example, gastrointestinal absorption is determined principally by gastrointestinal pH, motility, epithelial permeability, surface area and blood flow. Distribution can occur to various body compartments (ie, plasma, extracellular fluids or total body water) and is affected by the size

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of the compartments, the extent to which the drug is bound to plasma proteins (principally albumin), blood flow to tissues and binding of drug to tissues. The volume of tissue to which a drug is distributed to is inversely related to plasma drug concentration: thus, if the volume of distribution is small (ie, the drug is distributed only to extracellular fluid), plasma drug concentrations tend to be higher than if the drug is distributed to total body water. Drugs which are highly protein bound have a small volume of distribution. In the bound form, drugs are inactive and inaccessible to organs of elimination. Differences in the percent protein binding of a drug can result in profound differences in the availability of active drug (eg, a 99% bound drug has only 1% active; displacing only 1% of the bound drug [99 to 98% bound] doubles the amount of pharmacologically active drug. Since the determinants of plasma drug concentration are dose administered and the volume of tissue to which the drug is distributed, dose may need to be adjusted for differences in distribution. A dose may need to be increased to compensate for increased drug distribution; the reverse is true if the drug is distributed to a smaller amount of tissue or if less drug is protein bound. Drug metabolism occurs principally in the liver. Drugs which are sufficiently water soluble do not require metabolism. Such drugs are excreted largely unchanged in the urine and their disposition pattern and dosing regimens are usually similar in the dog and cat (e.g. aminoglycosides). In contrast, lipid-soluble drugs require conversion to a water soluble form before they can be excreted. The function of drug metabolism is to chemically alter a lipid-soluble drug to a watersoluble form, thus rendering it more conducive to excretion, usually via the kidneys. If metabolism does not occur, lipidsoluble drugs can accumulate to toxic concentrations. Most drug metabolism takes place in the liver in two phases, each catalyzed by specific enzymes. Phase I enzymes oxidize, reduce, or hydrolyze the drug; the chemical change usually increases water solubility, so that the drug is more susceptible to phase II enzyme activity. The majority of phase I enzymes are of the cytochrome P-450 system. They are located in the endoplasmic reticulum of the hepatocyte and are often referred to as microsomal enzymes. The effect of phase I metabolism on the drug's pharmacological activity varies with the drug and sometimes the species. The most common sequelae of phase I metabolism is conversion of the drug to pharmacologically inactive metabolites. However, these metabolites may also be more toxic than the parent compound (e.g., acetaminophen and phenytoin). A drug may also be converted to a metabolite with pharmacological activity similar to or even greater than the parent compound (e.g., aspirin, primidone, diazepam, propranolol). Finally, some drugs ("prodrugs") must be converted to the pharmacologically active form (e.g., hetacillin, cytoxan,imuran, primidone and prednisone). Phase II enzymes catalyze conjugation of large molecules such as glucuronide, glutathione, sulfate and acetyl groups and amino acids (e.g., taurine and glycine) to parent drugs or their phase I metabolites. The addition or conjugation of a large molecule almost always results in an inactive, water-soluble compound which can be excreted easily into bile or urine. An important role of phase II enzymes is conjugation and removal of products of phase I drug metab-

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olism which might be toxic. The most common phase II reaction is conjugation of glucuronide, catalyzed by a family of glucoronyl transferases. Drugs containing -OH, -COOH, NH2, -HN and -SH groups are particularly susceptible to glucoronidation. Examples include morphine, chloramphenicol, salicyclic acid and related compounds, and a few sulfonamides. Glutathione transferase (GSH) is another important phase II enzyme because it serves as a scavenger for toxic drugs and/or metabolites. Glutathione depletion by certain drugs may result in accumulation of potentially toxic compounds. The metabolic pathway of any particular drug depends upon the drug itself as well as the species. Many different families of enzymes are responsible for both phase I and phase II drug metabolism; within each family, the enzymes are characterized by substrate specificity. Thus, individual, intraspecies and interspecies variability is large. Differences in drug metabolism between species is both qualitative, due to metabolism by different enzymes, and quantitative, due to different rates and extent of metabolism. Biliary excretion is not a common route of elimination. The length of time that a drug stays in the body can be prolonged if a drug is eliminated in the bile, since enterohepatic circulation results in recycling of the drug and its effects. Renal excretion represents the most important mechanism by which drugs or metabolites are cleared from the body. Renal clearance of drugs is determined by renal blood flow, glomerular filtration (which is determined, in part, by drug protein binding), active tubular secretion and passive tubular resorption (which can be affected by urinary pH). Together, hepatic metabolism, biliary excretion and renal excretion comprise the primary mechanisms by which drugs leave (are cleared from) the body. Other less common routes are important for selected drugs (ie , lungs, etc). Disposition Parameters and Dosing Regimens. The dose of a drug is determined by the target concentration (ie, 20 µg/ml or mg/l phenobarbital or 10 µg/ml gentimicin) and the volume to which the drug is distributed in the animal (ie, 0.6 l/kg, phenobarbital and 0.25 l/kg gentamicin: 20 X 0.6 = 12 mg/kg loading dose phenobarbital; 10 mg/l X 0.3 l/kg = 2.5 mg/kg gentamicin). The cumulative effects of the disposition factors determine how long one can wait before administering the next dose (ie, before plasma drug concentrations fall below an unacceptable level). The interval is de termined by the time required for elimination of the drug from the plasma, commonly estimated by plasma elimination half-life, the time it takes for 50% of a drug to be eliminated from plasma. Half-life is determined by body clearance, but also by the extent to which a drug is distributed to the tissues. If a drug is extensively distributed, it becomes inaccessible to organs of elimination, and thus stays in the body longer. Thus, drug half-life is particularly important in determining the interval at which a drug is administered. Drug half-life also determines the point at which steadystate concentrations (ie, the maximum drug concentrations) will be reached. Steady-state is important for drugs whose half-life is longer than the dosing interval. Such drugs accumulate in the body (since most of the previous dose is still in the body when the next dose is given). Regardless of the drug, 3 to 5 half-lifes must elapse before steady-state concentrations are achieved. Recommended dosing regi-

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mens are most applicable when they are based upon controlled studies which describe the time versus plasma drug relationship. Clinical pharmacokinetics, the science of drug dosing regimens, and its relationship to drug disposition in veterinary medicine were recently well reviewed. While these same factors determine plasma drug concentrations in each species, unique differences in the cat can result in different plasma drug concentrations and thus adverse reactions when a drug is administered according to a dosing regimen used in another species. The factors which can alter drug disposition in the cat can be categorized as physiological (species and age), pharmacological (ie, drug interactions) and pathological (ie, disease-induced).

FACTORS WHICH AFFECT DRUG DISPOSITION IN CATS Role of Species Differences in Disposition. Species that are physiologically similar tend to have similar drug disposition patterns and the same dosing regimen can often be used for a particular drug.7 Thus, dosing regimens recommended for the dog frequently can be extrapolated to the cat. There are, however, some differences in drug disposition between the dog and cat species which can lead to development of adverse drug reactions in the cat if canine dosing regimens are used. Absorption. The rate and magnitude of drug absorption for most drugs appears to be similar for both the dog and cat, regardless of the route of administration. An exception may need to be made for slow-release preparations; rates and extent of absorption does vary among species. Diseases relatively unique to the feline gastrointestinal tract which can alter drug absorption include disorders of gastric motility (decreased absorption); chronic inflammatory bowel disease (either increased or decreased absorption, depending on the extent of lesions). Distribution. Although differences in drug distribution between the species tend to be minor, they can result in important differences in drug response. Blood volume of the cat (70 mls/kg) is less than that of the dog (90 mls/kg); plasma drug concentrations of drugs whose distribution is confined to the plasma compartment may therefore differ between the species. The same amount of drug (on a per/kg basis) will be diluted less in cats since the plasma volume is smaller. Thus, drug concentrations after administration of a mg/kg dose might initially be higher in cats compared to dogs. Organs that are well perfused (ie, heart, brain) may be more susceptible to toxicity. Cats are approximately the same size as the smaller dog breeds. Thus, doses determined for medium to large size dogs may not be appropriate for the cat since the smaller animals have a greater body surface area. As with any pediatric patient, body water comprises a larger proportion of body weight, which tends to dilute out the drug. Differences in plasma protein-binding characteristics (particularly albumin) may alter the distribution of drugs that are highly protein bound. The degree to which various drugs are protein-bound varies dramatically among the species. For a drug highly protein-bound, a difference of 10% in binding can be disasterous in some patients. Al-

though the elimination characteristics of many drugs have been established in cats, few studies have determined the extent of protein binding. The effects of disease can markedly alter distribution. The unhealthy cat does not maintain hydration as well as the dog; fluid imbalances resulting from dehydration or edema will alter drug distribution. The obese cat can represent a "sink" for drugs which are lipid soluble, thus lowering plasma drug concentrations potentially to submaximal level. Drug distribution is likely to be altered in cats with cardiovascular disease. Blood flow to the brain and heart is protected at the cost of blood flow to other organs. Thus, the heart and brain are more susceptible to toxicity. In addition, target organs are less likely to recieve drug. Metabolism. The most significant differences in drug disposition between the dog and cat probably result from differences in drug metabolism. Note that the cat is smaller than the dog and its body surface area/kg body weight is larger. Thus, like small dogs, we should be dosing cats at a higher dose simply because of its small size. However, other differences in metabolism tend to mitigate differences in surface area. Identification of phase I enzymes and their specific drug substrates is difficult and few species differences have been described. Deficiencies in methylation and hydroxylation have been described in the cat and may be responsible for different patterns of prodrug activation (eg., primidone) or adverse reactions to selected drugs (i.e., chloramphenicol). The recently described reaction of cats to diazepam may represent differences in the metabolites produced, or susceptibility of the feline liver to metabolite induced damage. Differences in phase II enzymes and their drug substrates have been better identified and account for many of the differences in drug disposition between the dog and cats. Most of these differences result from a deficiency of glucuronide conjugation in the cat. The deficiency reflects extremely low concentrations of some glucoronyl transferases. Thus, many drugs excreted as glucuronide conjugates in other species are characterized by a prolonged clearance rate and half-life in the cat. Toxic levels may accumulate much faster in the cat and exa ggerated pharmacological responses or toxicities occur more easily. For example, acetaminophen is toxic in the cat because it is not glucuronidated sufficiently fast. Excessive acetaminophen is shunted to phase I enzymes, resulting in the production of toxic metabolites. The toxic metabolites overwhelm the glutathione scavenging system of feline erythrocytes, resulting in methemoglobinemia. Cimetidine can be helpful in cats reactingadversely to acetaminophen (if administered within 48 hours) since it inhibits phase I drug metabolizing enzymes. Not all drugs which are conjugated with glucuronide are toxic in the cat. This is true for several reasons. First, the cat is deficient only in certain families of glucoronyl transferase. Cats can conjugate and excrete endogenous substrates such as bilirubin, thyroxine and steroid hormones as well as other species. However, metabolism of a variety of exogenous drugs, particularly phenols, and aromatic acids and amines, occurs at a much slower rate in the cat compared to other species. The degree of deficiency and potential toxicity depends upon the drug substrate. For example, some phenolic compounds are sufficiently conjugated while others are not. Second, glucuronide-conjugated drugs characterized by a wide safety

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margin are associated with few adverse reactions even if accumulation occurs. Finally, in the absence of glucuronide, drugs may be sufficiently metabolized by an alternative pathway. Some sulfates may be particularly well developed in the cat and many drugs which are excreted as glucuronide-conjugates in the dog may be excreted as sulfated compounds in the cat. However, other sulfate conjugating systems appear to be easily saturated in the cat. Unfortunately, alternate pathways of drug metabolism may also contribute to the toxicity of some drugs because they may involve phase I enzymes that catalyze the formation of toxic metabolites. Thus, drugs shunted to another pathway in the cat may be very toxic to the cat but minimally toxic in other species (e.g., acetaminophen). In summary, the sequelae of deficient glucoronidation conjugation in the cat depends upon the nature of the drug and the presence of alternate pathways of drug metabolism. Both drugs and toxic intermediates will accumulate if there are no other significant pathways of metabolism for the drug. An exaggerated pharmacological or toxic response should be expected for drugs whose half-life is prolonged and/or clearance is decreased. The effects of liver disease on feline drug metabolism have not been studied. It is likely that many diseases, and particularly hepatic lipidosis, have a profound effect on the ability of the liver to metabolize drugs. Drugs with a narrow therapeutic window and metabolized by the liver should be avoided in cats with liver disease. Renal Excretion. In contrast to hepatic metabolism, differences in renal excretion between the dog and cat do not appear to be profoundly important to drug disposition. The glomerular filtration rate of cats (2.5 to 3.5 ml/min/kg) is less that that of dogs (3-5 ml/min/kg), suggesting that renal clearance of drugs may be faster in dogs. Although this is true of inulin,differences have not been established for most drugs. Renal disease profoundly alters the rate of drug excretion in all species. In general, serum creatinine concentrations can be used to modify the dose (decrease in proportion) or interval (prolong in proportion to abnormality). The modification should be applied only to that portion of the drug eliminated by the kidney. Note that fluid imbalances in renal disease can also alter drug distribution. Differences in circadian rhythm (ie, diurnal versus nocturnal) probably plays a role in some differences between the dog and cat. This has been established for theophylline and is likely to be true for steroid hormones. The clinical significance of these differences has not been determined . Role of Species Differences in Target Tissues It is impossible to predict differences in drug reaction which can be ascribed to differences in target tissues since we really know very little about cats. Differences in response to selected drugs (eg, opioids; insulin; chlorinated hydrocarbons, etc) are known to be or thought to be reflections of differences in tissues. The increased sensitivity of feline erythrocytes to oxidation are discussed in Adverse Drug Reactions In cats in this same proceedings.

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RECOMMENDATIONS REGARDING EXTRAPOLATION OF DOSES Extrapolation should be based on a knowledge of the clinical pharmacology of the drug to be administered. The safer the drug, the safer the extrapolation. Use the Physician's Desk Reference to determine the safety and the determinants of disposition of a new drug. The sicker the cat, the more dangerous the extrapolation. Know the cat's health status, and avoid extrapolation if organs important to drug diposition are affected. Administration by the oral route is generally safer (although gastric irritation may be more likely). Avoid IV administration. Avoid, in general, drugs with long half-lives (> 12 hours). If the drug is administered at an interval that is less than the drug half-life, accumulation should be anticipated. Note that maximum adverse effects may not appear until accumulation has occurred at steadystate. In such instances, dosage reduction is again indicated. Be prepared to treat adverse effects if they occur. Note, that if the drug half-life is long, the time necessary for abatement of the adverse reaction will also be long. Water Soluble Drugs. As a general rule, extrapolation of doses for drugs that are water soluble is more appropriate since these drugs are distributed to extracellular fluids (normalizing volume of distribution); protein binding is likely to be negligible; and hepatic metabolism is minimized. Drug volume of distribution and renal elimination are often similar among species. Often, the interval used for such drugs can be extrapolated to cats. The dose administered, however, probably should be reduced to compensate for differences in blood volume. Lipid Soluble Drugs. In contrast to water soluble drugs, lipid soluble drugs are more likely to require hepatic metabolism. If acetylation is a major phase II route of elimination, it is likely that the drug may be metabolized faster in cats compared to dogs. Although glucuronidation does not necessarily indicate that elimination of the drug will be slower in cats, until an appropriate study has established the kinetics of the drug in cats, its use should be avoided. An exception might be made if 1. the drug can be measured; or 2. the drug is characterized by a wide therapeutic window. Slow-release preparations should be avoided in the cat only because rates of absorption among the species can be dramatic. Finally, preparations containing propylene glycol and other unknown carriers might need to be avoided because of adverse reactions in cats. Compounding. A major problem with extrapolating doses in cats occurs with preparations formulated for humans: the size of the tablet often precludes accurate dosing. Note that several pharmacies in the country (Island Pharmacy Services, Inc; PO Box 1412, Woodruff, WI 54568; fax 715 358 7021; 800 328 7060 or 715 358 7712) now cater specifically to veterinarians and thus, are prepared to address such problems. In addition, carrier agents or fillers can be purchased commercially and used to dilute drugs to more useable sizes.

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Diagnosi precoce della miocardiopatia dilatativa del cane e sue possibili implicazioni terapeutiche Michele Borgarelli Med Vet, Dipl. ECVIM-CA (Cardiology)

Alberto Tarducci DMV, Dipartimento di Patologia Animale, Università di Torino

La miocardiopatia dilatativa (MCPD) rappresenta la patologia acquisita del miocardio più comune del cane. La malattia è caratterizzata da una dilatazione progressiva, di uno (di solito il sinistro) o di entrambi i ventricoli, in seguito ad una disfunzione primaria della funzione contrattile. L’eziologia della MCPD resta sconosciuta nella maggior dei casi, sebbene siano state proposte alcune ipotesi eziologiche quali cause genetiche e metaboliche (i.e. carenza di carnitina e di taurina). Sono di solito affette le razze di grossa taglia, sebbene non manchino le segnalazioni in soggetti di razze di piccola e media taglia (Coc ker Spaniel). I cani colpiti dalla MCPD in forma clinica manifestano tipicamente i segni d’insufficienza cardiaca bilaterale quali dispnea, tosse, facile affaticamento, sincope, distensione giugulare e ascite. L’aritmia cardiaca di più frequente riscontro è rappresentata dalla fibrillazione striale, ma sono frequenti anche le extrasistoli ventricolari. Radiograficamente si osserva cardiomegalia generalizzata, edema polmonare, e versamento pleurico nei casi più frequenti. I segni tipici all’esame ecocardiografico sono rappresentati da ipocinesia ventricolare, aumento della distanza del punto di massima apertura mitralica dal setto (EPSS), dilatazione atrio ventricolare. L’esame ecocardiografico Doppler nella maggior parte dei soggetti colpiti con segni clinici evidenzia la presenza di un profilo mitralico di tipo restrittivo, lieve o moderata insufficienza mitralica e, aumento del rapporto tra il periodo pre espulsivo e quello eiettivo aortico (PEP/TEV). La MCPD è caratterizzata da un lungo periodo asintomatico nel corso del quale il cane non evidenzia i tipici segni d’insufficienza cardiaca. In questa fase la diagnosi è possibile solo attraverso l’esame ecocardiografico che permette di evidenziare in soggetti, altrimenti normali, la presenza di una dilatazione ventricolare associata ad ipocinesia diffusa. Nel Dobermann per esempio, la presenza di un numero di extrasistoli ventricolari superiore a 100/24h al monitoraggio Holter è stato associato a MCPD occulta (Calvert 1997a). Sempre nel Dobermann la presenza di un EPSS > 7 mm rappresenta l'indicatore più specifico e sensibile per individuare i soggetti con forma occulta, così come un diametro ven-

tricolare sinistro maggiore di 49 mm in diastole e di 42 mm in sistole. L'utilizzo di tali parametri richiede però la conoscenza dei normogrammi delle misure ecografiche specifiche per ogni razza, e pertanto non possono essere ritenuti validi in generale; per esempio sulla base di uno studio condotto dal nostro gruppo, nell'Alano, un valore di EPSS di 12 mm rientra ancora nell'intervallo della normalità.

PATOFISIOLOGIA Come risposta alla diminuzione della funzione contrattile si osserva l’attivazione di una serie di meccanismi neurormonali volti a mantenere una gittata cardiaca normale e di conseguenza la perfusione di organi vitali quali rene, cervello e lo stesso muscolo cardiaco. I principali meccanismi neurormonali coinvolti sono rappresentati dall’attivazione del sistema nervoso simpatico (SNS), del sistema renina-angiotensina aldosterone (SRAA), dall’aumento della vasopressina, dalla diminuzione dell’attività del sistema nervoso parasimpatico. Questi meccanismi permettono alla malattia di avere un lungo periodo asintomatico, ma in ultima analisi, sono responsabili del peggioramento della funzione cardiaca, poiché conducono alla ritenzione idrica e all’aumento delle resistenz e. Inoltre l’attivazione neurormonale esercita un effetto di crescita sul muscolo cardiaco e può di conseguenza giocare un ruolo essenziale nel fenomeno di “rimodellamento” del miocardio e del sistema vascolar e. Due recenti lavori hanno studiato l’attività del SRAA nel plasma di cani con MCPD sia in forma sintomatica sia asintomatica. Koch et al. riportano come sia l’attività della renina plasmatica (PRA) che le concentrazioni di aldosterone appaiano aumentate nei soggetti con MCPD in classe avanzata di insufficienza cardiaca, mentre la PRA appare aumentata solo in alcuni soggetti con malattia asintomatica. In un altro studio Tidholm et al. confermano questi dati dimostrando un significativo aumento della PRA e delle concentrazioni di aldosterone nei soggetti affetti da MCPD nella forma sintomatica rispetto ai soggetti normali o con forma asintomatica. L’apparente assente o scarsa

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attivazione del SRAA sistemico riportata da questi studi tuttavia non esclude la possibile attivazione dei SRAA tessutali. Infatti, alcuni lavori recenti hanno evidenziato che, a livello locale, il SRAA presenta un aumento precoce dell’attività in modelli sperimentali di insufficienza cardiaca, e che tale aumento dell’attività del SRAA tessutale possa svolgere un ruolo importante nella progressione dell’insufficienza cardiaca. L’attivazione del SNS rappresenta un altro dei meccanismi responsabili del progredire dell’insufficienza cardiaca su cui si è concentrata l’attenzione di molti ricercatori. È ormai accertato che sia il grado di mortalità che quello di gravità della disfunzione sistolica sono correlati ai livelli plasmatici di norepinefrina (NE). Livelli elevati di catecolamine plasmatiche sono stati anche osservati sia in pazienti umani con disfunzione ventricolare sinistra asintomatica che in cani con MCPD in forma asintomatica. Anche l’aumentata attività adrenergica è responsabile di molti effetti negativi sulla funzione cardiaca. Tali effetti possono essere riassunti nella sotto regolazione dei beta recettori miocarditi, nella diminuita risposta dei recettori adrenergici alle catecolamine, all’effetto tossico e trofico sui miociti cardiaci, all’esacerbazione dei fenomeni aritmici e alla progressione sia della disfunzione sistolica sia di quella sistolica. È interessante considerare che la causa stessa dell’insufficienza cardiaca può essere responsabile del diverso grado d’attivazione adrenergica. Ware et al. hanno dimostrato ad esempio che cani con MCPD presentavano concentrazioni di NE più elevate rispetto ai soggetti affetti da insufficienza mitralica. Recentemente il nostro gruppo ha evidenziato come nel cane i beta recettori linfocitari riflettano bene la distribuzione cardiaca dei recettori adrenergici. La valutazione dei recettori linfocitari può quindi risultare molto utile al fine di valutare la distribuzione dei recettori a livello cardiaco anche ai fini di valutazione dell’efficacia di eventuali terapie.

STUDI IN CORSO Al momento vi sono diversi studi in corso volti a valutare la prevalenza della malattia nelle diverse razze. Al momento il nostro gruppo sta valutando la prevalenza della malattia in un gruppo di Alani e di Dobermann. Per quanto concerne lo studio sui cani di razza Alano sono stati esaminati nel periodo di 3 anni 56 soggetti (24 maschi, 32 femmine). Tutti i soggetti sono stati sottoposti ad almeno 2 esami ecocardiografici nel corso del periodo di osservazione. Di questo gruppo di cani 4 soggetti sono stati considerati affetti alla prima visita, mentre altri 3 cani hanno sviluppato la malattia nel corso del periodo di osservazione. Per quanto concerne il gruppo di Dobermann sono stati studiati nel corso del 2000 sono stati studiati 54 cani (22 maschi, 32 femmine). Di questi soggetti 4 cani sono stati considerati affetti e 10 soggetti border line. Alcuni di questi soggetti (5 cani) sono stati riesaminati a distanza di 6 mesi dalla prima visita. Sulla base dei r eperti clinici, ecocardiografi-

42° Congresso Nazionale SCIVAC

ci ed elettrocardiografici, 3 di questi soggetti sono stati considerati affetti alla seconda visita, mentre 2 sono stati riclassificati normali. Sulla base dei dati preliminari di questi studi appare chiaro come la diagnosi di MCPD in forma subclinica richieda un’attenta valutazione di più parametri ma soprattutto come in molti casi sia necessario valutare i pazienti nel tempo per raggiungere una certezza nella diagnosi.

IMPLICAZIONI CLINICHE E TERAPEUTICHE Poiché l’anestesia ha dimostr ato esercitare un’importante influenza negativa sul decorso della malattia nei soggetti con MCPD in forma subclinica è importante sottoporre tutti i soggetti delle razze a rischio ad una completa valutazione dell’apparato cardiovascolare prima si sottoporre i pazienti a procedure chirurgiche. In un recente studio l’anestesia e le conseguenti procedure chirurgiche, infatti, sono state collegate ad un’esacerbazione dei fenomeni aritmici e ad un peggioramento della funzione sistolica ventricolare sinistra in un gruppo di Dobermann. Poiché la diagnosi di malattia in forma occulta rappresenta come precedentemente riportato in molti casi una sfida diagnostica, è essenziale a nostro parere che la valutazione ecocardiografica sia eseguita da cardiologi esperti, e che la diagnosi di MCPD subclinica sia posta solo dopo aver escluso tutte le altre possibili diagnosi di ipocinesia ventricolare sx (es. ipotiroidismo, miocardiopatia ipertensiva). Poiché l’attivazione neurormonale è precoce nei soggetti affetti dalla malattia può apparire logico che la terapia precoce con un ACE inibitore e/o un Beta bloccante possa dimostrarsi molto efficace nel rallentare la progressione della MCPD nei soggetti asintomatici. Tale supposizione deriva dal fatto che entrambi questi farmaci sono in grado di agire sui meccanismi neurormonali sopradescritti che appaiono essere strettamente correlati gli uni agli altri. Ad esempio è stato osservato che gli ACE-inibitori possono contrastare la sotto regolazione dei beta recettori adrenergici attraverso l’inibizione dell’angiotensina II. Al momento in medicina veterinaria esiste un solo studio volto a verificare l’efficacia della terapia in cani con MCPD in forma asintomatica. In tale studio l’utilizzo di un ACE inibitore in un gruppo di Dobermann si è dimostrato efficace nel ritardare la comparsa dei sintomi rispetto al gruppo di controllo. Tale studio comunque non ha valutato l’efficacia della ter apia sulla mortalità, poiché come end point è stato definito la comparsa della sintomatologia di insufficienza cardiaca. Ulteriori studi volti a dimostrare l’utilità di tali terapie per i pazienti con MCPD in forma subclinica sono comunque necessari prima di poter affermare con certezza che tali terapie siano di reale ausilio per i pazienti colpiti.

La bibliografia è disponibile per richiesta agli Autori.

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Metodiche per l’identificazione precoce delle cardiopatie congenite nel cucciolo Claudio Bussadori Med Vet, Dipl ECVIM-CA (Card) - Libero Professionista, Milano

I pazienti affetti da cardiopatie congenite costituiscono una piccola percentuale rispetto al totale dei pazienti cardiopatici comunemente visti nella pratica veterinaria; la suddetta percentuale aumenta notevolmente quando vengano presi in considerazione i soggetti al di sotto dell'anno di età. Un primo importante elemento di cui ci si può servire ai fini diagnostici è quindi sicuramente il segnalamento:la presenza di un soffio, solitamente di grado superiore ai III/VI, in un soggetto di età inferiore ad un anno appartenente (ma non necessariamente) ad una razza predisposta è un buon indice della probabile presenza di una cardiopatia congenita in quel soggetto. Per cardiopatie congenite si intendono quelle cardiopatie, non necessariamente ereditarie, che sono già presenti alla nascita del soggetto; in realtà all'interno di questa categoria vengono annoverate anche patologie che non rispondono a questa caratteristica. Infatti ,ad esempio, tutti i soggetti nascono con un PDA fisiologico ed è solo la mancata occlusione dello stesso nelle ore immediatamente successive alla nascita a renderlo patologico; allo stesso modo la stenosi subaortica solitamente non è presente alla nascita o è di grado molto lieve e peggiora progressivamente durante i primi 6-12 mesi di vita.Le cardiopatie congenite di più

frequente riscontro sono la stenosi polmonare, la stenosi subaortica e il PDA. Dopo aver emesso un sospetto diagnostico sulla scorta del segnalamento, dell'anamnesi e della visita clinica (le caratteristiche del soffio possono essere di grande aiuto), il sospetto deve essere confermato mediante l'impiego di alcune tecniche diagnostiche:esame radiografico, elettrocardiografico e, soprattutto, ecocardiografico.L'esame radiografico può fornire indicazioni significative: purtroppo talora, anche in presenza di una cardiopatia non lieve, l'esame radiografico può risultare del tutto negativo. L'esame elettrocardiografico risulta utile nell'individuazione di eventuali aritmie spesso associate ad alcune cardiopatie; le altre informazioni ottenibili da tale esame sono aspecifiche e possono essere utili nel contesto del totale delle informazioni ottenute più per supportare un sospetto diagnostico che per confermarlo. L'esame ecocardiografico riveste quindi un ruolo molto importante nello studio delle cardiopatie congenite non solo perché consente di evidenziare direttamente la presenza della lesione cardiaca, e quindi di emettere una diagnosi certa, ma anche e soprattutto perché fornisce gli elementi necessari a stabilire una prognosi ed una linea terapeutica adeguata.

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Emergenze cardiovascolari: edema polmonare acuto, shock cardiogeno, tamponamento cardiaco e aritmie Claudio Bussadori Med Vet, Dipl ECVIM-CA (Card) - Libero Professionista, Milano

EDEMA POLMONARE ACUTO

TAMPONAMENTO CARDIACO

Si sviluppa quando la pressione idrostatica del letto capillare polmonare arriva rapidamente a circa 23 mmHg ( normale: 5 mmHg). Inizialmente l'aumento della pressione nei capillari polmonari determina un passaggio di fluidi nell'interstizio, in un secondo momento il fluido arriva ad invadere gli alveoli impedendo la ventilazione delle regioni colpite, provocando una diminuzione del surfattante e quindi della compliance. L'edema delle pareti delle vie aree e la pressione dei fluidi nelle aree peribronchiali determina inoltre un aumento della resistenza delle vie aeree. Terapia: diuretici, (Furosemide 4 mg/Kg ogni 4 ore) riposo ed eventuale sedazione, ossigenoterapia, gestione della causa scatenante.

Si ha quando, per l'accumulo di fluidi al suo interno, la pressione intrapericardica supera quella diastolica delle cavità cardiache (inizialmente quella dell'atrio destro) impedendo un corretto riempimento in diastole il che a sua volta determina una diminuzione della gittata cardiaca. L'accumulo di liquidi all'interno del pericardio può essere acuto o cronico; in quest'ultimo caso sono solitamente necessarie maggiori quantità di liquido perché si aarrivi al tamponamento in quanto il pericardio si dilata e si distende per accogliere il surplus di fluidi al suo interno. Più frequenti cause di tamponamento: neoplasie (emangiosarcomi, chemodectomi, mesoteliomi), pericarditi e rotture atriali traumatiche. La terapia consiste nella pericardiocentesi ed eventualmente nella fluidoterapia (MAI DIURETICI!!).

SHOCK CARDIOGENO Si ha quando viene compromessa la funzione di pompa del cuore provocando una diminuzione del flusso sanguigno e della pressione arteriosa. Di solito si ha in concomitanza di insufficienza cardiaca acuta, ma può presentarsi anche in soggetti con insufficienza cardiaca cronica sottoposti a terapia diuretica eccessivamente aggressiva. Terapia: fluidoterapia, simpaticomimetici (dobutamina e dopamina), gestione della causa scatenante.

ARITMIA Deviazione dalla normale frequenza cardiaca o dal normale ritmo, sito di origine dell'impulso, dalla normale sequenza di attivazione degli atri e dei ventricoli. Possono essere individuate alla visita clinica o solo sospettate sulla base dell'anamnesi (es. sincopi).

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Ipertensione polmonare David Chiavegato Med Vet - Libero Professionista, Padova

La circolazione polmonare è garantita dal flusso ematico che nell’unità di tempo passa dall’arteria polmonare ai capillari ed arriva, tramite le vene polmonari, all’atrio sinistro. A questo si associa quella componente ematica derivante dalle arterie bronchiali che, in condizioni fisiologiche, non deve superare l’l% del totale flusso polmonare (shunt sx-dx fisiologico). La pressione arteriosa polmonare è sostanzialmente determinata dalla pressione sviluppata dalla camera ventricolare destra, dalla sezione traversa del letto vascolare, e in parte dalla viscosità del sangue . La pressione polmonare in un soggetto normale presenta un picco sistolico non superiore ai 30 mmHg ed un picco telediastolico che non supera i 10 mmHg, con una pressione media di circa 15 mmHg. La differenza artero venosa del piccolo circolo risulta, pertanto, essere di circa 10 mmHg; ciò significa che per spostare il sangue attraverso i polmoni è necessario un differenziale pressorio di soli 10 mmHg. Le basse resistenze vascolari che caratterizzano il circolo polmonare consentono uno sviluppo da parte della camera ventricolare destra di una bassa “pressione generatrice”. D’altro canto qualsiasi riduzione della sezione trasversa delle arteriole e delle arterie conseguente a vasocostrizione o ostruzione intra o extra murale può determinare un’ipertensione polmonare, che risulterà tanto maggiore quanto maggiore e più estesa sarà la riduzione della sezione trasversa del letto vascolare.

IPERTENSIONE POLMONARE SECONDARIA A CARDIOPATIE L’aumento della pressione atriale sx (Es.insufficienza o stenosi mitralica, patologie restrittive ventricolari sx, ecc.) determina per via retrograda un aumento direttamente proporzionale della pressione venosa polmonare e del letto capillare. L’ipotesi più accreditata in medicina umana è che esista una vasocostrizione riflessa arteriolare come espressione dell’ ipertensione cronica atriale sx o più semplicemente di ipossia cronica (edema interstiziale cronico). Tuttavia, in medicina veterinaria tale meccanismo non è stato ancora dimostrato con certezza. Nella circolazione polmonare anche stress pressori associati a sovraccarichi volumetrici, come in corso di shunt sx –dx post tricuspidali (difetto del setto interventricolare, dotto arterioso persistente), sono in grado di attivare il meccanismo di muscolarizzazione arteriolare sino alla vasculopatia obliterante tipica dell’ipertensione polmonare irreversibile (Sindrome di Eisenmenger). La comparsa di lesioni plessogeniche e necrotizzanti rende il fenomeno ipertensivo pressoché irreversibile, per cui una severa ipertensione polmonare, risulta condizionante in caso di necessità della correzione chirurgica di uno shunt.

IPERTENSIONE POLMONARE SECONDARIA A RIDUZIONE DEL DIAMETRO VASCOLARE

FISIOPATOLOGIA La vasocostrizione arteriolare deriva dalla modificazione dell’equilibrio fra le endoteline (fattore vasocostrittore di origine endoteliale) ed il fattore vasodilatatore endoteliale (EDRF). Entrambi questi fattori agiscono sulla muscolatura liscia della tunica media delle arterie ed arteriole favorendo o inibendo il fenomeno contrattile. La liberazione delle endoteline è condizionata dalla comparsa di fenomeni di ipossia o dalla liberazione di fattori quali le PGF 2 α, PG A, istamina, Tx A2, ADP e forse serotonina. La muscolarizzazione arteriolare, invece, sembrerebbe imputabile all’attivazione di cellule indifferenziate(periciti) che acquisirebbero una funzione mio fribroblastica con attività contrattile .

Questa condizione è riscontrabile in corso di trombo embolismo, di filariosi e stenosi periferica delle arterie polmonari (evento di estrema rarità). Il tromboembolismo polmonare (TEP) è da considerarsi complicanza frequente in corso di numerosi eventi procoagulativi (coagulazione intravasale disseminata, sindrome di Cushing, sindromi nefrosiche ecc) . La perdita di AT III, l’aumento dei fattori della coagulazione V, VIII, IX, X sono tipici della sindrome di Cushing, così come la deplezione di ATIII e del fattore XII sono caratteristici della sindrome nefrosica. Eventi emolitici si accompagnano a ingenti liberazioni di ADP, la quale agisce sia direttamente come vasocostrittore sia come attivatore dell’aggregazione pistrinica. Il TEP può presentarsi sia come evento acuto con ostruzione di un grosso vaso ( es: sindromi nefrosiche), sia come

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evento cronico in cui l’ipertensione polmonare si potrà osservare anche dopo ripetuti fenomeni tromboembolici (ex: sindrome di Cushing)

IPERTENSIONE POLMONARE SECONDARIA A PNEUMOPATIE CRONICHE Pneumopatie a carattere infiltrativo od ostruttivo ( es: infiltrazioni eosinofilliche, broncopatie ostruttive, neoplasie polmonari ecc.) possono essere caratterizzate da una riduzione della distensibilità del letto vascolare. È probabile comunque che il meccanismo principale dell’insorgenza di ipertensione polmonare sia legato anche all’attivazione endotelinica conseguente all’ipossia parenchimale. Spesso la risoluzione della patologia polmonare porta alla reversibilità del fenomeno ipertensivo.

DIAGNOSI La diagnosi dell’ipertensione polmonare rappresenta per il clinico a tutt’ oggi una sfida diagnostica talvolta ardua. La sintomatologia è frequentemente correlata ad una patologia sottostante sia essa cardiaca, polmonare o metabolica. Difficile pertanto individuare un corredo sintomatologico caratteristico. Nell’algoritmo diagnostico si deve prevedere un’attenta valutazione anamnestica individuando episodi polipnoici, dispnoici e/o tossigeni, episodi sincopali o aumenti dell’affaticabilità. Alla visita clinica si possono riscontrare mucose pallide e/o cianotiche, tachisfigmia, polso giugulare pulsante e/o ascite (aumento della pressione venosa periferica). La comparsa di un rinforzo e/o sdoppiamento del secondo tono può rappresentare un elemento di sospetto significativo. L’elettrocardiografia può evidenziare deviazioni assiali destre, Q profonde in D I ed S profonde in D II e D III . In caso di tromboembolismo gli esami di laboratorio possono svelare alterazioni del profilo coagulativo, che in molte situazioni si limitano ad un aumento dei D-dimeri. L’emogasanalisi può rivelare la presenza di ipercapnia con ipossia. Nel caso di shunt dx-sx la policitemia risulta essere un riscontro frequente e francamente suggestivo.

42° Congresso Nazionale SCIVAC

La radiologia toracica può risultare silente (ex: TEP cronico in corso di Sindrome di Cushing) come svelare patologie cardiache o pneumopatie. Una concomitante cardiopatia sinistra (es: insufficienza mitralica ) si può accompagnare ad edema polmonare ed ingrandimento delle camere cardiache destre. Un eventuale “shunt reversed” può essere sospettato da un aumento della radiotrasparenza dei campi polmonari, da un assotigliamento della componente vascolare periferca e dal “bulging” dell’arteria polmonare. L’evidenziazione di tortuosità e potature delle arterie, di aree di radiotrasparenza dei campi polmonari con o senza coinvolgimento dei settori cardiaci destri può essere sug gestivo di TEP. In campo umano, al sospetto di TEP si procede alla scintigrafia perfusionale e ventilatoria e successivamente, per una eventuale conferma, all’esame contrastografico selettivo. L’esame ecocardiografico è determinante sia per la diagnosi di cardiopatie sia per la valutazione morfo funzionale del ventricolo destro. L’entità delle alterazioni delle geometrie ventricolari sia in B dimensionale che in M mode (setto paradosso) possono svelare, in assenza di ostruzioni all’efflusso Vdx, in modo indiretto un coinvolgimento del circolo polmonare. La presenza del rigurgito tricuspidale consente la quantificazione della pressione ventricolare destra che, sempre in assenza di stenosi polmonari, fornisce una valutazione pressoria del circolo polmonare con un livello di attendibilità quasi sovrapponibile al cateterismo pressorio.

IPERTENSIONE POLMONARE PRIMARIA Questa definizione viene riservata a tutti quei quadri ipertensivi in cui, dopo attenta e meticolosa ricerca, non viene individuata una specifica eziologia (ipertensione polmonare idiopatica). Il fenomeno, seppure molto raro, è ben conosciuto in medicina umana. Le alterazione istopatologiche polmonari sono sempre riferibili ad una vasculopatia obliterante con diffuse lesioni trombotiche talvolta canalizzate. L’algoritmo diagnostico deve comunque seguire quanto esposto per l’ipertensione secondaria.

Bibliografia a disposizione.

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42° Congresso Nazionale SCIVAC

La gestion du temps d’attente Come gestire il tempo in sala d’attesa

Fabrice Clerfeuille DVM, MBA in Management, MBA in Marketing, PhD in Marketing, Marketing Professor at the Nantes University (France)

Comme pour d’autres activités de services, le client supporte une durée d’attente dans une clinique vétérinaire. Celle-ci ne pouvant être supprimé, voire diminuée, compte tenu de nos particularités professionnelles (activité irrégulière, urgences, consultations à durée imprévis i bl e, e t c. ) , il convient d’en limiter sa perception par le client. Cette variable est en effet majeure dans l’évaluation globale, par le client, du service délivré par la clinique. L’objet de cette présentation sera de mieux comprendre les différentes facettes de ce temps d’attente, de monter que certaines idées de gestion de ce temps sont totalement erronées, et qu’elle doit être gérée de façon différente en fonction de chaque client.

I – LES CONSTITUANTS DE LA PERCEPTION DU TEMPS D’ATTENTE Les attentes d’un client peuvent avoir plusieurs motifs qu’il est nécessaire d’appréhender. Chacune peut en effet être comblée différemment, certaines nécessitant d’occuper le client, d’autres de l’informer.

II – PERSONNALITÉ DU CLIENT ET PERCEPTION DE L’ATTENTE Selon la personnalité du client, le temps d’attente sera perçu différemment. Une même situation sera du coup vécue différemment selon le client.

Tableau 1 - Les différentes attentes, selon Maister1 L’attente inoccupée

Le client n’a rien à faire

L’attente incertaine

La durée probable de l’attente est inconnue

L’attente anormale

Un problème survient et n’est pas expliqué

L’attente anxieuse

Pour toutes sortes de raisons

L’attente injuste

Resquille ou erreur d’ordre de passage

L’attente solitaire

La présence d’autres clients réconforte

L’attente de résultat mineur

Attente pour presque rien

L’attente pré ou post service

Qui s’oppose à celle de sa délivrance

Tableau 2 - Les différents vécus d’une même attente, selon Durrande-Moreau2 L’attente plaisir

Elle est intégrée à une action plaisante, et fait partie du cérémonial. La supprimer amoindrirait le plaisir de l’action.

L’attente moment de transition

Elle est vécue comme un moment tampon entre plusieurs actions exigeantes. C’est l’occasion de respirer, de regarder autour de soi, ou de se préparer à l’action suivante.

L’attente soumise, neutre

Elle n’a pas de valence positive ou négative, mais sa nécessité est comprise et acceptée.

L’attente impatiente

Elle est ressentie négativement, soit en raison du caractère anxieux de la personne, ou en raison d’une situation ressentie comme anormale.

L’attente insupportable

Elle irrite profondément le client, qui peut exprimer de la colèr e. Comme toute émotion forte, elle laissera des traces dans la mémoire du client qui seront réactivées dans des situations comparables.

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III – RÈGLES THÉORIQUES DE LA GESTION DE L’ATTENTE Il est coutume de définir sept règles de limitation de cette perception du temps d’attente. Pour décontracter le client, il sera nécessaire de lui offrir un confort physique lors de son attente (places disponibl e s ,e spacées, propreté, odeurs agréables, couleurs chaudes, etc.) ainsi qu’un confort mental lié à l’absence de stress (occupation des enfants, chiens attachés, chats séparés, etc.). L’attente devra être intégrée au déroulement de la prestation en proposant au client des dérivatifs pour éviter cette notion de vide (occupations offertes).

Elle sera calibrée en recherchant les causes d’attente, en cherchant à les limiter. Ces temps d’attente seront régulés, en mettant en place des outils lors de circonstances exceptionnelles. En cas de situation dégradée, tout devra être mis en place pour que le client ne se focalise pas sur cet accident de fonctionnement. Il apparaît judicieux de proposer aux clients des occupations variées s’il le souhaite en fonction de sa personnalité. Ces activités ne seront pas imposées, mais mises à disposition. Enfin, les clients devront être informés des temps d’attente éventuels afin d’éviter leur impatience.

Tableau 3 - Les règles théoriques de la gestion de l’attente, selon Durrande-Moreau3 Règle

Objectif

Exemple d’actions

Décontracter

Pour éviter une activation trop grande.

Agir sur l’environnement, l’ambiance. Ne pas stimuler intellectuellement ou affectivement.

Intégrer

Pour que le client ait moins conscience d’attendre.

Eviter les aspects les plus typiques de l’attente.

Calibrer

Pour que les durées mo yennes et maximales soient fixées en référence à une norme.

Positionner le service sur le critère de durée et de régularité.

Réguler

Pour éviter le dépassement du maximum fixé.

Accroître les moyens en cas de besoin.

Réagir en situation dégradée

Pour permettre au client de prendre sa décision d’action.

Procéder à des informations en cas de retards.

Occuper

Pour décontracter, sans gêner les autres clients.

Bornes interactives, vidéo, etc.

Informer

Pour décontracter les impatients, ou pour leur permettre d’a gir.

Information en réponse à une question, sans devenir systématique.

Outils

Remarques

Musique d’ambiance

Pour décontracter les clients et couvrir certains bruits parasites (aboiements, etc.).

Vidéo

Moniteur bien exposé, programmes variés, programme imposé ou sur demande.

Mascotte

Chat, perroquet, volière, aquarium … selon les centres d’intérêts, la place disponible!

Questionnaires à remplir

Chaque client entrant est amené à remplir un questionnaire sur les antécédents de son animal.

Borne interactive

Outil séduisant mais individuel. Sans doute un outil conduit à se développer.

Distributeur de boissons

Nécessite d’être contrôlé pour son réassort et son état de propreté.

Fiches conseils

Fiches à disposition des clients sur des renseignements divers (alimentation, intérêt du tatouage, etc.).

Emplacement réservé aux enfants

Espace formé d’une petite ta ble, de deux chaises, d’un coffre contenant des revues, des lego, etc.

Revues récentes

Abonnement à trois revues différentes et présence des trois derniers numéros pour chacune.

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IV – OUTILS POUVANT ÊTRE UTILISÉS POUR RÉDUIRE CETTE PERCEPTION DU TEMPS D’ATTENTE De très nombreux outils peuvent être mis à disposition des clients pour limiter cette perception du temps d’attente. Ils ne nécessitent pour la plupart que peu d’investissement, et peu de place. Nous en citerons quelques-uns ci-dessous, cette liste n’étant bien sûr pas exhaustive. Ils doivent, bien entendu, être accompagnés d’une prise de conscience de tous les intervenant de la clinique qui devront tout mettre en œuvre pour limiter physiquement ces temps d’attente et informer dès que possible les clients d’éventuels temps d’attente exceptionnels. La perception du temps d’attente par le client, paramètre important du service global offert par la clinique nécessite donc d’être diagnostiquée client par client.

On peut considérer trois étapes dans cette réflexion : -repérage des temps d’attente dans l’exercice quotidien classique ; -ckeck-up des outils à disposition des clients pour limiter cette perception ; -mise en place de mesures correctives,organisationnelles ou matérielles.

Bibliographie 1. 2.

Maister D.H. (1985), “The psychology of waiting lines”, in The Service Encounter , eds Czepiel Lexington Books, 113-123. Durrande-Moreau A. (1994), “Qualité de service et Perception du Temps”, l’attente, propositions théoriques et études empiriques, Thèse de Doctorat, Université Pierre Mendès France, Grenoble. Durrande-Moreau A. (1997), “L’attente d’un service, quelles recommandations?”,Décisions Marketing, 11, 69-79.

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La qualité et les exigences du client La qualità e le esigenze dei clienti

Fabrice Clerfeuille DVM, MBA in Management, MBA in Marketing, PhD in Marketing, Marketing Professor at the Nantes University (France)

The search of quality is all around us in our society. Well informed, more active, consumers have now the capacities and the means to compare differents products or services which can answer to their needs. To compare the alternatives offered, they evaluate the quality and the price of the differents options. This tendency is also present in our profession and the search of quality is increasing more and more. Our presentation will follow three parts: definition and clients’expectations about quality, quality through the differents departments of the clinic, and the global management of quality.

I – QUALITY: DEFINITION AND CLIENTS’EXPECTATIONS Quality needs to be define to know exactly what it recovers in a Vet Clinic. We will be able then to study clients’expectations and find the adequation between theirs needs and the services offered.

A – Definition Quality is “the sum of the properties and characteristics of a product or a service which can answer to the conscious ou unconscious needs of the clients”. It’s a part of a quality global management destinated to the clients, and the engine of the economic development of the clinic. So, the perceived quality by the client means the adequation between his needs and the offered services.

1 - Expectations regarding the vet Pet owners declared the following needs : - High quality care towards the pet - A short waiting time and a diagnosis without delay - Clear explanations - Confidence in the follow up.

2 - Expectations regarding advice The vet is perceived as the most competent professional when a pet is concerned, especially if the pet is a special companion. Some examples of the types of service for which pet owners may be g rateful are: - Choice of a breed - Choice of a male or female for the existing pet - General advice on training - General advice on show dates, grooming, steps to be taken when an animal is lost, etc.

3 - Expectations concerning the premises Clients’expectations regarding the quality of the premises are predictable: - An accessible parking - Cleanliness (general aspect, upkeep, unpleasant smells, etc.) - Uncluttered public spaces.

B – Clients’expectations A qualitative survey has been carried out among pet owners by Hill’s in 1996 and 1997. This survey in five european countries shows how their expectations fall into six categories: - Expectations regarding the vet ; - Expectations regarding advice ; - Expectations concerning the premises ; - Expectations concerning the nurses ; - Expectations concerning payment ; - Expectations about new services.

4 - Expectations concerning the nurses Clients expectations towards vet nurses and other staff are precise: - They should be identifiable from the others professionnals of the Clinic - They should be competent technically but also in the area of communication - They should be kind with the animals.

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5 - Expectations concerning payment

C – Material ressources

Clients want: - To be able to consult a list of prices - To pay reasonable fees - To have the option of different methods of payment (immediate or in instalments).

Quality needs material ressources, either technical ones or commercial ones. Each of them needs to build a forecast budget and the calculation of a profitable threshold. The indirect incomes need also to be included: - Clients’loyalty - Winnings of clients by the communication developped - Developments of new services using the investments - etc.

6 - Expectations about new services Arising from dicussions on quality with pet owners, some services have been mentionned as desir able: - Loan of books about pets - Consultations on diet (obesity) - Health checks for old animals - Counselling when a pet companion dies - Puppy class.

II – QUALITY THROUGH THE DIFFERENT DEPARTMENTS OF THE CLINIC To answer to the differents clients’ expectations about quality, some differents ressources are needed in the Clinic. Four departments can be arbitrary presented: financial res sources, human ressources, material ressourcse and marketing ressources.

D – Marketing ressources Marketing ressources include all the communication tools used to show the quality of the clinic. Quality is based on services, so we need to materialize them in order that clients can see them. For example we can list: - a board containing some views of the differents areas of the clinic with their equipments - a photograph album showing some funny pictures of the clients pets - a newsletters for the clients showing the differents areas of the clinic - an information about the new equipments - etc.

III – Towards a quality management A – Financial ressources To increase quality, we need at first some material investments, human investments and time investment. These investments are, at least in the beginning, often consumer of profit. Choice of quality is a long term strategy, which needs a good financial health. A good management is the first condition to develop quality steps in our clinics. We have not enough time to be complete in this area but we have to keep in mind two recommandations: - To have an analytic accountancy which permit to follow the incomes and expenses of the differents services offered by the clinic; - To have some financial indicators to follow the quality of the clinic.

B – Human ressources Human ressources are the first indicator of quality for the clients. We need to motivate our nurses. Motivation is a mix between the level of perceived competence and the level of self determination in their job:

High perceived Compétence Obligation

Revolt

Interest

Resignation

Flight

Low perceived Compétence

Selfdétermination

To develop quality in our Clinic needs a global management. We propose below such a management: Study of the External Environment - Threats - Opportunities

Study of the Internal Environment - Strenghts - Weaknesses Quality objectives Plan - Do - Chec k Next Action

Such a Quality management can go until the ISO 9000 standard. It’s an international standard which gives the recommandations for quality management in any organization or enterprise and propose some tools to develop quality between the clients and the enterprise. A vet clinic in Hambourg has for example the ISO 9002 standard since 1997. Some countries prefer to develop their own standard for the vet profession like in the Netherlands (Koninklijke Nederlandse Maatschappij voor Diergeneeskunde). To conclude, it appears that all the actors of the vet profession go towards quality management: the suppliers due to the competition, the vets in front of the technology development and maybe also due to the competition, but also the person in charge of the vet ethic in the concerned countries. Europe will maybe think in the next future to elaborate a standard of quality in our profession with some procedures. Are we ready to do this change?

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La satisfaction de nos clients Come soddisfare i clienti

Fabrice Clerfeuille DVM, MBA in Management, MBA in Marketing, PhD in Marketing, Marketing Professor at the Nantes University (France)

Un client vient à la Clinique pour quatre grandes raisons: Un conseil Une consultation Un rendez-vous opératoire Un produit Sachant qu’il peut trouver moins cher et plus facilement, nous nous interrogerons sur les raisons de sa venue dans notre clinique en montrant que le client achète en fait un couple produit/service. La définition d’un service est difficile compte tenu de ses caractéristiques : – Un service est abstrait – On utilise indifféremment les termes produit et service (produits financiers, produits touristiques) – Le mot service n’est pas l’apanage du secteur des services (matériel informatique, constructeurs automobiles, etc.) – Le service a longtemps été défini comme un échange entre 2 personnes – La finalité du service est la même que celle d’un produit. Pour cet ensemble de raisons nous retiendrons cette définition: “Un service est une expérience temporelle vécue par le client lors de l’interaction de celui-ci avec le personnel de l’entreprise ou un support matériel et technique”. Elle révèle les trois caractéristiques communes des services: 1 - L’intangibilité des services 2 - L’interface entre le client et l’organisation 3 - La participation du client à la production des services Une clinique vétérinaire vend des couples produit/service, elle doit développer la qualité des services proposés aux clients. Développer la qualité des services, c ’est: 1 - Un facteur de différenciation 2 - Un moyen de valoriser sa vente 3 - Un outil de fidélisation

Pour développer la qualité des services, il est nécessaire d’envisager le rapport qualité / prix de l’acte effectué: sa valeur. Cela nous amène à développer les concepts de qualité intrinsèque d’un produit ou d’un service, de qualité perçue par le client et de qualité latente pouvant être proposée au client. Les tratégies d’augmentation de valeur perçue pour le client en augmentant la qualité ou en baissant le prix de l’acte sont envisagées. Le choix d’augmenter la qualité des services nécessite d’étudier les critères de satisfaction des clients. Ils peuvent être regroupés en quatre catégories: – les critères clés: ceux qui augmentent la satisfaction des clients au fur et à mesure qu’ils apparaissent lors de la prestation – les critères basiques: ceux que le client s’attend à trouver dans la clinique et dont l’absence va augmenter son insatisfaction – les critères secondaires: que ces critères soient présents ou absents, ils n’entraînent aucune satisfaction ou insatisfaction de la part du client – les critères plus: lorsque le client est confronté à ces c ri t è re s , le niveau de satisfaction du client augmente grandement. La présentation de ces critères nécessite des actions d i ff é re n t e s : – les critères clés: il faut les rendre plus visibles lors de la consultation – les critères basiques: il faut s’assurer d’un minimum de niveau de qualité sur ces critères – les critères secondaires: il faut matérialisezr ces services pour les faire passer en services clés – les critères plus: il faut re ch e rcher de nouveaux services afin d’augmenter la satisfaction des clients qui ne s’attendent pas à trouver ces services dans une clinique vétérinaire.

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Citologia e artrosi: cui prodest? Massimo Colosio Med Vet - Libero Professionista, Verbania

ANATOMIA E FISIOLOGIA DELLA CAPSULA ARTICOLARE E DEL LIQUIDO SINOVIALE La capsula articolare è un’importante struttura di connessione che unisce due estremità ossee mantenendo tuttavia una reciproca motilità. Essa è formata da due strati: quello più esterno fibroso, caratterizzato dalla presenza di numerose fibre collagene disposte parallelamente. Gli elementi cellulari sono rari, rappresentati principalmente da fibroblasti. Rari anche i vasi sanguigni. Particolare importanza rivestono le fibre nervose nelle componenti propriocettiva e dolorifica. Più internamente troviamo la membrana sinoviale costituita da un tessuto connettivo lasso, ricco di cellule di vasi sanguigni e linfatici, sul quale si adagiano, divisi da un’intima, da uno a tre strati di cellule sinoviali disposte in modo tale da simulare un epitelio di rivestimento tradendo le loro origini mesenchimali. Tali origini sono chiaramente rispettate nelle principali funzioni di queste cellule che si differenziano in sinoviociti di tipo A caratterizzati da attività di tipo macrofagico e sinoviociti di tipo B caratterizzati da attività di sintesi, in particolare dell’acido jaluronico. Il liquido articolare viene prodotto attraverso un processo di dialisi del sangue. È un liquido chiaro molto viscoso tendente al giallo. Svolge funzioni di vitale importanza per l’integrità dell’articolazione, in particolare provvede al nutrimento della cartilagine articolare che non è vascolarizzata. Le sostanze nutritive diffondono passivamente dalla membrana sinoviale e attraverso il liquido articolare raggiungono la cartilagine. Le funzioni meccaniche consistono nel lubrificare le superfici articolari rendendo agevole il loro scorrimento, mentre le caratteristiche di elevata comprimibilità del liquido articolare, rese possibili dall’estrema viscosità, impediscono alle cartilagini di venire in contatto nelle fasi di aumentata pressione intrarticolare, questa peculiarità viene meno in caso di deficit della sintesi di acido jaluronico o di una sua anomala degradazione con il risultato di una diretto contatto delle cartilagini e di una loro conseguente usura.

PRELIEVO DEL LIQUIDO SINOVIALE Le articolazioni dalle quali è possibile prelevare il liquido sinoviale sono la spalla, il gomito, il carpo, l’anca, il ginocchio e il tarso. Solitamente si esegue il prelievo in

anestesia generale (soprattutto per spalla e anca). Quando l’animale è molto tranquillo, l’articolazione facile da accedere e vi sono ectasie evidenti si può procedere con l’animale sveglio o sedato (ad esempio il carpo). La zona del prelievo va preparata mediante tricotomia e disinfezione chirurgica. Strumentario: siringhe sterili da 1, 2 o 5 ml con aghi 2022 gauge, provette con anticoagulante (EDTA, eparina).

MODALITÀ DEL PRELIEVO - Articolazione radio-carpica: il prelievo si esegue con il carpo in flessione inserendo l’ago cranialmente tra il radio e l’osso carpale radiale. - Articolazione intercarpica: il prelievo si esegue con il carpo in flessione inserendo l’ago cranialmente tra l’osso carpale radiale e il secondo e il terzo osso carpale. Questa cavità articolare è in comunicazione con quella carpo –metacarpale. - Articolazione del gomito: il gomito viene flesso e l’ago inserito dalla faccia caudo-laterale dell’articolazione in modo che risulti caudale e mediale al condilo laterale dell’omero. - Articolazione della spalla: la spalla viene leggermente flessa e l’ago inserito medialmente e centralmente alla cresta del tubercolo maggiore; si avanza con direzione ventrocaudale. - Articolazione del tarso: il prelievo si esegue inserendo l’ago con accesso cranio-mediale o cranio-laterale . - Articolazione del ginocchio: il ginocchio viene flesso per estendere la capsula. Si esegue pressione con un dito da un lato del legamento tibio-rotuleo. In questo modo si ottiene la protrusione della capsula dal lato opposto. L’ago viene inserito in questa zona in direzione obliqua verso lo spazio intercondiloideo della tibia. - Articolazione dell’anca: accesso laterale: il femore viene addotto e ruotato cranialmente e l’ago viene inserito cranialmente al grande trocantere del femore e fatto avanzare in direzione caudo-ventrale. accesso mediale: l’animale viene posizionato in decubito dorsale. Il femore viene abdotto fino ad essere perpendicolare al piano mediano. Punti di repere sono l’inserzione del muscolo pettineo e l’eminenza ileo-pettinea della pelvi. L’ago viene avanzato cranialmente con angolazione di 45°.

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ESAME DEL LIQUIDO SINOVIALE Parametri normali: Quantità

0,1 – 1 ml

Colore Torbidità

Tendente al giallo Trasparente

Viscosità Mucin Clot Test

Elevata Coagulo compatto

Gluc.liq/gluc. ematico Proteine totali

0,8 – 1,0 2 – 4 g/dl

Cellule nucleate PMN neutrofili

100 – 2000 mmc 1 –10%

Linfociti Istiociti

20-30% 30-40%

Sinoviociti

20-30%

Quantità: la quantità dipende dal tipo di articolazione e soprattutto dalla taglia dell’animale. Quando ci troviamo di fronte ad un campione molto esiguo, dobbiamo dare la precedenza all’esame citologico sul tal quale. In seguito vengono effettuati gli esami colturale, conta cellulare e valutazioni biochimiche. In corso di artropatia, solitamente ci troviamo di fronte ad un aumento della quantità del liquido. Torbidità: l’aumento di questo parametro corrisponde, di norma, ad un aumento del numero cellulare. Colore: spesso ci troviamo di fronte a campioni ematici; in questo caso bisogna distinguere una contaminazione iatrogena da una presenza di sangue preesistente e quindi patologica. Una prima indicazione si ha durante il prelievo, in quanto il sangue contaminante colora solo a tratti il liquido che si sta aspirando; mentre in campioni primariamente ematici il colore del liquido risulta essre costantemente rossastro. Un’altra importante informazione è data dal centrifugato in capillare del liquido: un PCV < 2%, supernatante trasparente sta ad indicare una contaminazione iatrogena, in questo caso citologicamente si evidenzia la presenza di piastrine; un PCV > 5% e supernatante emolitico invece indica un’emorragia acuta (da 12 a 48 ore), a livello citologico si possono riscontrare fenomeni di eritrofagocitosi; se invece il supernatante è itterico ci troviamo di fronte ad un’emorragia cronica (> 48 ore), eritrofagociti ed emosiderofagi caratterizzano il quadro citologico. Viscosità: è direttamente proporzionale alla concentrazione dell’acido jaluronico. La viscosità può essere valutata mettendo una goccia del liquido tra indice e pollice e allontanando le dita lentamente: una buona viscosità è data dalla formazione di un filamento di almeno 2 – 2,5 cm di lunghezza. Questa valutazione deve essere effettuata subito dopo il prelievo, in quanto nel liquido conservato in EDTA si assiste ad una diminuzione dell’acido jaluronico. Da un punto di vista citologico in campioni considerati con una normale viscosità gli elementi cellulari presenti, tendono a distribuirsi in filiere molto regolari. Mentre in campioni poco viscosi la loro distribuzione risulta meno lineare e continua. Mucin clot test: questo esame va eseguito su campini conservati in eparina; il liquido sinoviale viene aggiunto ad una soluzione al 2-2,5 % di acido acetico glaciale in rappor-

to di 1 : 4. La reazione porta alla formazione di un coagulo macroscopico. La valutazione del coagulo viene espressa attraverso una classificazione qualitativa: - buono se si forma un coagulo compatto in una soluzione trasparente - discreto se il coagulo ha un aspetto meno compatto in una soluzione leggermente torbida - povero se il coagulo è piccolo, friabile in una soluzione torbida - assente se si formano alcuni e piccoli flocculi in soluzione torbida. Rapporto tra il glucosio del liquido e quello ematico: un rapporto vicino ad 1 sta a significare un normale utilizzo metabolico del glucosio; un rapporto tra 0,5 e 0,8 indica la presenza di un’infiammazione asettica; un rapporto < 0,5 indica un’infiammazione settica. Proteine totali: normalmente la concentrazione è bassa (2-4 g/dl). La misurazione può essere effettuata con un refrattometro. Conta cellulare: può essere effettuata manualmente o con un contaglobuli elettronico. Fondamentale risulta essere la stima cellulare eseguita sul preparato tal quale a 400 ingrandimenti. Un campione a normale cellularità presenta circa 23 cellule per campo. Possiamo dire che un campione è caratterizzato da una normale cellularità, da un leggero, moderato o marcato aumento. Per quanto riguarda la conta manuale o con contaglobuli, il problema da affrontare è dato dalla viscosità e dal fatto che i diluenti per conta cellulare sono a base di acido acetico e quindi il loro utilizzo porta alla formazione del mucin clot. Una buona soluzione può essere quella di effettuare la conta su campioni conservati per qualche ora in EDTA in quanto questo anticoagulante porta ad una denaturazione anche se non totale dell’acido jaluronico. Il liquido in seguito viene diluito con una soluzione fisiologica in rapporto di 1 : 20 e quindi si esegue la conta cellulare in camera contaglobuli. Se si pensa di usare un contaglobuli elettronico bisogna eliminare completamente la viscosità del campione, anche e soprattutto per non danneggiare l’apparecchiatura. A questo proposito si consiglia di diluire il campione con una soluzione di jaluronidasi con concentrazione di 150 UI/ml in rapporto di 1:1. Parametri del liquido sinoviale in corso di artrosi: Quantità

Normale - aumento

Colore Torbidità

Lieve xantocromia Trasparente - aumentata

Viscosità

Normale - diminuita

Mucin Clot Test Gluc.liq/gluc. ematico

Normale-povero Normale - diminuito

Proteine totali

Normali - aumento

Cellule nucleate PMN neutrofili

Normali - aumento Normali - aumento

Linfociti

Variabili

Istiociti

Aumento

Sinoviociti

Aumento

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CITOLOGIA IN CORSO DI ARTROSI L’esame citologico del liquido sinoviale in corso di processo degenerativo rileva le alterazioni patologiche più caratteristiche quali: microemorragie, iperplasia della membrana sinoviale, erosione cartilaginea, erosione dell’osso subcondrale, infiammazione. Microemorragie: la presenza di microemorragie è resa evidente dal riscontro di eritrofagociti, emosiderofagi e da cristalli di ematoidina. Per una corretta interpretazione è di fondamentale importanza eseguire lo striscio su vetrino immediatamente dopo il prelievo in quanto le cellule macrofagiche mantengono in vitro le capacità fagocitarie, quindi il riscontro di eritrofagociti in campioni conservati in provetta può non essere correlato a microemorragie ma ad una contaminazione ematica durante il prelievo. Iperplasia della membrana sinoviale: di norma i sinoviociti esfoliano per lo più singolarmente nella componente liquida, mentre in corso di iperplasia della membrana sinoviale è possibile riscontrare tali cellule disposte in cluster di 6-10 elementi oltre ad un aumento del loro numero e della loro basofilia. Anche in questo caso per evitare false interpretazioni è importante eseguire lo striscio immediatamente dopo il prelievo e soprattutto non sottoporre il campione a centrifugazione in quanto tale metodica può “compattare” artificialmente elementi cellulari che sono esfoliati singolarmente. Erosione cartilaginea: a testimonianza di un danno erosivo a carico della cartilagine articolare possiamo riscontr are frammenti cartilaginei di forma irregolare visibili anche in preparati non colorati. In caso di preparati colorati tali frammenti assumono affinità tintoriali eosinofile o basofile in relazione allo strato cartilagineo di provenienza. Erosione dell’osso subcondrale: in corso di erosione ossea è possibile rilevare all’esame citologico la presenza di cellule multinucleate rapportabili ad osteoclasti. Infiammazione: quando il processo degenerativo assume car atteristiche infiammatorie il ruolo della citologia diventa più che mai importante nella ricerca di eventuali risvolti settici. Va considerato che spesso il paziente portatore di malattia artrosica è un soggetto anziano che in molti casi convive con patologie a decorso cronico (stomatiti, endocarditi, pielonefriti, prostatiti, cistiti, ecc.). In corso di batteriemie i germi si localizzano principalmente nei vari distretti del sistema reticolo-endoteliale, e la membrana sinoviale ne è parte integrante. A ciò si aggiunge che in corso di infiam-

mazione i sinoviociti di tipo A perdono in modo significativo la capacità di intraprendere attività fagocitarie venendo meno il loro ruolo difensivo. L’esame citologico può svelare la presenza di batteri sia all’osservazione diretta sia dal riscontro di polimorfonucleati neutrofili colpiti da processi degenerativi, in particolare la cariolisi. In questi casi l’indicazione è quella di proseguire l’analisi del liquido articolare con l’esame batteriologico. L’esame del liquido articolare in particolare della sua componente cellulare può dare importanti suggerimenti nei casi in cui il processo artrosico secondario ad una causa certa come ad esempio la rottura del legamento crociato anteriore riconosce concause di natura immunomediata. Il riscontro di una componente cellulare composta in maggior parte da elementi linfocitari e plasmacellule può essere indicativa di artrosinovite linfoplasmacellulare a sfondo immunomediato. Cosi come il riscontro di cellule LE (neutrofili che hanno fagocitato materiale nucleare sul quale hanno agito anticorpi antinucleari) è indicativa ma non patognomonica di LES.

CITOLOGIA IN CORSO DI ARTRITE REUMATOIDE In corso di artrite reumatoide i polimorfonucleati neutrofili caratterizzano il quadro citologico accompagnati da fenomeni degenerativi in particolare la picnosi. Possono inoltre essere presenti frammenti di materiale nucleare. In medicina umana sono descritti i ragociti che sono neutrofili contenenti inclusioni citoplasmatiche formate da immunocomplessi, visibili in vetrini non colorati ed esaminati a bassa luce e con campo bagnato. Nel cane sono rari.

CITOLOGIA IN CORSO DI SINOVIOSARCOMA Il sarcoma sinoviale è un evenienza rara nel cane, inoltre la diagnosi citologica dall’esame del liquido articolare risulta ardua perché tale neoplasia difficilmente esfolia nella componente liquida, inoltre l’insorgenza risiede in strutture paraarticolari e non nello strato interno di rivestimento della membrana sinoviale. Quando si sospetta questa patologia è utile associare alla citologia del liquido una citologia per agoaspirazione dei tessuti articolari.

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Blepharitis Blefarite

Michael Davidson DVM, Dipl ACVO - North Carolina State University, Raleigh, USA

SIGNALMENT AND BREED PREDISPOSITION Blepharitis, or eyelid inflammation is seen in all ages and breeds of dogs, and less commonly in cats. Juvenile pyoderma (puppy strangles), mycotic blepharitis and demodetic mange blepharitis are seen primarily in young dogs. Allergic blepharitis is seen in breeds predisposed to atop y, (e.g. West Highland white terrier, Shetland Sheepdogs, etc.), and bacterial blepharitis is common in dogs with sebborheic skin disorders such as the American Cocker Spaniel, Shi Tzu, and Lhasa Apso. Collies are predisposed to nodular granulomatous episclerokeratitis (NGE) which may have eyelid involvement.

“eosinophilic blepharoconjunctivitis" has been identified in cats, and is thought to have a similar pathogenesis as eosinophilic keratitis. 5) Bacterial blepharitis. This may be seen as a primary condition such as streptococcal infection in puppies, or more commonly as a secondary condition (for example, associated with sebborheic skin disease and secondary pyoderma). A chronic staphylococcal infection may also cause a hypersensitivity reaction. 6) Mycotic blepharitis such as Micosporum and Tricophyton spp. 7) Parasitic blepharitis including demodectic and sarcoptic mange

DIAGNOSTIC PLAN CLINICAL FINDINGS Findings may include hyperemia, edema, alopecia, ulceration, and exudate. A nodular swelling or mass lesion is seen with chalazion and NGE with eyelid involvement. and Secondary effects on eyelid function such as entropian, ectropian, or lagophthalmos may be evident. Conjunctival and corneal lesions are also commonly present concurrently.

A critical examination of the eyelids with magnification and a thorough physical exam to look for evidence of systemic manifestations of these specific diseases will usually establish a diagnosis. Cytologic evaluation of impression smears, fine needle aspirate or superficial tissue scrapings is useful with bacterial and parasitic blepharitis. Tissue biopsy may be necessary for the autoimmune disorders,especially to specifically characterize the disease. A fungal culture for dermatophytes established a diagnosis of mycotic blepharitis.

PATHOGENESIS A hordeolum results from inflammation of the glandular tissues of the eyelids and include an inflammation of the glands of Ziess or Moll (stye), meibomitis (often initiated by a staphylococcal infection) and chalazion (a granulomatous inflammation resulting from obstruction of the meibomian gland puncta). Other types of blepharitis have a pathogenesis specific for that condition (e.g. immune-mediated, inflammation secondary to microbial or parasitic toxins, etc.).

DIFFERENTIAL DIAGNOSIS 1) Hordeolum (stye or meibomitis) 2) Chalazion 3) Allergic blepharitis, often associated with generalized atopy 4) Autoimmune blepharitis, a large number of specific conditions including the pemphigus group, lupus (discoid and systemic), and drug reaction. A condition known as

TREATMENT PLAN This depends on the specific condition. Internal hordeolum are treated with topical and/or systemic antibiotics, hot compresses and manual expression of the lesions. Chalazion generally require excision and curettage and topical antibiotic therapy. Many types of blepharitis in dogs are associated with sebborheic or atopic dermatitis and the clinician must address these conditions with a systemic workup and treatment plan (for example investigation for an underlying metabolic or endocrine disorder, food allergy, etc). Systemic antibiotic therapy is necessary for the deeper bacterial blepharitis. For staphylococcal blepharitis specifically, I recommend first a course of systemic antibiotics, and if there is no response or recurrence a course of systemic antibiotics and corticosteriods, and if there is still an incomplete response, use of autologous or commercially available (Staph lysate) vaccines. Immunosuppressive therapy is nec essary for autoimmune blepharitis.

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Eyelid neoplasia Neoplasie palpebrali

Michael Davidson DVM, Dipl ACVO - North Carolina State University, Raleigh, USA

SIGNALMENT AND BREED PREDISPOSITION Eyelid neoplasia is very common in older-aged dogs of all breeds and somewhat less common in older-aged cats. The exception to the age distribution is canine (infectious) papillomas or papillomatosis and histocytomas, both of which may be seen in young dogs. Eyelid squamous cell carcinoma is more common in lightly pigmented cats. Fibrosarcoma of the eyelid may be associated with feline leukemia virus (feline sarcoma virus) infection.

CLINICAL FINDINGS Eyelid neoplasia manifests as a mass lesion,or less commonly an ulcerative lesion, generally on or near the eyelid margin. The lesion can be found in the cutaneous tissues with surface irregularity or in the subcutaneous tissue with no defect in the dermis. In dogs, the mass lesion is often pigmented to varying degrees, with a rough, irregular surface. In cats eyelid neoplasia is often presents with an ulcerated surface. Secondary chalazion are common with canine eyelid neoplasia.

PATHOGENESIS In dogs, most eyelid neoplasia are benign both histologically and clinically and become clinically important when it reaches a size to physically irritate or contact the conjunctiva and cornea. This manifest with ocular pain and discharge, conjunctival hyperemia and swelling, or corneal lesions manifesting as edema, fibrosis, vascularization and/or pigmentation. Marginal eyelid neoplasia in the dog often causes a obstruction of the meibomian gland puncta leading to a secondary chalazion, which can be as large or larger than the primary lesion. Larger eyelid masses may be associated with lagophthalmos or eyelid dysfunction. In cats eyelid neoplasia is generally malignant, often locally invasive. The lesions are important for the same reasons as in dogs, and also because of the potential for either local growth or invasions/destruction of adjacent tissues, or less commonly because of metastasis.

DIFFERENTIAL DIAGNOSIS A neoplastic mass or swelling in the eyelids must be distinguished from an inflammatory or cystic mass lesion by means cited below. Some types of immune mediated inflammatory masses, notably nodular granulomatous episclerokeratitis with eyelid involvement, may be very difficult to distinguish clinically from neoplasia. Many different types of neoplasia must be considered by the clinician. In dogs, the most common neoplasia is a sebaceous adenoma of the meibomian gland. This typically affects the eyelid margin, has a rough irregular surface, may be pigmented or pink in color, and are slow growing. Secondary chalazion are very common with this tumor. 0ther less common tumor types include a benign melanoma (seen on the eyelid skin, not the eyelid margin) and papilloma. Malignant tumor types include an adenocarcinoma of the meibomian gland, melanoma, histocytoma, mast cell tumor, and rarely squamous cell carcinoma or basal cell carcinoma. In cats, the most common eyelid neoplasia is squamous cell carcinoma. This lesion may involve the eyelid skin or palpebral conjunctiva, and may present as either a mass lesion or an ulcerative lesion, or both. Concurrent pinnal squamous cell carcinoma may be seen. Other types of neoplasia may include fibrosarcoma, lymphosarcoma, adenocarcinoma, mast cell tumor, and basal cell carcinoma. Adenomas and squamous papillomas of the eyelid are uncommon in cats.

DIAGNOSTIC PLAN Eyelid neoplasia is generally diagnosed by the characteristic clinical appearance and excisional biopsy at the time of definitive treatment. All suspected eyelid neoplasia should be examined histologically, even if the clinician feels the eyelid mass is benign (i.e. as is commonly seen in the dog). When difficulty arises distinguishing neoplasia from inflammatory or cystic masses, a fine needle aspirate with cytologic evaluation of the lesion may be useful. Exfoliative cytology may also be used, but many eyelid neoplasms are difficult to definitively diagnosis (or distinguish whether the lesion is benign or malignant) based on cytology alone.

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TREATMENT Neoplasia of the eyelid may be surgically treated using one of four general techniques: 1) excision and cryosurgery 2)excision with primary closure of the wound or 3) excision with a grafting procedure for closure of the wound. 4) intralesional chemotherapy, or 5)local radiation therapy. The first two options may be used on eyelid tumors involving less than 25-30% of the eyelid margin. Cryosugery may also be useful for large periocular squamous cell carcinoma in the cat. When a cryosurgical unit is not available, a V-lid resection (or for slightly larger tumors a four sided excision) may be used to treat small eyelid tumors. For tumors larger than

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1/3 of the lid margin, and when a full thickness excision of the affected lid and conjunctival is necessary, a tissue graft to restore the lid margin is necessary. A number of different techniques are applicable including a sliding H-graft, rotational graft, mucocutaneous subdermal plexus, cross lid flap, and Cutler-Beard procedure.(bucket-handle flap). Periocular squamous cell carcinoma in cats may sometimes be treated with intralesional carboplatin using 3-4 injections at 1mg/cm3 dosage repeated at 2 week intervals. Local radiation therapy may be used for large, malignant tumors of the eyelid but secondary effects of the radiation on the ocular tissues must be considered and an enucleation/exenteration may be necessary either before or after the radiotherapy.

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Swelling of the nictitans or medial canthal region Tumefazione della terza palpebra o della regione del canto mediale

Michael Davidson DVM, Dipl ACVO - North Carolina State University, Raleigh, USA

SIGNALMENT AND BREED PREDISPOSITION Prolapse of the nictitans gland is seen in young dogs and predisposed breeds include certain beagles, American cocker spaniels, bulldogs, Mastiffs, and Newfoundland and in cats, the Burmese breed. The basset hound and dachshund breeds are predisposed to cystic nasolacrimal lesions. Young, German Shorthaired pointers and giant breed dogs are predisposed to eversion/inversion of the nictitans cartilage. The German shepherd breed and greyhounds are predisposed to nictitans involvement with chronic superficial keratitis (pannus). The collie breed is predisposed to nodular granulomatous episclerokeratitis with nictitans involvement. Neoplasia of the nictitans affect primarily older aged dogs and cats.

CLINICAL FINDINGS These may include a mass lesion in the medial canthal region and/or thickening of the nictitans. Depending on the condition, hyperemia of the conjunctiva, ocular discharge, epiphora, pain (blepharospasm), and secondary corneal changes may also be seen.

PATHOGENESIS Swelling in this region can be due to normal ocular tissues that are malpositioned (nictitans gland, orbital fat) or deformed (cartilage), cystic lesions, inflammation, or neoplasia.

DIFFERENTIAL DIAGNOSIS 1) prolapsed nictitans gland. This condition occurs in young dogs of certain breed. It is thought to be the result of a weak connection between the vertical cartilage of the nictitans and the gland itself. Deformities of the cartilage may be concurrently present, either as a primary or secondary event. 2) Eversion/Inversion of the nictitans cartilage. This condition is seen in young (<1 year of age) giant breed dogs and German shorthaired pointers and results from excessive or imbalanced growth of the cartilage in relation to the nictitans.

3) Dacryocystitis. This condition results from an inflammation (often bacterial-induced) of the nasolacrimal system. Secondary obstruction may be seen with epiphora. A mucopurulent ocular discharge, disproportionately more severe than conjunctival hyperemia or chemosis, is characteristic. 4) Cystic dilatation of the nasolacrimal system (dacryops). This condition is seen in young dogs and is results from a congential malformation or displacement of a segment of the nasolacrimal system 5) Plasma cell infiltration. This is seen in German shepherd dogs, usually in conjunction with lesions of pannus (chronic superficial keratitis). 6) Orbital fat prolapse. This condition occurs predominately in older aged dogs and results from an age related degeneration or atrophy of the orbital septum with secondary prolapse of orbital fat into the subconjunctival space, or less commonly from rupture of the orbital septum from trauma. 7) Neoplasia of the nictitans. In dogs, this is most commonly an adenocarcinoma of the nictitans or hemangioma/hemangiosarcoma of the nictitans. In cats, squamous cell carcinoma and lymphosarcoma are most common. 8) Nodular granulomatous episclerokeratitis. This immune mediated condition affect predominately the lateral limbal region but eyelid or nictitans involvement may also be present. The collie breed is predisposed.

DIAGNOSTIC PLAN Physical inspection and manipulation of the nictitans with a Q-tip swab will give an indication of the character of the swelling. The nasolacrimal system should be flushed with a cannula. Cytologic evaluation of a conjunctival scraping from the surface of the nictitans (plasmoma, neoplasia) or fine needle aspirate (orbital fat prolapse, neoplasia, cystic dilation of the nasolacrimal system) may be useful. Biopsy of the affected region may be necessary for neoplasia or NGE.

THERAPY 1) Prolapsed nictitans gland. Surgical replace the gland by any number of techniques.

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2) Eversion/Inversion of the nictitans cartilage. Excise the scrolled cartilage, and leave the conjunctival wound to heal without suturing. 3) Dacryocystitis. Topical and systemic antibiotics, periodic flushing of the nasolacrimal system and/or cannulation of the NL system for 2-4 weeks. 4) Cystic dilatation of the nasolacrimal system (dacryops) requires surgical excision of the cyst. 5) Plasma cell infiltration is treated with topical corticosteriods or cyclosporin A.

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6) Orbital fat prolapse may not require treatment as it is often nonpainful. Excision of the herniated fat and closure of the orbital septum defect may be necessary. 7) Neoplasia of the nictitans (if primary) is treated by excision of the entire gland if the neoplasia is malignant, and the affected portion if benign. , 8) Nodular gra nu l o m atous episclerokeratitis is tre at e d with topical and systemic corticosteriods and/or oral azothiaprine.

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Anterior uveitis Uveite acuta anterior e

Michael Davidson DVM, Dipl ACVO - North Carolina State University, Raleigh, USA

SIGNALMENT AND BREED PREDISPOSITION Young dogs and cats are more likely to have infectious cases for anterior uveitis, whereas older dogs and cats more commonly have idiopathic or immune mediated uveitis. Male dogs are predisposed to certain types of infectious anterior uveitis, owing to a higher exposure rate to the specific organism. 5)

PATHOGENESIS Inflammation of the anterior uvea with a prominent prostaglandin/leukotrienemediated inflammation. Microbial agents, trauma, and neuronal reflexes (oculopupillary/axonal reflexes) may be involved. A hypersensitivity reaction (immune mediated) contribute to the pathogenesis in many cases.

CLINICAL SIGNS 1) 2) 3) 4) 5) 6) 7) 8) 9)

Photophobia Blepharospasm, epiphora Circumcorneal scleral injection/conjunctival hyperemia. Deep corneal vascularization Swelling of iris Miosis Ocular hypotony Poor response to topical mydriatic Aqueous flare (protein in aqueous humor as result of blood ocular barrier breakdown) 10) Fibrin, keratic precipitates (clumps of inflammatory cells adhered to ventral corneal endothelium), hypopyon 11) Corneal edema

DIAGNOSTIC PLAN 1)

DIFFERENTIAL DIAGNOSIS

1) 2) 3)

4) a)

Trauma Surgery Secondary to corneal or scleral inflammation (axonal and oculopupillary reflexes) Systemic infectious disease Fungal (histoplasmosis, blastomycosis, coccidioidomycosis, cryptococcosis)

b) Bacterial (brucellosis, leptospirosis, or uveitis can occur with any systemic bacterial disease, i.e., bacterial endocarditis, discospondylitis, UTI, pyometra, GI tract infection, deep pyoderma, etc.) c) Protozoal (toxoplasmosis) d) Rickettsial (Ehrlichia canis and Rickettsia rickettsii) e) Viral (canine infectious hepatitis, FeLV, corona virus of FIP, FIV) f) Algal (protothecosis) Lens-induced uveitis – common with cataracts – usually mild, decreases prognosis for successful cataract surgery. Infectious canine hepatitis – uveitis may occur with naturally occurring disease, or rarely response to vaccination with modified live vaccine. Uveodermatologic syndrome – granulomatous panuveitis and dermal depigmentation (VKH-like syndrome). An immune-mediated destruction of melanocyte-containing tissues, i.e., eyes and skin. Most common in Akita, Siberian husky and other Arctic Circle breeds, but any breed may be affected. Idiopathic** – In many cases of uveitis (in all species), a specific cause cannot be identified. Immunologically mediated factors are thought to contribute to most cases of idiopathic, recurrent uveitis. Anterior uveal neoplasia can mimic the signs of anterior uveitis. Secondary neoplasia is most commonly lymphosarcoma. Ocular melanoma and ciliary body adenoma/adenocarcinoma are the most common primary tumors.

4) 5)

A thorough ocular exam. Is there any evidence of primary ocular disease that accounts for the uveitis? Funduscopic examination is necessary as posterior uveitis (choroiditis, chorioretinitis) frequently occurs concurrently with anterior uveitis. A thorough physical examination is mandatory with all cases of uveitis. Clinical pathology including complete blood count, serum chemistries and serology for suspected microbial agents. Radiology – Thoracic, useful to rule out neoplastic and fungal diseases. Anterior chamber paracentesis and cytology – usually not diagnostic except in case of ocular lymphosarcoma

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Vitreal paracentesis: useful for diagnosis of mycotic endophthalmitis, generally only done in eyes with poor visual prognosis. Lymph node aspirate: indicated if lymphadenopathy present, especially useful in diagnosis of lymphosarcoma and systemic mycoses. Ocular ultrasound if can’t visualize intraocular structures, helps identify associated lesions.

3) 4) 5)

THERAPY

Mydriasis to prevent synechia, painful ciliary spasm and restore the blood/aqueous bar rier Topical corticosteriods – q 1 to 2 hrs initially, then 3 to 6 times daily. Indicated even in most cases of infectious

uveitis. (Note that most other topical steroid preparations don’t achieve adequate intraocular levels to be therapeutic). Topical nonsteroidal anti-inflammatory drugs – flurbiprofen (Ocufen®) – sometimes useful as adjunct therapy. Subconjunctival corticosteriods use with caution in systemic disease. Systemic corticosteroids – indicated in moderate to severe cases of uveitis, where the presence of a systemic infectious disease has been eliminated. Systemic nonsteroidal anti-inflammatory agents, useful when systemic steroids contraindicated. Chemotherapeutic agents such as azathioprine, cyclophosphamide - use with extreme caution in some cases of recalcitrant, idiopathic uveitis. Systemic antibiotics – rarely indicated .

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Cataract Cataratta

Michael Davidson DVM, Dipl ACVO - North Carolina State University, Raleigh, USA

SIGNALMENT AND BREED PREDISPOSITION Many breeds of dogs are predisposed to primary, heritable cataracts (the American College of Veterinary Ophthalmologists Genetics Book list over 75 predisposed breeds). Young animals are predisposed to cataracts from traumatic injury. Older aged animals are predisposed to cataracts secondary to intraocular neoplasia. Older aged male cats, because they are predisposed to immune mediated uveitis, may develop secondary cataracts. Older aged animals are at risk for developing age-related (senile) cataracts.

PATHOGENESIS All cataracts result from a disruption of the essential biochemical pathways or anatomic features of the lens that maintain lens transparency. Disruption of the cellular biologic processes results in cell membrane derangement, protein aggregation, osmotic influx of water and cellular swelling, accumulation of cellular byproducts and subsequent light scattering by lens fibers.

CLINICAL FINDINGS The specific findings depend on the location of the cataract in the lens (capsular, cortical, nuclear, equatorial, etc) and the stage of cataract development, which typically progresses from an incipient, immature, mature, and hypermature states. A blue to white appearance to the lens will be seen on direct focal illumination, and a dark appearance to the cataract will be seen on retroillumination using the tapetal or fundic reflection. Incipient cataracts refer to obstruction of <10% of the fundic reflection, immature refers to obstruction from 10-99%, mature refers to obstruction of the entire fundic reflection, and hypermature cataracts are those in which some lens content has resorbed. Other clinical findings may include signs of lensinduced uveitis, or lens displacement. Cataracts must be distinguished from lenticular sclerosis, a normal aging change causing translucency of the lens. This is accomplished by retroillumination of the lens.

DIFFERENTIAL DIAGNOSIS 1) Inherited cataracts* – most common etiology of cataracts in dogs. Many breeds are af fected. 2) Senility – “Senile” cataract may refer both to time of onset and etiology. With the latter, refers to an idiopathic change occurring with age. 3) Metabolic – Diabetic cataracts – as glucose levels increase in the eye with diabetes, hexokinase, the regulatory enzyme, becomes saturated. Glucose accumulates in the lens and begins to be metabolized through the sorbitol pathway. The sugar alcohols sorbitol and fructose accumulate within the cells of the lens since they penetrate cell membranes (including the lens capsule) poorly. The result is an intracellular accumulation of solutes and hypertonicity, which results in an accumulation of water within the lens fibers. Swelling of the lens fibers progresses and the fibers rupture forming vacuoles in the lens cortices. This continues until the entire lens becomes cataractous. Large majority of diabetic dogs eventually develop cataracts. Cataracts may also be seen with hypocalcemia. 4) Nutrition – Puppies and kittens, may develop cataracts from nutrient deficiency (i.e., amino acid). This usually does not occur unless puppies are orphaned within the first 2 weeks of life and fed exclusively milk replacer. Cataracts may or may not r egress, depending on extent. 5) Toxic. Certain drugs can cause cataracts, for example oral ketaconazole administration may cause cataracts. A more common example of a toxic cataract are dogs with progressive retinal atrophy (PRA) may develop cataracts secondary to by-products of retinal degeneration (dialdehyde) which diffuse through the vitreous to the lens, cataracts secondary to PRA begin in posterior cortex of lens. 6) Secondary to inflammation (anterior uveitis) 7) Persistent vascular remnants (PPMs, hyaloid remnants) 8) Trauma – usually requires lens capsule penetration.

DIAGNOSTIC PLAN A critical ophthalmic exam is necessary to stage the development of the cataract, identify the location within the lens, evaluate for any evidence of any underlying ocular disease that may have caused cataracts, evaluated for the pres-

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ence of lens induced uveitis and lens subluxation (common secondary findings). In dogs, a blood glucose level should routinely be performed. In cats, because the most common cause is an anterior uveitis, a systemic diagnostic workup is generally indicated. Prior to considering cataract surgery, an electoretinogram, ocular ultrasound, and gonioscopy should be performed.

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THERAPY There is no medical therapy for cataracts, and cataracts causing visual problems should be treated by lens removal. Phacoemulsification and intraocular lens implantation are the standard of care for dogs and the procedure is best performed by a trained veterinary ophthalmologists.

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Mydriasis Midriasi

Michael Davidson DVM, Dipl ACVO - North Carolina State University, Raleigh, USA

Mydriasis refers to an abnormally dilated pupil, characterized as such when the animal is evaluated in ambient room light. When the clinician encounters an animal with mydriasis, it is important to perform a thorough ocular examination, including a critical assessment of the pupillary light reflexes and menace response. After this evaluation, it is useful to categorize and consider two different clinical situations, mydriasis with and without apparent vision loss. The differential diagnoses for these two conditions can then be considered as follows: Mydriasis without visual deficit

1. mechanical dysfunction: - iris atrophy 2. neurologic: - efferent arm lesion (CN III) - pharmacologic blockade (i.e., topical atropine administration or exposure to natural plants with components that have parasympatholytic properties) 3. endogenous norepinephrine release by frightened animal being examined

Mydriasis with visual deficit

1. Neurologic (afferent arm lesion): - retina, optic nerve or contralateral optic tract lesion 2. iris mechanical dysfunction and disease process causing concurrent vision loss: - lens luxation - glaucoma - synechiae

**Note visual deficit c/out PLR deficit would infer a cortical lesion.

Perhaps the most common situation where an abnormally large pupil is seen is in the frightened or anxious animal. This occurs from endogenous norepinephrine release. Another common cause in older age animals is iris sphincter atrophy. This is diagnosed by evaluated the pupillary margin for a “scalloped”or ir regular appearance, and by the fact that this pupil will not constrict when topical 2% pilocarpine (a direct acting parasympathomimetic agent) is applied. It is also important to note that a pupillary light reflex deficit which includes mydriasis is more commonly the result of mechanical dysfunction (i.e. a disease such as iris atrophy, glaucoma, synechiae, lens luxation) compared with a neurologic problem. As a result, a critical ophthalmic exam should always be performed to rule out an underlying, primary ocular condition causing the mydriasis. If a neurophthalmic problem is identified, the lesion is either be in the afferent pathway (retina, optic nerve, optic chiasm, or optic tract) if vision is affected, or the efferent pathway (cranial nerve III) if vision is unaffected. The clinician should always perform a funduscopic examination to evaluate that part of the neuroophthalmic pathway that can be visualized, and perform a neurologic examination to look for concurrent deficits. The most common site for a bilateral afferent arm lesion is in the retina; the second most common site would be at the optic chiasm. Diagnostic tests for neurophthalmic conditions include electroretinography, visual evoked potential testing, radiographic imaging studies of the brain such at CT scan or MRI, and cerebrospinal fluid analysis.

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Blindness in dogs and cats Cecità nel cane e nel gatto

Michael Davidson DVM, Dipl ACVO - North Carolina State University, Raleigh, USA

Blindness in dogs and cats is a common sequel to a number of different ocular disease processes. In general, blindness results from a lesion in the ocular media that causes non transparency, or a lesion somewhere along the visual pathway which includes the retina, optic nerve, optic chiasm, optic tract, optic radiation and visual (occipital) cortex. When a clinician evaluates an animal with blindness, it is important to perform a thorough ocular examination to evaluate for media opacification. The pupillary light reflexes should be characterized and a complete funduscopic examination performed. The status of the pupillary light reflex can assist the clinician in localizing the site of the lesion. The following is an outline of the common diffe rential diagnoses (major cat ego ries or anatomic areas which may be involved) with blindness in dogs and cats.

Congenital Blindness A. maldevelopment of entire globe 1. microphthalmia 2. anophthalmia B. opacification of ocular media 1. persistent pupillary membranes 2. congenital cataracts 3. persistent hyaloid artery C. retinal dysfunction 1. severe retinal dysplasia with detachment 2. (early onset) rod-cone dysplasia 3. severe Collie eye anomaly with detachment D. visual pathway dysfunction 1. optic nerve hypoplasia 2. hydrocephalus

II. Acute Blindness A. opacification of ocular media 1. severe cornea ulceration/perforation 2. corneal edema (acute) 3. anterior uveitis 4. hyphema/hypopyon 5. cataracts (acute onset) 6. lens luxation 7. vitreal hemorrhage B. retinal dysfunction 1. glaucoma (retinal dysfunction) 2. sudden acquired retinal degeneration 3. retinal detachment C. visual pathway dysfunction 1. optic neuritis 2. proptosis of the globe with optic nerve damage 3. CNS lesions (trauma, inflammation, toxic,vascular, hypoxia, postictal, neoplasia) III. Gradual Blindness A. opacification of ocular media 1. corneal vascularization, scarring, edema, 2. cataracts (gradual) 3. chronic uveitis with secondary ocular changes B. retinal dysfunction 1. progressive retinal atrophy (rod-cone degeneration) 2. other types, retinal degeneration (e.g., nutritional, toxic, senile) C. visual pathway dysfunction 1. optic nerve neoplasia 2. CNS lesions (trauma, inflammation, toxic, vascular, hypoxia, postictal, neoplasia)

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42° Congresso Nazionale SCIVAC

Ocular consequences of trauma in raptors Traumatologia oculare nei rapaci

Michael Davidson DVM, Dipl ACVO - North Carolina State University, Raleigh, USA

SIGNALMENT All types of free living raptors may suffer from ocular trauma, and these lesions are common. Ocular trauma can have a profound influence on vision and release potential, so an assessment of the eye is critical in all injured or diseased raptors.

CLINICAL FINDINGS Orbital or periorbial bone fracture and collateral damage to other facial structures is common and may result in an obvious deformity of the facial anatomy. Abrasion or laceration of the eyelids, or the nictitans may occur. Corneal ulceration or corneal perforation with iris prolapse and secondary anterior uveitis is common. Traumatic anterior uveitis from either blunt or penetrating trauma may cause aqueous flare, hypotony, miosis, exudate in the anterior chamber, swelling of the iris or hyphema. Lens luxation is uncommon. Cataract may be seen as a late sequel to blunt or penetrating trauma. The most common traumatic lesions in the raptor eye are in the posterior segment and can include retinal hemorrhage, edema, or detachment, avulsion of the pectin, or scleral rupture. Varying degrees of pupillary light abnormalities and vision loss will be seen, depending on the severity of the lesions.

SOURCES AND TYPES OF OCULAR TRAUMA Studies suggest that many may result from the birds’ interactions with humans, although the specific nature of the trauma is often not determined. Flight into objects such as windows, buildings, automobiles, and trees; gunshot wounds; wounds from attempts of prey to escape the raptor; and thermal injuries are possible causes.

PATHOGENESIS Ocular trauma in raptors is generally caused by penetrating (sharp), blunt or thermal type injury. Penetrating injury involve the superficial ocular structures (eyelids, nictitans, cornea), and intraocular structures if the penetrating injury perforates the globe. Penetrating injury may be complicated

if caused by a gunshot wound or foreign body. Blunt traumatic injuries to the periorbit or globe cause lesions coup, countercoup, or direct ocular compression mechanisms. Coup lesions are induced by local trauma directly at the site of contact. Contrecoup injures is at the a location opposite the impact, that results in contusive forces at distant tissue interface (posterior segment of the eye). These lesions are common in raptors due to the tightly encased eye and the large lens which transfers force vectors posteriorly. Direct ocular compressive forces occur when the eye is compressed along the anterioposterior axis, with horizontal displacement of the fixed fluid volume within the globe; these lesions may damage the cornea or sclera, lens, or retina/choroid, which may be stretched and produce a tear. Thermal injury, from fire, smoke, or other heat sources causes burns and ulceration of the adnexal structures and corneal ulceration and edema. Intraocular tissues are typically spared.

DIAGNOSTIC PLAN A thorough ocular examination should be performed in all cases of suspected trauma to the eye in raptors, with particular attention giving to the posterior segment findings using indirect ophthalmoscopy. Cytological evaluation of the eyelids, conjunctiva, or cornea is useful to identify microorganisms or inflammatory cell type. Plain radiographic films of the orbital area may be useful to identify fractures or displacement of the orbital or periorbital bones or scleral ossicles. Ultrasound evaluation of the globe is very useful if the deep ocular structures cannot be visualized.

THERAPY Typically, trauma sufficient to result in orbital fractures or scleral ossicles causes sufficient collateral globe and head injury that surgical treatment or release of the bird is not practical. Small orbital bone fractures without displacement may be managed conservatively. Abrasion or laceration of the lid managed with application of a topical antibiotic ointment, and primary suturing of the wound, if present. If a laceration extends into the lid margin, careful attention should be given to reestablishing the normal margin surgically. Secondary microbial of the lids

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should be treated with systemic antibiotic therapy. Lacerations of the nictitans should be carefully sutured with 6 to 80 suture material. Ulcerative keratitis is treated with a topical antibiotic 3 times daily in uncomplicated cases and frequently (every 2-3 hours) if bacteria infection is identified. Surgical treatment with a conjunctival graft is performed for deep or infected corneal ulcers. Acute corneal trauma that is penetrating may be surgically repaired by direct corneal suturing with 7 to 8-0 absorbable suture material, with replacement or amputation of prolapsed uveal tract if present. Systemic broad-spectrum antibiotics should be administered whenever a ocular perforation is encountered. Chronic perforating wounds with anterior synechia are left untreated, if nonpainful.

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Traumatic anterior uveitis in the absence of corneal ulceration should be treated with a topical corticosteriods administered 3-6x daily, or with 0.1 to 0.25 cc subconjunctival injection of a corticosteriod if multiple times per day restraint of the bird is a concern. Substantial hyphema or fibrin strands which have not resorbed in 2-3 days may benefit from treatment by lysis with an intracameral injection of tissue plasminogen activator. Penetrating injury which severely traumatizes the globe may necessitate enucleation for relief of pain. While systemic anti-inflammatory therapy is sometimes used in birds with posterior segment injury from trauma (i.e. retinal hemorrhage, edema or detachment), there is no evidence to suggest that this is of any benefit, and no treatment is beneficial.

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Medical management of chronic renal failure in the cat Trattamento medico dell’insufficienza renale cronica nel gatto

Stephen DiBartola DVM, Dipl ACVIM - Ohio State University - Columbus, Ohio, USA

Riassunto In questo lavoro viene presentata una rassegna della terapia medica dell’insufficienza renale cronica del gatto com prendente il trattamento nutrizionale, la terapia dell’iperparatiroidismo secondario renale, l’impiego dei leganti del fo sforo nella dieta, degli agenti di blocco dei recettori H2, della terapia sostitutiva con alcali, dell’integrazione con po tassio e della terapia sostitutiva endocrina con eritropoietina e calcitriolo. Viene anche discusso il trattamento dell’i pertensione. La relazione si conclude con una discussione del trattamento dell’ipertiroidismo e dell’insufficienza renale cronica concomitanti nel gatto.

This presentation will provide an overview of the medical management of chronic renal failure in cats including nu tritional management, treatment of renal secondary hyperparathyroidism, dietary phosphorus binders, H2 receptor blockers, alkali replacement, potassium supplementation and endocrine replacement including erythropoietin and cal citriol. Management of hypertension also will be discussed. The presentation will conclude with a discussion of the man agement of concurrent hyperthyroidism and chronic renal failure in cats.

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Principles of fluid therapy in the dog and cat Principi di terapia fluida nel cane e nel gatto

Stephen DiBartola DVM, Dipl ACVIM - Ohio State University - Columbus, Ohio, USA

Riassunto In questa relazione viene presentata una rassegna dei principi della fluidoterapia, fornendo una risposta alle seguenti domande: La fluidoterapia è indicata? Che tipo di fluidi si devono somministrare? Per che via bisogna farlo? Con che rapidità si devono infondere? Quanti fluidi si devono somministrare? Quando si deve sospendere la fluidoterapia?

This presentation will include an overview of the principles of fluid therapy and will answer the following questions: Is fluid therapy indicated? What type of fluids should be given? By what route should fluids be given? How rapidly should fluids be given? How much fluids should be given? And, When should fluid therapy be discontinued?

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Medical management of chronic renal Failure in the cat Approccio terapeutico alle pi첫 gravi nefropatie nel gatto

Stephen DiBartola DVM, Dipl ACVIM - Ohio State University - Columbus, Ohio, USA

Riassunto In questa relazione viene utilizzata la discussione di casi clinici per presentare una rassegna di parecchie nefro patie del gatto, quali glomerulonefrite, pielonefrite, linfosarcoma, nefropatia con deplezione di potassio e pseudoci sti perinefriche.

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Disorders of potassium Alterazioni del potassio

Stephen DiBartola DVM, Dipl ACVIM - Ohio State University - Columbus, Ohio, USA

Riassunto In questa relazione viene presentata una rassegna dell’equilibrio del potassio ed una discussione delle diagnosi dif ferenziali dell’iper- ed ipokalemia. L’approccio ai pazienti con disordini dei livelli sierici di potassio viene illustrato me diante casi clinici.

This presentation will include provide an overview of potassium balance and a discussion of the differential diagno sis of hyperkalemia and hypokalemia. Case examples will be used to illustrate the approach to patients with disorders of serum potassium.

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Disorders of sodium Alterazioni del sodio

Stephen DiBartola DVM, Dipl ACVIM - Ohio State Uni versity - Columbus, Ohio, USA

Riassunto In questa relazione viene presentata una rassegna dell’equilibrio del sodio ed una discussione delle diagnosi diffe renziali dell’iper- ed iponatremia. L’approccio ai pazienti con disordini dei livelli sierici di sodio viene illustrato me diante casi clinici.

This presentation will include provide an overview of water and sodium balance and a discussion of the differential diagnosis of hypernatremia and hyponatremia. Case examples will be used to illustrate the approach to patients with dis orders of serum sodium.

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Clinical approach to anemia in the dog and cat Approccio all’anemia nel cane e nel gatto

Common disorders in clinical hematology Alterazioni ematologiche più frequenti

Bernard Feldman DVM, PhD - Regional College of Veterinary Medicine - Virginia-Maryland, USA

FIRST EXAMINE THIS CASE (see below for the complete laboratory data from 3 days earlier) 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? .....................................................................................

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 (other than the leucogrma 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

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 labor atory screening that provides a complete hemogram:

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

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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 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

42° Congresso Nazionale SCIVAC

4. Decreased erythropoietin - al ways nonresponsive 5. Hemorrhage - nonresponsive early; responsive later 6. Hemolysis - nonresponsive early; responsive later 7. Maturation abnormality - usually nonresponsive but unpredictable

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.

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 patient’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

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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:

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 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% X 22% (patient’s Hct)/ 45% (mean canine Hct) = 2.5/2.0 = 1.27 basal r ate 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 of 3.5 million/ul, the absolute value is approximately 170,000/ul. 170,000 X 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 hema tocrits. 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 Case 1 - A West Highland White Terrier, male, 9 months of age, was presented for elective castration. On physical examination the clinician noticed pale mucous membranes and normal capillary refill time. No other physical examination findings were considered abnormal. Temperature, pulse, and respirations were normal. The owner had not observed any recent changes in the patient’s demeanor. The patient appeared alert and responsive. Case 2 - The patient is a 4 year old, intact male English Pointer, current on vaccinations, presented because of depression, inappetance, tachycardia, and tachypnea. Vomiting and diarrhea have been sporadic the past month but this appears to be worsening. On physical examination he has pale mucous membranes, rapid pulse and respirations, and slightly subnormal temperature. Case 3 - A 2 year old castrated male American Domestic Shorthaired cat was presented because of marked lethargy, depression and poor appetite for the past week. The patient had a temperature of 103 F, generalized lymphadenopathy, palpable abdominal lymph nodes and a tense, perhaps even splinted, abdomen. The patient was drinking and was not clinically dehydrated. The patient was never allowed out of the house and was FeLV, FIV. and FIP negative. Case 4 - An intact male 5 year old Old English Shepherd was presented because of fatigue and syncope. The history was vague but under questioning the owner noted deterioration for “months.” The mucous membranes appeared injected, temperature was normal, pulse was 100/min, there was hepatosplenomegally, and there are increased respiratory sounds. Case 5 - The patient is an elderly (14 year old) neutered male Terrier cross presented because of erratic appetite (eats for several days and then does not eat for several days). The owner says he appears to have aged more recently and appears feeble and ever so slightly debilitated. Physical exam ination reveals an alert but stoic patient who is slightly underweight. He has bilateral senile cataracts. Temperature, pulse, respiration are normal. The patient ate a normal meal last evening but ate “slower” than normal. The owner does not think he drinks more but the owner has two dogs and gives them a large bowl of water. Case 6 - A 44 pound mixed breed spayed female dog is presented to an emergency and critical care center because of traumatic injury - kicked by a horse. On presentation she was noted to be severely anemic - pale mucous membranes and poor capillary refill time. Aspiration of an enlarged abdomen revealed frank blood, hematocrit of 27%. The patient had a hematocrit of 9% and a total plasma protein of 4.6 g/dl. Because of the need for red cells the Blood Bank was contacted. Whole blood was the only blood product avail-

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CASE 1 HEMOGRAM 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 BT min PT sec FDP ug/ml

19 (37-55) 5.3 (12-18) 1.75 (6-8) 108 (60-77) 27.9 (31-35) 30 (19-24) 10 (0-1.5) 24 (0) 4+ aniso, polychr toxic granulation 440 (200-400) megathrombocytes – (<4.2) – (12) – (<10)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC (corrected) /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Disintegrated cells Unidentifiable cells Thrombin time (TT) sec APTT sec Antithrombin III %

6.7 (6.0-8.0) 250 (200-400) 2.0 (2-7) 28600 (6000-17500) 0 (0-400) 21021 (3000-11500) 4147 (1000-4800) 3289 (150-1350) 143 (100-1250) 0 (0) 0 (0) 0 (0) – (12) – (18) – (>85)

CHEMISTRY ALT mU/ml ALP mU/ml T. Bili mg/dl Gluc mg/dl S. Protein g/dl Albumin g/dl Chol mg/dl AG mEq/L

277 121 0.2 100 6.1 2.8 167 16

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl

19 0.8 145 4.0 110 22 9.8 5.2

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Epithelial cells Bacteria Urobilinogen

Unremarkable 3 0 0 Amorphous urates 2 Negative Positive

(4-66) (0-88) (0.1-0.6) (70-120) (5.3-7.8) (3.0 -4.0) (28-255) (12-20)

URINALYSIS (Cystocentesis) SG 1.022 Color Yellow Transparency Clear pH 7.5 Protein Trace Glucose Negative Ketones Negative Occult Blood Negative Bilirubin Negative

able. After crossmatch compatibility was established, 450 mls of 1.1, 1.2 negative and 7 positive blood was administered. The PCV of the donor blood was 49%. What is the patient’s PCV immediately posttransfusion? What is the patient’s PCV 12 hours posttransfusion? Case 7 - A three year old castrated male German Shepherd was presented with signs of depression, anorexia, ane-

(5-28) (<1.5) (145-153) (2.7-5.3) (110-119) (19-24) (9.8-11) (2.5-6.2)

mia, documented to be progressive over the past 6 months. He had received one transfusion (not typed or crossmatched) for the nonresponsive anemia, one month ago. During the past three weeks he has had interdigital abscesses and an abscess over the left inguinal lymph node. No foreign bodies were found. He has been treated with a variety of antibiotics without marked progress. The patient is febrile ((103.3) and has rapid pulse and respiration. He has moderate lymphadenopathy which, on aspiration, was called purulent.

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CASE 2 HEMOGRAM 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 BT min PT sec FDP ug/ml

18 (37-55) 4.5 (12-18) 4.16 (6-8) 43.9 (60-77) 25.5 (31-35) 17.2 (19-24) 3.3 (0-1.5) 1 (0) 4+ aniso, poik toxic vacuolation 720 (200-400) Unremarkable – (<4.2) – (12) – (<10)

5.6 (6.0-8.0) 500 (200-400) 2.0 (2-7) 17500 (6000-17500) 700 (0-400) 13828 (3000-11500) 600 (1000-4800) 1487 (150-1350) 787 (100-1250) 0 (0) 0 (0) 0 (0) – (12) – (18) – (>85)

CHEMISTRY ALT mU/ml ALP mU/ml T. Bili mg/dl Gluc mg/dl S. Protein g/dl Albumin g/dl Chol mg/dl AG mEq/L

29 77 0.3 56 4.9 2.4 84 14

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl

27 1.2 142 4.4 111 21 8.9 3.3

URINALYSIS (Cystocentesis) SG 1.043 Color Yellow Transparency Clear pH 7.1 Protein Trace Glucose Negative Ketones Negative Occult Blood Negative Bilirubin Negative

(4-66) (0-88) (0.1-0.6) (70-120) (5.3-7.8) (3.0 -4.0) (28-255) (12-20)

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Epithelial cells Bacteria Urobilinogen

(5-28) (<1.5) (145-153) (2.7-5.3) (110-119) (19-24) (9.8-11) (2.5-6.2)

2 2 0 MAP 1 Negative Negative

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CASE 3 HEMOGRAM 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 Plat morph BT min PT sec FDP ug/ml

8 5 3.45 43.5 33.3 15.5 0 0 Heinz bodies Doehle bodies 640 Some clumps – – -

SERUM CHEMISTRY ALT mU/ml 165 ALP mU/ml 89 T. Bili mg/dl 0.2 Gluc mg/dl 100 S. Protein g/dl 6.1 Albumin g/dl 3.1 Chol mg/dl 111 AG mEq/L 15 URINALYSIS (Cystocentesis) SG 1.042 Color Yellow Transparency Clear pH 6.9 Protein Trace Glucose Negative Ketones Negative Occult Blood Negative Bilirubin Negative

(30-45) (12-18) (5-10) (39-55) (31-35) (12.5-27.5) (0.2-1.6) (0)

(<4.2) (12) (<10)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC /ul Band Neutrophils Lymphocytes Monocytes Eosinophils Basophils Disintegrated cells Unidentifiable cells Thrombin time (TT) sec APTT sec Antithrombin III %

6.7 230 2.0 5100 0 306 4434 349 0 0 0 51 – – –

(6.0-8.0) (50-300) (2-7) (5500-19500) (0-120) (2500-12500) (1500-7000) (0-850) (0-1500) (0) (0) (0) (12) (18) (>85)

(4-66) (0-88) (0.1-0.2) (70-110) (3.9-7.7) (2.1-3.3) (117-174) (12-20)

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl

31 1.1 150 4.0 119 20 8.9 4.7

(5-28) (0,8-1.8) (147-156) (4.0-4.5) (117-123) (17-21) (8.2-10.2) (4.5-8.1)

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Epithelial cells Bacteria Urobilinogen Fat droplets

0 0 0 Amorphous phosphates 0 Negative Positive Positive

(300-800)

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CASE 4 HEMOGRAM PCV % 83 (37-55) Hb g/dl 39.6 (12-18) RBC x 106/ul 13.8 (6-8) MCV fl 60.2 (60-77) MCHC g/dl 35.6 (31-35) MCH pg 21.4 (19-24) Retics % 1.5 (0-1.5) Nrbcs/100wbc 1 (0) RBC morph, slt. aniso, polychr WBC morph toxic granulation Plat x 103/ul 94 (200-400) Plat morph many microforms BT min – (<4.2 ) PT sec – (12 ) FDP ug/ml – (<10) SERUM CHEMISTRY ALT mU/ml 89 ALP mU/ml 131 T. Bili mg/dl 0.7 Gluc mg/dl 6 S.Protein g/dl 6.7 Albumin g/dl 3.3 Chol mg/dl 277 AG mEq/L 23 Ammonia ug/ml – Base Excess

URINALYSIS (Cystocentesis) SG 1.045 Color Pink Transparency Clear pH 6.9 Protein Trace/1+ Glucose Negative Ketones Negative Occult Blood Positive, 1+ Bilirubin Positive, 1+

(4-66) (0-88) (0.1-0.6) (70-120) (5.3-7.8) (3.0 -4.0) (28-255) (12-20) (<120) (+ 2.5)

7.0 200 3.0 8600 172 5504 2150 688 86 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) (12) (18) (>85)

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl Arterial pH pO2mmHG pCO2mmHG HCO3mEq/L

19 0.2 147 3.6 111 18.7 10.1 3.5 7.6 90 24.5 18.4

(5-28) (<1.5) (145-153) (2.7-5.3) (110-119) (19-24) (9.8-11) (2.5-6.2) (7.31-7.42) (85-95) (29-36) (17-24)

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Epithelial cells Bacteria Urobilinogen

0 2 0 Amorphous phosphates 0 Negative Positive

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CASE 5 HEMOGRAM 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 BT min PT sec FDP ug/ml CHEMISTRY ALT mU/ml ALP mU/ml T. Bili mg/dl Gluc mg/dl S.Protein g/dl Albumin g/dl Chol mg/dl AG mEq/L Ammonia ug/ml Base Excess pCO2mmHG

26 8.3 3.62 71.8 32 22.9 0 0 slt. aniso normal 230 normal – – –

(37-55) (12-18) (6-8) (60-77) (31-35) (19-24) (0-1.5) (0)

12 81 0.1 102 5.4 2.7 279 21 – –

URINALYSIS (Cystocentesis) SG 1.015 Color Yellow Transparency Clear pH 6.9 Protein 1+ Glucose Negative Ketones Negative Occult Blood Positive, 1+

(<4.2 ) (12 ) (<10)

6.0 (6.0-8.0) 450 (200-400) 3.0 (2-7) 12400(6000-17500) 256 (0-400) 9984 (3000-11500) 1020 (1000-4800) 884 (150-1350) 125 (100-1250) 131 (0) 0 (0) 0 (0) – (12) – (18) 77 (>85)

(4-66) (0-88) (0.1-0.6) (70-120) (5.3-7.8) (3.0 -4.0) (28-255) (12-20) (<120) (+ 2.5) (29-36)

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl Arterial pH pO2mmHG HCO3mEq/L

38 1.8 143 5.3 112 16 8.3 3.5 – – –

(200-400)

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Epithelial cells Bacteria Bilirubin

(5-28) (<1.5) (145-153) (2.7-5.3) (110-119) (19-24) (9.8-11) (2.5-6.2) (7.31-7.42) (85-95) (17-24)

3 3 3, fine granular MAP 2 Negative Negative

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CASE 7 HEMOGRAM 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 BT min PT sec FDP ug/ml

25 (37-55) 8.4 (12-18) 3.75 (6-8) 66.6 (60-77) 33.6 (31-35) 21.0 (19-24) 0 (0-1.5) 4 (0) 1+ aniso, lepto toxic vacuolation 210 (200-400) Some mega forms 6.1 (<4.2) 16 (12) 10 (<10)

8.0 (6.0-8.0) 500 (200-400) 9 (2-7) 18760* (6000-17500) 562 (0-400) 6375 (3000-11500) 7781 (1000-4800) 375 (150-1350) 0 (100-1250) 131 (0) 281 (0) 93 (0) – (12) 24 (18) 86 (>85)

* Metamyelocytes-842; myelocytes-1218; progranulocytes-656; myeloblasts-562 CHEMISTRY ALT mU/ml ALP mU/ml T. Bili mg/dl Gluc mg/dl S. Protein g/dl Albumin g/dl Chol mg/dl AG mEq/L

545 327 2.2 169 7.1 4.1 302 20

URINALYSIS (Cystocentesis) SG 1.034 Color Deep Yellow Transparency Clear pH 6.6 Protein Negative Glucose Negative Ketones Negative Occult Blood Negative Bilirubin 2+

(4-66) (0-88) (0.1-0.6) (70-120) (5.3-7.8) (3.0 -4.0) (28-255) (12-20)

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Epithelial cells Bacteria Urobilinogen

41 1.6 144 5.0 110 19 11 6.6

(5-28) (<1.5) (145-153) (2.7-5.3) (110-119) (19-24) (9.8-11) (2.5-6.2)

0 0 0 Bilirubin 0 Negative Negative

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Preventive medicine in hematology Medicina preventiva in ematologia

Bernard Feldman DVM, PhD - Regional College of Veterinary Medicine - Virginia-Maryland, USA

ANNUAL LABORATORY SCREENING FOR ELDERLY PATIENTS A methodology is provided for standardizing testing procedures based on the patient’s age and physical status. Factual laboratory data provide a common reference point to effectively deal with elderly patients. Elderly patients undergoing a surgical procedure are discussed in the accompanying materials concerning presurgical laboratory testing below. For the purpose of this discussion concerning elderly canine and feline patients, patients 5 years of age or older will be considered elderly. This, of course, encompasses large breed dogs. Small breeds of dogs and most cats of that age would be considered relatively young. The term “elderly” is certainly indefinite and the following discussion does require individual clinical interpretation. A comprehensive history and a careful, skillful physical examination almost always will uncover possible complications. The specific advantages of beginning to screen elderly patients on a regular basis using laboratory tests and col lating these data, will be in recognition of trends in what would otherwise be considered “normal” values and to determine if changes are significant and suggest further testing in individuals. It is difficult to overemphasize the importance of this information regularly obtained. In addition, physicians regularly recommend annual physical examinations and laboratory screening for their elderly human patients, in effect setting the stage for screening of elderly patients in veterinary practice. Minimum laboratory procedures needed to evaluate physical status include: 1) a complete hemogram, 2) urinalysis, 3) biochemical profile including SUN, ALT, alkaline phosphatase, total serum protein, albumin, globulin, electrolytes, calcium and phosphorus, and total carbon dioxide. Further studies and/or function tests will be required to evaluate the severity of any unusual problems unco vered. Determination o the patient’s physical status is essential. The following subclassifies patient physical status into three grades while excluding patients with severe systemic disorders or critically ill patients.

PHYSICAL STATUS Grade I – no obvious disease and no obvious systemic disturbances

Grade II – mild systemic disturbance. Examples would include obesity or patients with mild, treatable arthritis Grade III – patients with moderate systemic disturbance. Examples would include compensated renal disease or moderate evidence of cardiac disease without significant clinical signs

DEFINITIONS General laboratory screen – complete hemogram, SUN or creatinine, urinalysis Geriatric screen – complete hemogram, urinalysis, complete biochemical profile Expanded geriatric screen – complete hemogram, urinalysis, complete biochemical profile, blood gases, hemostatic testing Blood gases – pH, HCO3, CO2, arterial O2, ionized calcium Hemostatic screen – platelet count, fibrinogen, PT, APTT, Buccal mucosal bleeding time

BASIC LABORATORY DETERMINATIONS Age: 5-8 years General screen

8-10 years Geriatric screen

Grade II

Geriatric screen

Expanded screen

Grade III

Expanded screen

Physical Status Grade I

>10 years Expanded geriatric screen Expanded geriatric screen Expanded geriatric screen

Of course, additional examinations including cardiovascular examination and radiography and ultrasonography should be included in any complete workup when patients in Grade II or III are encountered. This methodology should provide a basis or a formula for laboratory workups in your practice. It is understood that when specific disease processes are uncovered or when specific organ functions need delineation, more sophisticated testing procedures should be sought. Provided here is a simplistic screening methodology.

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The clinical laboratory is not a substitute for clinical acumen. What it substitutes for on any occasion is an inadequate history when for any reason it is not known what has occurred to get the patient into his current condition. Even though a good history and complete physical examination will often establish a diagnosis, there are many times when insufficient information is obtained by these means alone. It then becomes necessary to specifically identify some of the physiological derangements which accompany the disease process. Although there may be a problem in assigning the appropriate physical status, an estimate is an appropriate starting point as long as the clinician errs in the direction of worsening physical status, that is,does not underestimate the patient’s physical status.

PRESURGICAL LABORATORY TESTING TO PREVENT POSTSURGICAL COMPLICATIONS Postsurgical complications, including hemorrhage, may be the result of surgery or from underlying disease. It is therefore appropriate to develop a regimen of preoperative testing, including hemostatic testing, with consideration as to type of surgical procedure before consideration of postsurgical complications.

MAJOR SURGERY AND APPROPRIATE LABORATORY SCREENS1 For the sake of structure, physical status and recommended tests have been placed in six categories (I-V and Emergency). Major procedures have been generally characterized as lasting longer than 30 minutes or any procedure on a canine or feline patient older than 8 years. Some assumptions include appropriate heartworm testing which has or will be accomplished, and the complete hemogram includes a platelet count (not estimation), total plasma protein and fibrinogen quantitation. Buccal mucosal bleeding time is always preferred to actual von Willebrand factor quantitation. If coumarin intoxication is suspected prothrombin time or proteins involved in vitamin K absence/antagonism (PIVKA) will be determined: I. A healthy patient presented for elective procedure with and excellent pr ognosis – complete hemogram; urinalysis, and abbreviated serum chemistry (serum urea nitrogen-SUN, creatinine, alkaline phosphatase-SAP, alanine aminotransferase-ALT). II. A healthy patient with local disease and no systemic signs – nonelective surgery (e.g., skin laceration) – and an excellent prognosis: complete hemogram; urinalysis; abbreviated serum chemistry (see above). III. A patient with disease causing moderate systemic signs and a good prognosis. Examples could include cardiac murmur, modest anemia, slight fever. Prognosis is good: complete hemogram; urinalysis; complete biochemical profile including electrolytes and total carbon dioxide (TCO2)

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IV. A patient with disease causing severe systemic signs. Examples could include ruptured urinary bladder, gastric torsion, or immune-mediated hemolytic anemia. Prognosis is guarded: Complete hemogram; urinalysis; complete biochemical profile (see above); blood gases; buccal mucosal bleeding time (BMBT); prothrombin time (PT), activated partial thromboplastin time (APTT) (or, at least, and activated coagulation time [ACT]). It would be ideal to be able to determine antithrombin III (ATIII) and D-dimer. Testing is dependent on facilities available. V. A moribund patient with a poor prognosis. An example could be endotoxic shock: all tests in IV above which can be accomplished within the clinician’s strategic time limit and facilities available. Emergency. This could involve patients in categories IIV above. Prognosis is variable. Testing depends on the facilities available and can be accomplished within the clinician’s strategic time limit. Testing would include those in IV above. The relative weight assigned to abnormalities detected during patient evaluation includes major, moderate and minor contributions. Major contributions include general health (nutrition, fluid and electrolyte balance, presence of sepsis. Systemic abnormalities would include the cardiovascular, respiratory and central nervous systems as well as the kidney and liver. Moderate contributions include abnormalities in the gastrointestinal or endocrine systems. Minor contributions include abnormalities in the musculoskeletal, ophthalmic, otic, integumentary, lymphatic or reproductive systems. Determination of surgical risk includes excellent, good, fair and poor. Excellent indicates little effect on the patient with minimal potential for complications and a high probability that the patient will return to normal after surgery. Good suggests some potential for complications as the result of the procedure but a high probability for successful outcome. Fair includes one or more serious problems detected a procedure associated with a moderate probability of complications, prolonged recovery, or permanent change in health status. Poor indicates significant chance of major complication and permanent change in health status. Surgery is undertaken only if higher risk is expected if surgery is not performed – surgery is necessary to preserve life. Postsurgical hemorrhage decreases circulating blood volume and oxygen carrying capacity and can result in cardiovascular collapse. Hemorrhage into a body cavity may be hard to recognize. Signs include pale mucous membranes, slow capillary refill time, weak pulses and increased heart rate. Healthy animals are able to sustain ten to twenty percent of blood volume without severe consequences. However, most postoperative patients cannot sustain this loss. Treatment with balanced electrolytes at two the three times the volume of blood loss can be administered rapidly. Central venous pressure should be monitored. Optimal packed cell volume is 25-30 percent which lowers blood viscosity and effectively increases afterload and improves cardiac output. Transfusion of blood components and/or colloids should be considered. Calcium containing solutions should not be used to dilute or flush intravenous lines as clotting will often result.

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UNDERLYING DISEASES LEADING TO POSTSURGICAL HEMOSTATIC COMPLICATIONS Inherited disorders include hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency, and von Willebrand disease (vWd). These problems are most efficiently diagnosed or suspected from the history and patient presentation. Usually there is systemic hemorrhage which occurs at a youthful age. The universal tests of hemostasis – PT and APTT – and the BMBT will help in defining these diseases. Inherited platelet disorders are numerous but are relatively rare. The most common acquired hemostatic disorders involves platelets – too few, too many, or too dysfunctional. Thrombocytopenia is most often associated with an immune, infectious or idiopathic etiology, with idiosyncratic drug reactions or chemotherapy, with microangiopathy most often associated with neoplasia, or as a significant complication of DIC. Thrombocytopathy is often associated with nonsteroidal antiinflammatory drugs. Specific client questioning is necessary to determine whether these drugs have been administered specifically or incidentally. Although virtually all drugs have been incriminated in humans in producing dysfunctional platelets, antimicrobials, antihistamines and such diverse drugs as lidocaine and halothane should be considered postsurgically. Coagulopathy is most associated with coumarin rodenticide intoxication, severe hepatic disease and, most commonly in the postsurgical state – DIC. Often DIC is accompanied by compensatory fibrinolysis.

HEMOSTATIC PROBLEMS INHERENT TO THE POSTSURGICAL STATE Thrombosis in the postsurgical state often results from catheter usage – endothelial cell damage - and excessive use of heparin in flushing catheters. The resultant activation and then reduction of ATIII concentrations becomes significant. Long term immobility of patients often results in thrombus formation and subsequent pulmonary embolism. Heartworm

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disease, gastric dilatation/volvulus, hyperadrenocorticism, nephrotic syndrome, diabetes mellitus, feline cardiomyopathy could result in renal or pulmonary thrombosis or distant thrombosis.

POSTSURGICAL ALTERATIONS OF THE FIBRINOLYTIC SYSTEM Lanevschi et al2 investigated whether alterations in constituents of the fibrinolytic pathway are significant in dogs undergoing surgery. Eighteen dogs were placed into three groups - major orthopedic trauma, minor trauma (ovariohysterectomy), and a control groups anesthetized with halothane anesthesia. Major trauma was associated with transient depletion of plasminogen at 24 hours with return to normal at 48 hours perhaps reflecting consumption at the site of clot formation. They also found immediate postsurgical depletion of alpha 2antipalsmin which rebounded after several hours. This analyte is the main systemic inhibitor of fibrinolysis. It should be noted that no dogs had observable postsurgical bleeding tendencies. The decreases in the two analytes, plasminogen and antiplasmin indicate active fibrinolysis. It was suggested t hat altered fibrinolysis in dogs undergoing major traumatic surgery should be considered in terms of baseline data and in preventive preoperative and postoperative care. 1.

Lazar T: Major surgery and appropriate lab screens; postsurgical hemostatic testing. Personal communications,VMRCVM, Blacksburg, VA,Summer 2000. Lanevschi A,Kramer JW, Greene SA, Meyers KM: Fibrinolytic activity in dogs after surgically induced trauma. Am J Vet Res 57:8, 1137-1140, 1996.

Suggested reading 1. 2.

Fossum TW: Preoperative assessment of the surgical patient. Small Animal Surgery, Mosby, New York, 1997, 18-21. Fries CL: Assessment and preparation of the surgical patient. Textbook of Small Animal Surgery, Second Edition, WBSaunders Company, Philadelphia, 1993, 137-141. Hackner SG: Approach to the diagnosis of bleeding disorders. Compendium on Continuing Education 17:3,331-346, 1995.

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Case studies in clinical biochemistry Analisi clinica e biochimica di casi clinici

Bernard Feldman DVM, PhD - Regional College of Veterinary Medicine - Virginia-Maryland, USA

CASE 1 A 1 year old male castrated Dachshund presented with anorexia, mild depression and occasional vomiting of several months’duration.

Significant laboratory findings Hemogram - decreased plasma protein; no anemia Urinalysis - alkaline pH, presence of bilirubin and bilirubin crystals; presence of cells may be result of cystocentesis Biochemical profile - decreased total serum protein, albumin, globulin; decreased serum urea nitrogen, creatinine; increased bilirubin with modest increases in alanine aminotransferase and alkaline phosphatase; increased chloride; decreased anion gap; decreased total calcium; decreased cholesterol

Interpretation Significant laboratory abnormalities suggest chronic hepatic disease. The decreased proteins (both plasma and serum) and decreased serum urea nitrogen suggest lack of hepatic production. Hypoalbuminemia has affected total calcium and anion gap. Decreased serum cr eatinine is not regarded as clinically significant. It may be caused by medullary washout, and diuresis associated with polydipsia and polyuria. Hyperbilirubinemia most often suggests cholestasis and is often accompanied by increases in alkaline phosphatase and cholesterol. Hypocholesterolemia may be observed in severe liver cell damage due to chemicals, drugs or hepatitis. It is also observed from numerous causes of malnutrition. There is no evidence of anemia as a potential cause of extrahepatic hyperbilirubinemia. In this patient hyperbilirubinemia was accompanied by bilirubinuria and the presence of urinary bilirubin crystalluria. The modest increase in alkaline phosphatase is considered significant in this patient while the modest increase in alanine aminotransferaseis considered insignificant. However this latter analyte abnormality should be reexamined with additional profiles at, at most, weekly intervals. Alkaline urinary pH is most commonly associated with systemic alkalosis and bactiuria. Comments on physiology - Hepatic encephalopathy is suggested in patients with neurologic and mental abnormal -

ities and evidence of hepatic disease. Blood ammonia is in creased in many of these patients but is not specifically cor related with neurologic signs. If blood ammonia is high enough, ammonuria with crystalluria may result. Occasion ally ammonium biurate crystals may be observed in urine sediment. Respiratory alkalosis due to hyperventilation is frequent. Hyponatremia is a frequent complication. The serum amino acid profile is abnormal. Routine cerebral spinal fluid examination is normal. Diagnosis is clinical with characteristic laboratory findings providing support without being specific. Hypocholesterolemia has been asso ciated with congenital portosystemic vascular abnormali ties. The reason is unknown. Aberrant lipid metabolism may result in red cell poikilocytosis and target cells. Focus on decreased cholesterol - Hypocholesterolemia may be observed in severe liver cell damage due to chemicals, drugs or hepatitis. It is also observed from numerous causes of malnutrition. It is most often observed in anorectic hospitalized patients in negative nitrogen balance. Hypocholesteroemia may be observed in congenital or acquired hepatic atrophy. Portosystemic vascular abnormality is an example of congenital cause. Focus on increased serum chloride - Serum chloride is used with sodium, potassium and carbon dioxide to assess electrolyte, acid-base, and water balance. Usual changes are in the same direction as sodium except increases associ ated with metabolic acidosis and bicarbonate depletion or metabolic alkalosis with bicarbonate excess when sodium concentrations may be appropriate. It is also increased with metabolic acidosis and prolonged diarrhea with loss of sodi um bicarbonate, renal tubular diseases with decreased acid secretion and decreased reabsorption of bicarbonate (hy perchloremic metabolic acidosis). Among the other causes of hyperchloridemia are excessive administration of some drugs such as ammonium chloride, saline, and glucocorti coids. Hyperchloridemia is observed in some cases of hy perparathyroidism, diabetes insipidus, dehydration, and in salicylate intoxication. Diagnosis - Chronic hepatic disease and liver failure caused by portosystemic vascular abnormality. Recommendations for further diagnostics - Diagnosis is suggestive only. Because of this patient’s historical de pression serum ammonia should be assessed. It would be in -

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CASE 1 HEMOGRAM

Value

Reference

Units

Red cell count Hemoglobin Hematocrit Total plasma protein MCV MCH MCHC Reticulocytes Absolute retic. count Metarubricytes White blood count Neutrophils Bands Lymphocytes Monocytes Eosinophils Basophils Platelets

8.13 16.2 48.7 5.2 60 19.9 33.3 Not done Not done 0 11.6 7.2 0.0 3.4 0.2 0.8 0.0 299

5.50 - 8.63 13.0 - 20.5 37.3 - 62.0 5.8 – 8.0 58 - 83 22.2 - 26.2 31.6 - 36.5 0 – 1.5 <75 0 5.4 - 16.6 3.2 - 10.7 0.0 - 0.2 0.8 - 5.6 0.0 - 1.1 0.0 - 2.4

x 106/mL g/dL % g/dL fL pg % % x 103/_L /100 WBC x 103/µL x 103/µL x 103/µL x 103/µL x 103/µL x 103/µL

179 - 473

x 103/µL

URINALYSIS (cystocentesis)

Value

Units

Specific Gravity: Color: Transparency: pH: Glucose: Bilirubin Ketone: Protein Blood: Urobilinogen Red blood cells White blood cells Epithelial cells Crystals

1.027 Yellow Clear 8.5 Negative 2+ Negative Negative Negative Present 1-3 per high powered field 2-4 per high powered field 2-4 per high powered field Bilirubin crystals (few)

CHEMISTRY

Value

Reference

Units

Total serum protein Albumin Serum urea nitrogen Creatinine Total bilirubin Alanine aminotransferase Alkaline phosphatase Sodium Potassium Chloride Total CO2 Anion gap + Potassium Total calcium Phosphorus Glucose Cholesterol

4.6 2.1 5 0.3 1.0 113 245 146 3.9 122 21.3 6 8.3 3.5 95 56

5.3 – 7.4 2.8 – 3.6 6.0 – 28.0 0.8 – 1.9 0.1 – 0.5 13 – 100 20 – 167 140 – 152 3.3 – 4.6 109 – 120 17.4 – 27.9 8 – 15 9.7 – 11.1 1.3 – 5.0 87 – 127 127 – 336

g/dL g/dL mg/dL mg/dL mg/dL U/L U/L mmol/L mmol/L mmol/L mmol/L mmol/L mg/dL mg/dL mg/dL mg/dL

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teresting to reexamine urine sediment for presence of am monium biurate crystals. Acid-base status should also be as sessed. Additional recommendations would include hepatic biopsy and reexamination of the biochemical profile at ap propriate intervals. Radiographic examination is necessary to determine extent of shunt and potential for surgical cor rection. Bile acid quantitation may be diagnostically useful for detecting congenital portosystemic vascular abnormali ties in nonicteric patients.

Suggested reading Maddison JE: Canine congenital portosystemic encephalopathy. Aust Vet J 65:245-249, 1988. Laflamme D, Mahaffey EA,Allen ES et al: Microcytosis in dogs with portocaval shunt. J Vet Int Med4:111-114, 1991.

CASE 2 A 9 month old, intact female mixed breed dog presented because of sporadically (past 4 months) passing blood colored-urine. Blood cultures had been negative. Micturation was normal. Hematocrit values over this period varied between 20 and 36%. A direct antiglobulin test was negative. the owner noted the dog appeared to pass red colored urine more after hospital visits.

Significant laboratory findings 1. Decreased plasma protein is slight 2. Mild macrocytic normochromic responsive anemia 3. Modestly increased number of bands with “normal”WBC 4. Red urine without obser vable RBCs 5. Proteinuria

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the interpretation indicated a relatively young red cell age supporting the presence of a regenerative anemia. 2. Osmotic fragility test was normal 3. Alkaline fragility test – marked increase of fragility Focus on PFK – This deficiency has been documented in English Springer Spaniels, American Cocker Spaniels, and in mixed breed dogs (probably having Spaniel in the back ground). The recurrent hemolytic episodes induced by alka losis is distinctive for this deficiency. The PFK deficiency blocks the glycolytic pathway resulting in decreased 2,3diphosphoglycerate. This, in turn, is associated with in creased intracellular chloride ion and thus an increase in RBC pH which places the cells at risk for hemolysis with rel atively mild alkalemia. Respiratory alkalosis is induced by hyperventilation due to vigorous exercise, excitement, or panting. Diagnosis - Hemolytic anemia due to PFK deficiency. Recommendations for further diagnostics 1. Red cell parasites – none seen; serology for babesiois/hemobartonellosis was negative 2. DNA test for PFK deficiency – patient is deficient. This is a PCR based test (Genetics Laboratory, University of Pennsylvania, School of Veterinary Medicine) – Patient was homozygous for a mutant allele .

Suggested reading Giger U, Harvey JW: Hemolysis caused by phophofrucktokinase deficiency in English Springer Spaniels: Seven cases (1883-1986). J Am Vet Med Assoc 191:1493, 1987. Giger U, Smith B, Woods C et al: Inherited phosphofructokinase deficiency in an American Cocker Spaniel. J Am Vet Med Assoc 201, 1569, 1992.

Interpretation The urine findings do suggest intravascular hemolysis with hemoglobinuria. These findings were consistent with what the client’s previous observation that the dog tended to pass discolored urine at home after spending time in the hospital. Given this dog’s 1) young age, 2) history of persistent unexplained regenerative anemia, and 3) recurrent pigmenturia that was linked to episodes of stress or excitement, a congenital or hereditary red cell defect was considered most likely. Comments on physiology - The information best fits a phosphofructokinase (PFK) deficiency that results in in creased RBC alkaline sensitivity whereby respiratory alka losis can precipitate intravascular hemolysis.

Focus on this patient’s red cell hemolysis 1. Electrophoretic analysis or RBC membranes revealed no evidence of major integral or peripheral membrane protein deficiencies (accomplished SDS-PAGE). However

CASE 3 An 8 year old castrated male DSH cat was presented because a history of anorexia and profuse vomiting for the past 2 days. Diarrhea was not reported. The patient was severely dehydrated (10-12%) and hypothermic (99 degrees F).

Significant laboratory findings Hemogram - increased plasma protein; increased hematocrit (RBC, Hb) Urinalysis - no significant abnormalities; pH may be increased Biochemical profile - increased total serum protein,albumin, globulin; increased serum urea nitrogen, creatinine, phosphorus; normal sodium and potassium despite severe dehydration: decreased chloride; markedly increased anion gap

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CASE 2 HEMOGRAM

Value

Reference

Units

4.15 11.0 33.5 5.7 80 – 33.3 6.2 237 0 13.5 9.99 0.41 2.97 0.14 0.00 0.00 371

5.50 - 8.63 13.0 - 20.5 37.3 - 62.0 5.8 - 8.0 58 - 83 22.2 - 26.2 31.6 - 36.5 0 - 1.5 <75 0 5.4 - 16.6 3.2 - 10.7 0.0 - 0.2 0.8 - 5.6 0.5 - 1.1 0.0 - 2.4

x 106/µL g/dL % g/dL fL pg % % x 103/_L /100 WBC x 103/mL x 103/µL x 103/µL x 103/µL x 103/µL x 103/µL

179 - 473

x 103/µL

URINALYSIS (cystocentesis)

Value

Units

Specific Gravity: Color: Transparency: pH: Glucose: Bilirubin Ketone: Protein Blood: Urobilinogen Red blood cells White blood cells Epithelial cells Crystals

1.027 Red Turbid Hemolyzed Negative Hemolyzed Hemolyzed 4+ 3+ Hemolyzed 0 1-2 2-4 Hemolyzed

CHEMISTRY

Value

per high powered field per high powered field per high powered field

Reference

Units

Marked hemolysis - Because of the intense hemolysis, biochemistry values were considered to be uninterpretable.

Interpretation The most interesting changes involve electrolyte. The sodium value is within the reference values despite the fact the cat was severely dehydrated (reflected by the increased urine specific gravity in the absence of proteinuria or glycosuria, severe azotemia suggested to be prerenal with the high specific gravity; and markedly elevated proteins, all suggesting the cat is, in reality, hyponatremic. The chloride is markedly decreased and the strong ion difference (SID) in this cat is 71.5 mmol/L (reference interval is 24-45) indicating a severe loss of chloride compared to sodium. Glucose is elevated. Urine pH appears elevated.

Comments on physiology - The vomiting certainly con tributed to chloride loss as compared to sodium. The vomiting certainly contributed to chloride loss but high intestinal ob struction had to be included in the differential as vomiting was acute. There is also evidence of a mixed acid-base disturbance since the bicarbonate is within reference interval or, at least, is high normal despite the fact that the anion gap is markedly in creased. The high anion gap indicates metabolic acidosis (pre renal azotemia + lactic acidosis due to severe dehydration) and the high normal bicarbonate indicating a concomitant metabolic acidosis secondary to vomiting and high intestinal obstruction. This also suggests that metabolic alkalosis is the primary problem. the high glucose value is secondary to stress.

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CASE 3 HEMOGRAM

Value

Reference

Hematocrit 45 28 - 40.0 Total plasma protein 10.6 6.0 - 8.0 ALL OTHER VALUES WERE CONSIDERED NORMAL (RBC and HB increased)

Units % g/dL

URINALYSIS (cystocentesis)

Value

Specific Gravity: Color: Transparency: pH: Glucose: Bilirubin Ketone: Protein Blood: Urobilinogen Red blood cells White blood cells Epithelial cells Crystals

1.050 Yellow Clear 7.2 Negative Negative Negative Negative Negative Present 0 0 0 0

CHEMISTRY

Value

Reference

Units

10.2 4.51 127 6.8 0.4 58 11 149 3.92 81.6 23.2 48.2 10.1 5.7 319 167

5.3 - 7.4 2.8 - 3.6 6.0 - 28.0 0.8 - 1.9 0.1 - 0.5 16 - 63 <50 145 - 158 3.6 - 5.3 110 - 125 14 - 24 8 - 15 9.7 - 11.1 10.96 - 1.96 80 - 160 127 - 234

g/dL g/dL mg/dL mg/dL mg/dL U/L U/L mmol/L mmol/L mmol/L mmol/L mmol/L mg/dL mg/dL mg/dL mg/dL

Focus on increased anion gap - MUD PILES M – mannitol U – uremia D – diabetic ketoacidosis (ketoacids) P – paraldehyde, proteins (especially myeloma proteins) I – indomethacin; abnormal ions L - lactic acid E - ethylene glycol S - salicylates

Units

per high powered field per high powered field per high powered field

Diagnosis - strong suspicion of complete high intestinal obstruction. Recommendations for further diagnostics - radiogra phy, ultrasound, exploratory. Radiographs using barium were performed 24 hours after the laboratory data were ac complished. these revealed blockage at the proximal duode nal level. An enterotomy revealed the presence of foam padding causing complete duodenal obstruction. Forty eight hours after surgery the electrolytes were within reference in terval. BUN and creatinine were close to the reference in terval. The cat made an uneventful recovery.

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Suggested reading de Morais HAS: Chloride ion in small animal practice: The forgotten ion. Vet Emerg Critical Care 2:1, 11, 1992. Russell KE, Hansen BD, Stevens JB: Strong ion difference approach to acid-base imbalances with clinical applications to dogs and cats. Vet Clin N America 26:2, 1185, 1995.

CASE 4 A 9 year old spayed female Greyhound was presented to determine treatment options for a previously diagnosed small thrombus in the caudal descending aorta. She was bright alert and responsive. She had a poor appetite resulting losing 3 pounds.

Significant laboratory findings Hemogram - mild leukopenia characterized by a lymphopenia; thrombocytopenia Urinalysis - marked proteinuria; 1 + blood but no RBCs observed Biochemical profile - decreased total serum protein, albumin; globulin is marginal; increased serum urea nitrogen, creatinine and phosphorus; decreased sodium and chloride; marked increase in potassium; increased anion gap; decreased total calcium; increased cholesterol, glucose

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is not compatible with life and must be due to error. There are no clinical signs associated with this finding. Hyperkalemia is associated with heart block and marked EKG abnormalities. The anion gap increase is suggestive of uremic acid and phosphate accumulation. Reruns on several instruments verified the marked hyperkalemia and the cause for error was sought. A rerun on a fresh plasma sample had similar results but potassium was considered normal. Focus on increased cholesterol - Hypercholesterolemia may be observed in a variety of pathological states. Included are hepatic cholestasis, hyperthyroidism, diabetes mellitus, hyperadrenocorticism, and nephrotic syndrome. The latter three are associated with hypercoagulable states due to platelet activation as a result of membrane cholesterol accumulation or loading. Focus on decreased serum total protein (hypoalbu minemia, +/-globulin) - Decreased serum protein results from lack of production – usually a late stage happening in hepatic cirrhosis, fibrosis, or neoplasia or increased renal or gastrointestinal loss. Renal protein loss is characterized by albumin loss. Gastrointestinal protein loss, often asso ciated with bleeding, results in decreases in both albumin and globulin. All albumin losing processes are associated with ATIII losing processes because of the similarity in molecular size. Any decrease in ATIII markedly increases the risk of thrombus formation. The decrease in ATIII is considered the single best indication of disseminated in travascular coagulation (DIC) when there is a primary in flammatory process.

Interpretation The hemogram reveals a leucopenia with a lymphopenia. Since stress is not evident without neutrophilia and monocytosis the lymphopenia can be secondary to renal disease (the hallmarks of renal disease are anemia, hypoproteinemia, hyperfibrinogenemia (not accomplished in this case), and lymphopenia. There was no history of glucocorticoid therapy. loss of lymph or disruption of lymph node architecture. Anemia in renal disease is often a late stage finding. Thrombocyopenia is secondary to consumption, decreased production, increased destruction, and splenic sequestration. The presence of a thrombus does suggest consumption. The urinalysis strongly suggests protein losing nephropathy. The slight hematuria may be the result of cystocentesis. Urinary or bladder hemorrhage or involvement could not be ruled out. The urinary loss of antithrombin III (ATIII) is suggested by the marked proteinuria and the presence of thrombus formation. Hyperglycemia may be due to stress or excitement. The azotemia is significant and with relatively poor concentration of the urine would suggest renal insufficiency. The hyperphosphatemia can also indicate reduced glomerular filtration. Since there is no physical indication of dehydration, and albumin is low, renal protein loss appears marked. The total protein is also low suggesting renal loss. The hyponatremia and hypochloridemia are typically associated with loss through vomiting or diarrhea. Ruptured urinary bladder is another possibility which could correlate with the azotemia. The hyperkalemia

Diagnosis - nephrotic syndrome and thrombosis sec ondary to amyloidosis. Recommendations for further diagnostics - Certainly a complete hemostasis profile – PT, APTT, FDP and ATIII should be accomplished. A urine protein to creatinine ratio should also be accomplished. Biopsy of liver, spleen and kid ney and examination for amyloid distribution may afford a better prognosis.

Suggested reading Green RA: Pathophysiology of antithrombin III deficiency. Vet Clin N America 18:95, 1988. Grindem CG, Breitschwerdt EB, Corbett WT et al:Epidemiologic survey of thrombocytopenia in dogs: A report on 987 cases. Vet Clin Path 20:38,1991.

CASE 5 An 11 year old spayed female cat previously diagnosed with diabetes mellitus was referred due to ketoacidotic crisis. The owner indicated the patient had been anorectic, adipsic, oliguric and had emesis. The patient was recumbent and had pale mucous membranes, and enlarged thyroid gland, and was 10% dehydrated. Thyroid tests suggested sick euthyroid syndrome.

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CASE 4 HEMOGRAM

Value

Reference

Units

8.43 20.0 55 5.4 65 – 36 Not done Not done 0 5.0 4.0 0.0 0.7 0.4 0.0 0.0 112

5.50 - 8.63 13.0 - 20.5 37.3 - 62.0 5.8 - 8.0 58 - 83 22.2 - 26.2 31.6 - 36.5 0 - 1.5 <75 0 5.4 - 16.6 3.2 - 10.7 0.0 - 0.2 0.8 - 5.6 0.0 - 1.1 0.0 - 2.4

x 106/µL g/dL % g/dL fL pg % % x 103/_L /100 WBC x 103/µL x 103/µL x 103/µL x 103/µL x 103/µL x 103/µL

179 - 473

x 103/µL

URINALYSIS (cystocentesis)

Value

Units

Specific Gravity: Color: Transparency: pH: Glucose: Bilirubin Ketone: Protein Blood: Urobilinogen Red blood cells White blood cells Crystals

1.019 Yellow Hazy 6.0 Negative 1+ Negative 4+ confirmed by SSA 1+ Present 0 0 0

CHEMISTRY

Value

Reference

Units

5.0 2.4 133 10.4 0.2 55 26 135 17.7 104 16.9 31.8 9.0 18.8 137 488

5.3 - 7.4 2.8 - 3.6 6.0 - 28.0 0.8 - 1.9 0.1 - 0.5 13 - 100 20 - 167 140 - 152 3.3 - 4.6 109 - 120 17.4 - 27.9 8 - 15 9.7 - 11.1 1.3 - 5.0 87 - 127 127 - 336

g/dL g/dL mg/dL mg/dL mg/dL U/L U/L mmol/L mmol/L mmol/L mmol/L mmol/L mg/dL mg/dL mg/dL mg/dL

per high powered field per high powered field

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Significant laboratory findings Patient’s FELV and FIV status was negative; urine culture was negative Hemogram - dehydrated with a low PCV; neutrophilic leucocytosis and lymphopenia Urinalysis - lack of much concentrating ability despite dehydration Biochemical profile - increased total serum protein, albumin, globulin; increased serum urea nitrogen, creatinine; borderline increased bilirubin with increases in alanine aminotransferase and alkaline phosphatase (this is a cat): decreased potassium, and marked increases in sodium and chloride; increased anion gap with metabolic acidosis; increased total calcium; increased cholesterol; decreased plasma pH; decrease in phosphorus

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Focus on phosphorus - Increases in phosphorus have many cause which basically are related to prerenal, renal, or postrenal causes. Hypophosphatemia is a frequent complication of insulin therapy in cats – uptake by cells as the result of insulin therapy. Anorexia complicates this. Hypophosphatemia may result from fluid therapy. Plasma magnesium concentration is regulated by the kidneys and may increase in these situations. Focus on increased anion gap - High anion gap with metabolic acidosis is most probably caused by lactic acido sis due to hypovolemic shock and/or ketoacidosis. As ke tones were not present, the former is most likely. Hyperpro teinemia can also contribute. It should be noted that al though there was a strong ion difference, acidosis instead of alkalosis was present. This is one instance where calculation of strong ion difference, sodium plus potassium minus chlo ride, without measuring lactate, would lead to false conclu sions regarding acid base balance.

Interpretation Anemia is severe and appears acute suggesting hemolysis. Significant biochemical abnormalities suggest hepatic disease most likely secondary to diabetes mellitus. The most important clinical finding is this patient’s hyperosmolarity. The increased proteins (total, albumin and globulin, increased serum urea nitrogen and creatinine are associated with dehydration. Hyperalbuminemia has affected total calcium. This patient’s bilirubinemia is only borderline. This most often suggests cholestasis and is often accompanied by increases in alkaline phosphatase and cholesterol. In this patient the additional increase in ALT does suggest by cholestasis and hepatocellular damage – most likely hepatic lipidosis. Hypocholesterolemia may be observed in severe liver cell damage due to chemicals, drugs or hepatitis. It is also observed from numerous causes of malnutrition. There is no evidence of anemia as a potential cause of extrahepatic hyperbilirubinemia. The modest increase in alkaline phosphatase is considered significant in this patient. Any increase or trend towards increase in this feline analyte suggests cholestasis in the cat. While the modest increase in alanine aminotransferase is considered insignificant. and bactiuria. Hypokalemia is a frequent finding in diabetic cats, especially those receiving insulin therapy. This finding is also observed as the result of gastrointestinal loss from vomiting, renal loss due to diuresis, cellular uptake facilitated by insulin therapy, and transcellular uptake following correction of acidosis. The patient was pseudohypernatremic and pseudohypernatremic due to hypotonic water loss - dehydration and adipsia. Hypophosphatemia is infrequent in diabetic cats. Anion gap increases could be due to lactic acidosis as ketones were not present. Comments on physiology - The serum chemistry results do not fit neatly into a class of diabetic complications such as diabetic ketoacidosis or hyperosmolar nonketotic dia betes. In this case the hyperosmolarity was caused primari ly by the hypernatremia and complicated by the mild hyper glycemia. Usually hyperosmolarity in diabetes is caused by hyperglycemia. In healthy animals, hyperosmolality stimu lates ADH release and tubular water absorption. In this pa tient this physiologic response was complicated by osmotic diuresis and endogenous glucocorticoids.

Focus on insulin resistance - This includes hyperadrenocorticism, hyperthyroidism, acromegaly, renal failure, and bacterial infections. Pancreatitis and exocrine pancreatic neoplasia could also potentially be factors to consider. Focus on hyperosmolarity and hypernatremia - Osmolarity in the cat greater than 340 mOsm/kg may induce neurologic signs, and inhibit thirst and drinking. Causes of hypernatremia include prolonged osmotic diuresis, severe dehydration and activation of the renin-angiotensin-aldosterone pathway due to dehydration. The hallmark of nonketotic hyperosmolar diabetes is lack of maintenance of hydration which causes decreased plasma volume and GFR, impaired glucose secretion, and increase in extracellular fluid osmolality. Diagnosis - Hypernatremia-associated hyperosmolar postketotic diabetes mellitus; metabolic acidosis with a high anion gap; normocytic normochromic nonregenerative ane mia; hepatic lipidosis.

Suggested reading Bruskiewicz KA, Nelson RW, Feldman EC et al: Diabetic ketosis and ketoacidosis in cats: 42 cases (1980-1995) J Am Vet Med Assoc 211:2, 188,1997.

CASE 6 A 4 year-old, intact, male English Pointer, current on vaccinations, presented because of pale mucous membranes, depression, inappetence, occasional loose stools, vomiting, tachycardia, and tachypnea. Vomiting and diarrhea have been sporadic but are worsening. The patient appears 5% dehydrated.

Significant laboratory findings Hemogram - decreased plasma protein with increased fibrinogen; microcytic hypochromic nonregenerative anemia

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CASE 5 HEMOGRAM

Value

Reference

Units

4.2 6.4 22 6.7 51.1 15.3 30.3 0 Not done 0 28.77 10.33 0.0 1.62 0.2 0.5 0.0 156

6.0-13.0 6.0-16.0 30.0 - 50.0 5.5 - 7.7 42 - 55 12.5 - 17.6 28 - 32.5 0 - 1.5 <75 0 5.0 - 20.0 2.5 - 12.5 0.0 - 0.3 1.8 - 7.0 0.0 - 1.1 0.0 - 0.85

x 106/µL g/dL % g/dL fL pg % % x 103/_L /100 WBC x 103/µL x 103/µL x 103/µL x 103/µL x 103/µL x 103/µL

300 - 700

x 103/µL

URINALYSIS (cystocentesis)

Value

Units

Specific Gravity Color/transparency pH: Glucose: Bilirubin Ketone: Protein Blood: Urobilinogen Red blood cells White blood cells Crystals

1.032 Yellow/clear 6.0 1000 mg/dL Negative Negative 30 mg/dL Trace Present 1-3 occasional Bilirubin crystals

per high powered field per high powered field few

CHEMISTRY

Value

Reference

Units

8.8 4.5 150 5.9 0.7 565 78 183 3.55 136.8 12.3 35 12.3 1.5 231 339 7.203

5.5 - 7.7 3.0 - 4.6 18 - 41 0.7 - 2.2 0.1 - 0.7 23 - 109 4.0 - 80 153 - 162 3.6 - 5.8 119 - 132 12.4 - 23.2 10 - 27 8.4 - 11.5 2.9 - 8.3 57 - 131 63 - 219 7.36 - 7.44

g/dL g/dL mg/dL mg/dL mg/dL U/L U/L mmol/L mmol/L mmol/L mmol/L mmol/L mg/dL mg/dL mg/dL mg/dL

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with thrombocytosis; neutrophilic leucocytosis with lymphopoenia and monocytosis Urinalysis - unremarkable Biochemical profile - decreased total serum protein, albumin, globulin; decreased calcium; decreased glucose; modest hyperkalemia, hyponatremia and decrease in bi carbonate with increased anion gap

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Recommendations for further diagnostics - Endoscopy and appropriate gastrointestinal cytology and biopsy; iron studies – serum iron, serum ferritin, serum total iron binding capacity.

Suggested reading Harvey JW, French TW, Meyer DJ:Chronic iron deficiency in dogs. J American Animal Hosp Assoc 18: 946,1982.

Interpretation Significant laboratory abnormalities focus on the microcytic hypochromic nonregenerative anemia with a suggested stress leucogram, thrombocytosis, and hyperfibrinogenemia. These findings suggest iron deficiency due to lack of intake, uptake or due to blood loss. Iron deficiency is one cause of reactive thrombocytosis. Hyperfibrinogenemia does suggest marked inflammation despite the lack of leucogram corroboration. This is due to the marked decrease in total protein with a concurrent increase in fibrinogen concentration. The decrease in total protein is notable because both albumin and globlulin are decreased suggesting intestinal loss. The decreased albumin is causing a pseudhypocalcemia which corrects into reference interval using appropriate calculations. The notable hypoglycemia. This may be associated with uptake due to gastrointestinal pathology. Among the many causes of hypoglycemia is prolonged functional starvation. There is no strong evidence of hepatic or renal disease. Electrolytes must be interpreted in light of the state of hydration. The recorded normonatremiais, most likely, more profound and due to total body sodium deficiency. Hyperkalemia is associated with tissue necrosis and acidosis. The acidosis is secretory in nature and consistent with bicarbonate loss due to diarrhea. The increased anion gap is most likely due lactic acid, perhaps secondary to lack of nutrient absorption. Comments on physiology - Iron deficiency can result from lack of intake, inflammation due to any cause, chronic blood loss from parasitism gastrointestinal ulceration or gastroin testinal neoplasia, portal caval abnormalities, and inflamma tory bowel disease specifically. True iron deficiency results in decrease in serum iron with increased serum transferrin (to tal iron bindiing capacity). In anemia of inflammation, iron is sequestered in the liver as ferritin or as precipitated hemo siderin. Hepatic iron accumulation is potentially hepatotoxic. Use of iron chelating agents is required when iron accumu lates in excessive amounts in the liver. Focus on decreased iron concentration - In order to study iron, nonhemolyzed blood must be collected in a trace miner al free test tube. Studies should include serum iron and trans ferrin concentrations (total iron binding capacity – TIBC). No other analytes are needed and only tend to obfuscate the da ta. True iron deficiency is marked by decreases in serum iron and increases in serum TIBC. Iron deficiency secondary to in flammation is characterized by decreases in serum iron and also decreases in serum TIBC. Hepatic iron stores can be ac curately estimated by species specific serum ferritin assays. Diagnosis - Inflammatory bowel disease; marked lym phocytic plasmacytic enteritis.

CASE 7 A six year old intact female miniature Poodle presented with a 3 day history of vomiting. The dog was given chicken bones (!). Temperature is 103.2F, pulse is 106, and the patient is panting. There is no abdominal pain but the patient is difficult.

Significant laboratory findings Hemogram - relative erythrocytosis with increased hematocrit and total protein; marked neutrophilic leucocytosis with a regenerative left shift and with notable lymphopenia and monocytosis. Hyperfibrinogenemia is suggested Urinalysis - glycosuria Biochemical profile - increased total serum protein, globulin, serum urea nitrogen, creatinine; modest increases in alanine aminotransferase and alkaline phosphatase; increased sodium, potassium and chloride; increased anion gap; decreased total calcium; increased lipase with normal amylase

Interpretation Significant laboratory abnormalities suggest pancreatic disease with secondary hepatic involvement. The hemogram suggests both dehydration and active, severe inflammation and stress (lymphopenia) with tissue necrosis (monocytosis). Glycosuria is expected when the renal threshold of 180 mg/dL is exceeded. Glycosuria without concurrent hyperglycemia would suggest renal disease. In this patient both glycosuri aa n d hyperglycemia do suggest diabetes mellitus. The increased proteins (both plasma and serum), borderline increase in albumin, globulin, serum urea nitrogen, creatinine and electrolytes all are compatible with dehydration. Urine specific gravity is similarly suggestive. The normal amylase with elevated lipase does suggest possible acute Pancreatitis but dehydration has confused this diagnosis. Nevertheless the hemogram data plus the hypocalcemia with normal albumin are consistent with a diagnosis of Pancreatitis. While the modest increases in alanine aminotransferase and alkaline phosphatase is considered insignificant. Mild hepatocellular degeneration and cholestasis, respectively, could account for these findings. Endogenous glucocorticoids must also be considered. However this latter analyte abnormality should be reexamined with additional profiles at, at most, weekly intervals. Alkaline urinary pH is most commonly associated with systemic alkalosis and bactiuria.

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CASE 6 HEMOGRAM

Value

Reference

Units

Red cell count Hemoglobin Hematocrit Total plasma protein Fibrinogen MCV MCH MCHC Reticulocytes Absolute retic. count Metarubricytes White blood count Neutrophils Bands Lymphocytes Monocytes Eosinophils Basophils Platelets

4.16 4.5 18 5.6 600 43.9 17.2 25.5 3.3 135 1 17.5 13.8 0.7 0.6 1.47 0.787 0.0 720

5.50 - 8.63 13.0 - 20.5 37.3 - 62.0 5.8 - 8.0 200-400 58 - 83 22.2 - 26.2 31.6 - 36.5 0 - 1.5 <75 0 5.4 - 16.6 3.2 - 10.7 0.0 - 0.2 0.8 - 5.6 0.0 - 1.1 0.0 - 2.4

x 106/µL g/dL % g/dL mg/dL fL pg % % x 103/_L /100 WBC x 103/µL x 103/µL x 103/µL x 103/µL x 103/µL x 103/µL

179 - 473

x 103/µL

URINALYSIS (cystocentesis)

Value

Units

Specific Gravity Color pH Glucose Bilirubin Ketone Protein Blood Urobilinogen Red blood cells White blood cells

1.043 Yellow 7.1 Negative Negative Negative Trace Negative Present 2 2

CHEMISTRY

Value

Reference

Units

4.9 2.4 27 1.2 0.3 29 108 142 5.4 111 16.0 20 8.9 3.3 56 84

5.3 - 7.4 2.8 - 3.6 6.0 - 28.0 0.8 - 1.9 0.1 - 0.5 13 - 100 20 - 88 140 - 152 3.3 - 4.6 109 - 120 17.4 - 27.9 8 - 15 9.7 - 11.1 1.3 - 5.0 87 - 127 127 - 336

g/dL g/dL mg/dL mg/dL mg/dL U/L U/L mmol/L mmol/L mmol/L mmol/L mmol/L mg/dL mg/dL mg/dL mg/dL

Transparency: Clear

per high powered field per high powered field

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CASE 7 HEMOGRAM

Value

Reference

Units

8.0 18 55 8.2 69 24 34 Not done Not done 0 41.2 34.0 2.5 0.8 3.9 0.0 0.0 213

5.50 - 8.63 13.0 - 20.5 37.3 - 53.0 5.8 - 8.0 58 - 83 22.2 - 26.2 31.6 - 36.5 0 - 1.5 <75 0 5.4 - 16.6 3.2 - 10.7 0.0 - 0.2 0.8 - 5.6 0.0 - 1.1 0.0 - 2.4

x 106/µL g/dL % g/dL fL pg % % x 103/_L /100 WBC x 103/µL x 103/µL x 103/µL x 103/µL x 103/µL x 103/µL

179 - 473

x 103/µL

URINALYSIS (cystocentesis)

Value

Units

Specific Gravity Color Transparency pH: Glucose Bilirubin Ketone Protein Blood Urobilinogen Red blood cells White blood cells Crystals

1.040 Dark yellow Clear 6.0 2+ Negative Negative Negative Negative Present Negative per high powered field Negative per high powered field Few magnesium ammonium phosphate crystals

CHEMISTRY

Value

Total serum protein 7.9 Albumin 3.6 Serum urea nitrogen 76 Creatinine 3.1 Total bilirubin 0,4 Alanine aminotransferase 110 Alkaline phosphatase 280 Sodium 162 Potassium 7.0 Chloride 130 Total CO2 22 Anion gap + Potassium 17 Total calcium 7.9 Phosphorus 4.8 Glucose 95 Cholesterol 330 Amylase is normal; Lipase is elevated

Reference

Units

5.3 - 7.4 2.8 - 3.6 6.0 - 28.0 0.8 - 1.9 0.1 - 0.5 13 - 100 20 - 167 140 - 152 3.3 - 4.6 109 - 120 17.4 - 27.9 8 - 15 9.7 - 11.1 1.3 - 5.0 87 - 127 127 - 336 4800 IU/L (800-1600 IU/L)

g/dL g/dL mg/dL mg/dL mg/dL U/L U/L mmol/L mmol/L mmol/L mmol/L mmol/L mg/dL mg/dL mg/dL mg/dL

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Comments on physiology - Data, clinical signs and his tory all suggest dehydration, primary Pancreatitis with pos sible secondary Pancreatitis and mild hepatic disease. Re curring Pancreatitis commonly cause diabetes mellitus. Transient marked hyperglycemia cane be a feature of Pan creatitis. In the treatment of Pancreatitis blood glucose should be monitored (do not use a glucometer!) through the recovery period. Although stress or endogenous glucocorti coids could elevate glucose, the concentration noted herein are too high for stress. With the existing dehydration and prerenal azotemia Pancreatitis is probable but not conclu sive. Treatment resulted in normalization of BUN and crea tinine with persistent elevation in lipase suggesting Pancre atitis. In this patient hyperglycemia was transient. Focus on increased electrolytes - with dehydration elec trolytes and protein will be elevated. Increased electrolytes in the face of dehydration suggest that electrolyte balance is normal. Focus on BUN, creatinine, urine specific gravity Azotemia is established on the basis of moderate elevations in these analyte. The prerenal nature of the azotemia is suspected because of strong evidence of dehydration implying reduced renal perfusion. There is no evidence in the urinalysis of primary renal or postrenal involvement. In fact, high urine specific gravity is strong evidence that renal tubular function is adequate as urine is being concentrated in the face of dehydration. Diagnosis - Acute Pancreatitis. Recommendations for further diagnostics - Ultrasonog raphy is useful in corroborating the laboratory diagnosis. Trypsinogen activation peptide (TAP) is a new analyte which promises to be diagnostically helpful in Pancreatitis. Trypsin like immunoreactivity (TLI) does not appear to be a useful analyte in the diagnosis of canine Pancreatitis.

Suggested reading Jacobs RM:Renal disposition of amylase, lipase ,and lysozyme in the dog. Vet Pathol 25:443, 1988. Jacobs RM: The origins of canine serum amylases and lipase. Vet Pathol 26: 525,1989.

CASE 8 A 5 year old male castrated mixed breed dog presented with a history of vomiting for the past 2 to 3 days. Other than evidence of dehydration (5%+) physical assessment was unremarkable.

Significant laboratory findings Hemogram - Elevation in RBC, HB, and PCV with elevation in total protein Urinalysis - Unremarkable except that with dehydration the specific gravity is less than 1.030. However the finding of an acid pH with increased total CO2 is unusual

121

Biochemical profile - marked increases in BUN, creatinine, total protein and albumin, with marked decreases in sodium and chloride and mar kedly increased total CO2

Interpretation There appears to be a relative erythrocytosis, dehydration, with elevated RBC, hemoglobin and PCV as well as total protein. There is a stress leucogram with notable presence of normal numbers of lymphocytes. Hypoadrenocorticism must be considered with this finding. Urinalysis is remarkable only because of the relatively low specific gravity. Increased total serum protein, albumin, and increased serum urea nitrogen, creatinine, low normal urine specific gravity are consistent with renal failure (renal azotemia). In this case the marked decrease in sodium and chloride cast some doubt on this interpretation. The sodium and chloride are lower than would be anticipated with renal failure. Sodium is low enough to directly cause decreased tubular concentrating ability. The possibility of prerenal azotemia with hyponatremia induced isosthenuria must be considered. The sodium to potassium ratio could also be considered suggestive of hypoadrenocorticism. The increased total CO2 coupled with the decreased sodium and chloride (chloride is relatively lower than sodium) confirms the diagnosis of metabolic alkalosis. Comments on physiology - Laboratory data do not lead to a specific disease diagnosis but rather to a differential di agnosis. Gastric vomiting, gastrointestinal foreign body, hy poadrenocorticism, and third space disease must be consid ered as primary problems; the electrolyte changes suggest that renal analyte abnormalities are most likely secondar y. Focus on decreased sodium and chloride - Marked decreas es in chloride and sodium are either the result of loss (medullary washout or in hypoadrenocorticism where tubular ability to re sorb sodium is impaired) or dilution in an expanded extracellu lar fluid compartment (such as ascites or edema). Though both electrolytes are decreased the chloride is relatively lower sug gesting greater loss of chloride due, perhaps, to vomiting. Focus on metabolic alkalosis - Metabolic alkalosis with a normal anion gap and decreased sodium and chloride sup ports the idea that azotemia is not associated with the or ganic acids of renal failure. The urine pH is 6.0 which, al though normal for the dogs is worthy of comment in light of the metabolic alkalosis. This is a case of paradoxical aciduria. If able, the kidneys would be expected to compen sate for the metabolic alkalosis by excreting bicarbonate ion thereby elevating the urine pH. In this case the electrolytes are exacerbating this problem and preventing compensation. Diagnosis - Gastrointestinal foreign body.

Suggested reading Robinson EP, Hardy RM: Clinical signs, diagnosis, and treatment of alkalmemia in dogs: 20 cases. J Amer Vet Med Assoc 192:943, 1988.

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CASE 8 HEMOGRAM

Value

Reference

Units

9.0 20 61 8.7 72 35 35 Not done Not done 0 21.0 16.7 0.0 2.5 1.6 0.2 0.0 344

5.50 - 8.63 13.0 - 20.5 37.3 - 62.0 5.8 - 8.0 58 - 83 22.2 - 26.2 31.6 - 36.5 0 - 1.5 <75 0 5.4 - 16.6 3.2 - 10.7 0.0 - 0.2 0.8 - 5.6 0.0 - 1.1 0.0 - 2.4

x 106/µL g/dL % g/dL fL pg % % x 103/_L /100 WBC x 103/µL x 103/µL x 103/µL x 103/µL x 103/µL x 103/µL

179 - 473

x 103/µL

URINALYSIS (cystocentesis)

Value

Units

Specific Gravity Color Transparency pH Glucose Bilirubin Ketone Protein Blood Urobilinogen Red blood cells White blood cells Epithelial cells Crystals/Casts

1.020 Yellow Clear 6.0 Negative Negative Negative Trace Trace Present 1-2 1-2 1-2 Negative

CHEMISTRY

Value

Reference

Units

7.7 4.2 109 2.3 0.3 56 140 121 5.2 71 39 15 10.6 5.0 110 260

5.3 - 7.4 2.8 - 3.6 6.0 - 28.0 0.8 - 1.9 0.1 - 0.5 13 - 100 20 - 167 140 - 152 3.6 - 5.3 109 - 120 17.4 - 27.9 8 - 15 9.7 - 11.1 1.3 - 5.0 87 - 127 127 - 336

g/dL g/dL mg/dL mg/dL mg/dL U/L U/L mmol/L mmol/L mmol/L mmol/L mmol/L mg/dL mg/dL mg/dL mg/dL

per high powered field per high powered field per high powered field

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Case studies in clinical hemostasis Più frequenti alterazioni dell’emostasi

Bernard Feldman DVM, PhD - Regional College of Veterinary Medicine - Virginia-Maryland, USA

CASE 1 An eight month old male Golden Retriever puppy was presented because of a swollen and painful left stifle joint -

one day’s duration. Owner related previous occasional minor joint problems and occasional hematuria. There was no history of epistaxis, gastrointestinal bleeding, purpura, polydipsia or polyuria.

CASE 1 HEMOGRAM 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 BT min PT sec FDP ug/ml

32 (37-55) 10.5 (12-18) 3.9 (6-8) 75 (60-77) 32.6 (31-35) 21.5 (19-24) 1.5 (0-1.5) 0 (0) Polychromasia Slight toxicity 175 (200-400) Some mega forms 4.0 (<4.2 ) 12 (12 ) 12 (<10)

5.7 (6.0-8.0) 475 (200-400) 5.0 (2-7) 17000 (6000-17500) 300 (0-400) 11000 (3000-11500) 5300 (1000-4800) 1350 (150-1350) 1250 (100-1250) 0 (0) 0 (0) 0 (0) 10 (12) 37 (18) – (>85)

CHEMISTRY ALT mU/ml ALP mU/ml T. Bili mg/dl Gluc mg/dl S. Protein g/dl Albumin g/dl Chol mg/dl AG mEq/L

61 102 0.3 109 5.0 2.6 175 15

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl

29 1.0 148 3.2 116 20 10.2 3.4

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Bilirubin Bacteria Urobilinogen

TNTC 1 1 hemoglobin Negative Negative Negative Negative

URINALYSIS (Cystocentesis) SG 1.027 Color Red Transparency Clear pH 7.2 Protein Trace Glucose Negative Ketones Negative Occult Blood Positive

(4-66) (0-88) (0.1-0.6) (70-120) (5.3-7.8) (3.0 -4.0) (28-255) (12-20)

(5-28) (<1.5) (145-153) (2.7-5.3) (110-119) (19-24) (9.8-11) (2.5-6.2)

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CASE 2 HEMOGRAM 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 BT min PT sec FDP ug/ml

40 (37-55) 13 (12-18) 5.1 (6-8) 73 (60-77) 33.1 (31-35) 19.8 (19-24) 1.4 (0-1.5) 0 (0) Polychromasia Normal 135 (200-400) Normal 1.8 (<4.2) 27 (12) 0 (<10)

5.9 (6.0-8.0) 350 (200-400) 3.0 (2-7) 12500 (6000-17500) 0 (0-400) 10000 (3000-11500) 1700 (1000-4800) 300 (150-1350) 500 (100-1250) 0 (0) 0 (0) 0 (0) 10 (12) 19 (18) – (>85)

CHEMISTRY ALT mU/ml ALP mU/ml T. Bili mg/dl Gluc mg/dl S. Protein g/dl Albumin g/dl Chol mg/dl AG mEq/L

54 17 0 97 5.2 2.9 112 21

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl

17 1.0 144 3.6 110 19 9.9 3.0

URINALYSIS (Cystocentesis) SG 1.033 Color Yellow Transparency Clear pH 6.4 Protein Trace Glucose Negative Ketones Negative Occult Blood Negative Bilirubin Negative

(4-66) (0-88) (0.1-0.6) (70-120) (5.3-7.8) (3.0 -4.0) (28-255) (12-20)

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Epithelial cells Bacteria Urobilinogen

CASE 2 A three year old intact female Irish Setter was referred for evaluation of recurrent epistaxis. These episodes, usually lasting 5-10 minutes, had been recurring for several years, especially in the summer. Blood loss was from both nostrils and was not apparently associated with trauma. Her past history revealed increased blood when she lost her puppy teeth and during estrus. There was no family history of excessive bleeding tendency. Physical examination was entirely within normal limits.

CASE 3 A 1 and 1/2 year old intact male Doberman Pinscher known to have factor VIII deficiency (hemophilia A) was presented because of sudden onset right hind leg pain. He

(5-28) (<1.5) (145-153) (2.7-5.3) (110-119) (19-24) (9.8-11) (2.5-6.2)

0 1 Negative Negative 1-2 Negative Positive

had been treated with cryoprecipitate with no obvious beneficial effects. During the past few hours the intensity of pain had increased and the leg was now carried in a flexed position. A tender mass was palpated in the right iliac fossa.

CASE 4 A 12 year old mixed breed male dog was admitted to the hospital for elective castration due to benign prostatic hypertrophy (no tumor palpable, symmetrical glandular size increase, difficulty urinating and defecating). He had previously been in excellent health and had an unremarkable history and no past history of bleeding.Surgery was uneventful but petechiae and ecc hymoses on the ventral abdomen were noted four days postoperatively.

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CASE 3 HEMOGRAM 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 BT min PT sec FDP ug/ml

34 (37-55) 11.5 (12-18) 5.3 (6-8) 69 (60-77) 31.5 (31-35) 21 (19-24) 0 (0-1.5) 0 (0) Normal Normal 85 (200-400) Some oval, large 2.2 (<4.2) 11 (12) – (<10)

5.4 (6.0-8.0) 450 (200-400) 2.0 (2-7) 18900 (6000-17500) 0 (0-400) 16400 (3000-11500) 1200 (1000-4800) 1300 (150-1350) 0 (100-1250) 0 (0) 0 (0) 0 (0) 10 (12) 37 (18) – (>85)

After cryoprecipitate was administered, the APTT was 36 seconds. Equal parts patient plasma and canine pooled plasma resulted in an APTT of 36 seconds CHEMISTRY ALT mU/ml ALP mU/ml T. Bili mg/dl Gluc mg/dl S. Protein g/dl Albumin g/dl Chol mg/dl AG mEq/L

57 77 0.3 72 4.9 2.4 389 16

URINALYSIS (Cystocentesis) SG 1.038 Color Brown Transparency Clear pH 6.4 Protein 1+ Glucose Negative Ketones Negative Occult Blood Positive Bilirubin Negative

(4-66) (0-88) (0.1-0.6) (70-120) (5.3-7.8) (3.0 -4.0) (28-255) (12-20)

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Epithelial cells Bacteria Urobilinogen

CASE 5 A two year old intact male Norwegian Elkhound was presented because of dyspnea and hemoptysis. The patient had a checkered history of vague minor illnesses, however this presentation was acute. The owner is a good observer and a good client.

CASE 6 An urgent consultation was requested for a patient in the intensive care unit. A seven year old, mixed breed, spayed female dog had returned from surgery following

41 0.5 146 4.0 112 23 9.9 4.3

(5-28) (<1.5) (145-153) (2.7-5.3) (110-119) (19-24) (9.8-11) (2.5-6.2)

0 5 Negative Negative 3-4 Negative Positive

extensive bowel resection for sarcoma. During surgery she was autotransfused from vacuumed abdominal blood. Over the 24 hour postoperative period she had received three units of whole blood for extensive intraoperative blood loss. Following surgery, oozing was observed from the abdominal drain tube and following venipuncture. During the immediate postoperative period (30 minutes) she had received 2 of the 3 units of blood. There was no previous history of bleeding and a hemostatic profile performed 24 hours presurgically was within reference intervals. Petechiae and purpura were noted on the lower limbs. Chest radiographs were normal and blood culture was negative.

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CASE 4 HEMOGRAM 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 BT min PT sec FDP ug/ml

44 (37-55) 14 (12-18) 6.2 (6-8) 71 (60-77) 34 (31-35) 22.5 (19-24) 0 (0-1.5) 0 (0) Normal Normal 65 (200-400) Some oval, large ND (<4.2) 11 (12) – (<10)

7.3 (6.0-8.0) 500 (200-400) 4.0 (2-7) 2200 (6000-17500) 0 (0-400) 1800 (3000-11500) 200 (1000-4800) 200 (150-1350) 0 (100-1250) 0 (0) 0 (0) 0 (0) 12 (12) 18 (18) – (>85)

CHEMISTRY ALT mU/ml ALP mU/ml T. Bili mg/dl Gluc mg/dl S. Protein g/d Albumin g/dl Chol mg/dl AG mEq/L

47 83 0.3 119 6.8 3.0 230 18

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl

22 0.4 151 4.7 113 24 10.2 5.5

URINALYSIS (Cystocentesis) SG 1.050 Color Yellow Transparency Turbid pH 7.7 Protein 2+ Glucose Negative Ketones Negative Occult Blood Negative Bilirubin Negative

(4-66) (0-88) (0.1-0.6) (70-120) (5.3-7.8) (3.0-4.0) (28-255) (12-20)

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Epithelial cells Bacteria Urobilinogen

CASE 7 At 2100 hours, a 5 year old, large, mixed breed intact male dog was bitten on his left forepaw, around the toes, by Crotalus atrox, the Western Diamond Backed rattlesnake. He was brought to an emergency clinic in the Tucson area 40 minutes later. There he was noted to have pain and swelling limited to the left front leg, mostly the paw region. Vital signs were normal. The leg was immobilized and an intravenous line was started in the right foreleg. During the evening the swelling was noted to extend up the left leg and pain extended to the left axillary area. The next day he developed abdominal pain and one episode of emesis occurred. On that morning, after skin testing, ten vials of antivenin (Crotalidae) polyvalent were administered over several hours. The following day the

(5-28) (<1.5) (145-153) (2.7-5.3) (110-119) (19-24) (9.8-11) (2.5-6.2)

4 5 1-2 coarse granular Negative 8-10 Negative Positive

dog was discharged with oral pain medication. He regained full use of his paw and leg. The following are the notable laboratory results: Test

Day 1

Day 2

Day 3

Time

2200

0400

2200

1000

Hb g/dl

14.0

12.9

12.2

11.5

PCV%

40.0

37.7

35.3

28.8

Plat/ul

30000

115000

96000

PT sec

11.5

>120

13.0

11.9

APTT sec 35.9

>120

30.4

28.8

Fibr mg/dl 100

<50

240

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CASE 5 HEMOGRAM 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 BT min PT sec FDP ug/ml

34 (37-55) 11 (12-18) 5.8 (6-8) 65 (60-77) 36 (31-35) 21 (19-24) 0 (0-1.5) 11 (0) Schistocytes Toxic granulation 200 (200-400) Normal 1.9 (<4.2) 10 (12) >40 (<10)

4.9 (6.0-8.0) 625 (200-400) 4.0 (2-7) 5100 (6000-17500) 0 (0-400) 4500 (3000-11500) 600 (1000-4800) 0 (150-1350) 0 (100-1250) 0 (0) 0 (0) 0 (0) 12 (12) 17 (18) 55 (>85)

CHEMISTRY ALT mU/ml ALP mU/ml T. Bili mg/dl Gluc mg/dl S. Protein g/dl Albumin g/dl Chol mg/dl AG mEq/L

64 54 0.2 93 4.5 1.2 672 17

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl

77 2.1 153 5.1 111 18 7.9 6.9

URINALYSIS (Cystocentesis) SG 1.021 Color Yellow Transparency Clear pH 6.5 Protein 4+ Glucose Negative Ketones Negative Occult Blood Negative Bilirubin Negative

(4-66) (0-88) (0.1-0.6) (70-120) (5.3-7.8) (3.0 -4.0) (28-255) (12-20)

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Epithelial cells Bacteria Urobilinogen

(5-28) (<1.5) (145-153) (2.7-5.3) (110-119) (19-24) (9.8-11) (2.5-6.2)

0 0 1-2 waxy MAP 0 Negative Positive

CASE 8

CASE 9

A two year old intact male Samoyed was presented because of a rash on the abdomen. The owner was grooming the dog and noticed numerous areas of irritation over the shoulders and over the hips. He appears to be bright, alert and active. Temperature, pulse and respiration are normal. The patient is current on vaccinations. The dog is shown in conformation classes. The most recent dog show where he competed was two weeks ago.

A four year old female Poodle was referred for evaluation of purpura. The owners remarked that previously she appeared to bruise easily but that they had noticed increased tendency to bruise during the past few days. She had been spayed without incident and had dental extractions one year ago without difficulties. History included involvement in a bicycle accident 10 months ago and subsequent though occasional pain during ambulation.

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CASE 6 HEMOGRAM 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 BT min PT sec FDP ug/ml D-dimers

22 (37-55) 7.6 (12-18) 3.2 (6-8) 65 (60-77) 31.5 (31-35) 20 (19-24) 0 (0-1.5) 4 (0) Poik/leptocytes Toxic vacuolation 25 (200-400) Mega forms ND (<4.2) 19 (12) 0 (<10) 10 (0)

6.0 (6.0-8.0) 200 (200-400) 4.0 (2-7) 10800 (6000-17500) 750 (0-400) 7750 (3000-11500) 1300 (1000-4800) 900 (150-1350) 100 (100-1250) 0 (0) 0 (0) 0 (0) 20 (12) 31 (18) 71 (>85)

CHEMISTRY ALT mU/ml ALP mU/ml T. Bili mg/dl Gluc mg/dl S. Protein g/dl Albumin g/dl Chol mg/dl AG mEq/L

214 650 0.8 112 5.5 2.8 333 24

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl

14 0.2 142 3.0 110 14 10.8 5.8

URINALYSIS (Cystocentesis) SG 1.011 Color Pink Transparency Clear pH 7.8 Protein 0 Glucose Negative Ketones Negative Occult Blood Positive

(4-66) (0-88) (0.1-0.6) (70-120) (5.3-7.8) (3.0 -4.0) (28-255) (12-20)

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Bilirubin Bacteria Urobilinogen

(5-28) (<1.5) (145-153) (2.7-5.3) (110-119) (19-24) (9.8-11) (2.5-6.2)

8 0 0 0 Negative Negative Positive

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CASE 8 HEMOGRAM 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 BT min PT sec FDP ug/ml

32 (37-55) 8.6 (12-18) 4.00 (6-8) 72.5 (60-77) 29.7 (31-35) 22.2 (19-24) 6.0 (0-1.5) 3 (0) Polychrom, aniso Appropriate 172 (200-400) Some mega forms 4.8 (<4.2) 13 (12) 10 (<10)

5.8 (6.0-8.0 300 (200-400) Hemol( 2-7) 10400 (6000-17500) 74 (0-400) 6848 (3000-11500) 1332 (1000-4800) 1541 (150-1350) 592 (100-1250) 0 (0) 0 (0) 0 (0) 13 (12) 16.5 (18) 91 (>85)

CHEMISTRY ALT mU/ml ALP mU/ml T. Bili mg/dl Gluc mg/dl S. Protein g/dl Albumin g/dl Chol mg/dl AG mEq/L

321 76 0.1 78 5.5 2.7 123 20

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl

33 1.2 146 4.7 112 21 10.0 3.8

URINALYSIS (Cystocentesis) SG 1.023 Color Yellow/red Transparency Clear pH 6.6 Protein 2+ Glucose Negative Ketones Negative Occult Blood Positive Bilirubin Positive

(4-66) (0-88) (0.1-0.6) (70-120) (5.3-7.8) (3.0 -4.0) (28-255) (12-20)

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Epithelial cells Bacteria Urobilinogen

(5-28) (<1.5) (145-153) (2.7-5.3) (110-119) (19-24) (9.8-11) (2.5-6.2)

13 0 0 Bilirubin 1 Negative Positive

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CASE 9 HEMOGRAM PCV % Hb g/dl RBC x 106/u MCV fl MCHC g/dl MCH pg Retics % Nrbcs/100wbc RBC morph WBC morph Plat x 103/ul Plat morph BT min PT sec FDP ug/ml

40 13 6.1 74 32.2 21 0.5 0 Doehle bodies Appropriate 280 No atypia 5.9 18 5

(37-55) (12-18) (6-8) (60-77) (31-35) (19-24) (0-1.5) (0)

(200-400) (<4.2) (12 ) (<10)

Plasma Protein g/dl Fibrinogen mg/dl Icterus Index units WBC (corrected) /ul Bands Neutrophils Lymphocytes Monocytes Eosinophils Basophils Disintegrated cells Unidentifiable cells Thrombin time (TT) sec APTT sec Antithrombin III %

5.9 (6.0-8.0) 550 (200-400) 2.0 (2-7) 18675 (6000-17500) 675 (0-400) 14450 (3000-11500) 3200 (1000-4800) 250 (150-1350) 0 (100-1250) 0 (0) 0 (0) 0 (0) 12 (12) 26 (18) 87 (>85)

Factor assays: II -10%; V-76%; VII-15%; VIII-86%; IX-25%; X-15% (normal > 70%) CHEMISTRY ALT mU/ml ALP mU/ml T. Bili mg/dl Gluc mg/dl S. Protein g/dl Albumin g/dl Chol mg/dl AGap mEq/L

57 56 0.2 119 5.4 2.8 98 19

URINALYSIS (Cystocentesis) SG 1.043 Color Yellow Transparency Clear pH 6.9 Protein Trace Glucose Negative Ketones Negative Occult Blood Negative Bilirubin Negative

(4-66) (0-88) (0.1-0.6) (70-120) (5.3-7.8) (3.0 -4.0) (28-255) (12-20)

SUN mg/dl Creatinine mg/dl Na mEq/L K mEq/L Cl mEq/L TCO2 mEq/L Ca mg/dl P mg/dl

Sediment Rbc/HPF Wbc/HPF Casts/LPF Crystals Epithelial cells Bacteria Urobilinogen

39 1.1 149 4.7 110 23 10.5 3.1

(5-28) (<1.5) (145-153) (2.7-5.3) (110-119) (19-24) (9.8-11) (2.5-6.2)

6 5 Negative Bilirubin 0 Negative Positive

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L’osteoartrosi nell’uomo: aspetti epidemiologici, patogenetici, diagnostici e terapeutici Antonella Fioravanti Med Chir - Facoltà di Medicina - Istituto di Reumatologia - Università di Siena

F. Nerucci Istituto di Reumatologia - Università di Siena

C. Tofi Istituto di Reumatologia - Università di Siena

R. Marcolongo Istituto di Reumatologia - Università di Siena

EPIDEMIOLOGIA L’osteoartrosi (OA) attualmente viene considerata come la più diffusa e la più comune patologia reumatolo gica; in Italia da sola rappresenta, infatti,il 72,6% delle malattie reumatiche e si calcola, pertanto, che circa 4 milioni di persone siano portatori di tale affezione. La frequenza della malattia aumenta progressivamente con l’avanzare dell’età; tale incremento tende ad essere di tipo aritmetico fino ai 50-55 anni e di tipo geometrico, specie per le donne, dopo i 55 anni. La diffusione dell’OA è destinata dunque a crescere nei prossimi decenni dato il graduale allungarsi della durata media della vita.

EZIOPATOGENESI L’etiologia dell’OA è ancora oggi sconosciuta; al momento si ritiene che la malattia riconosca un’origine multifattoriale, si ammette cioè che numerosi fattori predisponenti o scatenanti contribuiscano all’instaurarsi e all’evolversi della patologia (Tab. 1). L’età è considerata un fattore importante come dimostrato dai dati epidemiologici, tuttavia non si deve confondere il processo fisiologico legato all’invecchiamento della cartilagine articolare con la patologia artrosica vera e propria. I meccanismi attraverso i quali la senescenza articolare condiziona l’instaurarsi dell’OA sono in gran parte sconosciuti; le modificazioni anatomiche che si verificano a livello delle articolazioni ed i processi biochimici a carico della cartilagine articolare legati all’età favoriscono probabilmente l’intervento di altri fattori etiologici. Paradossalmente le alterazioni biochimiche della cartilagine senescente sono significati-

Tabella 1 - Artrosi e fattori di rischio - Età - Familiarità - Dismetabolismi - Traumi - Vizi di postura - Flogosi

- Sesso - Obesità - Razza e ambiente - Lavoro e sport - Displasie - Artriti da microcristalli

vamente diverse, se non contrastanti, rispetto a quelle che si rinvengono nella cartilagine artrosica. Si ammette pertanto che l’età rappresenti un semplice fattore di vulnerabilità della cartilagine articolare nei confronti di altri fattori, quali per esempio, quelli di tipo meccanico. Nella concezione attuale l’OA viene dunque nettamente distinta dal fisiologico invecchiamento della cartilagine articolare e definita come una vera e propria malattia il cui primum movens è stato individuato in una alterazione metabolica del condrocita. In seguito ad insulti di varia natura, questa cellula va incontro ad una sofferenza cui segue una alterata sintesi qualitativa e quantitativa dei componenti la matrice cartilaginea (collagene e proteoglicani) e la liberazione di una serie di mediatori ad attività condrolesiva. Le conseguenti lesioni cartilaginee determinano la liberazione di detriti nella cavità articolare che stimolano la reazione flogistica sinoviale ed un’ulteriore liberazione di sostanze infiammatorie ed enzimi catabolici. Nell’OA oltre alla degenerazione della cartilagine articolare ed alla flogosi sinoviale sono evidenti le modificazioni dell’osso subcondrale; a tale

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proposito molti sostengono che l’ispessimento della lamina ossea subcondrale giochi una parte importante nell’insorgenza e nell’evoluzione della malattia. La patologia artrosica coinvolge dunque non un solo tessuto, ma l’intera struttura articolare (cartilagine, sinovia, osso). Protagonista centrale della cascata patogenetica dell’OA è comunque il condrocita, cellula dotata di un ricco corredo enzimatico che gli consente di attuare sia i processi di sintesi dei costituenti la matrice cartilaginea, sia di degradare continuamente tali strutture al fine di rinnovare costantemente il tessuto cartilagineo. L’OA, in fondo, non è altro che il risultato ultimo di uno sbilanciamento tra i processi anabolici e catabolici condrocitari, con un netto prevalere dei secondi sui primi. Nel determinismo di tali eventi giocano un ruolo decisivo una serie di mediatori (enzimi, citochine, prodotti proflogogeni) dotati di attività condrolesiva. I condrociti sono dotati di un ricco corredo enzimatico in grado di degradare i costituenti della matrice. I principali enzimi coinvolti nella patogenesi dell’artrosi sono rappresentati dalle metalloproteasi che agiscono sulle fibre collagene (collagenasi, gelatinasi ed elastasi) e sulla proteina centrale dei proteoglicani (stromalisina o proteoglicanasi e aggrecanasi) e dalle serinoproteasi, cui appartengono gli attivatori del plasminogeno (tissue type PA o t-PA e urokinase type PA o u-PA) che determinano la formazione della plasmina in grado a sua volta di attivare le metalloproteasi (Tab. 2). Altri enzimi intervengono sui glicosaminoglicani (arilsolfatasi), sui prodotti di degradazione dei proteoglicani e del collagene (catepsine B e D) o sui fosfolipidi di membrana (fosfolipasi A2 o PLA2). Un ruolo importante dei processi degradativi è svolto anche dalla liberazione di specie reattive dell’ossigeno da parte delle cellule infiammatorie sinoviali e degli stessi condrociti. In particolare il Nitrossido NO inibisce la produzione dei glicosaminoglicani, stimola la liberazione delle metalloproteasi e media molte delle azioni svolte dall’interleuchina-1 (IL-1). Anche alcune citochine sono direttamente coinvolte nel processo artrosico; tra le più importanti ricordiamo l’IL-1, l’IL-6, l’IL-17 ed il tumor necrosis factor alfa (TNF-α). L’IL-1, in particolare, induce la sintesi condrocitaria delle metalloproteasi, la liberazione di NO ed inibisce la sintesi

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dei proteoglicani. La liberazione di queste sostanze condrolesive è d’altronde dovuta non solo ai condrociti, ma anche ad altri elementi cellulari (stanziali e non) come per esempio i sinoviociti, i macrofagi, i linfociti e i granulociti polimorfonucleati. La cartilagine possiede comunque anche dei meccanismi di difesa che agiscono a vari livelli. Tra questi vanno considerati gli inibitori enzimatici delle metalloproteasi (TIMP 1, 2 e 3), gli inibitori degli attivatori del plasminogeno (PAI 1 e 2), l’α-1 antitripsina, l’antagonista solubile del recettore per l’IL-1 (IL-1Ra) ed alcune citochine antiinfiammatorie come l’IL-4, l’IL-10 e l’IL-13 (Tab. 3). Un’altra via di difesa della cartilagine articolare è rappresentata da alcuni fattori di crescita come gli Insulin Growth Factor 1 e 2 (IGF1 e IGF2), il Basic Fibroblast Growth Factor (bFGF) ed il Trasforming Growth Factor beta (TGFβ), capaci di stimolare la sintesi dei proteoglicani e delle fibre collagene (Tab. 3).

ASPETTI CLINICI E DIAGNOSTICI I sintomi e i segni clinici dell’artrosi sono rappresentati dal dolore, dalla rigidità, dalla limitazione funzionale, associati nelle fasi avanzate, alle possibili deformità articolari. Il dolore è di tipo essenzialmente meccanico, ad insorgenza diurna ed in rapporto al carico articolare. Con il progredire della malattia, tende a presentarsi in maniera continua o subcontinua e, talora, persiste anche con il riposo. La rigidità articolare è di breve durata, presente al risveglio e particolarmente intensa dopo un periodo di immobilità protratta. Nelle fasi iniziali della malattia, la sintomatologia dolorosa, insieme alla contrattura antalgica dei muscoli, è responsabile della limitazione funzionale che, solo in fase più avanzata, può essere causata anche da ostacoli meccanici (per es. osteofiti). Al momento attuale non esistono indagini di laboratorio specifiche per la diagnosi e per il monitoraggio dell’OA. Gli indici aspecifici di flogosi sono generalmente normali,tranne alcuni episodici incrementi della VES. Il liquido si-

Tabella 2 - Enzimi, citochine ed altre sostanze ad azione condrolesiva

Tabella 3 - Sostanze ad azione riparativa ed inibitori della degradazione cartilaginea

- Metalloproteasi (collagenasi, gelatinasi, elastasi, stromalisina, aggrecanasi) - Attivatori del plasminogeno (t-PA, u-PA), Plasmina - Catepsine B e D - Arisolfatasi - Prostagandina E2 - Specie reattive dell’ossigeno - Sostanza P - IL-1, IL-6, Il-17 - TNFα

- TIMP1, TIMP2, TIMP3 - PAI-1 e PAI-2 - Alfa 1 antitripsina - Alfa 2 macroglobulina - IL-1 Ra - IL-4, IL-10, IL-13 - IGF-1, IGF-2 (Insulin Growth Factors) - TGF-beta (Transforming Growth Factor) - PDGF (Platelet-Derived Growth Factor) - BFGF (Basic Fibroblast Gr owth Factor)

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noviale è di tipo “non infiammatorio”, con aspetto limpido, viscosità conservata, coagulo mucinico compatto e leucociti inferiori a 2000/mmc. Un notevole interesse rivestono gli studi recenti relativi alla possibile individuazione di alcuni marker biochimici nel sangue, nelle urine e nel liquido sinoviale che dovrebbero permettere di quantificare l’entità del processo degenerativo cartilagineo. In particolare, è stato documentato in pazienti artrosici una elevata concentrazione sierica e/o sinoviale di prodotti di derivazione proteoglicanica, come il cheratansolfato, un aumento dello ialuronato nel plasma e delle piridinoline (aminoacidi con funzione cross-links tra catene adiacenti di collagene) nelle urine. Tali evidenze forniscono importanti spunti di ricerca nello studio della fisiopatologia dell’OA, ma non possono essere considerate definitive per una utilizzazione routinaria nella diagnosi precoce e nel monitoraggio terapeutico della malattia. Tra le tecniche strumentali la radiologia tradizionale rappresenta ancor oggi l’esame più utilizzato per la diagnosi, la stadiazione ed il monitoraggio dell’OA. Nella patologia artrosica risulta tuttavia frequente una discrepanza tra lesioni radiologiche documentabili e quadro clinico, potendo essere presente una modesta sintomatologia dolorosa associata ad avanzate alterazioni artrosiche e viceversa. Ciò probabilmente è dovuto al fatto che i sintomi spesso dipendono non tanto dalla gravità dei processi degenerativi (sclerosi, osteofiti, ecc.), quanto dai rapporti che si realizzano tra questi tessuti molli, le strutture sinoviali, nervose e vascolari. La radiologia tradizionale non è in grado di evidenziare direttamente tali strutture a meno di ricorrere a indagini invasive, quali la mielografia e l’artrografia, oggi in disuso ed ampiamente sostituite dalla radiologia digitale, dalla risonanza magnetica nucleare (RMN), dalla tomografia computerizzata (TC) e dall’ecografia articolare. Tuttavia l’esame radiologico standard, integrato con un buon esame clinico e anamnestico, spesso è sufficiente per formulare una diagnosi. Pertanto le metodiche più sofisticate sono ancor oggi da considerarsi di seconda istanza e da riservare a casi selezionati e clinicamente motivati. Un’altra tecnica spesso utilizzata nella diagnostica dell’OA è l’artroscopia che consente di visualizzare direttamente la cartilagine articolare, la membrana sinoviale e le strutture articolari. I moderni strumenti a nostra disposizione rendono possibile l’esplorazione di molte articolazioni, anche se il ginocchio rappresenta la sede più facile da studiare. L’osservazione diretta in artroscopia permette di definire la topografia e l’entità delle lesioni cartilaginee, la presenza di osteofiti marginali, le alterazioni della membrana sinoviale con villi ipertrofici cosiddetti “erba corta”, l’eventuale interessamento del legamento crociato anteriore e dei menischi, la presenza di depositi di cristalli di pirofosfato di calcio (condrocalcinosi) e di eventuali corpi liberi endoarticolari. L’artroscopia diagnostica permette di acquisire molti dati, tuttavia anche per il carattere invasivo, va riservata a casi ben selezionati ed eseguita in ambiente ospedaliero da personale qualificato.

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TERAPIA La terapia dell’OA comprende una serie di interventi diretti a combattere il dolore, ridurre gli episodi flogistici e la limitazione funzionale, rallentare l’evoluzione della malattia e, dove è possibile a rimuoverne le cause; i risultati migliori si ottengono generalmente attraverso il ricorso ben congegnato a più presidi terapeutici. La programmazione terapeutica dell’OA prevede una corretta informazione del malato, l’osservazione di alcune norme igieniche e di vita, la correzione di eventuali turbe dismetaboliche, endocrine e vascolari, la terapia farmacologica, fisica, occupazionale e chirurgica (Tab. 4). Il trattamento farmacolo gico si basa fondamentalmente su due categorie di farmaci ovvero i farmaci sintomatici che hanno lo scopo di determinare un rapido controllo della sintomatologia algica e funzionale e i farmaci ritenuti in grado di arrestare l’evoluzione della malattia (terapia di fondo). Il trattamento sintomatico si avvale degli analgesici minori o non narcotici e dei farmaci antiinfiammatori non steroidei (FANS). Nella scelta dell’uno o dell’altro tipo di molecola si deve tener conto delle condizioni generali e dell’età del paziente e della attività della malattia. Gli analgesici rappresentano i farmaci di prima scelta soprattutto in presenza di un dolore tipicamente di origine meccanica e con scarsa o nulla componente infiammatoria. I FANS trovano un’indicazione nelle riacutizzazioni flogistiche della malattia che possono per altro essere responsabili di un ulteriore aggravamento del danno cartilagineo. I FANS rappresentano pertanto uno strumento indispensabile ed irrinunciabile nel trattamento dell’OA, anche se la loro utilizzazione deve seguire alcune norme precise:valutazione dello stadio e dell’attività della malattia, delle sue caratteristiche evolutive, delle condizioni cliniche del paziente da trattare, scelta del preparato adattata al singolo caso, somministrazione a cicli di breve durata (5-7 giorni). Nell’OA, quindi, salvo rare eccezioni, l’utilizzazione dei FANS può avvenire in maniera intermittente, in rapporto alle riesacerbazioni dolorose e/o flogistiche della malattia. La scelta del FANS seguirà i presupposti

Tabella 4 - Programmazione terapeutica nell’artrosi - Informazione del malato - Norme igieniche e di vita - Correzione di eventuali turbe dismetaboliche, endocrine e vascolari - Terapia sintomatica - Terapia di fondo - Terapia intra-articolare - Terapia fisica - Chinesiterapia - Terapie termali - Terapia occupazionale - Ortesi - Terapia chirurgica

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teorici validi per ogni tipo di patologia reumatica cui vanno però aggiunte le considerazioni particolari concernenti il possibile effetto di questi farmaci sul metabolismo cartilagineo. Recentemente infatti è stata imputata ad alcuni FANS una potenziale azione condrolesiva dovuta ad una interferenza su alcune funzioni metaboliche del condrocita ed in particolare sulla biosintesi condrocitaria dei proteoglicani. L’effetto inibente sulla sintesi dei proteoglicani da parte dei FANS è peraltro più evidente nella cartilagine osteoartrosica rispetto al tessuto normale, fatto questo dovuto ad una più facile penetrazione di questi farmaci all’interno di una cartilagine già degenerata. Tale rilievo ha importanti ripercussioni sul piano terapeutico poiché i danni inducibili dall’uso di un FANS ad attività condrolesiva saranno tanto maggiori quanto più è avanzato il processo degenerativo cartilagineo. Va comunque precisato che i rilievi relativi all’effetto dei FANS sul metabolismo cartilagineo sono per ora desunti solo da esperienze in vitro su colture di cartilagine e di condrociti e in vivo su modelli animali di artrosi e non peraltro completamente estrapolabili alla patologia umana. Non bisogna infine dimenticare che alcuni dei danni indotti dagli antiflogistici sulla carilagine aricolare possono essere di tipo indiretto e legati alle loro proprietà analgesiche che consentono il mantenimento della funzione articolare e quindi il perdurare di una eventuale condizione di sovraccarico articolare, in grado di peggiorare lentamente il quadro anatomo-clinico. Tali considerazioni impongono pertanto la necessità di utilizzare nell’artrosi i FANS a cicli terapeutici di breve durata limitatamente alle fasi di riacutizzazione clinica della malattia con immediata interruzione al cessare della sintomatologia algica e/o flogistica. Le nuove acquisizioni in termini di etiopatogenesi dell’OA hanno dato un particolare impulso alla ricerca di possibili vie farmacologiche in grado di incidere sull’evoluzione della malattia. Negli ultimi anni l’industria famaceutica ha sviluppato un gruppo di sostanze cui è stato attribuito il ruolo ed il nome di condroprotettori il cui scopo fondamentale è quello di limitare i danni distruttivi e/o favorire i processi riparativi a livello della cartilagine articolare. In parti colare con il termine di condroprotettori si definiscono tutte le sostanze capaci di: – stimolare la sintesi di proteoglicani con caratteristiche il più possibile vicino al normale; – inibire la degenerazione della matrice cartilaginea; – conservare le condizioni di vitalità ottimali per i condrociti; – mantenere inalterate le caratteristiche del liquido sinoviale. L’uso di un condroprotettore nella terapia dell’OA potrà quindi rivelarsi utile soltanto nelle fasi precoci della malattia, quando ancora esiste un tessuto cartilagineo in grado di attuare una risposta di tipo riparativo. Al momento attuale numerose molecole, diverse tra loro, sia sotto il profilo chimico che del meccanismo d’azione, hanno dimostrato in vitro ed in vivo (nell’animale e solo parzialmente nell’uomo) un potenziale ruolo condroprotettivo. Tra questi sono compresi alcuni glicosaminoglicani aventi affinità chimiche e strutturali con i proteoglicani della sostanza fondamentale cartilaginea, la diacereina e poi un gruppo sempre più numeroso di molecole per le quali l’azione condroprotettiva è solo parzialmente dimostrata e le prove sperimentali e cliniche ancora in fase iniziale. Tra i

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farmaci presenti sul mercato ed attualmente utilizzabili per la terapia di fondo dell’OA si devono ricordare i glicosaminoglicani, come il galattosaminoglucuronoglicano solfato, la glucosamina solfato, l’acido ialuronico (solo per via intraarticolare) e la diacereina (Tab. 5). La condroprotezione rappresenta al momento attuale l’aspetto più nuovo ed originale della terapia medica dell’OA. La novità apportata dal concetto di trattamento condroprotettivo è quella di considerare la possibilità di arrestare il normale iter patogenetico della malattia ovvero di opporsi alla progressione dei fenomeni degenerativi catilaginei. Tuttavia non è possibile ignorare l’esistenza di una serie complessa di problematiche ancora oggi aperta sulla condroprotezione. In primo luogo i dati acquisiti sono soprattutto di tipo sperimentale, derivanti cioè da studi in vitro su colture di condrociti e di cartilagine e in vivo su modelli sperimentali animali o costituite da esperienze cliniche iniziali nell’uomo Una valutazione sulla capacità di queste sostanze di poter arrestare l’evoluzione dell’OA può derivare solo da una sper imentazione controllata a lungo termine (3-5 anni) nell’uomo, sperimentazione corredata da dati bioumorali e strumentali in grado di comprovare il reale effetto di fondo di questi farmaci. Rimangono infine da chiarire quali siano i tempi e le modalità più corrette per attuare una efficace terapia condroprotettiva, è necessario conoscere quali siano gli stadi clinico-radiologici in cui è ancora valido istituire una terapia di fondo, quali siano i preparati più idonei, la durata ed il ritmo dei cicli terapeutici e i tempi necessari per ottenere una valida risposta clinica. Le considerazioni esposte, pur esprimendo una serie di dubbi ed incertezze che ancora oggi pesano sul capitolo della condroprotezione, debbono costituire un impulso per future e rigorose verifiche scientifiche sui farmaci già entrati sul nostro bagaglio terapeutico ed uno stimolo alla ricerca di nuove molecole in grado di interferire nelle più fini modificazioni ultrastrutturali e biochimiche dell’OA.

Tabella 5 - Farmaci proposti come condroprotettori - Rumalon - Glicosaminoglicano polisolfato - Galattosaminoglucuronoglicanosolfato - Pentosanpolisolfato - Glucosamina solfato - Acido ialuronico - Diacereina - Oxaceprolo - FANS - Cortisonici - Bisfosfonati - Calcitonina - Tetraciclin

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Letture consigliate 6. 1. 2. 3. 4.

Brandt K.D., Doherty M., Lohmander L.S: Osteoarthritis. Oxford (UK). Oxford University Press, 1998. Carrabba M.,Galanti A., Paresce E.,Duci D.:Etiopatogenesi dell’artrosi. RMP 426 (Reumatologia 46): 5-20,1992. Faletti C.: La cartilagine articolare. Bologna. Timeo, 1997. Fioravanti A.: La terapia di fondo dell’osteoartrosi. In: Marcolongo R. (ed),I farmaci antireumatici:criteri di scelta ed orientamento decisionali. Castello d’Argile (BO). EDITEAM, 1998. Marcolongo R., Carrabba M., Cerase A.,Cervini C., Cingolani M., Ciocci A., Colombo B., Fioravanti A., Frizziero L., Galanti A . ,G rassi W., Pa-

7. 8.

rente C., Priolo F., Tajana G.: L’artrosi. Milano. Modern s.r.l.,1996. Moskowitz R.W., Howell D.S., Goldberg V.M., Mankin H.J.: Osteoarthritis,diagnosis and medical/surgical management. 2nd Edition. Philadelphia. Saunders Company, 1992. Pelletier J.P.: Pathophysiology of osteoarthritis. Osteoarthritis Cart. 7:371-374,1999. Pelletier J.P., Haraoui B., Fernandes J.C.: New and future therapies for osteoarthritis. In: Osteoarthritis (Clinical and Experimental Aspects) (ed. JY Reginster, JP Pelletier, J Martel-Pelletier, Y Henrotin), Springer-Verlag, Berlin, 1999, pp.387-408. Watt I.: Radiology and imaging. In: O’Doherty M. (ed), Color atlas and text of osteoarthritis. Barcellona. Ed. Wolfe, 1994.

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Vaccine issues for the future Argomenti vaccinali importanti per il futuro

Richard B. Ford DVM, MS, Dipl ACVIM - North Carolina State University - Raleigh, North Carolina (USA)

The rapid proliferation of companion animal vaccines, advances in diagnostic and vaccine technology, and concerns over vaccine safety are clearly among the key issues practicing veterinarians will face as we enter the next century. While many would argue that these are already issues,the future promises to be especially challenging as the vaccines we currently use and the protocols we currently recommend undergo unprecedented change. Veterinary medicine has, over the course of many years, done an excellent job of educating pet owners on the importance of vaccinating adult dogs and cats annually. And there is absolutely NO DEBATE over the health benefits that millions of animals have derived from the widespread availability of low-cost, highly effective vaccines. Today, however, in the face of concerns that vaccines might actually do harm to an otherwise healthy dog or cat, pet owners, as well as veterinarians, are questioning the need for widespread and routine (annual) vaccination. In the face of revised national vaccination guidelines for cats, annual vaccinations, a key incentive for pet owners to seek yearly health care services on behalf of their pets, is undergoing significant review. As a result, some veterinary practices will be challenged to explore a different practice "culture" as we enter the 21st Century.

ANNUAL VACCINATION In 1989 the AVMA Council on Biologic and Therapeutic Agents published immunization guidelines for dogs and cats.[REF: 1] In their report, booster vaccinations for all canine and feline vaccines were recommended annually (vac cines for canine Lyme disease, canine coronavirus, canine giardiasis, feline infectious peritonitis, feline Bordetella bronchiseptica, feline giardiasis, and feline Microsporum canis were not available at the time these recommendations were made). As recently as 1996, a survey of vaccination practices conducted in veterinary schools throughout North American indicated that annual revaccination of adult dogs and cats were routinely performed. [REF:2] It is reasonable to assume, therefore, that most practitioners currently recommend annual booster vaccinations to their companion animal clientele. However, recent publications [REFs: 3, 4, 5, 6] and guidelines outlined by a panel convened by the American Association of Feline Practitioners (AAFP) and the Academy of Feline Medicine (AFM) [REF: 7] suggest that current guidelines fail to address realistic duration of immunity

(DOI). At issue is the fact that a protective immune response is likely to persist for several years following vaccination and, in fact, routine administration of annual booster vaccines to dogs and cats is not necessary. Despite the absence of published DOI studies, a growing body of data supports recommendations for booster vaccination that include administering core vaccines (eg, feline panleukopenia, herpesvirus-1, calicivirus, canine distemper, canine parvovirus and rabies) at 3 year, or longer, intervals in adult animals. On the other hand, despite current recommendations it has been suggested that several vaccines routinely used in companion animal practice, such as canine parainfluenza virus, Bordetella bronchiseptica, and Leptospira serotypes, and feline chlamydia, fail to provide protective immunity for 12 months. [REF: 2] On the other hand, a realistic risk assessment may dictate revaccination at intervals more often than once every year in selected “at risk” animals. Companion animal vaccination guidelines are currently undergoing critical scrutiny by representatives from private practice, industry, and academia. Despite widespread recommendations for annual revaccination, information available today suggests that current vaccination practices in North America do not necessarily correspond with the body of knowledge pertaining to duration of immunity derived from licensed vaccines. As a direct result, companion animal practitioners should expect significant changes in the current standard of practice pertaining to the administration of vaccines to dogs and cats. Among the most significant changes anticipated in the future will be the recommendation to discontinue routine administration of annual booster vaccinations to adult dogs (distemper virus and parvovirus) and cats (panleukopenia, feline herpesvirus-1 and calicivirus). The incidence of canine distemper, canine parvovirus, and feline panleukopenia among vaccinated adult (>1 year of age) animals is virtually zero. The correlation between vaccination, the development of a “positive” antibody titer and protection from exposure to virulent virus is excellent. Furthermore, protection derived from immunization is sustained for periods as long as 5 or 6 years. Future vaccination standards for adult dogs and cats are likely to center around vaccination intervals of every 3 years. Vaccines intended to protect against diseases such as B. bronchiseptica, canine parainfluenza virus, canine adenovirus-2, and feline leukemia are not known to provide protection against challenge for more than one year. Annual

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boosters are likely to continue to be recommended for those animals considered at risk of exposure to diseases caused by these organisms. Although annual boosters are still recommended, the actual RISK:BENEFIT ratio derived from FeLV and FIPV vaccination simply does not appear to justify the number of cats receiving annual vaccines.

TITERS vs. ANNUAL VACCINATION What is the feasibility of performing annual antibody titers in patients rather than subject them to annual booster vaccination? Despite the fact that a (growing?) number of laboratories offer selected canine and feline antibody titers to veterinarians, there are a number of significant factors that, in this author’s opinion, do NOT justify offering this service to clientele on a routine basis. In addition to the fact that antibody concentration does NOT necessarily correlated with protection against disease, there are other compelling reasons that widespread acceptance and use of antibody determinations will not likely happen in clinical practice. First, standardized methods for determining antibody concentration in serum for the various vaccine antigens has note been achieved. The risk lies in the fact that a single serum sample, divided 3 times, and sent to 3 different laboratories, will quiet likely yield 3 different titers…and quite possibly, 3 different interpretations. What may be deemed “protective” by one laboratory could well be labeled “susceptible” by another. Furthermore, it is important to note that a vaccinated dog or cat that does NOT have a significant concentration of antibody may, in fact, have excellent immunity. A “negative” antibody titer does NOT necessarily correlate with susceptibility to infection. Likewise, the presence of antibody, even at very high levels, does not guarantee immunity subsequent to exposure. It should also be noted that over the next 5-10 years recombinant (genetically engineered) vaccines will quite likely become the predominant product used in the companion animal market. Although measurable antibody titers are expected to be associated with some of these products, others will NOT produce antibody that is measurable in vivo. The ability of recombinant vaccines to provoke immunity through cell-mediated immune (CMI) mechanisms further complicates in vivo assay of immune responses since measuring CMI responses is complex and availability is very much limited.

SELECTION OF ANTIGENS Not only is it perceived that veterinarians are vaccinating too often, it has been suggested that pets are inoculated with vaccines containing excessive combination of antigens. In fact, the real issue at hand for the future is to determine which vaccines are, in fact, indicated and which are not. Surveys of companion animal practitioners and veterinary teaching hospitals on vaccination protocols indicate there is considerable diversity within the profession on which vaccines should and should not be administered.

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In the future, vaccination protocols for dogs and cats will likely center around recommendations for administering socalled core and non-core vaccines. Core vaccines are those recommended for administration to every dog/cat presented to the practice. Recommendations for designating a particular vaccine as core are determined by 1) severity of disease, 2) transmissibility to other animals, and 3) the potential for a particular infection to be zoonotic. Non-core vaccines, on the other hand, would be recommended to clientele when a known or likely risk is anticipated or when an animal’s lifestyle represents a reasonable risk of exposure to the infectious agent. Examples include feline leukemia virus (FeLV) and feline infectious peritonitis virus (FIPV),and canine Lyme disease vaccine. Another issue pertaining to the selection of vaccines is the administration of modified-live virus (MLV) vs. killed virus vaccine. Although recommendations against adminis tration of multivalent, MLV vaccines were made several years ago [REF: 12] , most veterinarians continue to administer MLV biologicals. This is certainly justified since these products do provide a superior, sustained immune response. Furthermore, there is no data that demonstrates there are significant advantages for using killed virus vaccines over MLV vaccines. The suggestion that MLV vaccines pose an unreasonable safety risk is largely anecdotal and without scientific merit. Unfortunately, killed virus vaccines have in general NOT proved to be suitable alternatives. Selection of Antigens in the Shelter Environment: However…selecting core vs. non-core antigens described above is far easier in clinical practice than it is in a shelter environment. Clearly, there is no standardized formula for success considering the innumerable variables in the equation: shelter finances, “kill vs. non-kill”, staff experience/knowledge base with infectious disease (from cleaning to screening), census, concurrent illnesses, holding times, season of the year, construction, air exchange…to name a few. Personal observations over the last few years have led me to consider several approaches to vaccines & vaccination management in shelters…any one of which, depending on circumstances, might just work: FIRST…the Darwinian approach: don’t screen, don’t vaccinate anything, ever. Those that survive are the fittest…they win. While that’s the most economic approach, the downside is the risk of runaway infectious disease, which is particularly hard on the young animal population. SECOND…the Filtered approach: Using skilled personnel, trained to recognize sick animals, simply screen and remove those animals that are obviously sick. It a daily (at least) job and it obviously does nothing to prevent those who are about to become sick from spreading their illness. THIRD…the UNLIMITED FUNDS approach: Vaccinate every healthy animal on admission to the facility, hold them in quarantine for 14 days, during which time they are examined daily by a veterinarian. Those that survive leave quarantine and are driven, in a sealed luxury SUV to the main facility where they enter environmentally controlled housing, get 2 square meals a day, and have unlimited access to a graduate student doing animal-bond resear ch. …I’m not certain any one of the above strategies is significantly better than another. Vaccination is simply not the

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cornerstone of infectious disease control within a shelter environment. Facility construction, especially the ability to isolate, the ability to move air, and the ability to clean, becomes the critical factor. However, this is NOT to say there is NO role for vaccination. It’s just that prudent vaccine selection and monitoring of disease incidence are critical in the success of the program. In developing a shelter vaccination program, a few assumptions apply at the time of admission: • Assume infectious disease exposure has already occurred, or… • Assume that exposure will occur before a vaccine will effectively immunize. • Assume that puppies and kittens are at considerably more risk than adults. • Assume that healthy appearing adults are the reservoir of infection for puppies and kittens. • Assume that vaccination will not preclude development of clinical disease.

VACCINE SAFETY Among the most important issues facing practitioners today is that of vaccine safety. For most vaccines on the market today, it must still be assumed that the benefits of vaccination, when performed in accordance with currently published standards far outweigh the risk of vaccine-induced illness or disease. However, recent reports have raised serious concerns within the profession over the relationship between vaccination and delayed adverse events, specifically vaccine-associated fibrosarcoma in cats [REFs: 8, 9, 10] and immune-mediated hemolytic anemia in dogs. [REF: 11] Determining which vaccines pose a risk to which animals, and when, simply cannot be determined with the information available today. However, it is still the practitioner who assumes responsibility for not only recommending a particular vaccination protocol but for any consequences that might arise as a result of administering a vaccine (see LIABILITY section below). Concern over the risks associated with the use of attenuated (modified-live) vaccines,disease caused by residual virulence or disease attributed to contamination during manufacture, has sustained the market for inactivated products.[REF: 12] However, there are significant advantages associated with using attenuated vaccines, such as rapid-onset, sustained protection, the ability to stimulate cell-mediated immunity, and the ability to immunize by way of natural routes, that may not justify the decision to offer only killed vaccines to companion animal patients. The Adverse Event. Information on the behavior of individual vaccines used under everyday field conditions is maintained by the manufacturers and reported to the USDA Center for Veterinary Biologics.1 Such postmarketing surveillance also serves as an alert system for the rapid detection of vaccine-related events that appear to be unusual in nature or frequency. However, the single most significant factor that serves to compromise the effectiveness of the postmarketing surveillance program is the lack of adverse event reporting by practitioners. In many instances, not even

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deaths associated with vaccine administration are consistently reported. An adverse event is any undesirable occurrence following the use of immunobiological product, including illness or reaction, whether or not the product caused the event. Anecdotal surveys suggest that adverse event reports from veterinarians dramatically under-represent the number of reactions observed and regarded to be vaccine-associated. Despite efforts to categorize ad verse events as Type-1, -2, -3, etc, there are still no uniform standards used by practitioners, or manufacturers to classify frequency and type of event. However, the USDA has developed adverse event reporting guidelines that practitioners should use when addressing known or suspected adverse events associated with administration of any vaccine. Although only a few reports specifically address various causes of adverse events, reactions have been attributed to: preservatives, purity, contamination, virulence of attenuated agents, adjuvant, route of administration, concurrent administration of other vaccines, and the ordinal number of the vaccine (most immediate reactions occur subsequent to administration of the first vaccine as opposed to the second or third vaccine dose in a series). Neither the cause nor the exact frequency of delayed reactions, such as tumor formation or immune-mediated hemolytic anemia, are known. Reporting of adverse events remains the responsibility of the practitioner who administers the vaccine and observes the reaction. Reports should be made directly to the vaccine manufacturer, usually to the technical service section. Multidose (TANK) Vials. Veterinarians are advised to administer vaccine from single dose vials only. Administering vaccine from a multidose, or TANK, vial (typically 10doses per vial) containing killed virus vaccine carries the risk of delivering significantly different concentrations of adjuvant to each patient. Depending on the thoroughness with which the multi-dose vaccine is mixed prior to each dose administered, the adjuvant concentration in the last dose administered is commonly much higher than that administered in the first dose.

LIABILITY Discussions with vaccine manufacturers, practicing veterinarians, attorneys, as well as representatives from the AVMA Liability Trust suggest there is considerable confusion among practicing veterinarians over: 1) the use of vaccines in a manner not specifically recommended by the manufacturer (as published in the package insert), and 2) the liabili ty assumed when a vaccine causes, or is presumed to cause , a serious and/or expensive injury to the patient. It has been found that vaccination protocols for companion animals vary considerably throughout North America. Furthermore, it is the veterinarian who, after assessing the various risk factors unique to the individual patient, makes recommendation on which type of vaccine and which choice of antigens are to administered, which product, when, and how often. Veterinarians are not obligated to follow the recommendation outlined in the package insert for a specific product. Discretion in the administration of vaccines is acceptable

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as long as it meet provision defined the “standard of practice”. In the clinical setting, the “standard of practice” for administering vaccines is not to administer every vaccine licensed for a given specie as often as recommended on the package insert. It is to administer those vaccines necessary to protect the animal from diseases it is most likely to be exposed to.

RISK ASSESSMENT Providing effective immunoprophylaxis to the cat population does not require that all cats presented for vaccination be inoculated with each of the antigens for which a vaccine is currently licensed. Factors related to the individual patient, both intrinsic and extrinsic, as well as factors unique to the infectious agent should be taken into consideration when establishing recommendations when assigning a vaccination protocol to an individual cat. Some vaccines, designated CORE VACCINES, are recommended for administration to all cats seen by the practice. Recommendations for determining which antigens are deemed CORE should be based on the fact that: 1) the consequences of infection are particularly severe (eg, feline panleukopenia), 2) infection is zoonotic and potentially puts human health at risk (eg, rabies), or 3) the disease is prevalent and easily transmitted such that it poses a risk to the population of cats at large (eg, feline herpesvirus and calicivirus). The decision to vaccinate a cat with a vaccine that is not CORE should be based on the clinician's assessment of the individual animal's RISK PROFILE and takes into consideration information about the: 1) patient, 2) the patient's environment, and 3) the infectious a gent. Host Factors: Suboptimal response to vaccination is possible among cats that are malnourished, have concurrent infection or illness, or are receiving regular doses of immune suppressive drugs. Additional intrinsic factors considered to influence the outcome of infection include heritable resistance (and possible susceptibility) factors and stress. Age at the time of exposure is an important, independent variable in assessing an individual's risk to an infectious agent. Although no age-group can be considered entirely free of risk, kittens (less than 6 months of age) are generally more susceptible to infection than adult cats following exposure and, therefore, represent the principle target population for feline vaccination protocols. The presence of maternal antibody is an intrinsic host factor known to protect a kitten following exposure to an infectious agent. However, neutralization of vaccine antigen by maternal antibody is the single most common cause of vaccination failure in cats. Failure to vaccinate a kitten at an age when maternal antibody has declined sufficiently (approximately 12 weeks of age) will increase an animal's risk. Environmental Factors. Population density and opportunity for exposure to other cats (free-roaming or “indooroutdoor” activity) are among the most critical issues affecting the risk of exposure to an infectious agent. Cats and kittens living within multiple cat households and cluster populations are at substantially higher risk of infection than are cats living in 1 or 2 cat households. Furthermore, the intro-

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duction of new cats into a household/cluster poses a potential risk to the entire population. Geographic distribution of various infectious agents may r epresent significantly different exposure risk to cats living in different parts of the United States and should be considered when determining which NON-CORE vaccines would be appropriate. In multiple animal households, sustained high ambient temperatures and humidity, in addition to housing environments with fewer than 12 air exchanges per hour, increase the risk of animals’ exposure to respiratory pathogens. In kennels, a single puppy with parvovirus puts all other nonvaccinated puppies at risk for a month because of the long survival time of the virus in the environment. Agent Factors. Independent agent-associated variables, such as virulence, dose, and mutation do influence the outcome of infection but are difficult to objectively assess in the clinical setting. However, in the domain of risk assessment, it is the interaction between the agent and the host that dictates the outcome following exposure and infection. The severity of an infection, particularly a viral infection,is highly variable within a population of animals with similar exposure to the same agent. Clinical illness with the exact same pathogen may range from inapparent or mild to severe acute illness to chronic or latent infection. Considering the relative risk of an individual animals to a particular virus by performing a genetic analysis of the individual animal.

RECOMBINANT VACCINE TECHNOLOGY Recombinant vaccines are among the newest products in the rapidly emerging biotechnology/vaccine market. The technologic advance behind these products in the ability to isolate and splice (or recombine) gene-size fragments of DNA from one organism and transferring them to another by way of a vector virus or plasmid DNA. It has already been demonstrated that the hybrid organism resulting from the invitro exchange of genetic material has tremendous potential to deliver, safe and immunogenic DNA into the host animal and, as such, represents a truly new generation of vaccine development for the veterinary profession. The recombinant vaccines currently being introduced into companion animal practice appear to provide an exceptionally safe product, while efficacy and duration of immunity will still have to be established for each product. Nucleic acid or “naked” DNA vaccines are developed and some have already been shown to be effective against certain companion animal diseases. The DNA vaccines are completely unique in that only DNA is inoculated where it subsequently transfects host cells to produce vaccine antigen. The technology behind recombinant vaccines is quite sophisticated and has quickly moved routine vaccination of dogs and cats from the level of the whole organism to the subcellular level. The practice of administering attenuated, live agents, or whole killed products will surely change in the near future. [REF: 13] As we enter the 21 st Century, it is anticipated that even newer technologies will be introduced that will give rise to veterinary-label vaccines that are safer, have exceptional efficacy, and a duration of immunity that persists for several years, if not for the life of the patient.

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Veterinarians are encouraged to become familiar with recombinant vaccines, to understand the basic technology behind their development, and to become familiar with the potential advantages and disadvantages of each new product as it is introduced. Then, the clinician, considering both conventional and recombinant vaccines, will be able to administer the most appropriate product only as often and necessary to prevent significant disease.

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6. 7.

8. 9.

References 1. 2. 3.

Canine and feline immunization guidelines. AVMA Council on Biologic and Therapeutic Agents. JAVMA. 195:314-317, 1989. Mansfield PD. Vaccination of dogs and cats in veterinary teaching hospitals in North America. JAVMA 208:1242-1247, 1996. Phillips,TR and Schultz RD:Canine and feline vaccines. In Kirk RW (ed): Current Veterinary Therapy XI. W.B. Saunders, Philadelphia. 1992,pp. 202-206. Smith CA. Are we vaccinating too much? JAVMA. 207:421-425, 1995.

10.

11. 12. 13.

Bowlin CL: Proceedings from Perspectives on Vaccines in Feline Practice, Eight Annual Feline Practitioners Seminar. Columbus, Ohio, July, 1996. Larson RL and Bradley JS: Immunologic principles and immunization strategy. Comp Cont Ed Pract Vet. 18:963-971,1996. 1998 Report of the American Association of Feline Practitioners and Academy of Feline Medicine Advisory Panel on Feline Vaccines. JAVMA,212:227-241, 1998. Hendrick MJ and Goldschmidt MH. Do injection site reactions induce fibrosarcomas in cats? JAVMA. 199:968, 1991. Hendrick MJ, Kass PH, McGill,LD and Tizard IR: Postvaccinal sarcomas in cats. J Natl Cancer Inst. 86:341-343, 1994a. Kass PH, Barnes WG, Spangler WL, Chomel BB, et al. Epidemiologic evidence for a causal relation between vaccination and fibrosarcoma tumorigenesis in cats. JAVMA. 203:396-405,1993. Duval D and Giger U:Vaccine-associated immune-mediated hemolytic anemia in the dog. JVIM. 10:290-295, 1996. Tizard I: Risks associated with use of live vaccines. JAVMA. 196:1851, 1990. Adams LG, Ford RB, Gershwin LJ, and Schultz RD: Recombinant vaccine technology. Veterinary Exchange. Compendium Cont Ed Pract Vet (Suppl). 19:5-16, 1997.

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New vaccine technology Novità nella tecnologia vaccinale

Richard B. Ford DVM, MS, Dipl ACVIM - North Carolina State University - Raleigh, North Carolina (USA)

For thousands of years people have been selecting genetically superior or desirable animals and plants with the specific objective of producing a unique combination of genes in a particular line or breed. Using technology that was based largely on past experience, these “genetic engineers” have produced some of the most economically important varieties of plants and animals the world has ever seen. In the 1970’s, however, genetic engineers working at the cellular level introduced a truly new era of genetic selection as methods were developed for isolating individual genes, then reintroducing those genes into individual plants, animals and single-celled organisms. Today, that science is known as recombinant technology. In essence, recombinant technology is a rapidly emerging biotechnology that is concerned with isolating and splicing (or recombining), gene-sized DNA fragments taken from one organism to another. Once a fragment of DNA from one organism has been spliced to another DNA fragment,the hybrid molecule formed is called recombinant DNA. The newly formed hybrid DNA, once inserted into a cell, is a ble to replicate within the cell as that cell divides producing a genetically new and distinct cell. The potential applications of recombinant technology in veterinary medicine are numerous. Using recombinant DNA techniques, it will eventually be possible to perform prenatal screening for genetic defects. Beyond that, scientists are looking forward to the day when it may be possible to insert normal genetic material from one individual into an affected individual, thereby actually treating the genetic disease. However, aside from genetic screening and gene therapy, the immediate application of recombinant technology in veterinary medicine is based in the development of new vaccines. For the clinician, it truly represents a new era of vaccine development, one that will undoubtedly provide significant enhancements over existing vaccines while, at the same time, allowing scientists to explore means of protecting animals against diseases for which vaccines are not currently available.

GENE-DELETED VACCINES Gene deletion is a form of recombinant technology that results in the isolation and removal of disease producing genes in a pathogenic virus. Modification of the genetic codes in the virus allows that organism to survive, reproduce, and retain its immune-inducing ability without producing disease. This is a technology that has been applied to both viruses and bacteria.

VECTORED VIRUS VACCINES Another recombinant technology applied to pathogenic viruses permits the use of a genetically designed vaccine virus to provoke an immune response against two or more infectious diseases at the same time. Recombinant techniques are used to isolate and remove the immune-inducing genes from a pathogenic virus and actually insert them into a transport virus that has been reconstructed for use as a vaccine. The immune-inducing genes transported by the vector virus are transcribed following inoculation into the host. This results in immunity that will protect the patient against the disease-causing virus from which the immune-inducing genes were obtained.

SUBUNIT VACCINES By the 1970’s, it was generally apparent that isolated structural components of infectious organisms were immunogenic. Such noninfectious “subunit” vaccines would provoke protective immune responses with few undesirable side effects compared to inactivated, whole-agent vaccines. The introduction of recombinant technology has expanded the potential application of biosynthetic vaccines. The distinct advantage of subunit vaccines is that they contain only those immunogenic components necessary to provoke a protective response and exclude those components unnecessary for immunity. Safety is the first and foremost element of importance in subunit vaccines. They lack infectious material. Infection cannot be established in the vaccinant. This substantially reduces complications arising from vaccination of immunocompromised or pregnant individuals. In addition, extraneous antigens are lacking, which further reduces the allergenic potential. Subunit vaccines also exhibit considerable stability and potentially allow for wide distribution and prolonged storage. Interestingly, simple serologic tests can readily distinguish between vaccinants and those that have been infected. As a result, subunit vaccines contribute to not only disease control but to eradication programs as well. Recombinant technology has numerous applications in medicine. Among the most fervently pursued applications today are in the arena of vaccine development. The USDA has already recognized various types of recombinant technology appropriate to new vaccine development in veterinary medicine.

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ADVANTAGES OF RECOMBINANT VACCINES There are three fundamental goals in any immunization protocol: 1) to vaccinate those animals at risk of infection, 2) to vaccinate them at the appropriate stage of life, and 3) to vaccinate them with the best available product. When comparing advantages and disadvantages of specific vaccines, it is the third goal that becomes the focus of concern with respect to new vaccine technology. It is likely that the single-most important factor behind the intense investigation into recombinant vaccines is their potential for both enhanced safety and efficacy over modified-live and killed virus vaccines. It was as early as the tenth century in China and India that live-virus immunization was practiced, when pustular fluid from a patient with smallpox was inoculated into uninfected patients. This practice, today called variolation, caused moderate disease of varying severity and a 1–2% mortality. This contrasted to the 25% mortality of natural smallpox infection at that time. By the mid-1700’s the practice of variolation had been improved through the process of “attenuation” in which almost no disease occurred following vaccination. Today, in both human and veterinary medicine, live-virus and killed virus vaccines have had excellent records of efficacy, reasonable safety, modest cost, and good durations of protection. However, despite the millions of lives that have been enhanced through conventional vaccination, many researchers believe that a point of diminishing return has been reached in regard to vaccine improvements using conventional technology. It is reasonable to assume that new approaches to vaccine development must be tried if we are to make further impr ovements. Without having utilized recombinant vaccines in animals on a widespread basis, it is virtually impossible to define the advantages of recombinant technology over conventional technology in assessing the attributes of vaccine development. However, there are a number of potential advantages of recombinant vaccines that are worth noting. In particular, vectored virus vaccines used in third world countries have shown significant advantages in that they are easily administered in a single-dose regimen. These vaccines have proven to be simple to manufacture and, therefore, inexpensive to test. This is a critical factor given that the cost of the vaccine is very much related to the complexity of production and related costs of quality assurance and safety testing. Vaccinia virus vaccine, a human-labeled vectored virus vaccine, has proven to be very stable, an outstanding quality of the virus itself. Vectored virus vaccines also hold the potential of inducing a relatively long-lived immunity. Another important advantage in recombinant technology comes from the potential to develop a safe, effective adjuvant. In fact, some have claimed that this may be as important as the choice of the immunizing antigens. Utilization of recombinant DNA technology in vaccine development may lessen the frequency of adverse vaccination reactions and offer superior immunogenicity over existing vaccines, but genetically engineered vaccines are not without some risk. Vectored virus vaccines (vaccinia vaccination) administered to humans are rarely associated with

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adverse reactions,such as exanthematous disease and central nervous system disease (encephalitis resulting in cerebral impairment, hemiplegia, convulsions, and coma). While it is not possible to extrapolate either type or incident of adverse reaction in humans to what might be expected in animals, it must be assumed that widespread inoculation of animals with modified viruses will be associated with reports of undesirable side effects. On the other hand, subunit vaccines contain noninfectious, protective subunit immunogen that is produced in or by a biologic system. As such, vaccines falling into this category are free of modified (attenuated, recombinant, or genetically altered) live agents, inactivated (killed) whole agents, and chemically synthesized or nonproteinaceous immunogens. While this may enhance the safety of subunit vaccines, adjuvants are commonly incorporated into these vaccines to enhance the immunogenicity of the product. Adjuvants are capable of causing adverse reactions which must be considered as subunit products enter the market.

WHAT ARE THE RISKS? Vectored recombinant vaccines employ recombinant technology to remove immune-inducing genes from a diseasecausing virus. Subsequently, those genes are inserted into another virus that has been reconstructed for use as a safe vaccine. It is this virus that becomes the so-called “gene transport,” or vector vehicle. In essence, such technology allows the clinician to provide heterologous immunity using a “transport vector” virus that is essentially benign. There are 3 highly attenuated, highly efficacious poxvirus vectors that are available for use in both veterinary and human medicine. One of these viruses, the NYVAC strain, has been assigned a biological safety level–1 (BSL–1). This is the lowest level for biosafety containment recommended by the Recombinant DNA Advisory Committee of the National Institutes of Health.

WHAT IS THE IMPACT IN COMPANION ANIMAL PRACTICE? From the clinician’s perspective, there are numerous justifications for pursuing advanced technology with respect to vaccine development. Factors such as enhanced efficacy, improved duration of immunity, rapid development of new vaccines for emerging diseases, and availability of vaccines at reasonable cost are all key issues that will be considered in the future. Perhaps the most critical vaccine issue facing veterinarians in the future is that of vaccine safety. New vaccines and new vaccine technologies will justifiably be scrutinized critically for the impact they will have on the frequency and types of adverse reactions. However, it is most difficult to speculate on whether or not recombinant technology will yield vaccines that are significantly safer than vaccines used today. The use of recombinant technology in vaccine development has significant potential to produce vaccines that are not only highly efficacious but extremely safe. As new vaccines developed through recombinant technology are intro-

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duced into veterinary medicine, vaccine safety will be the major concern within the community of practitioners. In the broadest sense, the term safety has far-reaching concerns to the profession at large. Short-term versus long-term effects of vaccinations, concurrent administration of recombinant vaccines with conventionally developed vaccines, and administration of recombinant vaccines to immune-suppressed individuals are just a few of the issues that must be considered as these vaccines are introduced.

WHAT IS THE DURATION OF IMMUNITY? Enhanced duration of immunity is one of the potential benefits to be recognized through the introduction of recombinant vaccines. However, whether the duration of immunity for recombinant vaccines is similar to or better than conventional vaccines is a most difficult question to answer. To date, the actual duration of immunity for the companion animal vaccines commonly used in small animal practice has not been established. The fact is, most of these vaccines have a duration of immunity that exceeds 1 year. Annual booster recommendations for most conventional vaccines used today are likely to be excessive for many of the antigens used in routine vaccination protocols. It is quite likely, as recombinant vaccines are introduced into veterinary medicine, the actual duration of immunity will vary from one antigen to another and, in all likelihood, will equal or exceed the duration of immunity derived from conventional vaccines. The objective of any vaccination program is to offer the best possible protection for an animal against an infectious disease. To achieve the objective, several factors must be considered, including the type of vaccine used, the inclusion of adjuvants, and the frequency and route of administration of the vaccine. In addition, the overall health and nutritional status of the animal, its environment, age, and genetic makeup are all factors that play an important role in the eventual outcome of any immunization protocol. Any one, or combination, of these factors will influence the response of the immune system and the subsequent ability of a vaccine to immunize.

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In general, antigen-antibody reactions show a high level of specificity. In other words, the binding sites of specific antibodies directed against a particular antigen are usually very specific and not complementary to determinants on other antigens. Recombinant technology takes advantage of this specificity by offering the immune system an opportunity to respond maximally to the immunogenic portion of an antigen without the presence of the disease-causing portion. Ideally, not only is the risk to the patient minimized but the immunogenicity is actually enhanced. Consequently, dogs and cats that have received vaccines by conventional technology are likely to respond well to vaccines developed through recombinant technology.

WHAT DOES RECOMBINANT TECHNOLOGY MEAN FOR THE FUTURE? Given the ability to manipulate the genetic constituency of infectious organisms, recombinant vaccine technology will have numerous potential applications in the development of future vaccines. This not only includes refinement and improvement of existing viral vaccines, but offers opportunity for the development of vaccines against a number of pathogenic organisms. For example, it is quite feasible that, in the future, vaccines will be available to the veterinarian that target specific parasitic infections, an expanding array of bacterial infections, and even some systemic mycotic infections. Considering the emerging vaccine technology, veterinary medicine stands to benefit considerably in the future from vaccines that offer very specific advantages over conventional vaccines. In the end, the overall value of these vaccines to the profession, our patients and their owners, will be determined by the complex benefits:cost:risk equations that must be considered as this technology is introduced into veterinary medicine. Recombinant technology promises to play a critical role in human and veterinary medicine during the 21st century. The long-term future only promises more and more valuable products.

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Canine ehrlichiosis Erlichiosi canina

Richard B. Ford DVM, MS, Dipl ACVIM - North Carolina State University - Raleigh, North Carolina (USA)

It was called “Tropical Canine Pancytopenia”. And it affected military working dogs, most of which were German Shepherds, assigned to bases in Southeast Asia during the war in Viet Nam. The clinical disease was characterized as a serious bleeding disorder, usually uncontrollable epistaxis, weakness and lethargy. Hematology did little more than demonstrate significant thrombocytopenia, leukopenia, and non-regenerative anemia, but there were no tests available to confirm the reason for this sudden-onset marrow ‘shut down’. The first reports of Canine Pancytopenia appeared in the US literature during the early 70’s. But with most US locations not being especially “Tropical”,the disease initially received little attention from practitioners. If we only knew then what we know now… …that Tropical Canine Pancytopenia is, in fact, Canine Ehrlichiosis, a potentially fatal disease caused by the obligate, intracellular rickettsiae, Ehrlicia canis; …that the disease has wo rl dwide distribution among dogs…it isn’t limited to Viet Nam; …that infection is transmitted by the common brown dog tick (Rhipicephalus sanguineus); …that hospital confirmation of infection, although possible, is very difficult; and, …that a rapid, in-hospital ELISA test is available for the detection of E. canis antibody in suspect patients…

BACKGROUND In recent years, it has become increasingly apparent that ticks living in different regions of the world are capable of transmitting an eve r- growing number of human and animal pathogens. Molecular evidence suggests that simultaneous infection with multiple tick-borne pathogens may not be the unusual occurrence that it was once thought to be. This is particularly true in dogs living outside that have extensive tick exposure. For example, as the number of documented tick-borne pathogens continues to increase and as molecular evidence of co-infection also increases, the relative importance of tick control measures in human and animal disease prevention becomes more important. Although numerous examples exist, recently recognized human infection with organisms such as Babesia microti, Ehrlichia chaffeensis, Human Granulocytic Ehrlichiosis (Ehrlichia equi), Borrelia burgdorferi

(Lyme disease), and several bartonella species (e.g, cat scratch disease) serve to illustrate the growing number of new vector-borne infectious agents. Of comparative medical interest is the fact that dogs, cats, and humans can all be infected with most tick-borne pathogens. Although current knowledge of tick-borne diseases in cats is substantially less than that of canine infections, several factors may play a role in minimizing clinical illness associated with tick-borne disease in cats: decreased pathogenicity of tick - b o rne pat h ogens in cat s , fa s t i d i o u s grooming behavior and early removal of ticks (most ticktransmitted pathogens require a 24–48 hour period of attachment to the host before there can be successful transmission of infectious organisms).

THE ORGANISM Ehrlichiosis described in veterinary and human tickborne diseases are caused by gram-negative pleomorphic, o bl i gate intracellular bacteria of the family Rickettsiaceae. The infection within the mammalian hosts is characterized by a tropism or leukocytes. The organisms then multiply within endosomes, producing cytoplasmic inclusion bodies called morulae. Two types of Ehrlichia infection are described: monocytic Ehrlichia (a disease infecting lymphocytes and monocytes) and granulocytic Ehrlichia (infecting neutrophils and eosinophils). However, the clinical manifestations of ehrlichiosis are highly variable and are now known to be caused by a variety of rickettsial species. At least 10 different ehrlichial species have been documented to infect dogs either naturally or under experimental conditions. Ehrlichia canis infection in dogs was first described in Algeria in 1935. But it wasn’t until the late 70’s and early 80’s that the etiologic agent of Tropical Canine Pancytopenia was actually identified as Ehrlichia canis, a Rickettsial parasite capable of infecting dogs, other Canidae (fox, coyote, jackal) and even humans. The tick-borne infection, now known to have wo rl dwide distribution, is among the most important vector-borne diseases affecting dogs today. Serologic evidence of infection has been reported from diverse geographic regions, including Africa, the Middle East, Asia, Indonesia, southern Europe, North America, the Caribbean, as well as numerous locations throughout the US.

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The incidence of disease does tend to be regional and seasonal because of the disease pattern determined by geographic range and feeding activity of the tick vector. Following a tick bite, the incubation period for all ehrlichioses is 1–3 weeks. Effective transmission of the organism to the mammalian hosts occurs only after an extended feeding period (48–72 hours) by the tick vector. It is important to note that canine and human seroprevalence studies conducted in the US suggest that the incidence of subclinical ehrlichial infection in both dogs and humans is far greater than the incidence of clinical disease. Although tick-vectors and domestic animals are known hosts for many species of Ehrlichia, most of the information on canine infections has been centered on E. canis infection. The arthropod vector of E. canis is the brown dog tick, Rhipicephalus sanguineus. Mammalian reservoirs, in addi tion to the dog, include the coyote, fox, and jackal. Ticks acquire E. canis through normal feeding, as either larvae or nymphs on rickettsemic hosts, and transmit the infection as nymphs or adults. Adult ticks can survive for up to 568 days and transmit infection to susceptible dogs for at least 155 days after infection. This permits the vector and pathogen to survive over winter and infest and infect susceptible dogs the next spring.

THE SPECTRUM OF CLINICAL ILLNESSES Cainine ehrlichiosis is a complex infection involving 3 phases: acute, subclinical, and chronic. Characteristic signs associated with the acute infection include fever, anorexia, lethargy and lymphadenomegaly. It’s during this phase that the most dramatic changes in laboratory parameters occur. In particular, affected dogs are likely to have severe (<70,000…and occasionally < 50,000 platelets/µL), mild to moderate leukopenia, and a non-regenerative anemia. Signs develop 1 to 3 weeks following significant exposure and persist for 2-4 weeks. A subclinical phase typically lasts from 40 to 120 days during which time affected dogs appear to be quite normal, leaving owners with the impression that the dog simply “got over what it had”. Untreated dogs are likely to enter a chronic phase during which clinical signs are particularly vague. Affected dogs may appear healthy or they may slowly develop chronic weight loss, peripheral edema, or manifest spontaneous bleeding in the form of petechiae, retinal hemorrhages, or epistaxis. Oftentimes, the first observed clinical manifestation of chronic ehrlichiosis is associated with prolonged bleeding from venipuncture sites. During the US involvement in the Vietnamese War, a severe, hemorrhagic syndrome was described among German shepherds (used as military working dogs). However…and this is important…recent studies have de-emphasized the role of hemorrhages as a frequent component of clinical infection. Other infrequently encountered clinical manifestations include neurologic abnormalities, such as ataxia or seizures, pancytopenia associated with bone marrow suppression, and polyarthritis.

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DIAGNOSIS For patients presented with clinical signs consistent with ehrlichiosis, establishing a diagnosis and implementing treatment early in the course of disease is generally associated with a better outcome. Dogs that receive initial treatment during the chronic phase of infection have a much poorer prognosis for recovery.

CLINICAL SIGNS Most dogs with ehrlichiosis manifest lethargy, mild weight loss and anorexia. Spontaneous bleeding may occasionally be reported by the owner and is manifested by dermal petechiae or ecchymoses and epistaxis (the most common bleeding sign). Lymphadenomegaly and splenomegaly occur in about one-fourth of affected patients. Fever is characteristic in the acutely infected dog. Also characteristic of the acute infection is anterior uveitis and retinal disease (e.g. chorioretinitis, retinal hemorrhage). However, the suspicion of ehrlichiosis is clouded by the extreme variability of clinical signs involving multiple organ systems. Seizures, stupor, ataxia with upper or lower motor neuron dysfunction, vestibular disease, tremors, and hyperesthesia have been associated with meningitis and/or bleeding into the central nervous system. Morulae have been found in cells from the CSF in some instances. Dogs with ehrlichiosis may develop lameness with an associated stiff gait secondary to polyarthropathy. Arthralgia may result from hemarthrosis or immune complex deposition within the synovial membrane.

HEMATOLOGY Typically the diagnosis of ehrlichiosis is based on the physical signs, and hematologic abnormalities, particularly thrombocytopenia. The most common hematologic changes include nonregenerative anemia (82%), thrombocytopenia (82%) and leukopenia (32%). A small number of dogs will present with pancytopenia associated with bone marrow hypoplasia, a condition more often seen in German shepherd dogs.

BIOCHEMISTRY The most frequent biochemistry abnormalities include hyperproteinemia (33%), hyperglobulinemia, hypoalbuminemia (43%) and mild to moderate elevations of alanine aminotransferase and alkaline phosphatase activities.

CYTOLOGY In dogs with significant and serious clinical signs, an effort should be made to identify morulae in leukocytes from blood smears or in tissue aspirates from spleen, lymph node or bone marrow. The presence of morulae obviously confirms the diagnosis. However, the ability to actually demonstrate morulae in clinical practice is rare.

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SEROLOGY In most instances, confirmatory diagnostic testing for ehrlichiosis is based on positive results of the indirect fluorescent antibody (IFA) test. Although IgG antibody may be detected as early as 7 days, it may require 28 days following the initial infection in some dogs. Western immunoblotting and polymerase chain reaction (PCR) methods have been shown to identify antibody titers among dogs during early (< 8 days) infection. However, Western blot and PCR testing are not routinely available to clinicians. Although the IFA test is the preferred serologic test for ehrlichiosis, samples must be sent to an outside laboratory…which can significantly delay diagnostic assessment of individual patients.

THE IDEXX SNAP TEST FOR E. CANIS Of importance to clinicians attempting to establish a diagnosis of ehrlichiosis is the recent introduction of an InHospital, ELISA-based test for E. canis antibody. IDEXX Laboratories has developed a highly specific assay for E. ca nis antibody that has been combined with their Canine Heartworm Antigen test. This test correlates exceptionally well (96.9%) with high positive (1:600) IFA test results for E. canis antibody. A dog that is positive for E. canis antibody on the IDEXX Snap Test: A. …has been exposed to E. canis and seroconverted but healthy. NOTE: among healthy dogs living in endemic areas, a positive antibody test may simply represent fre quent exposure to E. canis through tick infestation. Treatment may not be indicated…or, B. …is in the subclinical or chronic phase of the infection. Empiric treatment is justified with follow-up evaluation within 10-14 days…or, C. …is in the acute phase of infection, especially if clinical and laboratory findings have recently been documented. Treatment is indicated. A positive IDEXX Snap test for E. canis antibody alone does not represent diagnostic confirmation of infection. However, it does represent an important advancement in hospital-based patient assessment. Faced with any of the diverse, often vague, clinical and laboratory findings associated with ehrlichiosis, the ability to perform rapid, hospitalbased serologic assessment of suspect patients significantly extends the clinician’s “diagnostic reach”. A negative IDEXX Snap test for E. canis antibody does

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not rule out infection. In the presence of clinical signs and laboratory parameters consistent with ehrlichiosis, the patient simply may not have developed a detectable antibody titer. Treatment is justified and the patient should be retested in 2-3 weeks.

TREATMENT Several antimicrobials have been found to be effective in treating canine ehrlichiosis. The most common drugs used today are doxycycline, 5–10 mg/kg, PO, bid, for 10–21 days, or minocycline, 10 mg/kg, PO, bid, for 10 days. Other drugs that have been used include tetracycline, oxytetracycline, chloramphenicol,imidocarb dipropionate (5 mg/kg, IM, given 1 time, repeated in 2–3 weeks). Dramatic clinical improvement generally occurs within 1 to 2 days following the onset of therapy in dogs with acutephase disease. In thrombocytopenic patients, the platelet count should reach normal values within 14 days. However, experience among veterinary teaching hospitals in the United States suggests that most clinicians empirically prescribe short-term corticosteroid therapy (2–7 days) at the same time antimicrobial therapy is initiated. Prednisolone is most frequently administered at a dose of 1–2 mg/kg, PO, for 7–10 days. A variety of supportive treatment modalities have been attempted in pancytopenic dogs: whole blood transfusions (which will NOT significantly increase platelet numbers). Colony stimulating factors (such as granulocyte colony stimulating factor (eg, Neupogen), and human recombinant erythropoietin (eg, Epogen) have been tried but their value in managing ehrlichiosis has not been established. Since there is no vaccine currently available for ehrlichiosis, chemoprophylaxis (long-term antimicrobial therapy) and tick control measures are the primary means of prevention.

Additional reading Neer TM: Ehrlichiosis. Chapter 28 in CE Greene (ed): Infectious Diseases of the Dog and Cat. WB Saunders,Philadelphia. 2nd Edition. pp.139147. 1998. Beaufils JP: Ehrlichiosis: Clinical aspects in dogs and cats. Comp Cont Education Pract Vet. 19: 57-61, 1997. Lappin MR: ELISA Tests: Methods and interpretation. In JD Bonagura (ed): Kirk’s Current Veterinary Therapy XIII. WB Saunders, Philadelphia. 2000. pp. 8-11. Greig B: Granulocytic ehrlichioses. In JD Bonagura (ed): Kirk’s Current Veterinary Therapy XIII. WB Saunders, Philadelphia. 2000. pp. 289-302.

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Feline infectious peritonitis Peritonite infettiva del gatto

Richard B. Ford DVM, MS, Dipl ACVIM - North Carolina State University - Raleigh, North Carolina (USA)

As long as we've known about, tried to diagnose, and attempted to treat feline infectious peritonitis (FIP), it still eludes us! This infection of kittens and adult cats is caused by a feline coronavirus. But that's the easy part...everything about this disease, from pathogenesis to transmissibility, is difficult to understand...and the more we learn about it, the more complex it becomes! The first references to the fact that cats infected by this virus developed disease were described as early as 1960. However, it was not until 1966 that FIP was described as a distinct clinical entity and the infectious nature of the disease was described. Although the initial name, "feline infectious peritonitis," has remained the popular name for this disease, the virus by no means is restricted to the peritoneum. In fact, coronaviruses are a widely distributed group of viruses capable of infecting several species of birds and mammals. They can cause upper respiratory and gastrointestinal disease, hepatitis, vasculitis, peritonitis, pleuritis, and encephalitis. Perhaps the best known of these viruses are the FIP virus in cats, canine coronavirus in dogs, and transmissible gastroenteritis virus of swine. The feline enteric coronavirus (FECV), another very common virus known to infect the GI tract of kittens-especially those living in multiple-cat households, has "traditionally" been described as causing mild, transient diarrhea in kittens. In other kittens, infection causes no clinical signs at all...but...THAT'S WHAT WE USED TO THINK! Some compelling evidence about the role of the FECV in the pathogenesis of FIP has recently been published and sheds quite a different picture of this so-called benign virus.

EPIZOOTIOLOGY The overall prevalence of FIP is not precisely known. In the general population, it has been reported by some sources to be less than 1% of all cats presented to university teaching hospitals. In multiple cat households and catteries, the prevalence is probably considerably higher. Nonetheless, deaths appear to be sporadic and unpredictable. Under the worst conditions, the morbidity (clinical illness) due to FIP is typically around 3-4% in cluster households. (NOTE: that compares to 28%-30% for FeLV endemic households). Clinical FIP is seen primarily in cats between six months and five years of age, with the highest incidence occurring between six months and two years. In our experience, how-

ever, we have diagnosed fatalities caused by FIP in cats as young as two months of age. FIP infection in adult cats must be regarded as a chronic infection that has persisted for months or years. This may account for the fact that clinical signs attributed to FIP virus are occasionally recognized in adult cats 10 years of age and older despite an excellent his tory that the cat has lived indoors as the lone cat in the household for all of its life! Don’t disregard the fact that the infection was likely acquired from the queen and coronavirus transmission occurred during the first several weeks of life.

THE CLINICAL DISEASE Generally speaking, FIP occurs in two distinct forms: an effusive form characterized by peritonitis or pleuritis, or both, and a noneffusive, or dry, form that causes granulomatous lesions in major organs, such as lymph nodes, kidneys, the eyes, and the central nervous system (CNS). Effusive FIP is characterized by a widespread vasculitis that is responsible for the outpouring of protein- and fibrin-rich fluid. Although antibody titers do not correlate with immunity, titers will rise simultaneously with the development of lesions of effusive FIP. Cell-mediated immunity is probably the only beneficial protective response in this disease, since antibody actually appears to enhance virus uptake by phagocytic cells, a preferred site for virus replication. The noneffusive form of FIP, clearly the most difficult to diagnose, is characterized by a dramatic granulomatous reaction in localized tissues, such as the nervous system or the eye. Again, antibody is not protective. Cell-mediated immunity, if the response is strong enough, will prevent the development of signs of illness in the infected cat. Cell-mediated immunity does not always lead to complete elimination of the virus. Apparently, virus can persist in the body of some cats for an indefinite period of time. With advancing age or drug-induced immunosuppression (FeLV infection or steroids), the FIP infection may again become active.

TRANSMISSION OF FIP VIRUS The actual route by which FIP virus is spread is still not known. It appears most likely that infection results following direct contact, either by ingestion (most likely) or by inhalation of virus, between an infected cat and a susceptible

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cat. The virus is probably excreted into the environment by a number of routes, including oral and respiratory secretions, feces, and possibly, urine. It appears that close, sustained contact between cats (esp. a carrier queen and her kittens) is required for effective transmission of the virus. The potential for transmission by insects is not known. Transmission in utero is strongly supported by several reports, however, this route has not been definitely proven. FIP virus is relatively unstable outside the host. However, recent studies suggest that infectious concentrations of virus can persist for as long as two weeks, considerably longer than previously thought, under laboratory conditions. For what it's worth, most common household detergents rapidly inactivate the virus and disinfectants, including Clorox bleach diluted 1:32 in water. However, the fact is that by the time clinical signs develop and a kitten or cat becomes moribund, there is very little virus around to disinfect.

DIAGNOSIS OF CLINICAL FIP Clearly, the effusive form of FIP is far easier to diagnose than the noneffusive form. Once a pleural or peritoneal effusion develops, gross and microscopic examination of the fluid is usually sufficient to make a clinical diagnosis. In the noneffusive form, the disease is far more difficult to diagnose because of the virus's ability to localize in discrete organs and the absence of obvious clinical signs. Hematology and Biochemistry: In both the effusive and noneffusive forms of FIP, the total white blood cell (WBC) count is typically elevated with an absolute neutrophilia and a normal to low lymphocyte count. Cats with concurrent feline leukemia virus (FeLV) infection may have profound panleukopenia. In most cases of FIP, a mild to moderately severe anemia exists. Fluid Analysis: Peritoneal and pleural effusions (when present!) are characteristic and essentially diagnostic. The fluid is light to dark yellow in color and has a sticky, viscous consistency. The fluid is technically an exudate since it is high in protein (characteristically from 5 to 12 g/dL) and has a high Specific Gravity ranging from 1.017 to 1.047. Cytological assessment of the fluid is not particularly impressive. Despite the high viscosity, expect the fluid to be relatively hypocellular consisting principally of WBCs, predominantly neutrophils and macrophages, with occasional mesothelial cells. To get down into the diagnostic “weeds”, an Albumin:Globulin ratio (determined on abdominal fluid) that is greater than 0.81 is highly predictive for ruling out a diagnosis of FIP. Likewise, an albumin concentration (in the abdominal effusion) greater than 48% of the total protein or a gammaglobulin less than 32% of total protein are very good predictors that the effusion is not due to FIP. On the other hand, an effusion in which the globulin fraction is greater than 32% of the total protein (in the fluid) is highly predictive of FIP. Plasma Proteins: Of particular importance in the diagnosis of the noneffusive form of FIP is the fact that approximately 75% of the cats affected have plasma proteins

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that are greater than 7.8 g/dl. Characteristically, the albumin is lower than normal and the globulin fraction is abnormally high. [READ THIS] Electrophoresis of the serum proteins, routinely available through most commercial clinical pathology labs, will demonstrate an increase in the gammaglobulin fraction of serum in about 75% of cats affected with the NONEFFUSIVE form of FIP. The elevated serum globulin level, combined with evidence of ocular/CNS disease is highly suggestive of the noneffusive form of FIP. This is a particularly important diagnostic tool in cats suspected of having FIP but in which a significant accumulation of fluid is lacking. FeLV Status: While many reports suggest that 40-50% of cats with FIP will also have a positive FeLV test, this assertion has not been established as a consistent finding. Only one report has shown such a high correlation between FIP-positive and FeLV-positive cats. Clinical experience indicates that the percentage of FIP cats that are FeLV positive is consider ably lower. In no way should FIP be considered one of the FeLV-related diseases. Histopathology: Biopsy is the only "test" that CAN confirm an antemortem diagnosis of FIP. Any FIP diagnosis made without histologic confirmation must be considered presumptive.

ANTIBODY vs. ANTIGEN TESTING Several assays are currently available to detect coronavirus antibody in serum. REMEMBER: THERE IS NO FIP ANTIBODY TEST. Commercial laboratories offering an "FIP-antibody titer" are actually reporting "coronavirus antibody titers." While it has been proposed that the disease can be diagnosed by virtue of a high antibody titer, none of the so-called antibody tests for FIP are diagnostic. It is critical to note that a laboratory report of "positive" titer refers only to the presence of a significant level of antibody. IN NO WAY DOES A "POSITIVE" TEST INDICATE A DIAGNOSIS OF FIP. Furthermore, the diagnosis of FIP can not be made on the basis of a single coronavirus antibody titer determination. A positive titer certainly does not indicate that a cat is doomed to develop FIP at some future date. Titer Applications: Despite all the frustration associated with interpreting coronavirus antibody tests, there are some situations in which determination of antibody titers can be of use to the practitioner: 1. Based on the current knowledge of feline coronavirus serology, there is little or no value in performing routine antibody titer screening. While the presence of antibody does not diagnose the disease, knowledge that coronavirus antibody is absent may be helpful in ruling out FIP virus as the culprit in a disease outbreak. However, a NEGATIVE titer, as reported by a laboratory, may, in fact, NOT BE A "ZERO" TITER. If compelled to perform titers, check with the laboratory to determine the meaning of "NEGATIVE". Cats dying of fulminate FIP typically have a low or "NEGATIVE" titer. 2. Determination of coronavirus antibody titers is a poor

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clinical aid in the diagnosis of a sick cat with signs suggestive of FIP. A positive coronavirus titer may be the least significant test to perform compared any other diagnostic procedureavailable. 3. Recently available through commercial laboratories is the reverse transcriptase-polymerase chain reaction (RTPCR) assay for coronavirus antigen. The assay offers the ability to detect viral antigen in effusions, serum, plasma, and in feces. This is NOT an FIP Test! The value of RTPCR is that can detect viral antigen (compared to antibody). It does not distinguish between FIPV and FECV or any other feline coronaviruses…of which there appear to be a bunch! The RT-PCR assay does not distinguish between FIPV and the FECV however, it has allowed investigators to study feline coronavirus shedding patterns of cats living in cluster households. This, combined with evidence that FECV is, in fact, the parent of FIPV, has provided new, clinically germane information about this complex disease:

IMMUNITY TO FIP VIRUS Although the nature of the immune response to FIP virus infection in cats is not well understood, experimental infection is successfully accomplished via the oral, oronasal, or intratracheal routes. Clinical signs associated with infection develop after the virus crosses the nasal and gut mucosal barrier, infects macrophages and monocytes, and causes an immune-mediated disease leading to the oftentimes fatal vasculitis.

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The FIP VACCINE (TOPICAL) Pfizer Animal Health provides the only approved vaccine for use in preventing Feline Infectious Peritonitis, PRIMUCELL. It is a temperature sensitive (therefore, modified live) virus "designed" to grow only at the cooler temperatures of the upper respiratory tract. The vaccine virus will not replicate at core body temper atures. Therefore, it is effective only if exposure is VIA the oronasal mucous membranes (and this is the presumed MOST common route of infection); the vaccine is administered intranasally (applied directly onto the oral-nasal mucosa). Protection is apparently mediated by Secretory IgA produced at the level of the upper respir atory tract and oral mucous membranes combined with an enhanced cell-mediated immune response. The vaccine has been specifically developed so that it does NOT stimulate detectable levels of serum neutralizing antibody. THIS IS GOOD...coronavirus antibody is NOT protective against FIP and cats that have circulating coronavirus antibody may actually have a more severe disease subsequent to infection, a phenomenon referred to as Antibody Dependent Enhancement (ADE) of infection. Earlier concerns that the vaccine may actually, and inappropriately, stimulate circulating antibody, should be disregarded. In the clinical setting, there is NO evidence that ADE is associated with PRIMUCELL administration. The vaccine is regarded as being quite safe. In a challenge of immunity test conducted at Pfizer, 17 of 20 cats (85%) vaccinated intranasally were protected against a rigorous FIP virus challenge that killed 10 of 12 (83%) of nonvaccinated controls. On a second challenge of the surviving cats, 16 of the remaining 17 (94%) survived, while only 2 of the remaining 6 (33%) nonvaccinated controls survived. Still to be determined are issues such as protection conferred in the real world, the duration of immunity (remember...serum antibody titers are not necessarily predictive of immunity nor duration of immunity), and impact of vaccination on latent FIP infections.

➢ The common Feline Enteric Coronavirus (FeCV) appears to be the parent of FIPV.

➢ There is good evidence that certain cat breeds, and lines within breeds, are predisposed to FIP. Persian cats predominate, Balinese, Birman, and Himalayan are mentioned frequently as well.

Additional reading (FIP) 1. 2.

➢ The risk of FIP is greatest among cats living in cluster (multiple-cat) households.

➢ Infection is most likely to occur in kittens as

opposed to adult cats; clinical signs may require many years to develop if they develop at all. 6.

➢ Coronavirus shedding in infected cats is bimodal....more on the significance of this fact during the presentation...

Sparkes,AH,et al:An appraisal of the value of laboratory tests in the diagnosis of feline infectious peritonitis. JAAHA. 30:345-350, 1994. Pedersen, NC: Virologic and immunologic aspects of feline infectious peritonitis virus infection,in Lai, MC,Stohlman, SA (eds):Coronaviruses, vol 28,New York, Plenum Press, 1987. pp. 529-550. Foley, JE et al: Patterns of feline coronavirus infection and fecal shedding from cats in multiple-cat environments. JAVMA. 210:1307-1312, 1997. Foley, JE et al: Risk factors for feline infectious peritonitis among cats in multiple-cat environments with endemic feline enteric coronavirus. JAVMA. 210:1313-1318, 1997. Barlough, JE, and Stoddart, CA: Feline coronaviral infections. In Greene, CE (ed): Infectious Diseases of the Dog and Cat. WB Saunders,Philadelphia. 1990, pp. 300-312. Weiss, RC: Feline infectious peritonitis and other coronaviruses. In Sherding, RG (ed): The Cat: Diseases and Clinical Management. Churchill Livingstone, New York. 1994. pp. 449-477. Addie DD and Jarrett O: Feline coronavirus infection. Chapt 11 in CE Greene (ed): Infectious Diseases of the Dog and Cat., Second Edi tion. Philadelphia,WB Saunders. 1998, pp. 58-69.

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FeLV and FIV: testing vs. vaccination FeLV e FIV: test diagnostici contro vaccinazioni

Richard B. Ford DVM, MS, Dipl ACVIM - North Carolina State University - Raleigh, North Carolina (USA)

Simply stated , the goal of vaccination is to sensitize or prime the recipient’s immune system such that it can generate memory cells capable of mounting a heightened immune response following exposure to a specified pathogen. In veterinary medicine, there is little question that it has been possible to achieve this goal. The widespread use of attenuated (modified live) and inactivated (killed) vaccines has effectively and inexpensively prevented millions from death and suffering following exposure to infectious organisms. However, among the most controversial issues facing companion animal practitioners today are those that focus on vaccine safety and vaccination strategy. Are we vaccinating with too many vaccines, too often? Is there a cause-and-effect relationship between the administration of modified-live virus vaccines, tumor formation, or immune-mediated diseases? How many antigens per dose of vaccine are too many? For a given disease, which vaccine is the best? Although these are difficult questions without simple answers, the future promises to be especially challenging as the vaccines we use and the protocols we recommend undergo unprecedented change.

VACCINATION AGAINST FELINE LEUKEMIA VIRUS INFECTION Of the various retroviruses known to infect cats, there is only one for which a commercial vaccine market has emerged: Feline Leukemia Virus (FeLV). Since the introduction of the first FeLV vaccine almost 20 years ago, several vaccines, both univalent and combination preparations, have become available and are in routine use throughout North America, Europe and the United Kingdom. However, for the practicing veterinarian, assessing the real benefits the individual cat derives from vaccination remains a difficult, if not perplexing, issue. The fact that a large number of unvaccinated cats (over the age of 4 months) are naturally resistant to FeLV infection, that latent (undetectable) infections are known to occur, and that the various studies designed to compare FeLV vaccines are difficult, or impossible, to interpret, makes it particularly challenging to determine which FeLV vaccine provides the best level of protection in the population at risk. Also at issue are concerns over the asso ciation of FeLV vaccination with vaccination-site fibrosarcomas in cats, a significant finding that has caused veterinarians to question the role of routine FeLV vaccination in clinical practice.

Yet, despite concerns over FeLV vaccine safety and efficacy, it does appear that the prevalence of FeLV within the domestic cat population has declined over the last decade. Two factors are most likely to have pla yed a major role in this decrease: vaccination and in-hospital testing for FeLV antigen in sick cats and cats presented for routine vaccination. Although vaccination of cats at risk of exposure to FeLV has merit in preventing infection and subsequent transmission of virus to other cats, the ability to identify and isolate, or remove, infected cats, is the most effective means of protecting the population of cats against exposure. Testing cats prior to FeLV vaccination is particularly important because: 1) vaccination will neither reverse the FeLV-positive status nor will it prevent the development of solid tumors, 2) healthy, FeLV-positive cats remain infectious following vaccination, and 3) any FeLV-positive cat could develop clinical signs of illness at any time following exposure. Of the various FeLV vaccines available today, all vaccines are killed, or inactivated, products, i.e. they are not capable of replicating within the host nor causing infection. In addition, none of the FeLV vaccines on the market today interfere with either the ELISA nor IFA tests for FeLV antigen. Although some vaccines do contain FOCMA (feline oncornavirus cell membrane-associated antigen), this protein is not regarded as having immunogenic value in preventing either FeLV infection nor tumor formation. Vaccination of kittens should consist of 2 vaccine doses administered at a 2 to 3 week interval beginning as early as 8 or 9 weeks of age. A 2-dose regimen is required at the time of administration of the first vaccine, regardless of the cat’s age. Cats presented for the second dose of vaccine at more than 4 weeks following the first dose should be given a third dose 2 to 3 weeks later. Administration of an annual booster is recommended. Regardless of the vaccine used during the initial 2-dose regimen, it is not necessary to use vaccine from the same manufacturer when administering subsequent annual boosters. The decision to vaccinate an individual cat against FeLV is not necessarily a simple one. All cats are not at equal risk following exposure to an infectious organism and the recommendation that all cats presented to the practice be inoculated with FeLV vaccine is not justified. Ultimately, it is a combination of the various host, environmental, and agent factors that influence the outcome of infection and therefore define the individual animal’s risk. Among the recognized risk factors for FeLV, age is among the most important. Clearly, it is the kitten, 4 month of age and younger, that is

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at greatest risk of infection following exposure to FeLV. Natural resistance to infection among adult cats is significant. Adult, indoor cats living in 1- or 2-cat households are at such a low risk of infection that it is difficult to justify routine FeLV vaccination. On the other hand, the risk of infection increases substantially within multiple-cat households and open catteries, particularly those in which new cats are regularly introduced into the household. Risk of infection is especially high in either single- or multiple-cat households when there is frequent exposure to untested, unvaccinated stray cats. The value of prevaccination testing for FeLV antigen (ELISA) has been thoroughly reviewed and is recommended for all cats prior to initial inoculation. Although associated with minimal risk, healthy, FeLV positive cats derive no benefit from FeLV vaccination.

VACCINATION AGAINST FELINE IMMUNODEFICIENCY VIRUS (FIV) The goal of achieving an effective, safe vaccine against FIV has yet to be accomplished. Although considerable research effort is currently underway to develop an FIV vaccine, it is likely to be several months or years before a vaccine is introduced into companion animal medicine. A prototype FIV-vaccine developed in Scotland is being evaluated in Europe. FIV, unlike FeLV, poses several impediments to developing a successful vaccine: frequent mutation and recombination of the virus in nature, various virus subtypes, and difficulties involved in identifying and isolating immunogenic fractions of the virus. Recent advances made in vaccine development technology suggest several potential opportunities for an FIV vaccine. Given that FIV is predominantly an intracellular vaccine, a peptide vaccine, derived from an entire peptide or a short sequence of amino acids from an FIV protein, is well suited to a stimulate cell-mediated immune response. Use of a recombinant vector vaccine, similar to that already introduced for use in dogs, is another FeLV vaccine development strategy suited to an FIV vaccine.

FeLV AND FIV: TESTING VS. VACCINATION Clearly, one of the most significant technologic advances introduced into clinical practice within the last 10 years has been the ENZYME-LINKED IMMUNOSORBENT ASSAY, or ELISA. The ability to perform in-hospital, sameday screening for feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), and canine parvovirus (CPV) are among the most important value-added services offered by the companion animal practitioner today. The feline retr oviral infections, FeLV and FIV, continue to represent a major threat to the health of the domestic cat population. Extensive surveys have consistently demonstrated that among sick cats presented to veterinarians, from 11% to 16% are FeLV-positive while from 6% to 9% are FIV-positive. Retrovirus infection is best prevented by eliminating

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opportunities for exposure of susceptible cats and kittens to infected cats. However, in the clinical setting, it is unreasonable to assume that recommendations for avoiding contact with FeLV/FIV–infected cats constitutes a practical approach to prevention. Fundamental to the strategic management of feline retrovirus infection is the opportunity to vaccinate at-risk cats against FeLV. However, routine FeLV vaccination of cats presented to the practice only represents one component of a prevention strategy. Since the available FeLV vaccines are unlikely to confer complete protection in all vaccinated cats and that there is currently no FIV vaccine available suggests that the risk of retrovirus infection among susceptible cats is still significant. In accordance with current guidelines, it is recommended that the FeLV and FIV status of all cats seen by the practice be established. However, the commitment to perform routine screening of cats for retroviral infection raises important issues pertaining to interpretation of test results and follow-up actions needed to further manage those households with confirmed FeLV and/or FIV positive cats. C u rrent testing re c o m m e n d ations outlined by the AAFP/AFM have recently been published and are summarized in a 1997 edition of ALTERNATIVES: A Veterinary Clinical Update. (A Supplement to Compendium on Con tinuing Education, published by Veterinary Learning Sys tems, Volume 19; Nbr. 12). The current ELISA technology used for in-hospital retrovirus testing in cats is remarkably sensitive and accurate assuming proper technique and specimen handling are used. These same tests are recommended for routine screening of both healthy and sick cats presented to the practice. Fundamental to the proper use of ELISA-based testing for the diagnosis of FeLV and FIV infected cats is an understanding that FeLV tests are designed to detect the p27 antigen (core antigen) while FIV tests detect the presence of antibody. In clinical practice, these facts have important implications. For example, the FeLV test can detect FeLV virus in the blood (serum or plasma) of young kittens; a positive test is consistent with infection. It is important to note that FeLV tests designed to detect the presence of virus in tears and/or saliva are also ELISA-based tests. However…these tests are significantly less sensitive/specific (ie, large numbers of false-positive and false-negative results) than tests utilizing blood, serum, or plasma. Saliva and tear tests should not be used for routine screening of individual cats. It should also be noted that neither maternal antibody nor recent FeLV vaccination interferes with the ELISA-based FeLV test. The reader is refer red to Figure 1 for guidelines on interpreting the various test results in cats at various stages in the course of FeLV infection. ELISA-based FIV tests are not reliable in kittens less than 6 months of age. Since antibody response to FIV infection requires weeks or months to become detectable, a negative test result could occur in an exposed, infected kitten that has not seroconverted. On the other hand, uninfected kittens from FIV infected queens may test positive as a result of having acquired maternal FIV antibody; detectable levels of maternal FIV antibody can persist for as long as 6 months.

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ORONASAL INFECTION via saliva

From 2 weeks to 6 months

1st: 2nd: 3rd: 4th :

Local lymphoid tissue, esp. tonsils Circulating lymphocytes/monocytes Systemic lymphoid tissue Bone marrow

Possible Latent Infection (up to 15%?)

Regressive Infection (~98%)

Progressive Infection (~2%)

Transient, self-limiting infection

Progressive immune suppression developing over months to years; approximately 20% will develop solid tumors

FeLV Negative

Neutralizing Ab + Healthy Cat

FeLV Positive

± Neutralizing Ab Sick Cat

Figure 1 - FeLV Testing in the Clinical Setting.

Among healthy cats with a positive ELISA test for either FeLV or FIV, follow-up testing is recommended. The clinician should repeat the ELISA test in 1 to 3 months. As noted in Figure 1, waiting 1-3 months is justified in healthy cats with a positive test considering the possibility that the infection is early (transient) and a protective neutralizing antibody may still develop. Alternatively, the indirect fluorescent antibody (IFA) could be submitted in an attempt to confirm infection. As many as 80% of FeLVpositive cats will die within 3 years from illness associated with the infection. The ELISA-based FIV antibody test is not a confirmatory test. Confirmation of infection is predicated on a positive Western blot assay. In contrast to FeLV, the FIV-infected cat may live for months or years with its infection; early detection and treatment of associated illness will enhance longevity and quality of lif e. Cats infected with either FeLV or FIV are considered to be shedding virus. As such, strong precautions are recommended to prevent unnecessary exposure to healthy, susceptible cats.

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Zoonoses Zoonosi

Richard B. Ford DVM, MS, Dipl ACVIM - North Carolina State University - Raleigh, North Carolina (USA)

In legal terminology, the specialized vocabulary of the legal profession, the term “zoonoses” has not been defined. In medical terms, it refers to “infectious diseases shared by animals and humans.” Of particular importance in both human and veterinary medicine are those zoonoses known to be transmitted directly from animals (vertebrates) to humans. To date, there are about 250 zoonotic infections known to be transmitted from animals to humans,with about 20 to 30 resulting from contact with cats and/or dogs. Transmission can occur through inhalation, ingestion, bites, or scratches. Arthropod vectors, while certainly capable of transmitting infectious organisms from animals to humans, pose a threat to humans and animals alike, but these infections are likely to occur simultaneously and independently of each other. Medical–legal issues centering on zoonoses have not received a great deal of attention in either legal or medical communities. However, the increased risk of infection among immunocompromised individuals brings to the table a new level of concern over the legal implications of zoonotic infections resulting from contact with animals, particularly pet dogs and cats. Surveys have shown that at least 50% of individuals with HIV infection have pets. Furthermore, it has been reported that over 90% of HIV-infected people have been advised by their physician to give up their pets because of the risk of acquiring infection. It is interesting to note that only 5% of these individuals have followed this advice. The question at hand, therefore, becomes, “How real is the threat of an individual acquiring a pet-associated infection?” Obviously, pets offer important physiologic and psychological benefits for people…this seems to be particularly important among individuals with chronic or terminal illnesses. And for patients deemed at greater than normal risk for acquiring a zoonotic infection, eg, the HIV-infected patient, pets provide unconditional companionship when their disability may alienate friends, and even family. In fact, the health impact of isolation (from people as well as pets) may be far greater than the potential risk of acquiring a zoonotic infection. From the perspective of the legal profession, the categories of concern for the veterinary profession, arising from the risk of exposure to a known or suspected zoonotic infection, include: • Failure to warn and individual that a particular disease (in an animal) might be transmitted to a person. • Improper execution of a health certificate.

• Delegation of duties to assistants without providing appropriate supervision. • Poor sanitation standards. • Failure to isolate animals with known or suspected zoonotic infections.

ANIMAL BITES TO HUMANS Although over 1 million people are reportedly bitten by dogs every year, it has been estimated that this represents only half of the dog bites that actually occur. Accounting for approximately 1% of all emergency room admissions, dog bite wounds cost over $30 million in annual health care costs. In the last 10 years, a number of significant facts have been learned about animal bites to humans. For example, dog bites to humans are more likely to occur in males (especially young boys) than in females. From one-half to twothirds of dog bite victims are less than 20 years old and many of these are less than 10 years old. About half of all bites are from dogs owned by neighbors and are inflicted by medium or large-sized dogs. Arms and hands are the most likely part of the body to sustain injury from bite wounds. About 65% of all facial bites occur in children less than 10 years old. Although dogs appear to inflict more bite wounds than cats, the likelihood of infection developing subsequent to a bite wound is greater in cats than in dogs. Wound infection is most common in those victims who are more than 50 years of a ge, when wounds are not properly nor adequately cleansed, when there is more than a 24 hour delay in seeking treatment, and when wounds occur on the hands. While an animal bite to a human is not, per se, a zoonotic disease, the potential for significant injury or infection does exist. Recently, renewed concern has developed over the ability of the dog to cause severe, even fatal, sepsis in humans following the inoculation of resident oral bacteria via bite into human tissue. It is interesting to note that, although infections from dog bites are a major concern, cat bites and human bites are much more likely to become infected. The likelihood of infection following a dog bite is only 3 to 5% (gram negative, aerobes) while infection rates following human or cat bites can be as high as 50% (esp. Pasteurella multocida). The DF-2 organism, now recognized as Capnocytophaga canimorsus, has surfaced as one of the resident organisms in dog saliva that, following bite-wound contamination, can

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cause sepsis in humans leading to severe morbidity or death. At particular risk are individuals who have experience splenectomy or are otherwise immune compromised. This group of gram-negative rods has a propensity to cause disseminated intravascular coagulation (DIC) and symmetric peripheral gang rene in asplenic patients. True incidence of bacteremia after dog bite is considered to be underestimated. Penicillin is the treatment of choice in affected patients.

ANIMAL ASSOCIATED OPPORTUNISTIC INFECTIONS With almost 60% of US households having pets, it is not surprising that the risk, and the incidence, of opportunistic infections among immune suppressed individuals (cancer patients and HIV-positive) has increased. While the risk has increased, levels of pet ownership remain the same. This fact alone is of particular significance to the companion animal practitioner: risk awareness/risk assessment, on behalf of the pet owner, is becoming an increasingly important part of private practice. Several bacterial, fungal, and protozoal infections of animals are now being confirmed as secondary infections among immune suppressed humans, including: Toxoplas mosis, C ry p t o s p o ri d i u m , M i c ro s p o ri d i a , S a l m o n e l l a , Campylobacter, Giardia, Rhodococcus equi, Bartonella sp. (previously called Rochalimaea), Bordetella bronchisepti ca (yes! “kennel cough”), and Listeria monocytogenes. Among the animal-associated opportunistic infections, Bartonella — the cause of Cat-Scratch Disease — is perhaps the most important. Still, it is important to appreciate the fact that pet-associated zoonoses present a small risk to even the immune suppressed client; risk awareness combined with practical suggestions for avoiding exposure can significantly reduce any risk. The benefits of animal companionship far outweigh the risks to human patients. Prohibiting pet ownership by immune suppressed individuals is generally NOT warranted.

CAT-SCRATCH DISEASE (CSD) “Technically, this disease does not fit the definition of a zoonotic infection in that the causative organism does not create an infection in cats. In fact, cats are apparently inno cent bystanders capable of transmitting the small, gramnegative bacillus that causes a benign, chronic regional lym phadenitis in humans.” …AT LEAST THAT’S WHAT WE USED TO SAY… A number of recent studies published in the last 4 years have prompted us to do a complete turn-around on CSD. As it turns out…Cat Scratch Disease (CSD) is one of several infectious disease syndromes of humans caused by Bartonella sp…a member of the family Rickettsiaceae. In fact, CSD, caused by Bartonella henselae, is the most common of these persistent syndromes associated with necrotizing inflammation in lymph nodes. It is estimated to affect an estimated 22,000 people in the US annually! Given newer isolation techniques and an increasing number of immunocompro-

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mised people, it is likely that the reported incidence of Bar tonella-associated diseases in humans will increase substantially. It appears that the domestic cat serves as the reservoir for the CSD causative organism and may, in fact, be the principal source of human infection. Human Infection: Most of the cases of CSD occur in persons under 21 years of age. The disease does appear to have a predilection for males, but is not known to be transmitted human to human. However, CSD usually develops following a scratch, lick (on abraded skin or in the eye), or very rarely a bite from a young cat. Cats capable of transmitting CSD were not thought to become ill as a result of carrying the infectious organism. However, studies now show that Bartonella bacteremia does occur in healthy and ill cats. Following inoculation into a human, the patient first develops tender and moderately enlarged regional lymph nodes near the inoculation site. In many patients, swollen lymph nodes are the only clinical sign observed in CSD. One third of the patients have fever. Less than one third have fatigue, anorexia, vomiting, or weight loss. Occasionally, a headache and/or sore throat develops. The incubation period in humans is three to ten days. On the skin, one or more papules or pustules will develop. Skin lesions may last from one to three weeks; some may persist for up to ten weeks. Lymph nodes usually swell about two weeks after the scratch. Rarely, infected humans develop CNS involvement characterized by meningitis, polyneuritis and/or myelitis with paraplegia. Neurologic signs are sudden in onset and occur from one to six weeks after the swelling of lymph nodes. Rarely, patients have been reported to have seizures followed by coma persisting for one to four weeks. The most severe clinical manifestations occur in immunocompromised individuals, especially those with advanced HIV infection. The diagnosis of CSD in humans is confirmed on lymph node biopsy. Laboratory studies are otherwise not diagnostic for CSD. Blood culture studies in cats have demonstrated significantly high recovery (40–50%) of Bartonella. Prognosis: The prognosis for CSD in humans is excellent with the exception that immunocompromised individuals are at significant risk of developing severe disease subsequent to infection. Lymph node swelling usually regresses within two to four months. Humans are reported to develop lifelong immunity following infection. Fatal complications and irreversible clinical findings are almost nonexistent. Prevention: CSD does not require isolation nor quarantine since it is not transmitted from one human to another. Specific preventative management strategies for individuals who are considered at risk of exposure (eg, veterinarians/veterinary technicians) have not been defined. However, sufficient evidence does exist to warrant the recommendation that individuals (humans) known to be immunocompromised should take measures to avoid contact with cats. Rochalimaea-related illnesses are being recognized with increasing frequency in immunosuppressed individuals as other forms of the cat scratch syndrome, eg, disseminated CSD and bacillary angiomatosis. These conditions are not related to the bacillary angiomatosis caused by Rochalimaea quintana, which has not been associated with cats.

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TICK-BORNE ZOONOSES Lyme Disease (borreliosis). Strictly speaking, Lyme disease is a zoonotic infection. However, it is NOT transmitted directly by affected dogs/cats to susceptible people. Because of its “epidemic” prevalence (more than 14,000 cases have been recognized since 1990), and the common misconception that pet dogs represent a threat to humans, borreliosis is presented in this discussion. Lyme disease, or borreliosis, is caused by the spirochete Borrelia burgdorferi. Although the disease first was recognized and defined in the 1970’s, conservative estimates indicate that the human infection was recognized in Europe more than 80 years ago. Even in North America, Lyme disease almost certainly existed for thousands of years before its discovery. The spirochete is transmitted to animals and people through the bite of the deer tick (Ixodes spp.) and less commonly by the lone star tick. The disease is most prevalent in humans and animals in the Northeastern US, the upper Midwest, and (quite interestingly) California. Infection in humans is characterized by distinct clinical stages. The characteristic red skin lesion (erythema migrans, or EM) that occurs on the skin of Caucasians appears 2 to 30 days after the initial bite. The red lesion then expands into a large bull’s eye appearing lesion with a bright red border and a lighter center. The infection may remain localized or it may spread via the blood to several other areas in the body. During this time, the patient experiences severe headache, neck stiffness, fever, chills, musculoskeletal and joint pain, profound fatigue and lethargy lasting several weeks. Patients with systemic symptoms may exhibit neurologic or cardiac abnormalities. Neurologic manifestation includes meningitis-like symptoms with facial palsy and peripheral radiculoneuropathy. Atriventricular block is the most common cardiac complication of Lyme Disease. Arthritis, especially in large joints such as the knee, may develop any time within two years following initial infection. Recurrent attacks may occur for many years. Diagnosis of Lyme Disease is based on antibody titers to B. burgdorferi. Cultures and direct examination for spirochetes is complex and is not a reliable diagnostic method in a clinical setting. Initial treatment consists of tetracycline or doxycycline therapy for 5–10 days. Penicillin V and erythromycin are acceptable alternatives for children and pregnant women. Despite treatment, about 50% of patients will experience recurrent episodes of headache, musculoskeletal pain, and lethargy for several years. NOTE: Research has proven that the duration of the tick attachment is a key factor in the transmission of Lyme’s Disease. There are many unsafe and ineffective folk methods advocated for tick removal (eg, cigarette butt, finger nail polish, petroleum jelly, isopropyl alcohol). Tweezers are the most common instrument used. However, ordinary tweezers may also accelerate the spread of tick-borne diseases by squeezing too hard on the tick’s body actually facilitating injection of the organism into the bite wound. Use caution when removing ticks from humans as well as from animals. Rocky Mountain Spotted Fever (RMSF) and Human Granulomatous Ehrlichiosis (HGE). The importance of tick-transmitted Rickettsial infections has received more a t-

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tention recently with the recognition that the organism causing ehrlichiosis in dogs is capable of infecting humans. Symptoms of both RMSF and ehrlichiosis are similar with the exception of the extensive cutaneous rash that occurs on the skin, especially the palms, of humans infected with RMSF. In dogs, infections can range from mild or chronic, with death being the common outcome of untreated infections. Transmission occurs by way of the Brown Dog Tick only. Flu-like symptoms predominate in infected humans. Human contact with dogs is NOT required for exposure through infectious ticks. Ehrlichiosis appears to be particularly dangerous in splenectomized individuals who experience rapid onset septicemia, respiratory failure, and death. Diagnosis is based on clinical signs and hematology findings, exposure to ticks (not necessarily dogs), and antibody titers. Tetracycline or Doxycycline are indicated for individuals infected with either RMSF or ehrlichiosis. The prognosis for recovery is excellent in individuals who receive treatment on a timely basis.

BUBONIC PLAGUE The Bubonic Plague, also called the Black Death, is a bacterial disease carried by fleas that feed on rats. The disease has afflicted humans for more than 1000 years and still exists in this country today. The factors responsible for its alternate rise and fall remain a mystery. In the 14th century in Europe, Bubonic Plague killed over 20 million people, about one-fourth of the population of Europe, in a four year period. Subsequent to this period of the Great Dying, repeated epidemics occurred in several of the following centuries. During the period of the Black Death, people were inclined to attribute the disease to unfavorable astrological combinations or malignant atmospheres (“miasmas”), neither of which could be translated into a public-health program of any sort. Although the prevalence of Bubonic Plague is considerably less today, pneumonic plague still occurs sporadically in various parts of the world, including the US, especially in the Southwestern states and Colorado. Not until 1894 was it discovered that a gram-negative, rod-shaped bacillus, Yersinia pestis (previously Pasteurella pestis), caused Bubonic Plague.

CLINICAL SIGNS The name, Bubonic Plague, derives from one of the early signs of the disease: the appearance of large, painful swellings (buboes) in the lymph nodes of the arm-pit, neck, or groin of the victim. Three days after the appearance of the buboes, people were characteristically overwhelmed by high fever, became delirious and broke out in black splotches that were the result of hemorrhaging under the skin. As the disease progressed, the buboes continued to grow larger and more painful; often they would burst, a particularly painful, agonizing aspect of the disease. In some cases, blood would become directly infected, leading to massive hemorrhage and rapid death. In others, plague was transmitted as pneumonia (pneumonic plague) that caused hemoptysis and death within a few days.

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PATHOGENESIS Plague bacilli are found at low frequency in many wild rodent populations throughout the world and are transmitted from one rodent to another by fleas…in this case, the oriental rat flea Xenopsylla cheopis. When a flea bites an infected rat, it ingests the bacilli, which in turn replicate within the flea’s digestive tract forming a solid mass that obstructs the lumen of the gut. The flea, now unable to ingest blood, becomes ravenously hung ry. In a feeding frenzy it repeatedly bites its animal host, regurgitating plague bacilli into the host’s bloodstream with every attempted meal. These injection sites act as foci for the spread of bacilli. The disease spreads rapidly in this manner. As the number of live rats decreases (they, too,die of the infection), the fleas move to other available warm-blooded hosts on which they would not normally feed, such as humans and their domesticated animals. This is the pathway most responsible for the start of an epidemic. It should be noted that an essential requirement for an epidemic among humans is an outbreak in a rodent population. In addition, the two populations must be in very close proximity for transmission to be successful.

TREATMENT Even patients with pneumonic or septicemic disease can be cured if treatment is initiated within the first 15 to 20 hours of infection. In most cases, antibiotic treatment is dramatically effective. Oral tetracycline or chloramphenicol are recommended for individuals who do not require hospitalization. Str eptomycin (IM injections) is the drug of choice and is administered for 7 to 10 days. However, streptomycin can be difficult to obtain today. In critical patients, intravenous chloramphenicol or aminoglycosides are recommended for a minimum of 7 days.

CONTROL By the 16th century, it was widely believed the plague spread as a result of a “contagion.” Human infection was thought to take place either directly through physical contact with a sick person or indirectly through clothes or bed sheets. In response, many towns in England recommended plague victims be locked up in their homes or transferred to special “pest houses.” This turned out to be one of the worst possible means of fighting the plague, a disease of “locality.” To confine people is to maximize their chances of being bitten by a plague-carrying flea. In one case, in the village of Eyam in Derbyshire, a local rector persuaded the entire community to enter into quarantine when the plague erupted there in 1666. One by one, the parishioners who remained faithful to their contaminated homes fell victim to the disease. A mortality rate of 72% (and a morbidity of near 100%) was the extraordinary price paid for a misconceived theory. Effective control depends on elimination of endemic rodent foci and combating rodent epizootics. Total elimination of rat populations is, in reality, a very difficult, impractical task to accomplish. Immunization of humans is possible but

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not done regularly in this country. Flea control, when possible, is the most effective means of reducing disease prevalence in the face of an outbreak. DDT has been a popular favorite for killing fleas on a large-scale basis, but experiences in southeast Asia have revealed the emergence of DDT-resistant fleas.

FELINE TOXOPLASMOSIS Perhaps the coccidian parasite that has caused more concern as a zoonotic infection than any other disease is that of Toxoplasma gondii. The organism is a common environmental organism capable of infecting a very wide range of animals, including fish, reptiles, and birds, as well as mammals. Cats, however, are the only definitive host. The life cycle of toxoplasmosis in the cat is extremely complex and not entirely understood. Nevertheless, the cat is able to excrete unsporulated (NONinfectious) oocysts in the feces. The oocysts are capable of becoming infectious to other animals and humans as early as one day (usually 3 to 5 days) following excretion in the feces. In the clinical disease in cats, the T. gondii is capable of causing a wide variety of signs since it can localize in a number of organs. The exact type of infection that results and the degree of clinical illness depends on the animal’s age at the time of infection, its immune status, the strain of parasite, and the route of infection. In most animals, toxoplasmosis is a subclinical disease. In other words, outward clinical signs are not evident, yet the cat does harbor the organism. Generally, clinical illness in cats is characterized as interstitial pneumonia and is most likely to develop in immune suppressed cats, eg, those with FeLV or FIV infection. By far the most concern over toxoplasmosis in humans occurs in prenatal infections. Congenital toxoplasma infections are the result of in utero infection of the unborn fetus. The resulting clinical signs depend on the stage of pregnancy at the time that infection occurs. The fetus appears to be most susceptible during the last trimester of gestation. However, the most severe outcomes occur when the human fetus is infected very early in pregnancy. In this country, there are still approximately ten thousand congenital infections reported in humans each year. The in utero infection in humans results only when acute infection occurs in a susceptible pregnant female. A woman that has become chronically infected, then becomes pregnant, is unlikely to transmit the organism to the fetus. These pregnancies are usually uncomplicated. Perhaps of most concern to our clientele is the possibility of a cat transmitting toxoplasmosis to a woman during pregnancy. It should be emphasized that, although possible, there has never been a documented case of prenatal toxoplasma infection in a human caused by a cat. Nonetheless, the concern remains, and many pregnant women will present their cat to a veterinary hospital for “testing.” It is most important to understand the strict limitations associated with the toxoplasmosis antibody test available today. In all probability, a cat with a positive titer is protected against disease. The only definitive diagnosis test is finding oocysts in the feces or finding evidence of the organism in tissue.

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While it is important to advise clients on the potential risk of toxoplasmosis to the unborn fetus, it is only rarely necessary to separate or eliminate a cat from a household. Despite the association between human infection and exposure to cats, the frequency and risk of human infection is most likely to be associated with ingestion of infected meat (particularly, pork, goat, or lamb). Also, the ingestion of raw goat’s milk may be a source of human toxoplasmosis. Risk of exposure and contact of affected meat can be avoided by heating and cooking all meat to greater than 150°F. Freezing of meat, however, is not a consistently reliable method of killing of toxoplasma organisms. Therefore, all meat should be adequately cooked. Good personal hygiene also dictates that hands be washed well after handling raw meat.

FELINE LEUKEMIA VIRUS AND FELINE IMMUNODEFICIENCY VIRUS Among the most complex infections recognized in veterinary medicine today are those caused by feline leukemia virus (FeLV) and the feline immunodeficiency virus (FIV). Caused by a retrovirus, FeLV and FIV are capable of being horizontally transmitted (ie, it’s contagious) from one cat to another. The virus replicates in many tissues, including bone marrow, salivary glands and blood cells, and is capable of inducing profound immunosuppression; in some animals the virus may actually induce the formation of cancer. The clinical correlation between retrovirus infection in cats and human AIDS (also caused by retrovirus) is striking. In fact, much of what we know about the FeLV infection in cats is applicable to aids in humans. It has been proposed that the disease FeLV causes be changed to FAIDS. It is well established today that far more cats die from immunosuppression caused by FeLV than die from tumors or leukemia. In fact, leukemia is a rare syndrome in cats infected with FeLV. In veterinary medicine, two sensitive and specific screening tests are available to diagnose the infection. The in-hospital diagnostic test kit (ELISA) is an excellent test used to detect the presence of FeLV virus antigen and/or FIV antibody. It is important to note that a positive test denotes infection. Confirmatory testing includes the IFA (indirect fluorescent antibody) for FeLV positive cats and the Western blot for FIV positive cats. The question then arises, once a cat has been determined to be positive for the virus, what are the consequences of infection and the risk of transmission to humans?

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Most statistics cite that FeLV positive cats (by IFA methods) will not live beyond three years from the time of detection. There are a small number of cats that can, in fact, live a normal life span despite being positive for the virus. However, these are rare. It is also possible that a very small number of positive cats may become FeLV negative after a period of months. Most FeLV positive cats are capable of transmitting the disease to other cats through bodily fluids, such as urine, blood, saliva. Saliva is the most important means of transmitting either virus among cats. To date, attempts to treat FeLV or FIV positive cats has not been successful. Attempts have included using anti-reverse transcriptase therapy as well as immunomodulation, eg, human alpha-interferon and Acemannan. None of these have proven effective. Temporary remission of solid tumors in the chest of cats has been accomplished using radiation or chemotherapy. However, this has resulted in only transient remission of clinical signs.

PUBLIC HEALTH CONSIDERATIONS During the past several months, FeLV has received a great deal of attention in the popular press. This has generated considerable concern among cat owners. This is particularly true among those who have or are in contact with FeLV-positive cats. Because FeLV is a contagious disease, considerable concern has been raised about the possible danger of FeLV infection in humans. In 1969, studies showed that FeLV would grow in human tissue in cell culture. In addition, injecting large doses of virus into newborn pups induced malignant lymphoma. Unfortunately, one epidemiological study linked prior contact with “sick cats” to subsequent development of childhood leukemia. However, there was no evidence to support the fact that “sick cats” had FeLV. Recentl y, veterinarians were shown to have a higher death rate from leukemia than a controlled population of physicians and dentists. Still, a definitive link to the FeLV virus has not been established. However, attempts to find FeLV or antibody to any of the FeLV components in humans have not been conclusive. No person has ever been found to be viremic with FeLV. Hence, the fact remains that no case of human leukemia has ever been linked to FeLV. ALTHOUGH IT IS IMPOSSIBLE TO PROVE A NEGATIVE HYPOTHESIS, NEITHER FeLV NOR FIV ARE REGARDED AS POSING A THREAT TO HUMAN HEALTH, REGARDLESS OF A PERSON’S HEALTH STATUS.

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Diaphragmatic hernia repair Ernie diaframmatiche

Theresa W. Fossum DVM, MS, PhD, Dipl ACVS - Texas A & M University, USA

TRAUMATIC DIAPHRAGMATIC HERNIAS

Radiography/Ultrasonography

General Considerations and Clinically Relevant Pathophysiology

Definitive diagnosis of pleuroperitoneal DH is via radiography or ultrasonography. Ultrasound examination of the diaphragmatic silhouette is helpful in animals in which the herniation is not obvious radiographically (i.e., hepatic herniation, pleural effusion). If significant pleural effusion is present, thoracentesis may be necessary for diagnostic radiographs. Radiographic signs of DH include loss of the diaphragmatic line, loss of the cardiac silhouette, dorsal or lateral displacement of lung fields, presence of gas or a bariumfilled stomach or intestines in the thoracic cavity, and pleural effusion. Positive-contrast celiography may occasionally be needed for the diagnosis. Prewarmed water-soluble contrast agent is injected into the abdominal cavity at a dosage of 1.1 ml/kg (dose is doubled if ascites is present), the patient is gently rolled from side to side or the pelvis is elevated, and films are taken immediately following the injection and manipulation. Criteria used in evaluating these films should include the presence of contrast medium in the pleural cavity, absence of a normal liver lobe outline in the abdomen, and incomplete visualization of the abdominal surface of the diaphragm. Positive-contrast celiograms should be interpreted cautiously since omental and fibrous adhesions may seal the defect, resulting in false negative films.

Diaphragmatic hernias (DH) are commonly recognized in small animal practices and may be congenital or occur following trauma. Congenital pleuroperitoneal hernias are seldom diagnosed in small animals because many affected animals die upon, or shortly after, birth. Most DH in dogs and cats are a result of trauma,particularly motor vehicle accidents. The location and size of the tear(s) depend on the position of the animal at the time of impact and location of the viscera. Traumatic DH are often associated with significant respiratory embarrassment; however, chronic DH in asymptomatic animals are not uncommon.

Diagnosis Signalment. There is no breed predisposition for traumatic DH; however, a majority of afflicted dogs are young males between 1 and 2 years of age. History. The duration of DH may range from a few hours to years. In one report 20% were diagnosed greater than 4 weeks after injury. The animals may be presented in shock following the injury. They often suffer from associated injuries, such as fractures. With chronic DH, clinical signs are most often referable to either the respiratory or gastrointestinal systems and may include dyspnea, exercise intolerance, anorexia, depression, vomiting, diarrhea, weight loss, and/or pain following ingestion of food.

Differential Diagnosis Any disorder that causes respiratory abnormalities (i.e., pleural effusion, pneumothorax, pneumonia, etc.) should be a differential for traumatic DH. The concurrent presence of pleural effusion in many animals with liver herniation may make diagnosis of DH difficult (see above).

Physical Examination Findings Animals with traumatic DH are frequently presented in shock; thus clinical signs may include pale or cyanotic mucous membranes, tachypnea, tachycardia, and/or oliguria. Cardiac arrhythmias are common and are associated with significant morbidity. Other clinical signs are dependent upon which organs herniate and may be attributed to the gastrointestinal, respiratory, or cardiovascular systems. The liver is the most common herniated organ and is often associated with hydrothorax due to entrapment and venous occlusion.

Medical Management If the animal is dyspneic, oxygen should be provided by face mask, nasal insufflation, or an oxygen cage. Positioning the animal in sternal recumbency with the forelimbs elevated may help ventilation. If moderate or severe pleural effusion is present, thoracentesis should be performed. Fluid therapy and antibiotics should be given if the animal is in shock.

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Surgical Treatment Traumatic DH have a higher mortality when surgery is performed either less than 24 hours or greater than 1 year following the injury. Surgical repair of DH should be delayed until the patient has been stabilized; however, herniorrhaphy should not be unnecessarily delayed. Animals with herniation of the stomach should be carefully evaluated for gastric distention and operated on as soon as they can safely be anesthetized because acute gastric distention within the thorax may cause rapid, fatal respiratory impairment.

Preoperative Management Prophylactic antibiotics should be given before anesthetic induction in animals with hepatic herniation. Massive release of toxins into the circulation may occur with hepatic strangulation or vascular compromise. Premedicating such patients with steroids may be beneficial. An ECG should be performed on all trauma patients before surgery.

Anesthesia Chamber or mask induction should be avoided in animals with DH. Before induction, supplementing the inspired oxygen will improve myocardial oxygenation. Because of the animalâ&#x20AC;&#x2122;s already compromised ventilation, drugs with minimal respiratory depressant effects should be used. Injectable anesthetics, which allow rapid intubation, are used for induction. Inhalation anesthetics should be used for anesthetic maintenance. Intermittent positive pressure ventilation should be performed and high inspiratory pressures avoided to help prevent reexpansion pulmonary edema. The lungs should be allowed to slowly expand after surgery. Nitrous oxide is contraindicated in patients with DH. Drugs such as methylprednisolone may be beneficial for preventing reexpansion pulmonary edema in animals with chronic DH.

Figure 1 - From: Fossum, TW: Small Animal Surgery, Mosby Publishing Co., St. Louis, Mo, 1997.

Suture Materials/Special Instruments For diaphragmatic closure use either a nonabsorbable suture material such as polypropylene or an absorbable material such as polydioxanone (PDS) or polyglyconate (Maxon) suture.

Surgical Techniques Postoperative Care and Assessment Make a ventral midline abdominal incision; if increased exposure is needed, extend the incision cranially through the sternum. Replace the abdominal organs in the abdominal cavity (if necessary, enlarge the diaphragmatic defect). If adhesions are present, dissect the tissues gently from thoracic structures to prevent pneumothorax or bleeding. With chronic hernias, debride the edge of the defect before closure. Close the diaphragmatic defect with a simple continuous suture pattern. If the diaphragm is avulsed from the ribs, incorporate a rib in the continuous suture for added strength (see Figure 1). Remove air from the pleural cavity following closure of the defect. If continued pneumothorax or effusion is likely, place a chest tube. Explore the entire abdominal cavity for associated injury (i.e., compromise of the vasculature to the intestine, splenic, renal, or bladder trauma) and repair any defects.

Patients should be monitored postoperatively for hypoventilation and oxygen provided, if necessary. Reexpansion pulmonary edema (RPE) is a potential complication associated with rapid lung reexpansion following DH repair. Postoperative analgesics should be provided.

Prognosis If the animal survives the early postoperative period (i.e., 12 to 24 hours) the prognosis is excellent, and recurrence is uncommon with proper technique. Reported mortality rates for animals with traumatic DH have varied from 12% to 48%. Reported survival rates for animals with traumatic DH who are treated surgically are close to 75%.

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PERITONEOPERICARDIAL DIAPHRAGMATIC HERNIAS General Considerations and Clinically Relevant Pathophysiology Peritoneopericardial diaphragmatic hernias (PPDH) are less commonly recognized by small animal clinicians than are traumatic diaphragmatic hernias. Although they are often associated with respiratory embarrassment, asymptomatic PPDH is common. PPDH may arise in human beings due to trauma (the diaphragm forms one wall of the pericardial sac in human beings); however, they are always congenital in dogs and cats because there is no direct communication between the pericardial and peritoneal cavities after birth. The most widely accepted theory regarding the embryogenesis of this defect is that the hernia arises because of faulty development or prenatal injury of the septum transversum. This could be a result of a teratogen, genetic defect, or prenatal injury. Cardiac abnormalities and sternal deformities often occur concomitantly with PPDH. The combination of congenital cranial abdominal wall, caudal sternal, diaphragmatic, and pericardial defects has been reported in dogs, often associated with ventricular septal defects or other intracardiac. It is not known whether this condition is heritable; however, several breed predispositions have been recognized (see below). Polycystic kidneys have been reported in association with PPDH in cats.

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clude an enlarged cardiac silhouette, dorsal elevation of the trachea, overlap of the heart and diaphragmatic borders, discontinuity of the diaphragm, gas-filled structures in the pericardial sac, sternal defects, and dorsal peritoneopericardial mesothelial remnants (see below). Contrast studies (i.e., nonselective angiogram, barium contrast study) should only be undertaken if a definitive diagnosis cannot be made on plain films or with ultrasound. Ultrasonography is useful because there is often discontinuity of the diaphragmatic outline. Hepatic herniation is usually evident.

Differential Diagnosis The most common differentials for PPDH are pericardial effusion and cardiomegaly. Ultrasound and echocardiography are useful to distinguish these abnormalities from PPDH.

Surgical Treatment Diagnosis Signalment. Although PPDH are congenital, it is not uncommon for the diagnosis to be made when the animal is middle-aged or older because clinical signs are variable and may be intermittent. Weimaraners and cocker spaniels may be at increased risk. History. Clinical signs may be referable to the gastrointestinal, cardiac, or respiratory systems and include anorexia, depression, vomiting, diarrhea, weight loss, wheezing, dyspnea, exercise intolerance, and/or pain following ingestion of food. Neurologic signs may occur due to hepatoencephalopathy.

Physical Examination Findings Physical examination findings in animals with PPDH may include ascites, muffled heart sounds, murmurs due to displacement of the heart by visceral organs or due to intracardiac defects, and concurrent ventral abdominal wall defects. The most commonly herniated organ is the liver, and associated pericardial effusion is common.

Radiography/Ultrasonography A tentative diagnosis of PPDH may be made based on history, clinical signs, and physical examination, but radiography and/or ultrasonography are essential for a definitive diagnosis. Radiographic signs of PPDH are presented in-

Surgical repair should be performed as early as possible (generally when the animal is between 8 and 16 weeks of age) when it is unlikely that adhesions will be present and the pliable nature of the skin, muscles, sternum, and rib cage facilitates closure of large defects. Early correction of PPDH may prevent acute decompensation and the potential development of acute postoperative pulmonary edema.

Preoperative Management Prophylactic antibiotics should be given before anesthetic induction in animals with hepatic herniation. Upon repositioning of the liver into the abdominal cavity of animals with hepatic strangulation or vascular compromise, a massive release of toxins into the bloodstream may occur. Premedicating such patients with steroids may be beneficial.

Anesthesia Chamber or mask induction should be avoided in animals with PPDH. Before induction, supplementing the inspired oxygen will improve myocardial oxygenation. If the animal’s ventilation is already compromised, drugs with minimal respiratory depressant effects should be used. Injectable anesthetics that allow rapid intubation are preferred. Inhalation anesthetics should be used for anesthetic maintenance. Intermittent positive pressure ventilation should be performed; however, high ventilatory pressures should be

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avoided to help prevent reexpansion pulmonary edema. The lungs should be allowed to slowly expand after surgery. Nitrous oxide is contraindicated in patients with diaphragmatic hernia. Drugs such as methylprednisolone may be beneficial in animals with chronic diaphragmatic hernias.

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For diaphragmatic closure use either a nonabsorbable suture material such as polypropylene or an absorbable material such as polydioxanone (PDS) or polyglyconate (Maxon) suture.

coesophageal ligament is lax or stretched and allows the gastroesophageal junction to be displaced through the hiatus into the caudal mediastinum. Malpositioning or lack of support of the gastroesophageal sphincter reduces gastroes o p h ageal sphincter pre s s u re and leads to ga s t ro esophageal reflux. Gastroesophageal reflux and subsequent esophagitis and megaesophagus are responsible for most of the clinical signs. Hiatal hernia is occasionally secondary to trauma and has occurred concurrently with respiratory distress. Trauma may damage diaphragmatic nerves and muscles, resulting in hiatal laxity and subsequent herniation. In patients with upper respiratory obstruction, reduced intrathoracic pressure during inspiration has been theorized to contribute to esophageal re fl u x and visceral herniation. Hiatal hernia has been reported with tetanus. With hiatal hernias, the stomach commonly slides in and out of the thorax. If the hernia is large enough, other abdominal viscera may also be cranially displaced into the thorax. Various types of hiatal abnormalities have been described. In patients with sliding or axial hiatal hernias, the gastroesophageal junction is located within the thoracic cavity. In patients with paraesophageal or rolling hiatal hernias, the gastroesophageal junction is usually located in a normal position and the gastric fundus or other abdominal viscerae are displaced through the hiatus and located within the thorax. Some hiatal hernias are a combination of sliding and paraesophageal hernias with the gastroesophageal junction and gastric fundus both displaced.

Postoperative Care and Assessment

Diagnosis

These patients should be monitored postoperatively for hypoventilation and oxygen provided, if necessary. Reexpansion pulmonary edema (RPE) is a potential complication associated with rapid lung reexpansion following diaphragmatic hernia repair. Pulmonary hypoplasia may be present in patients with PPDH, contributing to the development of high intrapleural pressures and RPE. Postoperative analgesics should be provided.

Signalment. Hiatal hernias may occur in a variety of dog and cat breeds; however, males and Chinese Shar-pei dogs appear to be predisposed to this condition. Most symptomatic animals have signs relating to congenital hiatal hernia before reaching 1 year of age, although diagnosis may occur later. Patients with acquired hernias may develop signs at any age. History. Regurgitation is the primary clinical sign in symptomatic individuals, but many patients are asymptomatic. Other signs may include vomiting, hypersalivation, dysphagia, respiratory distress, hematemesis, anorexia, and weight loss.

Surgical Techniques Make a ventral midline abdominal incision. If increased exposure is needed, extend the incision cranially through the sternum. Enlarge the diaphragmatic defect if necessary, and replace the abdominal organs in the abdominal cavity. If adhesions are present, gently dissect the tissues from thoracic structures, resecting or debriding necrotic tissue as necessary. Debride the edges of the defect and close with a simple continuous suture pattern. Do not close the pericardial sac. Remove air from the pericardial sac and/or pleural cavity following closure of the defect. If continued pneumothorax or effusion is likely, place a chest tube. Repair concomitant sternal or abdominal wall defects.

Suture Materials/Special Instruments

Prognosis If the animal survives the early postoperative period (i.e., 12 to 24 hours) the prognosis is excellent and recurrence is uncommon with proper technique. The prognosis is worse in patients with PPDH who have concurrent cardiac abnormalities.

Physical Examination Findings

HIATAL HERNIAS

Radiography/Ultrasonography

General Considerations and Clinically Relevant Pathophysiology

Hiatal hernias usually appear as a mass near the esophageal hiatus in the caudodorsal thoracic region on survey radiographs. However, with sliding hernias, several radiographs may be necessary to identify the herniation because herniation may be intermittent. The presence of gas in the herniated portion aids in identification of the

Hiatal hernias are usually caused by congenital abnormalities of the hiatus that allow cranial movement of the abdominal esophagus and stomach. The phre n i-

Affected patients may be thin upon physical examination.

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mass as herniated stomach. Varying degrees of megaesophagus and pneumonia may be noted. A positive contrast esophagram should show the gastroesophageal junction, rugal folds, or both cranial to the hiatus. Occasionally, strictures may be identified. Fluoroscopy may demonstrate hypomotility, delayed clearing of the distal esophagus, or gastroesophageal reflux. Compressing the abdomen while observing fluoroscopy may help identify hernias. Esophagoscopy can confirm mild to severe esophagitis (inflammation, mucosal erosion), gastric reflux, or strictures. Gastric mucosa that has entered the thoracic cavity can sometimes be identified. Some hiatal hernias are intermittent (sliding) and require multiple radiographs and/or flouroscopy to diagnose. Do not confuse hiatal hernias with peritoneopericardial or traumatic diaphragmatic hernias, despite their sometimes having a similar radiographic appearance.

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Anesthesia Positive pressure ventilation may be necessary if pneumothorax is created during hiatal manipulations. Nitrous oxide should not be used in these patients. Negative intrathoracic pressure is reestablished by thoracentesis or tube thoracostomy after hiatal manipulations are complete.

Surgical Anatomy

Esophageal stricture, neoplasia, extraluminal masses, vascular ring anomaly, esophageal foreign body or perforation, esophagitis,esophageal intussusception, esophageal diverticulum,and megaesophagus are other potential causes of regurgitation.

The esophageal hiatus is one of three openings in the diaphragm. The esophageal hiatus is more centrally located than the caval foramen (located ventrally) or aortic hiatus (located dorsally). The esophagus passes through the esophageal hiatus along with the vagal nerve trunks and esophageal vessels. The esophageal hiatus is surrounded by the phrenicoesophageal ligament, the thickened collagen fibers of which are weakened, stretched, or in some way defective in hiatal hernias. The terminal 1 to 2 cm of the esophagus lies within the abdominal cavity caudal to the diaphragm. The esophagogastric junction and gastroesophageal sphincter are in the abdomen and regulate movement of ingesta between the esophagus and stomach.

Surgical Treatment

Surgical Technique

Affected patients may benefit from medical treatment for ga s t ro e s o p h ageal reflux or esophagitis; however, surgery is generally recommended in symptomatic animals with congenital disease. A number of surgical techniques have been described for correction of this condition. Diap h rag m atic hiatal reduction and plicat i o n , esophagopexy, and left-sided fundic gastropexy are described here. Gastropexy is probably the most important step in the repair. If esophagitis is severe and oral intake is to be prohibited for several days, a tube gastropexy. allows early alimentation without further esophageal irritation. Sphincter enhancing procedures such as a Nissen fundoplication (antireflux procedure) are performed by some surgeons instead of the aforementioned techniques. However, fundoplication or other antireflux procedures are only indicated in patients with evidence of gastroesophageal reflux. In dogs and cats, p ri m a ry incompetence of the caudal esophageal sphincter has not been documented in association with hiatal hernia, and therefore antireflux procedures are not routinely recommended.

Make a cranial ventral midline incision extending caudal to the umbilicus to expose the diaphragm and stomach. Retract the left lobes of the liver medially to expose the esophageal hiatus. Pass a stomach tube (28-32 French) to help identify and manipulate the esophagus. Grasp the stomach and reduce the hernia with gentle traction. Examine the hiatus. Dissect the phrenicoesophageal membrane, freeing the esophagus from the diaphragm ventrally. Preserve the vagal trunks and esophageal vessels during dissection. Place an umbilical tape sling around the abdominal esophagus to displace it caudally and facilitate manipulations. Perform a diaphragmatic hiatal plication/reduction, esophagopexy, and left-sided fundic gastropexy. Accomplish diaphragmatic hiatal plication/reduction by excoriating or debriding the margins of the hiatus and then place three to five sutures (2-0 polydioxanone or polypropylene) to appose the edges and narrow the hiatus. Plication should occur around a large stomach tube (28-32 French). The hiatus is reduced to 1 or 2 cm, a size that allows passage of one finger. Esophagopexy is accomplished by placing sutures (3-0 or 2-0 polydioxanone or polypropylene) from the remaining margin of the hiatus through the adventitia and muscular layers of the abdominal esophagus. Either a left-sided tube gastropexy or incisional gastropexy completes the repair. The fundus is fixed with slight to moderate caudal traction to prevent cranial movement of the gastroesophageal junction into the thorax. Evacuate air from the chest via thoracentesis or tube thoracostomy and lavage and close the abdomen.

Differential Diagnosis

Preoperative Management Reflux esophagitis and aspiration pneumonia should be treated before anesthetic induction. Feeding frequent, small meals of high-protein/low-fat foods may be beneficial. If megaesophagus is present, feeding affected animals in a standing, upright position may decrease regurgitation.

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Postoperative Care and Assessment Patients should be postoperatively monitored for dyspnea resulting from pneumothorax and air should be evacuated from the thorax as necessary. Nasal oxygen may benefit dyspneic animals. Analgesics should be provided as necessary to control pain. Affected animals may continue to regurgitate after surgery because of persistent esophagitis. Treatment of esophagitis and aspiration pneumonia should be continued postoperatively. Feeding from an elevated platform may be beneficial in animals with concurrent megaesophagus. Postoperative radiographic studies may be beneficial in patients with persistent clinical signs to identify persistent herniation, obstruction, or ulceration.

Complications Dysphagia is common for several days; however, if it continues beyond that time, the hiatus may have been

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over-reduced, requiring reoperation. Infection may occur if the esophageal or gastric lumen is penetrated with sutures or tubes. Potential problems after antireflux procedures include gastric dilatation, necrotic gastritis, and acute death.

Prognosis Objective data comparing medical and surgical treatment in animals with hiatal hernias is not available. The prognosis without surgery is good in asymptomatic patients; however, symptomatic patients who are not surgically repaired may develop severe esophagitis and stricture. The prognosis is good with the described surgical repair; however, aspiration pneumonia must be controlled for a favorable outcome. Patients with ga s t ro e s o p h ageal sphincter incompetence may benefit from additional antireflux procedures.

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Pleural effusion: chylothorax and pyothorax Versamenti pleurici: chilotorace e piotorace

Theresa W. Fossum DVM, MS, PhD, Dipl ACVS - Texas A & M University, USA

CHYLOTHORAX General Considerations and Clinically Relevant Pathophysiology In most animals, abnormal flows or pressures within the thoracic duct (TD) are thought to lead to exudation of chyle from intact, but dilated, thoracic lymphatic vessels (known as thoracic lymphangiectasia). These dilated lymphatic vessels may form in response to increased lymphatic flows (due to increased hepatic lymph formation), decreased lymphatic drainage into the venous system because of high venous pressures, or both factors acting simultaneously to increase lymph flows and decrease drainage. Any disease or process that increases systemic venous pressures (i.e., right heart failure, mediastinal neoplasia, cranial vena cava thrombi, or granulomas) may cause chylothorax. Trauma is an uncommonly recognized cause of chylothorax in dogs and cats because the TD heals rapidly following injury and within 1 to 2 weeks the effusion resolves without treatment. Possible causes of chylothorax include anterior mediastinal masses (mediastinal lymphosarcoma, thymoma), heart disease (cardiomyopathy, pericardial effusion, heartworm infection, foreign objects, tetralogy of Fallot, tricuspid dysplasia, or cor triatriatum dexter), fungal granulomas, venous thrombi, and congenital abnormalities of the TD. It may occur in association with diffuse lymphatic abnormalities including intestinal lymphangiectasia and generalized lymphangiectasia with subcutaneous chyle leakage. In a majority of animals, despite extensive diagnostic work-ups, the underlying etiolo gy is undetermined (idiopathic chylothorax). Because the treatment of this disease varies considerably depending on underlying etiology, it is imperative that clinicians identify concurrent disease processes prior to instituting definitive therapy.

Diagnosis Signalment. Any breed dog or cat may be affected; however, a breed predisposition has been suspected in the Afghan Hound for a number of years. More recently it has been suggested that the Shiba Inu breed may also be predisposed to this disease. Among cats, Oriental breeds (i.e., Siamese and Himalayan) appear to have an increased prevalence. Chylothorax may affect animals of any age; however, in one study older cats were more likely to develop chy-

lothorax than were young cats. This finding was believed to be indicative of an association between chylothorax and neoplasia. While Afghan hounds appear to develop this disease when middle-aged, affected Shiba Inu's have been less than one year of age. A sex predisposition has not been identified. History. Coughing is often the first (and occasionally the only) abnormality noted by owners until the animal becomes dyspneic. Many owners report that they first noticed coughing months prior to presenting the animal for veterinary care; therefore, animals that cough and do not respond to standard treatment of nonspecific respiratory problems should be evaluated for chylothorax. Coughing may be a result of irritation caused by the effusion, or may be related to the underlying disease process (i.e., cardiomyopathy, thoracic neoplasia).

Physical Examination Findings The most common physical examination finding in animals with pleural effusion is dyspnea. The dyspnea may be marked by a forceful inspiration with delayed expiration, making the animal appear to be holding it's breath. This respiratory pattern is particularly noticeable in cats. Increased bronchovesicular sounds may be heard dorsally and lung sounds may be absent ventrally (usually bilaterally, but occasionally unilaterally). Most animals with chylothorax present with a normal body temperature, unless extremely excited or severely depressed. Additional findings in patients with chylothorax may include muffled heart sounds, depression, anorexia, weight loss, pale mucous membranes, arrhythmias, murmurs, and pericardial effusion.

Radiography/Ultrasonography If the animal is not overtly dyspneic, thoracic radiographs should be taken to confirm the diagnosis of pleural fluid. Taking dorsoventral (rather than ventrodorsal views) and "standing lateral" radiographic views, minimizing handling, and supplementing oxygen by face mask during the radiographic procedures may help prevent further compromise of respiration. If the animal is not dyspneic and only small amounts of fluid are suspected, ventrodorsal and expiratory views may help delineate the effusion. Radiographic signs associated with pleural effusion include blurring of the cardiac silhouette, interlobar fissure lines, rounding of lung

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margins at the costophrenic angles, widening of the mediastinum, separation of the lung borders from the thoracic wall, and scalloping of the lung margins at the sternal border. The latter may be the earliest radiographic sign of pleural effusion. Ultrasonography should be performed prior to fluid removal because the fluid acts as an "acoustic window" enhancing visualization of thoracic structures. Ultrasonography is used to evaluate cardiac function, valvular lesions and function, congenital cardiac abnormalities, the presence of pericardial effusion, and mediastinal masses. The presence of pleural fluid will often prevent satisfactory radiographic evaluation of the structures of the thoracic cavity. Since adequate visualization of the entire thorax is necessary in order to rule out anterior mediastinal masses such as lymphosarcoma or thymoma, radiographs should be repeated following removal of most of the pleural fluid. Animals that have collapsed lung lobes that do not appear to re-expand following removal of pleural fluid should be suspected of having underlying pulmonary parenchymal or pleural disease, such as fibrosing pleuritis. Although the etiology of the fibrosis is unknown, it apparently can occur subsequent to any prolonged exudative or blood-stained effusion. Diagnosis of fibrosing pleuritis is difficult. The atelectatic lobes may be confused with metastatic or primary pulmonary neoplasia, lung lobe torsion, or hilar lymphadenopathy. Radiographic evidence of pulmonary parenchyma that fails to re-expand after removal of pleural fluid should be considered possible evidence of atelectasis with associated fibrosis. Fibrosing pleuritis should also be considered in animals with persistent dyspnea in the face of minimal pleural fluid.

Laboratory Findings Fluid recovered by thoracentesis should be placed in an EDTA tube for cytologic examination. Placing the fluid in an EDTA tube rather than a "clot-tube" will allow cell counts to be performed. Although chylous effusions are routinely classified as exudates, the physical characteristics of the fluid may be consistent with a modified transudate. The color varies depending on fat content of the diet and the presence of concurrent hemorrhage. The protein content is variable and often inaccurate due to interference of the refractive index by the high lipid content of the fluid. The total nucleated cell count is usually less than 10,000 and consists primarily of small lymphocytes or neutrophils, with lesser numbers of lipid-laden macrophages. Chronic chylous effusions may contain low numbers of small lymphocytes due to the inability of the body to compensate for continued lymphocyte loss. Non-degenerative neutrophils may predominate with prolonged loss of lymphocytes or if multiple therapeutic thoracocenteses have induced inflammation. Degenerative neutrophils and sepsis is an uncommon finding due to the bacteriostatic effect of fatty acids, but can occur iatrogenically due to repeated aspirations. To help determine if a pleural effusion is truly chylous, several tests can be performed including comparison of fluid and serum triglyceride levels, Sudan III stain for lipid

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droplets, and ether clearance test. The most diagnostic test is comparison of serum and fluid triglyceride levels. If the effusion is truly chylous it will contain a higher concentration of triglycerides than simultaneously collected serum.

Differential Diagnosis Any cause of respiratory distress or coughing should be considered a differential diagnosis. Once pleural effusion has been identified, differentials include diseases causing exudative pleural effusion, such as pyothorax. Although chylous effusions have a characteristic appearance, the physical characteristics of chylous effusions and other exudative ef fusions may be similar. Additionally, the appearance and cell populations of chylous effusions can be altered by diet and chronicity. "Pseudochylous effusion" is a term that has been misused in the veterinary literature to describe effusions that look like chyle, but in which a ruptured TD is not found. Given the known causes of chylothorax in dogs and cats, this term should be reserved for effusions in which the pleural fluid cholesterol is greater than the serum cholesterol concentration and the pleural fluid triglyceride is less than or equal to the serum triglyceride. Pseudochylous effusions are extremely rare in veterinary patients, but may be associated with tuberculosis.

Medical Management If an underlying disease is diagnosed it should be treated and the chylous effusion managed by intermittent thoracocentesis. If the underlying disease is effectively treated the effusion often resolves; however, complete resolution may take several months. Surgical intervention should be considered only in animals with idiopathic chylothorax, or those that do not respond to medical management. Chest tubes should only be placed in those animals with suspected chylothorax secondary to trauma (very rare!), with rapid fluid accumulation, or following surgery. Electrolytes should be monitored as hyponatremia and hyperkalemia have also been documented in dogs with chylothorax undergoing multiple thoracentesis. A low-fat diet may decrease the amount of fat in the effusion, which may improve the animal's ability to resorb fluid from the thoracic cavity. Commercial low fat diets are preferable to homemade diets; however, if commercial diets are refused, homemade diets are a reasonable alternative (see Fossum, Small Animal Surgery). Medium chain triglycerides (once thought to be absorbed directly into the portal system, bypassing the TD) are transported via the TD of dogs. Thus, they may be less useful than previously believed. It is unlikely that dietary therapy will "cure" this disease, but it may help in the management of animals with chronic chylothorax. Clients should be informed that with the idiopathic form of this disease there is no effective treatment that will stop the effusion in all animals. However, the condition may spontaneously resolve in some animals after several weeks or months. Benzopyrone drugs have been used for the treatment of

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lymphedema in people for years. Whether these drugs might be effective in decreasing pleural effusion in animals with chylothorax is not known; however, preliminary findings suggest that > 25% of animals treated with Rutin (Table 1) had complete resolution of their effusion at 2 months after initiation of therapy. Determination of whether the effusion resolved spontaneously in these animals, or was associated with the drug therapy requires further study.

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Surgical Anatomy The TD is the cranial continuation of the cisterna chyli and is generally said to begin between the crura of the diaphragm. In cats the TD lies between the aorta and azygous vein on the left side of the mediastinum; whereas, in dogs it lies on the right side of the mediastinum until it reaches the 5th or 6th vertebrae, then it crosses to the left side. The TD terminates in the venous system of the neck (left external jugular vein or jugulo-subclavian angle).

Surgical Treatment Positioning Surgical intervention may be warranted in animals that do not have underlying disease and in whom medical management becomes impractical or is ineffective. Surgical options in animals that do not have severe fibrosing pleuritis include mesenteric lymphangiography and TD ligation, passive pleuroperitoneal shunting, active pleuroperitoneal or pleurovenous shunting, and pleurodesis. Only TD ligation and active pleuroperitoneal shunting will be described here. The mechanism by which TD ligation is purported to work is that following TD ligation abdominal lymphaticovenous anastomoses form for the transport of chyle to the venous system. Therefore, chyle bypasses the TD and the effusion resolves. Unfortunately, TD ligation results in complete resolution of pleural effusion in only about 50% of animals operated. The advantage of TD ligation is that if it is successful it results in complete resolution of pleural fluid (as compared to palliative procedures such as passive or active pleuroperitoneal shunting). Disadvantages include that operative time is long (which is problematic in debilitated animals), there is a high incidence of continued or recurrent chylous or nonchylous (from pulmonary lymphatics) effusion, and mesenteric lymphangiography may be difficult to perform (particularly in cats). Without mesenteric lymphangiography, complete ligation of the TD cannot be assured; however, this technique may not be uniformly successful in verifying complete ligation of the TD. Some small branches of the TD system may be present and yet not fill with dye during lymphangiography.

Preoperative Management Food is withheld 12 hours prior to surgery. Cream or oil may be fed 3 to 4 hours prior to surgery to help visualize lymphatics, or alternately, methylene blue may be injected into a lymph node at surgery.

If a thoracic approach to the TD is used (see below), the left side (cats) or right side (dogs) of the thorax and abdomen are prepared for aseptic surgery. If a transdiaphragmatic approach is used, the cranial abdomen and caudal chest are prepped.

SURGICAL TECHNIQUE Mesenteric Lymphangiography For a thoracic approach,make a left paracostal incision (or for a transdiaphragmatic approach make a cranial midline ab dominal incision), exteriorize the cecum, and locate an adja cent lymph node. If necessary, inject a small volume (0.5 - 1 ml) of methylene blue into the lymph node to increase lymphatic vi sualization. Avoid repeated doses of methylene blue due to the risk of inducing a Heinz body anemia or renal failure. Find a lymphatic near the node to catheterize by gently dissecting the mesentery. Cannulate the lymphatic with a 20 or 22-gauge over-the-needle catheter and attach a 3-way catheter and ex tension tubing (filled with heparinized saline) to the catheter with a suture (3-0 silk). Place an additional suture around the extension tubing and through a segment of intestine to prevent dislodgement of the catheter. Dilute 1 ml/kg of a water soluble contrast agent (i.e., Renovist7) with 0.5 ml/kg of sterile saline. Inject this mixture into the catheter and take a lateral thoracic radiograph while the last ml is being flushed into the catheter. Use this lymphangiogram to help identify the number and lo cation of branches of the TD which need to be ligated. Repeat the lymphangiogram following TD ligation (see below) to iden tify branches that were not occluded. Embolization of the TD with cyanoacrylate injected through a mesenteric lymphatic catheter has been reported in dogs. Advantages of TD embolization are that direct visualization of the TD is not required which negates the need for a thoracotomy or diaphragmatic incision. Disadvantages of this procedure are the same as those for mesenteric lymphangiography and TD ligation (i.e., not all TD branches may fill with the cyanoacrylate mixture and collateralization may occur past the obstruction).

Table 1 - Benzopyrones for treatment of chylothorax* Rutin**- 50 mg/kg; PO; TID

Thoracic Duct Ligation

* efficacy is unproven at this time **obtained at health food stores

Perform an intercostal thoracotomy (right side for dogs, left side for cats) at the 8th, 9th, or 10th intercostal space or make an incision in the diaphragm (see note above). Locate

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the TD and use hemostatic clips and/or silk (2-0 or 3-0) su ture to ligate it (see below). Visualization of the TD can be aided by injecting methylene blue into the lymphatic catheter.

Active Pleuroperitoneal or Pleurovenous Shunting Commercially made shunt catheters (see below for ordering information) are available and can be used to pump pleural fluid into the abdomen (Figure 1) or into a vein (i.e., jugular, azygous, caudal vena cava). Two types of shunts are available: a pleuroperitoneal shunt (Table 2) and an ascites (peritoneovenous) shunt (Table 3). The latter is meant to pump fluid from the abdomen into a vein and does not require manual pumping (i.e., it acts in an active fashion). This shunt can be placed from the pleural space into a vein (pleurovenous); when used in this manner, manual pumping is required (the shunt will not act in an active fashion). A potential complication of pleurovenous shunt placement is formation of a right atrial and/or ventricular thrombi. This complication may be life-threatening; therefore, pleuroperitoneal shunting is preferred if there is no reason to believe that the animal may not reabsorb the fluid from its abdominal cavity (e.g., presence of diffuse lymphatic disease or cardiac dis-

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Table 2 - Pleuro-peritoneal shunt specifications* ! 27 cm fenestrated pleural end ! two one-way valves ! 49 cm fenestrated peritoneal catheter ! each complete pump of the reservoir dome transfers 1.5 ml of fluid *Denver Biomaterials, Inc. (800-824-8454).

Table 3 - Pleurovenous (peritoneo-venous) shunt specifications* ! 27 cm fenestrated pleural end ! single or double one-w ay valves** ! 66 cm fenestrated venous catheter ! double valve: comes in a standard flow rate (26-40 ml/min at 10 cm head of water) and a low flow rate (< 26 ml/min at 10 cm head of water) * Denver Biomaterials, Inc. **This shunt comes in a single and double-valve form; the double valve catheter is indicated when placed in a pleurovenous fashion.

Figure 1 - From: Fossum, TW: Small Animal Surgery, Mosby Publishing Co., St. Louis, MO, 1997.

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ease). Close observation of these patients for several weeks following pleurovenous shunt placement is necessary and preoperative heparinization and maintenance on heparin, aspirin, or other anticoagulants may be warranted. Pleuroperitoneal shunts go from the pleural space to the abdomen. They are generally safer than pleurovenous shunts. Both types of catheters are placed under general anesthesia. Place the pump chamber and tubing in a bowl of steril ized, heparinized saline. Prime the pump by compressing the valve repeatedly until the system is filled with fluid and flow is established. Expel any remaining air bubbles from the tub ing or valve. Make a vertical incision over the middle of the 6th, 7th, or 8th rib. Bluntly insert the pleural end of the shunt catheter into the thoracic cavity. For a pleuroperitoneal shunt, create a tunnel under the external abdominal oblique muscle using blunt dissection and pull the pump chamber through the tunnel. Place the efferent (peritoneal) end of the catheter into the abdominal cavity just caudal to the costal arch through a small skin incision and a preplaced pursestring suture in the abdominal musculature. For a pleurove nous shunt, tunnel the efferent (venous) end of the catheter over the shoulder to the ventral cervical region. Make a small incision over the jugular vein and insert the venous end of the catheter into the vein. Using fluoroscopy, place the distal end of the catheter at the caudal aspect of the cra nial vena cava, just proximal to the right atrium (the venous end of the catheter may be shortened if necessary). Alternately, the venous end of the catheter may be placed in the azygous or caudal vena cava through an ab dominal incision. Make sure that the pump chamber overlies a rib so that the chamber can be effectively compressed.

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signs may be not be obvious as long as the animal is receiving antibiotics. Despite the disease warranting a guarded prognosis in most cases, with prompt and aggressive therapy successful treatment is possible.

Etiology The route by which the pleura becomes infected is usually not evident. Possible routes of infection include hematogenous spread, migrating foreign objects such as plant awns, penetrating wounds (particularly bite wounds in cats), extension from diskospondylitis, extension from pneumonia (e.g. aspiration pneumonia), pulmonary neoplasia and abscessation, pulmonary or thoracic wall trauma, and post operative infection. Although diseases that result in immunosuppression (e.g. FeLV and FIV) should be excluded in animals with pyothorax, there is no evidence that development of this disease requires debilitation or an increased susceptibility to infection. Although there is no known breed predisposition, medium to large breed dogs (especially sporting breeds) have a high incidence of this disease.

Clinical Signs and Physical Exam Findings Pyothorax frequently has an insidious onset and any known trauma often occurred weeks prior to presentation. Most animals present for evaluation of dyspnea. Additional signs are those associated with systemic infection: elevated temperature, anorexia, lethargy, and weight loss. Occasionally owners report episodes of coughing or "choking". Physical examination and radiographic findings are those of pleural effusion.

Postoperative Care and Assessment If chylothorax resolves spontaneously or after surgery, periodic reevaluations for several years are warranted to detect recurrence. Fibrosing pleuritis is the most common, serious complication of chronic chylothorax. Immunosuppression may occur in patients undergoing repeated and frequent thoracentesis due to lymphocyte depletion.

Prognosis This condition may resolve spontaneously or following surgery. Untreated or chronic chylothorax may result in severe fibrosing pleuritis and persistent dyspnea. Euthanasia is frequently performed in animals that do not respond to surgery or medical mana gement.

PYOTHORAX Pyothorax, or purulent pleuritis, is the result of either a bacterial, viral, or fungal infection of the pleural space. Although dry pleuritis occurs in animals it is seldom recognized clinically. Lack of appropriate initial therapy of this disease is usually associated with chronic recurrent infection; such animals are often euthanized even though clinical

Diagnosis Hematologic examination of affected animals often shows an elevated white blood cell count and WBC toxicity may be noted in some animals; however, a normal leukogram does not preclude a diagnosis of pyothorax. Empyematous fluid is generally a thick, creamy purulent exudate, which varies in color and is often flocculent. Because pyothorax is frequently associated with anaerobic bacteria the exudate is often foul-smelling. Obligate anaerobes are commonly isolated when proper anaerobic culture techniques are used (see below). In cats, Bacteroides, Pasteurel la, Fusobacterium, Actinomyces, and Clostridium are the most frequent isolates. The bacteria most commonly isolated from canine pyothorax exudates are Actinomyces, Bac teroides, and Fusobacterium. Because many treatment failures in pyothorax are due to lack of recognition of anaerobes, care should be taken to identify and appropriately treat these organisms. Although Nocardia has previously be reported as a common finding in dogs with pyothorax most of these were probably due to Actinomyces viscosus. Examination of gram-stained smears is essential with pyothorax because anaerobes are often very difficult to culture. The specimen should be examined under low power for the presence of neutrophils. If multiple, different forms of bacteria

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are found, without neutrophils, the specimen may have been contaminated by normal flora. Once bacteria have been located, they should be examined under oil immersion. Anaerobic infections should be suspected whenever multiple morphologic forms of organisms are seen on a gram-stained smear. Since aerobes and facultative anaerobes often outgrow obligate anaerobes, delays in culturing collected specimens may allow overgrowth of these organisms. Specimens should be preserved in commercially prepared CO2 containers or inserted into semisolid transport media. Aspirated materials should be promptly inoculated onto media since oxygen can diffuse through the walls of plastic syringes.

The addition of antibiotics to the lavage fluid offers no advantage over the use of appropriate systemic antibiotics. If they are used, the systemic dose should be decreased in order to minimize toxicity. The use of proteolytic enzymes is controversial and is no longer recommended by most authors. However, the addition of heparin (1500 units/100 ml of lavage) appears to be beneficial. Lavage may be required for 5-7 days. If no improvement occurs during this time period an underlying etiology (such as a foreign body) should be aggressively sought.

Decortication Management Management of these animals needs to be aggressive. Following the diagnosis, a chest tube should be placed. If available, continuous suction devices are ideal, however, most animals can be managed with intermittent aspiration. Lavage should be performed 3 or 4 times daily. Isotonic fluid, such as saline or lactated Ringer's solution (warmed to room temper ature) should be used at a dosage of 10 ml/kg body weight. The fluid is allowed to remain in the thoracic cavity for one hour and is then removed.

If the pyothorax is chronic or localized, or the patient remains dyspneic in the absence of significant volumes of pleural fluid, surgical intervention may be warranted. Long standing empyema may resorb, leaving a pleural "peel" which is a thick sheet of fibroblasts and inflammatory cells attached to the visceral pleurae. This pleural peel may inhibit normal expansion of the lung tissue. Decortication is recommended in human beings if lung entrapment is suspected. Decortication should be performed once the empyema is mature, but before it adheres to the pleura and becomes vascularized (3 - 4 weeks is recommended).

CHARACTERISTICS OF BACTERIA THAT COMMONLY CAUSE PYOTHORAX

BACTERIA

OXYGEN REQUIREMENTS

GRAM'S STAIN

Actinomyces

Facultative anaerobe

Bacteroides

Obligate anaerobe

MORPHOLOGY

ANTIBIOTIC SENSITIVITY

gram-negative

small rods; may form filaments; often beaded and difficult to discern in clinical specimens; may form sulfur granules

Penicillin (includes penicillin G, ampicillin and amoxicillin), cephalosporin, clindamycin, chloramphenicol, erythromycin

gram-negative

bacilli; pleomorphic and may be beaded or cocci, often stain poorly and are difficult to see

most Bacteroides - penicillin, cephalosporin, clindamycin, chloramphenicol, metronidazole fragilis - amoxicillin + clavulonic acid , clindamycin, chloramphenicol, metronidazole

Clostridium

Facultative anaerobe

gram-positive

rods; large, freguently most Clostridium - penicillin, encapsulated, motile, spores chloramphenicol, metronidazole uncommon from clinical specimens perfringens - penicillin, cefoxitin, clindamycin, chloramphenicol, metronidazole, erythromycin

Fusobacterium

Obligate anaerobe

gram-negative

bacilli; often have a cigar-shaped appearance

penicillin, clindamycin, chloramphenicol, metronidazole

Klebsiella

Facultative anaerobes

gram-negative

rods; mucoid and encapsulated

cephalosporin, gentamicin, tobramycin, ticarcillin

Pasteurella

Facultative anaerobe

gram-negative

coccobacilli; pleomorphic, bipolar staining

penicillin, ampicillin

Pseudomonas

Aerobe

gram-negative

rods; slender, motile

carbenicillin, gentamicin, tobramycin, amikacin, ticarcillin, cefotaxime, moxalactam

bolded type = drug of choice

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Trauma of the respiratory tract Traumi a carico dell’apparato respiratorio

Theresa W. Fossum DVM, MS, PhD, Dipl ACVS - Texas A & M University, USA

TRACHEAL TRAUMA

PNEUMOTHORAX

Tracheal trauma is uncommon but may occur secondary to bite wounds, gunshot wounds, endotracheal intubation, or other injury. Small lacerations will often heal on their own with conservative therapy; however, the sequelae of tracheal trauma may be stricture or severe acute respiratory distress necessitating temporary tracheostomy or tracheal resection and anastomosis.

Pneumothorax is an accumulation of air or gas within the pleural space. Traumatic pneumothorax may be classified either as “open” or “closed”. An open pneumothorax is one in which there is free communication between the pleural space and the external environment. With a closed pneumothorax, air accumulates due to leakage from the pulmonary parenchyma, bronchial tree, or esophagus. A tension pneumothorax occurs when a flap of tissue acts as a one-way valve so that there is a continuous influx of air into the pleural cavity on inspiration which does not return to the lung on expiration. Spontaneous pneumothorax occurs due to air leakage from the lung, but without trauma as a precipitating cause. Cysts are closed cavities or sacs lined by epithelium and are usually filled with fluid or semi-solid material. Bullae are non-epithelialized cavities produced by disruption of intra-alveolar septae. A bleb is a localized collection of air that is contained within the visceral pleura. Traumatic pneumothorax is the most frequent type of pneumothorax in dogs. It most often occurs due to blunt trauma (i.e., vehicular accidents, being kicked by a horse), which causes parenchymal pulmonary damage to the lung and a closed pneumothorax. When the thorax is forcefully compressed against a closed glottis, rupture of the lung or bronchial tree may occur. Alternately, pulmonary parenchyma may be torn due to shearing forces on the lung. Pulmonary trauma occasionally results in subpleural bleb formation,similar to those seen with spontaneous pneumothorax. Open pneumothorax occurs less commonly, but is also frequently due to trauma (i.e., gun shot, bite or stab wounds, lacerations secondary to rib fractures). Some penetrating injuries are called “sucking chest wounds” because large defects in the chest wall allow an influx of air into the pleural space when the animal inspires. These large, open chest wounds may allow enough air to enter the pleural space that lung collapse and marked reduction in ventilation occur. There is a rapid equilibration of atmospheric and intrapleural pressure through the defect, interfering with normal mechanical function of the thoracic bellows which normally provides the necessary pressure gradient for air exchange. Pneumomediastinum may be associated with pneumothorax, tracheal, bronchial, or esophageal defects, or may be due to subcutaneous air migration along fascial planes at the thoracic inlet. Spontaneous pneumothorax occurs in previously healthy animals without antecedent trauma and may be primary (i.e., an absence of underlying pulmonary disease) or secondary

Temporary Tracheostomy Tracheostomy allows air to enter the trachea distal to the nose, mouth, nasopharynx, and larynx. A tracheotomy is performed, and either a tube is inserted (temporary tracheostomy) or a stoma is created (permanent tracheostomy) to facilitate airflow. A nonreactive tube that is no larger than one half the size of the trachea should be selected. Cuffed or cannulated autoclavable silicone, silver, or nylon tubes are recommended. Polyvinyl chloride and red rubber tubes are irritating and should be avoided. If the animal is being placed on a respirator, a cuffed tube is necessary. Temporary tracheostomy is most commonly performed to provide an alternate airflow route during surgery or as an emergency p ro c e d u re in seve re ly dyspneic patients. Tube tracheostomies are usually maintained for a short time. Make a ventral midline incision from the cricoid cartilage extending 2 to 3 cm caudally. Separate the sternohyoid muscles and make a horizontal (transverse) tracheotomy through the annular ligament between the third and fourth or fourth and fifth tracheal cartilages. Do not extend the incision around more than half the circumference of the trachea. Alternatively, make a vertical tracheotomy across the ventral midline of cartilages 3 through 5. Suction blood and mucus from the lumen, widen the incision, and insert the tracheostomy tube. Facilitate tube placement by encircling a cartilage distal or lateral to the incision with a long stay suture. Place tension on this suture to open the incision. Alternately, open a hemostat in the incision or depress the cartilages cranial to the horizontal incision. Resect a small ellipse of cartilage if tube insertion is difficult. Appose the sternohyoid muscles, subcutaneous tissue, and skin cranial and caudal to the tube. Secure the tube by suturing it to the skin or tieing it to gauze that is tied around the neck.

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From: Fossum, TW: Small Animal Surgery, Mosby Publishing Co., St. Louis, Mo, 1997.

(underlying disease such as pulmonary abscesses, neoplasia, chronic granulomatous infections, pulmonary parasites such as Paragonimus, or pneumonia are present). Based on the histologic appearance of the pulmonary lesion, both cysts and bullae have been reported in dogs. Primary spontaneous pneumothorax in dogs may be due to rupture of subpleural blebs; the remaining lung tissue may appear normal. These blebs are most commonly located in the apices of the lungs. Secondary spontaneous pneumothorax is more common in dogs than the primary form. In these animals, the subpleural blebs are associated with diffuse emphysema or other pulmonary lesions. It has been shown that volume strain from expansive pressure within the lung increases disproportionately at the apex as height increases. A majority of affected people are cigarette smokers, suggesting that the underlying pulmonary disease could be a result of interference of the normal function of alpha-1-antitrypsin in inhibiting elastase. It is believed that alpha-1-antitrypsin is inactivated in people who smoke, allowing increased elastase-induced destruction of pulmonary parenchyma.

age. For similar reasons, males may be more commonly affected than females. Although traumatic pneumothorax occurs in cats, it is less common than in dogs. Spontaneous pneumothorax usually occurs in large and “deep-chested”; however, it may occur in small dogs. Dogs of any age may develop spontaneous pneumothorax; in one study the average age was 6.3 years (range 1 to 13 years). Male and female dogs appear to be equally affected. History. Pneumothorax secondary to trauma usually results in acute dyspnea. The history of trauma is often vague or unknown, complicating the differentiation of traumatic from spontaneous pneumothorax. Although the history of dogs with spontaneous pneumothorax varies depending on underlying etiology, most animals present with an acute history of dyspnea. Occasionally a chronic cough or fever may be noted. Recurrence of dyspnea in an animal previously treated for pneumothorax suggests spontaneous rather than traumatic pneumothorax.

Physical Examination Findings Diagnosis Signalment. Traumatic pneumothorax is most common in young dogs because they are more likely to be hit by cars or receive other trauma that may result in pulmonary dam-

Most animals with pneumothorax have bilateral disease and present with an acute onset of severe dyspnea. Other evidence of trauma (i.e., rib fractures, limb fractures, traumatic myocarditis, pulmonary contusions) may be evident in animals sustaining trauma. Most animals with pneumothorax

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exhibit a restrictive respiratory pattern (i.e., rapid, shallow respirations). If hypoventilation causes hypoxemia they may appear cyanotic, and the heart and lung sounds are often muffled dorsally. Dogs are able to tolerate massive pneumothorax by increasing their chest expansion. Respiration becomes ineffectual in animals with tension pneumothorax as the chest becomes barrel-shaped and fixed in maximal extension. This condition is life-threatening. Occasionally, subcutaneous emphysema will be noted in animals with pneumomediastinum and pneumothorax. The air may migrate from the mediastinal space to the thoracic inlet and be noticeable under the skin over the neck and trunk.

age may improve ventilation. Surgical intervention is seldom required in animals with traumatic pneumothorax. Thoracentesis should be performed as necessary to prevent dyspnea while the pulmonary lesion heals, usually within 3 to 5 days. Recurrence is uncommon. Conversely, animals with spontaneous pneumothorax commonly have recurrence of the pneumothorax if they are not operated. An open chest wound should be covered immediately with any readily available material. Once admitted to the hospital a sterile occlusive dressing should be applied as rapidly as possible and intrapleural air evacuated by thoracocentesis or tube thoracostom y.

Radiography/Ultrasonography

Surgical Treatment

Thoracic radiographs should be delayed until after thoracentesis in dyspneic animals. Pneumothorax usually occurs bilaterally in animals because air easily diffuses across the thin mediastinum. Pneumothorax results in an increased width of air-filled space in the pleural cavity. The most sensitive view is a horizontal-beam, laterally recumbent thoracic radiograph. On a recumbent lateral thoracic radiograph the lungs collapse and retract from the chest wall and the heart usually appears to be elevated from the sternum. This apparent elevation of the heart is not noticeable on a standing lateral radiograph. Partially collapsed or atelectic lung lobes appear radiopaque when compared to the air-filled pleural space. As the lungs collapse, the vascular pattern will not extend to the chest wall; this may be particular ly noticeable in the caudal thorax on a ventrodorsal view. Radiographs should be carefully evaluated for underlying pulmonary disease (i.e., abscess, neoplasia) or associated trauma (i.e., rib fractures, pulmonary contusion). Pulmonary blebs found in some animals with spontaneous pneumothorax are seldom visible radiographically. This is probably because the large blebs have ruptured causing the pneumothorax. In such cases, surgical identification of bulla is necessary. Air-filled bullae may be incidental findings on thoracic radiographs of some animals. Pneumomediastinum is characterized by the ability to visualize thoracic structures (i.e., aorta, thoracic trachea, vena cava, esophagus) that are not usually apparent on thoracic radiographs.

Surgical therapy of animals with traumatic pneumothorax is seldom necessary. However, non-surgical management of spontaneous pneumothorax usually results in a less than satisfactory outcome. Mechanical pleurodesis of the lungs may decrease the recurrence of pneumothorax in animals operated for spontaneous pneumothorax. Mechanical pleurodesis damages the pleura such that healing results in adherence of the visceral and parietal pleural. Postoperative pneumothorax or pleural effusion must then be prevented as they will result in separation of the parietal and visceral pleura, precluding adhesion formation.

Medical Management Medical management of an animal with pneumothorax consists of initially relieving dyspnea by thoracentesis. If the pleural air accumulates quickly or cannot be effectively managed with needle thoracentesis, a chest tube should be placed. Tube thoracostomy is typically required in animals with spontaneous pneumothorax. Intermittent or continuous pleural drainage may be used, depending on the speed with which air accumulates. Continuous drainage may cause quicker resolution of pneumothorax in animals with large, traumatic defects. Providing an enriched oxygen environment may be beneficial, particularly in animals with concurrent pulmonary trauma (e.g., pulmonary contusion/hemorrhage). Providing analgesics to animals with fractured ribs or severe soft tissue dam-

Preoperative Management An EKG and thoracentesis should be performed prior to anesthetic induction. Pre-oxygenating these animals is often beneficial. Perioperative antibiotics are seldom warranted and may prevent culturing bacteria from infected pulmonary tissue during surgery.

Anesthesia Care should be used when anesthetizing and ventilating animals with pneumothorax and/or pulmonary bullae. Intermittent positive pressure ventilation (IPPV) may rupture intact bullae or accelerate air leakage from the damaged lung or bronchial tree. Therefore, do not exceed inspiratory pressures of 10 to 12 cm H 2O pressure in these animals until the chest cavity is opened; then, the adequacy of ventilatory pressures should be reevaluated. Because IPPV may induce a tension pneumothorax, immediate treatment of this condition (i.e.,needle thoracentesis, chest tube placement) may be necessary and should be anticipated. The use of nitrous oxide is contraindicated in patients with pneumothorax.

Surgical Technique If an underlying pulmonary lesion is readily identified (i.e., pulmonary abscess or neoplasia) and can be localized to one hemithorax, an intercostal thoracotomy allows lobectomy to be performed more readily than from a medi-

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an sternotomy approach. However, diffuse, bilateral pulmonary disease with multiple bullae is usually present in dogs with spontaneous pneumothorax. A median sternotomy allows visualization of all lung lobes, plus partial resection of any diseased lobes. Mechanical pleurodesis should be performed in dogs with spontaneous pneumothorax to decrease recurrence. Identify and remove diseased lung. If the source of the pleural air is not evident, fill the chest with warmed, sterile saline or water and look for air bubbles when the anesthetist ventilates the animal. If multiple, partial lobectomies are necessary, use an automatic stapling device to decrease operative time. Perform pleural abrasion using a dry gauze sponge. Gently abrade the entire surface of the lung and parietal pleura. Prior to closure, fill the chest cavity with warmed fluid and look for air bubbles when the animal is ventilated to ensure that there are no further air leaks. Place a chest tube and remove residual air before recovering the animal. Postoperatively, if continuous air leakage is present, or pleural effusion develops, place the animal on a continuous suction device. In animals with an open pneumothorax, definitive closure of large thoracic wall defects may require mobilization of adjacent muscle in order to provide an air-tight closure.

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tension tubing, 3-way stopcock, and syringe. The appropriate site for thoracentesis should be selected based on physical examination findings or, if available, radiographic findings. Usually, aspiration of either side of the thorax will adequately drain the contralateral hemithorax since the mediastinum in dogs and cats is thin and permeable to fluid. However, with some diseases, particularly chylothorax and pyothorax, unilateral effusions may occur due to thickening of the mediastinum associated with chronic inflammation. Perform thoracentesis at the 6th, 7th, or 8th intercostal space, near the level of the costochondral junction. Clip the selected site and perform a local anesthetic block, if needed (rare!). Aseptically prepare the site and introduce the needle into the middle of the selected intercostal space. Use care to avoid the large vessels associated with the posterior aspect of the rib margins. Advance the needle into the pleural space. Aspirate fluid while the needle is being advanced to allow prompt recognition of the appropriate depth of needle placement. With the bevel of the needle facing inward, orient the needle against the rib cage to prevent damage to the lung surface. Gently aspirate fluid and place 5 ml samples in an EDTA tube and clot tube for analysis of cell counts and biochemical parameters, respectively. Additionally, make 6 to 8 direct smears for cytologic evaluation and submit samples for aerobic and anaerobic cultures.

Pleurodesis Mechanical pleurodesis has been advocated in numerous studies in the veterinary literature to prevent recurrence of spontaneous pneumothorax in dogs. This technique typically involves abrading the surface of the lung and body wall with a dry gauze sponge during open thoracotomy. Although, clinical studies suggest that this technique is effective, necropsy studies evaluating the mechanism of mechanical pleurodesis are not available. We have recently investigated mechanical pleurodesis and our studies suggest that any reduction in recurrence of pneumothorax is more likely related to fibrosis of the visceral pleura than it is to obliteration of the pleural space.

Prognosis With appropriate monitoring and care, the prognosis is excellent for animals with traumatic pneumothorax in which therapy is initiated prior to extreme dyspnea or respiratory arrest. In a recent study of dogs with spontaneous pneumothorax, 100% of those treated with needle thoracentesis alone and 81% of those managed with chest tubes had recurrence of pneumothorax. The times until recurrence varied from 3 days to 30 months. Three of 12 dogs (25%) undergoing thoracotomy had recurrence; only 1 of these had intraoperative pleural abrasion performed.

NEEDLE THORACENTESIS Needle thoracentesis is performed with a small gauge (#19 to #23) butterfly needle attached to a 3-way stopcoc k and syringe, or an over-the-needle catheter attached to an ex-

Chest Tube Placement Chest tube placement should not be attempted in an animal with severe respiratory distress. Generally, stabilization and improved ventilation can first be accomplished by removing some pleural air or fluid via needle thoracentesis. In critically ill patients, chest tubes can occasionally be placed without the use of general anesthesia; local anesthesia (i.e., local anesthetic infiltration or an intercostal nerve block) being sufficient. However, most animals with pleural cavity disease benefit from intermittent positive pressure ventilation and oxygen supplementation during tube placement. When general anesthesia is used, control of the animalâ&#x20AC;&#x2122;s airway (via endotracheal intubation and positive pressure ventilation) and oxygen therapy should be r apidly achieved. Treatment of pleural cavity disease varies depending on the underlying etiology. For traumatic pneumothorax, intermittent needle thoracentesis may be sufficient in some animals to prevent dyspnea while the lung heals, but chest tubes are occasionally required. However, chest tube placement and continuous drainage of air in animals with spontaneous pneumothorax that have undergone mechanical pleurodesis is recommended to allow pleurodesis. With some types of pleural effusion (i.e., pyothorax), tubethoracentesis and thoracic lavage are mandatory in the primary treatment of most affected animals. Incorrectly placed or improperly managed chest tubes are extremely dangerous in animals. However, if precautions are taken to assure that the animal cannot remove the tube prematurely, or that if the animal chews on the tube a pneumothorax will not occur, chest tubes simplify the management of some animals with pleural effusion or pneumothorax. The choice of which side to place the chest tube is made

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by evaluating the radiographs. Occasionally, bilateral chest tubes may be necessary; however, in most dogs and cats the mediastinum is permeable to fluid or air, allowing drainage of both hemithoraxes through a single tube. The exception to this may be in chylothorax or pyothorax. Components of a tube thoracostomy include a chest tube, an apparatus to connect the tube to a syringe or to a continuous suction bottle, and a device to collect the drained material (syringe or collecting bottle). Commercially available tubes are usually made of polyvinyl chloride or silicone rubber and are less reactive than red rubber feeding tubes. Commercial tubes come with a metal stylet that simplifies tube placement, but may increase the risk of perforating lung tissue when compared to red rubber feeding tubes. The latter are usually inserted using a large hemostat or Carmalt clamp. Commercial chest tubes come in various sizes ranging from 14 to 40 French. The size of the thoracostomy tube should approximate the diameter of the mainstem bronchus; however, smaller tubes may be adequate for removal of air, while larger tubes may required with more viscous effusions. If a commercial tube is used, it can be attached via a five-in-one connector (Christmas tree adaptor) to either a 3-way stopcock or tubing from a continuous suction device. The ends of red rubber feeding tubes can be cut to accommodate a 3-way stopcock; attaching these tubes to a continuous suction device is generally not recommended due to their tendency to collapse.

GUIDELINES FOR ESTIMATING CHEST TUBE SIZE: Cats & Dogs < 7 kg

14 – 16 Fr

Dogs 7 - 15 kg

18 – 22 Fr

Dogs 16 - 30 kg

22 – 28 Fr

Dogs > 30 kg

28 – 36 Fr

Clip and prepare the lateral thorax for aseptic surgery. In order to allow sufficient drainage, place additional holes in the tube by bending the tube and removing a notch with a pair of sterile scissor. Holes should not be greater than onethird the circumference of the tube. If using a commercial tube with a radiopaque line, place the last hole through the line in order to allow identification of its position on a thoracic radiograph. Make a small skin incision in the dorsal one-third of the lateral thoracic wall at the level of the 10th or 11th intercostal space. Advance the tube subcutaneously in a cranioventral direction for 3 to 4 intercostal spaces and introduce the tube through the muscle and pleura using the stylet or a large hemostat. When using a trocar tube, firmly grasp the tube 2 to 4 cm from the body wall with one hand while using the other hand to “pop” the tube through the intercostal musculature and pleura. This will prevent the tube from being inadvertently pushed further into the thorax than anticipated and damaging the lung or other thoracic structures. Feed the tube in a cranioventral direction to a predetermined point and before completely removing the trocar, clamp the tube with a hemostat. Place a purse-string suture in the skin around the tube (do not enter the lumen of the tube) and leave both ends of the suture long. Use this suture to perform a “Chinese-finger trap” or “Roman-sandal” suture. Connect the chest tube to a 3-way stopcock in order to increase the ease of thoracic drainage. Use a five-in-one (Christmas tree) adaptor or a female Luer lock (with small tubes) between the tube and the 3-way stopcock to ensure an air-tight seal. Use suture to secure the tube to the connecting devices so that they will not become inadvertently dislodged, resulting in a pneumothorax. For added safety when the chest cavity is not being suctioned, clamp the tube where it exits the body wall with a hemostat or C-clamp. Verify appropriate placement of the chest drain radiographically, prior to covering it with a loose bandage. Drainage may be either intermittent or continuous. Generally, intermittent pleural drainage is adequate; how-

From: Fossum, TW: Small Animal Surgery, Mosby Publishing Co., St. Louis, Mo, 1997.

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ever, in some situations (i.e., spontaneous pneumothorax, pleurodesis) continuous suction is preferable. Heimlich valves should only be used in medium to large dogs, since small dogs and cats may not develop sufficient expiratory pressure for effective drainage. Additionally, these valves are prone to malfunction if fluid is aspirated into the apparatus. “Milking” or “stripping” of chest tubes to prevent obstruction of the tube by clots has been recommended in the veterinary literature; however, these techniques generate high intrapleural pressures and may cause pulmonary damage.

Chest Tube Removal With pleural effusion, remove the tube when the drainage decreases to a volume that is consistent with that caused by the presence of the tube itself (i.e., 2.2 ml/kg b.w./day). The tube can be removed in patients with pneumothorax once negative pressure has been achieved for 12 to 24 hours. Culture the end of the tube following removal if the tube has been present for several days, or if the animal shows signs of infection. Suture the skin incision with 1 or 2 simple interrupted sutures.

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Continuous Thoracic Suction If fluid accumulation is so rapid that intermittent drainage is not practical,or if adherence of the visceral pleura to the body wall is desired, continuous suction may be used. Two and three-bottle systems and commercial suction units are available for veterinary use and are economical and simple to use. A continuous 10 to 15 cm negative pressure on the thorax effectively aspirates pneumothorax, increasing the likelihood of spontaneous sealing of large pulmonary defects. Slightly greater pressures may be necessary (up to 20 cm water) when viscous fluid is being drained. Connect the chest tube to a bottle that serves as an underwater seal (filled with 2 to 3 cm of sterile water) which in turn is connected to a suction bottle (also partially filled with water) attached to a suction device. Vary the amount of suction by raising or lowering the level of water in the suction bottle. A rigid plastic vent tube opened to room air serves to allow air to be aspirated into the bottle as the vacuum is applied. A third bottle interposed between the chest tube and the underwater seal bottle serves to collect fluid and prevent the level from rising in the underwater seal bottle as fluid is drained from the chest. This bottle is unnecessary in animals with pneumothorax. Alternately, a commercial continuous suction device may be used.

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Surgery of the lungs, bronchi, and intrathoracic tracheaChirurgia di polmoni, bronchi e trachea intratoracica

Theresa W. Fossum DVM, MS, PhD, Dipl ACVS - Texas A & M University, USA

Many practitioners prefer to refer animals requiring thoracic surgery, yet knowledge of basic principles of thoracic surgery allows many procedures to be performed by competent surgeons in non-referral setttings. Animals with traumatic lesions that impair respiration (e.g., flail chest), or those with acute respiratory impairment (i.e., ruptured bullae, ruptured pulmonary abscess) often require emergency stabilization (e.g., stabilization of rib segments, thoracentesis, oxygen therapy) prior to surgery. With large neoplastic lesions, positioning the animal in sternal recumbency, or in lateral recumbency with the affected side down, and providing oxygen (i.e., nasal insufflation or oxygen cage) is often beneficial. Blood gas analysis or evaluation with pulse oximetry is warranted preoperatively in patients undergoing thoracic surgery to detect and define the severity of respiratory impairment. Unexplained abnormalities should be investigated because ventilatory impairment due to non-surgically correctable disease (i.e., diffuse micro-metastasis) will occasionally be identified. Anemia should be corrected prior to surgery, if possible.

Anesthetic Considerations Pulmonary neoplasia or other space-occupying lesions may prevent normal lung expansion and produce hypoxemia. With pneumonia or emphysematous lesions, ventilation/perfusion disturbances are common. Animals with respiratory dysfunction may have oxygen administered by face mask or nasal insufflation prior to induction to ensure that hemoglobin is optimally saturated and that hypoxemia does not occur during intubation. Sedation with acetylpromazine should be avoided in severely affected patients because of hypotension. Anticholinergics can be used in animals with bradycardia (i.e., heart rate < 60 bpm). Nitrous oxide should be avoided in patients with respiratory compromise. Opioids may cause severe respiratory depression and should be administered only when oxygen can be provided. Endotracheal intubation must be accomplished rapidly in animals with respiratory dysfunction and anesthesia should be maintained with an inhalation anesthetic (i.e., isoflurane or halothane). In compromised animals, intubation of a bronchus rather than the trachea may be disastrous; therefore, both sides of the chest cavity should be auscultated to ensure proper endotracheal tube placement. It may be difficult to maintain an adequate depth of anesthesia in animals with severe pul-

monary disease with inhalation anesthetics alone; supplementation with opioids may be necessary. All animals with open chest cavities require intermittent positive pressure ventilation (including those with diaphragmatic hernias). High ventilatory pressures should be avoided in patients with chronically collapsed lung lobes, pneumonia, or pulmonary bullae. Thoracotomy procedures often produce substantial pain and postoperative analgesic ther apy is indicated. Placement of bupivacaine into the thoracic cavity following thoracic closure (interpleural), or performing an intercostal nerve block (i.e., divide bupivacaine and inject dorsally and ventrally in the incised intercostal space and 2 intercostal spaces cranial and caudal to the incised space) may decrease postoperative pain and promote improved ventilation in the postoperative period. Patients given bupivacaine interpleurally should be placed with the affected side down for 20 minutes. Injectable analgesics (i.e., oxymorphone, butorphonal, or buprenorphine may also be used. Although opioids are respiratory depressants, their analgesic effects often outweigh their negative respiratory effects. If hypoventilation occurs after administration of these drugs, oxygen should be given by nasal insufflation. Pulmonary edema (reexpansion pulmonary edema; RPE) may develop in some animals with chronically collapsed lung lobes following surgery that allows reexpansion. Although the origin of RPE is unknown and probably multi factorial, it does not appear to be associated with cardiac failure. Beginning usually within a few hours after surgery, the patient typically develops progressively worsening dyspnea and tachypnea. Hypoxemia develops and persists, despite intense oxygen therapy. Contrary to the experience in human beings in which RPE is usually unilateral and therefore not life-threatening, the condition is rapidly fatal in most animals. Reoxygenation of chronically collapsed lungs is thought to release superoxide radicals which cannot be effectively scavenged, resulting in increased pulmonary capillary permeability and pulmonary edema. Chronically collapsed lung tissue may have decreased mitochondrial superoxide dismutase and cytochrome oxidase activity. Prophylaxis and therapy of patients with RPE is difficult and poorly understood. Reexpansion of chronically collapsed lung tissue should be accomplished slowly (i.e., the thorax may be closed with 1 or 2 lung lobes collapsed, allowing them to re-expand slowly) and high ventilation pressures (i.e., > 25 cm H2O pressure) should be avoided. Current recommenda-

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tions for treating RPE include the use of positive end-expiratory pressure ventilation and drugs which stabilize pulmonary capillary membranes (i.e., methylprednisolone). A number of other pharmaceutical agents are currently being investigated, but conclusive evidence of their beneficial effects is not yet a vailable.

Antibiotics Animals with underlying pulmonary disease or trauma (i.e., pulmonary contusions) are at increased risk to develop pulmonary infections. These patients should be monitored carefully and prophylactic antibiotics (e.g., cefazolin) provided, or therapeutic antibiotics initiated at the earliest sign of infection (i.e., leukocytosis and/or fever). Appropriate use of prophylactic antibiotics depends on the length of surgery, type of surgery being performed, animalâ&#x20AC;&#x2122;s immune status, and the underlying disease process. Young, healthy animals undergoing thoracotomy for relatively short procedures (e.g., ligation of a patent ductus arteriosus) generally do not require prophylactic antibiotics. Debilitated animals undergoing thoracotomy for removal of large neoplastic lesions (which may contain focal areas of necrosis) are likely to benefit from prophylactic antibiotic therapy. Prophylactic antibiotics should be given intravenously at induction and generally discontinued within 12 to 24 hours.

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dorsalis cranialis, levatores costarum, and diaphragm. Additional expiratory muscles include the rectus abdominous, external abdominal oblique, internal abdominal oblique, transversus abdominous, serratus dorsalis caudalis, transversus costarum, and iliocostalis. The lungs of dogs and cats have deep fissures which create distinct lobes allowing the lungs to alter their shape in response to alterations in thoracic cavity shape (i.e., that caused by diaphragmatic movement or flexion or extension of the spine). These fissures also allow individual lobes to be isolated and removed without compromising integrity of the surrounding lobes. The left lung is divided into a cranial lobe with a cranial and caudal part, and a caudal lobe. The right lung is larger than the left and is divided into cranial, middle, caudal, and accessory lobes. The cardiac notch is a small area overlying the heart where lung tissue is not interposed between the heart and body wall. It is usually located at the ventral aspect of the 4th intercostal space and is larger on the right side. The pulmonary arteries carry non-aerated blood from the right ventricle of the heart to the lungs, while the pulmonary veins return aerated blood from the lungs to the left atrium. The left pulmonary artery lies cranial to the left bronchus; whereas, the left pulmonary veins are ventral to it. On the right side, the pulmonary artery lies dorsal and slightly caudal to the right bronchus and the pulmonary veins lie craniodorsal and ventral to it.

THORACOTOMY Surgical Anatomy Thoracic cavities of dogs and cats are compressed laterally so that the greatest dimension is dorsoventral. The ribs, sternum, and vertebral column form the thoracic skeleton. The sternum is composed of 8 unpaired bones and forms the floor of the thorax. The first and last sternebrae are known as the manubrium and xiphoid, respectively. There are usuall y 13 pairs of ribs. The 10th, 11th, and 12th ribs do not articulate with the sternum, but instead form the costal arch bilaterally. The cartilaginous portion of the 13th rib terminates free in the musculature. The space between the ribs is known as the intercostal space and is generally 2 to 3 times as wide as the adjacent ribs. Blood supply to the thoracic wall is provided by the intercostal arteries. The intercostal arteries lie caudal to the adjacent rib, in conjunction with a satellite vein and nerve. A typical intercostal nerve begins where the dorsal branch of the thoracic nerve divides and runs distally among the fibers of the internal intercostal muscle. In most intercostal spaces, intercostal vessels and nerves are covered medially only by pleura. Muscles of the thorax serve not only a structural function, but are also important in respiration. The deepest muscles of the thoracic wall are the intercostal muscles. The fibers of the external intercostal muscle arise on the caudal border of each rib and run caudoventrally to the cranial border of the next rib. This muscle is important primarily in inspiration. The internal intercostal muscles, on the other hand, run from the cranial border of one rib to the caudal border of the preceding rib, primarily functioning to aid expiration. Other inspiratory muscles are the scalenus, serratus

Thoracotomy may be performed by incising between the ribs or by splitting the sternum. The approach used depends on the exposure needed and underlying disease process. Regardless of the type of thoracotomy performed, a large area should be prepared for aseptic surgery to allow extension of the incision, if needed. Depending on which left lobe is affected, a left lateral thoracotomy at the 4th, 5th, or 6th intercostal space will provide adequate exposure for lobectomy. A left 4th intercostal space thoracotomy allows exposure of the right ventricular outflow tract, main pulmonary artery, and ductus arteriosus. Bilateral removal of the pericardial sac can be difficult from this approach. A right intercostal thoracotomy provides exposure of the right side of the heart (auricle, atrium, and ventricle), cranial and caudal vena cava, right lung lobes, and azygous vein. Median sternotomy affords exposure to both sides of the thoracic cavity. Bilateral, partial lobectomy is easily performed from a median sternotomy; however, complete lobectomy is often difficult. The caudal vena cava, main pulmonary artery, and both sides of the pericardial sac can be isolated and manipulated via this approach. A loose bandage should be placed on the thorax after surgery.

Intercostal thoracotomy With the dog in lateral recumbency, select the site for incision. Locate the approximate intercostal space and sharply incise the skin, subcutaneous tissues, and cutaneous trunci muscle. The incision should extend from just below the ver-

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tebral bodies to near the sternum. Deepen the incision through the latissimus dorsi muscle with scissors), then palpate the first rib by placing a hand cranially under the latissimus dorsi muscle. Count back from the first rib to verify the correct intercostal space. Transect the scalenus and pectoral muscles with scissors perpendicular to their fibers, then separate the muscles fibers of the serratus ventralis muscle at the selected intercostal space. Near the costochondral junction, place one scissor blade under the external intercostal muscle fibers and push the scissors dorsally in the center of the intercostal space to incise the muscle. Incise the internal intercostal muscle similarly. Notify the anesthetist that you are about to enter the thoracic cavity and, after identifying the lungs and pleura, use closed scissors or a blunt object to penetrate the pleura. This allows air to enter the thorax, causing the lungs to collapse away from the body wall. Extend the incision dorsally and ventrally in order to achieve the desired exposure. Identify and avoid incising the internal thoracic vessels as they course subpleurally near the sternum. Moisten laparotomy sponges and place them on the exposed edges of the chest incision. Use a Finochietto retractor to spread the ribs. If further exposure is needed, a rib adjacent to the incision can be removed; ho wever, this is seldom required. If a chest tube is to be placed, do so before closing the thorax. The tube should not exit from the incised intercostal space. Close the thoracotomy by preplacing 4 to 8 sutures of heavy (3-0 to No. 2, depending on the animalâ&#x20AC;&#x2122;s size) monofilament absorbable or non-absorbable suture around the ribs adjacent to the incision. Approximate the ribs with a towel clamp or rib approximator, or have an assistant cross two sutures to appose the ribs, then tie the remaining sutures. Tie all the sutures before you remove the rib approximator or towel clamp. Suture serratus ventralis, scalenus, and pectoralis muscles with a continuous suture of absorbable suture material. Appose the edges of the latissimus dorsi muscle similarly. Remove residual air from the thoracic cavity using the preplaced chest tube or an over-theneedle catheter. Close subcutaneous tissues and skin in a routine fashion.

Median sternotomy When performing median sternotomy, 2 to 3 sternebrae should be left intact cranially or caudally (depending on where the lesion is located) to decrease postoperative pain and prevent delayed healing caused by sternebral shifting. If exposure of the lungs or heart is necessary (i.e., in dogs with spontaneous pneumothorax or for pericardiectomy) the sternotomy should extend from the xiphoid cartilage cranially to the 2nd or 3rd sternebrae. If exposure of the cranial mediastinum is desired, the sternotomy should extend from the manubrium caudally to the 6th or 7th sternebrae. With the dog in dorsal recumbency, incise skin on the midline over the sternum. Expose the sternum by a combination of sharp incision and blunt dissection of the overlying musculature. Transect the sternebrae longitudinally on the midline with a bone saw, chisel and osteotome, or bone cutters. In young animals, heavy scissors may be adequate;

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however, avoid crushing the bone. Splitting the sternebrae on the midline will facilitate closure. Take care that the underlying lung and heart are not damaged while completing the sternotomy. Place moistened laparotomy sponges on the incised edges of the sternebrae and retract the edges with a Finochietto rib retractor. If a chest tube is to be placed, do so before closing the sternotomy. Do not exit the tube from between the sternebrae; exit it from between the ribs or through the diaphragm. Close the sternotomy with wires (dogs > 20 kg) or heavy suture (cats and dogs < 20 kg) placed around the sternebrae. Suture subcutaneous tissues with a simple continuous suture of absorbable suture material. Remove residual air from the thoracic cavity and close skin routinely.

Partial lobectomy Partial lobectomy may be performed to remove a focal lesion involving the peripheral one-half to two-thirds of the lung lobe, or for biopsy. Partial lobectomy may be performed via a lateral 4th or 5th space intercostal thoracotomy or median sternotomy. Identify the lung tissue to be removed and place a pair of crushing forceps across the lobe, proximal to the lesion (Figure-1). Place a continuous, overlapping suture pattern of absorbable suture material (2-0 to 40) 4 to 6 mm proximal to the forceps. A second row of sutures may be placed in a similar manner to the first. Excise the lung between the suture lines and clamps, leaving a 2 to 3 mm margin of tissue distal to the sutures. Oversew the lung with a simple continuous suture pattern of absorbable suture (3-0 to 5-0). Replace the lung in the thoracic cavity and fill the chest cavity with warmed, sterile saline solution. Inflate the lungs and check the bronchus for air leaks. Remove the fluid before closing the thorax. Partial lobectomy may also be performed with stapling devices [e.g., thoraco-abdominal (TA) stapler. The stapling equipment comes in various sizes that produce staple lines 30 mm, 55 mm, or 90 mm long. Select the staple size based on the width of the lung so that the staple line extends across the entire width of the lung to be removed, but does not extend beyond the edges. If air leaks or hemorrhage are noted, place a simple continuous suture pattern of absorbable suture material along the lung margin. The stapling devices compress tissue to a thickness of either 1.5 mm (3.5 mm long staples) or 2.0 mm (4.8 mm long staples). Avoid stapling excessively thick or fibrotic lung as this may result in large air leaks or hemorrhage. Check the lung for leaks and close as described above.

Complete lobectomy Complete lobectomy is best performed through a lateral thoracotomy. If the lung contains large quantities of purulent material, prevent excessive fluid from draining into the proximal bronchi and trachea by clamping the bronchus near the hilus prior to manipulating the lobe. Similarly, torsed lung lobes should be removed without untwisting the pedicle to prevent release of necrotic material trapped in the lung.

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Figure 1 From: Fossum, TW: Small Animal Surgery, Mosby Publishing Co., St. Louis, Mo, 1997.

Dogs can survive acute loss of up to 50% of their lung volume; however, transient respiratory acidosis and exercise intolerance may occur. Identify the affected lobe(s) and isolate them from the remaining lobes with moistened sponges (laparotomy or 4x4’s depending on the animal’s size) (Figure 2). Identify the vasculature and bronchus to the lobe. Using blunt dissection, isolate the pulmonary artery supplying the affectedlobe and pass a ligature of nonabsorbable or absorbable suture material (2-0 to 3-0) around the proximal end of the vessel. Do not compromise the lumen of the parent vessel from which this vessel arises. Place a 2nd ligature in a similar fashion distal to the site where the vessel is to be transected. A transfixing suture may be placed between these sutures, proximal to the transection site, to prevent the first suture from being inadvertently dislodged. Transect the artery between the distal 2 ligatures. Ligate the pulmonary vein in a similar fashion. Identify the main bronchus supplying the lobe and clamp it with a pair of Satinsky or crushing forceps proximal and distal to the selected transection site. Sever the bronchus between the clamps and remove the lung. Suture the bronchus proximal to the remaining clamp with a continuous horizontal mattress suture pattern, or in cats and small dogs place a transfixing ligature around the bronchus. Prior to removing the clamp, secure a suture in the bronchus distal to

the clamp and after removing the clamp, oversew the end of the bronchus with a simple continuous suture pattern. Fill the chest cavity with warmed, sterile saline solution. Inflate the lungs and check the bronchus for air leaks. Remove the fluid and close the chest as described above.

PULMONARY NEOPLASIA Primary pulmonary neoplasia is less common than metastatic neoplasia in dogs and cats. The diaphragmatic lobes are most frequently involved, with the right lung lobes more often affected than the left. Classification of primary lung tumors is usually based upon the predominant histologic pattern since specific anatomic localization of tumor origin is not always possible and more than one tumor type may be present. Adenocarcinoma is the most common histologic type found in dogs and cats; squamous cell carcinoma and anaplastic carcinomas are less common. Primary pulmonary tumors of connective origin (e.g., osteosarcoma, fibrosarcoma, hemangiosarcoma) are rare. Although most pulmonary tumors are malignant, benign tumors (i.e., papillary adenoma, bronchial adenoma, fibroma, myxochondroma, and plasmacytoma) have been reported. Pulmonary neoplasms are highly aggressive and tend to metastasize early. Most

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Figure 2 From: Fossum, TW: Small Animal Surgery, Mosby Publishing Co., St. Louis, Mo, 1997.

anaplastic carcinomas and squamous cell carcinomas have metastasized at the time of diagnosis, while approximately one-half of adenocarcinomas have done so. Metastasis is often to the lung itself and/or regional lymph nodes.

abscesses may result in pyothorax and/or pneumothorax. In some parts of the country, pulmonary abscesses are common secondary to inhalation or thoracic penetration of plant material (e.g., foxtails) that migrate through the lung.

PULMONARY ABSCESSES

DIAGNOSIS

Pulmonary abscesses are rare, but they may occur as a complication of foreign bodies, neoplasia, bacterial pneumonia, aspiration pneumonia, fungal infections, or parasites. Abscesses secondary to neoplasia may be sterile or infected. The most common organisms cultured from abscesses associated with necrotizing pneumonia in dogs are Escherichia coli, Pseudomonas spp., and Klebsiella spp. Rupture of pulmonary

Signalment. Pulmonary abscess may occur in dogs or cats of any age, breed, or sex. History. The animal may present with a persistent lowgrade fever, varying degrees of respiratory distress, weight loss, lethargy, and/or anemia. The duration of illness may vary from hours to days or even weeks. Rupture of a pulmonary abscess that causes pneumothorax may result in acute dyspnea.

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Physical Examination Findings Physical examination findings vary depending on whether pneumothorax and/or pleural effusion are present. Most animals are febrile and moist rales may be heard over the mass.

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tomy. A median sternotomy approach is preferred if multiple opacities are present involving both sides of the thorax. If the animal is dyspneic, thoracentesis should be performed prior to surgery. Antibiotic therapy should be initiated after the mass and/or pleural space have been cultured if not before.

Radiography/Ultrasonography SURGICAL TECHNIQUE Pulmonary abscesses generally appear as nodular or cavitary radiopaque lesions on thoracic films. The walls of the abscess are poorly defined in general. If pleural effusion is present, thoracentesis may be necessary before a definitive diagnosis can be made. Ultrasound evaluation of thoracic masses may help differentiate noncavitary from cavitary lesions.

Laboratory Findings Leukocytosis with a degenerative left shift may be present, or the leukogram may be normal. If the infection is chronic, a nonregenerative anemia may be present.

Differential diagnosis Abscesses should be differentiated from other nodular or cavitary pulmonary lesions (i.e., granulomas, Paragonimus, neoplasia) by cytology and/or histologic examination of samples obtained by fine-needle aspiration or surgery. Preoperative aspiration of the mass may help differentiate between these lesions and provide samples for culture; however, care should be used to avoid causing pyothorax. Ultr asound is often useful in locating the appropriate site for aspiration. Some nonneoplastic lesions can be managed without surgery (e.g., Paragonimus); however, a definitive diagnosis may require surgical biopsy.

Identify and remove the diseased lung. Submit the lung for bacterial and/or fungal cultures and for histologic examination. Explore the remainder of the chest cavity for the presence of foreign matter. Palpate all the lung lobes which can be reached to identify other pulmonary lesions. Free remaining lung lobes of adhesions so that all lobes are moveable and remove loculated areas of exudate. Remove sheets of fibrin that cover the lung lobes. Place a chest tube before thoracic closure.

Postoperative care and assessment Appropriate antibiotics should be continued for 3 to 6 weeks if infection is present. Pyothorax should be treated with thoracic lavage. Postoperative analgesics should be provided.

Prognosis The prognosis for animals with pulmonary abscesses depends on the underlying cause. With appropriate management, the prognosis of animals with abscesses associated with nonneoplastic disease is good .

LUNG LOBE TORSION Medical manageent Initial therapy is aimed at stabilizing the animal if it is dyspneic. Thoracentesis should be performed if pleural fluid or air is present. Appropriate antibiotics should be given based on results of culture and sensitivity testing. A broadspectrum antibiotic with a good anaerobic spectrum should be chosen. Antibiotic therapy should be continued for 3 to 6 weeks. If pyothorax is present, chest tubes should be placed and the thorax lavaged. Some animals will respond to medical management and the abscess will resolve. If after several days there is no improvement in clinical signs or lung e xpansion, or pleural fluid is loculated and does not resolve, surgical intervention is warranted.

Surgical treatment Solitary pulmonary abscesses that do not resolve with medical therapy are best managed by partial or complete lobectomy of the diseased lung performed via an intercostal thoraco-

Any mechanism that increases mobility of a lung lobe seems to favor development of a torsion. Partial collapse of the lung (i.e., with pulmonary disease or trauma) frees it from its normal spatial relationships with the thoracic wall, mediastinum, and adjacent lung lobes. They may enhance mobility. Pleural effusion or pneumothorax, along with subsequent atelectasis of lung lobes, can allow increased movement of a lobe, predisposing to torsion. Although LLT has been reported to cause chylothorax in dogs, it is more likely that the chylothorax caused the LLT. LLT has been reported secondary to previous thoracic surgery, where lung lobes are manipulated and may remain partially collapsed after thoracic closure. Torsion of a lung lobe results in venous congestion of the affected lobe; however, the arteries remain at least partially patent, allowing blood to enter. As fluid and blood enter the alveoli, lung consolidation occurs and the lobe becomes dark-colored and firm, similar in shade to the liver. The shape of the affected lobe is often altered and it may appear displaced from its normal location within the thorax radiographically. Pleural fluid usually accumulates due to continued venous congestion.

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Diagnosis

Differential diagnosis

Signalment. Deep-chested, large-breed dogs, especially Afghan hounds, are more commonly affected. LLT in Afghan hounds may be associated with chylothorax. In large breeds, LLT has been reported to occur spontaneously, without previous history of disease or trauma. LLT has also been reported in small breeds but is usually secondary to primary pleural effusion, thoracic surgery, or trauma. LLT is rare in cats. Middle-aged dogs are more commonly affected, but LLT may occur in animals of any age. History. Affected animals usually have some degree of respiratory distress. Coughing and hemoptysis can also occur, and may be chronic in nature. Some animals may be anorexic and depressed. Frequently there is a previous history of pleural effusion, pneumothorax, pneumonia, and/or trauma.

Disease such as pneumonia, pulmonary thromboembolism, contusion, neoplasia, atelectasis, hemothorax, diaphragmatic hernia, and pyothorax can mimic radiographic changes seen with LLT. Bronchoscopy may aid diagnosis of LLT once partial or complete occlusion of the affected bronchus is visualized. Bronchial mucosa at the site of obstruction may appear folded and edematous. Demonstration of LLT at surgery provides the definitive diagnosis.

Physical Examination Findings Pleural effusion is consistently present in animals with LLT; therefore, findings often include muffled heart and lung sounds. Other findings may include depression,anorexia, coughing, fever, dyspnea, hemoptysis, hematemesis, and/or vomiting.

Radiography/Ultrasonography Thoracic radiographic changes are variable depending on the volume of pleural fluid, presence or absence of preexisting disease, and duration of the torsion. The most con sistent finding is the presence of pleural effusion accompanied by an opacified lung lobe. Initially, air bronchograms will be present in the torsed lobe and can be seen extending toward the abdomen. Air bronchograms eventually disappear as fluid and blood fill the bronchial lumen. The presence of a noninflated, radiopaque lung lobe that persists after removal of pleural fluid should increase suspicion for LLT. Positional radiographs using horizontal beam x-rays (lateral decubitus or upright VD) are often helpful. Pleural fluid secondary to LLT may persist around the affected lobe rather than fall to the dependent side. Failure of the lobe to reinflate in the Aup@ or nondependent hemithorax is another indication of LLT.

Laboratory Findings Laboratory findings with LLT are va ri able. Fluid analysis may reveal a sterile, inflammatory effusion or chyle, or the fluid may be bloody. Pleural effusion of any etiology, however, can initiate a secondary LLT, making results of pleural fluid analysis variable and confusing. The appearance of blood in a previously nonhemorrhagic pleural fluid may indicate occurrence of LLT. An inflammatory leukogram may be present; however, changes in the leukogram may reflect the initial disease process rather than the LLT.

Medical management Initial therapy is aimed at stabilizing the animal and alleviating respiratory distress before surgery. Thoracentesis should be performed to remove pleural fluid. Persistent or massive pleural effusion may require placement of a chest tube. Oxygen therapy given by oxygen cage or nasal insufflation is beneficial to some animals. Underlying diseases such as pneumonia should be identified and treated with appropriate antibiotic therapy. Intravenous fluid therapy is beneficial before and during surgery to maintain hydration.

Surgical treatment Spontaneous correction of a torsed lung lobe is uncommon due to swelling of the lobe and rapid formation of adhesions. The treatment of choice for LLT is lobectomy of the affected lobe. Unless LLT is diagnosed very quickly (i.e., immediately after a surgical procedure), damage to the pulmonary parenchyma is generally severe enough that attempts to salvage the lobe are not warranted. Recurrence has been reported following surgical correction where lobectomy was not performed. Prophylactic antibiotics are warranted in animals with LLT. Pleural effusion should be removed prior to anesthetic induction in animals that have compromised ventilation.

SURGICAL TECHNIQUE Clamp the affected pedicle with a noncrushing forceps to prevent release of toxins into the bloodstream, prior to attempting to derotate it. Untwisting the lobe before its removal may help facilitate identification of the vascular structures and bronchus for ligation; however, in some cases, the lobe cannot be easily returned to its normal position due to extensive adhesions. Check the remaining lobes for position and normal expansion. Culture pulmonary parenchyma following removal of the lobe. Submit excised tissue for histologic examination to help determine underlying causes (i.e., pneumonia,neoplasia). Place a chest tube before closing the thoracic cavity.

Postoperative care and assessment Antibiotics should be continued if there is evidence of infection and postoperative analgesics should be provided. The chest tube should be removed when the effusion de-

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Figure 3 From: Fossum, TW: Small Animal Surgery, Mosby Publishing Co., St. Louis, Mo, 1997.

creases to less than 2.2. ml/kg/b.w.. Oxygen therapy may be warranted in some patients in the postoperative period, particularly if there is underlying lung disease such as pneumonia. If dyspnea remains after surgery, thoracic radiographs are indicated to rule out LLT in a remaining lobe.

TRACHEAL RESECTION/ANASTOMOSIS Removal of a tracheal segment may be necessary to treat tracheal tumors, stenosis, or trauma. Depending on the degree of tracheal elasticity and tension, approximately 20% to 60% of the trachea may be resected and direct anastomosis achieved. The split cartilage technique is preferred because it is easier to perform and results in more precise anatomic alignment with less luminal stenosis than many other techniques. Diseased trachea exceeding the limits of resection and anastomosis may be managed with permanent tracheostomy, intraluminal silicone tubes, grafts, or prostheses with variable success (Figure 3). Expose the involved trachea through a ventral cervical, midline, lateral thoracotomy, or median sternotomy approach. Mobilize only enough trachea to allow anastomosis without tension. Preserve as much of the segmental blood and nerve supply to the trachea as possible. Place stay sutures around cartilages cranial and caudal to the resection sites prior to transecting the trachea. Resect the diseased trachea by splitting a healthy cartilage circumferentially at each end

or incising annular ligaments adjacent to the intact cartilages. Use a No. 11 blade to split the tracheal cartilages at their midpoint. Transect the dorsal tracheal membrane with Metzenbaum scissors. Preplace, and then tie, three or four simple interrupted sutures (3-0 or 4-0 polypropylene) in the dorsal tracheal membrane. Retract the endotracheal tube into the proximal trachea during resection and placement of sutures in the dorsal tracheal membrane. Remove blood clots and secretions from the lumen and advance the tube distal to the anastomosis after dorsal tracheal membrane sutures are placed. Complete the anastomosis by apposing the split cartilage halves or adjacent intact cartilages with simple interrupted sutures beginning at the ventral midpoint of the trachea. Space additional sutures 2 to 3 mm apart. Place three or four retention sutures to help relieve tension on the anastomosis. Place and tie these sutures so that they encircle an intact cartilage cranial and caudal to the anastomosis, crossing external to the anastomotic site. Lavage the area and appose the sternohyoid muscles with a simple continuous pattern. Close subcutaneous tissues and skin routinely. If tension-relieving sutures do not adequately relieve tension at the anastomosis, further mobilize the trachea, make partial-thickness incisions through annular ligaments proximal and distal to the anastomosis, or restrict head and neck movement after surgery. Prevent full extension of the neck by placing a suture from the chin to the manubrium or fixing a muzzle to a harness to maintain mild to moderate cervical flexion. Maintain the muzzle for 2 to 3 weeks.

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Cardiovascular surgery Chirurgia cardiovascolar e

Theresa W. Fossum DVM, MS, PhD, Dipl ACVS - Texas A & M University, USA

General principles and techniques Animals requiring cardiac surgery often have prior cardiovascular compromise that should be corrected or controlled medically when possible, prior to anesthetic induction. Congestive heart failure, particularly pulmonary edema, should be managed with diuretics (e.g., furosemide) and ACE inhibitors (e.g., enalapril, lisinopril) before surgery. Cardiac arrhythmias should be recognized and treated. Ventricular tachycardia should be suppressed before surgery with class I antiarrhythmic drugs (i.e., lidocaine, procainamide). Lidocaine is effective for management of ventricular tachyarrhythmias during and immediately after surgery. Supraventricular tachycardia may require management with digoxin, beta-adrenergic blockers (e.g., esmolol, propranolol, atenolol), or calcium channel blocking drugs (e.g., diltiazem) prior to surgery. Atrial fibrillation should be controlled prior to surgery with digoxin to lower the ventricular response rate below 140 bpm. This may require the addition of beta-adrenergic blockade or calcium channel blocking drugs if digoxin alone does not decrease the ventricular rate sufficiently. Animals with bradycardia should undergo an atropine response test before surgery. If bradycardia is not responsive to atropine, temporary transvenous pacing or constant intravenous infusion of isoproterenol (see management of bradycardia) may be required. Most animals should undergo evaluation by echocardiography prior to cardiac surgery as an incomplete or inaccurate diagnosis can have devastating consequences. With the advent of Doppler echocardiography, cardiac catheterization is no longer routinely necessary prior to cardiac surgery.

Anesthetic considerations Preanesthetic medication is appropriate for most animals undergoing cardiac surgery (Tables 1 & 2). Parenteral opioids (i.e., oxymorphone, butorphanol, buprenorphine, or fentanyl) induce sedation with minimal cardiovascular effects. All opioids have the potential to produce respiratory depression and/or bradycardia. Anticholinergics (i.e., atropine or glycopyrrolate) should be administered as needed to treat bradycardia when using an opioid. Benzodiazepines (i.e., diazepam; 0.2 mg/kg up to 5 mg and midazolam; 0.2 mg/kg up to 5 mg), have minimal cardiopulmonary effects and can be combined with opioids to enhance sedation.

Table 1 - Selected anesthetic protocols for use in stable animals with cardiovascular disease Premedication: give atropine (0.02 - 0.04 mg/kg; SC or IM) or glycopyrrolate (0.005 - 0.011 mg/kg; SC or IM) if indicated plus oxymorphone* (0.05 - 0.1 mg/kg; SC or IM); or butorphanol (0.2 - 0.4 mg/kg SC or IM); or buprenorphine (5 - 15 Fg/kg; IM) Induction: thiopental (10 - 12 mg/kg; IV) or propofol (4 - 6 mg/kg; IV) Maintenance: isoflurane or halothane *use 0.05 mg/kg in cats

Table 2 - Selected anesthetic protocols for use in animals with heart failure, hypovolemia, dehydration, or those in shock Dogs: Induction: oxymorphone (0.1 mg/kg; IV) plus diazepam (0.2 mg/kg; IV). Give in incremental dosages. Intubate if possible. If necessar y, give etomidate (0.5 - 1.5 mg/kg; IV). Alternately, give thiopental or propofol at reduced dosages. If there are no contraindications to ketamine, reduced dosages of diazepam and ketamine may also be used. Maintenance: isoflurane Cats: Premedication: butorphanol (0.2 - 0.4 mg/kg; SC or IM) or buprenorphine (5-15 Fg/kg; IM) or oxymorphone (0.05 mg/kg; SC or IM) Induction: diazepam (0.2 mg/kg IV) followed by etomidate (0.5 - 1.5 mg/kg; IV). Alternatel y, if not vomiting, mask or chamber induction can be used or give thiopental or propofol at reduced dosages. If there are no contraindications to ketamine, reduced dosages of diazepam and ketamine may also be used. Maintenance: isoflurane

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There may be an unpredictable behavioral response (e.g., excitation, aggressiveness) to benzodiazepine administration in some animals. Induction of anesthesia should be undertaken with caution in animals with cardiopulmonary compromise. Thiobarbiturates should be avoided in patients with significant cardiac disease because they cause dose-dependent cardiac depression and are arrhythmogenic. Propofol (Diprivan7, Rapinovet7) produces rapid induction, but causes essentially the same cardiovascular compromise as thiobarbiturates. Ketamine combined with diazepam also is appropriate for induction of compromised patients, but should be avoided in animals with mitral insufficiency because it increases the regurgitant fraction. Diazepam has minimal cardiopulmonary effects and helps offset the negative effects of ketamine (i.e., muscle rigidity and potential for seizures). Time to intubation is longer than with other agents, but is still considered relatively fast. Opioids can be used for induction of very sick and compromised dogs; however, opioids do not truly induce anesthesia; therefore, intubation may be difficult in alert animals. Etomidate is not arrhythmogenic, maintains cardiac output, and offers rapid induction. Mask induction with isoflurane is discouraged in patients with cardiopulmonary disorders because of the high inspired concentrations and time necessary to achieve intubation. Anesthesia can be maintained with an inhalation agent in most cardiac patients. For compromised patients, isoflurane is the inhalation agent of choice. The insoluble nature of isoflurane allows rapid induction, recovery, and change in the depth of anesthesia. It depresses contractility less than other inhalation agents and is less arrythmogenic. Adjunct intravenous opioids can be administered to decrease the levels of isoflurane necessary to achieve adequate anesthesia. Opioids combined with low concentrations of isoflurane may not produce adequate muscle relaxation which may make administration of a nondepolarizing muscle relaxant desirable. Atracurium (0.1 - 0.2 mg/kg IV) is a short acting muscle relaxant that is not dependent on metabolism or excretion to terminate its action (it must be used with intermittent positive pressure ventilation). Thoracic surgery always requires controlled ventilation. Controlled ventilation can be achieved by manually squeezing the reservoir bag or by a mechanical ventilator attached to the anesthetic machine. Ideally, mechanical ventilation should achieve a tidal volume of 10 to 15 ml/kg of body weight at an inspiratory pressure of 20 cm of water. Assuring adequate ventilation is accomplished by optimizing tidal volume, inspiratory pressure, and respiratory rate to achieve ventilation with the least risk of causing pulmonary injury or cardiovascular compromise. Ultimately, the goal of mechanical ventilation is to maintain normocapnia. Ventilation can be monitored by measurement of end tidal CO2 by capnography, or arterial CO 2 by blood gas analysis.

Techniques Cardiac surgery is not fundamentally different from other types of general surgery and similar principles of good surgical technique (i.e., atraumatic tissue handling, good he-

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mostasis, and secure knot tying) apply. Consequences of poor surgical technique are often devastating. Cardiac surgery differs from other surgeries in that motion from ventilation and cardiac contractions adds to the technical difficulty of performing these procedures. Approaches which provide limited access to dorsal structures (e.g., median sternotomy) require that surgeons incise, suture, and/or ligate structures located deep within the thorax. Ligature placement using hand ties are useful in such situations and the ability to place hand-tied knots (vs. instrument tying) should be considered a fundamental skill for cardiac surgeons. Secure knot tying is critically important to successful cardiac surgery. Hand tying knots is fast and produces tighter and more secure knots than instrument tying. The one-handed knot tie technique is suited best to the fine sutures used in cardiac surgery. Tight knots are facilitated by throwing the first 2 or 3 throws in the same direction before finishing with square knots for security. Closure of cardiovascular structures requires precise suturing techniques and good instrument handling skills to minimize hemorrhage. Using fine suture with swedged-on atraumatic needles (see suture materials below) and carefully following the needle contour when suturing (to minimize the size of needle tracts) are important. Palming of needle holders is a good skill for fast suturing, but should be avoided when suturing inside the thoracic cavity. Finer control is gained by grasping instruments with fingers placed in the instrument rings.

Suture materials/special instruments Polypropylene is the standard suture used for cardiovascular procedures. The most common sizes used are 3-0, 4-0, and 5-0. These sutures should be available with swedged-on taper-point cardiovascular needles in a variety of sizes. Some procedures require that suture be double-armed (i.e., with needles at both ends). Teflon pledgets are useful for buttressing mattress sutures in ventricular myocardium or great vessels. Successful cardiac surgery requires proper surgical instrumentation. Most of the basic instruments required for general surgery can be used for cardiac surgery; however, a few specialized instruments are desirable for thoracic surgery. The standard thoracic retractor is a Finochietto retractor. It is helpful to have at least two sizes to accommodate different sized animals. Self-retaining orthopedic retractors can substitute as thoracic retractors in small dogs and cats. The standard tissue forceps for thoracic surgery is a DeBakey tissue forceps. At least two DeBakey forceps should be available, and it is helpful if one has a carbide inlay for grasping suture needles. Metzenbaum scissors are the standard operating scissors for cardiac surgery. Curved Metzenbaum scissors are more versatile than the straight design. Potts scissors (45 0 angle) are desirable for some cardiac surgery. Needle holders should be long and available in different sizes to accommodate a variety of suture needle sizes. Mayo-Heger, Crile-Wood, and Castroviejo needle holders represent a good selection of sizes for thoracic surgery in animals. Angled thoracic forceps are an impor-

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tant instrument for cardiac surgery and should be available in a variety of sizes. Vascular clamps are non-crushing clamps used for temporary occlusion of cardiovascular and pulmonary structures. They come in a variety of sizes and shapes including straight, angled, curved, and tangential. The most versatile shape for most cardiac surgery is a medium-width tangential clamp.

Postoperative care and assessment Patient monitoring and postoperative care are the cornerstones of successful cardiac surgery. The level of supportive care required for cardiac surgeries depends on the patient and surgical procedure performed. A working knowledge of cardiopulmonary function and good patient observation skills are as important to successful patient management as advanced monitoring devices. Evaluation of ventilation is important after any thoracic surgery. Poor ventilatory efforts may first be noted in the period after surgery when the influence of anesthetic drugs are still present, but ventilatory support has been discontinued. Hypoventilation may also occur from uncontrolled pain. Total ventilation can be assessed directly by measuring the volume of expired gas with a respirometer. Tidal volume should be at least 10 ml per kg of body weight. Ultimately, the best measure of alveolar ventilation is arterial CO2 tension (PaCO2). Alveolar hypoventilation is present when PaCO2 is increased above 40 mm of Hg. Treatment of hypoventilation should be directed at correcting its underlying cause if possible. Drugs that are known to depress ventilation (i.e., opioids and muscle relaxants) should be used with caution in the perioperative period, and the risk of ventilatory depression weighed against the risk of hypoventilation due to pain. Pleural air or fluid should be evacuated if present. Injury or dysfunction of the neuromuscular ventilatory apparatus should be corrected, if possible. If hypoventilation is severe and the cause is not immediately correctable, positive pressure ventilation is indicated. Systemic blood pressure is directly proportional to cardiac output and systemic vascular resistance. Measurement of blood pressure provides a good assessment of cardiovascular function especially during and immediately after surgery. Indirect techniques for measuring blood pressure include the oscillometric method, the basis of monitors such as the Dinamap7 , or Doppler method. Doppler technique provides only systolic pressure, but is useful for evaluating blood pressure trends during and after surgery. Indirect methods of blood pressure assessment are less invasive, but are also less accurate than direct measurements. Direct measurement of blood pressure requires placement of an arterial catheter. Arterial catheters have the additional advantage of providing access for arterial blood gas analysis. An arterial catheter can be placed percutaneously into a dorsal pedal artery of the hindlimb. Direct blood pressure measurement also requires a pressure transducer and monitor, or a manometer. The therapeutic goal is to maintain a mean blood pressure above 65 mm of Hg and systolic blood pressure above 90 mm of Hg. Blood pressure can be elevated by increasing either cardiac output or

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systemic vascular resistance. In most instances, the more appropriate therapeutic strategy to correct hypotension is to improve cardiac output. Maintenance of adequate vascular volume is the most important aspect of maintaining adequate cardiac output. Central venous pressure should be maintained between 5 and 10 cm of water. Indications for arterial pressor therapy are rare. Inotropic and pressor support can be obtained by constant intravenous infusion of epinephrine. Long term inotropic support is maintained by dobutamine. Monitoring the electrocardiogram for disturbances in cardiac rhythm is important for animals undergoing cardiac surgery. Sinus tachycardia is the most common rhythm disturbance in surgery patients. Therapy for sinus tachycardia should be directed at correction of its underlying cause and improvement of cardiac output. Ventricular dysrhythmias including premature ventricular complexes (PVC) and nonsustained or sustained ventricular tachycardia are frequently encountered during and after cardiac surgery. Frequent PVCs, particularly when they occur with a short coupling interval (i.e. R on T phenomena), and rapid ventricular tachycardia should be suppressed in the perioperative period. Continuous intravenous infusion of lidocaine is effective in most instances. Ventricular fibrillation is a form of cardiac arrest that req u i res immediate electrical defi b ri l l ation. If card i a c surgery is performed frequently, equipment for defibrillation should be available.

PATENT DUCTUS ARTERIOSUS The ductus arteriosus is a fetal vessel that connects the main pulmonary artery and descending aorta. During development it shunts blood away from the collapsed fetal lungs. Normally it closes shortly after birth during the transition from fetal to extrauterine life. Continued patency of the ductus arteriosus for more than a few days after birth is termed "patent ductus arteriosus". PDA is the most common congenital heart defect of dogs; it also occurs in cats. PDA causes a left-to-right shunt that results in volume overload of the left ventricle and produces left ventricular dilation and hypertrophy. Pr ogressive left ventricular dilation distends the mitral valve annulus causing secondary regurgitation and additional ventricular overload. This severe volume overload leads to left-sided congestive heart failure and pulmonary edema, usually within the first year of life. Atrial fibrillation may occur as a late sequela due to marked left atrial dilation. Rarely, dogs with PDA develop suprasystemic pulmonary hypertension that reverses the direction of flow through the shunt causing severe hypoxemia and cyanosis (Eisenmenger=s physiology). Right-to-left PDA can occur as a late sequela to untreated PDA. When right-to-left PDA is noted in very young animals it may be due to persistent pulmonary hypertension after birth. Reversal of PDA lessens the risk for developing progressive left-sided heart failure, but causes severe debilitating systemic hypoxemia, exercise intolerance, and progressive polycythemia.

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Diagnosis CLINICAL PRESENTATION Signalment - PDA is seen more commonly in purebred, female dogs. Maltese, Pomeranians, Shetland sheepdogs, English springer spaniels, keeshonds, bischon frise, miniature and toy poodles, and Yorkshire terries are at increased risk to develop PDA. A genetic basis has been established in poodles. History - Most young animals with PDA are asymptomatic or have only mild exercise intolerance. The most common complaint in symptomatic animals with left-to-right shunts are cough or shortness of breath (or both) due to pulmonary edema. Animals with right-to-left or reverse PDA may be asymptomatic or have exercise intolerance and hindlimb collapse on exercise.

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dence of biventricular enlargement and marked enlargement of the pulmonary artery segment. Pulmonary arteries may also appear tortuous. A right-to-left PDA can be documented by performing a saline bubble contrast echocardiogram. Observing bubbles in the descending aorta, but not in any left sided cardiac chamber, is diagnostic.

Laboratory findings Laboratory abnormalities are uncommon in animals with left-to-right shunting PDA; however, animals with right-toleft shunts are commonly polycythemic. Polycythemia occurs in response to increased erythropoietin production due to chronic hypoxemia.

Differential diagnosis Physical examination findings The most prominent physical finding associated with PDA is a characteristic continuous (machinery) murmur heard best at the left heart base. The left apical cardiac impulse is prominent and displaced caudally and a palpable cardiac Athrill@ often is present. Femoral pulses are strong or hyperkinetic (water hammer pulse) due to a wide pulse pressure caused by diastolic runoff of blood through the ductus. Tall R waves (> 2.5 mV) or wide P waves on a lead II electrocardiogram are supportive of the diagnosis, but not always present. Atrial fibrillation or ventricular ectopy may be present in advanced cases. The physical examination findings in animals with rightto-left or reverse PDA differ from those with left-to-right shunts. "Differential" cyanosis is typically present (i.e., cyanosis is most apparent in the caudal mucous membranes), but cyanosis may also be noted in the cranial half of the body in some animals. Cyanosis occurs because there is admixture of non-oxygenated blood (from the pulmonary artery) with the oxygenated aortic blood. Femoral pulses are normal. A systolic cardiac murmur, rather than a machinery murmur, is often present. However, a murmur may not be ausculted if polycythemia is present or if left and right sided pressures are nearly equal and shunting of blood through the ductus is minimal.

The characteristic physical examination findings (i.e., continuous murmur, bounding arterial pulses) makes diagnosis of PDA straightforward in most affected animals. A combination of aortic stenosis/aortic insufficiency or ventricular septal defect/aortic insufficiency results in a to-andfro murmur which may be difficult to differentiate from continuous PDA murmurs. In some animals where the diastolic component of the PDA murmur is difficult to detect, other differentials would include subaortic stenosis, pulmonic stenosis, atrial septal defect, and ventricular septal defect. Differentials for dogs with right-to-left PDA include tetralogy of Fallot, right-to-left shunting atrial or ventricular septal defects, or other complex forms of cyanotic heart disease (rare).

Medical management Animals with pulmonary edema should be given furosemide for 24 to 48 hours prior to surgery. If atrial fibrillation is present, the ventricular response rate should be controlled using digoxin (with or without _-adrenergic blockers or calcium channel blockers) prior to surgery. If hemodynamically significant arrhythmias are present they must be controlled. Complete resolution of clinical signs of congestive heart failure may be difficult with medical management alone.

Radiography/echocardiography Thoracic radiographs typically show left atrial and ventricular enlargement, enlargement of pulmonary vessels, and a characteristic dilation of the descending aorta on the dorsoventral view. Echocardiography provides information that further confirms PDA and helps rule concurrent cardiac defects, but is not invariably required to establish the diagnosis. Echocardiographic findings that support a diagnosis of PDA include left atrial enlargement, left ventricular dilation and hypertrophy, pulmonary artery dilation, increased aortic ejection velocity, and a characteristic reverse turbulent Doppler flow pattern in the pulmonary artery. With right-to-left PDA, thoracic radiographs show evi-

Surgical treatment Surgical correction of PDA is accomplished by ligation of the ductus arteriosus. Ligation of PDA is considered curative and should be performed as soon as possible after diagnosis. Secondary mitral regurgitation usually regresses after surgery due to reduction in left ventricular dilation. Inadvertent ductal rupture during dissection is the most serious complication associated with PDA repair. The risk of this complication decreases as the surgeon's experience increases. Small ruptures, especially those on the back side of the ductus, often respond to gentle tamponade, but will enlarge

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and worsen if dissection is continued. Large ruptures must be controlled immediately with vascular clamps and then repaired with pledget-buttressed mattress sutures. Once bleeding is controlled, a decision must be made whether to continue surgery, or to abandon surgery in favor of repair at a later time. Second surgeries are more difficult due to adhesions at the surgical site, so complete occlusion should be attempted during the initial procedure, if possible. Often, simple ductal ligation is not possible after a rupture has occurred. In such instances, surgical alternatives include ductal closure with pledget-buttressed mattress sutures or ductal division and closure between vascular clamps. The divided ductal ends are closed with a continuous mattress suture oversewn with a simple continuous pattern. Ductal closure without division is safer than surgical division, but re-cannulation of the ductus may occur. Because ductal division requires added technical expertise, it should be undertaken only by experienced surgeons.

Surgical anatomy The ductus arteriosus in dogs and cats is usually wide (1 cm), but relatively short (< 1 cm). It is located between the aorta and main pulmonary arteries, caudal to the origin of the brachycephalic and left subclavian arteries. As a result, most mixing of oxygenated and non-oxygenated blood occurs in the descending aorta in dogs with reverse PDA. Thus, normally oxygenated blood is supplied to the head and neck, while desaturated blood is presented to the caudal half of the body (see comments on differential cyanosis above). The left vagus nerve always passes over the ducts arteriosus and must be identified and retracted during dissection. The left recurrent laryngeal nerve can often be identified as it loops around the ductus.

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Suture materials/special instruments Heavy silk (No. 1 or 0) or cotton tape are suitable materials for ductal ligation. Right angle forceps are best suited for blunt dissection of the PDA and passing ligatures. Angled or tangential vascular clamps are required for surgical division of PDA, or for repair of inadvertent ruptures. Polypropylene mattress sutures (4-0), buttressed with Teflon pledgets, are used for repair of ruptured PDA.

Postoperative care and assessment Postoperative pain should be treated with systemic opioids and local anesthetic techniques. Bupivicaine may be used intercostally or intrapleurally to supplement analgesia. Young animals should be fed as soon as they are fully recovered from surgery. Thoracostomy tubes are occasionally placed prior to thoracic closure (e.g., if intraoperative bleeding occurred). They can generally be removed within 12 to 24 hours after surgery.

Prognosis Dogs with untreated PDA usually develop progressive left-sided congestive heart failure and pulmonary edema. Seventy percent of dogs with untreated PDA die before 1 year of age. Dogs with PDA may also develop suprasystemic pulmonary hypertension that reverses the direction of the shunt causing severe hypoxemia, cyanosis, and exercise intolerance. Ligation of a completely reversed PDA is contraindicated.

VASCULAR RING ANOMALIES SURGICAL TECHNIQUE Perform a left 4th space intercostal thoracotomy. Iden tify the left vagus nerve as it courses over the ductus arte riosus and isolate it using sharp dissection at the level of the ductus. Place a suture around the nerve and gently re tract it. Isolate the ductus arteriosus by bluntly dissecting around it without opening the pericardial sac. Pass a right-angle forceps behind the ductus, parallel to its trans verse plane, to isolate the caudal aspect of the ductus. Then, dissect the cranial aspect of the ductus by angling the forceps caudally approximately 45 degrees. Complete dissection of the ductus by passing forceps from medial to the ductus in a caudal to cranial direction. Grasp the su ture with right-angle forceps. Slowly pull the suture be neath the ductus. If the suture does not slide easily around the ductus, do not force it. Regrasp the suture and repeat the process, being careful not to include surrounding soft tissues in the forceps. Pass a second suture using the same maneuver. Alternatively, the suture may be passed as a double loop and the suture cut so that you have 2 strands. Slowly tighten the suture closest to the aorta first. Then, tighten the remaining suture.

Vascular ring anomalies are congenital malformations of the great vessels and their branches that cause constriction of the esophagus and signs of esophageal obstruction. The most common type of vascular ring anomaly is a persistent fourth right aortic arch, right dorsal aortic root, and rudimentary left ligamentum arteriosum (left sixth arch). The left pulmonary artery and the descending aorta are connected by the ligamentum arteriosum. The esophagus is encircled by the ligamentum arteriosum (or patent ductus arteriosus) on the left, the base of the heart and pulmonary artery ventrally, and the aortic arch on the right. The esophagus is constricted by this vascular “ring” and begins to dilate cranially as food accumulates. Food not passing beyond the constriction is intermittently regurgitated. Chronic regurgitation predisposes to aspiration pneumonia. Approximately 95% of those diagnosed with vascular ring anomalies will have a persistent right aortic arch (PRAA). Persistent left vena cava occurs in conjunction with PRAA in about 40% of the cases. Abnormal location of the great vessels mechanically interferes with function of the esophagus and sometimes the trachea and other adjacent structures. The severity of clinical signs and degree of esophageal stricture depend upon the vascular structures involved. Other types of vascular ring

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anomalies include: (1) persistent right aortic arch with persistent left subclavian artery, (2) persistent right aortic arch with persistent left ligamentum arteriosum and left subclavian artery, (3) double aortic arch, (4) normal left aortic arch with persistent right ligamentum arteriosum, (5) normal left aortic arch with persistent right subclavian artery, and (6) normal left aortic arch with persistent right ligamentum arteriosum and right subclavian artery. Six pairs of aortic arches surround the esophagus and trachea during early fetal life. Normal maturation and selective regression of these arches form the adult vasculature. All vascular ring anomalies have resulted from abnormal development of arches three, four, and six. The mechanism of inheritance is thought to involve single or multiple recessive genes. In the embryo the first and second aortic arches disappear and the fifth arches are incomplete and inconsistent. The third arch joins the dorsal aortic arch and continues an teriorly as the right and left internal carotid arteries. The third arch also forms the brachiocephalic trunk. The dorsal aortas disappear between the third and fourth arches. Normally the left fourth aortic arch and the dorsal aortic root persist to form the permanent aortic arch. The left sixth arch becomes the ductus arteriosus and the right fourth ar ch contributes to the right subclavian artery.

Diagnosis Signalment. Vascular ring anomalies occur in both dogs and cats, but are more common in dogs. German shepherds, Irish setters, and Boston ter riers are the most commonly affected dog breeds. Siamese and Persian cats have been diagnosed more often than other cat breeds. Males and females are equally affected. The condition may affect multiple animals in a litter. Vascular ring anomalies are present at birth. Clinical signs are usually evident at the time of weaning, most being diagnosed between 2 and 6 months of age. The condition may not be recognized until later in life if obstruction is partial and signs are mild. Early diagnosis and treatment of PRAA may improve the prognosis. History. The classic history is acute onset of regurgitation when solid or semisolid food is first fed. Regurgitation of undigested food occurs soon after eating early in the disease; later it may occur at variable times (minutes to hours). Affected animals may grow slower than litter mates and appear malnourished. They often have a voracious appetite, some immediately eating the regurgitated food. Coughing with respiratory distress may be a result of aspiration pneumonia and/or tracheal stenosis secondary to a double aortic arch.

Physical examination findings Affected animals are often thin and small. An enlarged esophagus may sometimes be palpated at the thoracic inlet and neck. The thoracic inlet and caudal neck area may bulge when the chest is compressed. Murmurs are rare; an occasional patient may have a continuous murmur associated with concurrent patent ductus arteriosus. Pneumonia may be suggested by auscultating coarse crackles or finding fever.

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Radiography/ultrasonography/endoscopy Thoracic radiographs may reveal a dilated esophagus cranial to the heart containing air, water, or food. The trachea may be displaced ventrally and the esophagus may overlap it. Signs of pneumonia may be identified. Positive contrast radiography using a barium suspension or barium with food will demonstrate esophageal constriction at the base of the heart with varying degrees of esophageal dilatation extending cranially. The caudal esophagus is usually a normal size, although sometimes it is dilated. Fluoroscopy is beneficial in evaluating esophageal motility. The dilated esophagus does not usually demonstrate normal peristaltic contractions. Although not routinely performed, angiography is beneficial in preoperatively identifying the type of vascular ring anomaly and other cardiac anomalies. Echocardiography may also be beneficial. Endoscopic examination of the esophagus helps rule out other causes of esophageal stricture or obstruction and may reveal esophageal ulceration. Tracheoscopy is not routinely performed, but may document tracheal lumen narrowing secondary to external compression.

SURGICAL TREATMENT Surgical treatment of PRAA is described below. Other types of vascular ring anomalies can be managed in a similar fashion. A persistent left vena cava often covers the left ventral area of the vascular ring . A persistent right ligamentum arteriosum and some aberrant right subclavians should be approached from the right side. Angiograms are helpful in patients with double aortic arches to determine which arch is dominant and if adequate circulation can be maintained after transection of the other arch. It may not be possible to relieve constrictions caused by a double aortic arch. If the animal is severely debilitated, place a gastric feeding tube for several days before surgery. Some surgeons attempt to decrease esophageal lumen size if the esophagus is severely dilated and not expected to return to normal size. This is accomplished by placing a series of nonpenetrating “plication” or “gathering” sutures in the accessible lateral esophageal wall. Alternatively a portion of the esophagus may be resected. These techniques are not recommended routinely because they increase the risk of complications. Surgical transection of the constricting structure(s) is recommended before esophageal dilatation becomes severe. Transection is feasible with most vascular ring anomalies with the exception of some double aortic arches. Perform a lateral thoracotomy at the left fourth (fifth) intercostal space for patients with PRAA. Pack the cranial lung caudally to expose the mediastinum dorsal to the heart. Identify the aorta, pulmonary artery, ligamentum arteriosum, vagus, and phrenic nerves . Identify the anomalous structure(s). If a persistent left cranial cava is present, dissect and retract the vena cava to improve visualization. If a prominent hemiazygous vein is also present, dissect, ligate, and divide it. If a constricting subclavian artery is identified, isolate, ligate, and transect it. Incise the mediastinum, dissect, and elevate the ligamentum arteriosum. Double ligate the ligamentum arte-

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riosum and then transect it. Pass a ballooned catheter or large orogastric tube through the constricted esophagus to aid identification of constricting fibrous bands and to dilate the site. Dissect and transect these fibrous bands from the esophageal wall. Lavage the area, reposition the lung lobes, place a thoracostomy tube if necessary, and close the thorax routinely.

Postoperative care and assessment Postoperative analgesics should be provided as described on p. 650. The patient should be closely monitored for dyspnea and the chest tapped if necessary. Nasal oxygen may benefit dyspneic patients. If a thoracostomy tube has been placed, the thorax should be aspirated at regular intervals (initially every 15 to 30 minutes) and the volume of air and fluid collected at each interval noted. Thoracostomy tubes can generally be removed the day of surgery or by the next morning in these patients. Antibiotics should be continued in debilitated patients if thoracic contamination occurred or if pneumonia exists. Pediatric patients should be closely monitored for hypoglycemia in the postoperative period. Oral intake can be resumed within 12 to 24 hours of surgery. Initially a canned food gruel should be fed with the animal in an upright posture. This stance should be maintained for 10 to 20 minutes after eating to help prevent distention of the dilated esophagus and help reestablish esophageal muscle tone and esophageal siz e. Owners may gradually reduce the amount of water in the food 2 to 4 weeks after surgery if minimal regurgitation has occurred with gruel feeding. Hopefully, addition of water can ultimately be eliminated without increased regurgitation. Animals who can eat solid food without regurgitation should be allowed to eat with the bowl on the floor while standing normally. This feeding practice is continued unless regurgitation frequency increases. Some animals can eventually be fed any type food from a normal stance, while others must continue eating gruel from an elevated stand. The esophagus should be reevaluated with an esophogram 1 to 2 months after surgery to assess persistent dilatation and motility. Sometimes the esophagus returns to a normal size and function. Other times the esophagus remains severely dilated with poor motility. If esophageal constriction occurs, balloon dilation may be beneficial. Owners should be advised against breeding affected animals because it is believed to be a genetic disorder.

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The right atrium is a common primary site for hemangiosarcoma accounting for 40 to 50% of canine cases of hemangiosarcoma. Other reported primary cardiac sites for hemangiosarcoma include the right ventricular free wall, interventricular septum, and main pulmonary artery. Primary cardiac hemangiosarcoma has not been described in cats, but metastasis of hemangiosarcoma to the heart is reported. Chemodectomas can arise from the aortic body at the base of the heart (e.g., between aorta and pulmonary a rt e ry, between aorta and right atrium, or between pulmonary artery and left atrium) or from the carotid body in the neck. Aortic body chemodectomas account for approximately 80% of chemodectomas and occur in older dogs. Chemodectomas occur rarely in cats. Residence at altitude and chronic hypoxia are thought to increase the risk for developing these tumors. Chemodectomas can cause pericardial effusion which probably accounts for the most common clinical presentation of this disease. However, chemodectomas are just as often an incidental finding in older dogs undergoing thoracic radiographs or echocardiography for other reasons. Ectopic thyroid adenomas and carcinomas account for approximately 5 to 10% of all heartbase tumors in dogs.

Diagnosis Signalment - German shepherds older than 8 years of age have been identified as having increased risk to develop hemangiosarcoma. Boxers, English bulldogs, and Boston terriers are the most common breeds to develop chemodectomas. History - Animals with cardiac neoplasia may present for evaluation of dyspnea,cough, syncope, congestive heart failure, or may be asymptomatic .

Physical examination findings The most common clinical presentation for right atrial hemangiosarcoma is acute or chronic cardiac tamponade resulting from intrapericardial hemorrhage. Animals with chemodectomas may present for evaluation of congestive heart failure, signs of cardiac tamponade, pleural effusion, or may be asymptomatic

Radiography/echocardiography CARDIAC NEOPLASIA Cardiac neoplasia is relatively uncommon in small animals. The most important cardiac neoplasms in dogs are right atrial hemangiosarcoma and heart base chemodectoma. A variety of primary intramural and intracavitary neoplasms have been reported in dogs including hemangiosarcoma, fibrosarcoma, chondrosarcoma, rhabdomyosarcoma, ectopic thyroid carcinoma, fibroma, and myxoma. Lymphosarcoma and metastatic neoplasia are the most frequent causes of cardiac neoplasia in cats.

Thoracic radiographs in animals with chemodectomas may show dorsal elevation of the terminal trachea, pleural or pericardial effusion, pulmonary edema, or increased perihilar density. Selective angiography has been used to identify chemodectomas in dogs. Suggestive findings on angiography include identifying tortuous, aberrant vessels at the base of the heart, displacement of the aortic arch, and/or filling defects in the left atria. Angiography is also useful for identifying intracardiac lesions. Echocardiography frequently is useful in identifying masses on the right atrial appendage or at the cardiac base

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Differential diagnosis Cardiac neoplasia must be differentiated from other causes of pericardial effusion, congestive heart failure, or cardiac arrhythmias. Endomyocardial biopsy may be used to make a definitive diagnosis of intracardiac neoplasia. Differentials for radiographic masses near the heart base include hilar lymphadenopathy, left atrial enlargement, aberrant parathyroid or thyroid tissue, and fibrosing pleuritis or pericarditis.

Surgical treatment Pericardiectomy and excision of the right atrial tumor provides palliative relief of signs for atrial hemangiosarcoma. Chemodectomas are highly vascular, slow growing, and moderately locally invasive. Surgical excision of aortic body chemodectomas is possible depending on size, location, and degree of invasiveness of the tumor. However, many animals with chemodectomas and clinical signs associated with pericardial effusion benefit from pericardiectomy without tumor excision. Surgical excision of intramural or intracavitary primary cardiac tumors has been attempted rarely in small animals. Surgical excision of well-defined primary cardiac tumors utilizing inflow occlusion or cardiopulmonary bypass is possible in selected cases. However, given the high malignancy of most primary cardiac tumors, echocardiographic, angiographic, and endomyocardial biopsy findings should be considered carefully in selecting appropriate cases for surgery.

SURGICAL TECHNIQUE Right atrial hemangiosarcoma Perform a median sternotomy or right 4th space inter costal thoracotomy. Clamp the atrial appendage with a tan gential vascular clamp and excise the appendage. Close the atriotomy incision with a continuous mattress suture pat tern. Remove the vascular clamp and oversew the incision with a simple continuous suture pattern. Perform a peri cardiectomy if pericardial effusion is present. Alternatively, the right atrial appendage may be excised with a TA stapling instrument. Chemodectoma The surgical approach for removing chemodectomas depends on the suspected location of tumor. The tumor is sharply dissected from the walls of the great vessels and atria. Use care to avoid rupturing these structures during dissection. Use electrocautery to decrease hemorrhage dur ing excision of these highly vascular tumors.

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is approximately four months. Long term survival of up to several years is possible after surgical removal of an aortic body chemodectoma. In older animals with incidental asymptomatic chemodectoma, the risks of surgical excision should be weighed against the likelihood that the tumor will be slow growing and can remain asymptomatic for a long period of time.

BRADYCARDIA Bradycardia can result from extrinsic causes such as exaggerated vagal tone or electrolyte imbalance, or from intrinsic degenerative disorders of the heart. Sinus bradycardia results from a predominance of parasympathetic influence and often is accompanied by other parasympathetically-mediated rhythms (i.e., sinus arrhythmia, wandering pacemaker, or low-grade second degree atrioventricular block). It is generally considered a physiologic rather than pathologic rhythm. Atrial standstill occurs when the atria fail to conduct an electrical impulse. The cardiac impulse may arise in the sinus node and be conducted to the atrioventricular (AV) node via internodal pathways in the atria (i.e. sinoventricular rhythm) or an escape rhythm may develop. Transient atrial standstill is caused by hyperkalemia. Persistent atrial standstill occurs as a result of a heritable muscular dystrophy syndrome that involves the cardiac atria, ventricles, and scapulohumeral skeletal muscles. Frequent and long sinus pauses may result from degeneration and malfunction of the sinus node. Sick sinus syndrome is the clinical result of sinus node malfunction and is characterized by frequent syncopal and near-syncopal episodes. Sick sinus syndrome may also be accompanied by frequent supraventricular tachycardia. Atrioventricular (AV) block results when there is a delay or block of cardiac impulse conduction through the AV node. First degree AV block is a prolongation of conduction through the AV node and usually results from exaggerated parasympathetic influence on the AV node. Second degree (incomplete) AV block is characterized by intermittent failure of impulse conduction through the AV node. Low-grade (infrequent) second degree AV block usually results from exaggerated parasympathetic influence on the AV node. High grade (frequent) second degree AV block is more likely the result of intrinsic disease of the AV node. Third degree (complete) AV block is a complete failure of conduction through the AV node and strongly implies intrinsic degenerative or infiltrative disease of the AV node. Third degree AV block causes complete AV dissociation and development of a slow ventricular escape rhythm. The result is low and unresponsive cardiac output.

Prognosis Diagnosis The prognosis for right atrial hemangiosarcoma is poor. Micrometastasis is considered present in virtually all cases at the time of diagnosis. Pericardiectomy and excision of the right atrium is palliative. Median survival after surgery

Signalment - English springier spaniels and Siamese cats are predisposed to persistent atrial standstill. Small breed dogs, particularly miniature schnauzers, are predisposed to

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sick sinus syndrome. Third degree AV block occurs in German shepherds and other large breed dogs. History - Clinical signs associated with bradycardia include weakness, exercise intolerance, collapse, and syncope. The relatively short duration of syncopal episodes (usually only a few seconds) and lack of tonic clonic motor activity or postictal signs help distinguish syncope from neurologic seizures with which it is sometimes confused. Physical examination findings/electrocardiography Sinus bradycardia is recognized on the electrocardiogram as a normal but slow rhythm with normal P-QRS-T complexes. It is often accompanied by other vagal-mediated changes (i.e., sinus arrhythmia, wandering pacemaker, and low grade second degree AV block). Sinus bradycardia is abolished by exercise or atropine administration. Electrocardiographic abnormalities associated with transient atrial standstill are bradycardia, small or absent P waves, and shortening and widening of the QRS complexes. Diagnostic rule outs for hyperkalemia include obstructive uropathy, acute renal failure, uroabdomen, acute muscle necrosis, severe acidosis, adrenocortical insufficiency, diabetic ketoacidosis, and iatrogenic potassium intoxication. Electrocardiographic abnormalities associated with persistent atrial standstill are similar (e.g., an absence of P waves and a slow supraventricular or ventricular escape rhythm). Electrocardiographic findings associated with sick sinus syndrome include intermittent severe bradycardia, sinus pauses that last several seconds, supraventricular escape complexes, and occasionally paroxysmal supraventricular tachycardia. Sick sinus syndrome causes frequent syncopal attacks and places the animal at substantial risk for sudden death. Sick sinus syndrome is usually not responsive to acute administration of atropine. First degree AV block is recognized by a prolongation of the P-R interval on an electrocardiogram. Second degree AV block is intermittent failure of impulse conduction through the AV node. On an electrocardiogram, it is recognized as a P wave that is not followed by a QRS-T complex. Low grade second degree AV block is characterized by occasional Adropped complexes@ after several normal complexes and usually is abolished by atropine. High grade second degree AV is characterized by more dropped complexes than conducted complexes and usually does not respond to atropine. Third degree AV block is recognized on an electrocardiogram by complete dissociation of the P waves and QRS-T complexes and the presence of a slow ventricular escape rhythm. Third degree AV block is not atropine responsive.

Radiography/Echocardiography Thoracic radiographs are usually normal or show mild to moderate cardiomegaly. With transient atrial standstill, echocardiography shows a lack of atrial motion and little or no flow through the mitral valve during the atrial filling phase. Echocardiography is also used to rule-out concurrent valvular or congenital abnormalities.

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Surgical treatment Cardiac pacemaker therapy is indicated for bradycardias that are the result of intrinsic cardiac disease, are not responsive to atropine, and are associated with clinical signs.

Preoperative management Most bra dy c a rdias are ex a c e r b ated by anesthetic drugs. Therefore, some accommodation for maintaining an acceptable cardiac rhythm during permanent pacemaker implantation usually is necessary. Preanesthetic medication with an anticholinergic drug (e.g., atropine or glycopyrollate) is indicated, but ra re ly sufficient to prevent worsening of bradycardia during anesthesia. Temporary transvenous pacing is the most reliable method of maintaining an adequate heart rate during pacemaker implantation. Constant intravenous infusion of isoproterenol is an altern at ive, but less reliable, means of maintaining heart rate during permanent pacemaker implantation. Perioperative antibiotic therapy during pacemaker implantation is indicated to reduce the risk of implant associated infections.

Anesthesia Temporary pacemakers can be implanted in dogs under oxymorphone sedation (0.05 - 0.1 mg/kg; IV) plus diazepam (0.1 - 0.2 mg/kg; IV) and a local anesthetic block with lidocaine. Once the animal is paced, etomidate (0.5 - 1.5 mg/kg; IV) can be administered for intubation. Anesthesia should be maintained with isoflurane and oxygen.

Surgical technique Epicardial pacemaker implantation in small animals is accomplished through a midline celiotomy and diaphragmatic incision. The transdiaphragmatic approach has several advantages including avoidance of a thoracotomy and abdominal placement of the gener ator. Perform a celiotomy which extends cranially to the lev el of the xiphoid. Make a vertical midline incision in the diaphragm and expose the cardiac apex. Open the peri cardium and retract it gently with tissue forceps to expose the apex of the left ventricle. Implant a screw-in electrode into the left ventricular apex by turning the electrode tip a specified number of rotations (see instruction sheet ac companying pacemaker; usually 2.5 turns). Bring the lead wire into the abdominal cavity through the diaphragmatic incision and connect it to the pulse generator using a small screw driver. Place the pulse generator in a pocket created between the transverse abdominis and internal ab dominal oblique muscles. Avoid using electrocautery once the permanent pacemaker is functioning. Do not suture the pericardium. Close the diaphragm and abdomen in rou tine fashion.

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Suture materials/special instruments

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Modern cardiac pulse generators are compact, have a long battery life, are pr ogrammable after implantation, and generally are capable of a variety of sophisticated pacing modes. A 3 letter code identifies the intended site of cardiac sensing, intended site for cardiac pacing, and pacing mode. The most commonly used pacing mode in small animals is VVI, which stands for ventricular-sensing, ventricular-pacing, inhibited mode. This means that the pacemaker is intended to pace the cardiac ventricles, but will sense naturally occurring ventricular impulses and inhibit its own output when they occur. This demand function prevents competitive rhythms between the heart and pacemaker should spontaneous intrinsic ventricular activity occur. Most recent model pulse generators are powered by lithium cells that have a life of 8 to 12 years. Pacemakers that have exceeded their shelflife for implantation in humans but still have several years of useful battery life left can often be obtained for a fraction of the cost of new pacemakers. Modern pacemakers are programmable by radiofrequency after implantation for several indices (i.e., pacing rate, stimulus voltage, and sensing voltage). Cardiologists or pacemaker technical representatives usually can provide appropriate programmers for setting pulse generator parameters before and after surgery. Dogs are paced at rate of 70 to 110 bpm depending on size and nature of the animal. Ideally, the stimulus voltage should be approximately 2 times the measured stimulus capture threshold. A voltage of 4 to 5 V is usually adequate. Pacemaker electrodes are either endocardial (transvenous) or epicardial. Endocardial electrodes may be unipolar or bipolar, and are intended for placement in the right ventricle via a jugular vein. Endocardial electrodes may be used for temporary or permanent cardiac pacing. Endocardial electrodes have the advantage of less invasive placement, but require facilities for cardiac catheterization and have a higher incidence of catheter dislodgement. Permanent endocardial electrode placement requires pulse generator implantation in the neck. Epicardial leads are unipolar and require open thoracic surgery for implantation on the epicardial surface. The screw-in epicardial electrode has the advantage of not requiring epicardial sutures and allows a minimal thoracic approach for implantation.

to sense intrinsic cardiac impulses and inhibit their output when intrinsic rhythms occur. Failure of either of these functions can cause serious problems for the patient. Paced beats are recognized on an electrocardiogram by the presence of a stimulus artifact just prior to the QRS-T. A stimulus artifact will be present on the electrocardiogram regardless of whether the stimulus captures the heart. Failure to pace is recognized on an electrocardiogram by the presence of a stimulus artifact that is not followed by a QRS-T. Evaluation of paced beats for the presence of a T wave is important since artifacts that mimic the QRS complex may be present and can be misleading. Failure to pace also is recognized by its failure to generate an arterial pulse. Early failure to pace can be caused by an inadequate stimulus voltage or a faulty connection between the electrode and generator. Late failure to pace can be caused by depletion of the generator battery, electrode breakage or dislodgement, or fibrosis leading to increased impedance at the electrode-myocardial interface. Failure to pace may be correctable by adjusting the pacing stimulus voltage of the generator. Radiographs are useful for evaluating for lead breakage, disconnection, or dislodgement. Failure to sense intrinsic cardiac impulses can lead to competitive rhythms between the heart and pacemaker. Competitive rhythms are harmful because they result in tachycardia and place the patient at risk for ventricular fibrillation. Failure to sense is recognized on the electrocardiogram by the presence of an intrinsic cardiac impulse between two paced impulses with a normal pacing interval. Failure to sense may or may not be accompanied by failure to pace. Failure to sense can be caused by a failing generator battery or by increased impedance at the electrode-myocardial interface. Failure to sense may be correctable by adjusting the sensing voltage threshold of the generator. Premature ventricular complexes are often observed in the immediate postoperative period after pacemaker implantation. The origin of the ventricular complexes is usually consistent with the site of electrode implantation. Ventricular ectopy usually is self limiting and not a major problem as long as the pacemaker is sensing the premature complexes. Ventricular tachycardias that exceed 150 bpm should be suppressed with lidocaine therapy.

Postoperative care and assessment

Prognosis

Pacemaker function should be monitored closely for the first 48 hrs postoperatively, and thereafter every 3 to 6 months. Recognition of normal pacemaker function is an important aspect of pacemaker management after surgery. Demand (VVI) pacemakers should be monitored both for their ability to pace or capture the heart, and for their ability

Animals showing clinical signs of severe exercise intolerance or syncope as a result of bradycardia are at risk for sudden death or development of congestive heart failure. Pacemaker therapy is extremely effective in preventing these consequences and restoring reasonably normal activity to animals with clinically relevant bradycardia.

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Surgical management of tracheal collapse Collasso tracheale: analisi delle esperienze personali su vantaggi e svantaggi dei differenti metodi proposti per il trattamento

Theresa W. Fossum DVM, MS, PhD, Dipl ACVS - Texas A & M University, USA

Tracheal collapse is a commonly recognized disease of toy and miniature-breed dogs (e.g., Toy Poodles, Yorkshire Terriers, Pomeranians, Maltese, Chihuahuas) associated with tracheal cartilage flaccidity and flattening. Either sex may be affected and most animals are middle-aged when clinical signs are noted; however, animals as young as one year of age may be diagnosed with this condition. The etiology of tracheal collapse is unknown and probably multifactorial, but may include genetic and nutritional factors, neurologic abnormalities, and cartilage matrix degeneration. In affected animals, the cartilages usually collapse in a dorsoventral direction, with the cervical trachea collapsing during inspiration and the thoracic trachea collapsing during expiration. With tracheal collapse, clinical signs often progress with age and include abnormal respiratory noise, dyspnea, exercise intolerance, cyanosis, and syncope. Clinical signs are more severe in obese animals. Respiratory noises include wheezing, hacking, coughing, and stridulous breathing, although some dogs do not make abnormal respiratory noises. The cough may be productive or nonproductive but is classically a “goose honk” cough. Coughing often becomes cyclic and paroxysmal and gagging is common. Signs may be elicited or exacerbated by tracheal infections or tracheal compression. Second-hand smoke may also precipitate clinical signs. Differential diagnoses that should be considered include other causes of chronic coughing or respiratory distress such as brachycephalic syndrome, tonsillitis, laryngeal collapse, laryngeal paralysis or paresis, bronchitis, tracheobronchitis, allergies, heartworm disease, pulmonary disease, chronic mitral valvular disease, hypoplastic trachea, tracheal stenosis, and tracheal neoplasia. Tracheal hypoplasia is a congenital form of tracheal stenosis that occurs when tracheal cartilages are abnormally small and abnormally shaped. The tracheal cartilages are circular (the ends appose or overlap), rather than C-shaped, causing tracheal rigidity. The dorsal tracheal membrane is narrow or absent. Tracheal hypoplasia (Table -1) primarily affects brachycephalic breeds, especially English bulldogs. Affected dogs may have other congenital abnormalities such as stenotic nares, elongated soft palate, and megaesophagus. They may have continuous respiratory distress, coughing, and recurrent tracheitis, or may have intermittent signs that are mild or moderate. This condition can typically be diagnosed on radiographs and must be differentiated from tracheal collapse. Treatment consists of symptomatic medical

therapy (i.e., antibiotics, cough suppressants) and correction of other airway obstructions (e.g., resection of nares, palate, saccules); however, because the entire length of the trachea is involved, surgical correction is not feasible. Traumatic stenosis may occur following trauma or surgery. If only a segment of the trachea is involved, the narrowed area may be treated by balloon dilation or tracheal resection and anastomosis may be performed.

Diagnosis Palpation of the trachea may reveal flaccid tracheal cartilages with prominent lateral borders and may elicit paroxysmal coughing. A soft end-expiratory noise may be auscultated in some dogs with intrathoracic tracheal collapse and probably represents the walls of the trachea snapping together during expiration. Abnormal heart sounds may be associated with concurrent cardiac disease. Electrocardiography may reveal sinus arrhythmia or evidence of cor pulmonale or left ventricular enlargement. The first step in diagnosing tracheal collapse is usually to perform inspiratory and expiratory lateral radiographs of the neck and thorax. Because the collapse is dynamic (the cervical trachea collapses on inspiration and the thoracic trachea on expiration), both inspiratory and expiratory films should be taken to evaluate the entire trachea. Radiographs are diagnostic in approximately 60% of patients with moderate to severe tracheal collapse. Fluoroscopy, though seldom available in veterinary practices, facilitates evaluation of the dynamic movement of the trachea and mainstem bronchi through all phases of respiration. Special attention should be paid to evaluating the mainstem bronchi because animals with mainstem bronhial collapse are unlikely to benefit from surgical repair of their collapsing cervical tra-

Table 1 - Radiographic Diagnosis Of Hypoplastic Tracheas • ratio of tracheal lumen diameter at the thoracic inlet to the thoracic inlet diameter (TD/TI) < 0.20 • ratio of tracheal lumen diameter at the midpoint between the thoracic inlet and carina to width of the 3rd rib (TT/3R) < 3.0

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chea. Presently, there is no clinically used method to stent collapsing mainstem bronchi; however, a recent publication investigated intraluminal stents for mainstem bronchial collapse and concluded that such a technique might be useful in affected dogs. In addition to evaluating the trachea on radiographs, thoracic radiographs should also be evaluated for cardiomegaly and pulmonary disease. If tracheal collapse is suspected, but radiographs were non-diagnostic, tracheoscopy should be performed. It is also recommended as a procedure to evaluate the trachea prior to surgery in all dogs, irregardless of radiographic findings. Prior to performing tracheoscopy, laryngoscopy should be performed to rule out associated conditions causing upper airway disease. Laryngeal paresis, paralysis, or collapse is present in approximately 30% of dogs with tracheal collapse. Laryngoscopy must be performed under light anesthesia. During tracheoscopy, tracheal conformation should be evaluated as the scope is withdrawn to determine the location and severity of the collapse. The entire trachea is usually collapsed; however, one area of the trachea is often more severely affected and is used for classification purposes. Grade I tracheal collapse is a 25% reduction in lumen diameter with the trachealis muscle being slightly pendulous and the cartilages maintaining a somewhat circular shape (Table-2). Grade II collapse is a 50% reduction in lumen diameter with the trachealis muscle stretched and pendulous and the cartilages beginning to flatten. Grade III collapse is defined as a 75% reduction in lumen diameter with the trachealis more stretched and pendulous and the cartilages nearly flattened. In grade IV collapse the lumen is essentially obliterated; tracheal cartilages are completely flattened and may invert to contact the trachealis muscle. Tracheal cultures and brushings taken during tracheoscopy are useful in selecting antibiotics. Positive tracheobronchial cultures are found in more than 50% of animals with tracheal collapse.

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Medical Treatment Medical therapy is recommended for all animals with mild clinical signs and those with less than 50% collapse. Medical therapy for dogs with tracheal collapse (Table 3) includes antitussives (i.e., butorphanol tartrate, hydrocodone bitartrate), antibiotics (i.e., ampicillin, cefazolin, clindamycin, enrofloxacin), bronchodilators (i.e., aminophylline, oxtriphylline), and/or corticosteroids (i.e., dexamethasone, prednisone). Sedation with acepromazine (0.05 to 0.2 mg/kg [maximum 1 mg] intravenously, intramuscularly, or subcutaneously, TID) and/or diazepam (0.2 mg/kg intravenously BID) and supplemental oxygen may be required in severely dyspneic patients. Weight reduction should be instituted for obese patients. Exercise restriction is recommended. Affected dogs should be maintained in an environment free of smoke and other respiratory irritants or allergens. Response to medical therapy is usually transient and the disease typically progresses.

Surgical Treatment Surgery is recommended for all dogs with moderate to severe clinical signs, a 50% or greater reduction of the tracheal lumen (without significant mainstem bronchial collapse; see above), and those refractory to medical therapy. Dogs presenting with laryngeal paralysis or collapse, generalized cardiomegaly, and chronic pulmonary disease are poor surgical candidates. Coughing and dyspnea caused by laryngeal, pulmonary, or cardiac disease are unlikely to improve without appropriate therapy. Respiratory distress and death may occur in animals with severe laryngeal dysfunction or bronchopulmonary disease .

Table 3 - Medical Therapy of Tracheal Collapse Table-2 - Classification of Tracheal Collapse

butorphanol tartrate (Torbutrol®) - 0.5 - 1.0 mg/kg; PO; BID to TID

Grade I • 25% reduction in lumen diameter • trachealis muscle is slightly pendulous • cartilages are more circular than flattened

hydrocodone bitartrate (Hycodan®) 0.2 mg/kg; PO; TID to QID

Grade II • 50% reduction in lumen diameter • trachealis muscle somewhat stretched and pendulous • cartilages mildly flattened

clindamycin (Antirobe®) - 11 mg/kg; PO; BID

Grade III • 75% reduction in lumen diameter • trachealis muscle is stretched and pendulous • cartilages nearly flat Grade IV • tracheal lumen is obliterated

ampicillin - 22 mg/kg; IV, IM, SC, PO; TID cefazolin (Ancef®, Kefzol®) 20 mg/kg; IV, IM; TID enrofloxacin (Baytril®) - 5 - 10.0 mg/kg; PO or IM; BID aminophylline dogs - 11 mg/kg; PO , IM, IV; TID cats - 5 mg/kg; PO; BID oxtriphylline elixir (Choledyl®) - 15 mg/kg; PO; TID dexamethasone (Azium®) 0.2 - 0.5 mg/kg; IV, IM, SC; BID; up to 2 mg/kg for emergency treatment prednisone - 1 - 2 mg/kg; PO; SID to BID

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Figure 1 - From: Fossum, TW: Small Animal Surgery, Mosby Publishing Co., St. Louis, Mo, 1997.

The goal of surgery is to support the tracheal cartilages and trachealis muscle, while preserving as much of the segmental blood and nerve supply to the trachea as possible. Many techniques have been described. Currently, the only techniques that meet this goal are placement of individual rings or modified spiral ring prostheses (Figure 1). Generally only the cervical trachea and most proximal portion of the thoracic trachea are supported, even when cervical and thoracic tracheal collapse are present. Readers are referred to

surgical textbooks for descriptions of tracheoplasty using individual ring prostheses. Patients with concurrent laryngeal paralysis or laryngeal collapse may also require arytenoid lateralization or permanent tracheostomy, respectively. The main complication of tracheoplasty is laryngeal paralysis. The segmental blood and nerve supply to the trachea travels in the lateral pedicles on each side of the trachea. The left recurrent laryngeal nerve is located in the lateral pedicle; the right is sometimes located within the carotid sheath.

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Surgical treatment of laryngeal paralysis Emiplegia laringea: analisi delle esperienze personali su vantaggi e svantaggi dei differenti metodi proposti per il trattamento

Theresa W. Fossum DVM, MS, PhD, Dipl ACVS - Texas A & M University, USA

LARYNGEAL COLLAPSE Laryngeal collapse occurs secondary to chronic upper airway obstruction or trauma. Trauma may fracture or disrupt the laryngeal cartilages and allow medial collapse. Laryngeal collapse due to chronic upper airway obstruction and cartilage fatigue or degeneration is most common. The obstruction causes increased airway resistance, increased negative intraglottic luminal pressure, and increased air velocity. These forces displace laryngeal structures medially with permanent cartilage deformation and fatigues the cartilages. Increased inspiratory effort irritates the mucosa causing inflammation and edema. This further obstructs the airway causing more airflow resistance and increasing the effort of breathing. Laryngeal collapse is described in three stages. Stage 1 is commonly referred to as laryngeal saccule eversion. Medial deviation of the cuneiform cartilage and aryepiglottic fold or aryepiglottic collapse is Stage 2 collapse, while Stage 3 collapse is medial deviation of the corniculate process of the arytenoid cartilages or corniculate collapse. Stages 2 and 3 are advanced stages of laryngeal collapse. Diagnosis of laryngeal collapse that occurs concurrently with other upper respiratory abnormalities (i.e., elongated soft palate, stenotic nares) is easily overlooked on oral examination. If response to treatment is less than expected following appropriate surgery for these abnormalities, laryngeal collapse may be present.

LARYNGEAL PARALYSIS Laryngeal paralysis causes upper respiratory obstruction and mild to severe dyspnea. Because of dysfunction of the laryngeal muscles, recurrent laryngeal or vagus nerves, or cricoarytenoid ankylosis, acquired or congenital neurologic causes are most common. The intrinsic laryngeal abductor and adductor muscles are innervated by the recurrent laryngeal nerves. Subsequent atrophy of the cricoarytenoideus dorsalis muscle causes the cartilages to remain in a paramedian position during inspiration, preventing maximal air intake and increasing airflow resistance. Ineffective laryngeal adduction and closure during swallowing predisposes the patient to aspiration of food and secretions causing subsequent aspiration pneumonia. Congenital, inherited laryngeal paralysis occurs in the Bouvier de Flanders, Bull Terriers, Siberian Huskies, and Dalmatians. Laryngeal paralysis in Bouvier's is due to de-

generation of the nucleus ambiguous. Polyneuropathy associated with dying-back of peripheral nerves causes laryngeal paralysis in Dalmatians. Acquired laryngeal paralysis is usually idiopathic but may occur secondary to trauma, disease (e.g., polyneuropathy, myopathy, Chagas disease [Trypanosomiasis], hypothyroidism, neoplasia), or may be iatrogenic following surgery. It affects one or both sides of the larynx; however, unilateral paralysis is often asymptomatic . Surgical treatment is recommended for patients with laryngeal paralysis who have moderate to severe signs of respiratory distress. The goal of treatment is to enlarge the glottis without exaggerating aspiration of food or saliva. Many surgical techniques have been described to treat laryngeal paralysis including partial laryngectomy, lateralization, castellated laryngofissures, and muscle nerve pedicle transposition. Vocal fold excision enlarges the ventral aspect of the glottis, is effective in mild-moderate cases, and is relatively easy to perform. However, glottic stenosis occurs in approximately 20% of the cases and is difficult to treat successfully. Partial arytenoidectomy (corniculate process) enlarges the dorsal aspect of the glottis. Its success is dependent on the skill of the surgeon. Serious complications and death occur in up to 50% of the cases following partial arytenoidectomy. The modified castellated laryngofissure technique is a combination of vocal fold excision, lateralization and laryngofissure creation to enlarge the glottis. This technique is effective but technically difficult. Muscle-nerve pedicle transposition can successfully reinnervate the larynx and improve function, but the process takes 5 to 11 months before clinical improvement is seen. Arytenoid lateralization is recommended as it gives consistently good results (> 90%) with few complications.

Unilateral Arytenoid Lateralization Make a skin incision just ventral to the jugular vein begin ning at the caudal angle of the mandible and extending over the dorsolateral aspect of the larynx to 1 to 2 cm caudal to the lar ynx (Figure 1). Incise and retract subcutaneous tissues, platys ma, and parotidoauricularis muscles. Retract the sternocephali cus muscle and jugular vein dorsally and the sternohyoid mus cle ventrally to expose the laryngeal area. Palpate the dorsal margin of the thyroid cartilage. Incise the thyropharyngeus mus cle along the dorsolateral margin of the thyroid cartilage lami na. Place a stay suture through the thyroid cartilage lamina to retract and rotate the larynx laterally. Identify the cricoary -

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Figure 1 - From: Fossum, TW: Small Animal Surgery, Mosby Publishing Co., St. Louis, Mo, 1997.

tenoideus dorsalis muscle. Disarticulate the cricothyroid articu lation with a # 11 blade or scissors. Palpate, identify, and disar ticulate the cricoarytenoid articulation at the muscular process. Using curved Metzenbaum scissors transect the sesamoid band (interarytenoid ligament) between the two corniculate processes being careful not to penetrate the laryngeal mucosa. Place a polypropylene suture (2-0 to #2) through the muscular process of the arytenoid cartilage and the caudal one-third of the cricoid cartilage near the dorsal midline to mimic the direction of the cricoarytenoid muscle. Alternatively, place the suture through the muscular process and the most caudodorsal aspect of the thyroid cartilage. Muscular process-to-thyroid cartilage sutures tend to pull the arytenoid laterally while muscular process-tocricoid cartilage sutures tend to rotate the arytenoid laterally. Tie the suture with enough tension to moderately abduct the ary tenoid cartilage. Have an assistant verify abduction by intraoral visualization of the larynx. If abduction is insufficient the suture can be repositioned to achieve better abduction. Lavage the sur gical site. Appose the thyropharyngeus muscle with a cruciate or simple continuous pattern (3-0 polydioxanone). Appose subcu taneous tissues and skin routinely.

Partial Laryngectomy Partial laryngectomy may be done via an oral approach or a ventral laryngotomy approach. Vocal fold resection and

unilateral resection of the corniculate, cuneiform, and vocal processes of the arytenoid cartilage should be performed. Partial laryngectomy via an oral approach is extremely difficult in small dogs because of limited exposure. Via an oral approach - Grasp the corniculate process and retract it medial with biopsy forceps. Use a long-handled scalpel or scissors to excise the corniculate process and the proximal half and base of the cuneiform process. Do not ex cise the aryepiglottic fold or the distal half of the cuneiform process. Remove the vocal fold, vocal process, and vocal muscle with biopsy forceps and/or Metzenbaum scissors. Control bleeding by applying pressure with gauze sponges. Via a laryngotomy approach - Make a ventral midline in cision over the larynx. Separate the sternohyoid muscles and incise the cricothyroid membrane and thyroid cartilage on the midline. Retract the edges of the thyroid cartilage with small Gelpi forceps. Visualize the arytenoid cartilages and vocal folds. Have an assistant visualize the larynx per os to help de termine how much to remove. After incising the mucosa over the corniculate, cuneiform, and vocal processes of ONE ary tenoid cartilage, excise them with scissors or a scalpel. Also excise the vocal fold on that side (if necessary excise the vocal cord and process on the opposite side). Excise redundant mu cosa and suture the defect with 4-0 to 6-0 absorbable suture material in a continuous pattern. Suture the thyroid cartilage with interrupted sutures that do not penetrate the laryngeal lu men. Close subcutaneous tissues and skin routinely.

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Epidemiologia della filariosi felina nel Nord Italia Claudio Genchi Med Vet - Facoltà di Medicina Veterinaria, Università degli Studi di Milano

Laura H. Kramer Facoltà di Medicina Veterinaria, Università degli Studi di Parma

La sieroprevalenza di anticorpi contro Dirofilaria immi tis è stata valutata in 1045 campioni di sangue di gatti, per la grande maggioranza asintomatici e residenti in varie aree del Nord Italia, al fine di valutare la diffusione del parassita nella popolazione felina e il rischio di infestazione. La ricerca degli anticorpi è stata eseguita sul plasma utilizzando un kit del commercio (Heska™ Solo Step™ Filariosi Felina, Heska Corporation). Tutti i campioni sono stati inoltre esaminati per presenza di microfilarie circolanti mentre solo i campioni positivi al test anticorpale sono stati sottoposti anche alla ricerca degli antigeni circolanti del parassita adulto (PetCheck®, IDEXX Laboratories Inc.). Dei 980 campioni appartenenti a soggetti di età superiore all’anno e mai sottoposti a trattamento chemioprofilattico contro il parassita, 157 sono risultati positivi alla ricerca degli anticorpi (16%). Di questi, 5 (3%) sono risultati positivi anche al test per la ricerca degli antigeni. Sette campioni sono risultati positivi anche alla ricerca delle microfilarie circolanti (0,7% dell’intero campione esaminato). La percentuale di soggetti positivi varia da un minimo del 9% in provincia di Alessandria e di Brescia a valori compresi tra il 18% di Pavia e il 26-27% di Verona e Treviso. Nessuna risposta positiva è stata osservata in gatti residenti in zone esenti da filariosi canina quali la provincia di Sondrio o dove l’infestazione nel cane è sporadica come la province di Genova e La Spezia. L’età non è risultata un fattore discriminante mente i maschi hanno presentato valori significativamente superiori a quelli osservati nelle femmine (P<0.05). La prevalenza anticorpale è risultata significativamente superiore nei soggetti che vivevano prevalentemente all’esterno (P=0.008) o che potevano frequentare sia l’ambiente interno sia quello esterno (P=0.005) rispetto a quella

osservata nei soggetti che vivevano prevalentemente in casa, per i quali è stata comunque osservata una prevalenza del 10%. Quattro campioni di plasma dei 25 pr ovenienti da gatti sottoposti a profilassi e 3 dei 40 ottenuti da gatti di età inferiore all’anno hanno dato risposte positive di varia intensità al test anticorpale. Per quanto riguarda l’utilizzo nella pratica dei test di immunomigrazione rapida, come quello utilizzato in questa indagine, vale la pena di ricordare che l’intensità della risposta colorimetrica della banda di positività è in generale variabile. L’intensità della risposta può elevata (talvolta la banda di positività compare prima di quella di controllo) bassa, o lieve e la reazione positiva compare allo scadere del tempo di reazione indicato dalle metodiche dei test utilizzati. Tenuto conto che le reazioni aspecifiche sono da considerarsi rare (la specificità del test da noi utilizzato è stata valutata in lavori sperimentali pari al 98,5%), risposte di lieve intensità indicano bassi livelli di anticorpi circolanti (< 20 AbU/ml) e sono nella maggior parte dei casi indicative di infestazioni abortite, di infestazioni prepatenti o infestazioni pregresse esitate con la morte spontanea del parassita nonostante il permanere degli anticorpi in circolo. Le risposte francamente positive o di elevata intensità sono più facilmente correlabili a risposte antigeniche positive e sono indicative della presenza del parassita adulto in sede polmonare o cardiaca. Sulla base di queste considerazioni, è possibile affermare che i test anticorpali rappresentano il primo approccio diagnostico alla malattia nel gatto che deve essere poi confermato tramite ulteriori approfondimenti diagnostici. In caso di bassa positività anticorpale è buona norma ripetere il test dopo 2-4 mesi per l’accertamento dell’evoluzione dell’infestazione.

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Periodontal disease – Prevention is the key! La prevenzione come regola fondamentale e prima opzione terapeutica in odontostomatologia veterinaria

Cecilia Gorrel BSc, MA, Vet MB, DDS, MRCVS Hon FAVD, Dipl EVDC - Pilley, Nr Lymington - Hants, REGNO UNITO

Periodontal disease is probably the most common disease seen in small animal practice1. The great majority of dogs and cats over three years of age have a degree of disease, which warrants intervention. There is strong circumstantial evidence that a focus of infection in the oral cavity may cause disease in distant organs as a consequence of dissemination of oral bacteria via the blood stream2. Also, periodontitis often causes discomfort to the affected animal. Thus, maintaining periodontal health in our domestic pets is not a cosmetic concern, but a general health and animal welfare issue. Periodontal disease is a collective term for a number of plaque-induced inflammatory conditions affecting the periodontium of the tooth. Gingivitis is the term used when the inflammatory response is limited to the gingiva. Gingivitis is reversible. The aim of treatment in the gingivitis patient is to restore the gingiva to health. Untreated gingivitis may progress to periodontitis, when the inflammatory responses involve the periodontal ligament and alveolar bone. The end result of periodontitis is loss of the tooth due to the destruction of its supporting apparatus. In practical terms, periodontitis is generally irreversible. The aim of treatment in the periodontitis patient is thus to prevent progression of existing lesions, and, perhaps more importantly to prevent the development of new lesions. In fact, prevention is the key for successful management of periodontal disease!

as yet not possible to state whether the microbiota found in deep pockets are the cause or an effect of periodontitis. Many microbial products have little or no direct toxic effect on the host; instead they possess the potential to activate nonimmune and immune inflammatory reactions. It is these inflammatory reactions, which actually cause the tissue damage. Other conditions, such as concurrent systemic diseases, physical or psychological stress and malnutrition may impair the host’s ability to mount an appropriate inflammatory response to the presence of plaque on the tooth surfaces, and can, as such, aggravate periodontitis but do not cause destructive tissue inflammation per se.

AETIOLOGY AND PATHOGENESIS

PREVENTION

The primary cause of gingivitis and periodontitis is accumulation of plaque on the tooth surfaces. Calculus (tartar) is a secondary aetiologic factor. The main significance of calculus is that it provides a surface, which harbours plaque. The pathogenesis of periodontal disease is by no means fully elucidated. The plaque bacteria and their products, as well as the inflammatory reactions of the host contribute to the destruction of the periodontium. The pathogenic mechanisms involved in periodontal disease include: 1. direct injury by plaque micro-organisms, 2. indirect injury by plaque micro-organism via inflammation. Although numerous microbiological studies have been performed, the association between specific periopathogens and periodontitis remains to be conclusively proven, and it is

Preventing periodontal disease relies on reducing the plaque burden. Mechanical plaque control is the mainstay of periodontal disease prevention and therapy. Adjunctive chemical plaque control is indicated in some situations.

CLINICAL CONSIDERATIONS Undisturbed plaque accumulation will result in gingivitis. However, all animals with untreated gingivitis will not progress to periodontitis. Clinically healthy gingivae can be maintained by frequent (usually daily) plaque removal. Animals with clinically healthy gingivae will not develop periodontitis3. The aim of periodontal therapy is to prevent all gingivitis, and consequently periodontitis. In animals with established periodontitis, the aim of therapy is to prevent new lesions from developing and also arresting progression of existing disease.

MECHANICAL PLAQUE CONTROL 1) Toothbrushing Toothbrushing is the single most effective means of removing supra-gingival plaque4,5. A toothbrush cleans around 1 mm below the gum line. It is the mechanical action of the brushing rather than any component in the toothpaste, which provides the benefit.

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2) Dietary texture In the last few years attempts have been made to control accumulation of dental deposits (plaque and calculus) by means of diets or dietary adjuncts specifically designed for this purpose6,7,8,9,10,11,12. Most of these products do reduce the rate of accumulation of plaque and calculus and consequently result in a reduction in gingivitis. None of these methods have been shown to maintain clinically healthy gingivae in the absence of tooth brushing13. A reduction in gingivitis may not be sufficient to prevent the development of periodontitis. Longer-term studies are required to investigate the effect of reducing gingivitis in relation to development of periodontitis.

CHEMICAL PLAQUE CONTROL Chlorhexidine is the gold standard against which other agents are tested. Chemical plaque control is generally used as an adjunct to mechanical plaque control.

THE ROLE OF ANTIBIOTICS IN PERIODONTAL THERAPY It is generally recognized that antimicrobial treatment is of secondary importance in the treatment of periodontal disease, compared to mechanical removal of dental deposits and periodontal pocket management14,15,16. Where follow-up mechanical plaque control is successfully instituted, no benefit can be shown as a result of including antimicrobial therapy with mechanical debridement as compared to mechanical debridement alone17; however, in dogs where no postscaling homecare is provided, there is a demonstrable longterm retardation effect following short-term antimicrobial therapy18. Consequently, systemic antimicrobial therapy cannot be recommended as prevention and/or first line treatment of periodontal disease, and definitely not in the absence of mechanical periodontal therapy. However, systemic antimicrobials are an accepted and useful adjunctive modality in the treatment of periodontal disease in specific situations, e.g. severe local infection, dangers of bacteraemia to a systemically ill or immune compromised animal.

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disease. Plaque starts to form on a clean tooth surface within minutes and calculus within a few days. Undisturbed plaque accumulation will result in gingivitis within a few weeks3,13. The effect of periodontal therapy has very shortterm effects if unaccompanied by home care11.

2) The role of professional therapy Even with good home care, most animals will require professional periodontal therapy at regular intervals. The goal of periodontal therapy is to provide an environment, which the owner can keep clean. The rate of plaque and calculus accumulation varies between animals, but does seem to remain relatively constant for the lifetime of the individual animal. It is important to identify the individual timing for professional intervention. It is also important to remember that this interval may change with age and concurrent medical problems.

In summary The goal should be to prevent gingivitis and thus periodontitis. An oral hygiene programme consisting of home care measures and professional intervention at regular intervals should be identified for each animal. Continuous reinforcement of the owners' motivation is most important.

References 1.

MANAGEMENT OF PERIODONTAL DISEASE IN GENERAL PRACTICE

1) Client education and institution of an oral hygiene programme

Every effort should be made to educate dog and cat owners. If a suitable oral hygiene programme performed by the owner, i.e. home care, is instituted at an early age, it is possible to completely prevent periodontal disease. This should be the goal. The owner must be made aware that it is the daily oral hygiene measures performed at home which are the most important aspect of both preventing and treating periodontal

9. 10.

11.

12.

Gorrel C,Robinson J: Periodontal Therapy and Extraction Technique. In:Crossley, DA, Penman S, eds. Manual of Small Animal Dentistry. United Kingdom: British Small Animal Veterinary Association, 139149,1995. DeBowes LJ et al. Association of Periodontal Disease and Histologic Lesions in Multiple Organs from 45 Dogs. J Vet Dent 13 (2):57-60, 1996. Lindhe J, Hamp S-E, Loe H. Plaque Induced Periodontal Disease in Beagle Dogs. A 4-year Clinical,Roentgenographical and Histometrical Study. J Periodontol Res 10:243-255, 1975. Tromp JA, Jansen J, Pilot T. Gingival health and frequency of toothbrushing in the beagle dog model. Clinical findings. J Clin Periodontol 13; 164-168,1986. Tromp JA, van Rijn LJ, Jansen J. Experimental gingivitis and frequency of tooth-brushing in the beagle dog model. Clinical findings. J Clin Periodontol 13; 190-194, 1986. Logan E I. Oral Cleansing by Dietary Means: Results of Six-Month Studies. Proceedings of a Conference on Companion Animal Oral Health, University of Kansas, March 1-3, 1996. Gorrel C, Rawlings JM. The Role of a ‘Dental Hygiene Chew’ in Maintaining Periodontal Health in Dogs. J Vet Dent 13 (1): 31-34, 1996. Gorrel C, Rawlings JM. The Role of Tooth-brushing and Diet in the Maintenance of Periodontal Health in Dogs. J Vet Dent 13 (3): 139143,1996. Gorrel C, Rawlings J, Markwell P. Effect of Two Dietary Regimens on Gingivitis in the Dog. J Small Animal Practice 38: 147-151,1997. Gorrel C, Inskeep G. Benefits of a Dental Hygiene Chew on the Periodontal Health of Cats. Proceedings,Annual Congress of the British Small Animal Veterinary Association, 2-5 April, 1998. Gorrel C, Bierer TL. Longer Term Benefits of a Dental Hygiene Chew on the Periodontal Health of Dogs. Proceedings, 11th Annual Veterinary Dental Forum,1997. Gorrel C,Bierer TL. Benefits of a New Dental Hygiene Chew on the

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13.

14.

15.

Periodontal Health of Dogs. Proceedings, Annual Congress of the British Veterinary Dental Association, 1 April,1998. Gorrel C et al. The Effect of Daily Toothbrushing on Ging ivitis and Plaque Accumulation in the Dog. Proceedings, 11th Annual Veterinary Dental Forum, 1997. Sarkiala E, Harvey CE. Systemic antimicrobials in the treatment of periodontitis in dogs. Seminars in Veterinary Medicine and Surgery 8(3): 197-203, 1993. Henke CL, Colmery BH. Treating canine dental infections with oral

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clindamycin hydrochloride. Vet Med, Feb: 197-199,1987. Hennet, Ph. Utilisation de la spiramycine et du metranidazole lors de maladie parodontale chez le chien. Rec Vet Med 167:1029-1036, 1991. Loesche WJ. Rationale for the use of antimicrobial agents in periodontal disease. Int J Technol Assess Health Care 6:403-417,1990. Sarkiala E., Asikainen SEA, Kanervo A, Junttila J & Jousimies-Somer HR. The efficacy of tinidazole in naturally occurring periodontitis in dogs:bacteriological and clinical results. Vet Microbiol 36:273288, 1993.

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Periodontal disease in the cat Malattie periodontali nel gatto, lesioni odontoclastiche erosive dei denti del gatto e stomatite cronica: cosa c’è di nuovo

Cecilia Gorrel BSc, MA, Vet MB, DDS, MRCVS Hon FAVD, Dipl EVDC - Pilley, Nr Lymington - Hants, REGNO UNITO

Periodontal disease (a collective term for plaque-induced inflammatory lesions of the periodontium) is probably the most common disease seen in small animal practice1. The great majority of dogs and cats over three years of age have a degree of disease, which warrants intervention.

flamed gingivae to health and of then maintaining clinically healthy gingivae. However, adult cats are often not amenable to tooth brushing and mechanical reduction of accumulation of dental deposits (plaque and calculus), thus reducing the severity of gingivitis by dietary means, is a useful adjunctive measure and should be highly recommended to pet owners.

CLINICAL CONSIDERATIONS Undisturbed plaque accumulation will result in gingivitis. However, all animals with untreated gingivitis will not progress to periodontitis. Clinically healthy gingivae can be maintained by frequent (usually daily) plaque removal. Research in dogs show that animals with clinically healthy gingivae will not develop periodontitis 2. It is assumed that the same holds true for the cat.

PERIODONTAL DISEASE IN GENERAL VETERINARY PRACTICE In a general practice situation, the great majority of cats will have gingivitis, as most pet owners do still not perform daily plaque removal. Many animals, especially middle aged or older individuals will also have periodontitis of one or several teeth. It is important to differentiate between the gingivitis patient and the one who also has evidence of periodontitis, as treatment options will differ. In the cat, it is also particularly important to identify other dental problems, commonly FORL, so that these can be dealt with appropriately.

THE GINGIVITIS PATIENT Gingivitis is reversible. Removal or adequate reduction of plaque will restore inflamed gingivae to health. Once clinically healthy gingivae have been achieved, these can be maintained by daily removal or reduction in the accumulation of plaque. In short, the treatment of gingivitis is to restore the inflamed tissues to clinical health and then to maintain clinically healthy gingivae thus preventing periodontitis. There is as yet no magic bullet that we can feed our pets to prevent periodontal disease. Daily tooth brushing remains the single most effective means of restoring in-

SUMMARY FOR TREATMENT OF GINGIVITIS • Educate the owner to understand the disease process • Institute an appropriate home care r egimen • Professional periodontal therapy (supra- and sub-gingival scaling and polishing) under general anaesthesia to remove dental deposits (plaque and calculus) • Regular professional check-ups to ensure that the owner is following recommendations and to boost the owner’s motivation.

THE PERIODONTITIS PATIENT As already stated, untreated gingivitis may progress to periodontitis. It is important to remember that periodontitis is a site-specific disease, i.e. it may affect one or more sites of one or several teeth. In most instances in a practice situation, periodontitis is irreversible. The aim of treatment is thus to prevent development of new lesions at other sites and to prevent further tissue destruction at sites which are already affected. Tissue destruction in periodontitis is assessed by a number of parameters. The factors that must be evaluated for each patient are periodontal probing depth, evidence of gingival recession, and evidence of furcation involvement. In many cases, measurement of periodontal attachment level (PAL) by means of probing and loss of alveolar bone by means of radiography is also indicated. The findings should be recorded on a chart. Home care is also a most important aspect of treating periodontitis. Following professional therapy, the owner must prevent or remove the accumulation of plaque on a daily basis. If the cat is not amenable to homecare, then extraction of teeth affected by periodontitis is recommended.

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SUMMARY FOR TREATMENT OF PERIODONTITIS • Educate the owner to understand the disease process • Institute daily tooth brushing regimen by the owner +/- adjunctive chemical plaque control • Professional periodontal therapy; this includes supra- and sub-gingival scaling and polishing, rootplaning and extraction of unsalvageable teeth under general anaesthesia • Regular professional check-ups to ensure that the owner is following recommendations and to boost the owner’s motivation

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• Be prepared to extract affected teeth if the owner cannot maintain a standard of plaque control which halts progression of established lesions

References 1.

Gorrel C,Robinson J: Periodontal Therapy and Extraction Technique. In:Crossley, DA, Penman S, eds. Manual of Small Animal Dentistry. United Kingdom: British Small Animal Veterinary Association, 139149,1995. Lindhe J, Hamp S-E, Loe H. Plaque Induced Periodontal Disease in Beagle Dogs. A 4-year Clinical, Roentgenographical and Histometrical Study. J Periodontol Res 10:243-255, 1975.

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Le patologie iatali del cane e del gatto: un problema di difficile interpretazione Massimo Gualtieri Med Vet - Istituto di Clinica Chirurgica e Radiologia Veterinaria - Università degli Studi di Milano

Con il termine “patologie iatali” si intende un grande numero di processi patologici a carico dello sfintere esofageo inferiore (LES) e dello iato esofageo diaframmatico che conducono, nella quasi totalità dei casi, ad una esofagite da reflusso. I fattori responsabili delle lesioni esofagee in seguito a reflusso sono numerosi, ovvero carattere del materiale refluito, efficienza del meccanismo di svuotamento esofageo, volume e frequenza del reflusso, tempo di permanenza del materiale refluito in esofago e integrità della barriera mucosa esofagea. La lesione che ne deriva può essere limitata, nei casi lievi, alla sola mucosa oppure coinvolgere lo strato muscolare e condurre anche a formazione di stenosi o a perforazione. Le patologie iatali possono essere determinate da anomalie di sviluppo dello iato esofageo (forme congenite), essere secondarie a cause che alterano la pressione del LES (ernia iatale, vomito cronico, ritardato svuotamento gastrico, anestesia generale, posizionamento chirurgico [Trendelembur], posizionamento di sonde rinogastriche o faringostomiche che oltrepassano lo sfintere esofageo inferiore) o a cause traumatiche (improvviso aumento della pressione intra-addominale). I segni clinici della “malattia da reflusso” dipendono in parte dalla gravità delle lesioni esofagee, in parte dalla natura della lesione che la determinano. In generale possono essere costituiti da anoressia, disfagia, odinofagia, salivazione profusa e rigurgito frequentemente costituito dall’emissione di saliva spessa, biancastra e filante associati o meno a tosse, dispnea e febbre. Tra le patologie responsabili di disordini di questo distretto anatomico consideriamo l’incompetenza cardiale, l’ernia iatale esofagea (o da scivolamento), l’ernia iatale paraesofagea e l’intususcezione gastroesofagea. L’incompetenza cardiale può essere determinata dall’incoordinato funzionamento del muscolo dello sfintere esofageo inferiore e dei pilastri diaframmatici. Questi agirebbero sinergicamente nel proteggere l’esofago dal reflusso gastrico per cui il loro alterato funzionamento condurrebbe al passaggio ed al ristagno del succo gastrico (Ph 1.5–2.5) sulla mucosa esofagea con conseguente esofagite. Fattori concausali nella patogenesi della malattia da reflusso sono la peristalsi esofagea, lo svuotamento esofageo e la motilità gastrica. Nell’ernia iatale esofagea la porzione addominale dell’esofago e parte dello stomaco si dislocano cranialmente attraverso lo iato esofageo. Questa situazione e la perdita di sostegno del LES comportano una diminuzione della pres-

sione dello sfintere gastroesofageo ed il conseguente reflusso. Un altro fattore che può contribuire al manifestarsi del reflusso in questi casi è la trazione a cui viene sottoposto il legamento frenico-esofageo. L’ernia iatale esofagea è generalmente un’origine causa ta da una anomalia congenita dello iato esofageo. L’ernia può inoltre essere secondaria a traumi che ledono i nervi e i muscoli diaframmatici causando una lassità iatale, oppure si ritiene che possa insorgere in concomitanza di ostruzioni delle vie respiratorie superiori che causerebbero una zona d bassa pressione a livello esofageo. Tra le forme di ernia iatale quella da scivolamento (o assiale) è la più frequentemente osservata. Nell’ernia iatale paraesofagea lo sfintere esofageo inferiore e la porzione addominale dell’esofago restano in posizione normale, mentre il fundus gastrico ed eventualmente altri visceri addominali si dislocano nel torace attraverso lo iato alterato. Una causa più rara di reflusso gastroesofageo è costituita dall’intususcezione gastroesofagea. Questa grave lesione consiste nell’invaginamento della porzione gastrica del cardias nell’esofago distale con o senza altri organi quali milza, pancreas, duodeno, omento ed è in genere un evento acuto.

DIAGNOSI L’incompetenza cardiale, secondo l’opinione dell’Autore, può essere considerata come la principale causa di reflusso gastroesofageo nel cane e nel gatto. La diagnosi non è sempre agevole e si basa principalmente sui segni clinici e sull’esame endoscopico. L’esame radiografico contrastografico non si è dimostrato sufficientemente sensibile per la diagnosi (Fig. 1). I sintomi possono variare in funzione della gravità del danno esofageo ed essere rappresentati da anoressia, disfagia, scialorrea, rigurgito, tosse secca fino a vomito, ematemesi e dispnea. I disturbi respiratori sono spesso i primi sintomi a comparire ed a volte, specialmente nelle forme lievi, anche gli unici. Molto spesso, infatti, la presenza di reflusso non è necessariamente associata a lesioni esofagee. Endoscopicamente la valutazione corretta della continenza cardiale non è sempre agevole e la sua quantificazione dipende molto dall’esperienza dell’operatore. Inoltre bisogna tenere conto dei fattori che possono facilitare l’insorgenza di un reflusso durante l’esame endoscopico quali il decubito laterale, l’insufflazione d’aria, la somministrazione

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di farmaci per uso preanestetico o anestetico (diazepam, thiopentale sodico, alotano). Nell’incompetenza cardiale è infatti possibile osservare un’incompleta chiusura del cardias che può raggiungere livelli tali da permettere la visione della cavità gastrica già dall’esofago (Fig. 2). A ciò può essere associato un passaggio costante di liquido gastrico in direzione dell’esofago e segni più o meno marcati di esofagite. Nelle forme lievi o qualora manchino i segni appena citati, e particolarmente l’esofagite, porre diagnosi d’incompetenza cardiale è piuttosto difficile. I segni clinici associati all’ernia iatale esofagea e/o paraesofagea, possono avere anch’essi gravità variabile da occasionali episodi di anoressia, disfagia, scialorrea e rigurgito a vomito, ematemesi e dispnea. Questi sintomi possono essere del tutto sovrapponibili a quelli determinati da incompetenza cardiale. Quando ernie voluminose coinvolgono il sistema cardiopolmonare può verificarsi arresto cardiaco. Le ernie iatali possono anche essere asintomatiche e costituire reperto occasionale in corso di esame radiografico del torace o dell’addome o all’esame necroscopico. I segni clinici sono in genere più gravi nelle ernie congenite che in quelle acquisite. L’esame clinico dei soggetti affetti da ernia iatale è in genere poco significativo, tuttavia possono essere presenti febbre, disidratazione, scialorrea e crepitii polmonari. Nella maggior parte dei casi gli esami di laboratorio non sono significativi. Dal punto di vista radiografico buona parte dei casi di ernia iatale possono essere diagnosticati con l’esame diretto in cui si identifica un’immagine intratoracica caudo-dorsale con opacità dei tessuti molli e a contenuto gassoso oltre a megaesofago di vario grado. Nei soggetti con ernia iatale da scivolamento in cui l’esofago e lo stomaco si dislocano in maniera intermittente, può essere necessario applicare una pressione positiva all’addome per causare la dislocazione craniale dell’esofago distale e dello stomaco. La diagnosi dell’ernia iatale acquisita può essere più complessa e richiedere ripetuti studi radiografici contrastografici dell’esofago (Fig. 3). L’esofagografia con mezzo di contrasto è indicata per lo studio dello sfintere esofageo inferiore, dello iato esofageo e del cardia. Se lo studio contrastografico viene eseguito in associazione all’esame fluoroscopico è possibile valutare la motilità esofagea, il diametro e , in grado minore, la funzionalità dello sfintere esofageo inferiore in base all’estensione del reflusso gastroesofageo. I radiogrammi diretti del torace sono utili anche per valutare un eventuale interessamento polmonare riferibile a polmonite ab ingestis. La diagnosi definitiva di ernia iatale paraesofagea si effettua in genere identificando lo stomaco erniato mediante l’esame fluoroscopico e con l’ausilio di esami come l’esofagografia e la gastrografia dove è possibile evidenziare vari gradi di dislocazione dello stomaco in radiogrammi eseguiti in serie. L’esame endoscopico può confermare la presenza di un’ernia da scivolamento anche se ciò, nei casi di ernia ricorrente, non sempre è possibile. Si possono identificare un’esofagite da reflusso (in genere distale) e, con lo strumento in retroversione nella cavità gastrica (manovra “J”), la presenza di un’apertura simulante il cardias beante. Questa è in genere preceduta da un’area sacciforme rivestita da mu-

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Figura 1 Incompetenza cardiale: esame radiografico contrastografico.

Figura 2 Incompetenza cardiale: aspetto endoscopico.

Figura 3 Ernia iatale esofagea: esame radiografico contrastografico.

cosa gastrica che termina nello sfintere esofageo inferiore dislocato cranialmente nel mediastino (Fig. 4). Nell’ernia paraesofagea la giunzione gastroesofagea è situata normalmente e, con l’endoscopio spinto in cavità gastrica ed in completa retroversione, si può evidenziare una parte dello stomaco che si ernia anteriormente attraverso lo iato in cavità toracica. I segni clinici associati ad intususcezione gastroesofagea possono essere più drammatici ed imponenti rispetto alle precedenti forme. L’esofago infatti, aumentando notevolmente di volume, può comprimere il parenchima polmonare provocando grave difficoltà respiratoria e/o broncopolmonite ab ingestis, collasso cardiocircolatorio secondario all’ostruzione del ritorno venoso e dell’apporto arterioso. I dati di laboratorio non sono specifici e possono essere in relazione alla disidratazione o eventualmente allo shock. I radiogrammi mostrano una dilatazione esofagea distale, con una massa di tessuto molle endoluminale. Alla massa di tessuto molle possono essere associate le pliche gastriche. La trachea può essere deviata ventralmente e possono essere evidenti segni di polmonite ab ingestis. La normale bolla gastrica può essere assente o di ridotte dimensioni. L’intususcezione può essere anche dimostrata da studi con mezzi di contrasto sia positivi che negativi (Fig. 5).

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L’esofagoscopia mostra un esofago dilatato con la presenza di pliche di mucosa gastrica nel lume esofageo distale e può essere evidente l’esofagite (Fig. 6). A causa dell’ostruzione determinata dagli organi presenti nel lume può essere impossibile avanzare l’endoscopio nell’esofago distale o nello stomaco.

TERAPIA Il protocollo terapeutico è differente nelle varie forme descritte e si basa sulla terapia medica per quanto concerne il trattamento dell’esofagite da reflusso e per alcune forme lievi di incompetenza cardiale e di piccole ernie iatali con segni clinici lievi o moderati e sulla terapia chirurgica per le restanti forme. I pazienti sintomatici con ernia iatale congenita hanno in genere risposto meno bene alla terapia medica rispetto a quelli con ernia acquisita. In genere, i soggetti sintomatici con grosse ernie iatali o dislocazione permanente dello stomaco erniato e quelli che non rispondono al trattamento conservativo sono candidati al trattamento chirurgico. I soggetti con ernia iatale paraesofagea dovrebbero essere sempre trattati chirurgicamente. TERAPIA MEDICA – Si può ottenere la neutralizzazione o la soppressione della secrezione acida gastrica utilizzando antiacidi o antagonisti dei recettori H2 (cimetidina, ranitidina, famotidina, omeprazolo). Gli antiacidi inoltre aumentano la pressione dello sfintere esofageo inferiore in conseguenza all’aumento del pH del contenuto gastrico. I procinetici (metoclopramide, clebopride, cisapride) sono farmaci che riducono l’esofagite da reflusso aumentando la pressione dello sfintere esofageo inferiore. Possono anche ridurre la pressione intragastrica grazie agli effetti positivi sullo svuotamento gastrico. Anche il sucralfato è stato consigliato per fornire una barriera alla digestione peptica della mucosa. Importante è anche il controllo della dieta. Una dieta povera di grassi e liquida facilita lo svuotamento gastrico e può quindi ridurre l’incidenza del reflusso gastroesofageo. TERAPIA CHIRURGICA - Le procedure anti-reflusso sono indicate quando la patologia da reflusso gastroesofageo è causata da un’incompetenza primaria cardiale. Queste tecniche sono state sviluppate per creare una zona intraddominale ad alta pressione. Fundoplicazio secondo Nissen – Pr evia intubazione gastrica con una grossa sonda (da 23 a 32 French) che fungerà da supporto, la porzione di esofago addominale viene retratta caudalmente con una fettuccia morbida. La parete craniale del fundus viene fatta passare con una o due dita al di sotto dell’esofago verso il lato destro dell’addome. Il fundus viene poi suturato con se stesso con sutura a spessore parziale a punti staccati semplici. Ciascun punto incorpora la tonaca muscolare dell’esofago. Si applicano in seguito circa 4 punti di sutura in materiale non riassorbibile 2-0 o 3-0 per tenere in sede il manicotto. Il fundus dello stomaco dovrebbe formare un morbido manicotto attorno ai 2-4 cm distali dell’esofago in assenza di una tensione eccessiva sulla parete gastrica dislocata. Ernia iatale da scivolamento - Il paziente viene posto in decubito dorsale con il tavolo operatorio inclinato in modo che la testa ed il collo siano leggermente sollevati rispetto al-

Figura 4 Ernia iatale esofagea: aspetto endoscopico.

Figura 5 Intususcezione gastroesofagea: aspetto radiografico.

Figura 6 Intususcezione gastroesofagea: aspetto endoscopico.

l’addome. Si esegue una celiotomia medio-ventrale che si estende dallo xifoide all’ombelico. Si scontinua il legamento epatogastrico mentre i lobi epatici laterale e mediale di sinistra vengono retratti medialmente per esporre lo iato esofageo. Si esegue quindi un’incisione ventrale circonferenziale a 180° del legamento frenoesofageo avendo cura di non danneggiare il tronco vagale. Ciò consente di retrarre in addome i 2-3 cm terminali dell’esofago distale contenenti lo sfintere esofageo inferiore. I pilastri destro e sinistro del diaframma vengono avvicinati per ridurre lo iato ad un diametro di 1-2 cm, applicando da 4 a 5 punti di sutura staccati semplici, ravvicinati, in polipropilene o polidiossanone 2-0. L’esofago addominale viene ancorato in cavità addominale applicando da 2 a 4 punti di sutura staccati in polidiossanone 3-0 tra il diaframma circostante e la tonaca muscolare dell’esofago nel punto di passaggio attraverso lo iato esofageo (esofagopessi). Si esegue quindi una gastropessi del fundus alla parete addominale sinistra mediante tecnica con sonda o incisionale. La gastropessi con sonda ha il vantaggio aggiuntivo di ridurre il problema della “sindrome da replezione gassosa” che è stata segnalata in associazione alle procedure anti-reflusso. Inoltre fornisce una via per la nutrizione enterale nel caso che il paziente presenti una grave disfunzione esofagea preesistente o se insorge un’anoressia postoperatoria.

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Ernia iatale paraesofagea - Il trattamento chirurgico prevede, previa celiotomia medio-ventrale, la riduzione delle strutture erniate, la plicatura della crura diaframmatica, l’esofagopessi e la gastropessi. Intususcezione gastroesofagea – Previa celiotomia medio-ventrale, esplorare l’addome e localizzare il duodeno e lo stomaco. Applicare una trazione delicata sul duodeno e sullo stomaco per ridurre l’intususcezione. Se necessario, per permettere la riduzione completa dell’intususcezione, dilatare o allargare digitalmente lo iato esofageo. Esaminare la porzione distale dell’esofago, lo stomaco e qualsiasi altro viscere interessato per la presenza di trombosi vascolare, avulsione, ischemia o necrosi. Asportare il tessuto devitalizzato. Se lo iato esofageo è troppo ampio o lasso ridurne la dimensione fino a 1-2 cm. Eseguire una gastropessi incisionale a livello del fondo gastrico per prevenire la recidiva. Irrigare e chiudere l’addome. Trattamento postoperatorio e complicanze - Sulla base del decorso clinico e della valutazione radiografica di eventuali polmoniti lobari e delle dimensioni e motilità dell’esofago, si può somministrare una terapia medica postoperatoria a base di antibiotici, procinetici o antiacidi. I soggetti con grave esofagite non devono essere nutriti per via orale ma possono essere alimentati, se la funzionalità gastrica è normale, attraverso una sonda gastrostomica. Inizialmente sono raccomandabili piccole quantità di dieta liquida e a basso tenore di grassi. Le complicanze più frequentemente riportate sono la morte per polmonite ab ingestis e il vomito e/o rigurgito per-

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sistente. Questi segni possono essere attribuiti a dilatazione gastrica cronica e a ritardato svuotamento gastrico. Una paresi gastrica può verificarsi secondariamente ad interferenze con l’innervazione vagale gastrica oppure può essere causata da una disattivazione temporanea del pacemaker gastrico, situato nel corpo dello stomaco, causata dalla gastropessi. La sindrome da replezione gassosa è stata riportata in letteratura quale complicanza specifica della tecnica di fundoplicazio. Ciò potrebbe verificarsi a causa di un effetto combinato tra difficoltà di eruttazione dovuta alla fundoplicazio e paresi gastrica. Quale complicanza della riparazione dell’ernia iatale è possibile l’insorgenza di pneumotorace, che è una logica conseguenza della scontinuazione della membrana frenoesofagea e deve essere trattata come necessario durante la procedura chirurgica.

Letture consigliate Bright RM et al. Hiatal hernia in the dog and cat: a retrospective study of 16 cases. J. Small Anim. Pract. 31: 224,1990. Ellison GW et al. Literature review of hiatal hernia in small animals. J. Am. Anim. Hosp. Ass. 23: 391-399, 1987. Leib MS, Blass CE. Gastroesophageal intussusception in the dog: a review of the literature and a case report. J. Am. Anim. Hosp. Ass. 20: 783,1984. Prymak C,Saunders HM, Washabau RJ. Hiatal hernia repair by restoration and stabilisation of normal anatomy: an evaluation in four dogs and one cat. Vet. Surg. 18: 386-391,1989. Twedt DC. Disease of the esophagus. In: Ettinger SJ, Feldman EC. eds Textbook of veterinary internal medicine. Philadelphia: WB Saunders, 1124-1142, 1995.

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Triage, Managing the Emergency and Trauma Patient Primo approccio al paziente traumatizzato in emergenza

Tim B. Hackett DVM MS, Diplomate ACVECC, Assistant Professor Colorado State University, Fort Collins, CO USA

Riassunto La medicina d’urgenza costringe spesso a lavorare per salvare la vita di pazienti in condizioni critiche senza una diagnosi. Molte procedure come la ripresa delle radiografie possono rappresentare uno stress per un paziente debilitato e può essere necessario rimandarle al momento in cui le condizioni cliniche del soggetto siano state stabilizzate. Mentre si cerca di formulare una diagnosi, occorre prestare la massima attenzione alle funzioni respiratorie, cardiache e neurologiche, per ripristinare l’ossigenazione tissutale. I clinici che operano in situazioni di emergenza devono imparare a stilare rapidamente l’elenco delle possibili diagnosi differenziali ed a stabilire nello stesso tempo l’ordine di priorità dei test diagnostici, mentre ripristinano le funzioni vitali degli apparati principali.

Emergency medicine often involves working to save critically patients without a diagnosis. Many procedures such as radiographs can stress a debilitated patient and may have to wait while the patient is stabilized. Close attention to res piratory, cardiac and neurologic function is necessary to restore tissue oxygen delivery while working toward a diagno sis. The emergency clinician must learn to quickly develop differential diagnoses while prioritizing diagnostic tests at the same time they are restoring function to the most vital organ systems.

INTRODUCTION Small animal emergency patients can be some of the most challenging, intensive cases to manage from admission to discharge. Before the insult, these animals may have been very healthy however, with acute disease, these patients can decompensate with a variety of systemic complications affecting outcome. It is important that the clinician, if necessary, the surgeon and anesthesiologist remain alert to changes in patient condition. If surgery is necessary, it may be delayed until a patient has been stabilized. For most, to stabilize means to correct hemodynamic, cardiopulmonary and electrolyte problems before subjecting the patient to the systemic depression of general anesthesia. The word "stabilize" should not be an excuse to delay surgery. For some conditions, surgery is required to correct the immediate threats to lif e.

INITIAL ASSESSMENT Assessment of the emergency patient should be accomplished using an orderly and systematic routine. This routine is administered to each patient. An initial, brief physical examination is performed to identify any life threatening

problems. Attention is directed toward the respiratory and cardiovascular system. Obviously, those injuries or diseases which interfere with vital physiological functions should receive the highest priority. These patients have problems which pose an immediate threat to life, and usually involve the respiratory system, cardiovascular system, or neurological system. The purpose for the initial assessment of the emergency patient is to identify life-threatening physiological problems. Whenever a problem is identified immediate therapy is begun. The "primary survey" is an assessment of the ABCDE's: • Airway--Is the patient having difficulty breathing? Are there obstructions to the airway? • Breathing--Is the patient dyspneic? What is the color of the mucous membranes? Does the dyspnea get worse with positional changes of the animal? Is there evidence of thoracic penetration or is there a flail chest? Are the peripheral veins distended? • C i rc u l ation--Is there evidence of hemorrhage or severe fluid loss. Is the hemorrhage arterial or venous? Are the mucous membranes pale and tacky? Are the femoral pulses weak and rapid? Are the extremities cold?

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• Disability--Is there evidence of neurological disease or injury? What is the posture of the animal? Is the animal bright, alert and responsive? Does the animal respond to painful stimuli? Are the pupils dilated, constricted, of equal size, and responsive to light? • Examination--Are there lacerations? Petechiation? Is the animal in good condition? Is the abdomen painful? Is there evidence of debilitation or concurrent disease?

INJURIES AFFECTING VITAL FUNCTIONS Respiratory function represents the highest priority in the emergency patient. These injuries require immediate recognition and treatment. Breathing pattern is observed and differential diagnoses ranked before the patient is stressed with closer examination or radiographs. The cardiovascular system is the second most important system. Clinical evidence of shock includes tachycardia, weak peripheral pulses and signs of poor tissue perfusion. Perfusion can be assessed subjectively by examining nonpigmented mucous membranes. Pale or gray mucous membranes are seen when peripheral vasoconstriction shunts circulation to the animals core. Cold extremities, hemorrhagic

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diarrhea, decreased mentation and poor urine output are commonly seen when organ function is compromised. A rapid neurological evaluation is the final step in the primary survey. Its purpose is to establish the patient's level of consciousness, pupillary size and reaction, and to note any abnormal postures of the animal. Normal pupillary function implies that the midbrain and third cranial nerve are intact. Symmetric or diffuse diencephalic lesions will produce small reactive pupils while asymmetric anisocoria with bilateral reactivity is most likely a structural lesion. Midbrain damage can produce midposition and unreactive pupils. Dilated unreactive pupils which develop from miotic pupils imply brain stem lesions and a grave prognosis. Skeletal motor responses induced with stimulation may also assist in defining the location of the lesion and suggest prognosis. Decerebrate rigidity is characterized by quadrilateral rigidity and opisthotonos. Prognosis is generally regarded as grave for decerebrate patients. Treatment of the brain trauma patient is directed to treating cerebral edema in order to preserve brain function. Abdominal disease can be occult. Internal injury requires careful physical examination combined with radiography, ultrasonography and abdominocentesis to decide the location and severity of the problem.

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Practical techniques for fluid therapy in the small animal patient Tecniche pratiche di fluidoterapia nel paziente in emergenza

Tim B. Hackett DVM MS, Diplomate ACVECC, Assistant Professor Colorado State University, Fort Collins, CO USA

INTRODUCTION

ROUTES OF FLUID ADMINISTRATION

When an animal is pre s e n t e d, it is important to fi rs t a dd ress blood volume re s t o ration needs. The history must include info rm ation rega rding the amount and frequency of fluid loss. It is ve ry useful to know the animal's exact body weight befo re the onset of illness fro m the owner or from current medical re c o rds. If there are acute decreases in body we i g h t , most of these losses can be at t ri buted to water losses. This will allow a more accurate assessment of dehy d rat i o n . L i fe - t h re atening fluid loss should be identified and t re ated befo re time is spent on detailed history or phy sical ex a m i n ation. A b n o rmal mucous membrane color, slow cap i l l a ry re fill time, t a chy c a rd i a , t a chy p n e a , we a k pulse, cool ex t remities or obvious blood loss re q u i re immediate action to re s t o re circ u l ating volume and tissue oxygen delive ry.

Many routes of administration have been used in veterinary patients. The oral, intravenous, subcutaneous, and intraosseous (intramedullary) routes are preferred. Oral fluid replacement is the safe and reliable. This is done either voluntarily (free choice) or fo rc i bly using some sort of feeding tube. Vomiting, megaesophagus, aspiration pneumonitis, or shock are contraindications to oral fluid administration. Intravenous administration of fluids is preferred in mild to severe dehydration, hypotension, shock, vomiting, and any condition where significant continuing losses are anticipated. Subcutaneous fluid administration is overused and often abused in veterinary medicine. With dehydration, peripheral vasoconstriction results in poor fluid uptake from the subcutaneous spaces. I n t raosseous or intra m e d u l l a ry administration involves giving the fluid via the bone marrow. This is an extremely useful emergency technique. Not only is the bone marrow of the femur and humerus more easily accessed than small collapsed veins, but also the circulation to the bone marrow does not collapse in cases of hypotension and shock.

REHYDRATION During your physical examination you will be observing physical parameters which will guide you to assess the patient's hydration status and thus rehydration requirements. Changes in skin turgor should be assessed in a consistent manner and location. Usually, the lateral thorax is preferred. The skin is pulled up, quickly released, and the time to return to normal is noted. When an animal is 12% dehydrated the tented area of skin often remains tented for more than 5 to 10 seconds! Body weight is the best means for assessing fluid volume losses. Losses of lean body mass are never rapid; therefore, acute losses are generally fluid losses and thus become an accurate quantitative estimator of deficit volumes. Third-space losses involve the accumulation of large fluid volumes in cavities such as the pleural or peritoneal space and intestinal or gastric lumen, or in tissues around fracture or trauma sites. These losses result in decreased circulating volume without an actual change in body weight. Mucous membranes are good indicators of perfusion. Color and refill time, as well as moistness, should be assessed.

INTRAVENOUS CATHETER SELECTION S h o rt , p o ly v i nyl ch l o ride cat h e t e rs are designed fo r use in small, p e ri p h e ral art e ries and veins. The easiest to place, these cat h e t e rs should be used for short - t e rm p ro c e d u re s , in patients re q u i ring seve ral “ l i n e s ” at one time and in those wh e re central cat h e t e rs may be cont ra i n d i c ated (see Central Cat h e t e rs). A disadva n t age with some animals because tightly fl exed limbs can occlude venous dra i n age and impede the continuous fl ow of intravenous fl u i d. Central venous catheterization is essential in many critically ill patients. A large-bore, silicon or teflon, jugular venous catheter can be maintained for days. Incorporated into a bandage around the animal’s neck, these catheters tend to stay dryer, cleaner and can remain in

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longer than peripheral catheters. Central venous catheters are useful in obtaining a central venous pressure (CVP) that provides important information about fluid loading and the hearts ability to pump the fluid presented to it. Large central catheters can also be useful for repeated blood sampling. Central venous catheters should be avoided in patients with bleeding disorders, seizures or hypercoagulable states (autoimmune hemolytic anemia, hyperadrenocorticism, DIC, protein-losing nephropathy).

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INTRAOSSEOUS CATHETERIZATION Rather than struggle with a small, peripheral catheter, or the trauma of a vascular cut-down procedure in a small debilitated patient, an intraosseous catheter can provide short-term access. Placed in the medullary cavity of any long bone, the intraosseous space rapidly absorbs crystalloid fluids, colloids and drugs. Any needle with a stylet can be used. The needle can be placed in medullary space of the femur (dogs and cats), the humerus (dogs and cats), the tibia (ferrets, pocket pets) or the ulna (birds).

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Emergency Management of Intoxications Trattamento d’urgenza delle intossicazioni

Tim B. Hackett DVM MS, Diplomate ACVECC, Assistant Professor Colorado State University, Fort Collins, CO USA

INTRODUCTION

EMESIS

Any antidotal treatment of poisoning is useless if vital organ function is lost. Regardless of the type of poison, an initial assessment must be made of cardiopulmonary function and appropriate actions must be taken early to treat any problems identified. Using an “ABC” approach to any sick animal will keep the emergency team focused on life-threatening problems: AIRWAY – Be sure the animal has a patent airway. A quick oral exam and finger sweep can remove any obstruc tion. Visually inspect the larynx for swelling or obstruction. If the animal is obtunded, protect the airway by intubating the animal with a low-pressure cuffed endotracheal tube. BREATHING – Is the animal breathing? Are the breaths of adequate rate and depth? Is oxygen getting from the lungs into the tissues? Observation, auscultation, and examination of the mucous membranes can answer these questions. If the mucous membranes are pale or cyanotic, supplemental oxygen should be provided immediately. CIRCULATION – Check pulse quality, heart rate and rhythm. If pulses feel week or irregular, and electrocardiogram should be evaluated. Patients in shock should have an intravenous catheter placed, blood samples drawn and fluids ready to administer. If the heart rate is rapid and the pulse quality weak, Shock volumes of fluids should be given (90 ml/kg over an hour in a dog, 40 ml/kg in a cat).

Vomiting is the best way to remove stomach contents. It is more effective than gastric lavage. Emesis should be con sidered anytime that an animal is presented within 2-3 hours of ingesting a poison. Emesis should not be induced in depressed or weak patients, the risk of aspiration is too great to justify the maneuver. Patients that have ingested caustic compounds such as cleaning solutions, acids, or alkalais should not be forced to vomit. These compounds can burn the esophagus, leading to the formation of strictures. Caustic solutions should instead be diluted with water or milk and activated charcoal solutions. Emesis can be induced reliably in small animals using apomorphine or xylazine. Syrup of Ipecac is an effective over-the-counter emetic. Hydrogen peroxide, salt and mustard have also been reported but are much less effective than emetic drugs.

TREATMENT GOALS With any poisoning, the goals are the same: Prevent further exposur e, decrease absorption, hasten elimination and provide supportive care. When available, an antidote should also be given. Transit of stomach contents usually takes about 2 hours. The time can vary with the quantity and type of food present in the stomach. If a patient has recently ingested any toxin, forced emesis and gastric lavage are practical ways to remove the toxin, preventing further exposure and decreasing absorption. Gastrointestinal decontamination involves either emesis or gastric lavage followed by activated charcoal and a cathartic. The cathartic speeds the passage of material in the intestinal tract allowing less time for absorption. Gastric decontamination should be considered in any suspected intoxication.

GASTRIC LAVAGE Gastric lavage is performed using a large bore stomach tube. The patient should be sedated or ideally anesthetized and intubated to protect the airway. A tube is placed in the esophagus to the level of the last rib. Correct placement in the stomach is confirmed by ausculting the stomach while someone blows into the tube. Instill warmed water slowly watching for signs of respiratory distress. Water is instilled and removed gently until the returning water is clear and free of debris.

ACTIVATED CHARCOAL Activated charcoal is a specially treated charcoal product that has been oxidized to form a large molecule with many large pores. Pre-mixed activated charcoal products often contain a cathartic (sorbitol is an example) to speed the transit of material through the gastrointestinal tract. The large pores on the activated charcoal stick to ingested material in a non-specific manner, which makes it an effective treatment for almost any intoxication. Keep in mind that these pores will fill with anything so ACTIVATED CHARCOAL SHOULD NOT BE MIXED WITH FOOD. Food will occupy binding sites on the activated charcoal decreasing its efficacy. Activated charcoal can be given by orogas-

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tric tube following gastric lavage, or by force feeding in alert patients. Activated charcoal is often repeated as poisons eliminated by the liver in the bile may be reabsorbed in the small intestine.

SUPPORTIVE CARE Many toxins result in respiratory and cardiovascular depression. Patients should be continually monitored for ade-

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quate oxygenation and ventilation. Depressed, obtunded, debilitated patients should be turned at regular intervals to prevent pulmonary atelectasis and pressure sores. Closed urine collection system may be employed to assess urine output and prevent soiling. Changes in packed cell volume, and total serum solids may require blood transfusion or other colloid support. Once everything has been done to prevent absorption and hasten elimination of any poison, excellent nursing care will provide the patient time to heal from the toxic insult.

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Managing complicated abdominal emergency cases Trattamento d’urgenza delle emergenze addominali complicate

Tim B. Hackett DVM MS, Diplomate ACVECC, Assistant Professor Colorado State University, Fort Collins, CO USA

INTRODUCTION Any patient with signs of intraabdominal disease may require emergency treatment for shock, even surgery before a definitive diagnosis is reached. The timing of surgery can often be delayed until a patient has been stabilized. For most, to stabilize means to correct cardiopulmonary and electrolyte problems before subjecting the patient to the systemic depression of general anesthesia. The word "stabilize" should not be an excuse to delay surgery and for some conditions, surgery is required to correct the immediate threats to life. By understanding the causes and pathophysiology of abdominal pain and trauma, the clinician can make appropriate decisions regarding medical treatments and the timing of surgery. There are three basic stimuli for abdominal pain: 1) Tension or stretching; 2) Inflammation; 3) Ischemia. Clinically there are six major sources of abdominal pain: 1) Hepatobiliary; 2) Gastrointestinal; 3) Pancreatic; 4) Splenic; 5) Urogenital; 6) Peritoneal.

INITIAL RESUSCITATION Animals with acute abdominal distress often present in shock. The shock may be due to inadequate volume, cardiac depression or tachyarrhythmias or maldistribution of blood flow. Regardless of cause, circulatory shock is reduced oxygen delivery to tissues. Since oxygen delivery (DO2) is a function of cardiac output (CO) and oxygen content (CaO2) of the blood anything we can do to improve these variables will help our patient. Cardiac output is determined by heart rate and stroke volume. Rapid heart rates decrease output because of poor ventricular filling. Heart rate can be optimizing by treating arrhythmias, reducing anxiety and pain, and providing volume. Volume in the form of intravenous fluids will also improve stroke volume. A large bore (16 to 18 g.) jugular catheter is preferred for volume loading. The jugular catheter will allow measurement of central venous pressure (CVP). By maintaining a central venous pressure of 5-10 cm of water, cardiac preload is optimized. The other half of the oxygen deliver equation is oxygen content. A function of oxygen saturation and hemoglobin content, this can be increased by maximally saturating the blood with oxygen (face mask, oxygen tent, or oxygen cage) and normalizing hemoglobin content (whole blood, packed red blood cells, hemoglobin substitutes). Abdominal disorders often cause fluid and electrolyte disorders. These are usually due to intractable vomiting, anorexia,diarrhea and third-space sequestration of fluid. In most animals,

restoration of a normal circulating blood volume will return the acid/base balance to normal. If large volumes of fluid are given, potassium should be added at a rate of 20-30 mEq/liter. Patients with urine in the abdomen, severe acidosis, hypoadrenocorticism or renal failure may have a significant hyperkalemia. If electrolytes are unavailable, patients should be rehydrated without additional potassium. Potassium containing fluids should never exceed a rate of 0.5 mEq/kg body weight/ hour.

THE SECONDARY SURVEY The signalment can give important insights into likely diagnoses. Take age, sex and breed into consideration to narrow likely diagnoses. Older animals are likely to suffer from neoplasia while younger active animals may suffer more infectious diseases or intoxications. Schnauzers are more likely to have pancreatitis while large, deep chested dogs are at increased risk of gastric dilatation volvulus. A careful history should be taken while the animal is being stabilized. How long has this problem been going on? Has this happened before? Are any other animals affected? Is the animal vomiting? Regurgitating? Is it productive? How often and when has the vomiting occurred? Any diarrhea? Blood or melena? Has there been any exposure to toxins or garbage? A recent fatty meal or overeating? Vaccines given? When? By whom? Is the animal spayed? last heat? breeding history? Is the animal taking any medications?A complete drug history is always important. Over the counter anti-inflammatory products can cause GI ulceration and with many new products available for people accidental exposure is common. NSAIDS can be especially harmful when combined with prescription corticosteroids. Vital signs are recorded and compared to admission values. Abdominal radiographs should be taken soon after admission and initiation of fluid resuscitation. They should be examined for evidence of free gas in the peritoneal cavity. If free gas is seen and there has not been recent surgery, abdominocentesis or trocharization, immediate surgical exploration is indicated. Gastric dilatation volvulus and gaseous distention of the small bowel are other indications for early surgical exploration. Loss of abdominal detail as seen with free abdominal fluid requires abdominocentesis or diagnostic peritoneal lavage (DPL). Animals with acute abdomen distress are identified as either critical requiring immediate surgery, urgent requiring surgery as soon as practical and non-surgical. Regardless of classification, all these animals should be evaluated at regular intervals, a non-surgical case may deteriorate rapidly necessitating surgery or other changes in treatment.

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Managing complicated respiratory emergency cases Trattamento d’urgenza delle emergenze respiratorie complicate

Tim B. Hackett DVM MS, Diplomate ACVECC, Assistant Professor Colorado State University, Fort Collins, CO USA

INTRODUCTION

AIRWAY SAMPLING

Respiratory distress in small animals can present a therapeutic dilemma. Patients can be so severely compromised that diagnostics and treatment can stress them to the point of respiratory and cardiac arrest. A diagnosis should not come at the expense of the patient. An induction chamber for cats and small dogs or a large oxygen cage can be valuable to give the patient added oxygen while the clinician can observe the patient in an attempt to localize the problem. Restraint for catheterization, radiographs and physical examination may have to wait until the patient is relaxed and breathing easier. Mild sedation with very low doses of acepromazine can be life saving by allowing the anxious dyspneic animal to breathe more efficiently.

Transtracheal aspiration biopsy (transtracheal wash, TTW) is one of the most useful techniques for the diagnosis of diseases of the respiratory system. The TTW can be easily performed in most dogs and cats in about 5 minutes. The goal of the TTW is to collect fluids from the trachea, bronchi and lower airways for cytology, culture, and antibiotic susceptibility. Other methods to collect pulmonary samples include fine needle aspiration (trans-thoracic aspirate), bronchoscopy, or surgically either by thoracoscopy or thoracotomy).

PHYSICAL EXAMINATION AND HISTORY A rapid shallow respiratory pattern suggests restrictive disease while a slow deep inspiratory pattern is seen with airway obstruction. With the restrictive pattern, auscultation can help differentiate pleural space disease (pneumothorax, hydrothorax) from parenchymal diseases (pneumonia, pulmonary edema). In the case of pleural effusion or pneumothorax, a thoracocentesis can provide a diagnosis at the same time it is providing the life-saving treatment. Signalment and history can help determine a cause of upper airway obstruction (playing with small toys, brachycephalic airway diseases, and laryngeal paralysis). Once the patient has been stabilized and calmed, treated for shock and hyperthermia definitive diagnostics can be performed. Some of the important emergency diagnostics will be r eviewed.

IMAGING Animals presenting with upper and lower respiratory signs should have a thoracic radiograph. Bronchial patterns develop as the peribronchiolar tissues become inflamed. Interstitial patterns develop with thickening of the fibrous structures of the lung. Alveolar patterns characterized by "Air bronchograms" are caused by fluid accumulation in the alveoli. Thoracic and cervical radiographs can be used to diagnose collapsing trachea, tracheal or laryngeal foreign bodies, and tracheal or laryngeal masses. Taking inspiratory and expiratory views of the trachea or through the use of fluoroscopy can assess airway dynamics.

ARTERIAL BLOOD GAS ANALYSIS Arterial blood gas analysis is becoming available in more veterinary hospitals. Blood gases can give the clinician important information about the patients acid base balance, oxygenation and ventilation. Arterial blood is sampled from the dorsal pedal or femoral artery. Blood gases should be measured within 10 to 15 minutes; however, values will be accurate for 3 to 6 hours if the sample is stored on ice. Serial blood gas analysis is the most objective way to monitor changes in pulmonary pathology, changes that may not be obvious on radiographs.

UPPER AIRWAY EMERGENCIES Laryngeal paralysis will present with varying degrees of exercise intolerance, stridor, voice change, inspiratory effort, cyanosis and hyperthermia. The same is also true of animals that aspirate foreign objects or have masses in the airway obstructing airflow. Supplemental oxygen and sedation can stabilize most of these patients. Some however may require a tracheostomy to restore necessary oxygen.

INTRATHORACIC RESPIRATORY EMERGENCIES Pulmonary edema and pneumonia can result in dyspnea and cyanosis. Since both result in an alveolar lung pattern the two conditions can easily be confused. It is necessary for the emergency clinician to distinguish the two since their treatments are very different. Pulmonary edema is usually due to congestive heart failure or massive catecholamine re-

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lease. Pneumonia is often found in very young or very old, immunocompromised individuals. Debilitated patients or those with esophageal dysfunction are also at high risk of aspiration and pneumonia. Pulmonary Thromboembolism (PTE) is the occlusion of the pulmonary vasculature by products of the coagulation cascade. This commonly results in tachynpea, dyspnea, and potentially, cyanosis. PTE occurs through 3 major mechanisms, damage to vascular endothelium, altered pulmonar y blood flow, and hypercoagulability.

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PTE in dogs and cats occurs most commonly with cardiac diseases, protein-losing nephropathy, hyperadrenocorticism, immune-mediated hemolytic anemia, dirofilariasis, disseminated intravascular coagulation, neoplasia and sepsis. Diseases of the pleural space cause a decreased tidal volume and a restrictive breathing pattern. Characterized by the rapid, shallow respirations and dull lung sounds, fluid and air in the pleural space can be diagnosed and treated by rapid thoracocentesis.

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Post-operative management of the trauma patient Trattamento postoperatorio del paziente traumatizzato

Tim B. Hackett DVM MS, Diplomate ACVECC, Assistant Professor Colorado State University, Fort Collins, CO USA

INTRODUCTION Patients recovering from trauma and related surgery develop a variety of predictable complications. Postoperatively these patients are at risk of organ failure. Acute respiratory distress, systemic inflammatory response syndrome (SIRS), sepsis, disseminated intravascular coagulation, acute renal failure and cardiac arrhythmias are just some of the problems seen regularly in our critical care practice. Anticipating multiple organ dysfunctions, monitoring critical hemodynamic and respiratory variables and treating abnormalities that are identified may support these patients supported during the post-operative period.

changes in fluid balance while serial physical examination will identify pulmonary edema and peripheral edema allowing the clinician to change the type of fluid retaining more in the vascular space. Serum albumin should be monitored and kept above 2.0 g/dl using plasma or whole blood transfusions. If unavailable, total solids should be monitored instead and kept above 3.5 g/dl. Persistent hypoalbuminemia is associated with increased mortality in critically ill animals. Dextrans 70 or Hydroxyethyl starch are the most commonly used synthetic colloids and can be g iven at a rate of 20 ml/kg/day.

ELECTROLYTES AND GLUCOSE CARDIOPULMONARY FUNCTION Critical care medicine revolves around oxygen and oxygen delivery to tissues. Shock whether due to loss of volume (hypovolemic), cardiac dysfunction (cardiogenic), or inappropriate blood flow (distributive) results in inadequate oxygen delivery. Oxygen delivery is dependent upon cardiac output and arterial oxygen content. Clinical variables that result in improved oxygen delivery include stroke volume, heart rate, oxygen saturation and hemoglobin concentration. Cardiac output and tissue perfusion is monitored by monitoring heart rate and rhythm (electrocardiogram), mucous membrane color and blood pressure. Specific therapies to improve cardiac output include fluids, positive inotropes, and specific antiarrythmic drugs. Arterial blood gas, pulse oximetry, and thoracic radiographs monitor respiratory function. Oxygen supplementation to patients with failure pulmonary function may restore oxygen saturation and improve oxygen delivery.

Calcium, sodium, chloride and potassium should be maintained within normal limits. Potassium should be added to maintenance fluids to avoid iatrogenic hypokalemia. Potassium containing fluids should never exceed a rate of 0.5 mEq/kg body weight/ hour. Blood glucose should be maintained between 100 and 200 gm/d. Drops in blood glucose or levels that are not above normal despite the addition of dextrose could be a sign of sepsis or paraneoplastic hy p og lycemia. Hypokalemia that does not rapidly correct with high levels of supplemental potassium may respond to magnesium supplementation. Hypomagnesemia is common in the critically people and animals. Magnesium can be replaced at 0.75 - 1 mEq/kg/ day by constant rate infusion in 5% dextrose in water. After 24 hours the animal can be switched to magnesium containing maintenance crystalloid fluid like Normosol-R (Abbott Laboratories, Chicago, IL) or Plasmalyte (Baxter Healthcare, Deerfield, IL).

URINE PRODUCTION FLUID BALANCE AND ONCOTIC PRESSURE Because of increased capillary permeability and decreased systemic vascular resistance, Postoperative patients with SIRS can experience large fluid movement from the vascular compartment into the interstitium resulting in tissue and pulmonary edema. Crystalloid fluids can lower fluid oncotic pressure. Patients with open abdomens or abdominal drains may have large protein and fluid losses. Daily body weight and physical examination will identify minor

Urine output reveals important info rm ation about renal blood flow and function. Recumbent and azotemic patients, and those at risk for multiple organ dysfunctions should have an indwelling urinary catheter in place with a sterile closed collection system. Low urine output (< 2 ml/kg/hour) in a hydrated patient may represent acute renal failure. Quick intervention with fluids, diuretics ( f u rosemide 1-2 mg/kg) and va s o a c t ive drugs like dopamine (3-5 µg/kg/min) may start urine flow and prevent permanent renal damage.

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COAGULATION

PAIN CONTROL AND PATIENT COMFORT

Disseminated intravascular coagulation (DIC) is a common component of SIRS. Examination of a blood smear for decreased platelets and fragmented red blood cells is inexpensive and easy. Activated clotting times should also be checked daily. More specific tests for fibrin degradation products (FDP’s) and Antithrombin III (AT III) levels may help guide therapy. Therapy is directed toward decreasing microthrombi (heparin, heparinized plasma), providing missing factors (fresh frozen plasma) and improving perfusion (fluid/colloid support).

Animals in constant stress will become immunosuppressed. It is vital to the care of the patient that it be made as comfortable as hospitalization will allow. The appropriate use of analgesics, padding, bandage changes and personal contact will have positive effects on the patients overall sense of well being.

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Management of the abdominal trauma patient Primo approccio al paziente traumatizzato in emergenza

Tim B. Hackett DVM MS, Diplomate ACVECC, Assistant Professor Colorado State University, Fort Collins, CO USA

TRIAGE

ABDOMINAL TRAUMA

Morbidity and mortality from trauma is devastating. Many traumatic deaths may be prevented if certain conditions are promptly recognized and quickly treated. Clinicians assessing the abdominal trauma patients should remain alert to the systemic complications of trauma. Assessment of the traumatized patient should be accomplished in an orderly and systematic routine. Attention is directed toward the respiratory and cardiovascular system. The purpose for the initial assessment of the trauma patient is to identify life-threatening physiological injuries. Whenever a problem is identified immediate therapy is begun. The "primary survey" is an assessment of the ABCDE's:

Abdominal injuries are often occult. Most injuries are caused by blunt trauma inducing lacerations of the liver and/or spleen, urological trauma, infarcted bowel, or reproductive organ damage during pregnancy. Blunt abdominal trauma cases are challenging diagnostic problems because the clinical manifestations may be delayed for hours or days. With blunt abdominal trauma, the physical examination is the most informative portion of the diagnostic evaluation and should be as complete as time and the patient's condition permit. Increasing abdominal size can be an important clue for intra-abdominal injury. Consequentl y, measurements of the abdominal girth at the umbilical level should be made soon after admission. This baseline measurement can be used to measure subsequent significant changes. A four quadrant abdominocentesis is our preferred means for confirming blunt abdominal injury. From the fluid obtained, a packed cell volume, total solids, cytology, and a blood urea nitrogen sample are submitted. Additionally, it is probably a good idea to submit some of the intra-abdominal blood for analysis of total bilirubin. With major biliary tree or common bile duct injury, the clinical signs of icterus are often delayed 4 to 6 weeks. If the packed cell volume of centesis fluid exceeds the peripheral packed cell volume, very likely there is either a splenic, hepatic or renal parenchymal laceration. Should plant debris or significant numbers of mixed bacteria be found with centesis of the abdominal fluid, a ruptured viscus is likely and exploratory surgery is indicated. It is very unusual to require surgery for a splenic or hepatic laceration. Using abdominal counter pressure bandages and avoiding excessively tight bandages these patients can often be treated with fluids alone. Patients with intra-abdominal hemorrhage may present in shock. Regardless of cause, circulatory shock results from reduced oxygen delivery to tissues. Since oxygen delivery is a function of cardiac output and the oxygen content of the blood anything that will improve these variables will help the patient. Patients in shock may need crystalloid fluids at a rate of up to 90 ml/kg in dogs and 60 ml/kg in cats. Patients should be closely monitored for signs of overhydration (pulmonary edema, serous nasal discharge, chemosis) during rapid infusions. The jugular catheter will allow CVP measurement. Whole blood or

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Airway--Is the patient having difficulty breathing? Are there mandibular injuries which are interfering with the airway? Has the bite wound disrupted the larynx or trachea?

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Breathing--Is the patient dyspneic? What is the color of the mucous membranes? Does the dyspnea get worse with positional changes of the animal? Is there evidence of thoracic penetration or is there a flail chest? Are the peripheral veins distended?

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Circulation--Is there evidence of hemorrhage? Is the hemorrhage arterial or venous? How large is the swelling associated with the extremity fracture? Are the mucous membranes pale and tacky? Are the femoral pulses weak and rapid? Are the extremities cold?

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Disability--Is there evidence of neurological injury? What is the posture of the animal? Is the animal bright, alert and responsive? Does the animal respond to painful stimuli? Are the pupils dilated, constricted, of equal size, and responsive to light? Is there an extremity fracture which might threaten a peripheral nerve?

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Examination--Are there lacerations? Where is the bruising and is this bruising getting worse? Are there multiple fractures? Is the abdomen painful? Is there evidence of debilitation or concurrent disease?

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packed red cell transfusion should be used to maintain a packed cell volume between 27% and 33%. With urological injury, the packed cell volume of the abdominal fluid will be lower than the peripheral packed cell volume due to hemodilution with urine. Emergency management of intraperitoneal rupture of the bladder, urethra, and/or ureters involves drainage of the abdominal fluid via

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an indwelling Foley catheter until the patient is sufficiently stable to undergo anesthesia and surgical repair. Prior to surgery, contrast studies of the kidneys, ureter, and bladder should be performed to assess the severity of injury using an excretory urogram. Additionally, if there is evidence of lower urinary tract injury, positive contrast urethrography and cystography are advocated.

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Early diagnosis of chronic (myxomatous) valvular disease Diagnosi precoce e trattamento delle valvulopatie acquisite

Jens Häggström DVM, PhD, DECVIM-CA (Cardiology) - Faculty of Veterinary Medicine Swedish University of Agricultural Sciences, P.O. Box 7045, 750 07 Uppsala, Sweden

Clarence Kvart DVM, PhD, DECVIM-CA (Cardiology) - Faculty of Veterinary Medicine Swedish University of Agricultural Sciences, P.O. Box 7045, 750 07 Uppsala, Sweden

Background: Chronic valvular disease (CVD) is, by far, the most commonly encountered cardiac disease in adult dogs. Dogs of small to medium-sized breeds are predisposed to CVD. The condition is slightly more prevalent among males, and its prevalence increases in with age. Mitral regurgitation (MR) attributable to CVD is characterized by a chronic progression in affected dogs. The progression from a soft apical systolic murmur being the only clinical sign to terminal stages may span over many years and shows great individual variation. The disease is, t h e re fo re, comparably benign and is often well tolerated until progressed cases associated with signs of heart failure. Accordingly, early diagnosis of CVD may not appear important; it does not matter if the diagnosis is missed at one examination because it will be diagnosed correctly the next time owing to the progression of CVD. However, knowledge of clinical findings in early stages may still be important because they may confuse a nonexperienced practitioner. Furthermore, as CVD is shown to be inherited as a multifactorial threshold trait, several breeding schemes have been initiated with the aim to reduce the incidence of the disease in various breeds, such as Cavalier King Charles Spaniel and Dachshunds). In these schemes, it is important that the disease is correctly diagnosed. Lastly, early diagnosis may be important in research settings.

CLINICAL CHARACTERISTICS OF EARLY CVD This abstract will focus on auscultation and echocardiography as early phases of CVD is usually not associated with any abnormal electrocardiographic or radiographic findings. Auscultation: The auscultatory findings are highly dependent on the stage of the disease. In early stages, in which

there is no or only mild MR, a clear midsystolic click is often found. By auscultation, however, even highly experienced observers may experience problems in identifying many of these clicks, suggesting that midsystolic clicks in the dog generally have a low intensity and often occur intermittently. Classically, early phases of CVD has been diagnosed by identification of a soft murmur with maximal intensity over the mitral orifice, indicating MR. With disease progression and as MR increases, the intensity of the murmur generally becomes more intense and it may radiate over to the right side of the thorax. At these stages, the intensity of the first heart sound is usually enhanced, indicating left ventricular hyperkinesia, whereas the intensity of the second heart sound decreases. A positive correlation has been documented between the degree of MR and murmur intensity . In agreement with that, the likelihood of finding a systolic murmur increases with increasing degree of MR. However, the likelihood of detecting a systolic murmur is also highly dependent on the degree of observer experience and whether or not dynamic auscultation is performed. It appears that the ability of physical maneuvers to increase the murmur intensity depends on the provoked increase in heart rate. The degree of MR relates not only to the intensity but also to the timing of the murmurs. Significant MR is associated with a holosystolic murmur whereas mild MR typically causes murmurs of shorter duration. In dogs with mild MR, the murmurs are typically early systolic; only a few dogs have a late systolic murmur and in those cases, it usually alternates with a holosystolic murmur. Echocardiography: Although CVD and MR are closely linked to each other, they are not the same thing. The former is a disease that leads to the later. Mitral regurgitation may be caused by a broad variety of underlying cardiac disorders. Today, we know that it is possible to echocardiographically assess several different manifestations of CVD prior to the development of audible mitral regurgitation. These include

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leaflet thickening and varying degrees of the valve leaflets bowing into the left atrium in systole, i.e. mitral valve prolapse. In dogs, the hinge points of the two leaflets (imaged in the right parasternal long-axis view) have been used to define the position of the mitral annulus in all recent studies assessing the presence and severity of MVP. Indeed, a recent study showed that leaflet thickness, degree of leaflet protrusion and degree of MR (jet size) all correlated well with each other over a broad spectrum ranging from clearly normal to clearly abnormal, insufficient valves. By combining several

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quantitative or semiquantitative measurements, rather than mainly focussing on whether or not abnormal leaflet protrusion is present, a better assessment of valve status will likely be obtained. However, as these echocardiographic abnormalities has been reported to be very frequent in young dogs of breeds with a predisposition to develop CVD, it makes them less useful in breeding programs because too many animals would be excluded from breeding . References are available on request.

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New and old therapeutic modalities of heart failure Protocolli terapeutici vecchi e nuovi per l’insufficienza cardiaca

Jens Häggström DVM, PhD, DECVIM-CA (Cardiology) - Faculty of Veterinary Medicine Swedish University of Agricultural Sciences, P.O. Box 7045, 750 07 Uppsala, Sweden

Clarence Kvart DVM, PhD, DECVIM-CA (Cardiology) - Faculty of Veterinary Medicine Swedish University of Agricultural Sciences, P.O. Box 7045, 750 07 Uppsala, Sweden

There is a considerable variation between different types of heart disease with regard to pathophysiology, progression and the type and severity of clinical signs they precipitate. The key for optimal treatment in dogs with heart failure is to treat the pathophysiology for each type of disease. The traditional goals of medical therapy in heart failure are to alleviate clinical signs of heart failure, improve pump function and unload the heart. Many of the old types of drugs we use have actions that helps us to achieve these goals. In more recent years, the term “cardioprotection” has been added to these goals. Cardioprotection means to protect the heart from negative long-term exposure of neuroendocrine factors. It is not surprising that many of the more recently developed drugs and drugs currently under evaluation helps us to achieve this last goal. Therapy of heart failure usually involves concurrent treatment with two or several drugs. This polytherapy vary in composition depending on the nature of the underlying cardiac insult. The cornerstone of all types of heart failure therapy is diuretics. They erase the clinical signs of congestion, i.e. pulmonary edema/ascites, by reducing the extracellular fluid compartment and, thereby, the blood volume. The most commonly used diuretic agents today are, in ranking order, loop-diuretics (furosemide), aldosterone antagonists (spironolactone) and thiazides. Diuretics have the negative effect of stimulating an increased activity of the renin-angiotensin-aldosterone system (RAAS). Furthermore, the diuretic actions of these drugs are frequently counteracted by compensatory hypertrophy within the nephrone. In many cases, a tolerance for the drug is developed and, eventually, refractoriness. Thus, they are, preferably, not used in singledrug therapy in chronic therapy of heart failure. Angiotensin-converting-enzyme (ACE) inhibitors are now consider to be a first line drug as a supplement to other heart failure therapy. The cause for this are solid evidence derived from large clinical trials of beneficial actions, in terms of increased survival and improved quality of life. Several studies have shown that ACE-inhibitors possess multiple actions of which vasodilation is one. In the dose

range that is recommended for use in dogs, the vasodilating actions of the drug is not prominent and side effects are rare. In combination with diuretics, the ACE-inhibitors have synergistic effect with the diuretic by counteracting the reflectory stimulation of RAAS. The benefits of this is that the ACE-inhibitor helps to limit the dosage of diuretic by decreasing the tendency of fluid retention, but also counteract a peripheral vasoconstriction and other negative effects on the heart. Finally, it should be pointed out that there is no evidence that support early intervention with ACE-inhibitors in asymptomatic dogs. The venodilators (most commonly nitroglycerine ointment) are currently used in acute heart failure with severe pulmonary edema and ascites to decrease the venous pressure and thereby the diastolic filling of the heart (preload). Arterial vasodilators (most commonly hydralazine) are used both in acute and chronic heart failure. In dogs suffering from heart failure attributable to dilated cardiomyopathy, their use is usually limited to short-term treatment of acute heart failure together with a positive inotrope to unload the heart (afterload). In dogs suffering from mitral regurgitation, they are also used for chronic treatment with the objective to decrease afterload and thereby counteracting the regurgitation. However, arterial vasodilators have the disadvantage of several side effects. The most important actions of cardiac glycosides on the failing heart include enhancement of parasympathetic input to the heart and positive inotropic effect on the myocardium. The enhanced parasympathetic input to the heart aids to decrease the heart rate, which may be important in heart failure. The positive inotropic effect has been shown in numerous experimental settings, but is difficult to establish in clinical settings involving heart patients. Most of the other positive inotropic drugs increase the force of ventricular contraction mediated through an inhibition of phosphodiesterase (amrinone, milrinone and pimobendan), acts as sympaticomimeticum (dopamine, dobutamine,) or increase the sensitivity of the contractile proteins to Calcium (pimobendan). Many of the postive inotropes have shown

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promising results in pre-clinical studies, but clinical studies in people have shown increased mortality during long-term treatment with phosphodiesterase inhibitors,probably owing to increased myocardial energy demand and oxygen consumption. It appears logic that drugs that have other desired effects, such as vasodilation, may compensate for the nega-

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tive effects of increasing the work load of the heart. The new drug pimobendan has both inotropic and vasodilating properties and is, therefore, of interest for treating dogs with reduced myocardial performance. References are available on request.

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Inflammatory bowel disease Malattie infiammatorie dell’intestino (IBD)

Edward J. Hall MA, VetMB, PhD, DipECVIM, MRCVS Department of Clinical Veterinary Science - University of Bristol, Langford, Bristol, England

Inflammatory bowel disease (IBD) is a collective term used to describe a group of disorders that are characterised by histological evidence of intestinal inflammation and are associated with persistent or recurrent gastrointestinal signs. However, indiscriminate use of the term 'IBD' to describe GI disease is no more useful than a dermatologist making a diagnosis of 'chronic dermatitis'. Whilst a number of recognised diseases are associated with chronic intestinal inflammation, idiopathic IBD is by definition of unknown cause and strict diagnostic criteria must be used to exclude the known causes before it can be deemed idiopathic. Even then, variations in the histological descriptions of the intestinal inflammation suggest that idiopathic IBD is not a single disease entity. The disease in dogs and cats bears little resemblance to IBD (Crohn's disease and ulcerative colitis) of man.

CAUSES OF CHRONIC BOWEL INFLAMMATION • Food allergy • Chronic infection • Giardia • Histoplasma • Toxoplasma • Mycobacteria • Protothecosis • Pythiosis • pathogenic bacteria • Associated with primary GI diseases • lymphoma • lymphangiectasia • Idiopathic • Lymphocytic-plasmacytic enteritis (LPE) • Eosinophilic (gastro)-entero-(colitis) (EGE) • Granulomatousenteritis (same as regional enteritis?) • Histiocytic ulcerative colitis (HUC) • Immunoproliferative SI disease (IPSID)

CLINICAL PRESENTATION Idiopathic IBD is probably the most common cause of chronic vomiting and/or diarrhoea in dogs. In cats vomiting without diarrhoea is the most common manifestation

of IBD. However, it is only the recent advent of endoscopic biopsy that has allowed such a frequent diagnosis to be made. There is no apparent sex predisposition for IBD; the disease is seen most frequently in middle-age dogs and cats although there is often a history of intermittent signs from an earlier age. Owners frequently comment that their pet has a "sensitive stomach", and they have learnt that signs may be controlled, at least in part, by dietary manipulation. Certain breeds are predisposed to certain types of IBD: LPE GSDs, Shar pei EGE GSD IPSID Basenjis HUCBoxers Ultimately IBD is a histological diagnosis, but there are clinical features in the presentation that are characteristic. Furthermore the nature and severity of the signs can be crudely correlated to the region affected within the GI tract, to the histological type of inflammation, and to its severity. The signs of IBD are variable and may wax and wane, sometimes with obvious precipitating events, e.g. stress, dietary change. An individual case may show some or all of the following signs: • vomiting • haematemesis • SI-type diarrhoea • large volume • watery • melaena • LI-type diarrhoea • haematochezia • mucus • frequency and tenesmus • abdominal discomfort / pain • excessive borborygmi and flatus • weight loss • altered appetite • polyphagia • decreased appetite / anorexia • hypoproteinaemia / ascites Gastric signs are seen more commonly if there is gastric or upper intestinal inflammation and, in cats, vomiting may

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be the predominant sign. LI-type diarrhoea may be due to colonic inflammation, but can also occur secondary to prolonged SI diarrhoea; alternatively both SI and LI may be primarily inflamed. The presence of blood in the vomit or diarrhoea is associated with more severe disease and, especially, eosinophilic inflammatory infiltrates. Severe disease is associated with weight loss and even a protein-losing enteropathy with consequent hypoproteinaemia and ascites. Milder inflammation may not affect appetite but post-prandial pain can be a significant problem even in the absence of other signs.

AETIOLOGY A number of known causes of intestinal inflammation are listed above. Very recent studies have demonstrated a marked inflammatory response: • an increase in the expression of inflammatory cytokine mRNA (by RT-PCR techniques): IL-2, IL-5, IL-12p40, IFNγ, TNFα, TGFβ • increased CD4+ T cells in lamina propria • increased IgG plasma cells If use of a controlled diet induces a long-term remission the intestinal inflammation may be a manifestation of a true food allergy, whereas dietary manipulation is only an adjunct to therapy of idiopathic IBD. However, whilst a positive response to an exclusion diet may suggest a food allergy, some cases on repeat biopsy show persistence of the inflammatory response despite the resolution of clinical signs. In these cases it is probably the high digestibility of the diet that is helping. The infiltration of the lamina propria in idiopathic IBD may reflect an immune response to dietary, microbial or selfantigens, and certainly some cases are successfully managed with an exclusion diet or antibiotics. However, most cases require treatment with immunosuppressive drugs suggesting that there is an underlying immune defect that causes intestinal inflammation, but that luminal antigens may exacerbate the problem.

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The tests that are routinely performed: • Haematology Sometimes there is a neutrophilia and occasionally a mild left shift in LPE, and proplasmacytes may be noted. The presence of an eosinophilia is not diagnostic of EGE and is not invariably present. Anaemia may reflect chronic inflammation or chronic blood loss. • Serum biochemistry There are no pathognomonic changes in IBD, but diseases of other organ systems will be recognised as a cause of the GI signs. Hypoalbuminaemia and hypoglobulinaemia are characteristic of a PLE, and hypocholesterolaemia is suggestive of malabsorption. Mild elevations in liver marker enzymes (ALT, ALP) may reflect liver damage secondary to the intestinal inflammation and uptake of toxins through the damaged intestinal mucosa, and are of no direct consequence. However, in cats, there is a recognised association between IBD, chronic pancreatitis and lymphocytic cholangitis. • Urinalysis Unremarkable in IBD. • Faecal parasitology Ideally three consecutive samples should be chec ked for hookworms, whipworms and Giardia. In reality it is usually easier to treat empirically with fenbendazole. • Faecal culture The isolation of Salmonella or Campylobacter may be significant. Detection of pathogenic E. coli is restricted to specialist labs with appropriate pathogenicity probe markers. • Folate and cobalamin Proximal inflammation may cause folate malabsorption, whereas distal inflammation may lower serum cobalamin. However, this is not a reliable indicator, but severe reductions of folate and cobalamin do usually correlate with severe, diffuse intestinal inflammation. • Imaging Plain radiographs are used to look for anatomical intestinal disease. Contrast studies rarely add further information in IBD unless there is very severe mucosal disease. Ultrasound examination permits the evaluation of the thickness of any mucosal infiltrate, and guided fine-needle aspiration can be attempted.

DIAGNOSIS The clinical signs of IBD are often suggestive of the diagnosis, but intestinal inflammation must be confirmed by intestinal biopsy. Endoscopy is the easiest method of biopsy, but has limitations, particularly the inaccessibility of the jejunum (and ileum). In some cases, especially if there is some doubt as to whether there might be an anatomical intestinal problem (e.g. tumour, intussusception) or extra-intestinal disease (e.g. pancreatitis), exploratory laparotomy and full-thickness biopsy is preferred. Before intestinal biopsy is undertaken, laboratory tests and imaging examinations are performed. They will not enable a diagnosis of idiopathic IBD to be confirmed, but they hopefully rule out the known causes of intestinal inflammation.

TREATMENT Immunosuppression The mainstay of treatment of idiopathic IBD is immunosuppression. Prednisolone (1-2 mg/kg PO q 12h for 2-4 weeks, then tapering to maintenance dose q48 h) is the drug of first choice. Cushingoid side-effects are common but usually transient. However, if dosages can't be reduced without relapse alternative drugs are required in the longterm. Recently, a locally active steroid, budesonide (Entocort SR), that is destroyed 90% first-pass through the liver, has been successful in maintaining remission with minimal hypothalamo-pituitary-adrenal suppression.

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Azathioprine (2 mg/kg in dogs and 0.3 mg/kg in cats PO SID) has good steroid-sparing properties, and maintenance with alternate day steroid azathioprine is often successful. Azathioprine is potentially toxic in cats, and chlorambucil is a safer alternative. Cyclophosphamide and cyclosporine are potent immunosuppressives, but are rarely used in IBD. In colitis, 5-amino salicylic acid derivatives (sulphasalazine, olsalazine, mesalazine) are useful anti-inflammatory drugs.

Motility modifiers Opioids (loperamide, diphenoxylate) reduce clinical signs by decreasing urgency to defaecate and easing gut pain, and may be useful as an acute symptomatic treatment. As well as enhancing segmental gut contractions, and hence delaying intestinal transit, these compounds probably have an important anti-secretory effect.

Antibacterials Mucosal damage in IBD can affect the animalâ&#x20AC;&#x2122;s ability to control the intestinal flora and secondary SIBO can occur. However, antibiotics are rarely needed despite immunosuppression. Yet occasionally, LPE is a response to SIBO; treatment with antibiotics reduces the inflammation and steroids may actually make the signs worse . Metronidazole is often used in IBD, especially in cats, although it is not clear whether it is its antibacterial activity, its efficacy against Giardia or its effect on cell-mediated immunity that is the important mechanism. Tylosin is also reported to be useful in IBD.

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clusion diet trial is probably indicated in all cases of IBD before immunosuppression, and clients are usually willing to try this approach before administration of drugs. Nevertheless, dietary modification can be very useful in the management of idiopathic IBD. Indeed an elemental diet is as effective as steroids in inducing remission in humans with a granulomatous type of IBD called Crohn's disease. In general highly digestible, single protein source diets are used in IBD. These 'hypoallergenic diets' limit the antigenic diversity the intestine has to cope with. They may also act as a 'sacrificial protein' whereby any hypersensitivity to a protein that develops whilst the intestinal immune system is compromised is not to a constituent of the patient's staple diet. Rice is the preferred carbohydrate source because of its high digestibility, but potato and corn starch are also glutenfree. Fat restriction is useful in reducing clinical signs as fat malabsorption may be present. Modification of the n3:n6 ratio may also modulate the inflammatory response. Finally, the diet should contain some moderately fermentable fibre (e.g. ispaghula, beet pulp) to ensure colonic health in particular.

References 1. 2.

4. 5.

Dietary modification If an animal responds completely to an exclusion diet, its bowel inflammation is most likely a result of a dietary sensitivity, and this is one situation where diet alone is success ful. In view of the side effects of immunosuppression, an ex-

6. 7.

Batt RM,Hall EJ. Chronic enteropathies in the dog. J Sm Anim Pract 1989;30:3-12. Breitschwerdt EB, et al. A hereditary diarrhetic syndrome in the Basenji characterised by malabsorption,protein losing enteropathy, and hypergammaglobulinaemia. J Am Anim Hosp Assoc 1980;16: 551559. Guilford WG. Idiopathic inflammatory bowel diseases. In: Strombeck's Small Animal Gastroenterology, eds. Guilford, Center, Strombeck, Williams,Meyer, WB Saunders,Philadelphia, 1996;pp 451-486. Jacobs FG, at al. Lymphocytic-plasmacytic enteritis in 24 dogs. J Vet Int Med 1990;4:45-53. Je rgens A E , et al. Idiopathic infl a m m at o ry bowel disease in d ogs and cats: 84 cases (1987-1990). J Am Vet Med Assoc 1992; 201:1603-1609. Johnson SE. Canine eosinophilic gastroenteritis. Sem Vet Med Surg 1992;7: 145-152. Rutgers HC, Batt RM, Kelly DF. Lymphocytic-plasmacytic enteritis associated bacterial overgrowth in a dog. J Am Vet Med Assoc 1988; 192:1739-1742.

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Microbiology of the oral cavity and rational use of antimicrobials Microbiologia del cavo orale e uso razionale degli antibiotici

Philippe Hennet Docteur vétérinaire, Diplomate, American Veterinary Dental College Diplomate, European Veterinary Dental College, Paris, France

1. MICROBIOLOGY OF THE ORAL CAVITY

* Antibiotics and antimicrobials

Bacteria are normal inhabitants of the digestive tract, the oral cavity being the first part of it. From the normal flora known as the indigenous or endogenous flora, specific bacteria may develop at the favour of a change in the micro-environmental conditions and set an opportunistic infection. Oral health is an equilibrium between endogenous bacteria and oral defence system. Oral defences is mainly based on physical barriers (keratinized epithelium, mucous production,salivary flush), production of chemical compounds (salivary enzymes and antibacterials, gingival fluid secretions …) and inflammatory reaction. It is estimated that 100 billion bacteria coming from all oral surfaces are shed daily in the saliva. The total plaque flora constitutes about 5 percent of the salivary flora. There may be about 300 different species that can be isolated from the dental plaque alone. One mg of dental plaque contains about 10 million of bacteria. The flora of clinically healthy gingiva is mainly composed of aerobic and facultative anaerobic bacteria. Subgingival flora associated with periodontitis is predominantly anaerobic: Porphyromonas spp. (previously asaccharolytic black-pigmented Bacteroides), Prevotella spp. (previously saccharolytic Bacteroides), Peptostreptococcus spp., Fusobacterium spp. and Spirochetes. High levels of Porphyromonas spp., particularly P. gingivalis, and Spirochetes are consistently associated with progressive periodontitis in the do g. Other oral infectious diseases include caries, periapical infection, odontogenic infections, osteomyelitis, stomatitis …

2. RATIONAL USE OF ANTIMICROBIALS * Antiseptics Antiseptics can be used prior to any oral surgery to reduce the bacterial load. They are also fully part of the prevention of plaque accumulation on tooth surface (plaque retardant agents) combined whenever possible to toothbrushing. The most effective plaque retardant agents to date, is chlorhexidine. It is incorporated in various oral solution, gel or toothpaste. Because of possible interactions with other chemical compounds, its effectiveness should be assessed in vivo prior to marketing commercial formulations.

antibiotic prophylaxis: a specific protocol should apply to animals at risk of developing systemic diseases consecutive to bacteremia. They include immunocompromised animals, animals with organic or metabolic failure, animals with heart disease and possibly animals with a prosthetic joint. Wound contamination may occur when healthy tissue is exposed to the oral flora during dental treatment. This is the case when crown height reduction and partial vital pulpectomy is performed as well as when healthy oral mucosa or bone is exposed during periodontal or oral surgery.

An injectable antibiotics such as amoxicillin or ampicillin can be used at a dosage of 20-25 mg/kg IV, IM 30 minutes before the procedure then 10-12-5 mg/kg IV, IM 4 hours after initial dose. -

antibiotic therapy: choice of the antibiotic must be based on knowledge of the predominant bacterial flora associated with the disease process, culture results (if specific anaerobic sampling and culturing techniques can be used), site of infection and physiologic status of the animal.

Without any doubt, periodontics is the branch of dentistry where antimicrobials are the most widely used and misused. It should be reminded that treatment of periodontal disease is scaling, root planing, polishing, and possibly dental extractions and periodontal surgery. Antibiotics should be use with discrimination because they may have potential side effects (superinfections, bacterial resistance, allergic and toxic reactions …) and they are unable to cure oral diseases when used alone. Systemic antibiotics may be helpful when dealing with a maxillo-facial cellulitis caused by pulpal infection. If a single-visit treatment is performed in such a case, antibiotic therapy should be used. Replantation of exarticulated and luxated teeth is associated with high risk of root resorption. It has been shown in dogs and in monkeys that after systemic antibiotic treatment at the time of replantation, there was no inflammatory root resorption or there were shallower resorptive cavities without inflammatory cells.

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Antibiotics most commonly used for oro-dental diseases include: • Amoxicillin : 10 mg/kg BID • Amoxicillin-Clavulanate: 12.5 mg/kg BID • Clindamycin : 5.5 mg/kg BID or 11 mg/kg SID

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• Doxycycline: 10 mg/kg SID • Metronidazole: 15-20 mg /kg BID • Metronidazole-Spiramycine: 12.5 –16 mg/kg (Metronidazole) + 75000-100000 UI /kg (Spiramycin)

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Management of advanced periodontal disease I denti si muovono: un problema da curare

Philippe Hennet Docteur vétérinaire, Diplomate, American Veterinary Dental College Diplomate, European Veterinary Dental College, Paris, France

Decision making when facing advanced periodontal disease must take into consideration deep periodontal pockets, loss of attached gingiva, alveolar bone resorption, tooth root resorption, infection of the pulpal tissue and likelihood of regular dental home care. Advanced periodontal disease has been described as a condition where there is a horizontal bone loss of more than 1/3 of supporting tissues (Hamp et al., 1984). This condition may be worsened by the presence of angular bony defect (infrabony pocket, interdental osseous crater) or furcation involvement in a multi-rooted tooth (Nyman S, Lindhe J, 1997). The name complicated periodontitis has been given.

ASSESSMENT OF THE SEVERITY OF PERIODONTAL LESIONS IS BASED ON: -

Gingival inflammation: spontaneous bleeding in the gingival sulcus or provoked bleeding while gently probing the periodontal pocket are signs of severe inflammation with ulceration of the sulcular or pocket epithelium. Detection of loss of attachment: the physiologic level of the epithelial attachment is the cemento-enamel junction. When probing the sulcular area, any penetration of the probe apical to that level indicates a loss of the attachment and subsequently periodontitis. If the gingiva margin has receded at the same time, the root surface will be exposed and no deep pocket will be seen. If no recession of the gingival margin occurs, loss of attachment will be seen with the presence of a deep pocket. Detection of bone loss in the furcation: the blunt periodontal probe is used at right angle to the tooth surface. No penetration of the probe in the furcation area should occur. If it is possible to penetrate with the probe between the roots, it indicates bone loss in the furcation. According to the amount of bone lost, a furcation index has been designed. Class 1 furcation is penetration of the probe less than a 1/3 of the width of the tooth, class 2 furcation is penetration more than a 1/3 but not to the full width, class 3 furcation is penetration to the full width. Mobility: can be easily assessed by moving laterally or vertically the tooth between two instruments or with a plier. Grade 1 mobility is 1 mm of lateral mobility, grade 2 mobility is 1 to 2 mm of lateral mobility and grade 3 mobility is more than 2 mm of lateral mobility and/or axial (vertical) mobility.

DETERMINATION OF UNSALVAGEABLE TEETH Decision regarding extraction of periodontally diseased teeth depends on the extent of the disease and on the willingness and ability of the owner to perform dental home care. Some teeth will have, without any doubt, to be extracted. Criteria for extraction may be mobility index of 3, loss of attachment greater than 2/3 of initial attachment and perio-endo lesions. Some teeth may be saved with proper periodontal treatment,including periodontal surgery and possibly reconstructive periodontal surgery, and if proper dental home care is performed. Without home care, treatment will be a failure and the tooth will have to be extracted at a latter date.

CONSERVATIVE TREATMENT OF ADVANCED AND COMPLICATED LESIONS The single most important part of the treatment is the non surgical treatment or initial phase of the periodontal treatment which aim is to eliminate the cause of the disease i.e. the dental plaque and associated calculus. After elimination of supragingival plaque and calculus, subgingival debridement is performed. This can be achieved with manual subgingival curets or with newest periodontal subgingival ultrasonic tips. This step is the most important as subgingival plaque/calculus is responsible of deep periodontal lesions. In some cases periodontal surgery may be used. The primary rationale for periodontal surgery is to expose root surfaces that are inaccessible, such as those associated with deep pockets or furcations, in order to improve the efficiency of subgingival work. Beside gaining access to root surfaces, other goals of flap procedures are surgical elimination of the periodontal pocket, induction of new attachment and bone regeneration in periodontal pockets and correction of gingival and mucogingival defects. Specific cases that may be surgically treated include: deep angular defects (> 6mm) without furcation exposure deep palatal pockets in upper canine teeth interradicular defects (furcation involvement) class II and III gingival recession defects class I, II and III Various flap techniques (minimal exposure, muco-gingival, apically positioned, coronally-positioned) may be used with or without bone surgery. In specific cases regenerative procedures can be attempted. -

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Feline Odontoclastic Resorptive Lesions (FORL): "neck lesions" Malattie parodontali nel gatto, lesioni odontoclastiche erosive dei denti del gatto e stomatite cronica: una panoramica delle attuali conoscenze

Philippe Hennet Docteur vétérinaire, Diplomate, American Veterinary Dental College Diplomate, European Veterinary Dental College, Paris, France

EPIDEMIOLOGY

POSSIBLE PATHOGENESIS

* Prevalence

* Inflammation

In the general population, by using only clinical assessment, 26 to 29% seem affected. In the sub-population of cats with oro-dental problems, prevalence is 43% to 62% (clinical assessment only) and 67% (clinical and radiological assessments). In a necrospy study in cats, there was 1.4 times more crown lesions, and 2.4 times more root and alveolar bone lesions detected by radiography than by clinical examination (Gengler et al., 1995). Prevalence does increase with age. No breed predilection was observed for most studies. Most commonly affected teeth are premolar, especially lower P3 and M1 and upper P4. Incisors and canines tend to be less affected. Buccal surface more affected than lingual or palatal surfaces.

* Anatomic abnormalities: Vasodentin-like structures ans osteodentin-like structures Lower microhardness of feline enamel and dentin

ETIOLOGICAL HYPOTHESIS Immune mediated inflammation: Calcium regulation Diet Mechanical trauma

TREATMENT Conservative treatments?

MICROSCOPIC FEATURES Three different phases can be re c og n i zed on histological sections: acute phase, chronic phase and remodeling phase [Okuda et al. (1992, 1995)]. During the acute phase, odontoclasts and /or osteoclasts (and pre c u rs o rs ) are attached to the surface of lacunae of intact dental tissue and are also found close to blood vessels in inflamed gingiva. There is no other pathologic changes on adjacent hard tissue and pulpal tissue. During the chronic phase, resorptions have progressed into the dentine and deposition of Bone-Cementum-like tissue (BC tissue) is seen on the surface of excavated dentin. Lesions are both in resorptive and reparative phases. On the surface of BC tissue, odontoblasts/osteoblasts - are seen. Not only tooth resorption but also alveolar bone resorption can be seen. No pulpal tissue involvment until late in the process can be seen. With development of pulpal inflammation, lesions can be considered as external/internal resorptive lesions. Reparative dentin does not seem to offer a protective effect (Lukman 1995).

Restorative treatment of feline odontoclastic resorptions has been advocated for many years in the same way human cavities would be treated. Material of choice is glass ionomer as minimal cavity preparation is necessary due to the binding ability of glass ionomer with calcium ions of dentin and enamel. More recently, newer materials such as micro-glass composite and compomer (combination of glass ionomer and composite material) have also been proposed. For many years, treatment choice has been based on a clinical staging of the lesion which considers mostly depth of the lesion and pulpal involvment (Mulligan's classification) (1). Restoration was recommended for class 1 and class 2 lesions whic h do not invade the pulpal tissue. In 1992, in a study performed at the Veterinary Hospital of the University of Pennsylvania (VHUP), the use of this classification as the sole criteria for decision making was questionned. Concerned by the practibility of restorative treatments in tiny cat teeth with lesions close to the gum line and /or extending below it, it was proposed to take into con-

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sideration the location of the lesion relative to the bony crest ("bone level classification") and subsequently emphasized the need for taking radiographs in each case before making any decision concerning treatment. The conclusion were that if restorative treatment was possible, it only concerns a very small pourcentage of teeth affected by FORL. Treatment made without considering these criteria cannot be considered done properly. Another point that was taken into consideration to determine whether restorative treatment of FORL was appropriate was the long-term result of these restorative treatments. Three major published studies have brought some new inlights on the question: US study (Lyon, 1992); German study (Roes F., 1993); Austrian study (Zetner K., Steurer I., 1995). They have shown similar results which can be averaged as a success rate of 25% at 15 months. Subsequently, restorative treatment cannot be proposed as the general treatment of FORL even though if it can be proposed in specific cases. However, in these cases the owner has to be informed on the success rate, lesions have to be selected on clinical

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and radiographical features and clinical and radiographical follow-up is necessary.

NON CONSERVATIVE TREATMENTS General treatment of FORL is subsequently non conservative i.e. extraction. The most conventionnal technique involves the use of thin dental elevators using a leverage technique. When teeth with FORL are ankylosed, standard leverage technique aimed to stretch the periodontal ligament cannot be used. Instead of that, the thin eventually sharpened elevator is used to dig a path in the bone along the root. Another described technique is called "root atomization". The root is pulverized using a bur and the high speed. Recently, planned retention of root fragment that are endodontically and periodontally healthy has been recommended (Dupont, 1995). Very strict selection criteria should be met to perform this technique and further long term results have still to be known. In no way this technique should be performed in cats presenting with chronic gingivitis-stomatitis.

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Limbal masses Masse a livello limbare

Thomas J. Kern D.V.M., Associate Professor, Ophthalmology, Cornell University, Ithaca, New York, Diplomate, American College of Veterinary Ophthalmologists

SIGNALMENT AND BREED PREDISPOSITION: Limbal masses may be classified as pigmented or nonpigmented. Pigmented limbal masses are most common in large breed dogs in middle age, especially German Shephe rd Dogs and their crosses and retrievers. Non-pigmented limbal masses occur in a wide variety of breed at va ri able ages, but American Cocker Spaniels are predisposed to episcleritis and Collies to nodular gra nu l o m atous episclerokeratitis (NGE). Limbal masses in cats are distinctly uncommon.

CLINICAL FINDINGS: Pigmented limbal masses, epibulbar melanomas, most often involve the dorsal and lateral limbus, usually unilaterally. They arise as expansile flat black discolorations of the sclera; typically the peripheral cornea adjacent to the melanoma is invaded. With time the masses thicken and protrude. Because they may be covered by the upper eyelid they often grow quite large before they are noticed. Conjunctivitis and uveitis are absent and the leading edge of corneal involvement may develop crystalline corneal degeneration. Non-pigmented masses, inflammatory in origin, usually also involve the the temporal and dorsal limbus. Focal episcleritis appears as a smooth pink subconjunctival nodule that enlarges; less commonly lesions arise multifocally. Conjunctivitis is variable. Diffuse episcleritis appears as generalized scleral redness and thickening and often simulates buphthalmos due to glaucoma. Either form may be uni- or bilateral. Occasionally anterior uveitis is present. Intraocular pressures are normal to low. Nodular granulomatous episclerokeratitis may resemble episcleritis in its early stages (without uveitis), but may be distinguished from it when/if similar nodules develop on the eyelids, nictitans, lips, planum nasale, and/or genitalia. Papillomas of the conjunctiva occasionally involve the limbus.

PATHOGENESIS: Pigmented limbal masses are almost always epibulbar melanomas. Fortunately they are behave as benign neoplasms insofar as metastasis is rare, although local extension may be wide. Episcleritis and NGE appear inflammatory and may

have an immune-mediated basis. Conjunctival papillomatosis is of viral origin.

DIFFERENTIAL DIAGNOSIS: Pigmented limbal masses: 1) Epibulbar melanoma 2) Uveal melanoma with scleral extension 3) Conjunctival nevus Non-pigmented limbal masses: 1) Episcleritis 2) Nodular episclerokeratitis 3) Conjunctival papillomatosis 4) Multicentric neoplasia (e.g., lymphosarcoma)

DIAGNOSTIC PLAN: Typical pigmented and non-pigmented masses are presumptively assessed as epibulbar melanomas, NGE, episcleritis, or papillomas; atypical masses may be biopsied. Complete ocular examination with tonometry should be performed.

TREATMENT PLAN: Therapy for epibulbar melanomas includes cryotherapy, diode laser ablation, and resection with scleral graft placement. Uveitis may follow cryotherapy and laser ablation; topical and systemic anti-inflammatory agents and topical 1% atropine control it. Resection may be technically difficult and requires that the scleral and corneal defects by replaced by fresh or frozen scleral grafts; complications include uveitis and local and intraocular infection. Recurrence is possible. Enucleation should be considered for extremely extensive epibulbar melanomas and the (rare) uveal melanoma that has breached the sclera. Focal unilateral episcleritis and NGE may be managed with single or repeated injections of repositol corticosteroids and topical steroid administration. Bilateral involvement with either is managed with oral corticosteroids (2.2 mg/kg/day) and/or azathioprine (2.2 mg/kg/day) for 2-3 weeks, then slowly tapered. Many dogs require maintenance therapy of one or both drugs to prevent recurrences. Conjunctival papillomatosis is typically self-limiting and often resolves spontaneously. Excision may cause lesions to multiply.

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Crystalline Deposits in the Cornea Depositi cristallini corneali

Thomas J. Kern D.V.M., Associate Professor, Ophthalmology, Cornell University, Ithaca, New York, Diplomate, American College of Veterinary Ophthalmologists

SIGNALMENT AND BREED PREDISPOSITION: Crystalline deposits in the cornea in dogs are a common bilateral inherited condition (corneal dystrophy) in many breeds, including Siberian huskies, American Cocker and other spaniels, Golden and other retrievers. Age at diagnosis is variable; onset is usually slow and signs are subtle. Deposits indistinguishable clinically from corneal dystrophy affect both dogs and cats with certain other corneal disorders and are called corneal degenerations.

CLINICAL FINDINGS: Uni- or bilateral crystalline corneal dystrophy typically involve the central and paracentral superficial cornea, are oval in shape and appear gray to white in color; neovascularization and conjunctivitis are absent. With time small lesions enlarge but rarely to the extent that vision is compromised significantly. In some breeds (eg, huskies) the peripheral cornea is affected circumferentially and deeper stromal layers are opacified. Corneal degeneration may be uni- or bilateral and may be adjacent to a corneal scar or area of active neovascularization but neither is necessarily present.

PATHOGENESIS: Corneal dystrophies are inherited in dogs; modes of inheritance are not known. Corneal degenerations occur secondary to other structural or functional ocular disorders. Dogs with focal or diffuse corneal neovascularization (e. g. ,d egenerative pannus, keratoconjunctivitis sicca) and those with lagophthalmos often develop crystalline keratopathy. Metabolic disorders of lipid metabolism (primary hyperlipidemia, hypothyroidism, etc.) and high-fat diets have been suggested as causes but proof is lacking. Many of the same breeds ( and not the same individual dogs) are commonly affected by both disorders.

DIFFERENTIAL DIAGNOSIS: Crystalline keratopathy: 1) Inherited corneal dystrophy 2) Corneal degeneration

DIAGNOSTIC PLAN: Presumptive diagnosis of corneal dystrophy is made when typical lesions are visible in one or both eyes of purebred dogs in the absence of other ocular disorders. Corneal degeneration is more likely in the presence of active corneal neovascularization, corneal melanosis, chronic corneal ulceration, keratoconjunctivitis sicca, and/or lagophthalmos. Laboratory investigation of potential hyperlipidemia and endocrinopathy and historical pursuit of dietary patterns may be performed.

TREATMENT PLAN: Therapy is not recommended for corneal dystrophy; visual impact is usually small to minimal and the lesions constitute a blemish. Breeding recommendations are controversial. Specific therapy for corneal degeneration is not usually recommended; control of the other associated conditions is aimed at their control. Occasionally the degeneration area is large and dense enough to cause blindness; if so, keratectomy may offer improvement but the condition often recurs. Dogs suspected of having lagophthalmos as the cause may be treated with ocular lubricant ointment 4-6 times daily; if lesions improve or resolve after 2-3 months of therapy it may be continued indefinitely. If hyperlipidemia and/or endocrinopathy have been identified appropriate treatment should be enacted. Inappropriate diets should be corrected.

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Non-healing Corneal Ulcers Ulcere indolenti

Thomas J. Kern D.V.M., Associate Professor, Ophthalmology, Cornell University, Ithaca, New York, Diplomate, American College of Veterinary Ophthalmologists

SIGNALMENT AND BREED PREDISPOSITION: Non-healing ulcers in dogs are most common in middleaged and older animals. Several breeds appear to be at increased risk: boxer, corgi, Golden retriever, poodle, Samoyed, others. Non-healing ulcers in cats are common in adult cats of all ages. Brachycephalic cats appear to be at somewhat higher risk than others: Persian, Himalayan, Burmese.

prominent neovascularization that develops with chronicity and more obvious ocular discomfort. In cats the feline herpesvirus is incriminated in most erosions, with and without delayed healing. The circumstances that delay healing are unclear. Some brachycephalic cats appear to develop erosions due to lagophthalmos and/or entropion. In either instance prolonged corneal ulceration is associated with development of corneal sequestrum, a unique feline form of corneal degeneration resulting in brown to black stromal discoloration and necrosis and persistent epithelial defects.

CLINICAL FINDINGS:

DIFFERENTIAL DIAGNOSIS:

Typical erosions are axial to paraxial with a surrounding lip of non-adherent epithelium. Because of the superficial nature of the lesion corneal thickness appears normal. Fluorescein stain pattern is distinctive: a central area of prominent dye retention with (immediate) staining of the surrounding cornea in a halo configuration. Mild corneal edema may surround the apparent epithelial defect. Epithelium may roll at the erosion=s edges. When touched with a cotton swab the epithelium at the edge easily lifts and moves. In most dogs and many cats neovascularization is absent unless the cornea has been treated/damaged by debridement attempts with tincture of iodine, phenol, or trichloroacetic acid. Mild miosis may indicate mild reflex uveitis. Blepharospasm and photophobia are usually present.

Dogs: 1) Inherited corneal (epithelial) dystrophy 2) Endocrinopathy: diabetes mellitus, hyperadrenocorticism 3) Eyelid defects: ectopic cilium, distichiasis, entropion, lagophthalmos, nasal folds 4) Trauma 5) Keratoconjunctivitis sicca Cats: 1) Feline herpesvirus 2) Eyelid defects: entropion, lagophthalmos, nasal folds 3) Trauma

DIAGNOSTIC PLAN: PATHOGENESIS: In dogs the condition is classified as a form of corneal dystrophy, although the structural and/or biochemical mechanisms involved are poorly understood. Erosions develop spontaneously. Trauma plays a causative in some non-healing erosions, which resemble the spontaneous ones. Endocrinopathies such as hypothyroidism have been postulated to be associated but proof is lacking. Dogs with diabetes mellitus and hyperadrenocorticism appear to have fragile epithelium which may be more prone to ulceration and retarded healing. Occasionally dogs with Cushing=s syndrome develop stromal mineralization, over which persistent epithelial defects develop. Chronic corneal ulceration secondary to eyelid defects (ectopic cilia, distichiasis, entropion) may be distinguished from erosions of this syndrome by the usually

In both dogs and cats complete ocular examination with careful examination of blinking ability, lacrimation, and eyelid conformation (including palpebral and membrana nictitans surfaces) is indicated. The non-healing erosion syndrome is presumptively diagnosed in the presence of typical erosion with redundant epithelial flap in the absence of responsible eyelid defects. In cats, feline herpesvirus infection is presumed. Laboratory confirmation may be attempted by viral isolation, PCR or fluorescent antibody testing of conjunctival or corneal epithelial samples. However, up to one-third of normal asymptomatic cats test positively and a negative test result does not preclude the diagnosis! Cats that develop recurrent herpetic keratitis should be screened for the feline leukemia and immunodeficiency viruses.

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TREATMENT PLAN: Dogs should be sedated and under topical ocular anesthesia undergo epithelial debridement and punctate or grid keratotomy. The non-adherent epithelium should be removed with a cotton swab wetted with eyewash as far as necessary to reach the limits of normal epithelial adhesion; this typically involves unmasking a much larger-than-apparent corneal erosion. The punctate or g rid keratotomy is performed with the point or edge of a 22 gauge needle over the entire exposed stromal surface and for 1-2 mm over the edge of normally adherent epithelium. For stubborn erosions the above may be combined with a membrana nictitans flap to increase the treatment success rate. Topical antibiotic and atropine ther apy should be prescribed, with followup examination scheduled for 2-3 weeks later. The large majority of erosions treated thus will heal; unhealed erosions subjected

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to a second round to this treatment protocol usually heal then. Owners should be warned that erosions may recur in the same or other eye, especially in dogs with diabetes mellitus or hyperadrenocorticism. Tear deficiency, rarely the proximate cause, should be addressed when present. Affected cats should undergo debridement of non-adherent epithelium with a cotton swab under topical anesthesia and be treated with topical anti-herpetic agents (vidarabine, trifluridine, idoxuridine) 4-6 times daily for 2-3 weeks. Topical antibiotic and atropine therapy accompanies this. Cats showing inadequate healing progress in 3 weeks may undergo a second debridement followed by punctate or grid keratotomy and continued topical antiviral therapy plus/minus nictitans flap. If stroma develops brown discoloration before or during re-epithelialization, prognosis for healing without keratectomy is guarded. Oral lysine has been recommended for cats with chronic or recur rent herpetic keratitis.

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Iridal Masses Masse o tumefazione dell’iride

Thomas J. Kern D.V.M., Associate Professor, Ophthalmology, Cornell University, Ithaca, New York, Diplomate, American College of Veterinary Ophthalmologists

SIGNALMENT AND BREED PREDISPOSITION: Pigmented iridal masses most commonly afflict Labrador and Golden retrievers. Pigmented iridal masses in cats and non-pigmented masses in both dogs and cats do not show strong breed predilections. Mature animals are most commonly affected.

CLINICAL FINDINGS: Pigmented iridal masses in both species are either focal to multifocal or diffuse solid tissue enlargements on or within the iris (neoplasms) or round cysts that transilluminate. Non-pigmented iridal masses resemble the pigmented ones in distribution and extent but lack dark brown or black coloration. Some truly non-pigmented masses that develop within heavily pigmented irides may be indistiguishable from primary pigmented ones. Dyscoria, posterior or anterior synechiae, abnormal pupillary excursions, and/or objective signs of uveitis (flare, cells, ciliary injection) may be present depending upon the etiology. Iris/ciliary cysts may be attached or free-floating; eventually most gravitate to the ventral anterior chamber, where they flatten and attach to the iris, cornea, or iridocorneal angle. Many cysts may develop simultaneously in one or both eyes but may not be visible until the pupil is dilated for examination. Vision may be affected if uveitis is present or if a large uveal cyst lodges in the pupil.

PATHOGENESIS: Pigmented iridal masses arise from native uveal melanocytes. In dogs solitary uveal melanomas are generally considered to be benign to low-grade malignant neoplasms with low metastatic potential. Uveal melanomas in cats are considered to be malignant (especially difffuse iris melanomas). Uveal cysts may develop de novo in adult animals or may be congenital. In dogs a pseudotumor-like iris swelling responsive to corticosteroids has been seen but remains unexplained. Granulomatous infiltration of the iris stroma may simulate neoplasia. Widely metastatic or multi-

centric neoplasms (e.g., hemangiosarcoma, lymphosarcoma) may spread to the iris and/or ciliary body. Primary ciliary body neoplasia may enlarge the base of the iris, simulating primary iris origin.

DIFFERENTIAL DIAGNOSIS: Pigmented iridal masses: 1) Uveal melanoma 2) Uveal cyst 3) Uveal pseudotumor Non-pigmented iridal masses: 1) Primary uveal neoplasm: amelanotic melanoma; ciliary body adenoma/adenocarcinoma; medulloepithelioma 2) Metastatic neoplasm to uvea 3) Granulomatous inflammation: systemic mycosis; immune-mediated; other

DIAGNOSTIC PLAN: Complete ocular examination including posterior segment examination after mydriasis and tonometry is indicated. Fine needle aspirate of solid iris masses may distinguish between pigment-cell and other (inflammatory, non-pigment cell neoplasm) origin, but definitive diagnosis is difficult and unreliable by this method. In certain cases iris biopsy may be justifiable. Complete physical examination and judicious thoracic radiography and abdominal ultrasound examinations to identify occult primary neoplasia or systemic mycosis may be indicated. Round pigmented masses that transilluminate and/or move about the anterior chamber are predictably uveal cysts.

TREATMENT PLAN: Primary uveal melanomas in dogs may be treated by diode laser ablation, (occasionally) transscleral cryoablation, or (rarely) en bloc resection. Alternatively, affected dogs may be monitored regularly without treatment for local tumor growth. Eyes that develop glaucoma or intractable

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uveitis should be enucleated and undergo histopathologic examination. Cats with primary uveal melanoma should undergo enucleation as well. Iris cysts usually do not require therapy. If problematic, they may be destroyed with Nd:YAG or diode laser ablation

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or simple needle aspiration. Idiopathic granulomatous inflammation may be treated with immunosuppressive corticosteroid or antineoplastic drugs. Systemic mycoses should be treated with specific antifungal drugs for extended periods.

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Chorioretinitis Corioretinite

Thomas J. Kern D.V.M., Associate Professor, Ophthalmology, Cornell University, Ithaca, New York, Diplomate, American College of Veterinary Ophthalmologists

SIGNALMENT AND BREED PREDISPOSITION: Chorioretinitis afflicts dogs and cats of all ages and most of its causes show no clear breed predilection. Arctic dog breeds are predisposed to uveodermatologic syndrome; age of onset is variable.

CLINICAL FINDINGS: Unless chorioretinitis involves both eyes extensively enough to cause vision impairment its presence is not suspected. On careful complete ocular examination mild anterior uveitis-aqueous flare and/or cells,miosis, ciliary injection-may be identified in some animals. Inappropriate mydriasis and abnormal pupillary light responses are evident if extensive retinopathy is present. On fundus examination active lesions appear indistinct, often raised; in the tapetal area reflectivity is locally reduced and in the non-tapetal fundus such lesions are prominently gray or white. Inactive tapetal area lesions are sharply marginated, hyperreflective and/or variably hyperpigmented; inactive nontapetal area lesions also have sharp margins but may appear to have locally increased or reduced pigmentation.

DIFFERENTIAL DIAGNOSIS: 1) Infectious diseases: Viruses: canine and feline distemper; FIP Protozoa: toxoplasmosis Systemic mycoses Bacteria: brucellosis, others Spirochetes: leptospirosis, borreliosis Rickettsia: ehrlichiosis, RMSF Algae: protothecosis 2) Immune-mediated inflammation: uveodermatologic syndrome, others?

DIAGNOSTIC PLAN: Complete physical and ocular examinations are indicated. Thoracic and/or abdominal radiography and abdominal ultrasonography may identify occult systemic disease. Specific serologic testing may suggest treatable infectious diseases. Skin biopsy of depigmented mucocutaneous sites may document uveodermatologic syndrome.

TREATMENT PLAN: PATHOGENESIS: Inflammation of the choroid involves the overlying retina and vice versa. Probably because of its extensive vascular supply, the choroid is frequently a site of involvement of disorders that cause vasculitis or hematogenous distribution of infectious agents and neoplastic cells. Immune-mediated disorders directed at melanocytes (e.g., uveodermatologic syndrome) target the choroid and retinal pigment epithelium for attack and destruction. Neurotropic viruses (e.g., canine distemper, neonatal feline distemper viruses) may infect the retina.

Specific antibiotic therapy, where available and indicated, should be prescribed for proven or presumptive infectious diseases (e.g., toxoplasmosis, mycoses, brucellosis, rickettsial and spirochete infections). Anterior uveitis should be controlled with topical antiinflammatory drugs and atropine. Dogs with uveodermatologic syndrome should be aggressively treated with immunosuppressive dosages of oral corticosteroids and/or azathioprine and maintained on a reduced dosage indefinitely.

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Retinal Detachment Distacco retinico

Thomas J. Kern D.V.M., Associate Professor, Ophthalmology, Cornell University, Ithaca, New York, Diplomate, American College of Veterinary Ophthalmologists

SIGNALMENT AND BREED PREDISPOSITION: Congenital retinal detachment that accompanies multiple ocular anomalies is inherited in a large number of dog breeds, including but not limited to Collies, Labrador retrievers, Samoyeds, American Staffordshire terriers. Congenital retinal detachment associated with retinal dysplasia syndromes is inherited in Mastiffs, Cavalier King Charles Spaniels, English Springer Spaniels, and others. Acquired retinal detachment may afflict dogs born with retinal dysplasia or optic nerve or posterior segment scleral colobomas. Breeds at risk for lens-luxation-associated glaucoma (primarily terriers) are at risk of retinal detachment as part of the syndrome. Shih Tzus, Bichon Frises, and Whippets are at risk for retinal tears and subsequent detachment. German Shepherd Dog and related breeds appear to be at increased risk for a presumptively inflammatory or immune-mediated choroiditis and secondary effusive retinal detachment. Arctic breeds are predisposed to the posterior and anterior segment forms of the uveodermatologic syndrome. Retinal detachment afflicts mature to elderly cats and has no prominent breed predilection.

CLINICAL FINDINGS: Vision is variably affected depending upon extent of retinal detachment and uni- or bilateral involvement. Relative to tonic mydriasis and abnormal pupillary light responses are typical. Funduscopic examination shows focal to multifocal or diffuse retinal elevation. Retinal detail is indistinct or obscured. Spectrum of detachment varies from small areas less than a disc diameter in area to 360 degree retinal elevation in a morning-glory pattern. If the retina is torn away from the ora ciliaris retinae the naked choroid and tapetum may be visible and the optic disc may be obscured. Vitreal hemorrhage from retinal vessels may variably obscure fundus detail. Hyphema may occur, especially in hypertensive cats.

DIFFERENTIAL DIAGNOSIS: Dogs: 1) Inherited ocular malformations: multiple ocular anomaly syndromes, retinal dysplasia syndromes; lens luxation syndromes 2) Immune-mediated inflammation 3) Trauma 4) Infections: systemic mycoses, protothecosis, others 5) Hypertension/renal disease Cats 1) Hypertension plus/minus renal disease/hyperthyroidism 2) Infections: systemic mycoses

PATHOGENESIS: Congenital retinal detachment probably develops as a result of abnormal early development of the relationships between the layers of the optic cup. Acquired retinal detachment develops because the retina is pushed off the choroid, pulled off, or perforated (torn). Choroidal effusion from inflammation or infection and choroidal hemorrhage from trauma or coagulopathy push the retina off. Resolving vitreal hemorrhage and vitreal degeneration create traction on the retina resulting in tears and detachment. The pathogenesis of hypertensive retinopathy, especially in cats, seems complex. Choroidal effusion secondary to hypertensive vasculopathy may progressively peel off the retina, while vitreal hemorrhage and associated degeneration pull it off the choroid. Renal disease may be interconnected in the pathogenesis of both the hypertension and its ocular sequelae.

DIAGNOSTIC PLAN: Complete ocular and physical examinations should be performed. In adult dogs and cats blood pressure should be measured and hemogram and serum panel should be ordered. In eyes with opaque media ocular ultrasound should

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be performed . Animals suspected of having an occult systemic disorder should undergo thoracic radiography and abdominal ultrasound as indicated.

TREATMENT PLAN: Animals with extensive or total retinal detachment are beyond help. Those with focal detachments may benefit from diode laser retinopexy of normal retina adjacent to the de-

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tachments. Dogs with presumptive inflammatory choroiditis should be treated with immunosuppressive doses of corticosteroids and/or azathioprine; if detachments resolve (they often do) drugs should be tapered to a maintenance dose; they can be discontiuned without relapse in some dogs (but not those with uveodermatologic syndrome). Dogs with inherited disorders should not be bred. Hypertensive cats should be treated with amlodipine to effect; reattachment often occurs but vision improvement is less predictable.

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Optic Neuritis Infiammazione del nervo ottico

Thomas J. Kern D.V.M., Associate Professor, Ophthalmology, Cornell University, Ithaca, New York, Diplomate, American College of Veterinary Ophthalmologists

SIGNALMENT AND BREED PREDISPOSITION: Dogs and cats afflicted with optic neuritis are adults of variable age. No breed predisposition is apparent.

3) Systemic mycosis: cryptococcosis, others 4) Sudden acquired retinal degeneration Cats: 1) CNS neoplasia: primary, metastatic 2) Systemic mycosis: cryptococcosis, others

CLINICAL FINDINGS:

Both: 1) Trauma

Affected animals are usually not identified until vision loss is profound and bilateral; onset is often but not always sudden. Animals are blind or nearly so. Tonic bilateral m ydriasis is typical; pupillary responses may be present but are reduced. Fundus examination may be normal or show optic disc swelling, hemorrhages, and peripapillary retinal elevation. Neurologic examination is typically normal except for vision related abnormalities.

PATHOGENESIS: In dogs granulomatous meningoencephalitis appears to be the predominant cause based on cerebrospinal fluid tap cytology and response to therapy. Primary and metastatic CNS neoplasia are important causes. In cats cryptococcosis and other systemic mycoses are common, as is CNS neoplasia. Rarely in both species, traumatic injury to the CNS may cause optic neuritis, usually accompanied by other major neurologic signs.

DIFFERENTIAL DIAGNOSIS: Dogs: 1) Granulomatous meningoencephalitis 2) CNS neoplasia: primary, metastatic

DIAGNOSTIC PLAN: Complete ocular, physical, and neurologic examinations should be performed. In dogs electroretinography documenting normal retinal function implicates optic neuropathy as the blindness = cause. In both species CSF tap results may implicate mycosis. The presence of mixed inflammatory cells, normal CSF protein concentration, and absence of organisms implicates the ocular form of GME. High CSF protein and xanthochromia may implicate neoplasia. Computed tomography and/or magnetic resonance imaging may be indicated to rule out a space-occupying mass of neoplastic or inflammatory origin.

TREATMENT PLAN: Dogs with presumptive GME should be treated with immunosuppressive doses of corticosteroids for 2-3 weeks. If vision improves the doses should be tapered to the lowest effective dose and maintained. Most such dogs eventually succumb to the generalized form of GME but progress may be slow. Cats and dogs with CNS cryptococcosis have a poor prognosis even with antifungal therapy. Tumors of the CNS causing optic neuritis are fatal; clinical signs may improve temporarily somewhat with corticosteroid therapy.

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Avian ophthalmology Anatomia, fisiologia ed esame clinico dellâ&#x20AC;&#x2122;apparato visivo degli uccelli

Thomas J. Kern D.V.M., Associate Professor, Ophthalmology, Cornell University, Ithaca, New York, Diplomate, American College of Veterinary Ophthalmologists

The ocular disorders of clinical importance in birds parallel those in mammals. Their discovery, identification, and treatment are a greater challenge, however, because of important differences in ocular anatomy and physiology; difficulties of examination due to small eye size; the limitations and risks inherent in necessary restraint; and husbandry practices which affect the availability and accuracy of medical histories. Surprisingly complete ocular examination and effective therapy are feasible in birds with ocular complaints if the clinician clearly appreciates clinically relevant ocular anatomy and physiology and masters the basic skills involved in avian ocular evaluation. Because ocular disorders in birds even more frequently than in mammals reflect systemic diseases, complete general history and physical examination of all birds with eye problems are indispensable.

CLINICAL ANATOMY AND PHYSIOLOGY The avian globe is very large in proportion to body size; the anterior segment is disproportionately smaller than the posterior segment. Avian eyes are typically: (1) relatively spherical or globose, (2) spherical but flattened anteroposteriorly, or (3) tubular. The combined volume of the eyes may exceed that of the cranial cavity. Eye shape is supported by a scleral endoskeleton consisting of ossicles anteriorly and hyaline cartilage posteriorly. The orbit is large, enclosed posteriorly,ventrally, and medially by bone. Much of the temporal and dorsal portions of the globe are unprotected by bone. In some species the equatorial diameter of the globe exceeds that of the diameter of the anterior bony rim. The orbits abut posteriorly, separated by only a thin bony or connective tissue septum. Extraocular muscles (four recti and two obliques) are present but rudimentary. Ocular motility is limited; head movement accomplishes ocular tracking in place of the conjugate ocular movements typical of mammals. The retractor bulbi is absent, replaced by the pyramidalis and quadratus muscles innervated by cranial nerve VI that move the membrana nictitans. A vascular plexus is present in the ventrolateral orbit. The intraorbital optic nerve segment is short. At least portions of cranial nerves I-VI course through the orbit. A subcutaneous infraorbital sinus, part of the cervicocephalic air sac system in some birds (eg, storks, albatrosses, psittacines) lies rostroventral to the globe and lateral to the nasal area. Such sinuses may communicate with

pneumatized sections of skull, extending into the upper beak, mandible, and/or orbit. Upper and lower eyelids and a third eyelid are present. In most birds, the lower eyelid is more mobile than the upper, covering a larger proportion of the cornea during blinking. Meibomian (tarsal) glands are absent. Similar to mammalian cilia, filoplumes are present near the margins of the relatively unfeathered lids. In precocial species eyelids are well-developed and functional, with an open palpebral fissure from hatching. In altricial species, the lids are joined and incompletely developed. Time to eyelid separation varies widely, even up to 3-4 weeks post-hatching. Eyelid separation begins centrally, progresses medially and laterally, and occurs over several days or longer. The membrana nictitans is thin, translucent, well-developed and mobile, under skeletal muscle (and some presumably voluntary) control. Movement is effected by contraction of the pyramidalis muscle surrounding the optic nerve, whose tendon passes through the sling formed by the quadratus muscle, drawing the third eyelid over the eye from dorsonasal to ventrotemporal. The presumptive major source of tears is the Harderian gland at the base of the nictitans lying between extraocular muscles. A lacrimal gland is present in the ventral orbit except in owls and penguins. Conjunctiva is present on the globe and lids; associated lymphoid tissue and the harderian gland make major contributions to the humoral immunologic defense of the ocular surface. Two puncta with canaliculi drain into a nasolacrimal duct. In some species (eg, budgerigar, many others) a nasal (salt) gland lies dorsomedial to the globe in the orbit. The cornea resembles that of mammals. The brown or colored iris contains complex muscular elements which include myoepithelium, striated and smooth muscles. The primary pupillary sphincter seems to be a circumferential striated muscle. Stromal pigments vary, resulting in a wide array of single and mixed colors. Iris coloration in some species is associated with age and/or sex. The usually circular pupil constricts quickly during accommodation and apparently voluntary control. Direct pupillary light reflexes are present but may appear slower than expected, especially in excited birds or ones stressed by restraint. A small degree of dynamic anisocoria may be normal. Because of complete decussation of optic nerve fibers, true consensual pupillary light reflexes are absent. The iridocorneal angle is well-developed. Accommodation, in some species amazingly rapid and extensive, is mediated by lenticular and, at least in some species, corneal mechanisms.

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The vitreous body is transparent. The retina is avascular. The fundus usually appears red to gray, variably streaked by visible choroidal vessels. A tapetum is absent. The oval optic disc is mostly obscured by the overlying pecten, a black, accordioned vascular prominence of variable shape. The pecten probably is involved in nutritional and metabolic support of the posterior segment and may have other functions. Photoreceptor type and function vary; rods, cones, and double cones with oil droplets may be present. Foveae may be absent (most domestic birds, some water birds and ground dwellers), single (owls, swifts, many others) or double (raptors, many passerines). Color vision and near-ultraviolet detection are well-developed.

CLINICAL EXAMINATION Thorough ocular examination may be performed using a transilluminator, low-power magnifying head loupe, and 30D, 40D, or 60D indirect condensing lens or direct ophthalmoscope. Additional diagnostic aids include culturettes, fluorescein dye strips, Schirmer tear tests, microscope slides, sterile scalpel blades, and Schiotz tonometer. Complete ocular evaluation consists of (1) history, (2) functional examination,and (3) morphologic examination. The functional examination assesses vision-directed behavior and eye-related reflexes, including palpebral, direct pupillary, corneal and menace reflexes. Consensual responses are absent but may be inadvertently simulated by stimulation of the opposite retina during elicitation of the direct PLR. Conjugate eye movements are minimal and globe retraction is absent. The morphologic ocular examination assesses the external eye and adnexa, anterior and posterior segments. Magnification greatly facilitates examination even in large birds. Swabs for culture should be collected prior to instillation of any diagnostic eye drops. Schirmer tear test is practical only for large birds; normal values must be estimated from normal fellow eyes or other birds of the species. Fluorescein dye testing and conjunctival and corneal cytology collection are performed as in mammals. Schiotz tonometry is feasible only in large birds; applanation tonometry is feasible even in relatively small ones. Normal values have been reported to be 11-25 mm Hg. Note: topical anesthetic should be used sparingly and to effect only, since potential for systemic toxicity exists! Mydriasis may be effected by general anesthesia, especially ketamine. Much less consistently and safely, partial dilatation may be induced by topical application of muscle paralyzing agents such as tubocurarine or vecuronium bromide. Note: respiratory paralysis has occurred, even in relatively large birds. Examination of the lens, vitreous and fundus is often limited by small pupil size, but can often be accomplished with persistence.

CLINICAL PROBLEMS Remember: Successful treatment is predicated on specific accurate DIAGNOSIS! While birds may be presented for many types of ocular c o m p l a i n t , s eve ral are especially frequent. Pe ri o c u l a r

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swelling results from disorders of the eyelids with or without the conjunctiva, infraorbital sinus, or nasal gland. Eyelid and conjunctival swelling are caused by infection, trauma, neoplasia, and nutritional deficiency. Bacterial pathogens include Staphylococcus, E.coli, Streptococcus, Pasteurella, Actinobacillus, Pseudomonas, and others. Viral pathogens identified include poxvirus, papillomavirus, papovavirus, goose parvovirus, and others. Reported parasites include Plasmodium, Knemidokoptes, and fly larvae. Traumatic in jury may cause ecchymosis, laceration, and/or excoriation. Although rare, several types of eyelid and conjunctival neoplasms have been reported. Hypovitaminosis A may cause conjunctival and eyelid hyperkeratosis and secondary changes. Infraorbital sinusitis may cause swelling ventromedial or medial to the eye. Inflammation of the nasal gland in certain poultry and salt excess in w aterfowl may cause periocular swelling. Conjunctivitis may be caused by infection, trauma, toxicities (eg, photosensitization by plants) and hypovitaminosis A. Pathogenic organisms include poxvirus, cytomegalovirus, paramyxovirus, Newcastle's disease, infectious laryngotracheitis, duck plague, influenza A, infectious bronchitis, quail bronchitis virus, infectious bronchitis, herpesvirus, adenovirus, pneumovirus, Toxo plasma, Streptococcus, Erysipelothrix, E.coli, Bordetella, Chlamydia, Mycoplasma, Hemophilus, Mycobacterium, C l o s t ri d i u m , C a n d i d a , A s p e rgi l l u s , C e rat o s p i ra , Oxyspirura, Philophthalmus, Thelazia, Setaria, and others. Keratitis, ulcerative and nonulcerative, is associated with trauma, infectious agents, burns, and general anesthesia. Idiopathic corneal degenerations and punctate keratitis have been seen. Uveitis is associated with infection, trauma, neoplasia, and immune-mediated disorders. Bacterial, mycotic, viral, and protozoal pathogens must be considered. Septicemia from many bacterial infections (eg, Salmonella, Mycoplas ma), fowl cholera (P. multocida), aspergillosis, candidiasis, Marek's disease, avian encephalomyelitis, toxoplasmosis, and others have been reported. Trauma causes uveitis directly or secondary to ischemia, corneal ulceration,etc. Primary uveal neoplasia is rare in birds except in chickens with Marek's disease. Lens-associated uveitis is caused by cataract resorption. One strain of chickens develops uveitis associated with generalized pigment loss. Cataract may be associated with blunt or perforating trauma, senescence, genetic disorders, malformations, toxicities, nutritional deficiencies, and other ocular disorders, such as retinal degeneration, uveitis, or glaucoma. Autosomal recessive cataract in canaries, cataract with optic nerve hypoplasia in turkeys, and cataract with crooked toes in Brahma chickens have been reported. Developmental malformations including cataract have been seen in raptors. Maternal vitamin E deficiency in turkeys and dinitrophenol fed to chickens have caused cataract. Avian encephalomyelitis causes uveitis and cataract in chickens. Chronic uveitis and retinal degeneration cause secondary cataract independent of their etiologies.

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Retinal disorders include inflammation, degeneration, malformation, and detachment. Choroiditis and/or retinitis have been associated with bacteremia, viremia, toxoplasmosis, and trauma, among other conditions. Developmental retinal degenerations have been well-described in chickens; idiopathic degeneration has been seen in many other species. Retinal dysplasia has been reported in raptors of several species. Detachment may result from choroidal effusion, retinal tears, or vitreal traction associated with trauma, inflammation, or dysplasia.

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formation, neoplasia, and toxicities. Systemic bacterial, viral, fungal, and parasitic infections cause multifocal neurologic deficits, including blindness. Lead and hexachlorophene toxicoses have been reported to cause reversible blindness in budgerigars.

References 1.

Optic neuropathy may be associated with inflammation, trauma, neoplasia, malformation, or chronic glaucoma. Trauma is probably the most important etiology. Pituitary adenomas are common in budgerigars. Optic nerve hypoplasia with cataract occurs in turkeys. The prevalence of chronic glaucoma in birds is not known. Central nervous system causes of blindness with normal pupil size and response include infections, trauma, mal-

Kern TJ. Disorders of the special senses. In:Altman RB, Clubb SL, Dorrestein GM, Quesenberry KE, eds. Avian Medicine and Surgery. WB Saunders,Philadelphia, 1997, pp 635-589. Williams D. Ophthalmolo gy. In: Ritchie BW, Harrison GJ, Harrison LR,eds. Avian Medicine:Principles and Application. Wingers Publishing, Lake Worth, FL,1994, pp 673-694. Kern TJ. Exotic animal ophthalmology. In:Gelatt KN, ed. Veterinary Ophthalmology, 3rd ed. Lippincott Williams and Wilkins, Philadelphia, 1999, pp 1273-1306. Shivaprasad HL. Poultry ophthalmology. In: Gelatt KN , ed. Veterinary Ophthalmology, 3rd ed. Philadelphia, Lippincott Williams and Wilkins, Philadelphia,1999. pp 1177-1209.

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Ocular disorders of wild birds Pi첫 frequenti patologie oculari negli uccelli selvatici, domestici e da voliera

Thomas J. Kern D.V.M., Associate Professor, Ophthalmology, Cornell University, Ithaca, New York, Diplomate, American College of Veterinary Ophthalmologists

INTRODUCTION Wild birds are commonly presented to veterinarians for evaluation and treatment of solitary ocular disorders or those associated with traumatic injury or systemic disease. Ocular examination of wild birds should be performed as in domestic animals; that is, as completely and methodically as anatomic limitations allow. Birds are subject to most of the ocular clinical signs which domestic animals demonstrate. Knowledge of normal ocular and adnexal anatomy is critical to understanding the limitations of ocular examination in birds as well as the pathophysiology of ocular disorders and their clinical management.

CLINICAL DISORDERS TRAUMATIC INJURY Probably the most common explanation for the ocular problems of wild birds presented to veterinarians for treatment is trauma. Sequelae to injuries to the adnexa, anterior and posterior segments is a major factor determining releasibility of many wild birds following therapy. Hyphema usually results from blunt or perforating injury and usually originates from the iris and ciliary body. Extensive hyphema may result in transient or permanent secondary glaucoma, posterior or anterior synechia formation and/or cataract. In most cases, conservative therapy consisting of topical antibiotic-corticosteroid therapy and enforced rest comprise the best approach. Ocular perforations should be repaired surgically if large or patent and systemic antibiotic therapy should be added. Eyelid lacerations should be repaired promptly to preserve and restore eyelid function. Corneal ulceration should be managed with topical antibiotic therapy are appropriate for similar lesions in mammals. (Note that atropine is not prescribed because it has no visible effect on the complex striated musculature of the avian iris and ciliary body). Deep and/or progressive corneal ulceration can be managed in birds with the same surgical procedures as in mammals (e.g., cyanoacrylate adhesive repair, direct corneal suturing, various conjunctival flap procedures). Post-traumatic cataract is a frequent cause for vision loss, especially in raptors. Frequently, other ocular injuries

resulting in intraocular fibrosis are the primary reasons for blindness, while cataract development is a secondary degenerative change. Retinal detachment may follow blunt or perforating trauma Retinal tears may be evident, especially near the pecten or in the peripheral retina. Perforating injury may result in infectious endophthalmitis, lens-induced endophthalmitis if the lens capsule was broached, or both. Prognosis for vision and retention of the eye in these instances is poor. Senile cataract development has been observed in aged captive wild birds, especially raptors. Cataract surgery has been successfully performed in several species. Uveitis most commonly follows trauma but may be associated with septicemia. Retinal lesions are commonly present in wild birds presented for examination, although their discovery is often impaired by ocular opacities or inability to adequately dilate the pupil. Acute retinitis or chorioretinitis appears similar to that in mammals as a fluffy lesion with indistinct borders. Chronic resolved lesions often appear hyper- or hypopigmented, usually with sharply demarcated borders. Large retinal tears may be obvious with the adjoining detached retina floating freely in the vitreous. Large retinal detachments, especially those with disinsertion from the ora ciliaris, may be visible simply on retroillumination behind the lens as a gray or white membrane. Ocular malformations have been described in free-living raptors, including multiple ocular anomalies with cataract, microphthalmos, and retinal dysplasia. Ocular neoplasia in wild birds appears rare.

INFECTIOUS DISEASES Infectious agents of many types affect the eyes of wild birds of various species. Actinobacillosis of the eyelids has been reported in waterfowl. Poxvirus infection involving the eyelids and periocular skin occurs in many susceptible species including quail, waterfowl, raptors, and other passerine birds. Conjunctivitis in passerine birds has been associated with numerous infectious agents including Newcastle's disease, paramyxovirus, poxvirus, cytomegalovirus, Streptococcus species, Erysipelothrix rhusiopathiae, Clostridium botulinum, Mycobacterium avian serotype II, Escherichia coli, Pseudomonas aerugi -

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nosa, Bordetella avium, Chlamydia psittaci, Mycoplasma sp., and Candida albicans. Chlamydial keratoconjunctivitis is a potential problem in wild birds as well as pet-caged birds. Mycoplasma gallisepticum has caused epidemic keratoconjunctivitis in house finches in the United States in recent years. Cryptococcal conjunctivitis has been reported in pheasants and ducks. Blepharoconjunctivitis caused by Acti nobacillus suis was identified in a Canadian goose. Parasites are occasionally found behind the third eyelid; spirurids (Oxyspirura sp.) afflict a variety of wild birds and the trematode, Philophthalmus gralli, has been noted in many species including waterfowl.

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References 1. 2. 3.

Kern TJ. Disorders of the special senses. In: Altman RB, et al., eds. Avian Medicine and Surgery, 2nd ed. WB Saunders,Philadelphia,1994. Murphy CJ. Raptor ophthalmology. Comp Cont Ed 9(3):241-259, 1987. Millichamp NJ. Exotic animal ophthalmology. In: Gelatt JN, ed. Veterinary Ophthalmology, 2nd ed. Lea and Febiger, Philadelphia, 1991, pp 680-705. Kern TJ. Exotic animal ophthalmology. In:Gelatt KN, ed. Veterinary Ophthalmology, 3rd ed. Lippincott Williams and Wilkins, Philadelphia, 1999,pp 1273-1306. Shivaprasad HL. Poultry ophthalmology. In: Gelatt KN , ed. Veterinary Ophthalmology, 3rd ed. Philadelphia, Lippincott Williams and Wilkins,Philadelphia, 1999. pp 1177-1209.

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Ocular disorders of reptiles and amphibians Oftalmologia nei rettili e negli anfibi

Thomas J. Kern D.V.M., Associate Professor, Ophthalmology, Cornell University, Ithaca, New York, Diplomate, American College of Veterinary Ophthalmologists

Reptiles and amphibians commonly suffer ocular complaints that require diagnosis and treatment. The facility and completeness of ocular examination in these species are limited by the relative size of the eye and inability to induce mydriasis. Husbandry practices often preclude the careful observation necessary for a useful history. Restraint may be both difficult and hazardous for veterinarian and patient. Ocular examination is greatly facilitated by use of magnification (eg, a low-power head loupe, reading magnifier, a 28D-40D indirect condensing lens). Pharmacologic mydriasis is not consistently possible; under general anesthesia pupils may dilate. Normal pupillary movements are generally rather sluggish so examination of the lens, vitreous, and fundus may be possible with patience either by direct ophthalmoscopy or indirect ophthalmoscopy using a 28D to 60D condensing lens, especially in animals of modest or large size. Fluorescein dye tests and conjunctival cytology are feasible in even small specimens. Anterior chamber paracentesis and Schiotz tonometry are possible in larger animals. Even more frequently than in domestic mammals, ocular disorders of r eptiles and amphibians prove to be manifestations of systemic disease and/or poor husbandr y. Thus, clinicians should perform complete physical examinations on all animals presented for (only) ocular problems and should assess husbandry and management practices by history and firsthand inspection, where possible.

REPTILES Important anatomic features of chelonians, lizards, crocodilians, and tuataras include: (1) well-developed eyelids, the lower more mobile and sometimes variably transparent, (2) third eyelid usually present, (3) Harderian and lacrimal glands present, (4) nasolacrimal puncta and duct absent in chelonians, (5) spherical globe, (6) recti poorly developed (except in lizards); retractor bulbi well-developed, (7) limited rotational eye movements (except chameleons), (8) scleral cartilage and/or ossicles (pattern varies), (9) accommodation achieved by lens deformation, (10) widely variable pupil shape, iris coloration and vascularity, (11) striated iris and ciliary muscles, (12) avascular retina, (13) conus papillaris overlying optic disc (lizards), (14) retinal pigment epithelial tapetum (crocodilians), (15) rods and cones present in most species, (16) fovea present in lizards, (17) complete decussation of optic nerve fibers.

The eyes of snakes are generally similar to the other four orders with these exceptions: (1) lids are fused to form transparent vascularized spectacle; surface is replaced by shedding (a few lizards have spectacles), (2) third eyelid, lacrimal gland, and scleral cartilage and ossicles absent, (3) Harderian gland secretions fill a subspectacular space between cornea and spectacle and are drained by a nasolacrimal duct to the roof of mouth near vomeronasal organ, (4) rudimentary retractor muscles, (5) scleral cartilage and ossicles absent, (6) accommodation by indirect lens deformation mediated by ciliary muscle pressure on vitreous, (7) mesodermal conus papillaris in some species. Common ocular disorders include external and periocular infections; corneal ulceration, degeneration, and opacities; uveitis; disorders involving the spectacle; nutritional problems; cataract; neoplasia; and malformations. Poxvirus causes blepharitis in young caiman, with spontaneous regression. Herpesvirus blepharitis afflicts young marine turtles, often with secondary bacterial infection. Fungal infection of the spectacle and periocular scales occasionally develops; endophthalmitis may result from perforation or septicemia. Bacterial blepharitis and orbital cellulitis occur in association with generalized infection, especially due to gram-negative bacteria like Pseudomonas and E. coli; poor husbandry and hygiene may be predisposing factors. Parasites may affect the adnexa. Ophionyssus mites often attach to the peripheral margin of snakes' spectacles. In green sea turtles eggs of the trematode Laraedius laraedii are disseminated intravascularly to the conjunctiva and eyelids, inducing fibromas, fibropapillomas, and fibrosarcomas. Aeromonas infection has caused conjunctivitis outbreaks in captive collections. Corneal ulceration results from trauma or extension of periocular or subspectacular space infections. Idiopathic lipid keratopathy has been observed. Corneal edema may result from inappropriate exposure of salt-water species to fresh water. Uveitis with hypopyon often has a systemic infection as its cause; Klebsiella, Aeromonas, Pseudomonas, and other bacteria have been incriminated. Treatment with systemic antibiotics is indicated. Disorders of the spectacle include retention following ecdysis and distension of the subspectacular space. Causes of retention of the spectacle are thought to involve low humidity, mite infestation,dehydration, debilitation, and previous injuries. Treatment is aimed at increasing humidity, soaking, ectoparasite control,lubrication with olive oil or petrolatum, topical acetylcysteine, followed by careful manual removal if necessary. Distension is caused by accumula-

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tion of inflammatory/infectious exudates and/or harderian gland secretions, frequently secondary to or causing nasolacrimal duct obstruction. Causes include traumatic perforation of the spectacle, ascending infection through the nasolacrimal duct from infectious stomatitis, and systemic infections. Treatment is potentially hazardous. Partial wedge excision of the spectacle followed by antibiotic flush has been performed with variable success. Extreme care should be taken to preserve the cornea! Surgical conjunctivoralostomy has been reported for nasolacrimal duct obstruction. Necrotic stomatitis should be treated if present. Hypovitaminosis A is common in chelonians, especially aquatic species, in which it causes squamous metaplasia of harderian and lacrimal glands and ducts. Glandular enlargement causes severe blepharoconjunctivitis and secondary bacterial infection. Parenteral vitamin A administration and improved husbandry should be implemented. Cataracts occur occasionally, especially in snakes and tortoises, as congenital or acquired opacities. Advanced age, trauma, previous or active uveitis, environmental and nutritional causes are likely. Lesions of the posterior segment have been reported rarely. Malformations occur occasionally, including cyclopia, microphthalmos, anophthalmos, and exophthalmos, with or without other somatic anomalies. Genetic, nutritional, and teratogenic factors have been suspected. Abnormal environmental temperatures maintained during gestation or incubation have been shown to promote some malformations.

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gland present, (6) nasolacrimal duct absent, (7) spherical globe with posterior scleral cartilage, (8) retractor bulbi the best developed extraocular muscle, (9) accommodation mediated by lens protraction and retraction, (10) variable pupil shape and iris color, myoepithelial dilator and sphincter muscles, (11) avascular retina with vitreal membrana vasculosa retinae, (12) retina contains rods and cones. Spontaneous ocular disorders have been infrequently reported in amphibians. Traumatic keratoconjunctivitis seems relatively common; secondary bacterial infection is a potential complication. Bacterial panophthalmitis was reported in a colony of fire-bellied toads (Bombina orientalis) associated with generalized visceral and neurologic disease due to Aeromonas hydrophila and Citrobacter freundii. Septicemic uveitis is probably more common than realized, associated with stress, overcrowding, and poor hygiene. Lipid keratopathy occurs fairly commonly in anurans. Although originally reported in Cuban tree frogs (Osteopilus septentri onalis), it has also been documented in species of leptodactylid, hylid, and ranid frogs as a corneal and/or hepatic lesion sometimes associated with generalized xanthomatosis. White's tree frogs (Litoria caerulea) seem to be commonly afflicted. Females may be most commonly affected. Dietary and hormonal and other factors as well may be involved.

References 1.

AMPHIBIANS Anatomic features of amphibian eyes include: (1) rudimentary development in urodeles (salamanders, newts), (2) better development in anurans (fr ogs, toads), (3) lids poorly developed, contain glands along superior margin, (4) false third eyelid formed by a conjunctival fold, (5) harderian

Millichamp NJ, Jacobson ER. Ophthalmic diseases of reptiles. In: Kirk RW, ed. Current Veterinary Therapy IX - Small Animal Practice. WB Saunders, Philadelphia, 1986, pp 621-624. Millichamp NJ. Exotic animal ophthalmology. In:Gelatt KN, ed: Veterinary Ophthalmology, 2nd ed. Lea and Febiger, Philadelphia, 1991,pp 685-689. Kern TJ. Exotic animal ophthalmology. In:Gelatt KN, ed. Veterinary Ophthalmology, 3rd ed. Lippincott Williams and Wilkins, Baltimore, 1999,pp 1273-1306. Williams DL. Ophthalmolo gy. In: Mader DR. Reptile Medicine and Surgery. WB Saunders, Philadelphia,1996, pp 175-184.

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Più frequenti alterazioni dell’emostasi George Lubas Prof. Associato di Ematologia ed Immunologia Clinica Veterinaria Dipl. Eur. College Veterinary Internal Medicine [Internal Medicine] Dipart. di Clinica Veterinaria - Università di Pisa - Viale Piagge, 2 - 56100 Pisa, Italia

GENERALITÀ Il sistema emostatico ha una fine equilibrio per mantenere l'omeostasi che consente la pervietà dei vasi ematici, riduce le perdite ematiche dall'endotelio vascolare danneggiato e facilita la riparazione tessutale. Il meccanismo emostatico coinvolge complesse interazioni tra elementi cellulari, proteine, fosfolipidi, mediatori chimici e catalizzatori. Consiste in una sequenza di variazioni fisiche e biochimiche scatenate da un insulto ai tessuti e/o ai vasi ematici, che com porta la trasformazione finale del sangue in un coagulo solido e la riparazione dell'endotelio vascolare leso (vedi Fig. 1). L'emostasi è un processo modulato, in cui intervengono fattori sia favorenti che inibenti e la susseguente fibrinolisi (dissoluzione coagulo); tutti devono essere in equilibrio dinamico altrimenti vi è un anormale sanguinamento od una eccessiva formazione di trombi. I tre elementi fondamentali dell'emostasi sono il vaso ematico, le piastrine (Plt) e i fattori plasmatici della coagulazione. Gli elementi che intervengono in ciascuna fase sinteticamente sono: Fase Vascolare - vasocostrizione, - pressione del sangue fuoriuscito nei tessuti circostanti. Fase Piastrinica (emostasi primaria): - accumulo immediato delle Plt al punto dell'insulto sul vaso ematico (sufficiente a esporre il subendotelio al flusso ematico),

Figura 1 - Visione complessiva del processo di emostasi.

- adesione delle Plt al collagene subendoteliale tramite l'esposizione dei recettori per il FvW ed il fibrinogeno, - variazione della forma delle Plt (da discoidale a sfera), - interazione delle Plt con le strutture subendoteliali, con il rilascio dei propri costituenti interni (ADP, serotonina, TxA2 e ATP) e di un fosfolipide di membrana (PF3), - aggregazione delle Plt mediata dal rilascio di ADP e TxA2 dalla massa delle Plt, - formazione del tappo emostatico primario (la massa delle Plt ripara il vaso ematico con un tappo labile per l'arresto del sanguinamento). Fase dei Fattori Plasmatici Coagulazione (emostasi secondaria, vedi Fig. 2): - sistema estrinseco, (di natura tissutale od extra vascolare), molto attivo e veloce nel cane e nel gatto, con attivazione sequenziale a cascata dei fattori Tromboplastina Tessutale (FIII) o Fattore Tissutale (TF) liberato dalle cellule endoteliali lese e della Proconvertina (FVII). Termina con l'accesso ai fattori comuni della coagulazione (vedi la via comune). - sistema intrinseco, (di natura intravascolare) con l'attivazione sequenziale a cascata dei fattori Hageman (FXII), Antecedente Tromboplastina Plasmatica (FXI), Christ-

Figura 2 - Cascata coagulativa, fase plasmatica.

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Figura 4 - Modulazione dell'emostasi tramite la fibrinolisi. Figura 3 - Modulazione dell'emostasi (mediante inibitori).

Diagnostica dell'emostasi: valutazione anamnestica e clinica mas (FIX) ed Antiemofilico (FVIII) e delle Plt, con il fosfolipide di membrana (PF3). Anche questo termina con l'accesso ai fattori comuni della coagulazione. - via comune con l'attivazione sequenziale a cascata dei fattori Stuart (FX), Proaccellerina (FV), Protrombina (FII), Fibrinogeno (FI) e Stabilizzante Fibrina (FXIII). I principali elementi inibitori dell'emostasi sono costituiti da (vedi Fig. 3): a) Endotelio, che ha meccanismi inibitori attivi tra cui le cellule endoteliali integre, la sintesi di prostacicline (PGI2), gli attivatori del plasminogeno, la trombomodulina, la captazione e la degradazione di ADP e l'inattivazione della trombina. Invece i meccanismi inibitori passivi sono i proteoglicani endoteliali equivalenti al solfato di eparina e la repulsione da carica elettrica negativa. b) Piastrine, tramite le PGI2 endoteliali che aumentano l'AMP ciclico (derivante dalle Plt) e l'ossido nitrico i quali inibiscono l'aggregazione delle Plt e il rilascio di ADP. c) Trombina, infatti l'adsorbimento di trombina è mediata dalla fibrina, vi è inibizione da parte degli FDP e l'attivazione della proteina C è regolata dal complesso trombina-trombomodulina. d) ATIII, unitamente ad eparina, inattiva la trombina ed inibisce le serine proteasi, tra cui FXa, FIXa, FXIa, FXIIa. e) Proteina C (Ca) inibisce i complessi che si formano tra "FVIII:C + Ca + PF3" e tra "FV + Ca + PF3" f) Proteina S, sinergizza con la proteina C. La fibrinolisi è la fase dell'emostasi che contribuisce alla dissoluzione del coagulo di fibrina, avvalendosi della Plasmina (vedi Fig. 4). Le caratteristiche della Plasmina sono di essere attivata da FXIIa, callicreina, Attivatore Plasminogeno tessutale (tPA) e proteina Ca, mentre è inattivata da α-2-antiplasmina e α-2-macroglobulina, ed induce la biodegradazione di FV, FVIII:C e fibrinogeno.

Nell'anamnesi è importante valutare i seguenti f attori: a) tendenza al prolungato sanguinamento patologico per traumi lievi ed a seguito di piccoli inter venti chirurgici; b) età del paziente (il giovane animale è sospetto di malattie ereditarie, l'adulto di malattie acquisite) c) esposizione a farmaci, agenti chimici, etc. (es. Warfarin, rodenticida; Aspirina, interferenza con Plt; Estrogeni, aplasia midollare) La visita clinica deve invece considerare: a) tipo di sanguinamento (vedi Fig. 5): (1) porpora emorragica su pelle e mucose (petecchie, soffusioni, vibici ed ecchimosi), (2) sanguinamento nei tessuti (muscoli ed occhio) e/o nelle cavità corporee (addome, torace, spazio pericardico, articolazioni, canale spinale), (3) sanguinamento massivo da un singolo sito (chirurgico o traumatico), (4) sanguinamento grave ed improvviso da diversi siti (es. dopo un prolungato intervento chirurgico), (5) comparsa di emartri, ematomi o grandi ecchimosi nei punti di trauma, (6) comparsa di ematuria, melena, ematemesi, epistassi ed emottisi, b) concomitanza di altre malattie (che inducono disordini secondari dell'emostasi, tra cui malattie immunologiche, neoplasie ematiche, epatopatie, splenomegalia, uremia ed esposizione ai raggi X).

Diagnostica dell'emostasi: prelievo del campione Vi sono delle norme generali e delle precauzioni da rispettare nel prelievo e nella conservazione dei campioni di sangue da impiegare per la valutazione dell'emostasi. Di seguito sono elencate le raccomandazioni standard, ma queste possono avere delle minime differenze da un laboratorio all'altro, per cui si suggerisce di consultarli preventivamente :

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Figura 5 - Differenze fra l'emostasi normale e quella che av viene in corso di trombocitopenia o di alterazione dei fatto ri della coagulazione.

1) i campioni devono essere prelevati con siringhe di plastica monouso, ottemperando un'accurata puntura venosa, preferibilmente dalla vena giugulare, evitando una suzione o un'aspirazione violenta che può determinare emolisi o schiuma; 2) l'anticoagulante di scelta per l'esecuzione delle prove della fase plasmatica e della fibrinolisi è il citrato di so dio al 3,8%, in rapporto di 1:9 con il sangue, per ottenere il plasma citrato; l'EDTA (1-2 mg di K3EDTA per mL di sangue) è riservato al solo conteggio delle piastrine; 3) i campioni di sangue appena prelevati devono essere trasferiti dalla siringa, togliendo l'ago, in provette di plastica munite di tappo, con l'appropriato anticoagulante e miscelati accuratamente, onde evitare l'attivazione del fattore XII e l'ammassamento piastrinico; si deve aggiungere la quantità di sangue esattamente proporzionale alla quantità di anticoagulante; 4) un rapporto alterato sangue - anticoagulante (in particolare il citrato di sodio) potrebbe falsare i risultati di laboratorio ottenuti, rendendoli inesatti; infatti esso influenza la disponibilità di calcio nel sistema di rilevamento dei tempi di coagulazione; il problema può insorgere nei soggetti policitemici, quando il rapporto standard 1:9 (0,225 ml. di citrato di Na al 3,8% per 2,275 ml di sangue) non è più rispettato a causa della riduzione del volume plasmatico a favore della massa cellulare. Ciò comporta che il plasma abbia un eccesso di citrato che determina un artificiale prolungamento delle prove di coagulazione. Questo si verifica per un abbassamento dei li-

velli di calcio nel sistema di rilevamento tramite fibrinometro, che di conseguenza ritardano la formazione del coagulo di fibrina; invece nei soggetti che sono anemici vi è un eccesso di plasma rispetto alla massa cellulare e si può assistere ad una riduzione del rapporto proporzionale di citrato che può mascherare la presenza di coagulopatie lievi,poiché vi è una riduzione artificiale dei tempi di coagulazione; è possibile applicare una formula per correggere la quantità di citrato necessaria in rapporto alle variazioni dell'ematocrito, che è la seguente: quantità di citrato di Na al 3,8% (da aggiungere al sangue) = 0,00185 x (volume di sangue da prelevare in ml) x (100 - valore ematocrito) ad es. 4 ml di sangue prelevati da un cane con un ematocrito del 65% (policitemico) richiederà 0,26 ml di citrato di sodio al 3,8%,mentre la stessa quantità di sangue cioé 4 ml, prelevata ad un cane con un ematocrito del 20% (anemico) richiederà 0,59 ml di citrato di sodio al 3,8%; i campioni di plasma citrato devono essere preparati, se possibile, da sangue fresco appena prelevato, mediante centrifugazione a circa 3.000 rpm ed analizzati il più presto possibile o conservati a -20°C; è consentito dilazionare al massimo di due ore la separazione del plasma dal campione di sangue, ottemperando nel frattempo comunque una conservazione del medesimo a +4/+10°C; il campione di sangue va conservato in provette con tappo; poiché le analisi sono effettuate presso laboratori distanti dal luogo di prelievo, i campioni di plasma citrato devono essere spediti refrigerati (talvolta congelati a seconda del test richiesto) per cui risulta opportuno l'uso di almeno due panetti ghiacciati posti ai lati del campione per arrivare al centro diagnostico come tali; ad ogni modo è bene prendere contatto con il labor atorio per la corretta normativa di spedizione; i campioni prelevati in K3EDTA debbono essere conservati in frigo a +4°C/+10°C in provetta chiusa con tappo ermetico; risulta opportuno l'esecuzione di strisci di san gue periferico, se possibile, senza anticoagulante, ovvero da sangue con anticoagulante, ma entro due ore dal momento del prelievo; le determinazioni dei vari test su plasma citrato debbono essere eseguite sempre in doppio e possibilmente impiegando come controllo della tecnica e dello strumento un pool di campioni di plasma citrato di soggetti sani con valori di riferimento nell'intervallo della normalità; si suggerisce di fare le analisi presso laboratori referenziati per la medicina veterinaria.

Diagnostica dell'emostasi: valutazione laboratoristica La scelta degli esami per la valutazione dell'emostasi dipendono della fase che si desidera esplorare e cioè sia quella piastrinica, vascolo-piastrinica o plasmatica sia nella parte finale della formazione del coagulo o nella fibrinolisi (vedi Tab. 1). Oggigiorno è comunemente accettato di effettuare un profilo emostatico che comprende almeno uno o più test per ciascuna fase.

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Tabella 1 - Impiego degli esami di laboratorio nelle più frequenti patologie dell'emostasi. Patologie

EMO

n°PLT

aPTT

Fibr

FDP

Trombocitopenia da consumo (es. ITP)

N/A

Trombocitopenia da ipo-produzione (es. Ehrlichiosi)

Difetto ereditario via intrinseca (es. emofilia A)

Difetto ereditario via estrinseca (es. carenza FVII)

Difetto ereditario via comune (es. carenza FX)

Malattia di von Willebrand (carenza FvW:Ag)

N/A

Difetti multipli dei fattori (es. intossicaz. antagonisti vit. K)

N/D

Coagulazione Intravasale Disseminata (CID)

N/D

legenda: ITP= trombocitopenia immuno mediata; *= inizialmente normale, ma poi può riprendere il sanguinamento; TE= tempo di emorragia; EMO = esame midollo osseo, valutato per la presenza di megacariociti; n° PLT = numero delle piastrine; PT= tempo di protrombina; aPTT= tempo di tromboplastina parziale attivato; Fibr= Fibrinogeno; FDP= prodotti di degradazione della fibrina/fibrinogeno; A= aumentato; D= diminuito; N= normale

ESAMI DELLA FASE PIASTRINICA Conteggio delle piastrine La conta di questi elementi è abitualmente effettuata oggigiorno impiegando contaglobuli appositamente predisposti. Si ricorda che questa determinazione è difficile nel gatto per le dimensioni simili tra Plt e RBC e per la facile aggregazione delle Plt. Pertanto è sempre consigliabile effettuare una stima della quantità delle piastrine sullo striscio ematico colorato. Infatti è possibile ottenere una stima media delle Plt contando questi elementi rilevati in un campo microscopico osservato a 1.000 ingrandimenti (valori normali 10-20, diminuiti inferiori a 10, aumentati oltre 20) e quindi moltiplicando per 10.000 (numero Plt su mcL). Si deve considerare la trombocitopenia quando il numero delle Plt scende al di sotto delle 100.000 su mcL. Il disturbo dell'emostasi relativo alla trombocitopenia si svela sempre quando il valore scende al di sotto di 20.000 su mcL e talora al valore di 10.000 su mcL. A volte i sintomi legati al disordine piastrinico possono rendersi evidenti quando queste cellule scendono a valori di 70.000 - 40.000 su mcL per la presenza di una concomitante trombocitopatia.

Morfologia delle piastrine Questa valutazione è possibile con l'esame dello striscio ematico che evidenzia sia la presenza di aggregati piastrinici nella coda del vetrino (falsa trombocitopenia) che il riscontro di piastrine con ampio volume cellulare (deviazione a sinistra),segnale di attiva trombopoiesi ovvero di anisocitosi piastrinica.

in g rado di contare le piastrine e di fornire la distribuzione dei volumi piastrinici,può essere utilmente impiegato per discriminare una rigenerazione o meno di questo compartimento cellulare. Infatti l'MPV risulta elevato nelle trombocitopenie immunomediate, mentre risulta basso nelle trombocitopenie da diminuita produzione.

Esame del midollo osseo rosso Questo esame valuta sia la presenza di megacariociti che la loro quantità negli elementi particolati; nel contempo si può esprimere anche una valutazione del loro aspetto morfologico.

Tempo Retrazione Coagulo (TRC) È un test molto semplice che consiste nel prelievo di sangue (senza anticoagulante, circa 2 mL) lasciato coagulare a temperatura ambiente, ovvero a 37°C, in provette di vetro; si compara la retrazione del coagulo del campione in esame con quello di un paziente sano dopo 2-4 ore e dopo 24 ore. Un coagulo normale si retrae nel tempo di 2-4 ore e dopo 24 ore sarà compatto. Questo esame valuta la trombocitopatia e la trombocitopenia, ma anche la presenza di fibrinogeno e di altri fattori legati alla coagulazione. Infine questo test risente anche dell'aumento dei fattori legati alla fibrinolisi, difatti in queste particolari condizioni il coagulo può dissolversi dopo 24 ore.

Adesività piastrinica Valutazione del MPV La valutazione di questo parametro (Mean Platelet Volume = volume piastrinico medio), misurato dai contaglobuli

Questo esame consiste nel far defluire sangue con anticoagulante attraverso un tubicino di plastica contenente sfere di vetro, avendo cura di valutare il numero delle Plt prima e dopo tale passaggio, impiegando sia il campione del pa-

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ziente che un campione di controllo e comparandoli. Valuta la trombocitopatia.

Aggregazione piastrinica Valuta la funzione piastrinica tramite l'impiego di un aggregometro foto ottico e di una stampante che registri la progressione dell'aggregazione delle Plt. La tecnica prevede che si aggiunga a Plasma Ricco di Piastrine (PRP) diversi agenti aggreganti (induttori) quali :ADP, adrenalina serotonina, e trombina (agenti aggreganti primari) ovvero collagene, acido arachidonico e ristocetina (agenti aggreganti secondari) e quindi si valuta l'aggregazione delle Plt. I tracciati che si ottengono sono in genere di 4 tipi e cioé : monofasico (per concentrazioni elevate di induttore), bifasico (con una concentrazione soglia dell'induttore), aggregazione primaria (l'induttore non innesca il 'releas’ Plt perché è in ridotte quantità ovvero per una ridotta reattività delle Plt) ed aggregazione primaria con disaggregazione. Gli agenti aggreganti primari danno luogo direttamente ad aggregazione con meccanismi indipendenti dalla loro capacità di causare la liberazione di ADP endogeno, da parte delle Plt. Gli agenti aggreganti secondari inducono la reazione di rilascio che porta ad aggregazione più intensa ed irreversibile (curva bifasica). Di recente è stato validata una procedura strumentale per valutare l'emostasi primaria ed in particolare quella piastrinica e vascolare. Si tratta dello strumento PFA-100™ (Dade Behring) che tramite l'impiego di particolari cartucce con un aggregante artificiale quale l'ADP è sensibile nel rilevare cani con difetti dell'emostasi primaria (valori normali da 55 a 86 secondi).

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Una volta eseguito il taglio si cronometra il tempo dal momento in cui appare la prima goccia di sangue e si arresta quando non compare più sangue, continuando a rimuovere la goccia ogni 20/30 secondi, avendo cura di non toccare i bordi della ferita. I valori normali sono di 1-5 minuti (pelle, unghia) e di 2-4 minuti (mucosa labiale), ma sono difficili da standardizzare. Un allungamento indica lesioni vascolari, difetti di funzionalità piastrinica, fragilità capillare e trombocitopenia.

ESAMI DELLA FASE PLASMATICA Si distinguono alcuni gruppi di esami in base alle attrez zature necessarie (uno dei limiti più importanti in ambito veterinario) e cioé test eseguibili senza fibrinometro, test semplici o particolari, eseguibili con fibrinometro ed infine test specialistici fattibili in laboratori attrezzati con fibrinometro, spettrofotometro o lettori di piastre ELISA.

ESAMI ESEGUIBILI SENZA FIBRINOMETRO Tempo di Coagulazione (TC) È un test molto semplice che consiste nel prelievo di sangue (senza anticoagulante, circa 2 mL) che si lascia coagulare a temperatura ambiente oppure a 37°C in tre provette di vetro che vengono controllate ad intervalli di 1-2 minuti, fino alla coagulazione dei campioni e misurandone il tempo intercorso. I valori normali variano da 3 a 12 minuti e raddoppiano qualora si impieghino provette di plastica o di vetro siliconato. Identifica generiche deficienze dei fattori del sistema intrinseco (vedi anche TRC).

ESAMI DELLA FASE VASCULO-PIASTRINICA Tempo di emorragia (TE) o di sanguinamento (TS) È un test semplice da effettuare sull'animale, che fornisce indicazioni su queste due fasi dell'emostasi. è definito come il tempo necessario per arrestare il sanguinamento da una piccola incisione standard su una definita area del corpo. Questa ferita standard può essere procurata con uno strumento chiamato Simplate® versione II oppure P, sterile, a perdere, che provoca due incisioni uniformi di 5 mm di lunghezza rispettivamente di 1 mm oppure di 0,5 mm di profondità. La lama caricata a molla è tenuta in un involucro di plastica pronta all'uso e quando viene fatta scattare provoca le due ferite. In alternativa può essere impiegato l'ago di Francke oppure una lama di bisturi a punta che viene preparata in modo tale da far sporgere solo pochi millimetri della punta tramite l'applicazione di un cerotto che fa da fermo di battuta. Il taglio può essere eseguito nelle seguenti regioni del corpo: a) sulla faccia interna padiglione auricolare (CBT = Cuticle Bleeding Time), b) sulla mucosa labiale (BMBT = Buccal Mucosal Bleeding Time), c) sull'unghia, tagliandola leggermente corta.

Tempo di Coagulazione Attivato (TCA o ACT) Questo test prevede di cronometrare da quando il sangue prelevato (2 mL) viene introdotto in una provetta di tipo vacutainer contenente terra di silicio (diatomite che funge da agente di attivazione da contatto) fino alla completa coagulazione; è necessario avere un apposito blocco riscaldatore a 38°C che serve a preriscaldare la provetta vuota prima del prelievo che quella quindi con il campione di sangue sotto esame; la provetta con il sangue del paziente infatti viene posta nel blocco riscaldante per 1 minuto circa e poi ispezionata ogni 5-10 secondi per accertarsi dell'avvenuta coagulazione. I valori normali sono: 70-80 secondi nel cane, inferiore a 65 secondi nel gatto. Identifica difetti della via intriseca o della via comune, ma è meno sensibile dell'aPTT nel rilevare deficienze dei fattori XII, XI, IX, X,VIII, V, II, I e può essere alterato dalla diminuzione delle Plt.

Prodotti di degradazione della fibrina (fibrinogeno) (FDP) Si usano antisieri umani monoclonali diretti contro i frammenti D e E (buona cross-reattività con altre specie) che so-

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ESAMI SEMPLICI, ESEGUIBILI CON FIBRINOMETRO Tempo di Protrombina (PT - OSPT)

Figura 6 - Azione della plasmina sul fibrinogeno, fibrina so lubile e fibrina insolubile.

no adsorbiti su particelle di lattice; la loro concentrazione è regolata in modo che l'agglutinazione macroscopica si verifichi quando il livello di FDP supera i 2 mcg/mL. Eseguendo il test con differenti diluizioni del plasma del paziente si può ottenere una concentrazione approssimativa degli FDP. Il test si può eseguire su plasma citrato o sul siero impiegando metodi appositi. Nell'impiego del siero il campione di sangue deve essere prelevato con provette addizionate di Trombina (che attiva la coagulazione e forma il fibrinogeno e quindi la fibrina). Nel cane e nel gatto i valori normali sono inferiori a 10 mcg/mL nel siero e inferiori a 2,5 mcg/mL nel plasma. Questo esame segnala una aumentata fibrinolisi, ma anche una fibrinogenolisi (vedi Fig. 6). Infatti la plasmina agisce sulla fibrina portando alla formazione di complessi ad alto peso molecolare (oligomeri X e Y), da cui per ulteriore degradazione si arriva alla formazione del frammento D-dimero, generalmente complessato con il frammento E tramite ponti ad idrogeno. Questo frammento è il prodotto terminale dell'azione della plasmina sulla fibrina insolubile; è costituito da due frammenti D che ad opera del fattore XIIIa ed in presenza di ioni calcio, vengono legati e sono resistenti all'azione della plasmina. Il D-dimero rappresenta un marker di fibrinolisi secondaria alla fibrinoformazione. La plasmina può svolgere la sua azione catalitica anche a livello del fibrinogeno e sui monomeri della fibrina non ancora trasformati in fibrina polimera insolubile. Infatti agisce formando un frammento X che ha una spiccata azione anticoagulante per la capacità di formare complessi solubili con i monomeri della fibrina impedendone la loro polimerizzazione. Proseguendo l'azione della plasmina sul frammento X, questa la cliva ulteriormente formando il frammento D precoce ed il frammento Y, che non è più coagulabile, ma che mantiene le proprietà anticoagulanti ed insieme al frammento X forma la ATVI (Antitrombina VI). Il frammento D precoce si trasforma in D tardivo, mentre il frammento Y si trasforma in frammento E ed in un ulteriore frammento D tardivo.

Questo esame (PT = Prothrombin Time; OSPT = One Stage Prothrombin Time) consiste nella misurazione del tempo necessario affinché avvenga la coagulazione di plasma citrato addizionando ioni calcio (cloruro di calcio) e un eccesso di tromboplastina tissutale, aggirando le richieste per l'emocoagulazione derivanti dai fattori V, V I I I : C ,I X e XII e del PF3. La tromboplastina tissutale reagisce con i fattori V, VII e X per formare protrombinasi che converte la protrombina in trombina e quest'ultima a sua volta agisce sul fibrinogeno per formare la fibrina. Il tempo richiesto per tale coagulazione è direttamente proporzionale alla velocità di conversione della protrombina in trombina e dipende dai livelli di protrombinemia. I valori normali sono (espressi in secondi): cane 7-10, gatto 9-13. Questo test identifica alterazioni nella concentrazioni dei fattori della via estrinseca e della via comune (fattori VII, X, V, II e I), come pure la presenza di inibitori dei fattori sopra citati che di anticoagulanti circolanti. Se viene eseguito in parallelo all'aPTT, che risulta normale, indica in genere la deficienza del solo fattore VII.

Tempo di Tromboplastina Parziale (aPTT) Questo esame (PTT = Partial Thromboplastin Time; aPTT = activated Partial Thromboplastin Time) consiste nella misura del tempo necessario affinché avvenga la coagulazione di plasma citrato addizionando ioni calcio (cloruro di calcio), caolino (fattore di attivazione per contatto) e cefalina (in sostituzione del PF3). Al posto del caolino possono essere impiegati la celite o la silice micronizzata, che sono in grado di rilevare la carenza del fattore di Fletcher, ovvero l'acido ellagico che invece non è in grado di stabilire questa carenza, ma che tuttavia è sensibile a carenze quantitative o qualitative del PF3. In sostanza la coagulazione in questo test si basa sul fatto che la tromboplastina plasmatica si formi in presenza di PF3 e dei seguenti fattori : FII, FV, FVIII:C, FIX, FX, FXI e FXII. I valori normali sono (espressi in secondi) : cane 11-19, gatto 14-20. Questo test identifica le alterazioni dei fattori della via intrinseca e della via comune (fattori XII, XI, IX, VIII:C, X, V, II e I), come pure la presenza di inibitori dei fattori sopra citati che di anticoagulanti come ad es. l'eparina. Se viene eseguito insieme al PT, che risulta normale, indica la deficienza solo dei fattori VIII, IX, XI e XII. Riesce anche ad identificare la deficienza del fattore di Flecther (precallicreina), infatti se l'aPTT si normalizza in seguito all'allungamento del tempo di incubazione con l'attivatore dell'aPTT, significa che era deficitario questo fattore.

Determinazione del Fibrinogeno Questo esame consiste nella misura del tempo necessario affinché avvenga la coagulazione di plasma citrato diluito

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addizionando un eccesso di trombina, che è espressione esclusiva della quantità di fibrinogeno presente in tale plasma. La diluizione del plasma minimizza l'interferenza di eventuali anticoagulanti presenti, come gli FDP o l'eparina. I valori dei tempi di coagulazione sono convertiti in valori di fibrinogeno, espressi in mg/dL, tramite una opportuna tabella (in genere allegata alla metodica). I valori normali sono : cane e gatto 200-400 mg/dL. Questo test identifica solo la ipofibrinogenemia.

ESAMI PARTICOLARI ESEGUIBILI CON FIBRINOMETRO Trombotest (PIVKA test) Questo esame consiste nella misura del tempo necessario affinché avvenga la coagulazione di plasma citrato (ma anche sangue intero citrato) mediante aggiunta di cefalina, tromboplastina, plasma bovino adsorbito e cloruro di calcio. I valori normali sono nel cane di 16-19 secondi. Questo test valuta sia la fase intrinseca che quella estrinseca; è un esame molto sensibile per la carenza di fattori legati alla Vit. K (FII, FVII, FIX e FX); infatti in assenza o carenza di Vit. K vengono sintetizzate dal fegato le cd. PIVKA (Protein Induced Vitamin K Absence or Antagonists = proteine indotte dall'assenza o dagli antagonisti della Vitamina K).

Tempo di Russell al Veleno di Vipera (RVVT) Questo esame consiste nella misura del tempo necessario affinché avvenga la coagulazione di plasma citrato addizionando la preparazione del RVV (Russell's Viper Venom, Stypven, veleno di vipera) e cloruro di calcio. Il RVV interagisce con FV, FX e PF3 per convertire la protrombina a trombina. Differisce dalla tromboplastina impiegata nel Tempo di protrombina poiché è indipendente dal FVII e richiede una fonte di PF3 per la sua azione catalitica. I valori normali sono nel cane di 17-21 secondi. L'RVVT rileva la diminuzione di PF3, Fibrinogeno, Protrombina, FV e FX, ma non quella del FVII. Se eseguito insieme al PT differenzia le deficienze di FVII da quelle di FX. Dal momento che l'RVVT misura il PF3 il test può risultare allungato nelle trombocitopenie e nelle trombocitopatie (da anormalità nel rilascio di PF3).

ESAMI SPECIALISTICI ESEGUIBILI IN LABORATORI ATTREZZATI Ricerca del fattore carente Con queste indagini è possibile risalire alla carenza dei fattori coinvolti nella cascata coagulativa impiegando il PT o l'aPTT congiuntamente all'uso di un pool di plasmi di controllo e di uno deficiente di un singolo fattore della fase plasmatica della coagulazione (meglio della stessa specie oppure dell'uomo). In sostanza questi test si basano sul grado con

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cui il plasma del paziente in esame corregge il plasma deficiente del singolo fattore, comparandolo con la correzione ottenuta invece con un plasma di controllo. Pertanto vengono impiegate una serie di diluizioni del plasma del paziente con l'aggiunta di plasma carente del fattore sotto indagine ed una serie di diluizioni del plasma del paziente con l'aggiunta di plasma di controllo. Il test del PT così modificato serve a determinare la deficienza di FV o di FVII, mentre il test dell'aPTT così modificato misura la deficienza di FVIII:C, FIX e FXI. Infine l'RVVT modificato consente di valutare la deficienza di FX. Questi sono esami quali/quantitativi utili nella diagnosi di coagulopatie ereditarie. Infatti il tempo di coagulazione del plasma del paziente se risulta allungato rispetto a quello del controllo, indica una diminuzione nel livello dello specifico fattore sotto indagine.

Determinazione di AntiTrombina III (ATIII) In questo test il plasma citrato in presenza di eparina rende attiva l'ATIII che diventa un immediato inibitore della trombina. L'inattivazione di quest'ultima è proporzionale alla concentrazione di ATIII. La trombina residua scinde il substrato cromogenico, che è dosato spettrofotometricamente. I valori normali sono : cane 100-300 mcg/mL, oppure 80120%.(comparati con un pool di plasmi normali). È un esame cardine nella diagnosi di Coagulazione Intravasale Disseminata e di trombosi.

Determinazione del fattore di von Willebrand (FvW) Si basa su due tecniche entrambe atte a rilevare la quota dell'antigene legato al FvW (FvW:Ag) : a) immunoelettroforesi 'rocket' con uso di antisieri umani cross reagenti con il FvW:Ag canino oppure con antisiero anti-FvW:Ag canino; b) kit ELISA, spettrofotometrico, quantitativo con doppio anticorpo monoclonale, che si basa sullo sviluppo di un cromoforo (OPD) il quale si libera a seguito dell'azione enzimatica sul substrato. I valori normali del FvW:Ag nel cane sano sono 70%180%, nel portatore 50-70 %, nell'omozigote inferiori al 50%. Questo test permette la diagnosi di von Willebrand ereditario o acquisito.

Determinazione del D-dimero Questa determinazione eseguibile sia con metodo immunologico (test semiquantitativo per a gglutinazione diretta di particelle di lattice sensibilizzate con anticorpi D-dimero monoclonale) che con metodo immunoturbidimetrico in ELISA (esame di valutazione quantitativa mediante applicazione della tecnica sandwich in presenza di anticorpi D-dimero monoclonale), consente di misurare nel plasma il neoantigene D-dimero derivante dall'azione della plasmina sulla fibrina insolubile. I valori normali nel cane e nel gatto sono inferiori a 28 mcg/mL. È un test elettivo nella diagnosi di Coagulazione Intravasale Disseminata.

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CONCLUSIONI

Bibliografia consultata

Questa nota ha cercato di enfatizzare e raccogliere le principali informazioni necessarie per inquadrare inizialmente, ma correttamente, un paziente affetto da disturbi dell'emostasi. Una particolare attenzione è stata posta sulla preparazione del campione per le analisi della fase plasmatica dell'emostasi che più risente degli errori pre-analitici. La lunga lista di esami della coagulazione non deve impressionare, ma è necessario nella pratica clinica adottare un profilo emostatico di base che consenta un corretto inquadramento diagnostico iniziale. Come universalmente è adottato si suggerisce di includere nel profilo emostatico di base la conta delle piastrine, il Tempo di Protrombina, il Tempo di Tromboplastina Parziale attivato, il Fibrinogeno ed i Prodotti di Degradazione della Fibrina e Fibrinogeno.

Brooks M, (1999), Hereditary Bleeding Disorders in Dogs and Cats, Vet. Med., 6:555-564 Couto CG, (1998),Disorders of Hemostasis,in :Small Animal Internal Medicine, Nelson RW, Couto CG, 2nd edit,Mosby St. Louis,1192-1206 Couto CG, (1999), Clinical Approach to the Bleeding Dog and Cat, Vet Med, 6: 450-459 De Gopegui RR, (2000), Hemostasis, Sect VIII, in : Schalm's Veterinary Hematology, Feldman BF, Zinkl CG, Nemi CJ, 5th ed., Lippincott Williams & Wilkins, Philadelphia, 519-593. Hohenhaus AE, (1999), Bleeding Disorders in Dogs and Cats, Proc. 17th ACVIM, 396-399 Kristensen AT, (2000), Hemostasis: Platelets - Clinical Platelet Disorders, Sect. VII, in : Schalm's Veterinary Hematology, Feldman BF, Zinkl CG, Nemi CJ, 5th ed., Lippincott Williams & Wilkins, Philadelphia,469-515. Lubas G, (1997), Appunti di Ematologia Clinica Comparata, III ediz., S E U Pisa, pp. 235. Mischke R, Nolte IJA, (2000), Hemostasis: Introduction, Overview, Laboratory Technique, in: Schalm's Veterinary Hematology, Feldman BF, Zinkl CG, Nemi CJ, 5th ed., Lippincott Williams & Wilkins, Philadelphia, 519-525.

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Fisioterapia riabilitativa nell'artrosi Stefano Malegori DVM, MRCVS - Oakland Small Animal Veterinary Clinic - Newry, Northern Ireland

Non più considerata semplice alternativa all’approccio medico o chirurgico, ma vero e proprio complemento terapeutico, la fisioterapia sta assumendo una sempre maggiore importanza nel trattamento dell'artrosi in medicina veterinaria. Allo scopo di migliorare la qualità di vita del soggetto affetto da artrosi, la fisioterapia riabilitativa si avvale di terapie manuali, strumentali e di un programma di esercizio attivo. La situazione clinica iniziale, gli strumenti terapeutici a disposizione e la collaborazione del proprietario condizionano sia l’impostazione iniziale che il proseguimento del programma riabilitativo. I pazienti affetti da artrosi presentano una limitazione nell'attività fisica, zoppia, dolore e disagio nel compiere movimenti quotidiani quali alzarsi, sedersi o salire le scale. La sintomatologia clinica varia quindi da riluttanza a compiere determinati movimenti, lieve zoppia, fino ad arrivare all'impossibilità di movimento, ed è destinata a peggiorare col tempo, comportando una riduzione progressiva dell'attività motoria del paziente. Le conseguenze di una diminuita attività a carico delle strutture dell'apparato locomotore si manifestano clinicamente con riduzione della mobilità articolare ed ipotrofia muscolare, instaurando un circolo vizioso che comporta un progressivo peggioramento della qualità di vita del soggetto. La fisioterapia viene utilizzata per prevenire, limitare o ridurre l'incidenza di queste problematiche. In molti casi un protocollo riabilitativo che si avvale di tecniche manuali facilmente eseguibili dal proprietario, quali massaggi e manipolazioni passive, e di un esercizio attivo controllato, è sufficiente - in associazione ad inter venti dietetici e farmacologici - ad assicurare al paziente uno stile di vita adeguato. La fisioterapia riabilitativa sta assumendo una sempre maggiore importanza anche nel trattamento post-chirurgico in ortopedia e traumatologia veterinaria, permettendo di ridurre notevolmente i tempi di recupero funzionale e di limi tare le conseguenze dell'immobilizzazione. Quando la gravità della sintomatologia clinica lo richiede, vengono utilizzate, oltre a massaggi e movimenti passivi, terapie strumentali quali ultrasuoni, LASER, campi magnetici pulsati (PMF) ed elettrostimolazione . I massaggi migliorano la circolazione venosa e linfatica, favoriscono il rilassamento e la distensione muscolare, riducono le aderenze tessutali ed abituano il paziente al contatto con il terapista. I movimenti passivi, che consistono nella mobilizzazione passiva di un'articolazione per l'ampiezza dell'escursione

articolare consentita, oltre ad avere le stesse funzioni dei massaggi permettono di mantenere od incrementare il range di movimento articolare (ROM), prevenendo l’insorgenza di contratture muscolari e periarticolari. Per mantenere o recuperare una normale omeostasi articolare, la sola mobilizzazione passiva non è tuttavia sufficiente, ma vi è la necessità di stress da carico che si hanno con l'esercizio attivo. L'esecuzione dei movimenti passivi deve essere lenta e delicata e non deve risultare dolorosa. La massima escursione articolare possibile deve essere mantenuta per 10 secondi cercando di ampliare l'ampiezza del movimento in caso di riduzione del ROM. I movimenti passivi possono interessare una singola articolazione o coinvolgere l'intero arto, rispettando comunque la biomeccanica delle strutture teno-muscolari. L'utilizzo delle terapie strumentali nella clinica dei piccoli animali è tuttora limitato, più che dal costo dei macchinari, dalla mancanza di letteratura specifica. Laserterapia e magnetoterapia (PMF) si sono dimostrate efficaci nella pratica clinica, ma il loro utilizzo è ancora basato su esperienze personali, non essendo a tutt’oggi disponibili protocolli di trattamento specifici per il cane. In Medicina umana e sempre piu spesso in Medicina Veterinaria nel trattamento di pazienti affetti da artrosi vengono spesso utilizzati gli ultrasuoni. In relazione all'apparecchio disponibile e variando i parametri utilizzati, è infatti possibile ottenere un aumento della temperatura tessutale fino ad una profondità di 5 cm, diminuendo il dolore, migliorando la circolazione (con conseguente aumento del metabolismo tessutale) ed aumentando l'estensibilità di muscoli e strutture periarticolari. Questo consente di ottenere una maggiore mobilità articolare, che deve essere mantenuta attraverso l’utilizzo di movimenti passivi ed esercizi attivi. L'elettrostimolazione è una terapia strumentale utilizzata con sempre maggiore frequenza in Medicina Veterinaria. Nonostante la confusione inerente la terminologia ed i numerosi effetti ed indicazioni terapeutiche, in riferimento all'ampia gamma di correnti, forme e caratteristiche d'impulso disponibili, l'elettrostimolazione viene utilizzata prevalentemente a scopo antalgico (TENS e trattamento endorfinico) ed eccitomotore. Attualmente quest'ultima modalità, basata sulla stimolazione dei motoneuroni, è quella con la più ampia applicazione clinica, essendo utilizzata allo scopo di prevenire l'ipotrofia muscolare e facilitare il recupero dell’attività di contrazione, in sostituzione od in associazione all'esercizio attivo. Applicando correttamente gli elettrodi sulla superficie cutanea è infatti possibile stimolare selettivamen-

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te i muscoli che risultano essere più interessati dalle conseguenze di una ridottà attività. Di fondamentale importanza nel trattamento dell'artrosi è il ripristino graduale e progressivo di un esercizio attivo, che si ottiene con il nuoto, l’esecuzione di esercizi statici e l’attuazione di un programma di deambulazione, allo scopo di: migliorare le capacità propriocettive, aumentare gradualmente la mobilità attiva, nonché la quantità di stress da carico a livello articolare, prevenire o recuperare l'ipotrofia muscolare. Il nuoto consente una mobilizzazione articolare ed un lavoro muscolare notevole senza sottoporre a stress da carico le strutture articolari e teno-muscolari. Essendo questo esercizio molto dispendioso da un punto di vista energetico la durata iniziale del lavoro non deve superare i 5 minuti e deve essere aumentata gradualmente in relazione alla risposta del paziente. Gli esercizi attivi definiti statici si riferiscono al mantenimento della stazione quadrupedale, a movimenti di seduto-in piedi, ad esercizi di pressione e di spostamento del baricentro. Lo scopo di questi esercizi è di migliorare la propriocezione e di far lavorare correttamente la muscolatura, soprattutto i muscoli ad azione antigravitaria che sono maggiormente predisposti all'ipotrofia muscolare in situazioni di ridotta attività motoria. L'esercizio seduto-in piedi permette di ottenere la contrazione e l'allungamento attivo di tutta la muscolatura degli arti posteriori. Durante lo svolgimento di questi esercizi è necessario far assumere al cane posture corrette. Il programma di deambulazione, che viene stabilito e modificato in relazione alle condizioni cliniche del paziente, è basato sull'utilizzo di passeggiate al guinzaglio con possibilità di variare durata, velocità e tipo di terreno. In linea di massima si inizia con brevi passeggiate su terreno non sconnesso ed in piano, di cui si aumentano progressivamente la durata e la velocità, sempre restando al passo. Molto utili possono essere passeggiate su pendii o scale. Queste ultime devono essere effettuate lentamente, in modo che il cane utilizzi un arto alla volta. L'utilizzo di terreni diversi come l'inserimento di figure ad otto e cerchi, la cui ampiezza viene ridotta progressivamente e che vengono effettuati sia in senso orario che antiorario, consente di aumentare le capacità propriocettive. Il tapis-roulant è uno strumento molto utile durante tutto il processo riabilitativo poiché abbiamo la possibilità di variare sia la velocità che l'inclinazione del tappeto. Possiamo quindi valutare e controllare meglio il movimento del paziente, modificando gradualmente la velocità e la durata dell'esercizio. Come l'idroterapia anche il tapis-roulant può essere particolarmente stressante per alcuni soggetti, necessitando di un periodo di adattamento.

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Lo svolgimento dell'esercizio attivo deve essere distribuito nell'arco dell'intera giornata e non concentrato in una singola seduta. Alla fine del programma di esercizio attivo il paziente non deve manifestare un peggioramento della sintomatologia. Se questo accade l'intensità e la durata del lavoro devono essere diminuite. Naturalmente il programma di riabilitazione di un paziente affetto da artrosi è personalizzato e nel suo sviluppo non si può prescindere da un'accurata valutazione clinica del paziente, dal controllo del peso, da una eventuale associazione di terapia medica e dalla disponibilità, in termini di tempo ed economici, da parte del proprietario. Fondamentale è la valutazione iniziale con un accurato esame clinico e, se ritenuto opportuno, con ulteriori strumenti diagnostici delle capacità cardio-respiratorie e dell'entità di esercizio fisico che può essere effettuata dal paziente. Stabilito il punto di partenza è opportuno prendere in considerazione l'età, il carattere e lo stile di vita del cane per valutare quella che può essere considerata una qualità di vita adeguata. Iniziato il programma di riabilitazione, il costante controllo della situazione clinica consente una valutazione dell'efficacia del trattamento e ne permette le eventuali modifiche. L’utilizzo della fisioterapia riabilitativa nella gestione di cani affetti da artrosi permette di migliorare la qualita di vita del paziente qualunque sia lo stadio della patologia. L’instaurazione precoce di un programma di riabilitazione, l’associazione ad una terapia medica e\o chirurgica e la collaborazione del proprietario sono i presupposti per ottenere i migliori risultati. La diffusione e l’ampliamento delle conoscenze scientifiche inerenti questo argomento sono necessari per poterne sfruttare al meglio le potenzialita.

Letture consigliate Kahn J., Principles and practice of electrotherapy 4E. Churchill Livingstone, 2000. Kitchen S. And Bazin S., Clayton’s Electrotherapy 10E. Philadelphia,WB Saunders,1996. Malegori S.,Olivieri M., Vallani C., Impiego della fisioterapia nella riabilitazione post-chirurgica in ortopedia veterinaria, Cinologia, anno 10, N.3, 1999,41-45. Millis L. And Levine D., The role of exercise and physical modalities in the treatment of osteoarthritis, Vet.Clinics of North America: small animal practice, Vol. 27, N.4, Jul. 1997, 913-930. Proceedings of the First International Symposium on Rehabilitation and Physical Therapy in Veterinary Medicine, Oregon State University, College of Veterinary Medicine & College of Health & Human Performance, Aug 7-11,1999. Taylor R.A., Principi basilari di fisioterapia per il cane sportivo. Cinologia, anno 8, N.3,1997, 43-48. Taylor R.A., Postsurgical physical therapy: the missing link. Compendium on Continuing Education for the Practicing Veterinarian 14: 1583,1992.

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Equilibrio e squilibrio dell’ossidazione nell’artrosi Alda Miolo Ricercatore Ce.D.I.S. (Centro Documentazione e Informazione Scientifica) - Innovet

Nel cane, l’artrosi può manifestarsi sia nell’invecchiamento, sia nei primi mesi di vita. Esistono dunque due età diverse – il periodo dell’accrescimento e l’età adulta/anziana – delle cui peculiarità, essenzialmente di ordine metabolico, è necessario tener conto per impostare un intervento complementare utilmente impiegabile nel trattamento dell’artrosi. L’omeostasi di un’articolazione dipende dal perfetto equilibrio tra processi biochimici degradativi (catabolismo) e potenzialità sintetiche (anabolismo), equilibrio che nell’artrosi va incontro ad un graduale e progressivo sbilanciamento, con il netto prevalere delle reazioni cataboliche su quelle anaboliche. Il ripristino di questo delicato bilanciamento è l’obiettivo di un approccio cosiddetto “di fondo” all’artrosi. Se nel cane giovane ciò può attuarsi con un intervento pro-anabolico, tramite cioè la stimolazione delle riserve metaboliche del distretto articolare, nel cane adulto/anziano questa strategia è destinata a fallire a causa del progressivo ed irreversibile depauperamento delle riserve metaboliche, diretta conseguenza dell’invecchiamento e/o della cronicizzazione del processo artrosico. In questo caso, il riequilibrio dovrà transitare attraverso interventi a significato anti-catabolico, che, inibendo le vie degradative, consentono di alleggerire il braccio catabolico della bilancia. Sulla scorta di questi presupposti, la relazione presenta il razionale di un approccio di fondo all’artrosi di tipo “nutraceutico”, basato, cioè,sulla somministrazione combinata per via orale di sostanze ad attività condroprotettiva e di molecole capaci di intervenire nel riequilibrio metabolico dei tessuti articolari, con modalità d’azione rispettivamente proanabolica ed anti-catabolica, a seconda che il target sia l’artrosi del cane giovane o quella del cane adulto/anziano. Per quanto attiene le sostanze condroprotettive, vengono discusse le caratteristiche chimiche e farmacologiche di NSCS 5/20 (una particolare frazione di condroitin solfato che, grazie al basso peso molecolare ed alla normosolfata-

zione, gode di un assorbimento selettivo e preferenziale, che ne garantisce la massima attività condroprotettiva e condroriparativa) e di glucosamina (un aminozucchero, la cui efficacia disease-modifying è stata di recente definitivamente comprovata). Per quel che riguarda le molecole capaci di influire sul riequilibrio metabolico articolare, vengono trattati nel dettaglio l’acido DL α−lipoico e i bioflavonoidi quercetina e rutina. 1. acido DL α−lipoico: si tratta di una molecola in grado di ottimizzare la biodisponibilità muscolare di energia e le riserve protettive dell’unità MTL (muscoli, tendini e legamenti). Mantenere e/o ripristinare la massima efficienza di questa delicata unità mio-teno-legamentosa, preposta a stabilizzare l’articolazione, assume una valenza particolarmente importante nel cane in crescita, dove fattori costituzionali, genetici e/o ambientali tendono frequentemente ad iper-sollecitarla, oltre il limite di recupero fisiologico. L’approccio di fondo, che all’NSCS 5/20 associa l’acido DL α-lipoico per l’artrosi del cane giovane, viene identificato come “condroprotezione MTL”. 2. Bioflavonoidi quercetina e rutina: si tratta di “fitomedicine” dotate di una triplice valenza anti-catabolica, che intervengono modulando i tre meccanismi patogenetici fondamentali dell’artrosi del cane adulto/anziano: stress ossidativo, infiammazione e condrodegenerazione. La loro capacità di neutralizzare i radicali liberi iperprodotti (ROS), di inibire gli effetti di citochine cataboliche (es. Il-1,TNF) e di bloccare l’attività dei principali enzimi ad attività condrolitica (metalloproteasi, MMP), rende quercetina e rutina sostanze ideali per contrastare il prevalere dei meccanismi catabolici tipico della malattia degenerativa articolare. L’approccio nutraceutico di fondo per l’artrosi del cane adulto/anziano, che all’azione di condroprotezione sinergica svolta dal binomio NSCS 5/20glucosamina, associa l’effetto anti-catabolico dei bioflavonoidi quercetina e rutina, prende il nome di “condroprotezione sopradditiva”.

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Patologie scheletriche dello sviluppo e prevenzione, ovvero ortopedia, nutrizione… e un po’ di Internet Carlo Maria Mortellaro Medico Veterinario, Istituto di Clinica Chirurgica e Radiologia Veterinaria, Facoltà di Medicina Veterinaria, Università degli Studi di Milano, Via Celoria, 10, 20133 (Mi)

Massimo Petazzoni Medico Veterinario Libero Professionista, via Lanzano 33, 26837 Mulazzano (Lo)

Mauro Di Giancamillo Medico Veterinario, Istituto di Clinica Chirurgica e Radiologia Veterinaria, Facoltà di Medicina Veterinaria, Università degli Studi di Milano, Via Celoria, 10, 20133 (Mi)

INTRODUZIONE La prevalenza delle patologie ortopediche presso 16 strutture Universitarie negli Stati Uniti, come riportato in uno studio del 1994, è risultata essere circa il 25% dei casi riferiti ed il 70% di questi soggetti presentava patologie a carico dello scheletro appendicolare1. La prevalenza delle patologie muscoloscheletriche nei cani con età inferiore ad un anno si aggira intorno al 22% ed il 20% del totale dei soggetti presenta una patologia scheletrica nella cui eziologia vi è una componente nutrizionale 2. I cani appartenenti a razze di taglia media, grossa e gigante sono frequentemente colpiti da patologie osteoarticolari quali displasia dell’anca (HD), displasia del gomito (ED) osteocondrosi (OC) e sue manifestazioni cliniche tra cui l’osteocondrite dissecante, solo per citare le più importanti. Queste patologie multifattoriali sono state da tempo variamente correlate dalla letteratura scientifica soprattutto internazionale all’eccesso nutrizionale ed alla iperintegrazione durante il delicato periodo dell’accrescimento ed è ormai appurato che l’energia ed il calcio giocano un ruolo fondamentale nell’espressione di malattie che comunque riconoscono una non trascurabile componente genetica (frequentemente implicata come fattore predisponente). Ogni malattia multifattoriale può essere considerata come l’espressione fenotipica di un genotipo suscettibile di una influenza ambientale genericamente intesa, tra cui, nel contesto in esame assume spiccata importanza la componente nutrizionale. Questo concetto può anche essere espresso attraverso la seguente formula:

FENOTIPO = GENOTIPO + INFLUENZA AMBIENTALE Ossia nel caso specifico ESPRESSIONE MALATTIA (HD o OC) = DNA + INFLUENZA NUTRIZIONALE Vale a dire che nell’espressione della malattia le componenti nutrizionale e genetica possono agire da coefficienti per aumentare la probabilità che la malattia stessa si manifesti in un dato individuo. Serva ad esempio l’interessante caso di due gemelle monozigote (ossia con patrimonio genetico identico) afroamericane della Carolina del Nord il cui padre ha sofferto di una grave forma di artrite che è “riuscito” a trasmettere ad una sola delle sue due figlie3. Avendo le gemelle lo stesso corredo cromosomico come è possibile che la malattia sia stata trasmessa ad una sola delle due? Probabilmente qualche fattore ambientale ha determinato l’espressione del fenotipo “artrite” in solo una delle due. È possibile che anche malattie quali la displasia dell’anca e l’osteocondrosi subiscano una influenza genetica ed una influenza nutrizionale per la loro espressione fenotipica. I fattori di rischio per lo sviluppo di una malattia osteoarticolare del periodo dell’accrescimento come quelle sopracitate sono numerosi ed includono: 1. l’appartenenza ad una razza predisposta per tale patologia scheletrica4 (fattore genetico); 2. la somministrazione ad libitum di un alimento (fattore nutrizionale)5; 3. un eccessivo apporto energetico con la dieta (fattore nutrizionale)5,6;

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4. un eccessivo apporto assoluto di calcio con la dieta (fattore nutrizionale)7,8,9,10, 5. una velocità di accrescimento eccessivamente rapida (fattore genetico e nutrizionale) 11,12. La prevenzione genetica delle patologie scheletriche del periodo dell’accrescimento potrà divenire realtà solo quando verrà studiata e disegnata la mappa genetica del cane così come è stato fatto per l’uomo (Progetto Genoma Umano) in cui sono già stati identificati i geni di oltre 1200 malattie come la fibrosi cistica, l’osteogenesi imperfetta e la distrofia muscolare. Fino a quel momento la cosiddetta “prevenzione” genetica potrà essere effettuata esclusivamente mediante il controllo dell’espressione fenotipica della malattia, così come da anni avviene in molti paesi con il controllo radiografico della displasia dell’anca nel cane. La prevenzione ambientale, ossia più specificamente nutrizionale, di malattie quali l’OC, la HD ed in minor misura l’ED può essere realizzata mediante il controllo di alcuni dei fattori di rischio sopra elencati. Numerosi fattori nutrizionali ed in particolare, come più sopra affermato, l’energia ed il calcio, possono influenzare “nel bene e nel male” la crescita di un cucciolo. In effetti il calcio è uno dei più importanti elementi nutrizionali fra quelli studiati nelle cause o concause di patologie scheletriche dei cani in accrescimento e tra queste un cenno particolare merita l’osteocondrosi. Più che lo squilibrio nel rapporto fra calcio ed il fosforo nella dieta è il livello assoluto di calcio somministrato con l’alimentazione ad influire incredibilmente in modo positivo o negativo sullo sviluppo schele trico del cucciolo 6. Livelli assoluti eccessivi di calcio nella dieta possono essere ottenuti in tre diversi modi: integrando una dieta casalinga in modo esagerato con quantità eccessive di minerale (troppi cucchiaini di polvere di calcio nella razione); sovraintegrando una dieta preconfezionata e quindi già bilanciata con troppo calcio (generalmente in polvere) oppure somministrando una dose eccessiva di alimento preconfezionato. È nota la tendenza, ancora oggi diffusa fra alcuni veterinari, allevatori e proprietari di cani (un tempo era una sorta di “must”) ad integrare con calcio in polvere le diete preconfezionate già bilanciare inevitabilmente generando un eccesso di questo minerale. Altre volte le diete casalinghe vengono integrate con dosi eccessive di questo minerale nella convinzione che un cane in crescita abbia un fabbisogno illimitato di calcio; l’idea che un cucchiaino da the faccia bene e che due facciano meglio sta alla base di numerose sovraintegrazioni dei calcio. Altre volte vi è la tendenza a somministrare al cucciolo un alimento per cani adulti con una densità energetica più bassa. Per soddisfare il fabbisogno energetico del cucciolo, che è almeno doppio rispetto a quello di un cane adulto, è necessario somministrare il doppio del quantitativo di cibo. Se le due diete contengono lo stesso quantitativo di calcio è inevitabile che il cucciolo avrà “subito” una doppia razione di calcio con un eccesso alimentare di questo minerale. Il senso di sazietà nel cane viene regolato da due meccanismi: il primo è dato dalla distensione delle pareti dello stomaco subito dopo l’assunzione del pasto mentre il secondo compare dopo l’assorbimento del cibo a livello intestinale (senso tardivo di sazietà). L’alimento

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preconfezionato secco con cui sempre più vengono alimentati i cuccioli di taglia media, grossa e gigante è disidratato e pertanto contiene solo una piccola percentuale di acqua (circa il 10%). Diversamente una bistecca contiene circa l’80% di acqua e solo circa il 20% ne costituisce la sostanza secca (quasi esclusivamente proteine). Somministrare ad un cucciolo 100 grammi in più di croccantini rispetto ai suoi fabbisogni corrisponde alla somministrazione di una bistecca da 450 grammi. Ma mentre una bistecca di circa mezzo Kg provocherebbe la distensione delle pareti gastriche, inducendo un immediato senso di sazietà, che lo inibirebbe dal continuare a mangiare, il cibo preconfezionato secco è molto concentrato e non fornisce un senso immediato di sazietà pur essendo adeguato dal punto di vista nutrizionale per una crescita corretta. Per questo motivo generalmente i proprietari dei cuccioli soddisfano le continue richieste di cibo dei loro cani momentaneamente insoddisfatti ed apparentemen te insaziabili. Inoltre, inspiegabilmente numerosi libri di cinologia continuano a suggerire l’integrazione vitaminica e minerale anche associata ad una alimentazione già bilanciata come quella preconfezionata di tipo industriale considerandola alla stregua di un dogma assoluto. Esaurita rapidamente la “questione calcio” e passando ora ad altri fattori di rischio precedentemente menzionati prendiamo in considerazione il ruolo svolto da una velocità di accrescimento eccessivamente rapida, fattore che se in una qualche misura è influenzato geneticamente, non può tuttavia disconoscere la complicità dell’elemento nutrizionale. Un rapido accrescimento, anche per un periodo relativamente breve, può portare ad uno sviluppo asincrono tra i vari segmenti scheletrici o tra i segmenti scheletrici e la loro componente mio-teno-legamentosa e contribuire quindi allo sviluppo di displasie osteoarticolari quali la succitata displasia dell’anca. Nel cane giovane lo scheletro matura in modo molto rapido e questa maturazione è la risultante di interazioni genetiche, ambientali e nutrizionali. La componente genetica deve essere controllata dagli allevatori eliminando dalla riproduzione i soggetti affetti o possibili portatori di tare genetiche. Il livello di attività fisica cui il cane è sottoposto e la temperatura dell’ambiente in cui il cane vive dipendono ovviamente dal proprietario mentre lo stato salutare dello stesso dipende dalla stretta collaborazione tra proprietario e Medico Veterinario. Il tipo di nutrizione è generalmente scelto dal proprietario sulla scorta dei suggerimenti del Medico Veterinario e dell’allevatore. Numerose variabili quali livello di attività fisica, attitudine e temperatura ambientale, influenzano notevolmente i fabbisogni del cane in crescita e conseguentemente il quantitativo di cibo da somministrare. La gestione del delicato periodo dell’accrescimento del cane mediante tabelle preconfezionate indicanti il quantitativo di cibo da somministrare giornalmente può risultare inadeguato e spesso può portare il cane ad eccessi nutrizionali. Questo perché la razione giornaliera viene calcolata solo in relazione all’età ed al peso del cucciolo senza considerare quindi variabili individuali come attività fisica e temperatura ambientale. Se consideriamo infine che 100 grammi di mangime secco corrispondono “in energia” ad una bistecca cruda di circa 450 grammi va da se che il cibo preconfezionato secco bene si presta a quegli eccessi prima paventati (il cibo preconfezionato umido viene difficilmente

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STUDIO A Materiali e metodi

somministrato a razze grosse o giganti per ragioni strettamente economiche). Spesso inoltre, Medici Veterinari, allevatori e proprietari, come più sopra ricordato, integrano la razione mediante minerali (calcio in primo luogo) e vitamine, soprattutto di quei soggetti destinati alle esposizioni di bellezza o alle prove di lavoro, che “devono” raggiungere precocemente il ring.

Uno studio clinico e radiografico è stato condotto su cani in accrescimento, appartenenti a razze grandi e giganti, portatori di zoppia agli arti anteriori e/o posteriori non riferibile a trauma, afferiti all’Istituto di Clinica Chirurgica e Radiologia Veterinaria dell’Università degli Studi di Milano nel periodo di tempo Aprile 1997 – Dicembre 2000. Allorché l’esame clinico e radiografico indirizzava la diagnosi verso una osteocondrite dissecante veniva eseguito uno studio radiografico completo a carico di tutte le articolazioni potenzialmente coinvolte da una lesione osteocondrale quali spalla, gomito, art. lombo-sacrale, ginocchio, e garretto; in tali soggetti veniva raccolta una accurata anamnesi alimentare mediante la compilazione di un questionario all’uopo elaborato. I soggetti con età superiore a 18 mesi venivano esclusi dallo studio perché un tale lasso di tempo trascorso non avrebbe garantito una raccolta attendibile dell’anamnesi nutrizionale. Per la stessa ragione venivano esclusi dallo studio anche i soggetti che non fossero stati accompagnati dai proprietari.

Obiettivi Lo scopo del primo studio presentato (studio A) è quello di investigare quale delle seguenti tipologie di integrazione calcica sia stata somministrata a soggetti risultati affetti da osteocondrite dissecante (OCD): A, eccesso di integrazione di una dieta casalinga; B, integrazione di una dieta preconfezionata; C, somministrazione in eccesso di alimento preconfezionato. Un secondo studio, studio B, non strettamente correlato al primo e per altro ancora in corso,ha come obiettivo il controllo delle curve di accrescimento (CCA) in una popolazione di 61 cani appartenenti alla razza Golden retriever e Bovaro del Bernese.

Tabella 1 N°

RAZZA

SESSO

ETÀ (mesi)

SEDE OCD

ECCESSO CALCIO

Border Collie

SPALLA sinistra

Golden Retriever

SPALLA sinistra

Mastino Napoletano

SPALLA sinistra

Rottweiler

SPALLA sinistra

Terrier Russo

SPALLA sinistra

Boxer

SPALLA destra

Cane Corso

SPALLA destra

Cane Corso

SPALLA destra

Rottweiler

SPALLA destra

Boxer

SPALLA bilaterale

Boxer

SPALLA bilaterale

Bracco Tedesco

SPALLA bilaterale

Bracco Tedesco

SPALLA bilaterale

Bracco Tedesco

SPALLA bilaterale

Cane Corso

SPALLA bilaterale

Dalmata

SPALLA bilaterale

Pastore Belga

SPALLA bilaterale

Terranova

SPALLA bilaterale

Terranova

SPALLA bilaterale

Terranova

SPALLA bilaterale

Pastore Tedesco

GINOCCHIO destro

incrocio

GINOCCHIO bilaterale

Golden Retriever

GOMITO destro

Rottweiler

GARRETTO bilaterale

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Risultati Ventiquattro soggetti sono stati inclusi nel presente studio perché affetti da OCD. Venti soggetti erano affetti da OCD scapolo-omerale (84%) di cui 11 bilateralmente e 9 monolateralmente, 2 soggetti erano affetti da OCD di ginocchio (8%) di cui uno monolateralmente ed uno bilateralmente, un soggetto da OCD di gomito (4%) monolateralmente ed un soggetto da OCD di garretto (4%) bilateralmente (Tab 1). L’analisi nutrizionale elaborata a partire dall’anamnesi alimentare raccolta ha rivelato che 22 cani su 24 (92%) hanno ricevuto durante i primi mesi di vita una quantità di calcio in eccesso rispetto ai propri fabbisogni metabolici per l’accrescimento in tre differenti modi: 3 su 24 (12%) attraverso la somministrazione di una dieta casalinga integrata mediante supplementazione minerale in polvere (A nella tabella); 8 su 24 (34%) attraverso la somministrazione di un alimento bilanciato, preconfezionato secco, somministrato in eccesso in aggiunta ad una integrazione minerale in polvere (B in tabella); 11 su 24 (46%) attraverso la somministrazione eccessiva di un alimento bilanciato preconfezionato secco (C nella tabella); due soggetti (8%) hanno ricevuto, durante il loro accrescimento, un adeguato apporto calcico.

Discussione Il presente studio clinico ha evidenziato una possibile correlazione tra l’eccesso di calcio, in vario modo integrato, e l’osteocondrite dissecante, che dell’osteocondrosi rappresenta la più frequente manifestazione clinica, per nulla smentendo, nonostante l’esiguità del campione esaminato, i risultati emersi dai numerosi lavori scientifici che si sono succeduti al riguardo dal 19745 ad oggi. È scaturito in modo inequivocabile che non tanto l’offerta di qualche “cucchiaio di troppo” di minerale sta all’origine dell’eccesso calcico (abitudine dai più ormai abbandonata e da taluni ritenuta ancora la sola forma di “oversupplementation”) ma soprattutto l’indulgenza dei proprietari nella concessione di sovradosaggi di un alimento considerabile bilanciato laddove somministrato in quantità adeguate (modalità più subdola, scarsamente conosciuta e per questo più pericolosa di oversupplementation). Ricordiamo ancora una volta che è il quantitativo assoluto di calcio assunto con la dieta ad essere chiamato in causa nell’eziopatogenesi dell’osteocondrosi e non il rapporto fra calcio e fosforo o fra calcio e gli altri elementi nutrizionali! Il dato relativo a due cani (casi 17 e 20 Tab 1) che sono risultati portatori di OCD scapolo-omerale, entrambi colpiti bilateralmente, e la cui anamnesi alimentare non ha evidenziato alcun eccesso calcico, potrebbe portare alla conclusione, forse semplicistica, che in tali pazienti la componente genetica abbia svolto un ruolo preminente o forse unico. È interessante notare che sebbene in numerosi casi la lesione fosse bilaterale (Tab. 1), in nessun caso sono state diagnosticate OCD multiple, ossia lesioni a carico di più articolazioni in un singolo soggetto contrariamente a ciò che è stato riportato da Olsson, in un lavoro del 1987, in cui 25 soggetti su 89 (28%) risultarono colpiti da OCD multiple all’esame autoptico13. Tuttavia un parallelismo stretto tra lo studio da noi condotto e quello di Olsson è solo parzialmen-

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te proponibile data la diversità delle due metodiche di indagine (clinico-radiografica, la nostra, versus quella autoptica di Olsson) 13.

STUDIO B Materiali e metodi 61 cani: 40 cuccioli di Golden Retriever e 21 di Bovaro del Bernese, provenienti da due diversi allevamenti, sono stati arruolati per il presente studio. Il controllo delle curve di crescita è iniziato all’età dello svezzamento (50 giorni) continuando fino all’età di 12 mesi per ogni soggetto. I proprietari sono stati istruiti circa l’importanza del controllo delle curve di crescita per la prevenzione delle displasie osteoarticolari, ed invitati a partecipare gratuitamente al progetto. I costi di tale programma sono stati sostenuti dall’allevamento. Al momento dell’adozione del cucciolo è stata raccolta accuratamente l’anamnesi ambientale ed i proprietari sono stati invitati a limitare l’attività fisica del cucciolo ad un’ora al giorno fino al raggiungimento dell’età matura. Il controllo della curva di crescita veniva effettuato ogni 710 giorni con la comunicazione, da parte del proprietario, del peso del cane via e-mail o tramite messaggio SMS. È stato impiegato un unico cibo preconfezionato secco specifico per cani di taglia grossa e gigantea ed i proprietari si sono impegnati a non apportare qualsivoglia integrazione. Settimanalmente, in base all’età del cane e al peso raggiunto è stato calcolato il fabbisogno metabolico di base di Energia Metabolizzabile in Kcal/giorno per soggetto (la dieta somministrata era considerata adeguatamente bilanciata per gli altri parametri quali proteine, acidi grassi insaturi, minerali, vitamine ecc.). Ai cuccioli venivano somministrati 3 pasti giornalieri fino al compimento del sesto mese di vita per poi proseguire con due pasti giornalieri fino al compimento dell’anno di età. Il fabbisogno di energia è stato calcolato secondo la seguente formula E(Kcal)=((30*Kg)+70)*X*Y dove X rappresenta la variabile per l’accrescimento e Y il coefficiente che considera la temperatura ambientale esterna (X = 3 per i primi 4 mesi di vita, X = 2 dal quinto mese di vita fino al raggiungimento dell’80% del peso stimato da adulto e X = 1,8 dall’80% al 100% della taglia da adulto). Y variava da 1 (durante il periodo estivo e per i soggetti mantenuti 24 ore su 24 in ambiente termoneutro) a 1,25 durante il periodo invernale per i soggetti che trascorrevano fino al 50% del tempo in ambiente esterno. I proprietari sono stati invitati a fare trascorrere almeno la notte ai propri animali in ambiente termoneutro (circa 20° C). Settimanalmente si controllava l’incremento ponderale medio giornaliero del cane ed il quantitativo di cibo da somministrare veniva ricalcolato per la settimana successiva. Il calcolo dei fabbisogni energetici veniva considerato solo indicativo per impostare un incremento ponderale giornaliero massimo di 100 grammi per il Golden Retriever e di 150 grammi per il Bovaro Bernese. Tutti i calcoli sono stati effettuati con l’ausilio del foglio elettronico Excel di Microsoft © (Tab. 2).

Hill’s Growth Larger Breed.

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Risultati Il metodo CCA proposto per il Controllo delle Curve di Accrescimento, basato sulla gestione settimanale dell’incremento ponderale medio giornaliero del cane, mediante l’uti-

lizzo di un foglio di lavoro elettronico (Tab 2, 3), ha consentito un adeguamento tempestivo della razione ed un aggiustamento immediato della curva di crescita dei 61 cuccioli inclusi nel presente studio. Un esempio di tale metodo è mostrato in tabella 3.

Tabella 2 A

Incremento (gr/gg)

stima alimento (gr/gg)

1 2

36150

3 4 5

giorni

settimane

mesi

Data

Peso cane (Kg)

cibo (gr/gg)

=+E7-G3

=+B7/7

=+B7/30

36200

3,5

150

=+E8-G3

=+B8/7

=+B8/30

36209

4,4

160

=+((F8-F7)*1000)/(E8-E7)

=+((F8*30)+70)*3/3,4

=+E9-G3

=+B9/7

=+B9/30

36217

5,2

170

=+((F9-F8)*1000)/(E9-E8)

=+((F9*30)+70)*3/3,4

=+E10-G3

=+B10/7

=+B10/30

36223

5,8

200

=+((F10-F9)*1000)/(E10-E9)

=+((F10*30)+70)*3/3,4

=+E11-G3

=+B11/7

=+B11/30

36230

6,6

200

=+((F11-F10)*1000)/(E11-E10)

=+((F11*30)+70)*3/3,4

=+E12-G3

=+B12/7

=+B12/30

36238

7,2

200

=+((F12-F11)*1000)/(E12-E11)

=+((F12*30)+70)*3/3,4

=+E13-G3

=+B13/7

=+B13/30

36241

7,6

200

=+((F13-F12)*1000)/(E13-E12)

=+((F13*30)+70)*3/3,4

=+E14-G3

=+B14/7

=+B14/30

36248

8,2

250

=+((F14-F13)*1000)/(E14-E13)

=+((F14*30)+70)*3/3,4

=+E15-G3

=+B15/7

=+B15/30

36251

8,7

250

=+((F15-F14)*1000)/(E15-E14)

=+((F15*30)+70)*3/3,4

=+E16-G3

=+B16/7

=+B16/30

36258

9,8

270

=+((F16-F15)*1000)/(E16-E15)

=+((F16*30)+70)*3/3,4

=+E17-G3

=+B17/7

=+B17/30

36267

10,9

300

=+((F17-F16)*1000)/(E17-E16)

=+((F17*30)+70)*3/3,4

=+E18-G3

=+B18/7

=+B18/30

36279

11,7

310

=+((F18-F17)*1000)/(E18-E17)

=+((F18*30)+70)*2/3,4

=+E19-G3

=+B19/7

=+B19/30

36289

12,8

330

=+((F19-F18)*1000)/(E19-E18)

=+((F19*30)+70)*2/3,4

=+E20-G3

=+B20/7

=+B20/30

36297

350

=+((F20-F18)*1000)/(E20-E18)

=+((F20*30)+70)*2/3,4

=+E21-G3

=+B21/7

=+B21/30

36302

14,5

380

=+((F21-F20)*1000)/(E21-E20)

=+((F21*30)+70)*2/3,4

=+E22-G3

=+B22/7

=+B22/30

36312

420

=+((F22-F21)*1000)/(E22-E21)

=+((F22*30)+70)*2/3,4

=+E23-G3

=+B23/7

=+B23/30

36321

17,5

450

=+((F23-F22)*1000)/(E23-E22)

=+((F23*30)+70)*2/3,4

=+E24-G3

=+B24/7

=+B24/30

36333

19,5

460

=+((F24-F23)*1000)/(E24-E23)

=+((F24*30)+70)*2/3,4

=+E25-G3

=+B25/7

=+B25/30

36346

20,5

470

=+((F25-F24)*1000)/(E25-E24)

=+((F25*30)+70)*2/3,4

=+E26-G3

=+B26/7

=+B26/30

36356

21,5

480

=+((F26-F25)*1000)/(E26-E25)

=+((F26*30)+70)*2/3,4

=+E27-G3

=+B27/7

=+B27/30

36371

22,5

490

=+((F27-F26)*1000)/(E27-E26)

=+((F27*30)+70)*2/3,4

=+E28-G3

=+B28/7

=+B28/30

36384

500

=+((F28-F27)*1000)/(E28-E27)

=+((F28*30)+70)*2/3,4

=+E29-G3

=+B29/7

=+B29/30

36394

520

=+((F29-F28)*1000)/(E29-E28)

=+((F29*30)+70)*2/3,4

=+E30-G3

=+B30/7

=+B30/30

36402

550

=+((F30-F29)*1000)/(E30-E29)

=+((F30*30)+70)*2/3,4

=+E31-G3

=+B31/7

=+B31/30

36408

550

=+((F31-F30)*1000)/(E31-E30)

=+((F31*30)+70)*1,8/3,4

=+E32-G3

=+B32/7

=+B32/30

36422

560

=+((F32-F31)*1000)/(E32-E31)

=+((F32*30)+70)*1,8/3,4

=+E33-G3

=+B33/7

=+B33/30

36437

29,3

570

=+((F33-F32)*1000)/(E33-E32)

=+((F33*30)+70)*1,8/3,4

=+E34-G3

=+B34/7

=+B34/30

36448

30,3

580

=+((F34-F33)*1000)/(E34-E33)

=+((F34*30)+70)*1,8/3,4

=+E35-G3

=+B35/7

=+B35/30

36458

31,5

590

=+((F35-F33)*1000)/(E35-E33)

=+((F35*30)+70)*1,8/3,4

=+E36-G3

=+B36/7

=+B36/30

36475

600

=+((F36-F35)*1000)/(E36-E35)

=+((F36*30)+70)*1,8/3,4

=+E37-G3

=+B37/7

=+B37/30

36485

33,5

600

=+((F37-F36)*1000)/(E37-E36)

=+((F37*30)+70)*1,8/3,4

=+E38-G3

=+B38/7

=+B38/30

36493

33,5

600

=+((F38-F37)*1000)/(E38-E37)

=+((F38*30)+70)*1,8/3,4

=+((F7*30)+70)*3/3,4

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Tabella 3 A

BARLUCATHOS

Progetto : MISURAZIONE ACCRESCIMENTO

Data di nascita 21/12/98

Alimentazione Tipo: Hill's - GROWTH Larger Breed

Incremento (gr/gg)

stima alimento (gr/gg)

21-12-1998 Gldn Retriever maschio

giorni

settimane

mesi

Data:

Peso cane (Kg)

alimento (gr)

1,7

9-02-1999

3,5

150

2,0

18-02-1999

4,4

160

100

178

2,2

26-02-1999

5,2

170

100

199

2,4

4-03-1999

5,8

200

100

215

2,7

11-03-1999

6,6

200

114

236

2,9

19-03-1999

7,2

200

252

3,0

22-03-1999

7,6

200

133

263

3,3

29-03-1999

8,2

250

279

101

3,4

1-04-1999

8,7

250

167

292

108

3,6

8-04-1999

9,8

270

157

321

117

3,9

17-04-1999

10,9

300

122

350

129

4,3

29-04-1999

11,7

310

371

139

4,6

9-05-1999

12,8

330

110

267

147

4,9

17-05-1999

350

128

288

152

5,1

22-05-1999

14,5

380

100

297

162

5,4

1-06-1999

420

150

324

171

5,7

10-06-1999

17,5

450

167

350

183

6,1

22-06-1999

19,5

460

167

385

196

6,5

5-07-1999

20,5

470

403

206

6,9

15-07-1999

21,5

480

100

421

221

7,4

30-07-1999

22,5

490

438

234

7,8

12-08-1999

500

115

465

244

8,1

22-08-1999

520

100

482

252

8,4

30-08-1999

550

125

500

258

8,6

5-09-1999

550

167

518

272

9,1

19-09-1999

560

482

287

9,6

4-10-1999

29,3

570

502

298

9,9

15-10-1999

30,3

580

518

308

10,3

25-10-1999

31,5

590

105

537

325

10,8

11-11-1999

600

561

335

11,2

21-11-1999

33,5

600

569

343

11,4

29-11-1999

33,5

600

569

154

Nella cella F2 (Tab. 2 in grigio) viene riportata la data di nascita del cucciolo trasformata dal foglio elettronico in valore numerico (Tab. 3). Nella colonna D (Tab. 2, 3) vengono riportate le date in cui si effettua la misurazione del peso del cane e nella colonna E il corrispettivo peso in Kg (Tab. 2, 3). La colonna F (Tab 2, 3) riporta il quantitativo di cibo da somministrare al cucciolo per i 7/10 giorni successivi. Nelle colonne A, B e C vengono calcolati rispettivamente i giorni, le settimane ed i mesi di età del soggetto (nella Tab 2 sono riportati i valori calcolati dalle formule espresse dalla Tab 3). Nella colonna A i giorni di età vengono calcolati sottraendo il valore "data odierna" (colonna D) al valore "data di nascita" (cella F2 in grigio). Le settimane ed i mesi vengono calcolati nelle colonne B e C dividendo per 7 e per 30 il valore della colonna A. La colonna G calcola l'incremento ponderale medio giornaliero degli ultimi 7/10 giorni sottraendo dal nuovo peso, l'ultimo peso misurato e dividendolo per i giorni trascorsi dall'ultima misurazione. Il risultato viene moltiplicato per 1000 per avere l'incremento giornaliero in grammi. La colonna H calcola i grammi di alimento da somministrare quotidianamente ai cuccioli. L'energia metabolizzabile calcolata in Kcal/giorno viene divisa per 3,4, valore che corrisponde alla densità energetica del cibo impiegato espressa in Kcal/Kg. Il valore restituito in grammi corrisponde alla quantità di cibo da somministrare. L'energia metabolizzabile viene calcolata secondo la seguente formula [(Kg*30)+70]*X dove X vale 3 per i primi 4 mesi di vita, vale 2 fino al raggiungimento dell'80% del peso stimato da adulto e 1,8 fino al raggiungimento del 100% dello stesso.

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Discussione L’ereditabilità della displasia dell’anca nel cane risulta oggi essere fra il 20 ed il 60%. Ciò significa che il rimanente 40-80% della manifestazione di questo fenotipo, è di origine ambientale. La concausa ambientale maggiormente responsabile di tale patologia multifattoriale potenzialmente invalidante, è da attribuire alla sovranutrizione e/o sovraintegrazione ma soprattutto ad una velocità eccessiva di accrescimento che privilegiando la struttura scheletrica a scapito della più tardiva maturità muscolare può essere all’origine di pericolose asincronie di sviluppo. Per tale motivo, il controllo della displasia dell’anca basato esclusivamente sullo studio radiografico dei riproduttori ha sortito, a distanza di anni, solo parziali risultati. Soggetti appartenenti a razze canine quali Bovaro del bernese, Labrador retriever, Golden retriever, Pastore tedesco, Terranova ecc., per le loro caratteristiche comportamentali ed attitudinali, vengono frequentemente impiegati come cani da lavoro (cani guida per non-vedenti, da ricerca, da valanga, antidroga ecc.) e tale impiego richiede, per l’addestramento, un notevole impegno in risorse umane ed un altrettanto importante sforzo economico. Pertanto il controllo dell’accrescimento, allo scopo di limitare o evitare nel cucciolo un rapido sviluppo e di conseguenza una possibile concausa di una displasia osteoarticolare, assume importanza e valore in tali soggetti Il metodo da noi proposto è risultato essere agevole, economico ed alla portata di tutti, pur prevedendo l’ausilio di mezzi telematici ed informatici quali Internet©, SMS© ed un foglio elettronico. Nonostante il numero dei soggetti considerati sia limitato (si consideri tuttavia che lo studio ha comportato un numero di messaggi e-mail e/o messaggio SMS superiore a 1200) e la verifica dell’utilità di tale sistema richieda tempi più lunghi nonché controlli clinico-radiografici specifici, il CCA ha consentito di correggere tempestivamente incrementi ponderali eccessivi e potenzialmente pericolosi per lo sviluppo di quelle patologie ortopediche dell’accrescimento più volte richiamate.

287

to, i cani soprattutto di taglia grossa-gigante vengono alimentati mediante diete preconfezionate adeguatamente bilanciate ma sfortunatamente e frequentemente somministrate in quantità eccessiva talvolta anche inadeguatamente ed inopportunamente integrate all’origine di patologie osteoarticolari in cui l’eccesso alimentare assoluto (carboidrati,proteine, grassi ecc) o relativo (calcio) svolgono un ruolo preminente. Infine, ricordiamo come una corretta gestione del periodo dell’accrescimento del cane dovrebbe prevedere una alimentazione studiata per categoria di taglia (nana, piccola, media, grossa e gigante) o addirittura per razza, evitando rigorosamente (giova ripeterlo) integrazione inutili o addirittura dannose.

Ringraziamenti Gli Autori desiderano ringraziare la Hill’s Pet Nutrition Italia per la collaborazione.

Bibliografia 1.

3. 4.

6. 7.

Conclusioni 9.

Nonostante tutto ciò che è stato scritto finora sulle riviste scientifiche e sulle testate a carattere divulgativo a proposito di iperalimentazione ed iperintegrazione e delle sue conseguenze sull’apparato osteoarticolare durante il periodo dell’accrescimento, vi è comunque la tendenza a fornire nutrienti ed integratori vitaminici e minerali in eccesso. In passato i cani venivano alimentati esclusivamente mediante diete casalinghe che hanno probabilmente causato patologie carenziali metaboliche quali l’iperparatiroidismo secondario nutrizionale ed in rare, se non sporadiche, occasioni il rachitismo. Oggigiorno, nell’era del consumismo spin-

10.

11.

12. 13.

Johnson JA, Austin C, Breuer GJ. Incidence of canine appendicular musculoskeletal disorders in 16 veterinary teaching hospitals from 1980-1989. Journal of Veterinary Comparative Orthopedics and Traumatology 1994; 7: 56-69. Hand MS, Thatcher CD, Remillard RL, Roudebush P, eds.Developmental Orthopedic Disease of Dogs. In: Small Animal Clinical Nutrition, 4th Edition,Mark Morris Institute, 2000; 505-528. Shreeve J. Secrets of the Gene. National Geographic, 1999, vol 4, n. 4:46-79. Corley EA, Hogan PM. Trends in hip dysplasia control:Analysis of radiographs submitted to the Orthopedic Foundation for Animals 1974 to 1984. Journal of the American Veterinary Medical Assiciation, 1985; 187: 805-809. Hedhammar A, Wu F, Krook L, et al. Overnutrition and skeletal disease. An experimental study in growing Great Dane dogs. Cornell Veterinarian 1974; 64 (suppl 5): 1-160. Lust G, Geary JC,Sheffy BE. Development of hip dysplasia in dogs. American Journal of Veterinary Research, 1973; 34:87-91. Hazewinkel HAW, Vandenbrom WE, Van’t Klooster AT, et al. Calcium metabolism in Great Dane dogs fed diets with various calcium and phosphorus levels. Journal of Nutrition 1991; 121: S99S106. Hazewinkel HAW, Goedgebuure SA, Poulos PW, et al. Influences of chronic calcium excess on the skeletal development of growing Great Danes. JAAHA, 1985; 21: 377-391. Schoenmakers I, Hazewinkel HAW, Voorhut G, et al. Calcium and Phosphorus absorption and retention in Great Danes raised on foods with different calcium and phosphorus content (abstract). European Society of Veterinary Comparative Nutrition 1997; 24. Voorhout A, Hazewinkel HAW. A radiographic study on the development of the antebrachium in Great Dane pups on different calcium intakes. Veterinary Radiology 1987; 28:152-157. D a e m m ri ch K. Relationship between nu t rition and bone grow t h in large and giant dogs. Jo u rnal of Nutrition 1991; 121: S 1 1 4 S121. Meyer H, Zentek J. Energy requirements of growing Great Danes, Journal of Nutrition 1991; 121:S35-S36. Olsson, S.E.:General and local factors in canine osteochondrosis. Veterinary Quarterly.,9:268, 1987.

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Anestesia totalmente intravenosa: esperienze cliniche Lorenzo Novello Medico Veterinario, Libero professionista, Padova

Marco Scandone Medico Chirurgo, Specialista in Anestesia, Rianimazione, Terapia Antalgica e Terapia Iperbarica, Servizio di Anestesia, Ospedale civile di Voghera (Pavia)

Stefano Pizzirani Medico Veterinario, Dottore di Ricerca, Dipl. ECVS, Libero professionista, Clinica Veterinaria Europa, Firenze

INTRODUZIONE L’anestesia totalmente endovenosa (TIVA) è una tecnica che permette l’induzione e il mantenimento dell’anestesia unicamente con farmaci endovenosi 1,2,3. Ogni singola componente dell’anestesia, e cioè ipnosi, analgesia, controllo del sistema nervoso autonomo e rilassamento muscolare, viene ottenuta e modulata attraverso l’uso di specifici farmaci endovenosi, evitando così di utilizzare il protossido o gli anestetici inalatori. Proprio per questo motivo la TIVA è particolarmente indicata per tutte quelle condizioni preesistenti o quelle procedure chirurgiche in cui l’uso del protossido e degli anestetici inalatori risulti sconsigliabile o addirittura controindicato. Tra le condizioni preesistenti ricordiamo: ipossiemia o ischemia, insufficienza cardiocircolatoria, pneumotorace, emergenze traumatologiche, ecc.; tra le procedure: chirurgia toracica, ricostruttiva tracheo-bronchiale, dell’orecchio medio e delle vie aeree, ventilazione monopolmonare, jet ventilation, ecc. 1,3 . La TIVA si propone anche come alternativa all’anestesia inalatoria per procedure diagnostiche e chirurgiche ambulatoriali, soprattutto quando siano importanti la velocità e la qualità del recupero e la riduzione degli effetti collaterali postoperatori 3 . Tuttavia, mentre in medicina la TIVA è una tecnica codificata e di provata efficacia, in veterinaria è stata documentata solamente la sedazione endovenosa, utilizzata per procedure diagnostiche e terapeutiche anche di lunga durata ma di limitata invasività 4,5,6 .

Scopo del nostro studio è stato valutare l’efficacia della TIVA nel controllare le quattro componenti classiche dell’anestesia generale (ipnosi, analgesia, protezione neurovegetativa, miorisoluzione) durante l’esecuzione di interventi di chirurgia maggiore e procedure diagnostiche invasive nel cane e nel gatto. È stata anche nostra intenzione fornire un modesto contributo alla tesi secondo la quale le tecniche anestetiche endovenose sono virtualmente applicabili a tutti i pazienti e a tutte le procedure chirurgiche, ricordando ovviamente che ogni paziente e ogni procedura sono leggermente diversi gli uni dagli altri e così di conseguenza la tecnica anestetica endovenosa applicata 3 .

PAZIENTI E METODI Abbiamo condotto un’indagine retrospettiva su 26 pazienti nei quali, dopo consenso informato del proprietario, l’anestesia generale è stata indotta e mantenuta unicamente con farmaci endovenosi. L’indagine ha riguardato interventi eseguiti presso cinque diverse strutture veterinarie: due Cliniche con Pronto Soccorso 24 ore, una Clinica con prevalente attività specialistica di referenza, e due Ambulatori con prevalente attività medicogenerica o di base. A differenza delle altre strutture citate, i due Ambulatori erano sprovvisti di apparecchio per l’anestesia inalatoria. Sono stati inseriti nello studio 19 cani, 6 gatti e una tigre (assimilata al gatto per la giovanissima età e la cattività in ambiente domestico) sottoposti ad interventi di chirurgia maggiore o a procedure diagnostiche invasive ad essa assi-

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milabili nel periodo 06/1999 – 09/2000. Abbiamo considerato criteri di esclusione: l’assenza di una cartella anestesiologica completa, perché ciò non ci avrebbe permesso di analizzare l’andamento di tutta la procedura e le condizioni pree post-intervento del paziente; l’assenza di anestesia generale, perché in tal caso non sarebbe stata una anestesia endovenosa ma bensì una sedazione endovenosa; l’utilizzo per il mantenimento dell’anestesia di agenti anestetici inalatori in associazione ai farmaci endovenosi di mantenimento, perché tale procedura non è una TIVA. L’età media è risultata essere 7.3 anni (min. 3 mesi, max. 14 anni) per i cani, 3.7 anni (min. 1,max. 6) per i gatti, 2 mesi l’età della tigre, la popolazione composta da 10 maschi (1 castrato) e 9 femmine (4 sterilizzate) per i cani, da 2 maschi (1 castrato) e 4 femmine (2 sterilizzate) per i gatti, maschio intero la tigre. Il peso medio espresso in kg è risultato essere 14,6 ± 11,1 per i cani , 3,9 ± 0,6 per i gatti, 4,5 il peso della tigre. Sono rientrati nello studio interventi di chirurgia addominale (5), ortopedica (1), toracica (5), vascolare (4), della cute ed annessi (8), neurochirurgia (2), interventi di detartrasi ed estrazione dentaria (2) e procedure diagnostiche invasive quali biopsie (1) e prelievo di midollo osseo (1). Le patologie concomitanti, o pregresse ma comunque significative ai fini dell’anestesia, sono risultate essere: anemia (3), contusione polmonare e miocardica (2), epilessia o episodi convulsivi (4), febbre d’origine sconosciuta (1), filariosi cardiopolmonare (2), fratture multiple (2), ingrandimento delle camere cardiache (2), insufficienza cardiaca valvolare (6), insufficienza epatica (1), insufficienza ventilatoria (3), ipertensione endocranica (2), setticemia (2). I pazienti sono stati classificati, in base alla Classificazione del rischio della Società Americana di Anestesia (ASA) (Tab. 1), in ASA 1 (4), ASA 2 (2),ASA 3 (7), ASA 4 (12) e ASA 5 (1). Circa 15 minuti prima dell’induzione 2 pazienti sono stati premedicati con acetilpromazina (Prequillan, Fatro) 0,02 mg/kg per via intramuscolare e 5 con medetomidina (Domitor, Vetem) 0,002 mg/kg diluita in soluzione glucosata 5% in infusione endovenosa continua in 10 minuti perché agitati e non collaboranti. Tutti i pazienti sono stati tranquillizzati e indotti con la sequenza diazepam (Diazepam 0,5%, Gellini) o midazolam (Ipnovel, Roche) 0,15 mg/kg, atropina (Atropina solfato, Galenica Senese) 0,01 mg/kg, fentanil (Fentanest, Pharmacia & Upjhon) 0,005-0,01 mg/kg o alfentanil (Fentalim,Angelini) 0,05-0,08 mg/kg e propofol (Rapinovet,

Schering-Plough) 1,5-3 mg/kg per via endovenosa, con successiva intubazione orotracheale e ventilazione assistita in ossigeno e aria (FiO2 tra 1.0 e 0.4). Per il mantenimento dell’anestesia sono stati utilizzati propofol in infusione endovenosa continua e fentanil o alfentanil in infusione endovenosa continua o in boli endovenosi ad intervalli. La condotta anestesiologica è stata guidata dal monitoraggio ed è stata ottenuta modificando i tassi di infusione dei farmaci utilizzati per il mantenimento all’interno dei seguenti intervalli: propofol 0,1-0,3 mg/kg/min, fentanil 4-8 mcg/kg/ora, alfentanil 1,2- 2 mcg/kg/min, atracurium 0.2 mg/kg in bolo ogni 25-50 minuti quando previsto. Per le infusioni continue si sono utilizzate pompe infusionali a siringaa. In 12 pazienti è stata eseguita miorisoluzione con atracurium besilato (Tracrium, Wellcome) 0,3 mg/kg e ventilazione controllatab, e in 21 pazienti come adiuvante all’anestesia per il controllo del dolore operatorio è stata utilizzata ketamina (Imalgene 1000, Merial) a dose di carico di 0,3 mg/kg per via endovenosa in 5 minuti e dose di mantenimento di 0,01 mg/kg/min in infusione endovenosa continua con interruzione della stessa 10 minuti prima del risveglio. In 18 pazienti che non presentavano controindicazioni al farmaco 10 minuti prima del risveglio è stato somministrato ketorolac (Lixidol, Roche) 0,3 mg/kg diluito in 20 ml di soluzione fisiologica in infusione endovenosa continua in 20 minuti per il controllo del dolore postoperatorio. Tutti i pazienti hanno ricevuto come da protocollo terapia infusionale con soluzione NaCl 0,9% o di Ringer a 10-20 ml/kg/ora per via endovenosa, con modificazione di tipo di fluido, dosaggi e velocità d’infusione quando necessario. In ogni paziente è stato eseguito un monitoraggio routinario dell’anestesia comprendente la valutazione clinica di frequenza cardiaca e respiratoria, colore delle mucose, tempo di riempimento capillare, volume del polso arterioso, diametro e posizione delle pupille, riflessi corneale e pupillare, presenza di lacrimazione oculare, tono della muscolatura mandibolare, qualità dell’induzione e del risveglio, e la misurazione strumentale di traccia elettrocardiografica, pressione arteriosac e

Vial Becton-Dickinson SE 400Bm a doppia via,Becton-Dickinson & Co., Division VIAL mèdical, Brezins, France. b Ohmeda OA 7700, BOC Co.,England. c Minidop ES-100VX con sonda veterinaria da 8 Mhz, Ichiyama GmbH, Dusseldorf, Germany.

Tabella 1 - Classificazione del rischio della Società Americana di Anestesia (ASA)* Classe ASA

Definizione

Classe I

Pazienti clinicamente sani senza malattie organiche, con patologia chirurgica localizzata

Classe II

Pazienti con lievi malattie sistemiche, compensati, senza segni clinici

Classe III

Pazienti con gravi malattie sistemiche, con segni clinici

Classe IV

Pazienti con malattie sistemiche invalidanti con pericolo di vita

Classe V

Pazienti in gravissime condizioni con sopravvivenza inferiore alle 24 or e

Classe E

Pazienti che richiedono interventi d’urgenza (si aggiunge la “E” se la procedura è eseguita in emergenza)

* Modificata da Romano E (ed). Anestesia generale e speciale. Torino:UTET, 1997,p 113.

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Tabella 2 - Procedure chirurgiche eseguite. Caso

Specie

Razza

Età (a/m)

Sesso

Peso (kg)

ASA

Procedura chirurgica

cane

cocker

mastectomia

cane

cocker

mastectomia

cane

meticcio

III

riduzione ernia perineale

cane

yorkshire

11a

mastectomia, detartrasi ed estrazione dentaria

cane

shih-tzu

III

ovarioisterectomia, detartrasi ed estrazione dentaria

cane

meticcio

12a

escissione neoplasia intratoracica

cane

shih-tzu

14a

III

orchiectomia, biopsia cutanea, biopsia epatica ecoguidata

cane

collie

riduzione ernia diaframmatica

cane

barbone

12a

cistotomia, asportazione neoplasia vescicale

gatto

c.e.

riduzione ernia diaframmatica

cane

maremmano

III

mastectomia

cane

doberman

chiusura patent ductus arteriosus

tigre

4,5

chiusura patent ductus arteriosus

cane

dalmata

11a

asportazione neoplasia intracranica

cane

boxer

asportazione neoplasia intracranica

cane

volpino

escissione insulinoma

cane

pastore tedesco

chiusura patent ductus arteriosus

cane

boxer

III

riduzione ernia peritoneopericardica

cane

maltese

1,5

chiusura patent ductus arteriosus

gatto

c.e.

riduzione e fissazione fratture multiple agli arti, caudotomia

cane

meticcio

III

escissione neoplasia palpebrale

cane

boxer

III

rx e biopsia ossea

gatto

c.e.

3.5

riduzione ernia diaframmatica

gatto

c.e.

3,5

ovarioisterectomia

gatto

c.e.

3.8

laparatomia esplorativa per sospetto focolaio settico in addome

gatto

c.e.

entropion

c.e.:comune europeo.

temperatura corporea centrale. 21 pazienti, operati presso le strutture meglio attrezzate, sono stati collegati ad un sistema di monitoraggio integratod per la misurazione di ECG, pressione arteriosa incruenta (metodo oscillometrico) o cruentae, ossimetria pulsatile con pletismogramma, capnometria (sistema “main stream”) con capnogramma e frequenza respiratoria, e ad uno spirometrof per la misurazione di volumi corrente e minuto espirati e rapporto inspirazione/espirazione. Nei pazienti in cui la pressione arteriosa è stata misurata con metodo cruento, sono state eseguite anche misurazioni

Nihon Kodhen Lifescope 14 Bedside Monitor, Nihon Kodhen Co., Tokio, Japan. e Monitoring kit con Transpac IV, Abbott Ireland LTD, Sligo, Rep. of Ireland. f Ohmeda OAV 7710, BOC Co., England.

saltuarie con metodo oscillometrico che hanno fornito dati numerici sovrapponibili. La valutazione clinica e la misurazione della pressione sono state eseguite e registrate come da protocollo ogni 15 minuti e ripetute in corrispondenza di stimoli chirurgici intensi o se necessario. I valori dei parametri misurati “in continuo” sono stati registrati come da protocollo ogni 15 minuti o ad ogni variazione significativa. In ogni paziente è stata valutata la profondità del piano anestetico nel corso dell’intera procedura chirurgica attraverso l’analisi di frequenza del polso, capnometria, diametro e reattività pupillare, lacrimazione e variazioni della pressione arteriosa, e le infusioni sono state modificate in presenza di risposte indesiderate intraoperatorie somatiche e vegetative. Intraoperatoriamente in 2 pazienti si sono verificate delle complicanze imputabili all’esecuzione della procedura chirurgica che hanno reso necessario l’uso di tecniche e farmaci diversi per periodi di tempo limitati, senza che per altro

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questi interferissero nel mantenimento dell’anestesia. Tutti i pazienti sono stati tenuti sotto stretta sorveglianza fino alla dimissione dalla sala risveglio o equivalente, e in 19 di essi è stato valutato il dolore post-operatorio con una scala a punteggio da zero a diecig. Le valutazioni, eseguite con frequenza oraria, si sono protratte per almeno 6 ore dopo il risveglio del paziente o la sospensione degli analgesici quando utilizzati. L’analisi statistica dei dati ottenuti è stata effettuata calcolando, sia per i cani che per i gatti, la media e la deviazione standard dei valori di frequenza cardiaca prima della sedazione (t0), di frequenza cardiaca, pressione arteriosa sistolica e capnometria a 10 minuti dall’induzione (t1), all’incisione della cute (t2) e della fascia (t3), alla sutura della fascia (t4) e della cute (t5), all’estubazione (t6). L’anestesia è stata classificata come efficace quando si è avuta assenza di risposte indesiderate somatiche e vegetative allo stimolo chirurgico o quando, al verificarsi di tali reazioni, si è ottenuto il loro rapido controllo attraverso modificazioni dei tassi di infusione dei farmaci utilizzati per il mantenimento dell’anestesia. Sono state considerate risposte in-

desiderate: variazioni superiori al 30% di frequenza del pol so e pressione arteriosa; variazioni superiori al 30% del valore della capnometria o alterazioni nel profilo dell’onda capnografica; alterazioni di diametro e reattività pupillare; lacrimazione; movimenti riflessi.

RISULTATI La popolazione di pazienti inseriti nello studio è risultata eterogenea e rappresentativa di tutte quelle procedure chirurgiche (Tab. 2) e condizioni preesistenti (Tab. 3) per le quali risulta indicato l’impiego della TIVA. La tecnica ha garantito ipnosi adeg u at a , efficace analgesia, assenza di risposte clinicamente significative anche agli stimoli chirurgici più intensi, immobilità e rilassamento muscolare. I valori di frequenza del polso, pressione art e ri osa, e capnometria espressi come media e deviazione standard sono contenuti nella Tabella 4, distinti in cani e gatti, e non evidenziano ai tempi considerati variazioni significative o comunque riconducibili ad un piano d’anestesia insufficiente. L’incidenza di risposte indesiderate intraoperatorie è stata del 27% (7/26), con prevalenza delle risposte vegetative (Tab. 5), e non si è evidenziata alcuna correlazione tra il mo-

Mathews KA. Pain assessment using a pain scale of zero to ten. Vet Comp Orthop Traumatol 1997; 10:129.

Tabella 3 - Patologie concomitanti o pregresse riscontrate e % sul campione. Patologia

n° pz (%)

Patologia

n° pz (%)

Anemia

3 (11.5)

Ingrandimento camere cardiache

2 (7.7)

Contusione polmonare e miocardia

2 (7.7)

Insufficienza cardiaca valvolare

6 (23)

Epilessia o episodi convulsivi

4 (15.4)

Insufficienza epatica

1 (3.8)

Febbre d’origine sconosciuta

1 (3.8)

Isufficienza ventilatoria

3 (11.5)

Filariosi cardiopolmonare

2 (7.7)

Ipertensione endocranica

2 (7.7)

Fratture multiple

2 (7.7)

Setticemia

2 (7.7)

* Modificata da Romano E (ed). Anestesia generale e speciale. Torino: UTET, 1997,p 113.

Tabella 4 - Valori registrati, espressi come media e (deviazione standard). cani

PA sist

FC/min

101 (24)

ETCO2

121 (15)

132 (14)

130 (15)

125 (15)

130 (15)

97 (18)

109 (20)

94 (20)

100 (20)

107 (22)

37,2 (3,2)

36,6 (3,3)

34,5 (7,8)

35,6 (2,5)

35,7 (2,6)

37,2 (2,2)

PA sist

133 (18)

134 (22)

125 (22)

127 (22)

140 (20)

FC/min

160 (14)

145 (3)

149 (1)

144 (1)

144 (4)

156 (4)

159 (16)

ETCO2*

gatti

• valori registrati in un solo paziente. LEGENDA. PA sist:pressione arteriosa sistolica; FC/min: frequenza cardiaca al minuto; ETCO 2 : CO2 di fine espirazione.

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Tabella 5 - Incidenza delle risposte indesiderate intraopera torie. % pazienti

n° pazienti

Nessuna risposta

Risposta somatica (movimenti)

7.7

Risposta vegetativa

19.3

* Modificata da Romano E (ed). Anestesia generale e speciale. Torino: UTET, 1997, p 113.

mento in cui si sono verificate tali risposte “indesiderate” e il momento in cui è stato applicato uno stimolo chirurgico intenso. Nei 19 pazienti in cui è stato valutato il dolore postoperatorio tale valutazione ha dato esito a punteggi inferiori a 3 in tutti i pazienti (punteggi tra 0 e 1 nel 89.5% del campione).

DISCUSSIONE L’eterogeneità della popolazione di pazienti inseriti nello studio ha permesso di valutare l’efficacia della TIVA in tutte le possibili condizioni d’impiego. L’indagine retrospettiva effettuata ha mostrato assenza di variazioni significative di frequenza del polso, pressione arteriosa, capnometria, alterazioni di diametro e reattività pupillare, lacrimazione, movimenti riflessi anche in presenza di stimoli intensi, e assenza di correlazione tra risposte indesiderate e intensità dello stimolo. Nei casi in cui si è avuta risposta somatica essa non ha interferito con lo svolgimento della procedura chirurgica, ed è sembrata ascrivibile a stimolazione nervosa, mentre le risposte vegetative sono sembrate ascrivibili a risposte vagali alla trazione dei visceri o risposte emodinamiche alla compressione della vena cava. In ogni caso tutte le risposte indesiderate sono state rapidamente controllate senza che si rendesse necessaria una sospensione, seppur temporanea, della procedura chirurgica. Inoltre esse non sono sembrate percentualmente superiori a quelle che si verificano in corso di anestesia generale eseguita con altre tecniche, anche se sembra opportuno ricordare che la bibliografia annovera tra gli inconvenienti della TIVA la maggior difficoltà nel controllare la profondità dell’aneste-

sia rispetto agli anestetici inalatori da parte dell’anestesista poco esperto nella metodica 1. Il monitoraggio dei parametri considerati si è protratto dall’induzione dell’anestesia fino al risveglio estendendosi al periodo pre e post anestetico, fino alla dimissione dalla sala risveglio o equivalente, per quanto riguarda qualità ed efficacia della premedicazione, qualità dell’induzione e del risveglio, tempi di recupero, valutazione del dolore postoperatorio. Ciò ha permesso di valutare la tecnica nella sua globalità, comprendendo periodi temporali estranei all’atto operatorio ma certamente non meno importanti ai fini della ricerca di una anestesia efficace in senso lato. Il riscontro di punteggi inferiori a 3, utilizzando la scala del dolore da 0 a 10 di Mathews, dimostrano l’efficacia della TIVA nel controllare il dolore perioperatorio, confermando che anche in questo essa non ha nulla da invidiare alle tecniche che oggi nel cane e nel gatto vengono utilizzate con maggior frequenza. Tale efficacia è risultata potenziata dall’uso associato, al termine dell’anestesia, di farmaci antinfiammatori non steroidei con elevata potenza analgesica e di tecniche di anestesia locoregionale 1,3 . Tale associazione si è rivelata utile e consigliabile in pazienti sottoposti ad interventi particolarmente invasivi o dolorosi (Tab. 6). Per quanto riguarda il monitoraggio intraoperatorio occorre comunque ricordare che tutti i segni utilizzati durante l’anestesia, che valutano l’attività del sistema nervoso vegetativo, indagano la profondità del piano anestetico in modo del tutto indiretto, e pertanto la loro attendibilità viene considerata dubbia dal momento che molti farmaci utilizzati durante un’anestesia (es. atropina) interferiscono con l’attività autonomica. La disponibilità di un monitoraggio semplice dell’attività cerebrale, la più importante funzione interessata direttamente dal procedimento anestetico, rappresenta a tutt’oggi l’alternativa ideale e ciò spiega la crescente popolarità in anestesia umana del monitoraggio dell’indice bispettrale (BIS), parametro derivato dall’elettroencefalogramma 7. In attesa che anche in medicina veterinaria la validità di tale metodica, per altro già studiata ed applicata in alcuni modelli sperimentali 8, venga definitivamente confermata ci siamo limitati al monitoraggio dei segni classici. In medicina la crescente disponibilità di farmaci endovenosi e le maggiori conoscenze riguardo le interazioni tra gli stessi hanno favorito la popolarità della TIVA e la sua diffusione anche al di fuori delle aree specialistiche, come la chirurgia cardiaca 3 . La vasta bibliografia che ne è scaturita ne ha inequivocabilmente dimostrato la vali-

Tabella 6 - Farmaci utilizzati per il controllo del dolore postoperatorio. Procedura chirurgica

FANS

ALR*

Chiusura Patent Ductus Arteriosus

ketorolac

mepivacaina

Escissione neoplasia palpebrale

ketorolac

lidocaina

Mastectomia

ketorolac

mepivacaina

Toracotomia per riduzione ernia diaframmatica

ketorolac

lidocaina

* Anestesia Loco Regionale.

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dità, arrivando ad affermare trattarsi di una tecnica anestesiologica virtualmente applicabile a tutti i pazienti e a tutte le procedure chirurgiche. Nel cane e nel gatto invece la bibliografia fin qui disponibile ha valutato l’efficacia clinica della TIVA solamente per procedure diagnostiche e terapeutiche di limitata invasività 4,5,6,9,10 . Alcuni studi poi hanno analizzato sperimentalmente alcune interazioni tra farmaci endovenosi e la loro capacità di controllare stimoli algici di intensità crescente. Peculiarità dei risultati da noi ottenuti, se comparati a quelli della bibliografia precedente, è l’estendere la validità della TIVA nel cane e nel gatto alla chirurgia maggiore, una interessante novità per la medicina veterinaria. Rimane da valutare l’aspetto economico, rappresentato dalla differenza di costi per l’acquisto dell’attrezzatura e dalla differenza di costo orario pro chilogrammo dei farmaci utilizzati rispetto all’anestesia isofluoranica bilanciata, attualmente considerata in medicina veterinaria lo standard qualitativo di ri fe rimento 12,13.

Ringraziamenti Ringraziamo il Sig. A. Pimazzoni (el.med.garda s.a.s. corso Don Gnocchi, 53 – 37016 Garda – VR) per il suppor to tecnico fornito per le infusioni.

Parole chiave Anestesia generale – Anestesia totalmente endovenosa (TIVA).

Bibliografia 1. 2.

CONCLUSIONI La TIVA, ottenuta con la combinazione farmacologica di un ipnotico (propofol), un analgesico (fentanil o alfentanil), ed eventualmente un bloccante neuromuscolare non depolarizzante (atracurium) e/o un adiuvante all’anestesia (ketamina), si è rivelata utile ed efficace in quei pazienti nei quali gli agenti inalatori erano controindicati o sconsigliabili, ma si è dimostrata anche una valida alternativa nei casi in cui non si disponeva di un apparecchio per l’anestesia inalatoria. I nostri risultati indicano che, durante l’esecuzione di interventi di chirurgia maggiore nel cane e nel gatto, l’uso della TIVA garantisce un’anestesia generale nelle sue quattro classiche componenti: ipnosi, analgesia, protezione neurovegetativa e miorisoluzione. “L’anestesia esiste da meno di 150 anni, farmaci ane stetici efficaci da meno della metà. La maggior parte degli anestetici endovenosi e delle tecniche attuali da meno di due decadi. Considerati i progressi degli ultimi cinque anni il fu turo dell’anestesia endovenosa, alle soglie del 21° secolo, si preannuncia interessante” Smith I, White PF. Total Intra Venous Anaesthesia. BMJ Books 1998.

5. 6.

7. 8.

10.

11.

12.

13.

Feltracco P, Vincenti E. Anestesia totalmente endovenosa. In: Romano E (ed). Anestesia generale e speciale. Torino:UTET, 1997, pp 253-260 Glass PSA. Intravenous infusion techniques:how to do it and why we should do it. Minerva Anestesiologica 1999; 65:219-231 (Atti SMART 1999) Smith I, White PF. Total Intra Venous Anesthesia. London: BMJ Books, 1998 Hall LW, Peshin PK. Short duration anesthesia for minor procedures in dogs. In Scientific Abstracts from 1996 ACVA meeting. Vet Surg 1997; 26:159 GlowaskiMM, Wetmore LA. Propofol: application in veterinary sedation and anestesia. Clin Tech Small An Pract 1999; 14:1-9 Thurmon JC, Tranquilli WJ, et al. Injectable anesthetics. In: Thurmon JC, Tranquilli WJ, Benson GJ (eds). Lumb & Jones’anesthesia. William & Wilkins, 1996, pp 210-240 Tufano R, Palomba R,et al. Utilità del monitoraggio BIS in anestesia generale. Minerva Anestesiologica 2000; 66(5):389-393 Greene SA, Tranquilli WJ, Benson GJ. Canine bispectral index varies inversely with sevoflurane anesthetic depth. Proceedings 7th World Congress of Veterinary Anaesthesia, Berne 2000, Sep 20-23,p 81 Keegan RD, Green SA. Cardiovascular effects of a continuous twohour propofol infusion in dogs. Comparison with isoflurane anesthesia. Vet Surg 1993; 22:537-543 Wetmore LA, Gowalski MM, et al. Observations on the clinical use of propofol in cats receiving repeated doses of radiation therapy. In: Scientific Abstracts from the 1996 ACVA meeting. Vet Surg 1997; 26:164 Pascoe PJ, Elkiw JE, Fisher LD. Dose response to propofol and propofol/ketamine infusion in cats. In:Scientific Abstracts from the 1996 ACVA meeting. Vet Surg 1997; 26:162 Steffe EP. Inhalation anesthetics. In: Thurmon JC, Tranquilli WJ, Benson GJ (eds). Lumb & Jones’ anesthesia. William & Wilkins, 1996,pp 297-329 Evans AT. The case for manteinance of general anesthesia with an inhalational agent. In: Haskins SC, Klide AM (eds). Opinions in small animal anesthesia. Vet Clin North Am (Small An Pract) 1992; 22:312-313

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Top 10 Secrets for Treating Cats with Cancer! I dieci principali segreti per trattare i tumori nei gatti

Gregory K. Ogilvie DVM, Diplomate ACVIM (Specialties of Internal Medicine, Oncology) Professor and Head of Medical Oncology Animal Cancer Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Ft. Collins, CO 80523 USA

FELINE CUTANEOUS SQUAMOUS-CELL CARCINOMA Incidence, Signalment, and Etiology Squamous-cell carcinomas occur mostly in adult cats especially around the head and neck, and particularly the ears, nose, and eyelids of cats lacking cutaneous pigment. In these locations the tumor is sunlight-induced in the same manner as described for dogs. Siamese cats appear less likely to develop cutaneous squamous-cell carcinoma than other felidae.(1) In a series of 90 cats with nasal planum SCC, 66 cats (73%) had some white skin or hair color.(2)

Clinical Presentation and History On the face and ears of cats lacking cutaneous pigment, there is a clear clinical progression of these lesions. Initially the area is erythematous and may have a waxy, dark crust that is easily removed. These lesions appear histologically as either actinic keratosis (precancer) or as carcinoma in situ (non-invasive cancer). Ulceration progresses if the lesion is untreated, with subsequent invasion and destruction of surrounding structures by the tumor.

Staging and Diagnosis Actinically induced cutaneous squamous-cell carcinoma in cats rarely, if ever, metastasizes. In a series of 90 cats with nasal planum SCC, 6 were found to have metastasis to mandibular lymph nodes and 1 to lungs (2). However, this often occurred late in the course of disease. Regional lymph nodes should be palpated, and fine-needle aspiration or biopsy performed if they are enlarged. Thoracic radiographs are not usually indicated for this tumor in cats. In a study of 90 cats, 17% were found to be in stage T1, 31% as T2, 37% as T3, and 15% as T4.

Prognostic Factors Tumor proliferative fraction, as measured by immunohistochemical detection of Proliferating Cell Nuclear Anti-

gen (PCNA) was found to be prognostic for control of nasal planum SCC in cats treated by radiotherapy.(2) In addition, tumor stage was found to be prognostic for tumor control. Cats with smaller tumors (T1) had not reached a median survival (i.e., fewer than half of the cats had tumor recurrence) but the average was 53 months while larger tumors (T3) were controlled for a median of 9 months(2).

Treatment While the synthetic retinoid 13 cis-retinoic acid has not been shown to reverse pre-neoplastic changes for SCC in cats,(3) newer retinoids such as etretinate have not yet been evaluated in this species. In view of the efficacy of etretinate in dogs, it would seem logical that these newer retinoids may also show efficacy for feline preneoplastic squamous-cell carcinoma. Resection of the pinna for aural SCC is effective in the majority of cats if adequate resection is achieved. Essentially the entire pinna should be removed. However, these tumors may recur locally, as can SCC of the eyelids and nasal planum. Actinically induced SCC in the cat is very sensitive to radiation therapy. Precancerous plaques and early lesions may be treated with brachytherapy radiation (e.g., strontium-90) at a single high dose. In a group of 25 cats treated with strontium-90, nearly 90% were free of tumor at one year with an average tumor-free period of 34 months. (4) Local current-field radiation hyperthermia (50oC for 30 seconds) was very effective in causing tumor regression in superficial SCC of cats.(5) Of 19 cats with SCC, 13 (68%) had complete regression. Tumors that did not extend 2 mm or deeper in tissue responded best. Duration of response was observed for only 2 to 6 months. For more advanced lesions, external-beam teletherapy produces long remissions. It should be remembered, however, that the cat is still susceptible to acquiring new tumors from sunlight exposure, and its behavior should be appropriately modified. Preferably cats should be protected from sunlight exposure during the middle part of the day. Ninety cats with SCC of the nasal planum were treated with orthovoltage-radiation therapy to a dose of 40 Gray in 4-Gray fractions(2). The median control of tumors for these cats was 14 months. However, advanced tumor stage (i.e., larger tumors) affected outcome adversely (see above). Fifteen cats whose tumors recurred were re-irradiated successfully.

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Two rapid freezes and 2 slow thaws with liquid nitrogen cryotherapy with a contact applicator is generally very ef fective for controlling nasal squamous cell carcinomas less than 1 cm in diameter.

Cryotherapy has been recommended as a treatment for SCC of the face in cats. In one study, however, this modality was consider ably less effective than either surgery or radiation therapy in achieving local tumor control(6). Eleven of 15 cats had local tumor recurrence within a median of 6 months after cryotherapy. We recently completed a study involving 87 cats with squamous cell carcinomas of the head that were treated with cyrotherapy. The median disease free interval was 14 months. Cats that had lesion less than 1 cm in diameter had a much higher probabillity of having tumors controlled than those with larger tumors. Therefore, we recommend that tumors that are larger than 1 cm in diameter be treated with other procedures other than cryothetherapy. Reminder: Cisplatin can cause severe, fatal pulmonary edema and pleural effusion if administered systemically. Therefore, Photodynamic therapy has been shown to be quite effective in controlling this tumor in cats. In one study, 7 of 11 feline SCCs of the pinna or nasal planum completely resolved using a chloroaluminum sulfonated-phthalocyanine photosensitizer, and 5 of these responses lasted 44 weeks or longer.(7) In another trial using aluminum phthalocyanine tetrasulfonate, long-term (3 to 18 months) responses were seen in 12 of 17 patients(8). However, toxicities, including 1 fatality, were more prevalent in this study. Paradoxically, cisplatin was used successfully in a unique collagen-matrix intralesional implant system to treat 118 feline squamous-cell carcinomas(1). In this study, 83% of cats had a > 50% reduction in tumor volume and 64% had complete resolution after 6 treatments. The lack of systemic toxicity seen in these cats was ascribed to the depot nature of the treatments and subsequent slow release of cisplatin. Sterilized sesame oil appears to function as a similar vehicle to collagen matrix, and may be used at a dose of 2 ml of sesame oil to 10 mg cisplatin in 1 ml of saline.(9) Mitoxantrone chemotherapy rarely brings objective response in feline oral SCC, but could be considered as an option for metastatic skin lesions.(10) When combined with external-beam radiation therapy, mitoxantrone has been shown to control oral SCC for a median of 170 days, which is sub-

If cryotherapy or intralesional chemotherapy is not indicat ed, a nosectomy procecure is well accepted by most cats and their owners for the treatment of squamous cell carcinoma of the nasal planum.

stantially longer than when either modality is used alone.(11) Three cats with dermal SCC showed partial responses of short duration to bleomycin chemotherapy.(12) Carboplatin is a new cisplatin-like compound that may be of value for treating metastatic squamous cell carcinoma. Alan Theon recently reported that when a carboplatin/sesame seed oil compound was used to treat cats with squamous cell caricinoma, the results were excellent.

Oral Squamous-Cell Carcinoma in Cats In contrast to the situation in dogs, oral SCC in cats is a highly aggressive disease that responds poorly to surgical treatment or to radiation therapy regardless of its location in the mouth. The longest control and survival rates have been obtained using a combination of radiation therapy and mitoxantrone chemotherapy.(11) The biggest problem for cats that have oral squamous cell carcinomas is that they do not maintain an adequate plane of nutrition. Appetite stimulants and very aromatic foods should be used whenever possible. Care should be

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ROUND (DISCRETE) CELL TUMORS This group of tumors may equally be called discrete cell tumors, and their appearance on cytologic preparations is that of clumps or individual cells that are round in appearance without obvious attachment to other cells. Round cell tumors include mast cell tumors, histiocytoma, lymphoma, plasmacytoma and transmissible venereal tumor.

MAST-CELL TUMORS Introduction Splenic mast cell tumors differ in the cat from the dog in that if it is just localized to this structure, resection can result in survival that exceeds 1 year.

taken when feeding baby foods because they often contain onion powder that can cause heinz body anemia. Carboplatin chemotherapy with or without radiation therapy appears to be resulting in good efficacy. The single most important prognostic feature appears to be bone involvement.

HEMANGIOMA-HEMANGIOSARCOMA IN CATS Incidence, Signalment, and Etiology Cutaneous hemangiomas and hemangiosarcomas are rare in cats, and occur mainly in older animals. This tumor is similar to squamous-cell carcinoma in that it is actinic, or sunlight-induced. Cutaneous hemangiosarcoma occurs commonly in cats from areas where actinically induced tumors are common(18) (California, Missouri, Florida), but not in cats from the northeastern United States.(18,19,20)

Masses composed of mast cells can be either reactive or neoplastic, and this can pose certain problems in nomenclature. Mast-cell tumors are a very common neoplasm of the and cat. Mast cells contain dark-staining granules that contain histamine, heparin, and other vasoactive amines. These characteristic granules make recognition of mast-cell tumors on cytology relatively simple. For further information please refer to the Mast Cell Tumor section.

MAST-CELL TUMORS IN CATS Incidence, Signalment, and Etiology Mast-cell tumors were the only cutaneous tumor diagnosed in cats younger than one year in one study.(1) In the same study, Siamese cats were three times more likely to develop cutaneous mast-cell tumors. Tumors in Siamese cats are usually subcutaneous and composed of "histiocytic" cells. These tumors may regress without therapy.(24)

Clinical Presentation and History The most common cutaneous mast cell tumors in cats are single, firm, and circumscribed dermal nodules.(25) Appearance of multiple similar masses is the next most common presentation. These tumors are usually histologically well-

Clinical Presentation and History Feline hemangiomas appear as solitary tumors in the dermis and subcutis without any site predilection. In contrast, feline hemangiosarcomas may have a predilection for the head (ear tips, nasal planum) and also have a predilection for non-pigmented skin. (17) They are usually solitary.

Treatment Surgical excision of cutaneous hemangioma usually has a good prognosis, although local recurrence following surgical excision of cutaneous hemangiosarcoma is frequent. Metastasis appears to be rare. It is there fo re app ro p ri ate to treat this tumor as a soft-tissue sarcoma in cats, with aggressive initial surgery as the best therapeutic approach.

Generalized mammary gland enlargement in a young cat that is not spayed may quite likely be fibroepithelial hyper plasia. These spontaneously resolve.

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differentiated and have a benign clinical course.(2) While most cutaneous MCTs in the cat are benign, in some studies, cutaneous tumors are associated with malignant disease evidenced by visceral involvement.(25,26) Lymphoreticular mastcell tumors are often seen in cats, with marked splenomegaly the most common finding. Diffuse cutaneous disease may occur with this form of MCT. Mastocythemia and bone-marrow involvement are seen in many of these cats, and the presenting signs of vomiting and anorexia are presumably owing to tumor degranulation. Intestinal mast-cell tumors have been described in cats; they are always malignant.

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The suspicion of MCT in a chronically vomiting cat with marked splenomegaly can be confirmed by fine-needle aspirate of the spleen. Less frequent sites for lymphoreticular mast-cell tumors in cats are the mediastinum (with resultant pleural effusion) and lymph nodes. These cats often have high numbers of circulating mast cells as well as anemia and other cytopenias from bone-marrow infiltration and erythrophagocytosis by malignant cells.

neoplasms and skin tumors. The incidence of mammary tumors in the cat is less than half that of dogs. Although there is no proven breed-associated predilection for mammary tumors, some investigators have suggested that domestic short-haired and Siamese cats have higher incidence rates than other cats. Siamese cats may have twice the risk of any other breed of developing mammary tumors. Mammary neoplasia has been reported to occur in cats from nine months to 23 years of age, with a mean age of occurrence of 10 to 12 years. One study suggests that the disease occurs at an earlier age in Siamese cats and the incidence reaches a plateau at about nine years of age. The majority of affected cats are intact females,however the disease is occasionally seen in spayed females and rarely in male cats. More than 80% of the feline mammary tumors are histologically classified as adenocarcinomas. The frequency of diagnosis of the specific types of adenocarcinomas differs slightly among pathologists, but most agree that tubular, papillary, and solid carcinomas are the most common. The majority of the adenocarcinomas have a combination of tissue types in each tumor. Sarcomas, mucinous carcinomas, duct papillomas, adenosquamous carcinomas and adenomas are rarely seen.

Treatment

Clinical Presentation and History

The treatment of choice for cutaneous MCT in cats is surgery; for solitary tumors, a good prognosis can usually be given. Some cats may develop multiple well-differentiated tumors, and these cats may be treated with multiple palliative surgeries or corticosteroids (1 mg/kg prednisone daily). For invasive or incompletely excised MCTs, radiation therapy appears to be a successful adjunct to surgery; however, data regarding tumor control and patient survival are not as well established as for dogs. Mitoxantrone caused a partial response in a feline mastcell tumor, but the drug has not been further evaluated for the treatment of this disease.(10) The treatment of choice for lymphoreticular MCTs in cats is splenectomy; long-term survival occurs in many cats receiving no other therapy. Response to splenectomy seems greater than would be explained by simple tumor mass reduction, as hematologic and other organ involvement apparently resolve. It is possible that splenic suppressor-cell activity may be reduced after splenectomy allowing for some control by the cat's immune system. For this reason the use of postoperative corticosteroids in these cats in controversial.(27.28)

Cats with mammary tumors are often presented to the veterinarian five months after they were initially noted. Thus, the tumors are usually in an advanced state of development when they are handled clinically. The mammary tumor often appears as a locally invasive mass that has metastasized frequently. The neoplasm may adhere to the overlying skin but rarely is adhered to the underlying abdominal wall. The tumor is usually firm and nodular. At least onequarter of affected patients have ulcerated masses. The infiltration of lymphatics may be clinically apparent as subcutaneous linear, beaded chains. Swelling due to tumor thrombi or decreased vascular return can cause discomfort, edema, and a change in the temperature in the pelvic limbs. The involved nipples are red and swollen and may ex-

Staging and Diagnosis

MAMMARY ADENOCARCONOMA Background Owners frequently present their cat with mammary mass for a “skin condition on the underside”. When a cat with a mammary mass is presented, a malignancy must be considered. At least 70-90% of feline mammary tumors are malignant. Mammary tumors are known to be at least the third most frequently occurring tumor in the cat, following hematopoietic

Radical mastectomy of the entire chain, not regional lumpec tomy is essential for local control for cats with mammary adenocarcinoma.

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udate a tan or yellow fluid. The tumor can involve any or all mammary glands and is noted equally in the left and right sides. A slightly higher incidence has been noted in the cranial two glands by some investigators. More than half of the affected cats have multiple-gland involvement. These tumors can be associated with chronic mastitis, uterine disease, and other unrelated tumors, as well as anemia, osteoporosis, ascites, and leukocytosis.

Staging and Diagnosis Before any diagnostic or therapeutic steps are taken, the health status of the cat must be fully assessed. A chemical screen, urinalysis, and a complete blood count should be done to identify any presurgical abnormalities. In several studies, more than 80% of the cats with a mammary malignancy had metastases to one or more of the following organs at the time of euthanasia; lymph nodes, lungs, pleura, liver, diaphragm, adrenal glands, and kidneys. (31-33) Thoracic radiographs in both the right and left lateral and ventrodorsal planes should be made to search for pulmonary, lymph node, and pleural metastases. Mammary tumor pulmonary metastases appear radiographically as interstitial densities. They range from those that are faintly seen, to those that are several centimeters in diameter, to miliary pleural lesions that can produce significant effusion. Sternal lymphadenopathy is occasionally seen. Whenever regional lymph nodes are evaluable, they should be assessed by fine needle aspiration cytology or biopsy. Aging changes in the lungs and pleura as well as inactive inflammatory lesions may stimulate metastatic disease. Treatment should not be withheld because of equivocal radiographic findings. Because of the high frequency of malignancy, an aggressive approach should be taken to confirm the diagnosis. A preliminary biopsy is not recommended unless it will change the owner's willingness to treat or the surgical procedure. Tissue for histopathology is taken at the time of mastectomy and should include the regional lymph nodes. If pleural fluid is removed from a cat with a mammary gland lesion, cytology should be done on the fluid to search for malignant cells. A variety of nonmalignant lesions must be considered in a differential diagnosis of mammary neoplasia. The most common benign growths are classified as cysts, papillary cystic hyperplasia, lobular hyperplasia, and mastitis. Fibroepithelial hyperplasia is a common benign lesion involving one or more glands and is frequently seen one to two weeks following estrus. The gland may be so large that the patient may walk with an abnormal gait and the skin overlying the mass may be discolored, *edematous, and painful. Cats with fibroepithelial hyperplasia are often young, intact females. The signs are similar to those seen with most malignant tumors. Because the benign masses closely resemble malignant neoplasms, they are often treated as malignancies.

Prognostic Factors In the last 20 years, little progress has been made in extending the survival time of canine and feline mammary tu-

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mor patients. Because stromal invasion is almost always present and metastases are frequently present at the time of surgery, a guarded to poor prognosis should always be given. Sixty-six percent of the cats that have had their tumors surgically excised have a recurrence at the surgical site. Most studies state that the time from tumor detection to the death of the cat is rarely over 12 months. The most significant prognostic factors influencing tumor recurrence and survival for cats with malignant mammary neoplasia are tumor size, the extent of surgery needed to remove the tumors, and histologic grading of the tumors. MacEwen has shown that tumor size is the most important of these prognostic factors. Following surgery, the median for survival for cats with tumors > 3 cm in diameter is 6 months; for cats with tumors 2 to 3 cm in diameter, the median for survival following surgery is 2 years; and for cats with tumors < 2 cm in diameter, the median for survival after surgery is approximately 3 years. Radical surgery, when compared with regional "lumpectomy", has been shown to reduce local tumor recurrence but not to increase the overall time of survival. Cats with well-differentiated tumors with few mitotic figures per high- power field live longer compared with those with tumors that are not as well-differentiated histopathologically. The one-year survival rate was high in cats with a tumor that did not show lymphatic infiltration. There is a good correlation between the grade of malignancy, method of growth, and prognosis. Patients with pulmonary metastatic disease rarely survive longer than two months. Mammary neoplasms in the cat have been treated in a variety of ways however, surgery is the most widely used treatment. There have been no reports documenting the efficacy of radiation therapy or commercially available biological response modifiers for the treatment of this disease. The biological response modifier, liposome-encapsulated muramyltripeptide-phosphatidyethanolamine (L-MTP-PE) may not be effective when used in combination with surgery or chemotherapy. The success of surgery is hindered by the invasive nature of the disease and its tendency for early metastasis. Radical mastectomy (i.e. removal of all glands on the affected side) is the surgical method of choice because it significantly reduces the change of local tumor recurrence. This procedure is frequently utilized regardless of the size of the tumor. Several surgical principles are observed when performing a mastectomy on feline mammary tumor patients. During or prior to surgery, a bacterial culture and antibiotic sensitivity testing may be indicated because of approximately one-fourth of mammary carcinomas are ulcerated. An en bloc resection is often employed in such a way that the tumor and draining nodes and vessels are removed by wide surgical excision and a partial or complete resection of the underlying tissue is done. If bilateral mastectomy is indicated, the affected glands and their associated lymph nodes are removed and a second surgery is performed 10 to 14 days later, the interim allows the skin to stretch for a complete closure at the second surgery. Early vessel ligation is essential; one study noted that two-thirds of the cases examined had tumor invasion of lymphatics and veins. Gentle handling of all damaged tissue is essential. Copious flushing of the

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VACCINE ASSOCIATED SARCOMAS

Very large resections, often including the dorsal spinous processes is needed to completely remove vaccine associat ed sarcomas of the intrascapular region.

surgery area after the tumor is removed helps eliminate exfoliated neoplastic cells. Although spaying has been shown not to decrease the incidence of recurrence, some believe that it is warranted because of the occasionally seen coexisting ovarian and uterine disease. (33) If the mammary mass is due to a benign condition such as fib ro epithelial hyperplasia, spaying often results in regression of the hyperplastic tissue. Regression may take up to five months. This condition often resolves spontaneously within a few weeks of diagnosis; in some cases without p e r fo rming an oophorectomy.

Radiation therapy Radiation therapy is not used routinely to treat feline mammary tumors. Presentl y, there are no major claims that radiation dramatically increases the survival rate of feline mammary tumor patients, however it may reduce local recurrence rates.

Chemotherapy Chemotherapy, alone or in combination with surgery, is not as successful for feline mammary tumors as it is for other feline tumors such as lymphoma. Cyclophosphamide has been used alone or in combination with other chemotherapeutic agents and has not consistently helped the feline mammary tumor patient. The combination therapy of doxorubicin and cyclophosphamide has been shown to induce short-term partial and complete responses in 50% of cats with metastatic or nonresectable local disease. This chemotherapeutic protocol has been shown to be toxic in some cats and does not prolong survival. Other drugs that may be used include mitoxantrone and taxol. The role of the later two drugs is still being elucidated, however both have some efficacy in cats with malignant neoplasia. Further studies are necessary to quantify the benefit of adjunctive therapy for mammary neoplasia in cats. Chemotherapy should be used by practitioners that are familiar with the use of these drugs and their side effects.

Recent epidemiologic studies have associated the administration of a number of vaccines and the development of soft tissue sarcomas in the cat. Vaccines have also been associated with hematological or immunological diseases. Perhaps the most disconcerting problem is the vaccine associated malignancy problem. In a recent epidemiologic study,(34,35) sarcomas were temporally associated with previous injection of various vaccines into specific body locations. Feline leukemia virus, rabies vaccination, and development of fibrosarcomas at the injection site within a year following vaccination were statistically associated. This study demonstrated a 5.5% increased risk of developing sarcomas in response to feline leukemia virus vaccination and a twofold increase in risk of development of sarcomas after rabies vaccination. The actual incidence of the tumor was estimated to be approximately one sarcoma per 10,000 feline-leukemia virus and rabies vaccines administered. No association between sex ,b re e d, and concurrent viral infections in the development of these sarcomas was found. The aluminum adjuvant in many of these vaccines may be associated with development of vaccine-associated sarcomas.(35-37) However, Kass, et al.,(35) demonstrated that certain aluminum-free vaccines may also be associated with development of these soft-tissue sarcomas. Increase in development of soft-tissue sarcomas following one vaccination was 50%, following two vaccinations was 127%, and following three or four vaccines simultaneously administered at the same location was approximately 175%.(35) Therefore, there appears to be a multifactorial association between vaccines and growth of sarcomas.(34,37) The development of sarcomas in response to vaccines, especially those that contain aluminum as an adjuvant, may suggest an association between foreign bodies and the growth of these neoplasms. This is not a new observation. Indeed, other metals such as arsenic, chromium, and nickel have been shown under an array of conditions to induce sarcoma formation.3,8 Histologically, vaccine-associated sarcomas are enveloped in dense, fibrous connective tissue and infiltrated with inflammatory lymphocytes and macrophages. Macrophages often obtain bluish-gray foreign material that electron-probe x-ray microanalysis identifies as aluminum and oxygen.(35,36) Other tumors develop in apparent association with other foreign bodies. For example, ocular sarcomas have been associated with foreign material in the eye.(38) In addition, osteosarcomas have been associated with metallic implants. Despite the compelling information, no specific etiology has been determined for the development of these sarcomas, only causal association. Additional research must answer the question of etiopathogenesis. Vaccine associated soft-tissue sarcomas are frequently located in such areas of previous vaccination as between the shoulder blades and in the hind leg. A diagnosis is made by fine-needle aspirate cytology or, preferably, incisional biopsy. The clinician should keep in mind that these soft-tissue sarcomas are encased in a pseudocapsule that is actually compressed tumor tissue. In addition, tendrils of tumor extend far beyond the site of palpable tumor. Radiation is very important for the treatment of cats with vaccine associated sarcomas. This may be given before or after surgery and is given along with chemotherapy in most cases.

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Treatment must be aggressive regardless of tumor size. These soft-tissue sarcomas are extremely aggressive and extend far beyond the palpable site. While the most effective treatment is not known, surgery should be employed whenever possible. In each case, extremely wide and deep surgical margins (> 3 cm), including all the soft-tissue structures and, if appropriate, any bony structures in the region of the postvaccinal sarcoma should be obtained. Essentially, the tumor and a large “cuff” of normal tissue surrounding the mass should be removed en bloc. All lateral and deep margins should be marked and submitted for histopathology after appropriate formalin fixation to determine presence of residual neoplastic disease. In some veterinary oncology centers, presurgical radiation therapy is routine to minimize the amount of viable tumor around the palpable tumor. If recurrence is noted or suspected after surgical removal of the tumor, radiation therapy can be directed widely around the surgery site. In addition, doxorubicin may be effective for controlling local disease for a period of time. In some centers, surgery, radiation therapy, and chemotherapy are used in conjunction to control this tumor. Until more effective treatments are known, the following recommendations may help prevent development of postvaccinal sarcomas: 1) avoid administering multiple vaccines in the same site; 2) administer vaccines in extremities (Rabies Right; Leukemia Left, FVRCP in the right shoulder) that may allow amputation as an effective treatment; 3) remove postvaccinal granulomas that persist several months after vaccination; and 4) continue research on different adjuvants to reduce the development of vaccine-induced sarcomas. Finally, many have questioned the wisdom of administering vaccines on a yearly basis,especially when using multivalent products

References 1. 2.

5. 6.

Miller MA, Nelson SL, Turk JR, Pace LW, Brown TP, Shaw DP, Fischer JR, Gosser HR. Cutaneous neoplasia in 340 cats. Vet Pathol 28: 389-395,1991. Brooks MB, Matus RE, Leifer CE, Alfierir AA, Patnaik AK. Chemotherapy versus chemotherapy plus radiotherapy in the treatment of tonsillar squamous cell carcinoma in the dog. J Vet Internal Med 2: 206-211,1988. Theon AP, Madewell BR, Shearn V, Moulton JE. Irradiation of squamous cell carcinomas of the nasal planum in 90 cats. Proc 13th Annual Conf Veterinary Cancer Soc. 147-148, 1993. Evans EG, Madewell BR, Stannard AA. A trial of 13-cis-retinoic acid for treatment of squamous cell carcinoma and preneoplastic lesions of the head in cats. Am J Vet Res 46: 2553-2557,1985. VanVechten MK, Theon AP. Strontium-90 plesiotherapy for treatment of early squamous cell carcinomas of the nasal planum in 25 cats. Proc 13th Annual Conferinary Cancer Soc 107-108, 1993. Grier RL, Brewer WG, Jr., Theilen GH. Hyperthermia treatment of superficial tumors in cats and dogs. J Am Vet Med Assoc 177: 227-233,1980. Atwater SW, Powers BE, Straw RC, Withrow SJ. Squamous cell carcinoma of the pinna and nasal planum. Fifty-four cats 91980-1991). Proc Vet Cancer Soc 11th Annual Conf 1991, 35-36. Roberts WG, Klein MK, Loomis M, al et. Photodynamic therapy of spontaneous cancers in felines, canines, and snakes with chloro-aluminum sulfonated phthalocyamine. J Natl Cancer Inst 83: 18-23,1993. Peaston AE, Leach MW, Higgins RJ. Photodynamic therapy for nasal and aural squamous cell carcinoma in the cat. J Am Vet Med Assoc 202: 1261-1265,1993. Theon AP, Pascoe JR, Carlson GP, Krag DN. Intratumoral chemotherapy with cisplatin in oily emulsion in horses. J Am Vet Med Assoc 202: 261-266,1993.

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11.

12. 13.

14. 15.

16. 17. 18.

19.

20.

21. 22.

23. 24. 25. 26. 27.

28.

29. 30.

31. 32.

33.

34. 35. 36.

37. 38. 39. 40.

Ogilvie GK, Moore AS, Obradovich JE, Elmslie RE, al et. Toxicoses and efficacy associated with the administration of mitoxantrone to cats with malignant tumors. J Am Vet Med Assoc, 202:1839-1844,1993. LaRue SM, Vail DM, Ogilvie GK, al et. Shrinking-field radiation therapy in combination with mitoxantrone chemotherapy for the treatment of oral squamous cell carcinoma in the cat. Proc. Eleventh Annual Conference of the Veterinary. Cancer Society, Minneapolis, MN Oct. 27-29, 1991. 99, Kalaher KM, Anderson WI, Scott DW. Neoplasms of the apocrine sweat glands in 44 dogs and 10 cats. Vet Record 127: 400-403,1990. London CA, Dubielzig RR, Ogilvie GK, al et. Ear canal tumors of dogs and cats: preliminary results of a VCOG retrospective study. Proc Vet Cancer Soc 13th Annual Conf, 1993,59-60. , Theon AP, Barthez PY, Madewell BR, Griffey S. Radiation therapy of ceruminous gland carcinomas in dogs and cats. J Am Vet Med Assoc, in press. Marino DJ, MacDonald JM, Matthiesen DT, Patnaik AK. Results of surgery in cats with cervminous gland adenocarcinoma. J Am Anim Hosp Assoc 30: 54-58,1994. Little CJL, Pearson GR, Hurvitz AI. Neoplasia involving the middle ear cavity of dogs. Vet Record 124: 54-57,1989. Hahn KA. Vincristine sulfate as single-agent chemotherapy in a dog and a cat with malignant neoplasms. J Am Vet Med Assoc 197: 796-798,1990. Miller MA, Ramos JA ,K re ager JM. Cutaneous vascular neoplasia in 15 cats:Clinical,morphologic and immunohistochemical studies. Vet Pathol 2 9 :3 2 9-336,1992. Scavelli TD, Patnaik AK,Mehlaff CJ, Hayes AA. Hemangiosarcoma in the cat: retrospective evaluation of 31 surgical cases. J Am Vet Med Assoc 187: 817-819,1985. Carpenter JL, Andrews LK, Holzworth J. Tumors and tumor-like lesions. In: Diseases of the cat: Medicine an Surgery, ed Holzworth J, WB Saunders Co, Philadelphia, PA, pp. 406-596, 1987. Lawler DF, Evans RH. Multiple hepatic cavernous lymphangioma in an aged male cat. J Comp Path 109: 83-87, 1993. Stobie D, Carpenter JL. Lymphoangiosarcoma of the mediastinum, mesentery and omentum in a cat with chylothorax. J Am Anim Hosp Assoc 2 9 :7 8-80,1993. Aronsohn MG, Carpenter JL. Distal extremity melanocytic nevi and malignant melanomas in dogs. J Am Anim Hosp Assoc 26:605-612, 1990. Wilcock BP, Yager JA, Zink MC. The morphology and behavior of feline cutaneous mastocytomas. Vet Pathol 23: 320-324,1986. Scott DW. Feline dermatology 1900-1978: a monograph. J Am Anim Hosp Assoc 16: 331-459,1980. Garner FM, Lingeman CH. Mast cell neoplasms of the domestic cat. Path Vet 7: 517-530,1970. Liska WD, MacEwen EG, Zaki FA ,G avery M. Feline sytemic mastocytosis: a review and results of splenectomy in seven cases. J Am Anim Hosp 15: 589-597, 1979. Andrews LK. Tumors and tumor-like lesions: mast cell tumors. In: Diseases of the cat (J. Holzworth, ed) WB Saunders Co, Philadelphia, PA 569-579,1987. Moore PF, A Rosin. Malignant histiocytosis of Bernese Mountain Dogs. Vet Pathol 23: 1-10,1986. Schmidt ML, Rutteman G, Wolvekamp P. Canine malignant histiocytosis (MH): Clinical and radiographic fundings. Tijdschrift voor Diergeneeskunde 117(suppl 1): 43-44,1992. Ogilvie GK, Moore AS. Mammary Neoplasia. Managing the Veterinary Cancer Patient. trenton NJ, Veterinary Learning Systems. 1995, 430-440. Ogilvie GK, Moore AS. Mitoxantrone chemotherapy in veterinary medicine. In: Current Veterinary Therapy XI. Kirk RW (ed), WB Saunders, Philadelphia, pp 399-401, 1992. Ogilvie GK: Principles of Oncology. In Handbook of Small Animal Internal Medicine. Morgan RV (ed) Churchill & Livingston, Philadelphia, 1992,799-812. Ogilvie GK. Feline Mammary Neoplasia. In, Feline Medicine and Surgery, Veterinary Learning Systems, Trenton, NJ, 1994:74-83. Hendrick MJ, Kass PH, McGill D, Tivard IR. Postvaccinal sarcomas in cats. J Natl Canc Inst 86:341-335, 1994. Kass PH, Barnes WG, Spangler WL, et al. Epidemiologic evidence for a causal relation between vaccination and fibrosarcoma tumorigenesis in cats. J Am Vet Med Assoc 203:396-405, 1993. Esplin DG, McGill LD, Meninger AG, et al. Postvaccinal sarcomas in cats. J Am Vet Med Assoc 202(8):1245-1247, 1993. Hendrick MJ, Brooks JJ. Postvaccinal sarcomas in the cat:histology and immunohistochemistry. Vet Pathol 31:126-129, 1994. Macy DM. Vaccine-associated sarcomas. Proceedings 12th Annual Veterinary Medical Forum - ACVIM. San Francisco, CA pp 854-856, 1994. Sinibaldi K, Rosen H, Liu S, et al. Tumors associated with metallic implants in animals. Clin Orthop Rel Res 118:257-266, 1976.

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Compassionate Cancer Diagnostics: New Diagnostic Tests for the Practitioner (aka: Three Golden Rules to Oncology-Biopsy! Biopsy! Biopsy!) Nuovi mezzi diagnostici a disposizione del veterinario pratico nella clinica oncologica

Several types of biopsies exist. A small core of tissue is obtained with a needle punch biopsy. A portion of the tumor is removed (generally the junction of normal and abnormal tissue) for an incisional or "wedge" biopsy. Incisional biopsies are preferred in cases where punch or needle biopsies cannot provide adequate tissues. Regardless, the biopsy must be performed so that it will not compromise subsequent curative resection. The entire tumor is removed in an excisional biopsy. Excisional biopsy is preferred in cases where knowledge of the tissue type would not change the definitive procedure (e.g. a solitary lung mass or a splenic mass). A preoperative biopsy should be performed prior to definitive therapy if: 1) the results will alter the type of therapy to be employed, or 2) the results will influence the owner's willingness to treat. 1

GUIDELINES1,2 • Biopsies do not negatively influence survival • A biopsy should be performed after consultation with the surgeon who will perform the surgery. • Obtain as large a sample as possible to enhance correct diagnosis by the pathologist. • The original architecture of the removed tissue should be maintained, therefore electrocautery or surgical instruments that crush or otherwise damage tissues should not be used. • Ensure the tissue is adequately fixed in 10% buffered neutral formalin (1:10 parts fixative). • Each biopsy should be placed into a separate, properly labeled container. • When possible, the entire lesion that has been resected and prepared properly should be submitted. • Biopsies should be submitted to a highly qualified veterinary pathologist.

cept, perhaps with bone marrow aspiration and biopsy. Therefore, before each biopsy, hemostatic abnormalities should be identified and corrected. Infection at the local biopsy site or sepsis is an uncommon but serious problem that must be avoided by strict aseptic technique. Lastly, a biopsy should not be performed if it would put the success of a definitive procedure at risk.

BIOPSY AS A PRELUDE TO DEFINITIVE THERAPY A palpable persistent mass or dominant nodule is the most common indication for biopsy as a prelude to definitive therapy.1-3 Because accuracy and sensitivity of diagnostic tests are improving, biopsies are being performed with increasing frequency to clarify the etiology of nonpalpable masses. When developing a diagnostic strategy for a pet with cancer, the clinician must consider the subsequent management of the disease.3 The first step in management of most palpable lesions is fine-needle aspiration cytology. If the cytologic diagnosis strongly suggests a malignant condition, a definitive procedure such as surgery can then be planned. Fine needle aspiration cytology can also confirm the presence of a benign process, eliminating the need for further diagnostic steps. If fine-needle aspiration cytology is not definitive then an open biopsy should be performed, guided by the surgeon who will perform the indicated surgery. Prior to a biopsy procedure, standard staging procedures must be performed to identify any concurrent disease and to identify any clinically evident metastatic disease. Staging is accomplished by certain diagnostic tests that determine the extent of the neoplastic disorder. The staging scheme often differs for each neoplastic disease, but often includes a complete blood count, biochemical profile, urinalysis, chest radiographs and cytologic evaluation of regional lymph nodes.

CONTRAINDICATIONS SKIN BIOPSY In each case, the risks and benefits of the biopsy should be evaluated and clearly described to the owner. In most cases, the risks are minimal. Uncontrollable hemorrhage is the most common complication with all biopsy procedures ex-

Baker’s biopsy punches are easy to use by obtaining superficial biopsies. The instrument (A) is placed on the tumor and then rotated in one direction (B) until the desired depth

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One contraindication for performing a biopsy is not know ing the anatomic sites that may result in serious problems. In this case, a nasal biopsy is obtained with a tube attached to a syringe. The cribriform plate (A) is the anatomic site of great importance when performing a nasal biopsy. One contraindication for performing a biopsy is not know ing the anatomic sites that may result in serious problems. In this case, a nasal biopsy is obtained with a tube attached to a syringe. The cribriform plate (A) is the anatomic site of great importance when performing a nasal biopsy.

is reached. Then the instrument is angled at a 45 degree angle while rotating the handle to “cut” off the base. A skin biopsy is essential to diagnose and evaluate potentially malignant skin conditions. Punch, incisional, excisional, and needle core biopsies are employed.1-3

PUNCH BIOPSY 1,3 Biopsy punches are disposable and available in diameters ranging from 2 mm to 6 mm. Generally, the larger biopsies are preferred so the pathologist has adequate tissue to make a histologic diagnosis. When possible, the junction between normal and abnormal tissue should be biopsied. Punch biopsies are usually inadequate to obtain tissue below the dermis; subcutaneous fat is rarely obtained in the average punch biopsy of the skin. Indication: Any dermal or epidermal lesion of unknown etiology.

The biopsy punch is placed at right angles to the skin surface. 6. The punch is rotated in one direction while at the same time firm downward pressure is applied until the subcutis is reached. 7. The punch is then angled almost parallel with the skin while still applying pressure along the long axis of the biopsy punch. 8. The punch is rotated to sever the base of the biopsied material. 9. The punch is removed. 10. The core of tissue is gently elevated with the point of a needle and the base severed with scalpel or iris scissors. 11. One to two sutures are placed to close the defect.

INCISIONAL BIOPSY 1-3 In some cases, the incisional biopsy is preferred over a punch biopsy because larger sections of tissue can be obtained for histologic diagnosis. In addition, if the lesion is biopsied at the junction of the normal and abnormal tissue, a "wedge" of tissue is obtained that retains a larger section of the tissue's architecture. This allows the histopathologist to better see characteristics of malignancy, such as invasion of normal tissue.

Technique Technique 1. The hair is clipped and the surgery site prepared with a surgical scrub. 2. Using a 25 gauge needle, approximately 2 to 3 mls of the local anesthetic agent lidocaine are injected around the lesion. It is important to not distort or disturb with lidocaine, the normal architecture of the tissue to be biopsied. 3. The biopsy area is scrubbed a final time after the lidocaine is injected. 4. The skin is stretched between the thumb and index fi n ge r.

1. The animal is placed under general anesthesia after routine screening tests have been performed to identify problems such as coagulopathies and metabolic disease. 2. The hair is clipped and the surgery site prepared with a surgical scrub. 3. After the region is draped, an elliptical or wedge incision is made at the margin of the normal and abnormal tissue. Care is taken to obtain adequate tissue and to ensure that a subsequent definitive surgery can successfully remove the tumor and the incisional biopsy incision.

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4. Vessels going to and from the tissue to be biopsied are carefully identified and ligated. 5. The specimen is lifted and severed at the base with either scissors or a scalpel blade. 6. The incision is sutured for closur e.

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histopathologic results are generally more accurate than fine needle aspirate cytology, but not as accurate as excisional biopsy.

Technique EXCISIONAL BIOPSY1-3 An excisional biopsy should be performed when tissue is required for a histologic diagnosis, but the lesion must be small enough and in an anatomic location that allows for wide surgical removal without compromising the normal tissue around it. In general, an excisional biopsy is preceded with at least a fine needle aspirate cytology to give the surgeon as much information as possible about the characteristics of the tumor prior to removal. For example, a mast cell tumor or a soft tissue sarcoma would require wide surgical margins (2 to 3 cm), whereas a sebaceous cyst or sebaceous adenoma could be treated with smaller margins.

Technique 1. This biopsy is performed in the same manner as an incisional biopsy except the lesion is excised completely, with adequate margins.

LYMPH NODE BIOPSY Lymph node biopsy is often important in the diagnosis, staging and proper therapeutic management of the pet with cancer.1-3 A biopsy is often performed after fine-needle aspirate cytology suggests the presence of a disease. Despite the accuracy of fine-needle aspirate cytology in determining certain diseases such as lymphoma, mast cell tumors, and the presence of metastatic solid tumors, a histopathologic diagnosis is always recommended prior to initiation of therapy. In each case, adequate tissue must be obtained for histopathologic diagnosis and special stains, if indicated. When possible, the submandibular lymph nodes should be avoided, they often are reactive in the normal animal because they drain the oral cavity where the bacterial count is usually quite high. These reactive cells are sometimes misdiagnosed as neoplastic cells. If a carcinoma or a sarcoma is suspected, a biopsy should not be performed unless an overall plan for definitive therapy is made because the biopsy procedure can "seed" the operative field with tumor cells if the principle of en bloc dissection is violated. As with all biopsies, the surgeon who will perform the definitive surgery should be consulted prior to the biopsy to ensure that incisions are properly placed for a subsequent definitive procedure.

NEEDLE CORE BIOPSY Needle core biopsy is generally safe and quick, and can be performed on an awake cooperative patient.1 The

The lymph node is grasped by an assistant and held firmly against the overlying skin, and the biopsy site is pr epared as noted in steps 1 and 2 above. Then: 1. Approximately 2 to 3 mls of 2% lidocaine are injected under the skin overlying the enlarged lymph node. 2. Using a number 11 surgical blade, a stab incision is made in the skin to allow ease of entry of the needle core biopsy instrument. 3. The needle core biopsy instrument is advanced through the incision and into the capsule of the enlarged lymph node for subsequent biopsy. 4. At least 3 to 5 biopsies are taken of the lymph node through the same stab incision. 5. The needle biopsy specimens are fixed in 10% buffered formalin as described above. A separate container should be used for each lesion that is biopsied. 6. The stab incision is sutured only if indicated.

BONE MARROW ASPIRATION Bone marrow aspiration and biopsy are essential procedures for determining cytologic and histologic abnormalities of the bone marrow that are caused by a wide variety of neoplastic, infectious, and myelodysplastic conditions.1-3 A bone marrow aspirate and biopsy are indicated when an abnormality in blood cell production is suspected or to appropriately stage an animal with a hematopoietic malignancy. Spring loaded “automatic” needle core biopsy instruments are great for obtaining lymph node or other tissue samples with a local block and lidocaine anesthesia. Bone marrow aspiration is performed to acquire a monolayer of cells for individual evaluation.1-3 To identify a wide variety of malignant and non-malignant disorders, Romanovsky (including Wright and Giemsa) stains are preferred. When the cytologic diagnosis of a cell type is not certain, additional special stains can be used including myeloperoxidase, Sudan black, and periodic acid Schiff. Bone marrow biopsies are beneficial for determining bone marrow cellularity, the presence and extent of fibrosis or granulomatous conditions, and the presence of nonhematopoietic malignancies.

Technique1-3 1. The hair is clipped and the bone marrow aspiration site is prepared with a surgical scrub. Preferred sites and patient positioning include:-dorsocranial or lateral aspects of iliac crest (patient is sternal); greater trochanter of the femur (patient is in lateral recumbency); greater tubercle of the proximal aspect of the head of the humerus (patient is in lateral recumbency)

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2. Using a 25 gauge needle, approximately 2 to 3 mls of the local anesthetic agent, lidocaine, are injected in and around the site where the bone marrow needle is to be introduced. Care is taken to deposit lidocaine in and around all of the tissues that extend from the skin to the bone. 3. The biopsy area is scrubbed a final time after the lidocaine is injected. A surgical drape can be applied for sterility. 4. The bone marrow site is identified, the skin is stretched between the thumb and index finger, and a small stab incision is made with a number 11 surgical blade in the area blocked with lidocaine. 5. The bone marrow needle with the stylette in place is advanced through the stab incision in the skin, subcutaneous tissue, and muscle down to the bone. It is crucial to keep the stylette in place because it has a tendency to back out during the procedure. A 1 to 1.5 inch long, 16 gauge Illinois or Rosenthal bone marrow needle is preferred for dogs, and a 1 inch long, 18 gauge Illinois or Rosenthal needle is preferred for the cat. After a sample is obtained for cytologic evaluation, if a biopsy is required, a Jamshidi needle is utilized . 6. With the stylette is place, the bone marrow needle is advanced into the bone using a corkscrew motion. The instrument should not be allowed to wobble and the instrument should be fixed firmly into bone like a nail that has been securely hammered into wood. When the needle is firmly fixed in the bone, the stylette is removed and the syringe is affixed. Many clinical pathologists suggest rinsing the syringe and bone marrow needle with

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EDTA before the procedure to reduce clotting of the bone marrow sample. 7. The bone marrow sample is then aspirated briskly into the 12 ml syringe; usually 1 ml is adequate. The aspiration may be accompanied with a few seconds of pain, but this cannot be pr evented. 8. If a sample is not obtained, the stylette is replaced in the bone marrow needle and the instrument is then advanced further into the bone for a second attempt at aspirating marrow contents. 9. Once marrow has been obtained, smears are prepared. This can be done a number of ways: Fine needle aspiaration without (A and B above) or without (C above) the syringe attached to the needle is an important clinical tool for obtaining cells for a diagnosis.

References 1.

Withrow SJ: Biopsy Principles, in Withrow SJ, MacEwen EG (eds): Clinical Veterinary Oncology, Philadelphia, JB Lippincott Co. 1989, pp 53-57. Morrison WB, Hamilton TA, Hahn KA, Richardson RC, Janas W: Diagnosis of Neoplasia. In Slatter D (ed): Textbook of Small Animal Surgery (2nd ed), Philadelphia, WB Saunders Co, 1993, pp 20362048. Avis F: Lymph Node Biopsy, in Wittes RE (ed) Manual of Oncologic Therapeutics 1991/1992. Philadelphia, JB Lippincott Co. 1991, pp 8-9.

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What Every Practitioner Should know about Life Threatening Emergences and the Cancer Patient Che cosa ogni veterinario dovrebbe conoscere sulle più gravi emergenze nel paziente oncologico

Cancer is a word that is feared throughout the world, regardless of what species is affected. A diagnosis of cancer sets in motion feelings of fear and urgency which spur our clients on to demand rapid response by the veterinary health care team to their concerns. This heightened level of emotion is first witnessed during the initial diagnosis of cancer and decision-making process, but is often most apparent in the emergency situation. In addition, dogs and cats hide their clinical signs until quite late in the disease, often facing cancer therapy in debilitated states; therefore, speed and decisiveness are key ingredients of successful emergency care. Therefore, canine and feline oncologic emergencies must be handled with extreme medical care and also with understanding. When an emergency or urgent situation is noted, the entire veterinary health care team should be equipped and prepared to provide timely compassionate care to meet the medical and non-medical needs of patientand caregiver alike. In some cases, this may mean referring the case to another facility. There are three types of emergencies: • True life-threatening emergencies • Medical problems that are perceived as being life-threatening by well-meaning, concerned clients • Emergencies of convenience, where the client would prefer to have the dog and cat evaluated immediately despite non-life-threatening emergencies, in order to accommodate the client’s personal needs or schedule Regardless of the type of emergency, the following information should be obtained: • A primary complaint • Vital signs, including but not limited to: 1. Airway and breathing ability 2. Heart rate, rhythm and character 3. Body temperature 4. Mucous membrane color and capillary refill • Complete physical examination • Complete history, including prior cancer treatment When a dog or cat is presented for an emergency, blood and urine samples should be obtained and an intravenous catheter placed as soon as possible. The blood and urine can be submitted at any time to determine pretreatment parameters based upon a complete blood count,biochemical profile, activated clotting time, and urinalysis. Essential information that is rapidly obtained and vital for initial decision-making

should include a urine specific gravity, packed cell volume, white blood cell count, and blood glucose. These should be obtained on admission. As soon as the diagnostic and therapeutic plan is initiated, the clients should be made aware of each and every aspect of the case. Measured, realistic information should be provided as soon as assessments are made and the information is available. It is also important to provide a cost estimate for initial care, as well as updates for ongoing supportive care. Utilizing the team approach to care is vital in the event of an emergency. The client is an integral member of that team and, once empowered with information, is placed in a decision-making role that allows for optimal medical care of the patient, while meeting the emotional needs of the caregiver and family. Ongoing communication allows for an open dialogue between team members regarding financial limitations, philosophy for continuing critical care in the face of diminishing hope, and advanced strategies for crisis situations, such as cardiac or respiratory arrest. Oncologic emergencies, while rare, are an inevitable consequence of cancer and cancer therapy. Therefore, planning for these uncommon and unwanted problems is essential in order to result in positive outcomes. It is important to recognize that the true “first step” in handling oncologic emergencies is actually prevention. This step occurs prior to the initiation of treatment and is the result of time spent with the caregiver educating about the nature of disease, effects of any and all medication administered, and the early and often subtle symptoms that when acted upon often prevent a true emergency from ever happening. Similarly, instructions about what the client can do at home to support his or her dog and cat are also quite helpful. Always remember, the client is perhaps the most important member of the veterinary health care team. The next step of planning includes educating and empowering the entire veterinary health care team to take an active role in supporting the patient and the client. The word cancer and cancer therapy often frightens veterinary health care team members as much as it does clients. There are a few common emergency situations that will be encountered. Developing a treatment strategy or “cookbook approach” to these emergency situations empowers the staff to intervene on behalf of the patient. In addition, providing the health care team with information that empowers them to respond

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to the emotional component of the emergency on the part of the caregiver is also essential. All members of the health care team must recognize that it is this emotional component of the disease cancer that magnifies the seriousness of almost any health problem.

NEUTROPENIA AND SEPSIS Emergencies are always frightening to clients/caregivers, but when an emergency occurs due to cancer or cancer treatment, the intensity of this fear is magnified by the emotional impact imparted by the cancer itself. Therefore, the canine and feline health care team must act swiftly to not only provide medical care for the patient, but also care for the emotional or non-medical needs of the client. Sepsis due to chemotherapy or cancer-related neutropenia is one of the more common emergencies handled in canine and feline cancer medicine. Bleeding due to thrombocytopenia is much less common. Both conditions are usually preventable by judicious monitoring and appropriate supportive care during cancer therapy. In addition, caregivers should be educated about the early clinical signs of neutropenia and thrombocytopenia induced by cancer treatment, thus empowering the client to assist in early detection and seek immediate treatment. In humans, sepsis is a common cause of death in cancer patients, exceeding all other causes combined.1–7 As the popularity of dogs and cats increases and the use of chemotherapy and radiation soar in private practice, this observation is likely to be repeated in canine and feline cancer medicine. Because dogs and cats tend to hide their symptoms until late in the disease, the condition of sepsis may be quite advanced when first recognized and requires prompt intervention by the canine and feline health care team. Neutropenia secondary to malignancy or mye l o dy splasia, or as a result of the mye l o s u p p re s s ive effects of chemotherapy or radiation therapy, is a common predisposing factor for development of sepsis in dogs and cats. Septic shock is the state of circ u l at o ry collapse that occurs secondary to overwhelming sepsis and/or endotoxemia. This syndrome is frequently fatal, with a mortality rate of 40% to 90%. The profound systemic effects of septic shock include: • Vasoconstriction leading to multi-organ failure • Cardiac dysfunction, in part from lactic acidosis • Increased vascular permeability, leading to hyperviscosity and hypovolemia • Liver dysfunction from splanchnic vascular pooling and tissue ischemia • Acute renal failure • Worsening neutropenia and thrombocytopenia • Coagulopathies • Severe gastrointestinal damage • Decreased insulin release • Initial hyperglycemia followed by hypoglycemia The bacteria that most commonly cause morbidity and mortality in canine and feline cancer patients arise from the dog and cat ’s own flora.8 The most important thing a clinician can do for the septic canine and feline cancer patient is

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to quickly identify the source and type of bacterial infection, and initiate therapy with broad-spectrum antibiotics as well as appropriate and aggressive supportive care. Factors such as prolonged hospitalization, the presence of urinary, venous, chest, endotracheal and other tubes or catheters, and antibiotic administration may result in increased susceptibility to increasingly resistant strains of organisms. These factors should be avoided or minimized wherever possible. Minimizing the chance for exposure to, or the opportunity for development of, resistant strains of bacteria enhances the chance for rapid recovery in response to appropriate antibiotic therapy.

Predisposing Factors The following are predisposing factors for neutropeniaassociated sepsis: • Defects in cellular immunity are a cause of sepsis in dogs and cats with cancer. Cellular immune dysfunction, while extraordinarily difficult to diagnose in the dog and cat, may be due to an underlying cause or the result of administration of antineoplastic agents and/or corticosteroids. These defects may result in various bacterial, mycobacterial, fungal, and viral infections. Humoral immune dysfunction is also associated with an increased prevalence of sepsis in human patients with cancer and may cause similar problems in animals. Agammaglobulinemic or hypogammaglobulinemic dogs and cats are suspected as being susceptible to infections. Multiple myeloma and chronic lymphocytic leukemia are common neoplasms associated with humoral immune dysfunction in people, and are likely causes in the dog and cat as well. • Neutropenia may be caused by the myelosuppressive effects of chemotherapy. The myelosuppressive effects of chemotherapeutic agents can be categorized as high, moderate, or mild. These drugs cause a nadir (lowest part of the white blood cell count) at different times after administration.). • Splenectomized dogs and cats are susceptible to overwhelming sepsis when infected with a strain of encapsulated bacteria against which they have not made antibodies. • Indwelling vascular or urinary catheters have been associated with an increased prevalence of sepsis. The longer a catheter is present, the higher the probability for infection, especially in neutropenic dogs and cats. • Frequent acquisition of blood samples greatly increases the risk of sepsis in dogs and cats with cancer. • Prolonged hospitalization can result in serious consequences, in part because the patient is continually exposed to bacterial strains that are resistant to the antibiotics most commonly used in that practice. • Malnutrition is a serious cause of debilitation and decreased resistance to bacterial infection, especially in those dogs and cats with neutropenia. • Dogs and cats with neurologic dysfunction or nonambulatory patients from any cause are at increased risk for sepsis as well.

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Whenever possible, these risk factors must be avoided or minimized, and associated problems recognized and corrected early to reduce the probability of sepsis. The first approach for clinician and client is to understand the myelosuppressive effects of various drugs. The myelosuppressive effects of chemotherapeutic agents can be categorized as high, moderate, or mild. These drugs cause a nadir (lowest part of the white blood cell count) at different times after administration. Clients and the veterinary health care team should be encouraged to be more vigilant for the clinical signs associated with neutropenia and thrombocytopenia around the time of the nadir for the drug being used. With monitoring of CBCs at the appropriate times, especially early on in the course of chemotherapy, the veterinarian will have a general idea of how low the white blood cell count is actually dropping. If the count appears too low (less than 1000/ul), or the patient becomes even mildly symptomatic, subsequent dose reduction should be considered . Further steps can be taken to minimize the risk of sepsis for the dog and cat with cancer. One logical step is to minimize the administration of immunosuppressive drugs, especially corticosteroids. Whenever a splenectomized dog and cat is treated for cancer, they should be watched carefully for complications,including sepsis. The risk of catheter-induced sepsis can be minimized by using aseptic technique and by placing a new catheter in a new site every 2 to 3 days. Strict aseptic procedures should be used, especially with dogs and cats that are myelosuppressed. The use of semipermanent indwelling catheters in patients with cancer may be safe if strict aseptic procedures are followed by caregivers and health care professionals. Proper aseptic technique and changing of catheters are especially important in dogs and cats with neurologic dysfunction, as these dogs and cats are at a much higher risk for sepsis. The duration of hospitalization should be limited whenever possible to limit exposure to resistant bacteria.

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• • • •

Mucous membrane pallor Marked mental depression Bloody diarrhea Signs of multi-organ failure Thrombocytopenia and neutropenia are often identified during the course of septic shock. Hyperglycemia is an early finding that often is followed by hypoglycemia. Cultures of urine and blood should always be obtained, even though they may be negative and require a significant amount of time for turn around. Appropriate broad-spectrum antibiotics and combinations must be available immediately for parenteral administration. When positive, the results of cultures will guide follow-up oral antibiotic selection. Metabolic acidosis is commonly identified. Blood and urine taken at the time of initial presentation can be very helpful for supporting a diagnosis of septic shock. At a minimum, samples should be obtained for a complete blood count (CBC), biochemical profile, and urinalysis on each dog and cat. These clinical pathologic findings are often combined with other tests. The absence of circulating neutrophils affects many of the commonly used clinical, laboratory and radiographic findings that may normally suggest a localized or systemic infection. For example: • Neutropenia results in a urinalysis without pyuria, despite infection. • Without a neutrophilic infiltrate, which otherwise would be responsible for many of the radiographic changes associated with pneumonia, chest radiographs often appear “normal” even in the presence of significant pneumonia.

•

Diagnosis Dogs and cats presented with septic shock secondary to neutropenia require immediate intervention and careful client support. Diagnostic and therapeutic interventions must begin concurrently for the patient’s benefit. The differential list for neutropenia is quite extensive. Obviously, the diagnosis of septic shock begins with the physical examina tion as a catheter is placed and blood samples are acquired for initial diagnostics. Mucous membrane color can be difficult to identify in dogs and cats, however, in some dogs and cats with septic shock,brick-red mucous membranes may be noted. In addition, some of the following signs may be identified on physical examination in dogs and cats in the hyperdynamic state of septic shock: 1–6 • Tachycardia • Short capillary refill time • Gastrointestinal signs • Altered mentation • Decreased blood pressure End-stage signs reflect a hypodynamic state and include: 1–6 • Hypothermia

•

• •

Thus, any suspicious sites should be cultured. This includes, but is not necessarily limited to: Blood cultures: Two, and preferably four, sets of blood cultures (aerobic and anaerobic) should be acquired. However, extreme care should be taken to be cognizant of the total volume of blood taken, including blood for hemograms, biochemical profiles and other tests, because these dogs and cats almost always have some degree of anemia of chronic disease. The timing of the sampling intervals is controversial, however, sampling every 20 to 30 minutes prior to initiation of antibiotic therapy may be adequate. At least 2 ml of blood should be injected into appropriate culture containers. Catheter cultures: If central venous catheters are present, cultures of the port should be obtained. Ideally, culture bottles that contain an antibiotic-binding resin or other antibiotic-binding substance should be included with each culture for patients on antibiotics. Urine culture:A cystocentesis specimen for urine culture and analysis should be acquired in each case. CSF culture: When neurologic signs are present, a cerebrospinal fluid (CSF) tap should be obtained and cultured appropriately. CSF should be sent for Gram stain, bacterial culture, cell count and differential, and glucose and protein determination. A cryptococcal antigen titer or India ink preparation should be performed in suspect cases. Acid-fast stains and culture are proba bly not indicated routinely.

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• Stool cultures: For dogs and cats with diarrhea, appropriate cultures should be done for clostridial bacteria, including appropriate assays for endotoxin. • Lung cultures: Chest radiographs and a transendotracheal wash should be taken, especially when the patient shows any sign of respiratory difficulty such as increased respiratory effort or a cough. Other diagnostic studies that should be considered include: • Complete blood count with differential,biochemical profile, and urinalysis • Chest and abdominal radiographs to look for signs of infection • Abdominal ultrasonography looking for pancreatitis, abscesses, abdominal effusion, etc. • Echocardiography to identify the presence of valvular endocarditis • Bronchoscopy, if pulmonary disease is suspected • Skin biopsy, if deep cutaneous infection is identified • Bone marrow aspirate or biopsy to determine the cause and severity of neutropenia • Percutaneous or laparascopic-guided liver biopsy or aspirate to evaluate for hepatic infection or abscessation • Exploratory laparotomy in select cases when other, less invasive tests are not successful, yet there is clinical evidence of disease in the abdomen • Blood gas analysis

Treatment1–8 Treatment for septic shock should begin as soon as the condition is suspected. This is usually at the time the dog and cat is initially presented for an acute, emergency condition. Treatment for the septic, neutropenic dog and cat is primarily directed at: • Restoring adequate tissue perfusion • Improving the alterations in metabolism • Controlling systemic infection Restoring Adequate Tissue Perfusion: Standard therapy includes crystalloid solutions and antibiotics. Although the use of hypertonic solutions for the treatment of shock is being investigated, balanced electrolyte solutions are cited in most canine and feline texts as “the first line of therapy.” The initial infusion rate for critical dogs and cats is 40 to 60 ml/kg IV for 1 hour, then 10 to 12 ml/kg/hour thereafter. The fluid rate should then be adjusted to meet the needs of each dog and cat as determined by monitoring body weight, heart and respiratory rates, central venous pressure, ongoing losses (e.g., vomiting and diarrhea), and urine output. During that first hour of fluid administration, it is vitally important to monitor at 15-minute intervals for evidence of fluid overload and adjust appropriately. Improving Alterations in Metabolism: When choosing the type of fluids, some authorities prefer a non-lactate containing fluid; lactate must be metabolized to bicarbonate by a functional liver that may be impaired during shock and

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sepsis. Normosol R and Plasmalyte  are examples of nonlactate-containing fluids with acetate and gluconate as buffers. Dextrose should be included in fluids when systemic hypoglycemia is identified during constant patient monitoring. Controlling or Preventing Infection: Asymptomatic dogs and cats with fewer than 1000 to 1500 neutrophils/µl should be started prophylactically on antibiotics. Trimethoprim-sulfa (7.5 mg/kg BID PO) is often recommended for prophylactic therapy in the asymptomatic, yet neutropenic, patient. Neutropenic dogs and cats in septic shock should be started on intravenous fluids and intravenous antibiotic therapy as soon as samples for bacterial cultures are acquired(Tables 33 and 3-4). Re-evaluation of the initial antibiotic regimen is mandatory when the identity and sensitivity patterns of the bacteria become available. For gram-negative infections, two antibiotics that are effective against the isolated organism are often recommended. Initially, broad-spectrum antibiotic therapy, often combinations of an aminoglycoside plus penicillin or 2nd generation cephalosporin (e.g., cefoxitine, cefamandole, cefaclor, cefuroxime, cefonicid, ceforanide, cefotetan, cefetazole), is commonly used in sepsis. If the infection doesn't respond within 12 to 24 hrs, the antibiotics should be changed. For gram-negative organisms, a different aminoglycoside, quinolone, or aztreonam may be used. Extended-spectrum penicillins (e.g.,ticarcillin,carbenicillin,azlocillin, piperacillin sodium, and mezocillin), 3rd generation cephalosporins (e.g., cefotaxime, moxalactam,cefoperazone, ceftizoxime, ceftriaxone, ceftazidime, cefixime), or impenam with cilastatin sodium have sufficiently broad spectrums to be used alone. Dogs and cats placed on aminoglycosides, particularly gentamicin, should be monitored for nephrotoxicity via urinalysis (urine sediment should be examined for the presence of casts) and measurement of BUN and creatinine concentrations. Other treatments include: • Corticosteroids: Steroids remain controversial in septic shock. Recommended doses in shock are hydrocortisone at 300 mg/kg, methylprednisolone or prednisone at 1030 mg/kg, or dexamethasone at 4-8 mg/kg. Short-term use (i.e., less than 2 days of massive doses) does not result in as many adverse effects as long-term use. • Glucose: If hypoglycemia is present, glucose at 0.25 g/kg IV bolus can be given, followed by infusions of 2.5- 10% glucose solutions as needed to maintain normal blood glucose levels. • Bicarbonate: Bicarbonate can be given if severe metabolic acidosis is present. The amount of bicarbonate to give can be calculated (i.e., base deficit x (0.3 x BW in kg)) or estimated (mild, moderate, or severe acidosis is treated with 1, 3, or 5 mEq bicarbonate/kg IV, respectively). Bicarbonate should be given slowly IV (i.e., over 20 minutes or more). • Neutrophil-Rich Transfusions: These transfusions have not been associated with beneficial responses in controlled trials. In addition, transfusion reactions and allosensitizations to specific antigens of the granulocytes may occur, and increased prevalence of severe pulmonary reactions may also be noted.

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• Hematopoietic Growth Fa c t o rs : Canine recombinant gra nu l o cyte colony-stimulating factor (rcG-CSF, 5 µg/kg/day SQ) and canine recombinant granulocytemacrophage colony-stimulating factor (rcGM-CSF, 10 µg/kg/day SQ) have been associated with an increased rate of myeloid recovery in dogs and dogs and cats with neutropenia. These hemat o p o i e t i c growth factors increase cell numbers and enhance neutrophil function, but are not yet available commercially. Human recombinant G-CSF and GM-CSF are commercially available; however, long-term use may induce antibody fo rm ation to the protein. Of the two human recombinant proteins, rhG-CSF induces the most profound increase in canine and canine and feline neutrophil numbers before development of antibodies is noted. • Transfusions of Fresh, Whole Blood • Other Options: Tumor necrosis factor antiserum, antibody to tumor necrosis factor, interleukin and interferon therapy, pooled immunoglobulin preparations, and monoclonal antibodies to neutralize endotoxin may be future treatments of choice.

THROMBOCYTOPENIA The cytotoxic effects of chemotherapeutic agents, bone marrow infiltration by a malignant process, and canine and feline infectious peritonitis most commonly cause a decreased platelet count. If a chemotherapeutic agent induces bone marrow suppression that results in cytopenia, thrombocytopenia usually occurs a few days after neutropenia and before a decrease in red blood cell numbers. Commonly identified abnormalities include a mixed hemostatic defect compatible with disseminated intravascular coagulation (DIC), thrombocytopenia, isolated prolongation of the activated partial thromboplastin time (APTT), and prolongation of both the APTT and one-stage prothrombin time (OSPT).

Predisposing Factors Thrombocytopenia can occur in any dog and cat with cancer that receives myelosuppressive chemotherapeutic agents. Drugs such as vincristine, bleomycin, and prednisone do not cause as significant a thrombocytopenia as do some of the more highly myelosuppressive agents ( e. g. , doxorubicin). Compared to many other myelosuppressive drugs, cyclophosphamide induces less suppression in platelet numbers. Dogs and cats with bone marrow infiltration by a malignant process are more sensitive to the cytotoxic effects of chemotherapeutic agents that can result in thrombocytopenia. Other conditions that affect the bone marrow are likely to make the marrow more sensitive to cytotoxic agents. Tumors that are frequently associated with coagulopathies may cause a consumptive thrombocytopenia. In addition, hypersplenism and chronic bleeding of any cause can result in a decrease in the number of platelets.

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Diagnosis Dogs and cats are often presented late in the course of clinical disease due to their ability to mask the early symptoms of illness. This is true for diseases or conditions that result in thrombocytopenia. Clinical signs include , but are not limited to, bleeding diatheses, melena, and weakness. The blood loss can occur into any organ and result in multisystemic abnormalities. An acute decline in the number of platelets may result in the development of clinical signs at higher platelet counts than if the decline in platelets is much slower. Therefore, if there is any suspicion that thrombocytopenia may be present (gingival hemorrhage, petechia or ecchymotic hemorrhages, or any of the above mentioned symptoms), proactive interventional and diagnostic measures should be taken after the physical examination is performed. A catheter should be placed and blood obtained with a small gauge needle for routine blood work (CBC with platelet count, biochemical profile, T4 and FeLV/FIV testing), and a urinalysis should be performed as well to complete a minimum database. Diagnosis is confirmed by obtaining platelet counts and by examining bone marrow aspirate or biopsy specimens. Bone marrow evaluation is essential and helps the clinician determine the cause of the thrombocytopenia. Clotting profiles (e.g., APTT, OSPT, and fibrin degradation products [FDPs]) may help determine if the thrombocytopenia is the result of a coagulopathy, such as DIC.

Therapy Thrombocytopenia-related clinical signs can be exacerbated when drugs that affect platelet function are administered during the time of overt or impending thrombocytopenia. Therefore, aspirin and aspirin-like drugs should be withheld from dogs and cats with thrombocytopenia. In addition, the use of heparinized saline for catheter maintenance can be a problem in some patients if multiple catheter “flushes” are performed. Obviously, dogs and cats with thrombocytopenia should be kept quiet and care should be taken during handling. Vincristine (0.5 mg/m2 body surface area) can be administered IV to induce premature release of platelets from megakaryocytes.8 Platelet counts increase 4 days after vincristine is given. Where available, platelet transfusions may be administered to specific dogs and cats that are, or have a high likelihood of, bleeding uncontrollably. Administering each unit of platelets with 30 to 60 ml of plasma is recommended. In dogs and cats with acute bleeding that is not responsive to other treatments of procedures, hemostatic, epsilon aminocaproic acid (Amicar ) can be given IV or PO (250 mg/m2 QID).9 Dose reduction should occur with the next administration of myelosuppressive chemotherapeutic agents.

References 1. 2.

Goodwin JK, Schaer M: Septic shock. Vet Clin North Am Small Anim Pract 19:1239–1258, 1989. Haskins SC: Shock, in Kirk RW (ed): Current Veterinary Therapy VIII. Philadelphia,WB Saunders,1983, pp 2–27.

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4. 5. 6. 7. 8. 9.

10.

11.

12. 13. 14.

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Kirk RW, Bistner SI: Shock, in Handbook of Veterinary Procedures Emergency Treatment, ed 4. Philadelphia, WB Saunders, 1985, pp 59–68. Parker MM, Parrillo JE: Septic shock, hemodynamics and pathogenesis. JAMA 250:2324–2230, 1983. Hardie EM,Rawlings CA:Septic shock. Compend Contin Educ Pract Vet 5:369–373, 1983. Wolfsheimer KJ: Fluid ther apy in the critically ill patient. Vet Clin North Am Small Anim Pract 19:361– 378,1989. Lazarus HM,Creger RJ, Gerson SL:Infectious emergencies in oncology patients. Semin Oncol 6:543–560, 1989. Couto CG: Management of complications of cancer chemotherapy. Vet Clin North Am Small Anim Pract 4:1037– 1053, 1990. Woodlock TJ: Oncologic emergencies, in Rosenthal S, Carignan JR, Smith BD (eds): Medical Care of the Cancer Patient, ed 2. Philadelphia,WB Saunders, 1993, pp 236–246. Hughes WT: Infectious Diseases Society of America: Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. J Infect Dis 161: 381–390, 1990. Peterson JL, Couto CG, Wellman ML: Hemostatic disorders in dogs and cats: a retrospective study and review of the literature. J Vet Intern Med 9:298-303, 1995. Quadri TL, Brown AE: Infectious complications in the critically ill patient with cancer. Sem in Oncology 27:335-346, 2000. Hackner SG: Approach to the diagnosis of bleeding disorders. Compend Contin Educ Pract Vet 17:331-349, 1995. Carr AP, Johnson GS:A review of hemostatic abnormalities in dogs and dogs and cats. JAAHA 30:475-481,1994.

HYPERCALCEMIA Hypercalcemia is the most common metabolic emergency in oncology.1–6 Lymphoma is the leading cause of hypercalcemia in dogs and cats. Other causes include multiple myeloma, squamous cell carcinoma, mammary adenocarcinoma, and primary hyperparathyroidism. Parathyroid carcinomas or adenomas are a rare malignancy associated with intractable hypercalcemia caused by elevated parathyroid hormone levels. A parathyroid hormone-related peptide (PTH-rp) is most commonly associated with hypercalcemia in dogs and probably dogs and cats as well, although the assay for PTH-rp in dogs and cats is not as routinely performed nor as reliable as it is in canine medicine. Although it has been suggested that bone metastasis can be associated with hypercalcemia, this is rare in canine and feline medicine. One recent retrospective study was conducted to characterize the diseases, clinical findings, and clinicopathologic and ultrasonographic findings associated with hypercalcemia (serum calcium concentration > 11 mg/dL) in 71 dogs and cats.7 The three most common diagnoses were neoplasia (n = 21), renal failure (n = 18), and urolithiasis (n = 11). Primary hyperparathyroidism was diagnosed in four dogs and cats. Lymphoma and squamous cell carcinoma were the most frequently diagnosed tumors. Calcium oxalate uroliths were diagnosed in 8 of 11 dogs and cats with urolithiasis. Dogs and cats with neoplasia had a higher serum calcium concentration (13.5 ± 2.5 mg/dL) than dogs and cats with renal failure or urolithiasis and renal failure (11.5 ± 0.4 mg/dL; P < .03). Serum phosphorus concentration was higher in dogs and cats with renal failure than in dogs and cats with neoplasia (P < .004).

Clinical Presentation The oncologic emergency secondary to hypercalcemia of malignancy revolves around clinical signs associated with a decreased ADH sensitivity of the distal convoluted tubules and collecting ducts, as well as the vasoconstrictive properties of calcium that result in decreased renal blood flow and a reduced glomerular filtration rate.1–4 The renal epithelium undergoes degenerative changes, necrosis, and calcification. The aforementioned physiologic and pathologic changes result in progressive renal disease, noted clinically as polyuria and polydipsia, followed by vomiting, hyposthenuria, and dehydration. Calcium may also affect the gastrointestinal, cardiovascular, and neurologic systems directly and cause anorexia, vomiting, constipation, bradycardia, hypertension, skeletal muscle weakness, depression, stupor, coma, and seizures.

Diagnosis Other diagnostic differentials that must be considered in dogs and cats presented for true hypercalcemia (Ca++ >11 mg/dl) include laboratory error, error in interpretation, hyperproteinemia from dehydration, acute renal failure, vitamin D and calcium toxicosis, granulomatous disorders, nonneoplastic disorders of bone, hypoadrenocorticism, and true hyperparathyroidism.2,5,6 It is important to interpret calcium levels in relation to serum albumin and blood pH. A correction formula that takes albumin into account is: adjusted calcium (mg/dl) = [calcium (mg/dl) – albumin (g/dl)] + 3.5 Acidosis results in an increase in the free, ionized fraction of calcium and can magnify the observed clinical signs associated with hypercalcemia. Serial serum calcium, electrolytes, BUN, and creatinine levels should be measured in all hypercalcemic patients. While controversial, elevated immunoreactive PTH levels in association with hyperphosphatemia may suggest ectopic hormone production. PTH-rp is not reliable in the dog and cat, but it may be helpful in some situations. Dogs and cats with multiple myeloma may have elevated calcium levels secondary to abnormal calcium binding to a paraprotein without an elevation in ionized calcium, and malnourished dogs and cats with hypoalbuminemia may have symptoms of hypercalcemia with normal serum calcium levels.

Treatment2,5,6 Treatment of an emergency secondary to hypercalcemia depends on the severity of the clinical signs and the presence of renal disease. Appropriate management of hypercalcemia almost always entails the use of intravenous saline in volumes that exceed daily maintenance (>132 ml/kg0.75/day or approximately >66 ml/kg/day, plus exogenous losses from vomiting and diarrhea, plus replacement fluids for dehydration). Potassium depletion should be prevented by addition of potassium chloride to fluids based on serum potassium levels.

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The rate of potassium administered intravenously should not exceed 0.05 mEq/kg/hr. In addition, dogs and cats should be watched carefully for signs consistent with overhydration and congestive heart failure. If the hypercalcemia is the result of a malignancy, effective antitumor therapy should be initiated as soon as possible. Thiazide diuretics or vitamins A and D (which may elevate calcium levels) should never be used with these dogs and cats. The most commonly used drugs for management of dogs and cats with hypercalcemia include: • Furosemide (1–4 mg/kg BID, IV or orally) and intravenous biphosphonates (e.g., etidronate, disodium palmidroate) may be used in addition to saline diuresis. Intravenous or oral biphosphonates have rapid hypocalcemic effects due to their inhibition of osteoclast activity. • Gallium nitrate produces concentration-dependent reductions in osteolytic response to parathormone and certain other types of lymphokines that cause hypercalcemia. Gallium nitrate infused at doses of approximately 100 mg/m2 daily for 5 consecutive days successfully reduces high calcium levels in 86% of human patients.8,9 • Mithramycin, a chemotherapeutic agent that decreases bone resorption by reducing osteoclast number and activity, also has been shown to be effective in people. Because mithramycin is a sclerosing agent, it must be given as a bolus (25 mg/kg IV once or twice weekly) through a newly placed intravenous line. If extravasation occurs, ulceration and fibrosis will develop. Mithramycin has not been used extensively in dogs or dogs and cats; in refractory patients, it may require twice-weekly dosing. • Salmon calcitonin (4–8 MRC U/kg SQ) may also be used in refractory patients. Calcitonin inhibits bone resorption and thus causes a fall in serum calcium levels within hours of administration. When administered at approximately 40 U/kg, salmon calcitonin may result in hypocalcemia for several days. • Corticosteroids are effective for treatment of hypercalcemia. Cort i c o s t e roids bl o ck bone re s o rp t i o n caused by osteoclast-activating factor, increase urinary calcium ex c re t i o n , inhibit vitamin D metabolism, and increase calcium absorption after long-term use. To be effective, high doses are ge n e ra l ly required for several days. Steroids should not be used until tissue diagnosis is made, p ri m a ri ly because lymphomas are the most common cause of malignancy-associated hypercalcemia and the indiscriminate use of steroids could make the diagnosis of lymphoma difficult to impossible. Most dogs and cats are effectively treated with hydration, antitumor therapy, and treatment with hypocalcemicinducing agents, such as mithramycin, calcitonin, or corticosteroids. Serum calcium should be monitored at least twice weekly.

HYPONATREMIA The emergency condition relating to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a

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rare and under-recognized , but important, cause of true hyponatremia in the cancer patient.6–8 As the name implies, SIADH is the presence of excessive quantities of antidiuretic hormone secondary to a malignancy. In SIADH, dogs and cats have a low plasma osmolality despite inappropriate urine concentration (high sodium). Because this situation also can occur in renal disease, hypothyroidism, and adrenal insufficiency, these disorders must be excluded to confirm the diagnosis of SIADH.

Predisposing Factors The condition of SIADH may be caused by a malignancy or drug that results in renal activation or enhanced release of antidiuretic hormone. SIADH has been identified in dogs and cats with lymphoma. Drugs in canine and feline medicine that can cause this condition include6–9: • Chlorpropamide • Vincristine • Vinblastine • Cyclophosphamide • Opiates • Thiazide diuretics • Barbiturates • Isoproterenol • Mannitol • Morphine • Other diuretics The abrupt withdrawal of steroids may also cause SIADH.6–9 When hyponatremia develops rapidly or sodium falls below 115 mg/dl, dogs and cats may develop mental status abnormalities, confusion, or coma. Serum and urine electrolytes, osmolality, and creatinine levels should be measured in suspect cases.

Diagnosis Clinical signs include anorexia, nausea, and muscle stiffness progressing to confusion, neurologic signs, coma and death. In SIADH, there is an inappropriately high sodium concentration in the urine for the level of hyponatremia in the serum. Therefore, urine osmolality is greater than plasma osmolality, but the urine specific gravity is never maximally dilute. The urea nitrogen value in the serum (BUN) is usually low because of volume expansion. Hypophosphatemia may be noted. Adrenal and thyroid function should be normal.

Treatment In an emergency setting, initial treatment should be directed at resolution of the hyponatremia. Fluids should be restricted to ensure that the dog and cat receives only the amount needed to maintain normal hydration and to keep serum sodium concentration within normal levels. In emergencies, demeclocycline may correct hyponatremia by reducing ADH stimulus for free water reabsorption at

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the collecting ducts. The most common side effect of demeclocycline is nausea and vomiting. Lithium carbonate and phenytoin have some use in treating SIADH. Hypertonic sodium chloride (3%–5%) can be used in an emergency situation; however, if not used carefully, this treatment may result in fluid and circ u l at o ry ove rl o a d. Furosemide can be used concurrently with hypertonic saline to reduce the volume overload. It should be noted that rapid correction of hyponatremia may lead to neurologic damage. The following formula may help to determine approximate amounts of sodium to administer for hyponatremia correction10: Na for replacement (mEq) = (desired serum sodium [mEq/L] – observed serum sodium [mEq/L]) × body weight (kg) × 0.6

HYPOGLYCEMIA Predisposing Factors Fasting hypoglycemia in the face of hyperinsulinemia occurs most commonly with insulinomas; however, other tumors of the liver (e.g., hepatomas and carcinomas) have also been associated with this condition.6–12 Liver disease (including glycogen storage diseases) and sepsis may mimic hypoglycemia of malignancy. In addition, because red blood cells can metabolize glucose rapidly, delay in separating red blood cells from the serum may lead to artificially reduced serum glucose concentrations.

Clinical Signs Before presenting with seizures, coma, and impending death, most dogs and cats have a history of exhibiting signs of fatigue, weakness, dizziness, and confusion associated with paroxysmal lowering of the blood glucose levels. Neurologic signs of hypoglycemia may mimic other CNS abnormalities, such as brain tumors, brain trauma, meningitis, or metabolic encephalopathy. Insulin-producing tumors can be diagnosed by identifying elevated insulin levels in association with low blood glucose concentrations. In some cases, the identification of malignancy-associated hypoglycemia may require periodic sampling during a 72-hour fast.11 Diagnosis is made when the blood glucose is dramatically reduced, but insulin levels are elevated. Although controversial, the amended insulin:glucose ratio has been advocated as a method to help diagnose insulin-producing tumors in domestic cats12:

Treatment6–12 In an emergency setting, medical management is often necessary before, during, and after definitive therapy, especially for insulinomas, which have a high metastatic rate. Glucose-containing fluids (2.5%–5% dextrose in 0.9% NaCl or other isotonic crystalloid solution) should be administered to meet fluid requirement needs and to maintain blood glucose concentrations within acceptable limits. It should be noted, however, that the administration of glucose may trigger the tumor to release more insulin; there fo re, a constant infusion of glucose to maintain normal serum glucose levels is pre fe rred to intermittent high-dose bolusing. A seizuring dog and cat with hyp og lycemia (<60 mg/dl) should be treated with 0.5 g dextrose/kg administered IV slowly over 3 to 5 minutes. Repeat doses may be needed. Prednisone (0.5–2.0 mg/kg divided BID PO) is often effective in elevating blood glucose levels by inducing hepatic gluconeogenesis and decreasing peripheral utilization of glucose. Diazoxide (10–40 mg/kg divided BID PO) may be effective in elevating blood glucose levels by directly inhibiting pancreatic insulin secretion and glucose uptake by tissues, enhancing epinephrine-induced glyco genolysis, and increasing the rate of mobilization of free fatty acids. Diazoxide’s hyperglycemic effects can be potentiated by concurrent administration of hydrochlorothiazide (2–4 mg/kg daily BID PO). Propranolol (0.2–1.0 mg/kg TID PO), a β-adrenergic blocking agent, may also be effective in increasing blood glucose levels by inhibition of insulin release through the blockade of β-adrenergic receptors at the level of the panc re atic β cell, inhibition of insulin release by membrane stabilization, and alteration of peripheral insulin receptor affinity. Combined surgical and medical management of pancreatic tumors has been associated with remission periods of 1 or more years. Upon stabilization of the dog and cat’s condition, surgical extirpation may be the best treatment for a tumor that causes hypoglycemia. Because many tumors (including insulinomas) that induce hypoglycemia as a paraneoplastic syndrome are malignant, surgery often is not curative. A partial pancreatectomy may be indicated for insulinomas; iatrogenic pancreatitis and diabetes mellitus are recognized complications.

References 1. 2. 3.

serum insulin (µU/ml × 100) = amended insulin:glucose ratio

serum glucose (mg/dl) – 30 Values above 30 suggest a diagnosis of an insulinoma or other insulin-producing tumor.

Besarb A, Caro JF: Mechanisms of hypercalcemia in malignancy. Cancer 41:2276–2285, 1978. Meuten DJ: Hypercalcemia. Vet Clin North Am Small Anim Pract 14:891–899,1984. Weir EC, Burtis WJ, Morris CA, et al: Isolation of a 16,000-dalton parathyroid hormone-like protein from two tumors causing humoral hypercalcemia of malignancy. Endocrinol 123:2744– 2755, 1988. Weir EC, Nordin RW, Matus RE, et al: Humoral hypercalcemia of malignancy in canine lymphosarcoma. Endocrinol 122:602–610, 1988. Kruger JM, Osborne CA, Polzin DJ: Treatment of hypercalcemia, in Kirk RW (ed): Current Veterinary Therapy IX. Philadelphia, WB Saunders, 1986, pp 75–90.

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6. 7.

10. 11.

Lowitz BB: Paraneoplastic syndromes, in Haskell CM (ed): Cancer Treatment, ed 3. Philadelphia, WB Saunders, 1990, pp 841–849. Savary KC, Price GS, Varden SL. Hypercalcemia in Cats: A Retrospective Study of 71 Cases (1991-1997) J Vet Intern Med 14:184-??, 2000. Glover DJ, Glick JH: Oncologic emergencies and special complications,in Calabrese P, Schein PJ, Rosenberg SA (eds):Medical Oncology: Basic Principles and Clinical Management of Cancer. New York, MacMillan, 1985,pp 1261–1326. Felds ALA, Jese RG, Bergaagel DE: Metabolic emergencies, in DeVita VT, Hellman S, Rosenberg SA (eds): Cancer Principles and Practice of Oncology. Philadelphia, JB Lippincott, 1985, pp 1874–1876. Franco-Saenz R: Endocrine syndromes, in Skeel RT (ed): Handbook of Cancer Chemotherapy. Boston, Little, Brown & Co, 1991, pp 379–404. Leifer CE, Peterson ME, Matus RE, Patnaik AK:Hypoglycemia associated with nonislet cell tumors in 13 dogs. JAVMA 186:53–62, 1985.

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12.

13. 14.

15.

16.

17.

Giger U, Gorman NT: Acute complications of cancer and cancer therapy, in Gorman NT (ed): Oncology. New York,Churchill Livingstone, 1986, pp 147–168. Sheafor SE, Gamblin RM, Couto CG: Hypercalcemia in two cats with multiple myeloma. JAAHA 32:503-8, 1996. McClain HM, Barsanti JA, Bartges JW: Hypercalcemia and calcium oxalate urolithiasis in cats: A r eport of five cases. JAAHA 35:297301, 1999. Marquez GA, Klausner JS, Osborne CA: Calcium oxalate urolithiasis in a dog and cat with a functional parathyroid adenocarcinoma. JAVMA 206:817-9, 1995. Mahoney CP, Cassady C, Weinberger E, Winters WD, Benjamin DR: Humoral hypercalcemia due to an occult renal adenoma. Pediatr Nephrol 11:339-42, 1997. Anderson TE,Legendre AM,McEntee MM:Probable hypercalcemia of malignancy in a cat With bronchogenic adenocarcinoma. JAAHA 36:52-55, 2000.

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Chemotherapy: Newest Advances for the New Millennium Chemioterapia: le più recenti acquisizioni per il terzo millenio

Cancer is the number one natural cause of death in dogs and cats in many industrialized nations. More and more clients from these countries are demanding advanced care for their pets with cancer. Therefore, there ia an increased demand for veterinarians who are willing to try chemotherapy for pets with cancer. Many advances in cancer chemotherapy have been made, resulting in improved quality and length of life for pets with a wide variety of malignancies. In addition, declining costs and increased availability of anticancer compounds is making this type of therapy quite attractive for the general practitioner. Veterinarians who do chemotherapy must make sure that they are very aware of the potential benefits and toxicoses of these drugs. Oral and written information should be given to the owner about these medicines with the goal of making the client as aware of these drugs as the attending veterinarian. Finally, the client should have access to advanced veterinary care at any time if any problems occur.

PRINCIPLES OF CANCER CHEMOTHERAPY The clinician should be knowledgeable about specific in dications and uses, dosage, timing, resistance and toxicity of chemotherapeutic agents.1-5 The following is a brief description of these important points.

Indications and Uses 1-4 The list of malignancies successfully treated with chemotherapeutic agents is increasing each year (Table 1 nad 2). Some of the tumors successfully treated include: leukemia, lymphoma, pulmonary lymphomatoid granulomatosis, multiple myeloma and other hematopoietic tumors, mammary neoplasia, canine thyroid carcinoma, squamous cell carcinoma, transmissible venereal tumor, canine hemangiosarcoma, osteosarcoma and oral malignant melanoma. As a general rule, combination chemotherapy is superior to single agent chemotherapy. The benefits of single drug treatment regimens versus multiple drug regimens include less toxicity and less expense.1-4 The disadvantages of a sin-

gle drug regimen are decreased efficacy and rapid development of tumor resistance. The development of tumor resistance is generally slower with combination chemotherapy than with single drug treatment regimens. The disadvantages of multiple antineoplastic protocols or approaches are increased cost and toxicity. When drugs are used in combination, several important points must be kept in mind.1-4 • Each drug in a combination must be effective when used alone. • Drugs with overlapping toxicities should be avoided unless they are arranged in a protocol to prevent superimposition of their toxicoses. • Drugs should be used at their maximum dosages. • The concurrent use of several chemotherapeutic agents sequentially are most effective when they have different mechanisms of action and act at different stages of the cell cycle. Dose: Drug dosages should be used to cause minimal toxicity with maximal effectiveness.1-7 The most effective dose of chemotherapeutic agents is often very close to the toxic dose. Doses of chemotherapeutic agents are often given on the basis of body surface area in square meters (m2 or m2/body surface area, Table 3). There are three possible exceptions to the dosing of chemotherapeutic agents on a meter squared basis are melphalan, doxorubicin and cisplatin. Melphalan is best dosed on a mg/kg basis when it is given intravenously because it is not excreted or metabolized in a complex fashion.8 Doxorubicin is more toxic for small dogs and cats; 9 the metabolism and elimination of this antitumor antibiotic appears to be delayed in these small animals when compared to larger size animals dosed on a per meter squared basis. Small dogs that receive cisplatin are more likely to vomit than large animals.10 Drugs that are dosed on a mg/m 2 method, small animals ultimately receive more per pound than large dogs and exhibit more toxicity. Further studies are necessary to determine if tumors respond better when the drugs are dosed per meter square or mg/kg. Some drug dosages are modified only when the efficacy of the chemotherapeutic agent can be enhanced or the toxicity diminished. When organ dysfunction delays metabolism or elimination of a drug, alterations in the dosa ge should be considered. Table 4 reviews some circumstances where dose

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modifications may be indicated for veterinary patients with altered liver or kidney function. 1-7 Timing: The timing of the administration of antitumor drugs is critical.1-7 Normal cells have better repair mechanisms than tumor cells which better enable them to correct cellular damage. Therefore, cytotoxic drugs must be given at proper intervals to allow the tumor cells to die while normal cells recover. If the proper timing of the drug dose is not used, increased toxicity or lack of efficacy occurs. The efficacy:toxicity ratio can be enhanced by altering either the dosage of the drug or the length of time the malignant cell is exposed to the drug (efficacy = dosage x time).1-7 The efficacy of a chemotherapeutic agent is directly related to the time the tumor cell is exposed to the drug. In addition, the acute and short term toxicoses of a drug is often directly related to the peak serum concentration of that agent. Constant, low level release of a drug increases the time the tumor is exposed to a drug and also reduces the peak serum concentration of that drug. The goal of enhancing efficacy while minimizing toxicoses seems to be a reality in veterinary medicine, For example, one sustained release product (OPLA-pt or polylactic acid impregnated with cisplatin) has been used to reduce local recurrence and the prevalence of metastases of osteosarcoma in the dog.11 This polymer reduces local recurrence after limb sparing surgery and delays metastases with minimal toxicity. Other investigators have shown that a wide variety of other chemotherapeutic agents have been implanted into a protein carrier matrix and a vasoactive drug to treat dogs with oral melanomas.12 The dogs treated this way de veloped a complete response (55%) and a partial response (20%). A similar but unrelated method for delivering chemotherapeutic agents over a sustained period of time is by intracavitary therapy. For example, dogs with mesotheliomas can be treated in the thoracic or abdominal cavities by administering cisplatin in saline.13 The cisplatin is used as therapy for the tumor lining the body cavity with very high concentrations of drug. In addition, the cisplatin becomes protein bound within the body cavity for later slow release locally and systemically over a prolonged period of time (days to weeks). In contrast, when administered systemically almost all of the cisplatin is eliminated within a few hours. Resistance: Drug resistance is, without a doubt, one of the most important challenges facing oncology.14-17 Biochemical mechanisms of resistance that have been identified include, but are not limited to: • Decreased drug uptake from the site of administration (e.g. intestinal tract) • Decreased drug-activating enzymes for drugs that require biotransformation • Increased drug-inactivating enzymes • Increased concentrations of the inhibited target enzyme • Altered affinity of the target for the drug • Increased DNA repair • Increase in an alternative metabolic pathway, bypassing the drug inhibition as with methotrexate • Increase in drug removal from the cell that is seen with the p-glycoprotein pump or altered drug binding to

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topoisomerase II which both contribute to the phenomenon known as multiple drug resistance (MDR) Many believe that the most important of the previously mentioned mechanisms is multiple drug resistance (MDR). This is mediated in one situation by increased expression of the membrane glycoprotein which mediates the efflux of vinca alkaloids, anthracycline antibiotics, actinomycin D, and epipodophyllotoxins such as VP-16 from the cell. This cell membrane pump occurs in many normal tissues including the kidney, liver, adrenal gland and large intestine and is induced in many malignant tissues. This cell membrane pump mediates resistance which results in decreased levels of the chemotherapeutic agent within the cell. MDR may be blocked by various agents including calcium channel blockers, amiodarone, and tamoxifen. The use of these agents and many others may be invaluable clinically, however a great deal more research is indicated before these agents are used in clinical practice routinely. It appears that "designer" drugs that have the ability to block MDR without having adverse effects are going to be needed before MDR can be treated effectively.

Toxicity1-7, 18-24 Several chemotherapeutic agents and their toxicities are noted in Table 1. The best approach is to prevent adverse effects before they occur. If that is not possible, then it is crucial to identify adverse effects early and initiate therapy before they become clinically significant. Cancer patients are often fragile and are often unable to handle adverse effects of these agents as easily as normal dogs. Bone marrow toxicity. Almost all chemotherapeutic agents cause some degree of bone marrow suppression. The key is to make sure that the patient has enough neutrophils prior to the start of chemotherapy and make sure that myelosuppression is not excessive. Should excessive myelosuppression occur, the most common source of bacteria that can result in sepsis is actually from the patient itself. Neutropenia and thrombocytopenia are early signs of bone marrow suppression. Anemia may develop later due to the longer life span of the red blood cell. Almost all animal with cancer have anemia of chronic disease that can be accentuated with the administration of chemotherapeutic agents that reduce bone marrow production of erythrocytes. Many antitumor drugs decrease blood cell numbers days to weeks after they are given. Some oncologists suggest that before a myelosuppressive chemotherapeutic agent is administered, a complete blood count should be performed to ensure there are at least 3,000 neutrophils/ml and 100,000 platelets/ml. These same clinicians suggest that the nadir (lowest neutrophil and platelet counts) should be above 1,500 and 60,000 neutrophils and platelets/ml, respectively. Patients that show clinical signs associated with bone marrow suppression (sepsis, bleeding, etc) should be treated early and aggressively. Some clinicians treat animals with antibiotics prophylactically if neutrophils are less than 1,000/ml. The treatment of clinically significant bone marrow toxicity includes:

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Table 1 - Chemotherapeutic agents used in veterinary medicine. (From Ogilvie GK, Moore AS. Managing the Veterinary Cancer Patient:A Practice Manual. Trenton, NJ, Veterinary Learning Systems, 1995 with permission)

CLINICAL BRIEFING Common Drugs

Potential Toxicoses*

Reported Indications ALKYLATING AGENTS

Cyclophosphamide

BAG; rarely sterile hemorrhagic cystitis

Lymphoma, sarcomas, mammary adenocarcinoma

Chlorambucil

BAG; cerebellar toxicity

Lymphoma, Chronic lymphocytic leukemia

Melphalan

BAG

Multiple myeloma

Thiotepa

BAG

Transitional cell carcinoma ANTIMETABOLITES

Cytosine Arabinoside

BAG

Lymphoma

Methotrexate

BAG

Lymphoma ANTIBIOTICS

Doxorubicin

BAG; unique colitis; cardiomyopathy; perivascular slough; allergic reaction during administration; rarely renal failure

Lymphoma; Sarcomas including hemangiosarcoma; thyroid carcinoma; mammary adenocarcinoma; mesothelioma

Mitoxantrone

BAG

Lymphoma; mammary adenocarcinoma; squamous cell carcinoma

Actinomycin D

BAG; perivascular slough

Lymphoma ENZYMES

L-Asparaginase

Anaphylaxis; disseminated intravascular coagulopathy; pancreatitis; pain on injection

Lymphoma

VINCA ALKALOIDS Vincristine

AG; peripheral neuropathy; perivascular slough

Lymphoma; sarcomas; mast cell tumor; transmissible venereal tumor; thrombocytopenia

Vinblastine

BAG; peripheral neuropathy; perivascular slough

Lymphoma; mast cell tumor

HORMONES Prednisone

Iatrogenic Cushing's disease

Lymphoma; mast cell tumor

MISCELLANEOUS AGENTS Cisplatin

BAG; potent emetic shortly at or after administration; nephrotoxicity; bimodal nadir; neuropathy, including ototoxicity (rare)

Osteosarcoma; transitional cell carcinoma; mesothelioma; testicular and ovarian neoplasia; squamous cell carcinoma; nasal adenocarcinoma; thymoma

Carboplatin

BAG; neuropathy, nephrotoxicity, and emesis (rare)

Osteosarcoma; squamous cell carcinoma

Taxol

BAG; diluent Cremophor EL causes acute allergic reaction upon administration

Lymphoma; mammary adenocarcinoma

Feldene

GI ulceration; nephrotoxicity

Transitional cell carcinoma; squamous cell carcinoma; pain relief

BAG: B=Bone Marrow Suppression; A=Alopecia; G=Gastrointestinal toxicity

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L—asparaginase, if given IV or IP can cause anaphylasis.

• Use aseptic techniques • Minimize trauma, especially in patients that are thrombocytopenic • Control of any bleeding with prolonged application of direct pressure or cold packs • If sepsis is suspected, culture urine, blood and, if indicated, any material obtained with a transtracheal aspirate. Treat with appropriate bactericidal antibiotics (eg: cephalosporins, trimethoprim sulfa, and when appropriate, aminoglycosides) • Discontinue drug(s) that induce excessive bone marrow suppression until the blood counts have recovered and subsequent administration of marrow-suppressant drugs should be done at a reduced dose, generally 25% dose reduction Gastrointestinal toxicity. The clinical signs of this side effect are vomiting and diarrhea. Treatment includes the use of antiemetics (e.g. metoclopramide, propulsid, chlorpromazine), motility modifiers (e.g. diphenoxylate in dogs), protectants and absorbants (e.g. kaolin and pectin), broadspectrum antibiotics if indicated, sulfasalazine for colitis and finally, support with fluids, warmth and nutritional therapy. Doxorubicin is commonly associated with development of colitis. These patients may benefit from a high fiber diet and early treatment if signs of colitis (fresh blood and mucus in the stool, straining to defecate, passing small amounts of stool frequently) are noted.9 Many clinicians will send clients home with meteclopramide and sulfasalazine to use if clinical signs of nausea or colitis are noted. This is very effective if the client is educated about the appropriate use of these drugs and if the patient is treated early and appropriately, not after the clinical signs have been present for some time resulting in significant metabolic disease . Allergic reactions. Allergic reactions are very rare, especially if the drugs are administered appropriately. Signs of hypersensitivity include urticaria, vomiting, diarrhea, hypotension and loss of consciousness. L-asparaginase is one of the most common drugs to induce an acute allergic or anaphylactoid reaction unless administered intramuscularly rather than intravenously or intraperitoneally.25 Doxorubicin can induce allergic reactions, especially if the drug is ad-

This dog has a local irritation from the inadvertent perivas cular administration of vincristine.

ministered rapidly. Animals with doxorubicin-induced allergic reactions develop cutaneous hyperemia, intense pruritus, head shaking and vomiting.9 Epinephrine and glucocorticoids should be given for acute allergic reactions. VP-16 (etoposide) which contains polysorbate 80 as a carrier and taxol which is formulated with a carrier Cremophor EL, can cause potentially life threatening side effects.26,27 The adverse effects are induced by the vehicles that keep the drugs in solution. These vehicles can cause massive degranulation of mast cells when either etoposide or taxol are administered intravenously. This can result in a severe drop in blood pressure and whole body edema and hyperemia. Because of the potential allergic reaction, these drugs should be administered with extreme caution. Premedication with diphenhydramine, cimetidine and glucocorticoids may prevent or reduce doxorubicin-, etoposide- and taxol-induced allergic reactions. Cardiac toxicity. All anthra cy cl i n e, antitumor antibiotics can cause cardiotoxicity. Doxorubicin is the most common anthracycline that has been shown to induce a dose-dependent dilat at ive (congestive) cardiomyo p at hy and nondose-dependent dysrhythmias in dogs.28-32 The lifetime dosage of doxorubicin is often limited to 150 to 250 mg/m2 to reduce the number of drug-induced cardiomyopathies. The treatment for dysrhythmias includes discontinuing the drug and use of antiarrhythmic agents if necessary. Doxorubicin should be discontinued if cardiomyo p at hy is detected. In addition, positive ionotropes such as digoxin, diuretics, a low salt diet and vasodilators may be employed.

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Table 2 - Tumors that have been shown to be effectively treated with chemotherapeutic agents. (Fro m :O gilvie GK. Chemotherapy, In: Withrow SJ, MacEwen EG (eds) Small Animal Clinical Oncology, Philadelphia, WB Saunders, CO 1996, p 73 with permission.)

Drug

Species

No. of animals

Overall response rate (%)

Complete response rate (%)

Median response duration (days)

Reference

LYMPHOMA Single agent therapy Mitoxantrone Epirubicin Idarubicin Actinomycin D Doxorubicin

Dogs, cats Dogs Cats Dogs, cats Dogs

44 35 13 12 21

41 82 -85 85

30 74 -70 76

127 143 -42 190

53-57 78,79 58 59, 78 50

Combination therapy LVPCD CVP CVPD VLCM VLCMP CVP VCM

Dogs Dogs Dogs Dogs Cats Cats Cats

55 -46 147 103 38 62

91 89 87 94 82 94 --

84 75 83 -62 79 52

252 180 210 140 -321 112

79 80 35 36 81 34 40

70 42 96

340 540 Cure

82 83 84

0 0

143 --

87 45

147 259

90 91

CHRONIC LYMPHOCYTIC LEUKEMIA Vincristine, chlorambucil, prednisone Melphalan, prednisone Vincristine

Dogs Dogs Dogs

20 37 42

85 92 96

THYROID CARCINOMA Cisplatin Doxorubicin

Dogs Dogs

10 16

60 18

TRANSITIONAL CELL CARCINOMA OF BLADDER OR URETHRA Cisplatin Doxorubicin, cyclophosphamide

Dogs Dogs

15 41

MAMMARY ADENOCARCINOMA Doxorubicin Doxorubicin, cyclophosphamide

Cats Cats

14 14

64 50

91 43

HEMANGIOSARCOMA (ADJUVANT) Doxorubicin, cyclophosphamide, vincristine

Dogs

172

134-413 300 days 257 200

11,85-94 62 95 96

OSTEOSARCOMA (ADJUVANT) Cisplatin Cisplatin doxorubicin Carboplatin Doxorubicin

Dogs Dogs Dogs Dogs

5-162 19 48 16

Urinary Tract Toxicity Cyclophosphamide can cause a sterile chemical cystitis and in rare cases, transitional cell carcinoma of the bladder.33 This may be more common when the drug is given IV vs orally. Clinical signs include stranguria, hematuria and dysuria. The treatment of this problem includes replacing the cyclophosphamide with a different alkylating agent (e.g. chlorambucil). Antibiotics are often indicated because the irregular bladder lining is susceptible to infection. Palliative therapy, while often not effective, consists of intravesicular instillation of dilute 1% formalin or a formulation of dimethyl sulfoxide (DMSO) specifically

designed for instillation into the bladder for severe cases. Most cases resolve with time (4-6 weeks). Local dermatologic toxicity. Many drugs when admin istered perivascularly can cause significant damage to perivascular structures. These include, but are not limited to doxorubicin, actinomycin D, vincristine and vinblastine.1-4,9 Treatment for this problem includes: • Stop the injection • Do not remove the needle or catheter

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• Aspirate the drug and 5 ml of blood back into the syringe • Administer the antidote, if known • For doxorubicin, vincristine and vinblastine perivascular injections, infiltrating the area with 4 to 6 ml of 8.4% sodium bicarbonate and approximately 8 mg of dexamethasone may be helpful, followed by the application of cold (doxorubicin) or warm (vincristine, vinblastine) compresses. • For deep ulcerative lesions secondary to extravasation, aggressive surgical debridement and skin grafts may be necessary. Alopecia. Dogs and cats can lose hair due to the administration of chemotherapeutic agents, although this is rare except for those animals with constantly growing haircoats (e.g. poodles, schnauzers, old English sheepdogs, etc). Cats may lose their whiskers. Neurologic toxicity. The vinca alkaloids and cisplatin may cause a peripheral neuropathy, although this has not been documented to occur with any significant frequency. Vincristine and vinblastine may cause a peripheral neuropathy, whereas cisplatin may cause ototoxicity.

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opment of sterile hemorrhagic cystitis occurs more commonly when the drug is administered intravenously and when compared to the dog, rare in the cat. The prevention of cyclophosphamide-induced sterile hemorrhagic cystitis and subsequent clinical and clinicopathologic evidence of cystitis should include:1-4,33 exclude patients with cystitis because they may be predisposed to the development of cyclophosphamide-induced sterile hemorrhagic cystitis; administer cyclophosphamide in the morning and providing easy access to fresh clean water to ensure adequate hydration; allow the patient to urinate just before owners retire for the night to prevent prolonged contact of cyclophosphamide metabolites with bladder mucosa; lightly salt food, administering furosemide, or when medically appropriate, prescribing prednisone, because these procedures enhance water consumption and subsequent urination. The drug does not decrease platelet numbers significantly (platelet sparing). Cyclophosphamide must be metabolized and activated in the liver; this should be considered when treating patients with advanced liver disease and an elevated total bilirubin. Because of this need for hepatic activation, cyclophosphamide must be given intravenously or orally. Cyclophosphamide is generally given orally, or intravenously at a dosage of 50 mg/m2 orally daily for 4 days every 3 weeks at 250 mg/m2 orally once every 3 weeks.

DRUGS As mentioned earlier, when drugs are used in combination, they are often most effective when they come from different groups. Drugs used in chemotherapy are classified as alkylating agents, antimetabolites, antibiotics, enzymes, plant alkaloids, nitrosoureas and synthetic anticancer drugs.

ALKYLATING AGENTS Some of the most effective drugs used in veterinary medicine are alkylating agents. These include cyclophosphamide and chlorambucil. Alkylating agents act by cross-linking DNA and are considered cell cycle non-specific.1-4 Cyclophosphamide. This alkylating agent is used alone or most effectively when used in combination with other drugs to treat lymphoma (when combined with drugs such as vincristine, prednisone, doxorubicin, mitoxantrone, cytosine arabinoside, methotrexate and L-asparaginase),34-40 soft tissue sarcomas (when combined with vincristine and doxorubicin),41 feline mammary adenocarcinoma (when combined with doxorubicin), 43 synovial cell sarcoma (when combined with doxorubicin), 34 hemangiosarcoma (when used alone or when combined with vincristine and doxorubicin or doxorubicin alone),41,42 oral tumors in cats (when combined with doxorubicin),44 thyroid carcinoma,45 and transmissible venereal tumors. 1-4 The most common doses include 50 mg/m2 orally once daily, three to four days per week or 250 mg/m2 orally every three weeks. The nadir occurs at day 10 and is periodically associated with vomiting, diarrhea,hair loss and occasionally sterile hemorrhagic cystitis. Transitional cell carcinomas have been shown to occur in a few dogs treated with cyclophosphamide. These bladder tumors develop secondary to the metabolites excreted in the urine. The devel-

Chlorambucil. Chlorambucil is used to treat animals with lymphoma (especially when substituted for cyclophosphamide in those patients with an induced sterile hemorrhagic cystitis) and chronic lymphocytic leukemia. 1-4 Remissions of over one year are frequently reported in cases of chronic lymphocytic leukemia treated with chlorambucil.45 The most common dosage employed ranges from 2 to 8 mg/m2 administered orally on a daily basis. Bone marrow suppression has been reported. Melphalan. Melphalan is used to treat multiple myeloma (also known as plasma cell myeloma) with remissions generally exceeding one year.1-4 One method of dosing is 7 mg/m2 daily, administered for 5 days, then no therapy for three weeks, has been recommended. Another dosing scheme uses a dosage of 0.05 to 0.1 mg/kg orally, once daily, until remission is obtained, and then 0.05 to 0.1 every other day thereafter. Toxicities are similar to those found with cyclophosphamide.

ANTIMETABOLITES Antimetabolites interfere with biosynthesis of nucleic acids by substituting them for normal metabolites and inhibiting normal enzymatic reactions. The dose of each drug differs with the different protocols. Methotrexate. Methotrexate has been used with variable results in combination with other drugs to treat lymphoma, myeloproliferative syndromes, transmissible venereal tumors, Sertoli cell tumors and osteosarcoma.1-4,36,37,39,40 Methotrexate, an inhibitor of dihydrofolate reductase that interferes with purine and pyrimidine synthesis, is given to

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ANTIBIOTICS Doxorubicin is the most effective antitumor antibiotic. These agents do not have significant antimicrobial activity despite the classification "antibiotic". Antibiotics form stable complexes with DNA, therefore, inhibit DNA or RNA synthesis. Examples include doxorubicin, bleomycin and actinomycin D. These drugs are cell cycle non-specific and may cause bone marrow suppression, gastrointestinal toxicity, and alopecia.

Doxorubicin causes more adverse effects to smaller dogs than biger dogs. Therefore, for dogs less than 10 kg, a dosage of 1 mg.kg is preferred to reduce adverse effects.

human patients at a very high dose and then reversed with leucovorin; this is rarely done in veterinary medicine. The drug has many toxicities,including myelosuppression, renal and hepatic damage, vomiting, diarrhea and hair loss. The most common dose used in veterinary medicine is 2.5 mg/m2 daily. 5-fluorouracil: This drug should never be used in cats because it can cause severe, potentially fatal neurotoxicity that is less commonly seen in dogs.1-4,47,48 The antineoplastic agent has been used to treat canine carcinomas with variable success. Several toxicoses have been reported when prescription 5-FU is dispensed to owners and then used in pet animals. The drug comes in a topical cream and has been used with variable results to treat superficial malignancies, including cutaneous lymphoma. Some investigators use the drug at a dosage of 150 mg/m 2 IV or intracavitarily weekly. Cytosine arabinoside: This antimetabolite has been used alone or in combination with other drugs to treat lymphoma and myeloproliferative disorders.1-4,49 The drug is ineffective for inducing a remission in dogs and cats with lymphoma when used as a single agent. Cytosine arabinoside has been innovatively administered intrathecally for treatment of dogs with lymphoma of the central nervous system and effectively reduces the development of central nervous system metastases when administered systemically to cats with renal lymphoma. Cytosine arabinoside can be administered at relatively high doses and infrequent intervals (e.g. 600 mg/m2 once every three weeks); the chemotherapeutic agent can also be administered at a low dose constant schedule (e.g. 10 mg/m2 daily or q12h SQ). The drug has a very short half-life in the dog, therefore, some investigators choose to administer 100 mg of the drug over a three day period with slow constant infusion to ensure the availability of aberrant nucleotide to the tumor cells at all times. Toxicities may include vomiting, diarrhea, myelosuppression, hair loss, etc.

Doxorubicin. This anthracycline antitumor antibiotic is the most effective anticancer agent in veterinary medicine. Doxorubicin has been used to treat lymphoma, thyroid carcinomas, sarcomas and feline mammary neoplasia.1-4,9,35-40,50,51,52 This antineoplastic agent has a broad spectrum of activity against a variety of tumors. The drug has been reported ot cause a unique renal toxicity in the cat at a total cumulative dose above 80 mg/m2 body surface area, however, recent research suggests this may not be a clinically important problem for most animals. The most common dose used in the dog is 30 mg/m2 IV. Most clinicians believe that the drug is less toxic if given slowly over approximately 20 minutes. Smaller dogs and cats should be treated at a dosage of 1 mg/kg over 20 minutes to reduce toxicity. Toxicities seen with doxorubicin include those of most cytotoxic drugs, including a unique colitis and dose-dependent card i o myo p at hy (> 250 mg/m2) and development of clinically significant renal toxicity. The cardiomyo p at hy is dose-dependent and cannot be successfully predicted in advance with standard clinical procedures other than with serial endomyocardial biopsies and gaited nuclear imaging studies. A variety of arr hy t h m i a s , especially supraventricular tachya rr hy t h m i a s , are often noted after cardiac damage occurs. 32 An allergic reaction (erythema of the skin, head shaking, or pruritis noted at or around the time the drug is administered) to the release of histamine can be reduced by pretreatment with diphenhydramine and glucocorticoids. Doxorubicin can induce a severe perivascular slough if given perivascularly. Mitoxantrone. This newer anthracycline-like anticancer agent comes in a multidose vial and is reported to be less toxic than its relative, doxorubicin. Mitoxantrone has been used for the treatment of lymphoma, squamous cell carcinoma, transitional cell carcinoma,mammary gland tumors, and a number of other neoplastic conditions.51-57 Unlike doxorubicin, this drug does not commonly cause allergic reactions, cardiomyopathy, cardiac arrhythmias, colitis and tissue damage at the site of extravasation. It is more myelosuppressive than doxorubicin and can cause alopecia and gastrointestinal disturbances. The effective dosage is 6.0 mg/m2 every two to three weeks in the dog, and 6.5 mg/m2 IV every two to three weeks in the cat. Idarubicin. Idarubicin is an expensive oral drug that is effective for the treatment of lymphoma in cats.58 The drug causes bone marrow suppression, gastrointestinal disturbances and whisker loss in cats.

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should be administered intramuscularly to reduce the probability of anaphylaxis. If the drug is administered intravenously, the potential for inducing an acute anaphylactic reaction is quite high. PEG-asparaginase (Enzon Inc, NJ) is a relatively new product that has equal efficacy to native L-asparaginase; it is administered at a dosage of 30 U/kg IV.60

Hormones Hormones are thought to interfere with cell receptors that stimulate growth. The most common example of hormones used for cancer treatment are the corticosteroids used to treat lymphoma and mast cell tumors.1-4 The dose of prednisolone that is used most frequently in veterinary oncolo gy is 30 mg/m2 daily for four weeks then 15 mg/m2 daily for another three weeks, followed by an every-other-day dosage at 15 mg/m2. Another dosage regimen is 1 mg/kg daily for four weeks, then 1 mg/kg every other day thereafter.

Plant Alkaloids Plant alkaloids bind to the microtubules to prevent the normal formation and function of the mitotic spindle, thus, arresting the cell division in metaphase (e.g. vincristine).

This dog has thrombocytopenia and is bleeding from multi ple sites. Vincristine can be used to boost platelet numbers.

Administration: Intravenous infusion (FDA approval pending). The intravenous product has been administered at a dosage of 0.20 mg/kg IV on days 1, 2 and 3 every three weeks. Actinomycin D. This drug has been used to treat bone or soft tissue sarcomas and lymphoreticular neoplasms including lymphoma and malignant melanoma.59 Work in our clinic suggests that this drug is not effective for the treatment of refractory cases of canine lymphoma. It is an inexpensive drug that is given slowly intravenously at a dosage of 0.7-1 mg/m2 every two to three weeks.

ENZYMES L-asparaginase. L-asparaginase inhibits the enzyme asparaginase synthetase and depletes asparagine in tumor cells. The drug is used to treat lymphoma and lymphoblastic leukemia and may be combined with other neoplastic agents.25,36,37 Asparaginase does not induce a sustained remission when it is used alone to treat lymphoma. The most frequently used dose is 10,000 U/m2 IM weekly. The drug

Vincristine. Vincristine is most commonly used in com bination with other chemotherapeutic agents to treat lymphoma and various sarcomas, including hemangiosarcomas and as a single agent to treat mast cell tumors. 1-4,34-41,59,61,62 It is the drug of choice for treatment of transmissible venereal tumors (TVT).1-4,61 Most TVTâ&#x20AC;&#x2122;s are cured rate with approximately 3-4 dosages. Mast cell tumors in the dog have been treated with vincristine, however many of these patients have serious adverse effects shortly after administration of the vinca alkaloid, presumably due to release of granules from dying mast cells. The drug can also cause premature release of platelets from megakaryocytes, therefore is a treatment for thrombocytopenia. Vincristine can be bound to platelets and re-infused to patients for treatment of immunemediated thrombocytopenia; this latter methodology is effective for reducing the platelet destruction by the reticuloendothelial system. Most oncologists use the drug at a dosage of 0.75 mg/m 2 IV q 1-3 weeks. Vinblastine. Vinblastine has been used to treat lymphoma and mastocytoma.1-4 Unlike vincristine, vinblastine results in myelosuppression. The most common dose used in veterinary medicine is 2 mg/m2 body surface area (BSA) administered weekly. Both vincristine and vinblastine are potent vesicants when administered outside the vein. Vinblastine is administered at a dosage of 2 mg/m 2 IV.

MISCELLANEOUS Cisplatin: Cisplatin is a heavy metal compound that is effective for the treatment of osteosarcoma adjuvantly, squamous cell carcinoma, bladder tumors and mesotheliomas. 1-4,

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The drug may cause myelosuppression (double nadir on days 5 and 16), alopecia, gastrointestinal toxicity, neurotoxicity (rare) and nephrotoxicity. Small dogs are more likely to develop toxicity than large ones. An aggressive fluid diuresis and eliminating dogs with pre-existing renal disease are essential to prevent nephrotoxicity. Although several saline diuresis protocols exist,72-75 a 4 hour diuresis protocol appears to be relatively safe. In that protocol, saline is admin istered intravenously to the dog at 25 mls/kg/hr for three hours. Cisplatin is then given at a dosage of 70 mg/m2 IV every three weeks over approximately 20 minutes using a slow intravenous administration schedule followed by saline administered at 25 ml/kg/hr for one more hour.75 Vomiting that occurs secondary to cisplatin therapy usually resolves within hours after therapy is complete. This may be prevented by pretreatment with butorphanol or serotonin antagonists. Cisplatin is administered by slow intravenous infusion during aggressive diuresis at a dosage of 70 mg/m2 every 3 weeks. Carboplatin This newer cisplatin like drug (300 mg/m2 IV q 3 weeks in the dog) is a relatively new chemotherapeutic agent that is similar to cisplatin except that nephrotoxicity and emesis are rare toxicoses.11 The drug is thought to have a spectrum of activity similar to cisplatin, but may be more bone marrow suppressive. It may be most effective when used to treat osteosarcoma.

SAFE HANDLING OF CHEMOTHERAPEUTIC AGENTS 75-77 Whenever handling chemotherapeutic agents, OSHA guidelines should be followed to the letter. These guidelines are outlined by local, regional and national organizations. As a general rule, pregnant workers or those breast feeding should be excluded from any possible exposure to chemother-

Cisplatin, carboplatin and doxorubicin have all been shown to be beneficial for the adjunctive treatment of osteosarcoma in the dog.

apeutic agents. Everyone in the workplace and all clients should receive oral and written information about the potential risks associated with the use of these drugs and methods on how they can reduce the risk of exposure. All bodily se cretions and excretions should be handled in a way to prevent exposure to these drugs. While it is beyond the scope of this section to outline safe guidelines, the following should be considered: • Wear latex gloves when handling chemotherapeutic agents • Never break tablets: round the dosage down to the next whole tablet • Make sure animal swallows medication • Store medication in an area separate from other drugs and food • Dispose of latex gloves in a closed plastic container • Wash hands after removing gloves • Dispose of all drugs and any disposables that come into contact with these drugs appropriately • Mix up the chemotherapeutic agents using guidelines established by OSHA including the use of a biological safety cabinet.

Table 4 - Possible effect of organ dysfunction on dosing of select chemotherapeutic agents. (From Ogilvie GK, Moore AS. Managing the Veterinary Cancer Patient: A Practice Manual. Trenton,NJ, Veterinary Learning Systems, 1995 with permission)

Drug

Organ Failure

Potential Dose Change

Doxorubicin Vincristine Vinblastine

Liver

Consider initial dose reductions of 50% when bilirubin > 1.5 mg/100 mls; escalate subsequent dosages if acceptable toxicity

Carboplatin VP-16

Kidney

Dose reduction directly proportional to creatine clearance; Note that the car rier in VP-16 can cause profound hypotension and cutaneous reactions

Bleomycin

Kidney

Decrease initial dose 50-75% if creatinine clearance < 25 mls/min/m2

Cyclophosphamide

Kidney (Liver)

Decrease initial dose 50-75% if creatinine clearance < 25 mls/min/m2; (activation of the drug in the liver may decrease efficacy)

Cisplatin

Kidney

Do not use with clinically evident renal failure; caution with any renal problems

Methotrexate

Kidney

Dose reduction directly proportional to creatine clearance

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Mast Cell Tumors: Hot New Diagnostics and Treatments for 2002! Novità scottanti per il 2002 nella diagnosi e nel trattamento del mastocitoma

Very few tumors present in such a wide variety of clinical signs: they are indeed the great impostors! They can look like anything and behave differently depending on the histologic type, location and the extent of the disease. The following is a brief discussion about these tumors. Some highlights are as follows: • Mast cell tumor granules do not stain well with Diff Quick type stains unless they are "soaked" in the alcohol for several minutes prior to staining. • Some important prognostic indicators include duration of presence, location and histologic type in the dog. • Mast cell tumors tend to metastasize to nodes, liver spleen and bone marrow...rarely to lungs. • lRadiation therapy is extremely effective for controlling local disease. • Prednisone and vincristine when used as single agents induce a remission (partial or complete) in about 23% of the tumors.

HISTORY AND CLINICAL SIGNS Mast cell tumors may exist in cutaneous or extracutaneous locations. The most common sites in the dog for mast cell tumors are the skin of the trunk and perineal re-

Mast cell tumors generally do not stain well with Diff Quick Stain unless the slide is placed in the methanol for at least 2 minutes prior to regular staining.

gion (50%) and the skin of the extremities (40%). The remaining 10% arise from cutaneous sites of the head and neck. Mast cell tumors are reported to arise in multiple cutaneous locations in approximately 11% of the cases. The majority of mast cell tumors are found in the head and neck region in the cat. Occasionally, the mast cell tumors are located strictly in the spleen of cats. Occasionally mechanical manipulation during examination of this tumor will result in degranulation of mast cell which results in erythema and wheal fo rm ations. This phenomenon has been observed in both dogs and cats and is considered of diagnostic significance when it is observed and is referred to as "Darier sign".

DIAGNOSIS OF MAST CELLS TUMORS Diagnosis of mast cell tumors often can be made by a fine needle aspiration cytolo gy but excisional biopsy is required if accurate histologic grading of the tumor is desired. Mast cell tumors are classified as round cell tumors along with lymphosarcoma, histiocytomas and transmissible venereal tumors.

Mast cells are granulated and are generally descrete. Note the lymphocyte at the end of the arrow as an indicator of size.

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Diagnostic workup of mast cells usually includes a number of procedures. These include a complete blood cell count (CBC), serum chemistry profile, and urinalysis. In addition, fine needle aspiration of the lesion, regional lymph nodes and examination of buffy coats or bone marrow helps to determine the extent of tumor involvement. A CBC is valuable in assessing animals with mast cell tumors because those animal patients with systemic mastocytosis occasionally have peripheral eosinophilia and basophilia in addition to circulating mast cells. Mastocytemia is a more common clinical phenomenon in the cat than in the dog. The CBC may also give evidence of gastrointestinal bleeding or gastrointestinal perforation. In general, mastocytosis associated with primary cutaneous tumors is more easily detected by examination of the buffy coat or bone marrow than by examination of peripheral blood. Care must be exercised in interpreting buffy coats since mastocytemia has been reported in a variety of acute inflammatory diseases of the dog including parvovirus infections. Peripheral mast cell counts may be high in cats with mastocytosis and have accounted for up to 25% of the total white cell count.

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Mast cell tumors are like an octopusâ&#x20AC;Ś the arms are often not detected clinically and are often left behind surgically.

Miscellaneous Tests

Buffy coat smears of blood samples may be examined microscopically for the presence of mast cells but bone marrow smears appear to be more sensitive and are not associated with as many false positives. Bone marrow evaluations should be performed in animals with mast cell tumors. Recent studies have demonstrated that normal dogs have less than 1 mast cell per 1,000 cells in the bone marrow. Veterinary investigators suggest mast cells in greater concentrations than 10/1,000 cells is abnormal.

Occult blood tests may be useful in evaluating patients with mast cell disease. The stools of dogs with mast cell tumors should be examined for the presence of gastrointestinal bleeding as evidence of GI ulceration. In many cases, feces may contain small amounts of blood that are insufficient to produce melena. Gastrointestinal bleeding can be identified by chemical tests based on blood peroxidase activity that involves catalyzing the conversion of hydrogen peroxide to water and oxygen. The most sensitive test contained orthotoluidine or benzidine as a chemical oxidizer to a color product. These tests are so sensitive that false positives may result if the diet has contained red meat for up to three days before testing. Therefore, careful examination of GI bleeding should be made in mast cell cases and indeed, many patients are routinely treated to block the effects of mast cell hyperhistaminemia or that results in increased gastric acid secretion in GI ulceration.

Lymph Node Aspiration

THERAPY

Any animal patient with mast cell tumors should be carefully examined for lymphadenopathy in areas draining the primary tumor. Enlarged lymph nodes should be examined for the presence of mast cells as evidence of tumor spread. Such findings have important implications with regard to therapeutic strategies.

Surgical considerations include wide surgical margins with at least 3 cm of normal looking skin around the tumor should be removed when possible. The 3 cm recommendation is a guideline and might not be feasible when the tumor is located on the face, lower limbs or in the inguinal region. It should be remembered that most mast cells extend laterally to adjacent tissue rather than deep into underlying muscles. All excised tumor should be examined histologically for the completeness of excision. Extension of the tumor beyond the surgical borders should prompt either wider excision or radiation therapy of the tumor bed. Approximately 50% of the mast cell tumors recur at the surgical site traditionally. Histologic grade is an important factor in predicting recurrence at the surgical site. Those that are undifferentiated tend to have a higher recurrence rate. Cats with mast cell tumors with splenic involvement often will benefit from splenectomy. Survival times of 10 weeks to 30 months have been reported following splenectom y, even in patients with evidence of sytemic mastocytosis.

Buffy Coat Smears and Bone Marrow Aspirate

Radiology Abdominal radiographs may be useful in evaluating dogs and cats. This is especially true in cats because of the high incidence of splenic involvement in this species with mast cell tumors. Chest radiographs rarely identify the presence of pulmonary metastases. In cases of mast cell tumors that invo l ve the hindlimbs, p e rineal or preputial area, abdominal radiographs may be helpful in detecting metastatic lymphadenopathy in the iliac and sublumbar lymph nodes.

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Grade II mast cell tumors in the dog are treated with surgery if they are localized. If they are unresectable, then radiation is very effective for controlling local disease. Chemotherapy may be indicate in those dogs with systemic disease.

Grade I mast cell tumors are generally treated with surgery alone.

Glucocorticoid therapy frequently results in partial or occasionally complete remissions in canine mast cell tumors. However, cats appear to be less responsive to glucocorticoid treatment. The effect of glucocorticoids is to reduce markedly the number of mast cells in the mast cell tumor. The exact mechanism by which glucocorticoids exert their cytotoxic effects on mast cell tumors is unknown although it may be similar to the effects of glucocorticoids on lymphocytes. The susceptibility of mast cell tumors might depend on the presence of intracytoplasmic glucocorticoid receptor sites. Glucocorticoid receptor sites have recently been found in the cytoplasm of canine mast cell tumors. Although sex steroid receptors for progesterone and estrogen have been recently described in dogs with canine mast cell tumors, the role of sex steroids in the treatment of canine mast cell tumors has yet to be investigated. The type of glucocorticoids administered appears to be unimportant but it has been suggested that intralesional corticosteroid may be more effective than systemic therapy for local disease. Fewer Cushingoid side effects have been seen with short-acting glucocorticoids such as prednisone or prednisolone when used in the dog. The usual dose of prednisone is .5 mg/kg orally administered once daily and that of triamcinolone is 1 mg for every cm diameter of tumor intralesionally, administered every two weeks. Remission times are usually 10 to 20 weeks. Dogs that are tumor free after six months however have a

low incidence of recurrence and therefore therapy is usually discontinued at this time. Tumor resistance may be caused by the emergence of mast cells with fewer or ineffective glucocorticoid receptors. Survival data based on histologic grade correlates with various chemotherapeutic regimens has not been reported. Vinblastine and prednisone or CCNU appear to be the most favored drug protocols for the treatment of mast cell tumors. The use of these drugs is always with surgery. Ancillary drug therapy is important with canine mast cells. Animals with mastocytosis or palpable mast cell disease should receive H2 antagonists. Cimetidine (Tagamet) reduced gastric acid reduction by competitive inhibition of the action of histamine on H2 receptors of the gastric parietal cells. Ranitidine (Zantac , Glasco? Inc, Fort Lauderdale, FL), a newer H2 antagonist that requires less frequent administration, is in some clinics. The objective of the therapy is to prevent gastrointestinal ulceration associated with elevated levels of histamine and to treat ulcers already present. Some new evidence indicates that cimetidine may also alter the immune response to this tumor as well as activation of certain alkylating agents. Dogs and cats with evidence of gastrointestinal ulceration and bleeding might also benefit from sucralfate (Karafate, Marion Labs Inc, Kansas City, MO) therapy. Sucralfate reacts with stomach acid to form a highly condensed viscous adherent paste-like substance tha t binds to the surface of both gastric and duodenal ulcer sites. The barrier formed at the ulcer site protects the ulcer from potential ulcerogenic properties of pepsin, acid and bile allowing the ulcer to heal. Because sucralfate interferes with absorption of cimetidine, these two drugs should be given at least two hours apart. The usual dosage of sucralfate is 1 gm given orally. H1 antagonists such as benadryl should be used along with cimetidine prior to and following surgical removal of canine mast cell tumors to help prevent the negative effects of local histamine release on fibroplasia wound healing. H1 antagonists also should be used with cryosurgery or hyperthermia therapy. Another recommended ancillary medication is an antiserotonin agent (cyproheptidine). The use of this drug is controversial since serotonin

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has only been identified in rat and mouse mast cells and definitive studies in the dog and cat are lacking. The use of drugs that stabilize mast cells (sodium chromoglycate) have been described in the treatment of human patients with mastocytosis but not in animals. Radiotherapy has been used alone or in combination with other treatment modalities. Most reports indicate remission rates of 48 to 77%. Doses of 3,000 to 4,000 rads were used in these studies. Total radiation therapy is usually fractionated and delivered over a period of three to four weeks. The use of radiotherapy is somewhat expensive and is confined to referral centers. Mast cell tumors in regional lymph nodes and bone marrow appear to be more resistant to the effects of radiotherapy than those confined to the skin. Response of mast cell tumors to radiation therapy may correlate to histologic grade but has not been studied.

PROGNOSIS The natural behavior of mast cells suggests prognosis of this tumor depends on the species, breed, histologic g rade, tumor location, clinical stage and growth rate. In general, cutaneous mast cell tumors car ry a more guarded prognosis in the dog than in cat. Mast cell tumors in the boxer are usually of a lower histologic grade than when found in other breeds. Mast cell tumors in Siamese are of the less malignant histiocytic type. Histologic grade has been shown to correlate with survival following surgical excision by at least two

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investigators. The higher the histologic grade (more undifferentiated tumor),the poorer the prognosis. This criteria has not had universal acceptance however, probably due to the precise nature of histologic grading as well as tumor heterogeneity. Clinical staging and the extensiveness of microscopic tumor masses beyond what might be detected clinically also plays an important role in the failure of universal acceptance of the histologic grading system. In the cat, in addition to the histologic grading system described for the dog, the histiocytic mast cell variant tends to carry a better prognosis than the traditional mast cell. Tumor location is considered by many investigators to be an important prognostic feature. Tumors located in the perineal or preputial area are likely to metastasize both locally and to deep lymph nodes. Clinical stage is a clinical means of assessing tumor spread of the disease process. The higher the clinical stage, the more guarded the prognosis. A high histologic grade, however, should increase the clinical stage at least one level. Growth rate but not tumor size is determined also to be an important prognostic indicator. Growth rate reported by Bostock indicates that dogs that have tumors that grow greater than 1 cm per week have only a 25% chance of living an additional 30 weeks.

Reference 1.

Ogilvie GK, Moore AS. Mast Cell Tumors. In: Managing the Veterinary Cancer Patient: A Practice Manual. Trenton: Veterinary Lear ning Systems. 1995:503-514.

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Strategies for Treating Lymphoma: A Case Based Approach Differenti strategie terapeutiche per il linfoma: un approccio basato su casi clinici

CANINE LYMPHOMA Canine lymphoma are rewarding to treat as long as a few secrets or rules are known. The following are a few important prognostic variables for canine lymphoma. • Clinical Stage: IV + V worse than I-III; dogs with clinical signs worse than if asymptomatic. • Hypercalcemia: worse when associated with an anterior mediastinal mass. • Sex: female dogs better than male dogs. Body size small dogs better than large dogs • Pretreatment corticosteroids: worse. • High grade: higher response rate and longer duration of remission. When considering treatment, one must remember that the more complex the protocol, the longer the first remission, higher the cost and toxicity. The following is a general overview of canine lymphoma.

BACKGROUND Malignant lymphoma (lymphosarcoma) is a lymphoproliferative tumor of solid lymphoid tissues with possible marrow metastasis and a leukemic phase. In dogs, it accounts for 5-7% of all tumors seen and occurs at an incidence rate of 24 cases per 100,000 dogs. It occurs most commonly between 5 and 12 years of age. Boxers, Cocker Spaniels, Fox Terriers, German Shepherds, Scottish Terriers and Golden Retrievers are at an increased risk when compared with other breeds. Etiology for the canine is unknown. In the cat, 90% of the cases are FeLV related and it occurs at an incidence rate of 41.6 cases per 100,000 cats. This accounts for one third of all feline neoplasms and is two and one-half times the rate of lymphoid neoplasia in man. There is a slight male>female predominance in cats.

CLINICAL SIGNS The clinical presentation of canine malignant lymphoma is most commonly that of a multicentric nature with periph-

eral lymphadenopathy being the most striking feature; however, any organ may be affected. In the cat alimentary involvement is the most common presentation. Other anatomic presentations for both the dog and the cat include anterior mediastinal, cutaneous, and unclassified (e.g. mucocutaneous, CNS, renal) forms. Ocular involvement (anterior uveitis, hypopyon, hemorrhage, infiltrate) is seen in approximately 20-25% of canine cases of malignant lymphoma. Involvement of the spleen, liver, and bone marrow is common in both dogs and cats.

DIAGNOSIS Once clinical findings compatible with a diagnosis of malignant lymphoma have been found, aspiration and cytology of accessible lesions should be completed. Malignant lymphoma is characterized by the replacement of normal lymph nodes by a uniform population of pleomorphic and bizarre lymphocytes. After a tentative diagnosis of malignant lymphoma has been supported through rapid cytologic methods, confirmation of the diagnosis may be conducted by biopsy. A tissue core may be obtained by Tru-Cut biopsy or, preferably, a node may be excised for final confirmation. If a dog or cat is to undergo therapy, clinical staging is mandatory. Clinical staging determines the extent of disease in the living animal. Once a baseline of data has been obtained, the clinical oncologist will be able to know which parameters should be monitored in order to reach complete remission. Clinical staging should include radiography of the thorax and abdomen, a complete blood count and platelet count, a bone marrow aspirate and core, an ophthalmic exam, measurement of representative enlarged lymph nodes and a biochemistry panel with special emphasis on calcium and protein levels. Abnormal findings beyond lymphadenopathy are rare, however marrow infiltrate with subsequent release of cells into the peripheral blood is occasionally seen. Hypercalcemia associated with a parathyroid-hormone-like substance is observed in some dogs with malignant lymphoma. This is most often encountered in dogs with anterior mediastinal lymphoma and bone marrow involvement.

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PROGNOSTIC FACTORS

has been made. With chemotherapy, dogs can survive for 6-10 months with an excellent quality of life. Dosage of chemotherapeutic agents for the cat is the same as for the dog except when Adriamycin is used. While dogs may receive Adriamycin every 21 days at a dosage of 30 mg /m2, cats appear to be more sensitive to the drug and many of them can only tolerate a dosage of 20 mg/m2 given every 21 days. Anorexia and renal failure have been reported as significant side effects in cats. Malignant lymphoma is one of the most responsive forms of cancer presented to the practitioner. With appropriate chemotherapy protocols, nearly 90% of animals placed on therapy should reach complete remission. Of those that reach remission, approximately 80-90% will maintain a reasonable (>6 mos) timeframe of excellent quality life. Cost is not inexpensive; however, it is within reasonable financial reach of many clients, thus allowing therapy to be possible. Although marginally effective, prednisone is inexpensive and often used in combination with other drugs to treat lymphoma. With prednisone therapy, the average pet lives 2 months. One-third of the dogs and cats treated with prednisone will go into complete remission, one-third will go into partial remission, and one-third will not respond at all. Adriamycin is one of the most effective single agent treatments for lymphoma in dogs. Of the dogs treated with adriamycin, 81% developed a complete and partial remission. The duration of remission is approximately 9 months. Dogs treated with Adriamycin and then switched to COP (cyclophosphamide, oncovin, prednisone) had a higher second remission rate compared to those started on COP and then switched to Adriamycin. The COP protocol is effective for inducing a remission in 75% of dogs with lymphoma. A median duration of remission of 6 months is commonly seen. Approximately twenty percent of the dogs treated with the COP regimen are in remission at 1 year. In one study, 79% of cats with lymphoma treated with COP achieved a complete remission whereas only 29 percent of cats treated for lymphoblastic leukemia achieved a complete remission. Cats with lymphoma treated with COP had a shorter remission time (64% achieved a complete remission, median remission 5 months) but proportionately more long-term, survivors than dogs. Cats with renal lymphoma tend to have recurrence of tumor in the brain, therefore cytosine arabinoside is frequently recommended as an additional therapy.

Prognostic factors are difficult to confirm due to the variation from study to study. Most treatment reports indicate that hypercalcemia and poor performance status are predictive of short remission and survival times. Animals with advanced clinical stages (World Health Organization Stage IV and V), or at least those with malignant cells in their bone marrows, are also considered to have a poorer prognosis than those animals with less advanced clinical stages (WHO Stage I-III). Some reports suggest that treatment with glucocorticoids prior to therapy with more aggressive chemotherapeutic agents cause a poorer response to therapy than seen in dogs which have not been treated with glucocorticoids, but this finding has not been consistently observed.

Histopathology Considerable controversy exists regarding the value of histopathologic classification of canine malignant lymphoma in regards to prognostic criteria. The Rappaport classification scheme is of little value because nearly all canine lymph node biopsies are classified as diffuse lymphocytic poorly differentiated, thus preventing subgroups of animals to be studied. The National Cancer Institute-Working Formulation (NCI-WF) allows biopsied tissues to be classified in several categories, but once again, the vast majority of classifications fall within either the diffuse large cell or immunoblastic groups and no consistent differences have been observed in remission or survival times for dogs in these two subgroups. Classification in other categories of the NCI-WF might show predictability, but so few cases of canine malignant lymphoma are classified in those categories that firm recommendations for pet owners based on these criteria is not possible.

Therapy Treatment for malignant lymphoma must be systemic in nature since it is a multi-system disease. Chemotherapy is most frequently utilized; however, some immunotherapy has been effective. Untreated, dogs affected with malignant lymphoma live an average of only six weeks once a diagnosis

COP Therapy Protocol for Dogs and Cats

Drug

Dose (mg/m2)

Cytoxan

250 PO

Vincristine

0.75 IV

Prednisone*

30 PO

Prednisone is given daily for the first 21 days,then every other day thereafter. Note that maintenance is continued on a 3 week schedule for at least 1 year.

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The addition of adriamycin to the COP regiment resulted in longer remission time (7 months vs 6 months). A complete remission was attained in eighty-four percent of dogs

treated with COPA. An additional 7% achie ved a partial remission. Twenty-two percent of dogs treated with the COPA protocol were in remission at one year.

COPA protocol for Dogs+ Drug

Cytoxan Adriamycin

250 PO

Vincristine Prednisone

Dose (mg/m2)

30 PO

X >

0.75 IV

30 IV

X >

This protocol can be used in cats if the dosage of adriamycin is reduced to 15-20 mg/m2. Adriamycin is given every other treatment during the maintenance phase for a total accumulative dosage for a total accumulative dosage of 250 mg/m 2. ** Prednisone is given daily for the first 21 days, then every other day thereafter. *

The addition of L-Asparaginase to the COP protocol increased the duration of remission, and the toxicity. The use of this protocol resulted in a complete remission in 76% of the dogs treated. The median duration of remission was 11 months with 48% still in remission at 1 year. Thirty-seven

percent of the dogs treated with this protocol developed toxicoses (vomiting, diarrhea, depression, anorexia). Twentynine percent were sick enough to require hospitalization. The bottom line is that the more drugs are added to the protocol, the longer the remission and the more the toxicoses.

ACOPA protocol for Dogs+ Drug

Dose (mg/m2)

Cytoxan

250 PO

Adriamycin

Asparaginase Vincristine Prednisone

30 IV 10,000 U/m

X 2

0.75 IV

30 PO

X X

X >

The COAP-L protocol has also been recommended for the treatment of lymphoma in dogs. COAP-L protocol for Dogs Drug

Dose (mg/m 2)

Cytoxan

50 PO q24hX4

Cytosine Arabinoside*

100 IV daily X 4 Days

Vincristine L-Asparaginase Prednisone

0.5 IV

X X

20,000 IP

20 mg/m PO BID X 7 days, the 10 mg/m 2 BID q48 hrs.

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The Animal Medical Center has been a proponent of a combination protocol for dogs and cats. Remission rates of 80% are reported with these protocols with a median dura-

tion of 10 months in the dog and 7 months in the cat. Thirty percent live one year while 10-15% survive two years.

AMC Protocol for Dogs + Drug

Dose

Cytoxan IV

200 mg/m2

Adriamycin IV

30 mg/m2

Vincristine IV

0.7 mg/m2

Asparaginase IP

400 U/kg

Methotrexate++ IV

0.5 mg/kg

Prednisone* PO

30 mg/m2

X X

X >

Prednisone is given daily for the first 3 weeks. Protocol is continued in sequence biweekly as described for weeks 8-14 for 12 months, biweekly for 6 months, and then monthly for 6 months.++ Maximum dose is 25 mg. +

AMC Protocol for Cats + Drug

Dose

Cytoxan IV

10 mg/kg

Adriamycin IV

20 mg/m2

Vincristine IV

0.025 mg/kg

Asparaginase IP

400 U/kg

Methotrexate IV

0.8 mg/kg

Prednisone PO

10 mg/kg

X X

14+

X X X

X >

Protocol is continued in sequence biweekly as described for weeks 8-14 for 12 months, biweekly for 6 months, and then monthly for 6 months.

COPA protocol noted above with less toxicity and less cost to the client.

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UNIVERSITY OF WISCONSIN-MADISON PROTOCOL - SHORT CANINE LYMPHOMA PROTOCOL TREATMENT DATE

DOSE

Vincristine, 0.5-0.7 mg/m2 IV

-------------------

------------------

Asparaginase, 400 U/kg IM

-------------------

------------------

Prednisone, 2 mg/kg PO dail y.

-------------------

------------------

Cytoxan, 250 mg/m2 PO or IV

-------------------

------------------

Prednisone, 1.5 mg/kg PO dail y.

-------------------

------------------

Vincristine, 0.5-0.7 mg/m2 IV

-------------------

------------------

Prednisone, 1.0 mg/kg PO daily.

-------------------

------------------

Adriamycin, 30 mg/m2 IV

-------------------

------------------

Prednisone, 0.5 mg/kg PO daily.

-------------------

------------------

Week 6

Vincristine, 0.5-0.7 mg/m2 IV

-------------------

------------------

Week 7

Cytoxan, 250 mg/m2 PO or IV

-------------------

------------------

Week 8

Vincristine, 0.5-0.7 mg/m2 IV

-------------------

------------------

Week 9

Adriamycin, 30 mg/m2 IV

-------------------

------------------

Week 11

Vincristine, 0.5-0.7 mg/m2 IV

-------------------

------------------

Week 13

Cytoxan, 250 mg/m2 PO or IV

-------------------

------------------

Week 15

Vincristine, 0.5-0.7 mg/m2 IV

-------------------

------------------

Week 17

Adriamycin, 30 mg/m2 IV

-------------------

------------------

Week 19

Vincristine, 0.5-0.7 mg/m2 IV

-------------------

------------------

Week 21

Cytoxan, 250 mg/m2 PO or IV

-------------------

------------------

Week 23

Vincristine, 0.5-0.7 mg/m2 IV

-------------------

------------------

Week 25

Adriamycin, 30 mg/m2 IV

-------------------

------------------

Week 1

Week 2

Week 3

Week 4

TOTAL Adriamycin dose to date

_______________________ mg

TOTAL Planned Adriamycin dose _______________________ mg

If in complete remission at week 25, all therapy stops and monthly reevaluations are instituted.

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Selected Reference Carter RF, Harris CK, Withrow SJ, et al. Chemotherapy of canine lymphoma with histopathological correlation:doxorubicin alone compared to COP as first treatment regimen. J Am Anim Hosp Assoc 1987;23:587-596. Cotter SM, Goldstein MA. Comparison of two protocols for maintenance of remission in dogs with lymphoma. J Am Anim Hosp Assoc 1987; 23:495-499.

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Cotter SM. Treatment of lymphoma and leukemia with cyclophosphamide, vincristine and prednisone II. Treatment of cats. J Am Anim Hosp Assoc 1983;19:166-172. Keller, E, MacEwen, E, Rosenthal, R et al. Evaluation of prognostic factors and sequential combination chemotherapy for canine lymphoma. J Vet Int Med, in press, 1994, in press. Matus RE. Chemotherapy of lymphoma and leukemia. In Kirk RW, Current Veterinary yTherapy X. WB Saunders, Co 1989;482-488.

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Impiego della toracoscopia nelle principali patologie intratoraciche di pertinenza chirurgica: tecnica e casi clinici Massimo Olivieri DVM - Clinica Veterinaria Malpensa - Via Marconi 27 - 21017 Samarate - Varese

La toracoscopia è l’esame endoscopico della cavità toracica e degli organi in essa contenuti. Questa indagine può essere utilizzata a scopi diagnostici e/o operativi per molte patologie intratoraciche del cane e del gatto. Normalmente viene utilizzata un’ottica rigida con angolo di visione variabile dai 0 ai 30 °.Nel gatto e nel cane sotto i 5 Kg. si usa un’ottica di 2,7 mm e, aumentando di diametro in maniera progressiva, si arriva ad utilizzare un’ottica di 8 mm nelle razze giganti. Ad essa si connette una fonte luminosa a luci calde o fredde variabile dai 150 ai 300 W. Nei sistemi di videoendoscopia viene collegata all’ottica una telecamera a 1 o 3 CCD. Essa permette di visualizzare le immagini ingrandite e ben illuminate su un monitor, facilitando le manualità dell’operatore. La toracoscopia nei piccoli animali viene effettuata in anestesia generale, rispettando tutte le norme di asepsi e antisepsi che si adottano per una toracotomia. Il posizionamento dell’animale viene scelto in funzione della localizzazione della patologia, e può essere in decubito laterale destro, sinistro, sternale o dorsale. L’intubazione del paziente è tracheale nel caso si voglia valutare l’espansione di entrambi i polmoni, bronchiale selettiva o “semi-selettiva”nel caso si voglia avere il polmone del lato da esplorare collassato o semi-collassato. Il monitoraggio di questi soggetti deve essere completo (ECG, pressione arteriosa, ossimetria, capnografia, temperatura) e l’anestesia ed il respiro assistiti da un anestesista. È necessario infatti ricordare che la patologia toracica sottostante può talvolta creare degli scompensi respiratori aggravati dal fatto che, per l’esecuzione della toracoscopia, è necessario indurre pneumotorace, con le alterazioni respiratorie ed emodinamiche conseguenti. I punti di entrata per l’ottica e per i canali operativi vengono scelti in funzione della localizzazione ed estensione della patologia da indagare. Questi punti non devono mai essere sopra la lesione poiché questo renderebbe più difficoltosa l’esplorazione e l’operatività su di essa.

Come prima cosa è necessario, utilizzando un ago appositamente studiato, l’ago di Verres, far entrare aria nell’emitorace che si desidera esplorare, per creare lo spazio virtuale che permette all’operatore di poter lavorare. Viene quindi effettuata un’incisione di pochi millimetri di cute, sottocute e fascia superficiale, proporzionale al diametro delle camicie per l’ottica e per gli strumenti operativi. Una volta introdotta l’ottica, viene esplorato l’intero emitorace. Localizzata la lesione, questa viene ispezionata, palpata, e vengono effettuati, nelle aree giudicate più significative dalla visione diretta, prelievi per esami colturali, citologici ed istologici. Alla fine dell’esplorazione si introduce, sotto visione, un drenaggio toracico, che viene lasciato durante le prime ore del risveglio e poi rimosso. Vengono infine dati due punti di sutura alla fascia superficiale e alla cute.

INDICAZIONI La toracoscopia risulta essere indicata in tutti i casi in cui sia necessario avere maggiori informazioni, a scopi diagnostici o operativi, su di una patologia intratoracica accertata o presunta, e non sia possibile ottenere le stesse informazioni con altre tecniche meno invasive (esame radiografico, esame ecografico) o si voglia evitare le più invasive (toracotomia, sternotomia). Le indicazioni cliniche più frequenti sono l’esplorazione dell’intero emitorace in corso di patologie quali il piotorace, il mesotelioma, il pneumotorace spontaneo, avendo in questo modo la possibilità di ottenere informazioni diagnostiche e prognostiche molto importanti. Una ulteriore indicazione è rappresentata dal prelievo bioptico sotto visione di masse intratoraciche. In questi casi è anche possibile valutare i rapporti contratti dalla massa con le parti adiacenti e, quindi, le problematiche connesse ad un eventuale intervento chirurgico. Infine le indicazioni operative per la toracoscopia attualmente più utilizzate nei piccoli animali sono la lobectomia parziale, il pneumotorace a grosse bolle, la pericardiectomia parziale o sub totale e la pleurodesi.

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Quadro clinico ed endoscopico delle più frequenti patologie laringee Massimo Olivieri DVM - Clinica Veterinaria Malpensa - Via Marconi 27 - 21017 Samarate - Varese

CENNI DI ANATOMIA CHIRURGICA

diametro della rima glottidea. Essi vengono distinti in muscoli adduttori ed abduttori. Tra questi ultimi riveste particolare importanza il muscolo cricoaritenoideo dorsale, essendo l’unico muscolo abduttore della laringe. Il principale muscolo adduttore è invece il tiroaritenoideo. La componente sensoriale della mucosa laringea e motoria del solo muscolo cricotiroideo deriva dal nervo laringeo craniale, che parte dal vago. Il nervo laringeo caudale, che origina dal nervo laringeo ricorrente, provvede invece all’innervazione motoria di tutti i rimanenti muscoli intrinseci laringei. La vascolarizzazione arteriosa proviene dall’arteria laringea craniale, diramazione della carotide esterna, mentre quella venosa dalla vena laringea craniale, che termina nella vena giugulare esterna. I linfatici locali drenano nel linfonodo retrofaringeo.

La laringe è una complessa struttura muscolo - cartilaginea formata da cinque grosse cartilagini (epiglottide, due cartilagini aritenoidi, cartilagine tiroide e cricoide), due piccole cartilagini (sesamoide ed interaritenoide), muscoli e legamenti. Nel suo insieme, essa è attaccata cranialmente all’apparato ioideo e caudalmente alla trachea, di cui ne rappresenta la naturale continuazione (Fig. 1)1. L’epiglottide è la cartilagine della laringe più craniale. Subito aboralmente a questa si trovano le due cartilagini aritenoidi, ciascuna composta da un processo cornicolato più dorsale e da un processo cuneiforme più ventrale, che si continuano direttamente, attraverso la piega ariepiglottica, nell’epiglottide. La cartilagine tiroide è la più grossa delle cinque e rappresenta la porzione più esterna della laringe, formandone buona parte delle pareti laterali e ventrali. Inoltre essa circonda l’aspetto laterale della cartilagine cricoide, con cui è articolata. Infine la cartilagine cricoide, a forma di anello, costituisce la parte principale della parete dorsale della laringe.Nella sua porzione cranio-dorsale essa si articola con la cartilagine aritenoide, mentre in quella più caudale con la cartilagine tiroide. La glottide è la parte più craniale della laringe, ed è costituita dalle cartilagini aritenoidi, dalle pieghe vocali e dalla rima della glottide. Per quanto riguarda i muscoli della laringe, se ne distinguono due tipi: estrinseci ed intrinseci. I muscoli intrinseci hanno un’importanza clinica rilevante poichè controllano il

La laringe riveste delle funzioni di vitale importanza sia per la respirazione che per la deglutizione. Inoltre ha anche la funzione di produzione della voce . Per quanto riguarda la respirazione (Fig. 2), durante l’inspirazione i due muscoli cricoaritenoidei dorsali si contraggono e, abducendo le due cartilagini aritenoidi, ampliano il lume della glottide, permettendo un facile passaggio dell’aria. Tale lume si richiude passivamente durante l’espirazione. In corso di attività intensa la rima glottidea rimane invece costantemente aperta, sia in inspirazione che espirazione.

Figura 1 - Anatomia della laringe (tratto da Evans, Chris tensen : Anatomy of the dog).

Figura 2 - Posizione delle cartilagini ariepiglottiche du rante le fasi respiratorie (tratto da Bojrab : Disease mecha nisms in small animal surgery).

FUNZIONE

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Durante la deglutizione, la protezione dal potenziale passaggio di liquidi o solidi nelle vie aeree è legata,oltre al sollevamento dell’epiglottide,anche alla chiusura totale della glottide. Questa avviene grazie all’azione attiva di muscoli, soprattutto del tiroaritenoideo. Se, per errore, del cibo pas sa nella laringe, recettori laringei evocano da un lato la tosse e dall’altro la chiusura totale della glottide.

SEGNALAMENTO ED ANAMNESI Il segnalamento del cane o del gatto affetto da disturbi respiratori delle prime vie aeree è di notevole aiuto al clinico per sospettare la presenza di patologie laringee. Infatti, molte di queste patologie riconoscono una base ereditaria che funge da fattore predisponente (per esempio l’eversione dei sacculi o il collasso laringeo nelle razze brachicefale) o determinante (per esempio la paralisi laringea giovanile congenita del Siberian Husky, del Bull Terrier, del Dalmata). Ci sono poi alcune patologie acquisite che hanno delle predisposizioni di razza, sesso ed età ben definite. Tra queste la più diffusa è la paralisi laringea idiopatica, che è tipica di soggetti di media età o anziani, più spesso maschi, di razze quali Labrador, Afgano, Pointer, Setter Irlandese. Nel gatto i problemi laringei sono molto meno frequenti rispetto al cane. L’anamnesi dei pazienti che hanno disturbi respiratori delle alte vie aeree è, in molti casi, simile per tutte le patologie di questo distretto anatomico e, spesso, poco specifica per problemi laringei2-3. Il proprietario riferisce che il suo cane ha difficoltà respiratorie, che si accentuano in situazioni di agitazione, di “stress”, o dopo affaticamento. Di solito sono associati rumori respiratori di vario tipo, tosse, cambiamenti della voce (più tipico di problemi laringei), disturbi legati alla deglutizione. Nei casi più gravi il proprietario segnala cianosi delle mucose, episodi sincopali, collassi. Tipicamente, nei mesi più caldi e umidi, questi disturbi tendono ad essere più accentuati e più pericolosi. Talvolta vengono riferiti anche disturbi neurologici o muscolari associati ai disturbi respiratori, che richiedono, oltre alla visita per le prime vie aeree, anche una specifica visita neurologica. Nell’ambito delle forme traumatiche che possono causare problemi laringei, i traumi più frequenti risultano essere sicuramente quelli da lotte tra cani. In questi casi i proprietari possono segnalare disturbi respiratori anche particolarmente gravi, con ferite penetranti e presenza di aria nel sottocute.

ESAME CLINICO L’esame clinico dei soggetti con disturbi respiratori deve essere fatto in condizioni di assoluta tranquillità, evitando situazioni di stress sia nelle manipolazioni che per un eventuale contenimento (prelievi di sangue, esame radiografico, induzione dell’anestesia…). Nei mesi più caldi questo deve essere effettuato in locali possibilmente condizionati e in assenza di altri animali. Nel caso in cui i soggetti siano ipertermici, è utile applicare borse di ghiaccio sulla testa, ascelle, inguine ed estremità. Spesso questi animali risultano essere particolarmente stressati al momento della visita e, nel caso in cui il paziente non si tranquillizzi in un ambiente

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idoneo, è indicato l’utilizzo di sedativi (Acepromazina 0,05 mg/Kg. e.v. o i.m., Diazepam 0,2 mg/Kg. e.v.). L’esame ispettivo permette di evidenziare stenosi delle narici nelle razze brachicefale, tachipnea, dispnea, respiro a bocca aperta, atteggiamenti di “fame d’aria”. Le mucose apparenti possono essere cianotiche nei casi più gravi. La temperatura di questi soggetti è spesso elevata. L’ispezione della glottide può risultare di non facile esecuzione, soprattutto nei soggetti brachicefali, e deve essere interrotta nei casi in cui i disturbi respiratori tendano ad esacerbarsi. Essa andrà poi completata in anestesia generale. La palpazione della laringe, da effettuare con molta attenzione nei pazienti con gravi disturbi respiratori, risulta essere particolarmente utile per la valutazione iniziale delle ferite penetranti, per ve ri fi c a rne l’entità, la presenza di ematomi, di enfisema sottocutaneo e di situazioni che possano richiedere la necessità di una tracheostomia d’urgenza. Essa risulta anche utile per valutare l’estensione di una eventuale neoplasia. L’esame auscultatorio diretto della laringe permette di evidenziare la presenza di eventuali rumori respiratori, che spesso nascondono i normali rumori auscultatori. Anche l’auscultazione polmonare e cardiaca sono importanti per individuare eventuali aree di ipo o iperfonesi e di aritmie cardiache che vanno sempre escluse, soprattutto nel caso in cui il proprietario abbia segnalato episodi sincopali o di collasso. L’esame clinico si conclude mediante l’ispezione diretta della laringe, in anestesia generale, mediante l’utilizzo di un laringoscopio o, molto meglio, di un endoscopio rigido o flessibile. L’endoscopio presenta numerosi vantaggi, tra cui una completa evidenziazione della laringe, sia della porzione più orale che di quella intraluminale.Inoltre fornisce delle immagini ingrandite, ben illuminate e, nel caso si disponga anche di una telecamera ,l a possibilita’ di lavorare in condizioni ottimali osservando le immagini su un monitor, lontani dal cavo orale. Prima dell’anestesia generale andrebbero effettuati esami ematologici, per escludere patologie metaboliche associate e per verificare che non sussistano eventuali controindicazioni all’anestesia generale. Si impone anche una visita cardiologica e relativi accertamenti nel caso in cui siano presenti problemi cardiaci. L’esame radiografico della laringe è utile soprattutto dopo traumi o in presenza di neoplasie. Informazioni importanti si possono invece ottenere dal torace per quanto riguarda patologie polmonari e cardiache eventualmente correlate.

ESAME ENDOSCOPICO: CONSIDERAZIONI ANESTESIOLOGICHE Prima dell’induzione è necessario avere pronto un set per un’eventuale tracheostomia d’urgenza, da effettuare nel caso subentrino problemi durante l’induzione o nella fase del risveglio. L’anestesia generale che viene effettuata in questi soggetti è da considerare a rischio4, e richiede l’assistenza da parte di veterinari con buona esperienza nel settore. Il loro monitoraggio durante l’anestesia deve quindi essere completo, rivolgendo particolare attenzione all’ossimetria. Le fasi più critiche sono rappresentate dall’induzione e dal risveglio. Per quanto riguarda la prima, per la

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Figura 4 - Collasso laringeo (tratto da Orton : Small animal thoracic surgery).

Figura 3 - Eversione dei sacculi laringei (tratto da Orton : Small animal thoracic surgery).

premedicazione vengono usate le stesse sostanze utilizzate per sedare i soggetti agitati. I farmaci scelti per l’induzione devono invece poter essere somministrati in piccole dosi successive e, soprattutto, non devono interferire con la motilità laringea. Rispondono a questi requisiti il propofolo a 4-6 mg/Kg. e.v. o il diazepam associato alla ketamina alle rispettive dosi di 0,27 mg/Kg. e 5,5 mg/Kg. e.v. I barbiturici non sono indicati poiché alterano la motilità laringea. Una volta indotti, l’intubazione deve essere effettuata rapidamente, tenendo presente che, in presenza di patologie laringee quali la paralisi bilaterale o il collasso laringeo, questa manualità può talvolta risultare difficoltosa. Anche il risveglio rappresenta un momento critico. Nel caso in cui siano state effettuate delle manualità nella laringe, questa fase risulta essere ancora più rischiosa. In questi casi si consiglia la somministrazione e.v. di desametazone alle dosi di 0,5 – 2 mg/Kg. Questo contribuisce a far diminuire l’infiammazione e l’edema laringeo, riducendo così i potenziali problemi correlati alla fase del risveglio. Questi soggetti vanno stubati il più tardi possibile, quando sono coscienti, per ridurre i rischi di apnee da risveglio. In tal senso è molto importante effettuare un’anestesia breve ed utilizzare isofluorano come gas anestetico, in modo tale da avere un risveglio rapido. Una volta stubato, il paziente deve essere costantemente assistito fino al risveglio completo.

ESAME ENDOSCOPICO: CONSIDERAZIONI ESPLORATIVE L’esame endoscopico della laringe permette di dare informazioni molto importanti sia dal punto di vista ispettivo che funzionale. Per quanto riguarda l’ispezione, si valutano le porzioni di laringe esplorabili, che devono apparire normo-conformate (Fig. 3), con mucosa non interessata da processi infiammatori. Successivamente, abbassando il piano di anestesia, si valuta la motilità delle cartilagini ariepiglottiche. Queste non devono essere collassate (Fig. 4), devono abdursi durante l’inspirazione e addursi durante l’espirazione. La presenza di un movimento paradosso, con abduzione durante l’espirazione, è tipico della paralisi laringea. In presenza di infiammazioni si effettua un tampone per esami colturali, mentre se sono evidenti tessuti iperplastici o neoformazioni, si eseguono prelievi per esami citologici ed istologici. Nel caso di sanguinamento dalla sede di prelievo, è molto importante avere un controllo totale dell’ emostasi prima del risveglio.

Bibliografia 1. 2. 3. 4.

Evans H.E.,Christensen G.C. (1979),Anatomy of the dog, Saunders, Philadelphia,518 – 526. Orton E.C., McCracken T.O. (1995), Small animal thoracic surgery, Lea and Febiger, Baltimore, 139 – 140. Bojrab M.J., Ellison G.W., Slocum B. (1998), Current techniques in small animal surgery, William and Wilkins, Baltimore, 357 – 359. Fossum T.W. (1997), Small animal surgery, Mosby, Baltimore, 609 – 612.

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Considerazioni sulla diagnostica della Peritonite Infettiva Felina (FIP) Saverio Paltrinieri Med. Vet. Dott. Ric, Istituto di Patologia Generale Veterinaria - Università degli Studi di Milano

Stefano Comazzi Med. Vet. Dott. Ric, Dott. Ric., Istituto di Patologia Generale Veterinaria - Università degli Studi di Milano

Valentina Spagnolo Med. Vet., Istituto di Patologia Generale Veterinaria - Università degli Studi di Milano

Margherita Cammarata Parodi Med. Vet., Istituto di Anatomia Patologica e Patologia Aviare - Università degli Studi di Milano

Wilma Ponti Med. Vet., Istituto di Microbiologia e Immunologia - Università degli Studi di Milano

INTRODUZIONE La Peritonite Infettiva Felina (FIP) è una patologia virale ad esito fatale causata da un coronavirus noto come Feline Coronavirus (FCoV).1 La forma meno patogena di FCoV, conosciuta come coronavirus enterico felino (FECV) causa lievi enteriti, 2 ma dopo mutazione può replicare all’interno dei macrofagi e con essi invade l’organismo:1 in presenza di un particolare stato immunitario dei gatti colpiti, induce fenomeni di ipersensibilità di tipo III o IV, responsabili delle diverse forme di FIP.3,4,5,6 Questi ceppi patogeni di FCoV, noti come FIP virus (FIPV) sono indistinguibili dal FECV, non solo morfologicamente e antigenicamente1,7 ma anche mediante analisi molecolare, dato che le mutazioni che contraddistinguono il FIPV dal FECV non sono costanti e non riguardano frammenti genici ben definiti.8,9 Pertanto la diagnosi di FIP mediante sierologia o ricerca del genoma virale non permette di riconoscere la variante patogena del FCoV.1,9,10,11 Nelle forme effusive la diagnosi è facilitata dall’analisi dei versamenti, che sono caratterizzati da un colore giallo carico, con presenza di fibrina, che tende a coagulare dopo esposizione all’aria e che conferisce al versamento un aspetto filante: 1 ulteriori informazioni diagnostiche possono essere tratte dall’analisi citologica, che mostra una cellularità aspecifica (neutrofili, linfociti, macrofagi) e la presenza

di un fondo proteico granulare,12 ma soprattutto dall’analisi proteica, che evidenzia una quantità di proteine superiore a 3,5 g/dl 13 con una concentrazione di γ-globuline superiore al 50%.13,14 La conferma della diagnosi di FIP si può avere con l’evidenziazione di FCoV nel versamento mediante immunofluorescenza diretta. 15,16 Nelle forme non effusive, al contrario, la diagnosi definitiva viene raggiunta solo mediante esame istologico,1,7 senza il quale si può solo rafforzare il sospetto clinico attraverso esami ematologici ed elettroforetici, che evidenziano alterazioni quali anemia, leucocitosi neutrofila, linfopenia, iperprotidemia, iperglobulinemia con aumento delle frazioni α2 e γ.13,17,18 Tali alterazioni, però, hanno un significato predittivo relativo, essendo presenti anche in gatti affetti da patologie diverse dalla FIP,13,17,18 o addirittura in gatti sani soprattutto se viventi in gruppo.19,20 L’insieme di tali riscontri rende problematica la diagnosi di FIP, soprattutto negli allevamenti felini, dove possono riscontrarsi sia false negatività in fase terminale, dovute ad eclissi anticorpali per la formazione di immunocomplessi,7 sia false positività dovute all’aspecificità delle alterazioni rilevabili in corso di FIP.13,17,21 Dal 1990 il nostro gruppo si occupa della patogenesi della FIP. In questo periodo ci siamo anche occupati della messa a punto di pannelli di test in grado di ridurre false negatività e false positività.5,6,15,16,18,21,22,23 Nel presente lavoro verranno analizzati retrospettivamente i dati

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raccolti negli ultimi 5 anni, in modo da verificare la ripetibilità nel tempo e su un’ampia casistica dei risultati preliminari già riportati.

MATERIALE E METODI Sono stati analizzati complessivamente 262 campioni di sangue, 134 dei quali prelevati da gatti sani, 36 dei quali d’allevamento, campionati 3 volte così da ridurre la variabilità individuale e 26 randagi viventi in colonie. I restanti 128 campioni sono stati prelevati da altrettanti gatti che presentavano sintomi compatibili con FIP. In particolare 86 casi includevano tra le diagnosi differenziali una forma di FIP essudativa, in base a sintomi quali presenza di versamenti, ipertermia, ittero; 42 casi presentavano sintomi quali febbre, sintomi neurologici (atassia, paralisi, fo rm e convulsive) o oculari (precipitati cheratici, uveite, corioretinite), ittero, masse addominali, che avrebbero potuto indurre il sospetto di FIP non effusiva. In occasione di ogni campionamento sono state allestite due provette, una con EDTA, l’altra senza anticoagulante. Utilizzando i campioni in EDTA sono stati effettuati un esame emocromocitometrico completo in contaglobuli (Hemat 8, SEAC, Firenze), con formula leucocitaria valutata microscopicamente su vetrino colorato con May Grünwald-Giemsa e conta reticolocitaria su vetrini colorati con blu brillante di cresile. Sul siero ottenuto dal campione privo di anticoagulante sono state dosate le proteine con metodo al biureto in autoanalizzatore discreto (Abbott VP, Abbott, USA) ed è stata effettuata un’elettroforesi su acetato di cellulosa. Su 43 dei sopracitati campioni di sangue, 25 prelevati da animali sani e 18 da gatti con FIP sono state quantificate mediante citofluorimetria (Becton Dickinson) le popolazioni linfocitarie utilizzando i seguenti anticorpi specifici per la specie felina forniti dal Prof. PF Moore dell’università di Davis (USA), in grado di riconoscere i seguenti antigeni: CD5 (linfociti T totali), CD4 (T helper), CD8 (T suppressor), CD21 (B). Sugli 86 versamenti prelevati sono stati eseguiti esami citologici su citocentrifugato colorato con May Grünwald Giemsa, elettroforesi e ricerca di FCoV mediante immunofuorescenza diretta (DIF) utilizzando un anticorpo specifico per FCoV (VMRD Inc.). La diagnosi finale è stata raggiunta nei casi di FIP mediante esame necroscopico e istologico, e in caso di altre patologie, in base ad esami sierologici specifici (FIV, FeLV, toxoplasmosi), ad esami istologici o alla risposta a terapie.

RISULTATI E DISCUSSIONE La presenza di FIP è stata confermata post-mortem in 83 casi, 64 in forma essudativa, 19 in forma non essudativa. Le altre patologie caratterizzate da presenza di versamenti erano rappresentate da neoplasie epiteliali (14 casi), epatopatie (3 casi), corpi estranei (2 casi) cardiopatie, uroperitoneo, ipertiroidismo (1 caso). Tra le patologie con sintomi compatibili con FIP non effusiva sono state riscontrate forme f ebbrili protratte di probabile origine infettiva, rispondenti a terapia antibiotica (8 casi), neoplasie di diversa origine (7 ca-

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si), emobartonellosi (3 casi), patologie neurologiche di diversa natura (3 casi), toxoplasmosi (2 casi). Per quanto riguarda la possibilità di diagnosi intravitale è risultata particolarmente efficace, nelle forme effusive, l’analisi dei versamenti. I versamenti che presentavano caratteristiche compatibili con FIP per quanto riguarda aspetto macroscopico, concentrazione proteica, percentuale di γ-globuline ed aspetto citologico sono risultati rispettivamente il 75%, il 91%, il 59% e l’85% dei versamenti effettivamente dovuti a FIP ed il 14%, il 63%, il 18% ed il 14% dei versamenti dovuti ad altre patologie. Inoltre il quadro citologico rivelava elementi cellulari diagnostici per altre patolo gie nel 68% dei casi. Infine il 97% dei versamenti con FIP è risultato positivo per FCoV mediante immunofluorescenza diretta (DIF), che invece è risultata negativa in tutti i versamenti non dovuti a FIP. A questo proposito, inoltre va sottolineato che negli unici due casi di FIP in cui il DIF test è risultato negativo, la diagnosi di FIP è stata comunque formulata in base agli altri parametri. Infine, valutando contemporaneamente tutti i parametri sopracitati è stato sempre possibile escludere la diagnosi di FIP in tutti i casi in cui il versamento era dovuto a patologie diverse dalla FIP. Non considerando i reperti riscontrabili nei versamenti, e valutando solamente i reperti ematici, i valori medi ricavati dai 128 gatti con FIP hanno permesso di evidenziare, rispetto ai gatti di controllo, i cui parametri risultavano sempre all’interno dei range di riferimento della letteratura,20,24 le alterazioni tipiche di tale patologia, quali anemia normocitica nomocromica, leucocitosi, neutrofilia, linfopenia, iperprotidemia, iperglobulinemia con aumento delle frazioni α2 e γ (Tab. 1). Ciò nonostante, la variabilità di tali riscontri nella popolazione con FIP è risultata elevata e anche molti gatti sani o con altre patologie presentavano le stesse alterazioni. L’analisi simultanea di più parametri ematologici ed elettroforetici ha comunque permesso di evidenziare almeno due delle alterazioni compatibili con FIP nell’89% dei gatti con FIP, nel 62% dei gatti con patologie diverse e nel 43% dei 134 campioni prelevati da gatti sani. Tali percentuali diminuiscono considerando la presenza di 3 (73%, 40%, 29%, rispettivamente), 4 (48%, 16%, 16%), 5 (16%, 9%, 6%), 6 (10%, 2%, 0%) parametri alterati contemporaneamente. Nessuno dei gatti sani o con altre patologie presentava contemporaneamente tutte le sette alterazioni compatibili con FIP precedentemente citate, che però erano presenti solo nel 4% dei gatti con FIP. Tali percentuali, tradotte in termini di sensibilità, specificità, valore predittivo positivo (PPV) e negativo (NPV) 25 (Tab. 2), mostrano quindi che l’aumento di specificità e di PPV ottenibile valutando contemporaneamente più parametri si associa ad una drammatica diminuzione di sensibilità e di NPV. Ciò significa che solo la presenza di tutte le alterazioni compatibili con FIP dà la certezza diagnostica, ma può determinare un buon numero di falsi negativi. Al contrario, la presenza di solo alcune delle alterazioni compatibili con FIP può essere rilevabile anche in gatti con patologie diverse o addirittura sani, se viventi in allevamenti o colonie feline. Ciò può portare a pesanti conseguenze soprattutto per gli allevamenti, nei quali è consigliato l’allontanamento dei gatti che presentano il minimo sospetto di FIP o addirittura dei gatti che condividono gli stessi ambienti: 1,26 la presenza di sintomi aspecifici quali transi-

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Tabella 1 - Valori medi (±D.S.) rilevati nei gruppi di gatti in esame e relativa analisi statistica. Controlli (C)

FIP (F)

Altre Patologie (A)

ANOVA

Eritrociti x 10 6/µl

8,0 ± 1,7

5,7 ± 2,0

6,3 ± 2,4

***

Reticolociti (%)

0,2 ± 0,3

0,3± 0,7

0,5 ± 1,5

RPI

0,0 ± 0,1

0,1± 0,1

0,1 ± 0,2

Hb (g/dl)

11,8 ± 2,5

8,5 ± 2,9

10,3 ± 3,9

***

A vs C,F

F vs C

Ht (%)

32,5 ± 6,7

25,1± 8,1

29,4 ± 11,3

***

F vs A

F vs C

MCV (fl)

41,1 ± 4,7

49 ,2 ± 46,0

48,4 ± 12,4

MCHC (%)

36,4 ± 3,8

34,4 ± 5,6

35,3 ± 4,9

14,9 ± 1,8

16 ,6 ± 13,8

16,7 ± 2,9

11,3 ± 5,4

16,0± 10,0

19,1 ± 12,1

***

C vs F,A

6,9 ± 4,0

12,9 ± 9,0

14,7 ± 9,9

***

C vs F,A

0,1 ± 0,2

0,8 ± 1,2

0,9 ± 2,0

***

C vs F,A

MCH (pg) 3

Leucociti x 10 /µl 3

Neutrofili x 10 /µl 3

Neutrofili band x 10 /µl 3

Eosinofili x 10 /µl

Tukey HSD test **

*** F vs C,A

C vs A

C vs F

0,9 ± 1,0

0,2± 0,4

0,5 ± 0,8

***

3,3 ± 1,9

1,7± 1,9

2,5 ± 2,2

***

Monociti x 10 /µl

0,1 ± 0,1

0,4 ± 0,7

0,5 ± 0,6

***

Proteine (g/dl)

7,5 ± 0,8

7,9 ± 1,5

7,0 ± 1,5

***

Rapporto A/G

0,9 ± 0,3

0,5 ± 0,3

0,8 ± 0,3

***

C vs A

F vs C,A

Albumine (g/dl)

3,5 ± 0,7

2,4 ± 0,8

2,9 ± 0,9

***

F vs A

C vs F,A

Globuline (g/dl)

4,0± 0,8

5,5 ± 1,5

4,2 ± 1,4

***

α1-globuline (g/dl)

0,4 ± 0,2

0,5 ± 0,3

α2-globuline (g/dl)

0,6 ± 0,2

1,1 ± 0,5

0,9 ± 0,5

***

β-globuline (g/dl)

0,7 ± 0,3

1,2 ± 0,9

1,0 ± 0,4

***

A vs C

γ-globuline (g/dl)

2,2 ± 0,8

2,7 ± 1,4

1,8 ± 1,0

***

F vs A

Linfociti x 10 /µl

C vs A C vs A

C vs F C vs F C vs F,A

F vs C

F vs A

F vs C,A C vs F F vs C,A; C vs A F vs C C vs A

* = P<0.05; ** = P<0,01; *** = P<0,001; ns = non significativo.

Tabella 2 - Sensibilità, specificità, valore predittivo positivo (PPV) e negativo (NPV) relativi al riscontro di alterazioni emato logiche o sieroproteiche utili ai fini della diagnosi di FIP (anemia, leucocitosi neutrofila, linfopenia, iperprotidemia, iperglobu linemia, iper-α2-globulinemia, iper-γ-globulinemia). N° di alterazioni riscontrate rispetto ai dati bibliografici 2

sensibilità

86,0%

70,9%

46,5%

15,1%

9,3%

3,5%

specificità

51,8%

68,4%

85,1%

93,0%

99,1%

100,0%

PPV

57,4%

62,9%

70,2%

61,9%

88,9%

100,0%

NPV

83,1%

75,7%

67,8%

59,2%

57,9%

torie ipertermie o disturbi neurologici di diversa natura in gatti non affetti da FIP nei quali le variabili sopra descritte (età, sovraffolamento, ecc...) abbiano determinato alterazioni ematologiche o sieroproteiche compatibili con la diagnosi di FIP potrebbe indurre l’allevatore ad allontanare questi

animali. Per tale motivo si è voluto verificare se fosse possibile riconoscere la situazione di “normalità” pur in presenza di tali alterazioni. L’esecuzione di esami ripetuti sui gatti sani, infatti, permette di delineare un profilo ematologico e proteico tipico di ogni gruppo. I range di normalità ottenuti

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Tabella 3 - Range di distribuzione dei valori nei diversi gruppi di animali sani e valori di riferimento della bibliografia. Gruppo 1 GC, FA

Gruppo 2 GC, FB

Gruppo 3 GA, FA

Gruppo4 GA, FA

Gruppo5 GC, FA

Gruppo 6 GC, FB

Gruppo 7 GA, nd

Valori di riferimento

Eritrociti x 10 6/µl

7,2-11,6

6,6-9,9

5,5-11,1

4,9-9,8

5,5-10,4

5,5-10,3

3,1-9,8

5,0-10,0

Reticolociti (%)

0,0-0,9

0,0-0,4

0,0-0,5

0,0-1,2

0,0-0,9

0,0-1,2

0,0-0,4

<0,5

RPI

0,0-0,2

0,0-0,1

0,0-0,3

0,0-0,2

0,0-0,3

0,0-0,1

Hb (g/dl)

10,3-14,5

10,7-15,5

5,0-15,4

8,2-13,9

8,7-14,6

9,4-15,8

5,0-15,3

8,0-15,0

Ht (%)

25,6-39,5

26,4-40,1

13,4-42,8

19,4-38,5

23,6-41,3

24,2-43,1

15,2-44,1

24,0-45,0

MCV (fl)

33,0-43,4

36,7-45,2

21,5-41,1

36,4-44,4

37,0-48,8

40,6-47,7

37,3-52,3

39,0-55,0

MCHC (%)

34,7-41,5

36,2-40,5

33,5-42,2

34,7-44,7

34,7-38,5

33,6-39,0

24,4-41,2

30,0-36,0

12,1-15,8

14,1-17,3

7,8-15,6

13,7-17,4

13,1-17,7

14,7-17,3

10,1-18,2

12,5-17,5

8,2-13,2

5,0-17,0

2,8-17,8

6,2-36,2

5,0-15,7

10,1-22,1

4,7-20,1

5,5-19,5

3,5-7,5

2,6-10,2

1,2-13,0

2,7-24,9

2,4-10,3

3,4-15,4

2,6-15,0

2,5-12,5

Neutrofili band x 10 /µl

0,0-0,2

0,0-0,7

0,0-0,2

0,0-0,7

0,0-0,3

0,0-0,8

0,0-0,4

<0,3

Eosinofili x 103/µl

0,1-3,1

0,2-5,6

0,0-1,9

0,0-1,5

0,2-1,2

0,2-2,5

0,0-1,4

0,0-1,5

Linfociti x 10 /µl

1,4-6,3

1,4-7,8

0,9-7,0

1,9-9,5

1,1-5,1

2,2-8,2

0,7-4,1

1,5-7,0

Monociti x 10 3/µl

0,0-0,2

0,0-0,4

0,0-0,3

0,0-0,4

0,0-0,2

0,0-0,3

0,0-0,4

0,0-0,9

Proteine (g/dl)

6,2-7,9

6,6-8,9

6,3-9,5

6,1-8,7

6,0-9,4

6,2-8,0

6,4-9,4

5,4-7,8

Rapporto A/G

0,5-1,6

0,6-1,3

0,4-1,3

0,4-1,2

0,6-1,5

0,7-1,3

0,4-1,3

0,4-1,2

Albumine (g/dl)

2,1-4,2

3,0-4,5

2,3-5,4

2,2-4,0

2,5-5,1

3,0-4,3

2,2-4,3

2,1-3,3

Globuline (g/dl)

2,5-4,8

3,0-5,5

3,0-6,9

3,5-6,0

2,8-4,5

3,1-4,5

2,9-5,7

2,6-5,1

α1-globuline (g/dl)

0,2-0,6

0,2-0,7

0,1-0,7

0,2-0,8

0,2-1,4

0,2-0,9

0,1-1,1

0,2-1,1

α2-globuline (g/dl)

0,3-1,1

0,4-1,0

0,3-0,9

0,4-0,9

0,4-1,2

0,3-1,0

0,4-0,9

β-globuline (g/dl)

0,3-0,9

0,5-1,0

0,4-1,6

0,4-1,2

0,3-1,8

0,4-1,3

0,4-1,4

0,9-1,9

γ-globuline (g/dl)

0,9-2,7

1,1-3,5

1,7-5,0

1,7-4,2

1,0-2,6

1,1-2,5

1,5-3,9

1,7-4,4

MCH (pg) 3

Leucociti x 10 /µl Neutrofili x 103/µl 3

GA = gestione aperta; GC = gestione chiusa; FA = incidenza di FIP alta; FB = incidenza di FIP bassa; nd = dato non disponibile.

nelle singole colonie, infatti, sono risultati non solo molto diversi (più elevati o comunque più ampi) di quelli riportati in letteratura per popolazioni feline di origine diversa, ma sono anche risultati notevolmente differenti tra i diversi gruppi (Tab. 3), e ciò non in tanto in dipendenza da una diversa prevalenza di FIP ma piuttosto in funzione delle caratteristiche di gestione. Le più evidenti alterazioni ematologiche e sieroproteiche rispetto ai limiti di normalità riportati dalla letteratura, infatti, sono state rilevati nei gruppi 3 e 4 e 7 (quest’ultimo costituito da gatti randagi), che erano caratterizzati da una gestione meno controllata e più “aperta”, con frequenti contatti con animali esterni, e che mostravano anche valori medi significativamente più elevati di quelli registrati negli altri gruppi. Al contrario le alterazioni non erano così evidenti nè differenti tra loro, nei gruppi 1 e 5, in cui l’incidenza di FIP negli ultimi anni era risultata simile a quella dei gruppi precedentemente citati e nei gruppi 2 e 6 in cui non erano rilevabili dall’anamnesi remota, casi di FIP.

Tutti questi gruppi, al contrario dei primi tre, erano caratterizzati da una migliore gestione e in particolare da ridotti contatti con animali esterni. Se da un lato questi dati confermano precedenti riscontri,19,20,24 dall’altro indicano che la sola presenza del virus nel gruppo, sembra non indurre alterazioni più evidenti di quelle imputabili al sovraffollamento. Solo in prossimità della comparsa dei sintomi clinici uno dei gatti del gruppo 3 ha mostrato linfopenia e iper-γ-globulinemia progressive, mentre nel gruppo 6, dove l’anamnesi recente rivelava la comparsa del primo caso di FIP al momen to del primo dei tre prelievi, era rilevabile linfocitosi, reperto correlabile alle alterazioni linfonodali riscontrate in gatti recentemente esposti al’infezione.27 Al di là di queste consi derazioni generali sulle caratteristiche ed ematologiche e sieroproteiche dei diversi gruppi, e considerando come range di normalità quelli ottenuti nei singoli gruppi, il numero di campionamenti in cui siano rilevabili alterazioni compatibili con FIP è sensibilmente inferiore a quello rilevabile dal

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Tabella 4 - Valori rilevati negli animali con FIP appartenenti ai gruppi 1, 3, 4 e 6. N° gatto

169

194

344

386

435

444

456

329

Eritrociti x 10 6/µl

4,52

4,90

5,82

8,10

5,52

6,94

6,41

4,01

Reticolociti (%)

0,10

0,12

0,17

0,01

0,22

0,02

0,31

0,01

RPI

0,02

0,03

0,00

0,05

0,01

0,08

0,00

Hb (g/dl)

7,1

8,6

6,8

9,8

9,6

11,5

9,7

5,6

Ht (%)

17,7

18,6

25,3

24,7

34,2

29,3

16,2

MCV (fl)

39,2

42,9

32,0

31,2

44,7

49,3

45,7

40,4

MCHC (%)

40,1

41,0

36,6

38,7

38,9

33,6

33,1

34,6

15,7

17,6

11,7

12,1

17,4

16,6

15,1

14,0

18,90

17,50

1,85

16,35

30,20

24,44

20,10

11,26

17,01

15,70

0,43

8,34

25,97

19,80

17,49

9,91

Neutrofili band x 10 /µl

1,51

0,18

0,02

0,16

0,00

1,47

0,00

0,79

Eosinofili x 10_/µl

0,00

0,18

0,09

0,00

0,40

0,00

Linfociti x 10 /µl

0,38

0,93

1,30

7,85

2,11

2,69

2,21

0,56

Monociti x 10 3/µl

0,00

0,53

0,02

0,00

2,11

0,24

0,00

Proteine (g/dl)

7,83

5,83

7,6

9,2

9,8

Rapporto A/G

0,50

0,49

0,32

0,41

0,18

0,24

0,50

0,29

Albumine (g/dl)

2,61

1,92

2,21

2,20

1,81

1,77

3,25

2,02

Globuline (g/dl)

5,22

3,91

6,80

5,40

10,19

7,43

6,55

6,98

α1-globuline (g/dl)

0,78

0,55

0,20

0,24

0,52

0,87

0,56

1,76

α2-globuline (g/dl)

1,88

1,03

0,41

0,65

0,86

0,74

1,36

0,59

β-globuline (g/dl)

1,06

0,95

0,96

0,86

1,15

1,10

1,41

1,65

γ-globuline (g/dl)

1,50

1,38

5,23

3,64

7,66

4,72

3,21

2,99

Gruppo di appartenenza

MCH (pg) 3

Leucociti x 10 /µl 3

Neutrofili x 10 /µl 3

confronto con i range di normalità riportati in letteratura:20,21,24 considerando i parametri utili per la diagnosi di FIP, solo il 15% dei campioni e il 15% dei gatti esaminati mostrava alterazioni di due parametri e solo il 4,4% dei campioni e l’8% dei gatti presentava alterati 3 parametri contemporaneamente. In nessun caso si sono rilevate alterazioni contemporanee di 4 o più parametri. La possibilità di falsi positivi, inoltre, diminuisce soprattutto nei gruppi 3 e 4 che, come si è detto, presentavano le più evidenti alterazioni: nel gruppo 3 la percentuale di campionamenti in cui erano presenti almeno 2 o 3 alterazioni compatibili con FIP è scesa dal 73% al 21%, dal 32% al 5%, e in nessun caso sono state rilevate contemporaneamente 4 alterazioni compatibili con FIP, che invece erano presenti nel 10% dei campioni, confrontando i risultati con i range della letteratura. Nel gruppo 4 si è osservato un andamento analogo, anche in termini quantitativi. La diminuzione delle false positività è particolarmente apprezzabile in considerazione del fatto che, al contrario, i reperti ematologici e sieroproteici di gatti provenienti dagli stessi gruppi, ma affetti da FIP, sono risultati comunque differenti non solo dai range della letteratura, ma

anche dai valori di normalità calcolati all’interno del gruppo di appartenenza (Tab. 4), con l’eccezione del gruppo 3. La fenotipizzazione citofluorimetrica dei linfociti circolanti evidenzia una diminuzione di tutte le sottopopolazioni linfocitarie nei gatti con FIP rispetto a quelli di allevamenti in cui tale patologia non era mai stata riscontrata (Tab. 5). Inoltre, la somma delle percentuali di linfociti T e B è inferiore al 100% dei linfociti e quella delle percentuali di linfociti helper e supressor è inferiore a quella dei linfociti T. Tale reperto è già stato riscontrato nell’uomo in corso di infezione da virus dell’immunodeficienza acquisita, ed è ritenuto conseguenza di alterazioni della membrana linfocitaria che non permettono la visualizzazione degli antigeni.28 Nell’insieme, tali riscontri confermano osservazioni preliminari da noi riportate,22 ma non possono essere considerati patognomonici da FIP, viste le numerose situazioni in cui essi possono essere riscontrati, prime fra tutte le altre patologie virali dei felini, quali l’immunodeficienza felina (FIV) e la leucemia virale felina (FELV). 29 Al contrario appare di particolare interesse il fatto che, rispetto ai controlli, i linfociti T helper diminuiscono, seppure in misura minore rispetto ai

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Tabella 5 - Valori medi (± D.S.) relativi alla tipizzazione citofluorimetrica delle popolazioni di linfociti circolanti. Gruppo 1 (FIP)

Gruppo 2 (Esposti al FIPV)

Gruppo 3 (Controlli)

ANOVA *

Tukey HSD test **

***

T (%)

47,3 ± 23,4

51,8 ± 11,2

65,5 ± 7,3

3 vs 2

3 vs 1

T4 (%)

30,1 ± 20,4

28,7 ± 7,7

41,5 ± 6,2

3 vs 1,2

T8 (%)

13,8 ± 9,3

19,8 ± 5,9

23,2 ± 5,4

1 vs 2,3

B (%)

21,1 ± 16,0

36,2 ± 10,8

30,5 ± 7,3

3 vs 1,2

2 vs 1

T+B (%)

68,4 ± 30,5

88,0 ± 10,9

96,0 ± 4,4

***

2 vs 1

3 vs 1

T4+T8 (%)

43,9 ± 21,6

48,5 ± 11,9

64,6 ± 7,7

3 vs 1,2

T x 10 3/µl

0,55 ± 0,50

1,43 ± 0,53

2,22 ± 1,17

***

2 vs 1,3

1 vs 3

T4 x 10 3/µl

0,37± 0,41

0,80 ± 0,32

1,41 ± 0,72

3 vs 2

3 vs 1

T8 x 10 3/µl

0,14 ± 0,11

0,56 ± 0,25

0,80 ± 0,50

***

1 vs 2

1 vs 3

B x 10 3/µl

0,23 ± 0,24

1,01 ± 0,44

1,10 ± 0,70

***

1 vs 2

1 vs 3

* = P<0.05; ** = P<0,01; *** = P<0,001; ns = non significativo.

gatti con FIP conclamata, anche in gatti di allevamenti FCoV endemici, quali possono essere considerati quelli in cui si sono riscontrati diversi casi di FIP negli ultimi anni.1,26 Negli stessi allevamenti, inoltre, si nota un aumento dei linfociti B, che, oltre a confermare precedenti riscontri rilevati istologicamente in linfonodi di gatti esposti a FIP,27 può assumere valore diagnostico in termini di identificazione di soggetti portatori se confermato da un’ulteriore ampliamento della casistica.

4. 5.

7. 8.

CONCLUSIONI L’analisi dei dati raccolti conferma il ruolo diagnostico dell’esame completo dei versamenti e degli esami ematologici e sieroproteici in corso di FIP. I dati rilevabili dai parametri ematici, in particolare, assumono valore diagnostico soprattutto quando vengono paragonati al profilo ematico degli animali sani del gruppo di origine: in questo modo, infatti, è possibile ridurre al minimo il rischio di false positività senza ridurre la possibilità di identificare correttamente i veri positivi. L’analisi delle popolazioni linfocitarie circolanti, infine, può essere un ulteriore ausilio diagnostico in corso di forme conclamate e potrebbe consentire il monitoraggio di gruppi di gatti FCoV-endemici.

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28.

29.

PONTI W., PALTRINIERI S., COMAZZI S., BARDOTTI M.,POLI G. (2000) Changes in blood lymphocyte subsets in feline infectius peritonitis (FIP)- affected and in FIP-exposed cats: flow cytometric analysis 5th International Congress of Veterinary Virology, Brescia JAIN N.C. (1993) Essential of veterinary hematology, Lea & Febiger, Philadelphia,USA ARMITAGE P.,BERRY G. (1985) Statistical methods on Epidemiology. Pag. 455-483 In:Armitage P.,and Berry G.:Statistical methods in medical research. Blackwell scientific publications, Oxford, 1985. ADDIE D., JARRET O. (1995) Control of feline coronavirus infection in breeding catteries by serotesting, isolation and early weaning. Fel Pract 23:92-95. KIPAR A., BELLMANN S., GUNN-MOORE d.a., LEUKERT W., KOHLER K., MENGER S., REINACHER M. (1999) Histopathological alterations of lymphatic tissues in cats without feline infectious peritonitis after long term exposure to FIP virus. Vet Microbiol 69:131-137. POTTER A., KIM C., GOLLAHON K.A., RABINOVITCH P.S. (1999) Apoptotic human lymphocytes have diminished CD4 and CD8 receptor expression. Cell Immunol 193:36-47 GUIOT A.L., RIGAL D., CHAPPUIS G. (1997) Spontaneous programmed cell death (PCD) process of lymphocytes of FIV-infected cats: cellular targets and modulation. Vet Immunol Immunopathol 58:93-106

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Preanesthetic evaluation what's important and what's not Esami preoperatori: che cosa è veramente importante?

Robert R. Paddleford DVM, DACVA, DACVECC, Department of Small Animal Clinical Sciences College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37901-1071

Every patient that is to receive a sedative, tranquilizer, narcotic and/or general anesthetic should have a preanesthetic evaluation performed. The preanesthetic evaluation is needed to 1) establish baseline physiological values and 2) determine any pathological conditions that may alter the patient's response to preanesthetic and anesthetic drugs. The preanesthetic evaluation should consist of a pertinent history, a physical examination and any laboratory, radiographic and/or other diagnostic examinations deemed necessary.

HISTORY The history should include: 1) the present medical/surgical problem the patient is being presented for; 2) the proposed operative procedure; 3) any current medications the patient is on; 4) any previous medical or surgical problems and; 5) any previous anesthesia experience, especially if there were complications.

PHYSICAL EXAMINATION The preanesthetic evaluation should include a thorough physical examination. An accurate weight must be obtained since all preanesthetic drugs, injectable anesthetic drugs and fluids are administered on a per kilogram basis. A rectal temperature should be taken to determine if the patient is normothermic, hypothermic or hyperthermic. A temperature of less than 100Β F should be considered hypothermic and a temperature greater than 103Β F should be considered hyperthermic. Careful evaluation of the cardiovascular and respiratory systems should be performed. The cardiovascular physical examination should include palpating the pulse to determine its rate, rhythm and character. The quality of the blood pressure can also be estimated by digitally palpating the femoral artery. Capillary refill time and mucous membrane color can be determined by examining the oral mucous membranes. The heart should be auscultated, both on the left and right sides of the chest, to determine if any heart murmurs are present. In addition, the heart sounds should be correlated with the pulse rhythm to determine if there are any pulse deficits.

Examination of the respiratory system should include observation of the rate, rhythm and depth of respiration. Both the right and left lung fields should be auscultated and mucous membrane color should be observed. Additional physical examination considerations should include the mental status of the patient i.e., is the patient calm, depressed, excited or vicious. This observation may determine what preanesthetic drugs are needed. The patient's nutritional status should be observed, including his/her hydration. An obese patient may need to have preanesthetic and anesthetic drug doses decreased to prevent a relative overdose and they may have difficulty ventilating once they are anesthetized. A very thin patient may have difficulty with drug redistribution, especially with the thiobarbiturates and there fo re have a prolonged anesthetic recovery period. A dehydrated patient may need additional fluid therapy intraoperatively and postoperatively. The age of the patient should also be considered. The very young or old patient may have decreased liver metabolism and therefore, recovery from most preanesthetic and injectable anesthetic drugs may be prolonged. Finally, has the patient been held off of food and water prior to anesthesia. Food should be withheld 12 hours prior to anesthesia and water 4 hours prior to anesthesia. This is to prevent regurgitation and aspiration of stomach contents during the anesthetic and post -anesthetic period.

LABORATORY AND OTHER DIAGNOSTIC TESTS The laboratory evaluation should include a complete blood count (CBC) which includes packed cell volume (PCV), total plasma protein, hemoglobin, red blood cell count, white blood cell count and estimated platelet numbers. The PCV is an indication of oxygen carrying capacity. Preoperatively it should be above 30 per cent. Intraoperatively and postoperatively it should be maintained above 20 per cent. Low PCV's are indicative of anemia and/or blood loss. PCV's of 60 per cent or more may be indicative of dehydration and can increase blood viscosity and decrease cardiac output. Elevated plasma proteins in combination with

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an elevated PCV are indicative of hemoconcentration and dehydration. Plasma proteins should be maintained above 3.5 grams per cent. Many preanesthetic and anesthetic drugs are reversibly bound to plasma protein making them inactive. If there is less plasma proteins, more of the drug is pharmacologically active and therefore, the drug will have an increased effect within the patient. In addition, very low plasma proteins cause a decrease in plasma oncotic pressure making the patient more prone to fluid overload and pulmonary edema. Hemoglobin levels and red blood cell counts give an indication of oxygen carrying capacity and anemia. The oxygen carrying capacity will influence the per cent of oxygen administered during anesthesia and the method of ventilation. The white blood cell count and differential can indicate

Table 1 - Normal Physiological Parameters in the Dog and Cat Dog

Cat

Temp (Î&#x2019;F)

101.5

Pulse Rate (per minute)

70-100

100-120

Respiratory Rate (per minute)

15-30

20-30

Capillary Refill Time

< 2 sec

PCV (%)

37-55

27-45

Hb (g/dl)

12-18

8-14

RBC (x 10 6/mm3)

5-9

5.5-10

WBC (x 10 3/mm3)

6-18

8-25

Total Plasma Protein (g/dl)

6-8

5-7

2.5-4.2

2.2-3.5

< 50

< 14

25-130

17-22

70-110

BUN (mg/dl)

8-25

10-30

Creatine (mg/dl)

< 1.5

Sodium (mEq/l)

140-155

142-155

Potassium (mEq/l)

3.6-5.5

Chloride (mEq/l)

115-120

Calcium (mg/dl)

8-12

8-11

Albumin (g/dl) Alanine aminotransferase (Sigma Frankel) (ALT, SGPT) Alkaline phosphatase (IU/l) (SAP) BSP (% retention) Glucose (mg/dl)

stress or infection and the platelet count is an indicator of hemostatic capability. It is important to evaluate kidney function in a patient since anesthesia generally decreases renal function. The kidneys also play a major role in the elimination of many preanesthetic and anesthetic agents following detoxification in the liver. In the cat, ketamine is excreted virtually unchanged via the kidney. It is vital to maintain proper kidney function in patients with existing renal disease to prevent renal shut down postoperatively. In addition, patients with renal disease may have prolonged recoveries from anesthesia. Creatinine and BUN levels as well as a urinalysis should be done in any patient with suspected renal impairment. It is important to know if a patient's liver is functioning properly prior to anesthesia. All preanesthetic agents and virtually all general anesthetic agents are detoxified by the liver. Therefore, patients with impaired liver function may often have prolonged anesthetic recoveries. They may also experience clotting difficulties. Elevations in alanine aminotransferase, alkaline phosphatase and BSP retention may be indicators of liver impairment. Blood glucose levels are very important in the diabetic patient. Hypoglycemia may produce marked CNS depression and if severe, may cause seizures. Electrolyte evaluation should include sodium, potassium, chloride and calcium levels. Decreased sodium levels can produce prolonged recoveries from anesthesia. A sodium concentration of greater than 130 mEq/L is desirable. Elevated potassium levels may cause marked bradycardia or cardiac arrest. Decreased potassium levels may produce an irritable myocardium and cardiac dysrhythmias as well as skeletal muscle weakness. Ideally potassium levels should be between 3.5 and 6 mEq/L. Increased and decreased calcium levels can lead to cardiac dysrhythmias and cardiac arrest. Calcium levels should be 8 to 12 mg/dl. Low chloride levels may be indicative of vomiting. Thoracic radiographs should be taken on all trauma patients and any patient with cardiac or respiratory problems. An electrocardiogram should be done on any patient suspected of having cardiac problems. After a thorough history, physical examination and laboratory evaluation, the patient's physical status is determined and assigned a number. Class I patients are patients with no organic, physiological or biochemical disturbances. Most patients for elective surgery will be in this category. Class II patients are patients with mild to moderate systemic disturbances caused by either the condition to be treated surgically or by other pathophysiological processes. Examples include mild dehydration, obesity, fractures and mild diabetes. Class III patients are patients with severe systemic disturbances or diseases that are not life threatening. Examples include compensated cardiac, liver or kidney disease and moderate respiratory insufficiency. Class IV patients are patients with severe systemic disturbances that are life threatening and include patients with obstructed intestines, severe respiratory disease, uncompensated cardiac, liver or kidney disease and massive internal hemorrhage. Class V patients are patients that are moribund and will probably die with or without surgical intervention.

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Perioperative monitoring what should i use and what does it tell me? Monitoraggio intraoperatorio: è un costo che vale la pena sostenere?

Robert R. Paddleford DVM, DACVA, DACVECC, Department of Small Animal Clinical Sciences College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37901-1071

INTRODUCTION The majority of perioperative monitoring is directed at cardiovascular and pulmonary parameters. This is because the majority of preanesthetic and anesthetic agents can depress or alter cardiopulmonary function. Noninvasive, continuous monitors seem to be the trend in perioperative monitoring in both human and animal patients.

PERIOPERATIVE ECG MONITORING Perioperative ECG monitoring is noninvasive, continuous and relatively easy to set up. The ECG is a direct measurement of myocardial electrical activity and can provide information on dysrhythmias, myocardial ischemia and electrolyte imbalance. It can also be used as a heart rate monitor. The ECG does not provide any direct information regarding mechanical function of the heart. Lead II is the most common lead monitored perioperatively. This is because lead II usually gives the largest am plitude of the P-QRS-T complex. However, exact placement of the ECG leads will depend on the position of the patient and the surgical field. It is also advisable to have a "freeze" mode on the ECG and/or a paper tracing for a permanent record. This allows one to compare later traces with earlier traces since changes in the ECG tracing can be very important in interpreting the events occurring in the electrical activity of the heart. Definitive diagnosis of cardiac dysrhythmias is dependent on the ECG. Perioperative cardiac dysrhythmias can result from a variety of etiologies including: hypoxia, hypercarbia, endogenous catecholamine release, hypothermia, electrolyte abnormalities, and anesthetic drugs (alpha-2 agonists, opioids, halothane, thiobarbiturates). When perioperative cardiac dysrhythmias occur, one must: 1) diagnose the specific dysrhythmia, 2) determine its underlying cause and 3) institute appropriate therapy depending on the etiology. The more common types of perioperative dysrhythmias include sinus bradycardia, sinus tachycardia, atrioventricular conduction block, and supraventricular and ventricular premature ventricular contractions. Several questions must be answered to properly identify the particular perioperative dysrhythmia.

1. Is the rate too slow or too fast? 2. Is the rhythm r egular? 3. Is there a consistent P-QRS-T wave form that is normal in shape and size? 4. Are there pulse deficits? 5. Is there a P w ave before every QRS complex? 6. Is the P-R inter val decreased? 7. Is there a compensatory pause after the P-QRS-T wave form in question? 8. Are the T waves abnormally large? 9. Is there S-T segment depression or slurring? Heart rates below 60 bpm in the dog and 80 bpm in the cat should be considered bradycardia. Bradycardia can be caused by a number of etiologies including: 1) excessive anesthetic depth, 2) increased vagal tone, 3) hypoxia, 4) drugs (opioids, alpha-2 agonists), 5) hypothermia, 6) hyperkalemia, and 7) myocardial conduction disturbances. Sinus bradycardia that decreases cardiac output and/or blood pressure should be treated. Specific therapy is directed at the underlying cause. Nonspecific therapy includes the administration of atropine (.011 mg/kg - .022 mg/kg IV). If the sinus bradycardia does not respond to atropine, then dopamine (2.5 to 20 µg/kg/min) or dobutamine (2.5 to 20 µg/kg/min) may be needed. Heart rates above 180 bpm in the dog and 200 bpm in the cat are considered sinus tachycardia. Sinus tachycardia is usually a result of an underlying stress or condition. Sinus tachycardia may be due to: 1) too light a level of anesthesia, 2) hypercapnia, 3) hypovolemia, 4) hypotension, 5) hypoxia, 6) drugs (dissociative agents, atropine), 7) hyperthermia and 8) hyperthyroidism. Treatment for sinus tachycardia is usually directed at the underlying cause and not at the sinus tachycardia per se. Atrioventricular conduction blocks (first, second and third degree heart blocks) have the same etiology as sinus bradycardia. The treatment for A-V conduction blocks is also the same as sinus bradycardia. Atrial and ventricular premature ventricular contractions can be caused by a variety of etiologies including: 1) too deep or too light a plane of anesthesia, 2) hypoxia, 3) hypercarbia, 4) hypovolemia or hypotension, 5) catecholamines (endogenous or exogenous), 6) hypokalemia, 7) hyperkalemia, 8) hypercalcemia, 9) certain anesthetics (halothane, alpha-2 agonists, thiopental), 10) endocarditis or myocarditis, 11) severe hypothermia (< 26Ε C), 12) endocardial stim-

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ulation, 13) intracranial disorders and, 14) high preload or afterload. The underlying cause for the premature atrial or ventricular contractions should be determined and treated whenever possible. Perioperative premature ventricular contractions should be specifically treated when: 1) they are increasing in frequency and/or severity, 2) they become multifocal and/or, 3) when they develop into ventricular tachycardia. Specific therapy is directed at the underlying cause. Nonspecific therapy includes evaluating the depth of anesthesia, instituting intermittent positive pressure ventilation with 100% oxygen and instituting or increasing fluid therapy. If the PVC's persist, are multifocal and/or ventricular tachycardia occurs, antidysrhythmic drug therapy should be considered. Lidocaine (1 to 5 mg/kg IV), procainamide (1 to 5 mg/kg IV), propranolol (0.05 to 0.3 mg/kg IV) and verapamil (0.05 to 0.15 mg/kg IV) have all been used to treat premature ventricular contractions. Perioperative ECG monitoring should not be used as the sole method of monitoring cardiovascular function. It does have limitations but it can provide invaluable information regarding myocardial electrical activity.

PERIOPERATIVE INDIRECT BLOOD PRESSURE MONITORING Arterial blood pressure is the product of cardiac output (heart rate x stroke volume) and peripheral resistance. Many preanesthetic agents and most general anesthetic agents effect one or more of these parameters and may cause hypotension. Blood loss during surgery may decrease venous return and stroke volume. The first indication of an impending anesthetic complication may be the development of hypotension. Adequate cerebral and coronary perfusion is considered to require a mean systemic blood pressure of 50 to 60 mmHg. Arterial blood pressure can be measured in animals by indirect and direct techniques. Direct measurements of arterial blood pressure are more accurate and continuous compared with indirect methods but require the introduction of a catheter into an artery by percutaneous or cutdown procedure. The catheter must be flushed hour ly or continuously. Indirect blood pressure monitoring can be done by digital palpation, sphygmomanometry, doppler instrumentation or oscillometric techniques. All indirect techniques are least accurate when vessels are small, there is patient movement, the blood pressure is low, and when vessels are constricted . Doppler instrumentation involves the application of a small piezoelectric crystal over an artery. Energy is transmitted into the underlying tissue. The energy frequency reflected from moving tissues is shifted slightly from that which was transmitted, and this frequency difference is converted electronically to an audible signal. Some Doppler instruments measure blood flow and are used for the measurement of systolic blood pressure; other instruments generate signals from the movement of the arterial wall and can be used to measure both systolic and diastolic blood pressures. Oscillometric technology measures changes in intracuff pressures caused by the changes in appendage size associat-

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ed with each pulse wave as the cuff is slowly deflated. Systolic, mean, and diastolic blood pressure and heart rate are computed and displayed. Many of these instruments can be set to recycle (remeasure) at discrete time intervals. Not all work well in small dogs and cats (measurements are more consistent in medium-sized and large dogs). All of these instruments are easily confused by motion artifact. Normal systolic, diastolic, and mean blood pressures are approximately 100 to 160, 60 to 100, and 80 to 120 mmHg, respectively. Systolic pressures below 80 mmHg and mean pressures below 60 mmHg are assumed to result in inadequate cerebral and coronary perfusion and warrant therapy. Hypotension may be due to hypovolemia, peripheral vasodilation, or reduced cardiac output. Hypovolemia is the most common cause. A multielectrolyte sodium-containing crystalloid replacement solution such as lactated Ringer's is usually the fluid of choice to start replacement therapy. Decreased cardiac output may be due to a variety of disorders. The underlying cause should be identified and corrected if possible. A sympathomimetic agent that causes minimal peripheral vasoconstriction should be used for prolonged support (dobutamine, dopamine). Hypotension is one of the most common anesthetic complications. Early recognition and treatment is dependent on monitoring the arterial blood pressure in patients at risk for developing hypotension. Direct blood pressure monitoring is the most accurate; however, indirect blood pressure monitoring techniques are easier to use and less invasive. Indirect techniques can be used to trend blood pressure changes during anesthesia and surgery.

PERIOPERATIVE END-TIDAL CARBON DIOXIDE MONITORING Capnography is the measurement of carbon dioxide concentrations in the expired air of a patient and can provide an indirect measurement of PaCO 2. Small amounts of gas are continuously aspirated from the breathing circuit of the patient and analyzed. Theoretically, the plateau of the end-tidal carbon dioxide measurement for each breath reflects alveolar gas which in turn rapidly equilibrates with the PaCO2 in a normally perfused, healthy lung. An end-tidal or peak carbon dioxide level of 5% corresponds to a PaCO 2 of approximately 40 mmHg. Increases in end-tidal carbon dioxide can occur with: 1) increased carbon dioxide production, 2) rebreathing, 3) decreased alveolar minute ventilation, 4) pulmonary disease, and 5) soda lime exhaustion. Decreases in end-tidal carbon dioxide can occur with: 1) increased alveolar minute ventilation, 2) airw ay occlusion, 3) breathing circuit disconnection and, 4) breathing circuit leakage. Low readings can also occur when these monitors are used with high flow nonrebreathing anesthetic circuits. End-tidal carbon dioxide monitors appear to be helpful in identifying hypoventilation, apnea, airway obstruction and breathing circuit disconnection in anesthetized patients. However if ventilation rates become excessive (> 60 breaths per minute) the accuracy of these monitors decreases.

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PERIOPERATIVE PULSE OXIMETRY MONITORING Pulse oximetry allows for the instantaneous estimation of arterial oxyhemoglobin saturation. The optical density of hemoglobin is measured using discrete wavelengths of light. Oxygen saturation of hemoglobin is a logarithmic function of the intensity of light transmitted through the hemoglobin as long as a constant light source intensity and hemoglobin concentration are maintained. Instruments sense the difference between light absorption during pulsations (assumed to be arterial) and background absorption (assumed to be due to venous blood, tissue and bone). Arterial PO2 and oxyhemoglobin saturation (SaO2) are not linearly related; however, SaO2 does provide information about tissue delivery of oxygen. Pulse oximeters consist of a probe, a microprocessor, and display components. Reliable pulse oximetry readings have been obtained when the probe has been applied to the toeweb, vulvar membranes or the shaved pinna of the ear. However, in anesthetized patients, the placement of the probe across the tongue seems to provide the most consistent and reliable readings. Recently, a rectal pulse oximetry probe has been developed.

357

There are several factors known to interfere with pulse oximetry readings. Included in these factors are: 1) patient movement, 2) pigmentation, 3) decreased perfusion, 4) hypothermia, 5) anemia and, 6) increased serum bilirubin. Generally, when the instrument tends to be inaccurate, it reads values lower than the actual SaO2. Therefore, this would normally lead to providing increased oxygen unnecessarily. The pulse oximeter can alert the anesthetist to episodes of hypoxia in the anesthetized patient. Pulse oximetry readings should be 95% or above. A pulse oximetry reading of 90% corresponds to a PaO2 of 60 mmHg which is considered hypoxia. Consistent readings in the 91% to 93% range indicate the oxyhemoglobin saturation is lower than normal and steps should be taken to remedy the problem. Conditions that can cause a low pulse oximetry reading include: 1) hypoventilation, 2) apnea, 3) decreased profusion, 4) airway obstruction, 5) inadequate or lack of oxygen supply to the anesthesia breathing circuit, and 6) pulmonary dysfunction. Pulse oximeters can provide a continuous, immediate, noninvasive estimation of oxygenation in the anesthetized patient. They are not fool proof and various factors can interfere with the accuracy of their readings. However, they can prove very useful as an additional monitoring device in the anesthetized patient.

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Anesthetic considerations for the geriatric patient Principi per lâ&#x20AC;&#x2122;anestesia nel paziente anziano

Robert R. Paddleford DVM, DACVA, DACVECC, Department of Small Animal Clinical Sciences College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37901-1071

It is often difficult to define a geriatric patient simply on the basis of chronological age. Some patients will have organ systems typical of a geriatric patient at a young age, whereas, some geriatric patients have organ systems more typical of younger patients. It has been suggested that a patient be considered as aged or geriatric when they have reached 75% to 80% of their life expectancy; however, ultimately each patient must be evaluated as an individual and not simply as a "geriatric" patient. The geriatric patient is likely to have more diseases than a young patient and have less functional organ reserve. This decreased organ reserve has been termed "elderly normal" and may not be apparent until the animal is stressed by disease, hospitalization, anesthesia and surgery and then overt organ failure may occur.

PHYSIOLOGICAL CHANGES ASSOCIATED WITH AGING Geriatric patients have a decreased cardiac reserve compared to younger patients and may have difficulty compensating for cardiovascular changes that occur during anesthesia. Geriatric patients have: 1) decreased baroreceptor activity, 2) decreased blood volume, 3) decreased cardiac output, 4) decreased blood pressure, 5) a decreased circulation time, and 6) vagotonia. In addition, the geriatric patient may suffer from progressive and degenerative myocardial disease. This is usually associated with chronic valvular disease and can lead to an increased myocardial work load and oxygen consumption and demand and thus make the myocardium extremely sensitive to hypoxemia. The decreased cardiovascular function capabilities of the geriatric patient make them very susceptible to anesthetic induced cardiovascular depression and hypotension. Respiratory function progressively diminishes as a patient ages. Physical changes occur in the geriatric patient's lungs and chest wall. There is a decrease in: 1) lung elasticity, 2) closing volume, 3) vital capacity, 4) respiratory rate, tidal volume and thus minute volume, 5) oxygen consumption, 6) carbon dioxide production, 7) maximal diffusion capacity for oxygen, 8) capillary blood volume and, 9) protective airway reflexes. There is an increase in: 1) anatomical dead space, 2) residual volume, 3) functional residual capacity, and 4) residual volume/total lung capacity. All of the above changes are considered normal and part of the aging process.

These changes in the respiratory system are significant in that even mild to moderate respiratory depression due to anesthesia may produce marked hypoxemia and hypercarbia and any pathological disease of the respiratory system, i.e. pneumonia, edema, pulmonary fibrosis, emphysema, etc., will be greatly exacerbated in the geriatric patient. The kidney is the major effective organ in fluid and electrolyte balance. Renal function may be greatly impaired in the geriatric patient. In man, normal aging changes occur in the kidneys and include: 1) decreased renal blood flow, 2) decreased glomerular filtration rate, 3) decreased concentrating ability, 4) nephron degeneration, 5) increased blood urea nitrogen levels, 6) a redistribution of blood flow from the cortex to the medulla due to renal cortical vascular dete rioration, 7) decreased distal tubular function resulting in a decreased ability to handle acid excretion, and 8) an increase in the urine volume necessary for excretion of the obligatory solute load. The functional renal reserve is diminished in the geriatric patient making them more susceptible to the decrease in renal function caused by anesthesia and the geriatric patient is much less tolerant of body water deficits or the excessive administration of fluid. The plasma half life of drugs dependent on renal excretion are increased in the geriatric patient. The aging process results in a reduction in the functional state of the microsomal enzyme systems of the liver. This reduction is present even when the standard biochemical function tests are normal. Geriatric patients often have a decreased hepatic blood flow most likely due to a decreased cardiac output. The plasma half life of drugs dependent on hepatic biodegradation are often increased in the geriatric patient. In man, aging is associated with a reduction in brain weight which is most likely a result of individual neuron degeneration. Myelin sheaths also degenerate which results in increased effects of the local anesthetics. There is strong evidence that neurotransmitters change with age. There is an increased destruction of neurotransmitters and a decrease in the production of neurotransmitters. The reduction in neurotransmitter function may be a result of the decreased quantity of neurotransmitter or perhaps a change in the receptors themselves. Thermoregulatory center function is decreased in the geriatric patient making them more susceptible to hypothermia produced by anesthesia. The autonomic nervous system looses some of its ability to respond to stress in the geriatric human patient. This appears to be most marked in the sympathetic nervous system.

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Despite this reduced response, there appears to be an enhanced response to iatrogenic epinephrine and norepinephrine thus leading to the conclusion that perhaps the autonomic nervous system output is decreased but the receptors are more sensitive.

ANESTHETIC CONSIDERATIONS IN THE GERIATRIC PATIENT A thorough and complete history should be taken from the owner with a special emphasis on: present medical/surgical problems, current medications, previous medical or surgical problems and previous anesthesia experience. A complete preanesthetic physical examination should be performed and a complete laboratory profile should be obtained with special emphasis on renal and hepatic function. An ECG and thoracic radiographs should be included.

Preanesthetic Medications Low dose acetylpromazine, 0.1 mg/kg intramuscular (IM) with a maximum total dose of 1.5 mg, can be very effective in a geriatric animal. Acetylpromazine has minimal respiratory depressant effects and minimal direct myocardial depressant effects. However, acetylpromazine may produce hypotension due to its ability to decrease peripheral vascular resistance. Acetylpromazine is contraindicated in animals with a history of seizures because it lowers the seizure threshold. Acetylpromazine undergoes extensive biodegradation in the liver and recovery from its effects may be greatly prolonged in animals with hepatic dysfunction. This may account for the prolonged recoveries that are often seen in the geriatric animal. The benzodiazepine derivative tranquilizer diazepam is considered a minor tranquilizer and may be very useful as a preanesthetic in the geriatric animal, especially when combined with an opioid drug. It has minimal cardiopulmonary depressant effects. Diazepam is not water soluble and is dissolved in propylene glycol, thus its absorption from IM injection sites may be unpredictable and erratic. If given IV, diazepam should be given slowly because propylene glycol is a cardiopulmonary depressant and may cause hypotension, bradycardia, and apnea when given rapidly IV. Diazepam may be used at a dose of 0.25 to 0.45 mg/kg IM or IV. It may be combined with an opioid such as meperidine (1 to 4.5 mg/kg IM or IV) or butorphanol (0.2 to 0.45 mg/kg IM or IV) for an effective neuroleptanalgesic in the geriatric animal. If the sedative-hypnotic xylazine is to be used in the geriatric animal, it must be used with extreme caution. Its marked cardiovascular effects and its unpredictable respiratory effects may limit its use in the aged animal. Xylazine's effect on respiration is variable and may range from minimal to marked depression of the rate and tidal volume leading to hypoxemia and hypercarbia. Opioids are often used alone or in combination with tranquilizers in the geriatric animal as preanesthetic medications. The ad vantages of the opioids are that they are anal-

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gesic, produce minimal direct myocardial depression, and can be readily antagonized. Opioids often slow the heart rate; however, this may be advantageous in the geriatric animal in that the slow heart rate may lead to a decreased myocardial oxygen demand and consumption and more forceful contraction. Anticholinergics may be used to treat sinus bradycardia produced by opioids if necessary. Butorphanol has been used as an effective preanesthetic and postanesthetic analgesic in the geriatric dog and cat. Butorphanol can produce a dose related respiratory depression similar to morphine; however, butorphanol seems to reach a ceiling beyond which higher doses do not cause significantly more respiratory depression. Butorphanol can produce decreases in heart rate, cardiac output, and blood pressure (BP), but the depression is less than with morphine and oxymorphone. Butorphanol is extensively metabolized in the liver. Butorphanol has good analgesic properties and fair sedation properties. Its effects are readily antagonized with naloxone. When it is combined with a tranquilizer such as diazepam or acetylpromazine, a very acceptable neuroleptanalgesic is produced. The dose range for butorphenol is 0.22 to 0.44 mg/kg IV, IM, or SC. The indiscriminant use of the anticholinergics, such as atropine or glycopyrrolate, should be avoided in the geriatric animal. This is to prevent an unwanted and potentially dangerous sinus tachycardia from occurring. If an animal does experience sinus bradycardia, atropine can be given to effect IV. If vagotonic drugs such as the opioids or alpha 2 drugs are to be used, then the use of an anticholinergic may be indicated. Half of the normal dose of anticholinergic may be given IM as a premedicant (0.02 mg/kg).

General Anesthetics Thiopental can be used to induce anesthesia and for short surgical procedures; however, the lowest possible dose necessary for the procedure should be used. The effects of thiopental on the cardiovascular system are variable depending on species and dose given. Thiopental may produce transitory cardiac dysrhythmias which are usually premature ventricular contractions and of a bigeminal nature. Thiopental is a potent respir atory depressant. Dissociative drugs tend to stimulate the cardiovascular system. Ketamine and tiletamine exert a selective positive inotropic effect on heart muscle that is independent of heart rate and/or the autonomic nervous system. They tend to cause an increase in heart rate, cardiac output, mean arterial BP, pulmonary arterial BP, and central venous pressure by either directly stimulating the central adrenergic centers or by indirectly preventing the uptake of the catecholamines. Increasing the heart rate can cause a marked increase in myocardial oxygen consumption and demands. Both drugs can produce apneustic ventilation, ie, a ventilatory pattern characterized by a prolonged pause after inspiration. Although the respiratory rate may decrease, the tidal volume usually remains normal. In some animals the dissociative agents can produce marked hypoxia and hypercarbia, especially when additional CNS depressant drugs are used in combination with them.

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Propofol is an injectable anesthetics approved for use in dogs. Propofol's rapid onset time is similar to thiopental. A single bolus injection of propofol produces a rapid onset of anesthesia (less than 60 seconds), lasting 5 to 10 minutes. Recovery is very rapid following even repeated doses of propofol. It is rapidly redistributed and rapidly metabolized. The total calculated dose of propofol used for anesthetic induction in the dog and cat is 2-6 mg/kg IV with the lower dose range used in patients that have received preanesthetic sedation. The drug is administered to effect. Approximately 1/3 of the dose is administered every 30 to 45 seconds until the desired level of anesthesia is produced. The total dose given will depend on the preanesthetic sedatives used, the degree of patient sedation and the physical status of the patient. Following propofol induction, anesthesia can be maintained with inhalation agents or by repeated bolus injections or continuous infusions of propofol at a rate of 0.2 to 0.4 mg/kg/min. The maintenance infusion is increased or decreased depending on the desired anesthetic level of the patient. The cardiopulmonary effects of propofol are similar to the barbiturates. Propofol may be suited for use in the geriatric patient since recovery times do not seem to be prolonged in patients with renal or hepatic dysfunction. However, because its cardiopulmonary depressant effects are very similar to the thiobarbiturates, it should be used with caution in any patient with preexisting cardiopulmonary disease or dysfunction.

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Inhalant anesthetics are proba bly the general anesthetics of choice in the geriatric animal, especially for procedures lasting longer than ten to 15 minutes. Halothane, isoflurane or sevoflurane can all be used .

MISCELLANEOUS CONSIDERATIONS Geriatric animals should be preoxygenated for two to five minutes before anesthetic induction to help prevent hypoxia from developing during induction. The animal should be intubated when a general anesthetic is used to provide a patent airway. Close monitoring of cardiovascular and respiratory parameters are essential and, if necessary, the geriatric animal's ventilation should be assisted or controlled. Adequate fluid replacement should be given to prevent a renal crisis and to help maintain a proper hemodynamic state. The rate of IV fluid administration will depend on the particular animal's needs, but will most likely by in the range of 10 to 20 mL/kg/h. Obviously the rate should be decreased in a geriatric animal where the risk of cardiovascular overload is a concern. Fluid therapy may need to be continued for several hours to several days following anesthesia and surgery. The intraoperative monitoring techniques should be continued into the postoperative period or until the geriatric animal has returned to its preanesthetized state.

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The perioperative use of fluids, blood products and adjunct medications Uso di cristalloidi, colloidi e derivati del sangue nel paziente critico

Robert R. Paddleford DVM, DACVA, DACVECC, Department of Small Animal Clinical Sciences College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37901-1071

Hypotension may occur during general anesthesia. Most of the preanesthetic and general anesthetic drugs have the potential to produce hypotension. Blood loss during surgery can further exacerbate the hypotension. The perioperative administration of fluids and/or blood products is used to help maintain cardiovascular stability and counteract hypotension.

ume expansion. Doses of 5 mls/lb (10 mls/kg) or more can produce hypernatremia. Hypertonic saline/dextran expands plasma volume by a factor of 4.5 times whereas Dextran-70 alone expands plasma volume by a factor of 2.1 times. After 30 minutes the effects of the hypertonic saline starts to dissipate; however, the effects of the hypertonic saline/dextran will last for several hours due to the longer dwell time of the dextran.

CRYSTALLOID FLUIDS Isotonic crystalloid fluids are probably the most common volume maintenance fluids administered during anesthesia/surgery. Balanced electrolyte solutions such as lactated Ringers or Normosol-R are often used. Normosol-R is compatible with the administration of stored blood products in the same IV line; whereas, lactated Ringers is not because it contains calcium. Crystalloids are usually administered at a rate of 5-10 mls/lb/hr (11-22 mls/kg/hr). To replace blood loss, crystalloids are administered at a rate of 3:1 or 4:1, i.e., for every 1 ml of blood loss, give 3 to 4 mls of crystalloid fluid. Crystalloids are freely permeable with a short vascular dwell time. Following IV administration, 25% to 30% of the dose of crystalloid remains in the vascular space after 1 to 2 hours.

COLLOIDS-HYPERTONIC SOLUTIONS These fluids are considered volume expanders. They are hypertonic solutions that draw the patient’s extravascular body water into the vascular space. The four main colloid solutions available are hypertonic (7.5%) saline, dextran, hetastarch and albumin.

Hypertonic Saline Hypertonic (7.5%) saline has been used both clinically and experimentally to treat hypovolemic shock. Hypertonic saline creates an osmotically induced fluid shift from the extravascular to the vascular space. Fluid shifts are normally very short-lived; therefore, it is often combined with Dextran-70 (7.5% NaCl + 6% Dextran-70) for a longer effect. A dose of 2-3 mls/lb (4-6 mls/kg) is usually adequate for vol-

Dextran Dextran is a large glucose polymer that distributes to the extracellular space but primarily remains in the intravascular space. Dextran-40 has an average molecular weight of 40,000 (10,000-90,000 molecular weight). Sixty to 70% of Dextran-40 is cleared from the intravascular space in 12 hours. Dextran-70 has an average molecular weight of 70,000 (20,000-200,000 molecular weight). Only 30 to 40% of Dextran-70 is cleared from the intravascular space by 12 hours. The larger the particle, the larger the intravascular “dwell time”; there, Dextran-70 is more often used. The smaller polymers are filtered by the kidneys and the larger ones are phagocytized and metabolized to carbon dioxide and water by the RE system. Dextrans improve hemodynamic parameters by increasing the intravascular volume because they draw extravascular fluid into the vascular space. Dextrans are excellent volume expanders because they have a long “dwell time” and are biodegradable. Dextrans expand blood volume to twice that of the volume infused, i.e., 500 mls of dextran expands to 1050 mls at 2 hours. The dose of Dextran-70 is 2-3 mls/lb (4-6 mls/kg). Up to 10 mls/lb (20 mls/kg) may be infused in 24 hours. Several complications have been associated with the use of dextrans. Dextran may increase bleeding problems in humans by decreasing platelet function and clotting factors (it has not been observed in animals). Impaired renal function may delay excretion. Dextrans will interfere with blood cross matching. They can overwhelm the RE system and decrease the immune response. Anaphylaxis has been reported in up to 5% of the human patients but not in animal. Clotting time may be prolonged but this does not seem to produce a clinical problem.

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Hetastarch (Hydroxyethyl Starch) Hetastarch is a synthetic starch resembling glycogen (30,000-2,000,000 molecular weight) that comes as a 6% solution in saline. Its “dwell” time is 24 to 48 hours. Smaller particles are excreted in the urine within 48 hours. Large particles are removed by the RE system and degraded and are hydrolyzed by amylase. Volume expansion is equal to or greater than Dextran-70 or albumin. It expands blood volume by at least 2 times the volume infused. It will produce an osmotic diuresis. Like other colloids, it has no oxygen transport abilities. The dose of hetastarch is 10 mls/lb/day (20 mls/kg). The entire dose can be given in 1 hour. As with other colloids, the initial volume expansion needs to be maintained with crystalloids. Hetastarch is indicated in patients with pulmonary edema who need volume expansion and in patients needing prolonged cardiovascular volume improvement.

BLOOD COMPONENT THERAPY The ideal hemoglobin for the critical patient is approximately 12 g/dl with a PCV of 38%. Packed cell volume above 45% may actually decrease cardiac output due to viscosity. Patients with supplemental oxygen therapy do well down to a PCV of 25%. Fresh whole blood is indicated in anemia (nonimmune) and hemorrhagic shock. Packed red cells are indicated in hemolytic anemia where the total plasma proteins are not decreased and in blood loss without hypoproteinemia. Fresh frozen plasma is indicated when hypoproteinemia (TPP < 4.0 g/dl) is present. Fresh frozen plasma has all the clotting factors except platelets and provides opsonins and complement. Massive blood transfusions can decrease calcium levels, decrease platelets and partial thromboplastin time. An acute blood loss of 10-20% can be replaced with crystalloid (3:1). If the PCV > 30% then continue crystalloid with the addition of colloids. If the PCV < 30% then consider giving whole blood or pac ked red cells. If the albumin is < 2.0 g/dl or the total plasma protein is < 4.0 g/dl then plasma or colloids should be considered. A cross match should be done on all patients if possible. However, cross matched blood does not totally preclude a reaction or sensitization. You should only infuse normal saline, Normosol or Plasmalyte with blood. Solutions containing dextrose cause hemolysis and solutions containing calcium cause coagulation. Blood components should be warmed to body temperature prior to administration and once warmed, they should be administered within 4 hours. Blood components should always be given IV or intramedullary. The rate for whole blood or packed cell administration should not exceed 10 mls/lb/hr (22 mls/kg/hr). If a patient has cardiac disease it should not exceed 2 mls/lb/hr (4.4 mls/kg/hr). The rate for plasma administration is 3-5 mls/lb/hr (6-11 mls/kg/hr). Complications of blood component administration can include hemolytic reactions (acute or delayed). Benadryl at a dose of .25-.5 mg/lb (.5-1.0 mg/kg) should be given IV

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along with a rapid acting corticosteroid such as prednisolone Na succinate at a dose of 10 mg/lb (22 mg/kg) IV. Fever, urticaria and/or vomiting may all occur. Sepsis has been reported with contaminated blood. Circulatory overload, coagulopathies (stored blood) and pulmonary microembolism have all been reported with the administration of blood products.

ADJUNCT THERAPY - CORTICOSTEROIDS Corticosteroids are often used in surgical and/or critical patients because of their numerous beneficial effects. Corticosteroids inhibit detrimental cascades and cellular products. They inhibit the arachidonic acid cascade (prostaglandins, leukotrines) and phospholipase A2. They inhibit leukocyte accumulation, oxygen derived free radical formation and complement activation. They also inhibit the release of platelet activating factor and interleukin-1. Corticosteroids improve regional blood flow. They stabilize cellular and intracellular membranes. They maintain capillary endothelial integrity, and they increase the sensitivity and density of beta-2 adrenoreceptors. Corticosteroids help prevent edema formation by improving capillary endothelial integrity and hemodynamics. They have anti-inflammatory effects. They promote the effects of the catacholamines by increasing the sensitivity and number of beta receptors. Corticosteroids promote the effects of antibiotics. The following corticosteroids have been used in both the dog and cat. Methylprednisolone Na succinate (Solu-Medrol) 7-15 mg/lb (15-30 mg/kg) IV Prednisolone Na succinate (Solu-Delta-Cortef) 7-15 mg/lb (15-30 mg/kg) IV Prednisolone Na phosphate (Cortisate-20) 5-7 mg/lb (10-15 mg/kg) IV - use in dogs only Dexamethasone Na phosphate 2-3 mg/lb (4-6 mg/kg) IV

ADJUNCT THERAPY VASOACTIVE DRUGS The use of vasopressors (inotropes/catacholamines) is controversial in shock except in anaphylaxis or pure neurogenic shock where vasopressors (epinephrine) are indicated. Vasoconstriction is frequently already excessive in shock and vasopressors may be detrimental. However, the dopaminergic vasoactive drugs may be useful especially after fluid replacement. They may help restore tissue blood flow by increasing cardiac output and producing vasodilation. The dopaminergic vasoactive drugs include such drugs as dopamine, dobutamine and dopexamine. They are given as a continuous infusion to effect. Generally, the dose for

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these drugs ranges from 1 to 2 up to as high as 40 micrograms/lb/min (2 to 90 micrograms/kg/min). In shock situations they are often started at a rate of 10 micrograms/lb/min (22 micrograms/kg/min). Dopamine is a dopaminergic, alpha and beta 1 receptor agonist. It increases cardiac output, heart rate and arterial blood pressure. It causes no change or decreases peripheral resistance. Dobutamine is a beta 1, beta 2 and alpha receptor agonist. Its strongest effects are against beta 1 receptors, followed by beta 2 receptors and then alpha receptors. It increases cardiac output and arterial blood pressure. It causes no change or increases heart rate and causes no change or decreases peripheral resistance. Dopexamime is a dopaminergic, beta 2 and beta 1 agonist. It is a stronger dopaminer-

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gic and beta 2 agonist than beta 2 agonist. It causes increases in heart rate and cardiac output. It causes no change or an increase in arterial blood pressure and greatly decreases peripheral resistance. The following is a quick way to calculate a dopamine drip. !

Patients weight in pounds x 2

! Add that number of mg of dopamine to a 500 ml bag of fluids !

Attach a microdrip set (60 drops/ml) to the bag of fluids

1 drop/second = 10 micrograms/kg/min

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Analgesics and analgesic techniques for the small animal patient Cosa c’è di nuovo nell’anestesia dei piccoli animali

Robert R. Paddleford DVM, DACVA, DACVECC, Department of Small Animal Clinical Sciences College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37901-1071

INTRODUCTION Pain is a perception. Unless there is higher center, organized recognition of a noxious stimulus, no response or adaptation in the patient will occur. Nociceptors respond to mechanical, thermal or chemical stimuli. They also respond to endogenous substances such as hydrogen ions, serotonin, histamine, b ra dykinin and prostaglandins. For humans, it is important that the patient verbally express or communicate the pain in some manner. Limitations in the recognition that pain exists in animal species results from the absence of verbal communication that expresses pain p e rc eption. The absence of this communicating link is a fundamental reason that pain is interpreted in an inconsistent manner by veterinarians. Animals do perceive pain but their expression of that pain is nonverbal. Signs of pain in animals may include but not be limited to an increased heart rate and/or respiratory rate, vocalization, unwillingness to move, salivation, inappetence, restlessness and/or aggressive behavior. Signs of chronic pain may include dullness or an unresponsiveness when touched or handled, loss of appetite or marked decreases in food and water intake and a rough haircoat or a failure to groom. The goal of pain management is not necessarily to eliminate all pain, but to reduce or eliminate pathologic pain associated with injury or surgery. Pain is treated to 1) make the patient feel better, and 2) decrease the tremendous physiologic responses that accompanies pain perception. Analgesic agents can be classified as peripheral acting agents, spinal cord level acting agents and central acting agents.

PERIPHERAL ACTING AGENTS Peripheral acting agents are either local anesthetic agents or nonsteroidal anti-inflammatory agents (NSAIDs). Local anesthetic agents prevent the conduction of nerve impulses and are injected directly into a nerve or nerves and/or infiltrated into the surgical site. Local anesthetic agents with a long duration of action (six to ten hours) are preferred. Agents such as bupivacaine or etidocaine are preferred. Lidocaine can be used but its duration of effect is only in the two hour range. One must be aware that local anesthetic

agents can produce toxicity (agitation, muscle tremors, seizures, coma and death) when excessive doses are used. The dose of bupivacaine should not exceed 1.0 mg/lb (2.0 mg/kg) and the dose for lidocaine should not exceed 2 to 3 mg/lb (4-6 mg/kg). NASIDs include drugs such as aspirin, phenylbutazone, dipyrone, flunixin meglumine, ketoprofen and ketorolac. These drugs inhibit pain by reducing the inflammatory response that sensitizes peripheral pain receptors. They have been used as both primary agents or supplemental agents in pain management. They may be considered primary therapy in the management of soft tissue pain (trauma, surgery). However, they may need to be supplemented with other analgesics in other pain etiolo gies. Flunixin meglumine (Banamine) is a NSAID that has been used in small animals for pain management. It seems to work well for soft tissue pain. It has a relatively long duration of action (8-12 hours). It does not seem to work as well for bone or orthopedic pain. One of its major disadvantages is that it can cause severe hemorrhagic gastritis and/or nephrotoxicity. The dose range is 0.02 to 0.5 mg/lb (0.05 to 1.0 mg/kg) SC, IM or IV in the dogs. In the cat the dose is 0.1 mg/lb (0.25 mg/kg) SC. High doses and/or repeated doses can cause hemorrhagic gastritis. The high doses should probably only be used BID or SID. Do not exceed two to four repeated doses. Carprofen is one of the newer NSAID’s which shows a lot of promise in small animals. It is a poor inhibitor of cyclo-oxygenase 1 enzymes. Inhibition of cyclo-oxygenase is probably responsible for many of the renal and GI problems seen with NSAID’s. The dose of carprofen is 0.5-1.0 mg/lb (1.0-2.0 mg/kg) SQ, IM or IV. It should be administered prior to surgery and has a dur ation of effect of up to 24 hours. At the present time, carprofen has only been approved for oral use in dogs in the United States. It has been approved for use in both the dog and cat in the UK and Europe. In Europe, the approved dose for carprofen in cats is 2 mg/lb (4 mg/kg) SC given once and not r epeated. Ketorolac is a NASID that has been used in the dog and cat for surgical pain control. This is an extralabel use of the drug. It is used in human patients for moderate to severe pain and is comparable to morphine in efficacy. Its duration of effect is 8-12 hours. Ketorolac has a strong potential to cause gastric ulcers. The recommended dose in the dog is 0.15 to 0.25 mg/lb (0.3-0.5 mg/kg) IV or IM given every 8 to 12

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hours for one to two treatments. The dose in cats is 0.1 mg/lb (0.25 mg/kg) IM given every 8 to 12 hours for one to two treatments. Contraindications for NASID's include 1) renal insufficiency, 2) dehydration, 3) hypotension, 4) conditions producing low circulating volume (congestive heart failure, ascites, diuretic therapy), 5) thrombocytopenia, 6) von Willebrand's disease, 7) concurrent use of corticosteroids and/or other NASID's, 8) evidence of gastric ulceration, 9) any GI disorders, 10) intervertebral disk disease, and or 11) liver disease.

SPINAL CORD ACTING AGENTS Spinal cord acting agents include the opioids (narcotics), alpha-2 agonists and tranquilizers. The opioids affect impulse processing and transmission at multiple levels of the CNS including the spinal cord. There are most likely multiple receptor sites involved. Opioids may be given systemically or as an epidural. The alpha-2 agonists (xylazine, detomidine, medetomidine, dexmedetomidine) inhibit pain impulse transmission in the spinal cord pain pathways at the interneuronal level. Stimulation of alpha-2 receptors in the CNS hyperpolarizes neurons and inhibits norepinephrine and dopamine storage and release. This leads to a decrease in the discharge rate of central and peripheral neurons resulting in sedation, analgesia and muscle relaxation. Alpha-2 agonists may effect other neuromodulators including endorphins and purines. Tranquilizers also act at the spinal cord level and can be used in combination with opioids. The benzodiazepines and phenothiazines have both been used. Tranquilizers are useful in calming agitated or anxious patients and are indicated in combination with opioid analgesics for additional relaxation and sedation. The primary benzodiazepine tranquilizers used are diazepam (Valium) or midazolam (Versed). The benzodiazepine tranquilizers may provide mild analgesia and muscle relaxation at the spinal cord level by inhibiting the neurotransmitters, glycine and gamma aminobutyric acid (GABA). The primary phenothiazine tranquilizer used has been acepromazine. It is not considered an analgesic agent but it may be used in combination with opioid analgesics to reduce agitation and to provide additional sedation. Acepromazine also provides additional relaxation at the spinal cord level.

CENTRALLY ACTING AGENTS Centrally acting agents act directly on the higher center s of the brain and include the opioids, sedative-hypnotics and tranquilizers. Tranquilizers (diazepam, midazolam, acepromazine) are not analgesics. They are enhancing drugs when used with opioids. They produce a calming effect by inhibiting activity in the hindbrain and thalamus. The opioids are analgesics and interact with specific receptor sites in the hindbrain and forebrain. The thalamus and cerebral cortex appear to have a high density of opioid receptors. For pain to be perceived, the pain signal transmission must reach the subcortical structures (thalamus, reticu-

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lar and limbic systems) and the cerebral cortex. The opioids activate central receptors which inhibits pain signal transmission to higher centers. This blocks the pain perception of the painful stimulus. The opioids also have modulating effects at the spinal cord level. There are several different opioid receptors that have been identified and include mu, kappa, sigma, delta, and epsilon. Mu receptors are involved with supraspinal analgesia, respiratory depression, euphoria, and physical dependence. Kappa receptors are involved with spinal analgesia and sedation. Sigma receptors produce dysphoria, hallucinations, respiratory and vasomotor stimulation. The endogenous opiopetins are derived from larger precursor peptides and include three distinct opioid systems in the CNS - 1) beta-endorphin, 2) dynorphins and, 3) enkephalins. Endogenous opiopeptins are released in response to pain and noxious stimuli. It is the opiopeptins which interact with the opioid receptors in the body producing the painful responses. The opioid analgesics may help attenuate pain in several ways. First, they interact with receptors in the mesolimbic system (nucleus raphe magnus and locus ceruleus in the brain stem, midbrain periaqueductal g ray area, several thalamic and hypothalamic nuclei). Opioids interacting with these receptors raise the pain threshold. Secondly, opioid analgesics interfere with calcium influx into select target neurons thus reducing transmitter release. This presynaptic inhibition of excitation neurotransmitter release may involve acetylcholine, norepinephrine, 5-hydroxytryptamine, glutamic acid , dopamine, substance P as well as other mediators. Finally opioid analgesics inhibit the release of substance P centrally. This may be responsible for the depression of transmission or impulses in certain central nervous system relays. Opioid analgesics can be divided into opioid agonists and opioid agonists-antagonists. Opioid agonists include morphine, meperidine (Demerol), oxymorphone (Numorphan), fentanyl, carfentanil, sufentanil, etc. Opioid agonists stimulate all central and peripheral opiate receptors inducing the full spectrum of opioid induced effects. The opioid agonists produce numerous CNS effects. They modify pain perception and help relieve anxiety and distress. They may produce dysphoria and hallucinations. Spinal cord reflexes may become exaggerated. Opioid agonists may produce excitement in some species (cats, horses, cattle, swine) when inappropriate doses are used. Opioid agonists can produce respiratory center depression even at doses that do not produce marked CNS depression. The respiratory depression can be significant. At normal doses, opioid agonists do not produce marked cardiovascular effects. Bradycardia due to increased vagal tone may occur and can be significant at times. Hypotension may occur as a result of histamine release or central depression of the vasomotor center. Venous tone decreases causing a reduced cardiac preload. In the dog, opioid agonists produce analgesia usually accompanied by profound sedation. On some occasions excitement and dysphoria may be seen. In the cat, opioid agonists produce analgesia but may cause a stimulatory effect. One may see mydriasis, apprehension, hypersalivation, ex-

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Table 1 - Oopioid agonists in dogs. Drug

Dose/Duration

Comments

Morphine

0.25-6.0 mg/kg/4-6 hrs (SQ or IM)

Vomiting, defecation

Meperidine

2-10 mg/kg/2-3 hrs (SQ, IM or IV)

Fewer side effects

Oxymorphone

0.22 mg/kg/2-4 hrs (SQ, IM or IV) (maximum dose of 4 mg at one time)

Excitement - especially when g iven IV, auditory hypersensitivity

Fentanyl

0.04-0.08 mg/kg/1-2 hrs (SQ, IM or IV)

Rapid onset

Table 2 - Oopioid agonists in cats. Drug

Dose/Duration

Comments

Morphine

0.1 mg/kg/4-6 hrs (SQ or IM)

Excitement with higher doses

Meperidine

2-10 mg/kg/2 hrs (SQ or IM)

Oxymorphone

0.22-0.44 mg/kg/2-4 hrs (SQ, IM or IV)

Can cause excitement

Table 3 - Opioid agonists/antagonists in the dog and cat. Drug

Dog

Cat

Butorphanol

0.2-0.4 mg/kg/2-5 hrs (SQ, IM or IV)

Same as dog

Buprenorphine

0.005-0.02 mg/kg/4-10 hrs (SQ, IM, IV)

0.005-0.01 mg/kg/4-10 hrs (SQ,IM,IV)

Nalbuphine

0.5-2.0 mg/kg/3-8 hrs (SQ, IM or IV)

1-2 mg/kg/3-6 hrs (SQ, IM or IV)

Table 4 - Fentanyl transdermal patch. Patch Dose

Dog (Duration 3-5 days)

Cat (Duration 3-5 days)

25 microgram

< 10 kg

Fold a 25 microgram patch in half

50 microgram

10-20 kg

---

75 microgram

20-30 kg

---

100 microgram

> 30 kg

---

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Table 5 - Oral opioid agonists and agonist-antagonists. Drug

Dose (mg/kg)

Dose interval

Formulation

Morphine

Dog: 0.3-3.0 Cat: 0.1-1.0

4-8 hours 4-8 hours

Tablets: 15, 30 mg (various manufact.) Solution: 4, 20 mg/ml (Roxane Laboratories) Suppositories: 5, 10, 20, 30 mg (Roxane Laboratories)

Morphine (time release)

Dog: 1.0-5.0

8-12 hours

MS Contin (Purdue Frederick) 15, 30, 60, 100 mg Oramorph SR (Roxane Laboratories) 30, 60, 100 mg

Codeine

Dog: 1.0-4.0

4-8 hours

Tablets: 15, 30, 60 mg (various manufact.)

Butorphanol

Dog: 0.2-1.0 Cat: 0.2-1.0

4-6 hours

Tablets: 1, 5, 10 mg (Fort Dodge Laboratories

Table 6 - Nonsteroidal antiinflammatory drugs. Drug

Dose

Dose Frequency

Flunixin meglumine

Dog: 0.05-1 mg/kg IV, SC, IM Cat: 0.25 mg/kg SC

12-24 hrs (Do Not Exceed 2-4 doses) One dose

Ketorolac (extralabel use)

Dog: 0.3-0.5 mg/kg IV, IM Cat: 0.25 mg/kg IM

Every 8-12 hrs for 1 or 2 doses Every 8-12 hrs for 1 or 2 doses

Carprofen

Dog: 2.0-4.0 mg/kg IV 2.2 mg/kg PO, IV, SC, IM Cat: 2.0-4.0 mg/kg SC

Initial dose Repeat in 12 to 24 hrs if needed Use only once

citement, and/or mania. In some cats this may occur even when appropriate doses have been given. Tranquilizers (especially acepromazine) combined with the opioid agonist help to prevent this stimulatory effect. Opioid agonists-antagonists include pentazocine, nalbuphine (Nubain), butorphanol (Torbugesic, Torbutrol) and buprenorphine (Buprenex). Opioid agonists-antagonists bind to opiate receptors but they either exert no action, which is indicative of competitive antagonists or they produce variable agonistic effects similar to the opioid agonists. These drugs will induce only select opioid effects and will reverse some actions of full agonists. The agonists-antagonists bind to the mu receptor but either exert no action or only limited action. When the agonists-antagonists bind to the kappa, sigma, delta and epsilon opioid receptors, they tend to exert effects similar to the opioid agonists. Butorphanol (Torbugesic, Torbutrol, Stadol) has been used as an effective preanesthetic and postanesthetic analgesic in the dog and cat. Butorphanol is a noncontrolled

synthetic opioid agonist-antagonist of the nalophane-cyclazocine class with a chemical structure similar to morphine but with pharmacological activity similar to pentazocine. Its analgesic potency is five times that of morphine, 15 to 30 times that of pentazocine and one-third to one-half that of oxymorphone. Butorphanol can produce a dose related respiratory depression similar to morphine; however, butorphanol seems to reach a ceiling beyond which higher doses do not cause significantly more respiratory depression. Butorphanol can produce decreases in heart rate, cardiac output, and blood pressure, but the depression is less than with morphine and oxymorphone. It is rapidly absorbed following IM injection with peak blood levels occurring in 15 to 30 minutes and analgesic activity lasting two to four hours. Butorphanol is extensively metabolized in the liver. It is rapidly and completely absorbed from the gastrointestinal tract; however, due to significant first pass hepatic metabolism, only 17% of the administered dose is available systemically. Its effects

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are readily antagonized with naloxone. Butorphanol has good analgesic properties and fair sedation properties. When it is combined with a tranquilizer such as diazepam or acepromazine, a very acceptable neuroleptanalgesic is produced. Butorphanol's main advantages is that it produces minimal respiratory depression, it produces minimal to moderate cardiovascular depression, it provides good analgesia, and it is a noncontrolled opioid that is readily antago n i ze d. Several general comments should be made regarding opioid analgesics.

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1. Systemic administration is the preferred route for most analgesics. 2. Dosing on a fixed time basis may not be adequate for some patients. 3. Patients should be monitored closely and the dose based on the patient's individual needs. 4. The frequency of administration will depend on the opioid, dose given and route of administration. A common mistake is to underadminister an analgesic drug by using a lower than therapeutic dose and less fre quent scheduling of administration.

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What’s new in small animal anesthesia Come identificare il miglior analgesico, la migliore tecnica analgesica e la migliore via di somministrazione

Robert R. Paddleford DVM, DACVA, DACVECC, Department of Small Animal Clinical Sciences College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37901-1071

Medetomidine (Domitor). Medetomidine is one of the newest alpha-2 agonists approved for veterinary use. It is extremely lipophilic, rapidly eliminated and more potent than other alpha-2 agonists. Medetomidine’s alpha-2 to alpha-1 receptor selectivity binding ratio is 1620 compared to 260 for detomidine and 160 for xylazine, thus making it approximately 10 times more potent than xylazine. The cardiopulmonary effects of medetomidine are similar to xylazine, although they may be more pronounced. Significant bradycardia and/or vagal induced dysrhythmias may be produced by medetomidine. The administration of an anticholingeric prior to the administration of medetomidine may be more effective at preventing bradycardia than trying to reverse it after it occurs. Significant respiratory depression may occur in some patients following medetomidine administration. This is especially true if higher doses are used and/or if it is used in combination with other CNS depressants. Medetomidine seems to produce less variation in potency and CNS depression between patients, compared to xylazine. Medetomidine is metabolized and eliminated in the same manner as xylazine. The effects of medetomidine can be antagonized by yohimbine, tolazoline or atipamezole. Atipamezole may be the most effective of the three because of its high alpha-2 to alpha-1 selectivity ratio. Medetomidine is recommended for use in only young, healthy, exercise tolerant dogs. It is recommended that it be used as a sole agent and not be combined with other CNS depressants. It is not recommended for use in patients with cardiopulmonary problems or in debilitated patients. The precautions and contraindications for medetomidine are the same as for xylazine. Propofol (Rapinovet)®. Propofol is one of the two new injectable anesthetics that has found widespread use in human anesthesia and has been approved for use in veterinary anesthesia. Propofol is a highly lipid soluble alkylphenol that is a rapid acting IV anesthetic. It is insoluble in water and must be solubilized in a lecithin containing emulsion. Propofol is formulated as 1% emulsion containing 10% soybean oil, 1.2% egg lecithin and 2.25% glycerol. Propofol can be used for short periods of anesthesia (5 to 10 minutes) following a single bolus. More prolonged anesthesia can be maintained using repeated bolus injections or continuous infusion.

Propofol's rapid onset time is similar to thiopental. A single bolus injection of propofol produces a rapid onset of anesthesia (less than 60 seconds), lasting 5 to 10 minutes. The induction is smooth and excitement free; however, transient local pain due to venoirritation may occur during induction. Propofol induced excitatory activity, such as movements, myoclonic twitching and muscle tremors, have been reported in some patients that did not receive preanesthetic sedative drugs. Recovery is very rapid following even repeated doses of propofol. It is rapidly redistributed and rapidly metabolized by glucuronidation and sulfonation. After 30 minutes, less than 20% of the dose can be recovered as unchanged compound. Total body clearance exceeds hepatic blood flow, and, although hepatic metabolism plays a major role in clearance, other tissues (lung) are also involved. Ninety percent of propofol is excreted in the urine as water soluble glucuronide and sulfate conjugates and there are no known active metabolites. Cats have a deficiency in their ability to conjugate phenols and, although the reported recovery times following single or repeated doses of propofol are similar in dogs and cats, continuous infusion may produce more prolonged recoveries in cats. The total calculated dose used for anesthetic induction in the dog and cat is 2-6 mg/kg IV. Lower doses are used in patients that have received preanesthetic sedation. The drug is administered to effect much the same way as thiopental. Approximately 1/3 of the dose is administered every 30 to 45 seconds until the desired level of anesthesia is produced. The total dose given will depend on the preanesthetic sedatives used, the degree of patient sedation and the physical status of the patient. Following propofol induction, anesthesia can be maintained with inhalation agents or by repeated bolus injections or continuous infusions of propofol. Propofol can be used at a maintenance infusion of 0.2 to 0.4 mg/kg/min. The maintenance infusion is increased or decreased depending on the desired anesthetic level of the patient. The cardiopulmonary effects of propofol are similar to the barbiturates. Propofol causes a decrease in cerebral blood flow and oxygen consumption. It causes direct myocardial depression, peripheral vasodilation, venodilation and hypotension. Propofol can produce respiratory depression. The incidence of apnea with propofol is comparable to the barbiturates, but the duration of apneic episodes may be

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slightly longer. The cardiopulmonary effects of propofol are dose dependent. Propofol's pharmacokinetics in patients with renal and hepatic dysfunction is similar to that in nondiseased patients, suggesting it would be suitable for patients with renal and/or hepatic impairment. Propofol has been safely used in sighthounds. Propofol is a drug that seems ideally suited for use as a continuous infusion for the maintenance of anesthesia. Recovery is rapid with minimal "drug hangover". There does not appear to be the problem of drug buildup with propofol when compared to the barbiturates or the dissociative agents. Myoclonic twitching, muscle tremors and muscle movements have been reported in humans and dogs during maintenance of anesthesia with propofol. During these episodes, anesthetic depth appeared adequate and arterial blood gases and pH were normal. Diazepam, 2.5 to 5.0 mg given slowly IV, has been used to control the m yoclonus when necessary. Propofol may be suited for use in the geriatric or high risk patient since recovery times do not seem to be prolonged in patients with renal or hepatic dysfunction. However, because its cardiopulmonary depressant effects are very similar to the thiobarbiturates, it should be used with caution in any patient with preexisting cardiopulmonary disease or dysfunction. Etomidate (Amidate®). Etomidate is another new injectable anesthetic used in human anesthesia. Etomidate is a carboxylated imidazole containing compound that is structurally unrelated to any other IV anesthetic. It is a sedativehypnotic with a rapid onset of action and a rapid recovery. It is a weak base dissolved in propylene glycol; therefore, IV infusion can be associated with pain and venoirritation. Etomidate has been used in veterinary anesthesia although it has not been approved for use at this time. The induction dose of etomidate in the dog and cat is 1.5 to 3.0 mg/kg IV. The dose is given to effect and will depend on the preanesthetic sedatives given to the patient and the physical status of the patient. A single bolus injection produces a rapid loss of consciousness with a duration of action of 5 to 10 minutes. Etomidate undergoes rapid hepatic hydrolysis to inactive metabolites. This results in a rapid recovery and a lack of accumulation when used in repeated boluses or as an infusion. At doses used to produce general anesthesia (3.0 mg/kg IV), etomidate produces no change in heart rate, cardiac output or mean arterial blood pressure. Cardiovascular stability may be better with etomidate because it better maintains baroreceptor-mediated responses. Etomidate can produce a mild to moderate dose dependent respiratory depression.

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Several adverse side effects have been reported with etomidate. Pain and phlebitis have been associated with the IV injection of etomidate. This may be due to the carrier agent propylene glycol. Excitement during induction and recovery have been reported. This can be partially or completely eliminated by using preanesthetic sedatives. Retching, myoclonus and apnea have been reported in humans and dogs during induction. Etomidate has been demonstrated to temporarily inhibit adrenal steroidogenesis in humans and dogs. Whether or not this inhibition is significant to the patient is controversial. Etomidate's minimal cardiopulmonary depressant effects and its rapid metabolism and recovery would make it seem ideally suited for the geriatric and high risk patient. Sevoflurane (Ultane). Sevoflurane is the newest of the volatile anesthetics to be approved for human use in the United States. It is a halogenated ether that is non-flammable and non-explosive at commonly used anesthetic concentrations. It is very insoluble in blood which accounts for its very rapid induction and recovery times (faster than isoflurane). Sevoflurane is nonpungent and has a non-irritating odor, making mask inductions easier. The minimum alveolar concentration for sevoflurane is 2.1 to 2.4% in the dog and 2.6% in the cat. It is less potent than isoflurane. Sevoflurane will react with soda lime or Baralyme to produce olefin, a nephrotoxic compound. The concentration threshold for nephrotoxicity in the rat model is within the clinically used concentration ranges. Sevoflurane is very stable and does not require a preservative. The vapor pressure of sevoflurane is 160 mm Hg at 20°C, making it a highly volatile agent. It should be used in precision, agent specific, out of circuit vaporizers. Changes in anesthetic depth can be rapidly achieved due to its decreased solubility in blood. The cardiovascular effects of sevoflurane are similar to isoflurane. It will produce a dose dependent decrease in cardiac output and blood pressure. It produces a dose dependent decrease in pulmonary function similar to other volatile inhalant anesthetics. Sevoflurane will produce decreases in both rate and tidal volume and, like other volatile anesthetics, it will depress the patient’s ability to respond to increases in arterial carbon levels and to decreases in arterial oxygen levels. Sevoflurane has not been associated with direct hepatocellular damage. Almost all of the inspired sevoflurane is excreted into the alveoli and exhaled during recovery. Only 3% of sevoflurane is metabolized.

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Ernia diaframmatica nel cane e nel gatto: studio retrospettivo su 29 casi (1996-2000) Guido Pisani Med Vet, Libero Professionista, Molicciara (SP)

Stefano Pizzirani Med Vet, DdR, Dipl ECVS, Libero Professionista, Firenze

INTRODUZIONE

MATERIALI E METODI

Il diaframma è una struttura muscolotendinea che separa la cavità addominale dalla cavità toracica,2, 7 e non è particolarmente resistente se comparato con la parete delle due cavità.1 L’ernia diaframmatica (ED) è la migrazione di visceri od organi addominali in cavità toracica. Tale dislocazione avviene attraverso ‘aperture’diaframmatiche di tipo congenito o acquisito. La lacerazione del diaframma può derivare da una violenta compressione dell’ addome in seguito a trauma ottuso oppure a ferita penetrante.9 Il sintomo clinico più comune è la dispnea.9, 11 La difficoltà respiratoria viene provocata da situazioni meccaniche (dislocazione di visceri o organi addominali in cavità toracica, chilotorace, idrotorace, emotorace, pneumotorace), da cause algiche (trauma, contusione polmonare, fratture costali), da condizioni metaboliche (shock). La concomitanza di alcune di queste cause è verosimile e la sintomatologia può essere più o meno evidente anche in relazione al tempo trascorso dal trauma. Eventi acuti manifestano algia e dispnea più evidenti, mentre situazioni croniche possono essere sintomatologicamente meno chiare. In entrambi i casi la sintomatologia può aggravarsi con il movimento o lo stress. Alcuni pazienti possono presentare esclusivamente sintomi gastroenterici derivanti da “paratopie”.9 Alcuni casi sono del tutto asintomatici. La diagnosi si fonda sui segni clinici (dispnea, cianosi, respiro discordante, intolleranza all’esercizio, intolleranza al decubito laterale) e sui r eperti radiografici. 8 La terapia dell’E.D. è esclusivamente chirurgica. Scopo del nostro lavoro è di valutare l’efficacia della riduzione chirurgica in corso di ED acuta e cronica e finalizzare statisticamente le informazioni che possano scaturire dall’analisi di cartelle cliniche di 29 pazienti.

Nel presente studio retrospettivo sono stati inclusi 29 casi di ED nel cane e nel gatto trattati fra il gennaio 1996 e il novembre 2000 presso il Centro Veterinario, MOLICCIARA (SP) e la Clinica Veterinaria EUROPA, FIRENZE. Le schede cliniche dei soggetti sono state valutate riguardo al segnalamento: specie, razza, sesso, età; presenza o meno di evento traumatico noto; tempo intercorso fra evento traumatico e ricovero; sintomi clinici presenti al momento della visita; diagnostica effettuata; patologie associate; tempo intercorso dall’incidente alla terapia chirurgica; procedura anestesiologica usata, tipo di ventilazione, tipo di circuito; accesso chirurgico; localizzazione dell’ernia e visceri erniati; tipo di sutura usato; introduzione di drenaggio toracico; complicanze perioperatorie; follow up a distanza. Per conoscere le evoluzioni cliniche riferibili o collegate alla terapia di ED, in alcuni casi, è stato introdotto un questionario telefonico.

RISULTATI La popolazione era costituita da 21 gatti (72,4%) ed 8 cani (27,6%). Fra i gatti 12 erano maschi (57,1%) di cui 1 maschio castrato (8,3%) e 9 femmine (42,9%) di cui 1 femmina sterilizzata (11,1%). Tutti i soggetti erano di razza europea comune. Il range di età variava da 1,5 mesi a 144 mesi (media 35,6). Fra gli 8 cani 2 erano maschi (25%) e 6 femmine (75%). La distribuzione fra le razze includeva 4 Segugi Italiani, 1 Barboncino nano, 1 Schnauzer medio, 2 meticci. Il range di età variava da 12 mesi a 48 mesi (media 28,5 mesi). Riguardo la causa dell’ED in 4 casi (13,7%) l’anamnesi non era indicativa della possibile eziologia mentre in 20 ca-

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si (68.9%) la causa determinante era un incidente automobilistico, in 4 casi (13,7%) una ferita da zanna di cinghiale ed in 1 caso (3,4%) veniva riferito che l’animale era stato calpestato dal proprietario. 15 pazienti (51,8%) sono stati sottoposti a visita clinica entro le 24 ore dal trauma, con media di 7,7 ore (range 2 – 20 ore), mentre 12 pazienti (41,3%) sono stati esaminati oltre le 24 ore dal trauma presunto causa (range 1 giorno-2 anni); 2 di questi hanno rivelato l’ED occasionalmente durante altre procedure chirurgiche ed il riferimento ad un trauma conosciuto è avvenuto a posteriori. In 2 casi (6,9%) l’insorgenza del trauma non è stata individuata. La visita clinica ha evidenziato dispnea in 27 casi (93.1%) di cui 11 (37,9%) come unico segno clinico, febbre in 2 casi (6,9%), versamento pleurico in 2 casi (6,9%), “addome di vespa” in 5 casi (17,2%), pneumotorace aperto con ferita sull’ ipocondrio in 3 casi (10,3%), patologie ortopediche in 3 casi (10,3%), lacerazione inserzione muscolare sull’ ipocondrio con ernia sottocutanea paracostale e ascellare 2 casi (6,9%), patologie vie urinarie 3 casi (10,3%), dilatazione toracica 1 caso (3,4%) fratture costali in 3 casi (10,3%). 9 casi (31%) presentavano patologie associate alla dispnea. In 2 pazienti (6,9%) l’ED è stata riscontrata occasionalmente nel corso di altri interventi chirurgici. Si è raggiunta una diagnosi tramite visita clinica e Rx toracica in 22 soggetti (75,9%), con proiezione latero-laterale (LL) in 19 casi (65,5%) e con in proiezione LL associata a proiezione dorso ventrale (DV) in 3 casi (10,3%), mentre la diagnosi è stata intraoperatoria in 6 casi (20,7%) di cui in 2 (6,9%) del tutto occasionali, autoptica in 1 caso (3,4%). La terapia chirurgica è stata effettuata sempre dopo la stabilizzazione del paziente. I protocolli anestesiologici sono stati variabili ma tutti i pazienti sono stati intubati e ventilati manualmente; in 19 gatti ed un cane si è utilizzato il circuito di Bain, in 2 gatti il circuito chiuso, nei restanti cani il circuito semiaperto. Solo 3 pazienti hanno ricevuto una premedicazione a base di acepromazina (0,02 – 0,035 mg/kg). tutti hanno ricevuto una rapida induzione seguita immediatamente dalla intubazione orotracheale e dalla ventilazione assistita. I 27 pazienti chirurgici sono stati suddivisi in tre gruppi: gruppo A) la terapia è stata affrontata nell’arco delle 24 ore dal trauma in 5 casi, con media di 7,7 ore; gruppo B) in 18 casi la terapia è stata effettuata oltre le 24 ore e non oltre i 10 giorni dal trauma, con media 3,2 giorni; gruppo C) in 3 casi la correzione ch i ru rgica dell’ED ha avuto luogo dopo mesi dal trauma, con media di 12,6 mesi; in 3 casi non è stata individuata l’insorgenza della causa traumatica scatenante. L’accesso chirurgico è stato tramite celiotomia mediana in tutti i gatti ed in 4 cani, sternotomia mediana in un cane, la toracotomia laterale ampliando la ferita da cinghiale in 3 casi. La localizzazione dell’ernia è stata destra in 16/29 casi (55,1%), sinistra in 9/29 casi (31%), bilaterale in 2/29 casi (6,9%), non riportata in 2/29 casi (6,9%). In 4/29 casi (13,7%) la lacerazione coinvolgeva uno o più iati. In 26/29 casi (89,6%) si è avuta dislocazione epatica mentre in 12/29 (41,3%) la dislocazione coinvolgeva lo stomaco.

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L’ erniorrafia è stata effettuata con Vicryl® (EP 2 – EP 3,5) a punti staccati in 25/27 (92,6%) casi, in sutura continua in 1/27 caso (3,7%) ; PDS® EP 1,5 a punti staccati in 1/27 caso (3,7%). Il drenaggio toracico ad aspirazione manuale è stato utilizzato solo in 2/27 casi (7,40%) di cui 1 era il paziente deceduto per le complicazioni settiche dovute alla toracocentesi eseguita prima della nostra valutazione. Nell’altro caso il paziente aveva un trasudato toracico modificato per la stenosi di un lobo epatico a livello di porta erniaria diaframmatica ed il drenaggio è stato mantenuto in posizione per 36 ore. Nei restanti 25/27 non si è utilizzato drenaggio toracico e si è osservata 1 complicazione (4%) consistente in pneumotorace riscontrato in terza giornata ed agoaspirato senza ulteriori complicazioni. Nel post-operatorio non ci sono state complicanze in 21 casi su 27 (77,7%) nei restanti casi si sono evidenziate complicanze. 2 pazienti (6,9%) sono deceduti durante la visita di pronto soccorso. 1 paziente (3,4%) ha subito un nuovo intervento di erniorrafia dopo 4 giorni dal primo per una nuova ernia in se de diversa dalla prima. 24/26 pazienti (92,3%) sono attualmente in condizioni cliniche normali con un follow-up medio di 20,8 mesi (range di 1-54 mesi). Un paziente (3,4%) appartenente al gruppo B è deceduto a 18 mesi dall’intervento per motivi non riferibili all’ ED. Un paziente (3,4%) appartenente al gruppo B è deceduto dopo 24 ore dall’intervento per complicazioni settiche dovute a toracocentesi diagnostica eseguita in una struttura diversa da quelle a cui si fa riferimento. Dei 26 pazienti sottoposti ad intervento chirurgico e con follow up, 25 (96,1%) mostrano risultati.

DISCUSSIONE L’incidenza dell’ED risulta più elevata nel gatto che nel cane e vista la stragrande maggioranza di soggetti non sterilizzati, è presumibile che la vita non casalinga sia un fattore di rischio predisponente. Le classi analizzate mostrano enormi variabili ed alcuni parametri (testimonianza diretta, attenzione del proprietario al proprio animale, abitudini ambientali del paziente, etc.) non sono riportati. L’analisi numerica e le indicazioni che si possono desumere sono solo relative alla percentuale di riuscita dell’intervento sul campo dei pazienti chirurgici considerato. La dispnea risulta essere il sintomo più frequente (93,1%) e nel 37,9% dei casi è l’unico segno riscontrabile. 27 pazienti sono stati sottoposti ad intervento chirurgico e di questi un soggetto è stato rioperato dopo 5 giorni per complicanze insorte. Di 26 pazienti si conosce un follow-up clinico sufficientemente lungo per poter affermare che la riuscita risulta del 96,1%. Tale percentuale di successo è comparabile con quelle riportate da altri autori 1, 9. Fattori negativi sembrano esulare dalla tecnica e dal protocollo e sistema anestesiologico utilizzato, (purchè con intubazione orotracheale e ventilazione assistita) e solo legati ad eventi contingenti e relativi a patologie avulse dal fatto di-

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slocativo. Il tempo intercorso fra l’evento traumatico e l’intervento non mostra influenze statisticamente rilevanti e questo è dovuto al fatto che pazienti cronici si sono stabilizzati spontaneamente, mentre quelli visitati in condizioni critiche sono stati stabilizzati ed operati rapidamente. Probabilmente vengono sottoposti a valutazione clinica soggetti capaci di reagire spontaneamente o quelli con proprietari presenti al trauma o particolarmente solerti. L’alta percentuale di riuscita in soggetti del gruppo C (3/3) indica che anche in caso di lesioni pregresse il recupero funzionale è completo. Complicazioni quali ernia iatale ed anuria da eccessiva tensione addominale post erniorrafia descritte da altri autori 3,4 non sono state da noi incontrate. Il numero esiguo dei casi e la supposizione di riuscita fatta su indicazioni cliniche può rendere valutazioni del genere attendibili in parte, ciononostante la comparsa di segni clinici evidenti descritti in simili complicazioni nel perioperatorio ed il follow-up lungo dei nostri casi possono attestare le nostre affermazioni. Le complicanze da noi riscontrate sono state una ernia diaframmatica in altra sede rispetto a quella operata in precedenza ed una ernia addominale parainguinale . L’uso del drenaggio toracico non è indispensabile alla buona riuscita. Si deve meticolosamente controllare che non esistano perdite emorragiche attive in torace. La tecnica di chiusura della cavità toracica deve essere effettuata con l’aspirazione del contenuto aereo pleurico. Talvolta può essere di ausilio far eseguire una ventilazione in insufflazione moderata e prolungata mentre si chiude l’ultimo punto; dopodiché si può eseguire una aspirazione ad ago per asportare l’aria residua in cavità pleurica. In casi di dubbio di tenuta della sutura si può riempire la cavità addominale di liquido a temperatura corporea e valutare la tenuta della sutura diaframmatica durante alcuni atti ventilatori operati dall’anestesista. Tale tecnica non presenta difficoltà ed elimina la gestione di pazienti con drenaggio toracico nel postoperatorio che oltre ad essere critica ed onerosa, può essere difficile soprattutto nel gatto. L’uso del drenaggio toracico è comunque indicato ove sussistano condizioni settiche in atto o in cui si sospetti una reazione flogistica pleurica postoperatoria. Considerando che sono stati seguiti 10 protocolli anestesiologici diversi, ma che tutti i pazienti sono stati intubati e ventilati, l’uso della rapida intubazione e la ventilazione assistita possono essere identificati come fattori favorenti la riuscita dell’intervento.

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CONCLUSIONI L’intervento di riduzione chirurgica dell’ED nel cane e nel gatto offre percentuali di riuscita elevate. La difficoltà tecnica dell’intervento non viene ritenuta particolarmente critica. L’osservazione dei principi di Halsted consente la facile gestione del postoperatorio anche senza l’ausilio di drenaggi toracici nella quasi totalità dei casi. L’attenzione al trattamento del paziente critico e della sua stabilizzazione metabolica prima dell’intervento, l’attenzione allo stress ambientale e iatrogeno, la rapidità dell’in tubazione dopo l’induzione e la ventilazione assistita, sono parametri ritenuti dall’autore fondamentali alla buona riuscita dell’intervento. Le convinzioni aneddotiche sulla gravità delle patologie dislocative toraciche andrebbero riconsiderate alla luce delle percentuali elevate di riuscita dimostrate dal presente studio retrospettivo e dalla letteratura internazionale più recente.

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Sullivan, M., Reid, J. (1990) Management of 60 cases of diaphragmatic rupture. Journal of Small Animal Practice 31,425-430 Orton, E.C. (1995) Diaphragm. In: Small Animal Thoracic Surgery. Williams & Wilkins, 169-174 Pratschke, K.M., Hughes, J.M.L., Skelly, C., Bellenger, C.R. (1998) Hiatal Herniation as a complication of chronic diaphragmatic herniation. Journal of Small Animal Practice 39, 33-38 Conzemius,M.G. Sammarco, J.L. Holt, D.E. Smith, G.K. (1995) Clinical determination of preoperative and postoperative intra-abdominal pressure in dogs. Veterinary Surgery. 24, 195-201 Kraje, B.J., Kraje, A.C., Rohrbach, B.W., Anderson, K.A., Marks, S.L., Macintire, D.K. (2000) Intrathoracic and concurrent orthopedic injury associated with traumatic rib fracture in cats: 75 cases (19801998). JAVMA. 216, 51-54 Wilson, D.V., (1992) Anesthesia for patient with diaphragmatic hernia and severe dyspnea. Vet Clin North Am Small Anim Pract. 22(2), 456-459 Miller, M.E.,Diaphragm. In Anatomy of the dog. W.B. Sauders Company. 178-181 Suter, P.F., (1984) Abnormalities of the diaphragm. In Thoracic Radiography A text atlas of thoracic disease of dog and cat. 179-204 Johnson K.A., (1993) Diaphragmatic, Pericardial, and Hiatal Hernia. In Slatter, D.: Text Book of Small Animal Surgery. Second edition.W.B. Sauders Company, 455-470 Bellah, J.R., (1998) Diaphragm. In Bojarab, J.M.:Current Techniques in Small Animal Surgery. Fourth edition. Williams & Wilkins,:315-321 Boudrieau, R.J., Pathophysiology of traumatic diaphragmatic hernia. In Bojarab, J.M.: Disease Mechanisms in Small Animal Surgery. Second edition. Lea & F ebiger, 1993: 103-108 Brooks, J.W., Traumatic diaphragmatic hernia. In Nyhus, L.M., Baker, R.J.,Mastery of Surgery. Little, Brown and Company, 338-342.

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The pathophysiology of canine non-specific dietary sensitivity Fisiopatologia dell’ipersensibilità alimentare nel cane

Vivian Rolfe BSc (Hons), PhD - Waltham Centre for Pet Nutrition, Leicestershire, REGNO UNITO

INTRODUCTION AND AIMS The term non-specific dietary sensitivity (DS) describes dogs, which produce loose faeces when fed certain diets. Approximately 15% of pet owners describe their dogs as having ‘sensitive digestions’. The pathophysiological mechanisms underlying the loose faecal consistency in this common condition are not known. At Waltham we investigated the immuno-physiological mechanisms DS. Groups of dietary sensitive and control dogs of various breed, age and sex were compared during a 8 week cross-over design trial. Dogs were fed test product A associated with well-formed faeces and product B which was associated with loose faecal consistency in sensitive dogs.

METHODS Faecal consistency was assessed using the 17-point Waltham Faeces Scoring Index. Colonic samples were obtained endoscopically and subjected to structural analysis by an independent histopathologist. Colonic electrolyte absorption was measured using dialysis bags in vivo, and water uptake from the colonic crypts measured in vitro using digital confocal microscopy. Additional colon samples were cultured for 24 hours in sterile conditions and the production of inflammatory mediators (PGE2 and NO) were measured in the culture media, and standardised against the protein con tent of the sample. Levels of serum and mucosal immunoglobulins (IgG, IgM, IgA, IgE) were measured using canine specific ELISA to determine whether there was an underlying inflammation.

SUMMARY OF RESULTS Numerous immunological and physiological parameters in sensitive dogs were significantly different from healthy controls. To summarise: Canine DS was associated with 1) loose faecal consistency. 2) mild lymphocytic-plasmacytic colitis. 3) reduction in colonic water and electrolyte transport function.

4) change in the inflammatory status of the colon, namely the release of pro-inflammatory eicosanoids and nitric oxide. 5) increased colonic IgA production. 6) increased serum IgG and produce higher levels of serum IgE antibody specific for wheat protein compared to control dogs.

CONCLUSION DS is associated with a mild inflammation, which actively involves the release of pro-inflammatory eicosanoids, nitric oxide and IgA in the gut. The inflammatory response leads to a reduction in the absorptive function of the colon, resulting in loose faecal consistency. This work has provided an important advance in our understanding of the mechanism of loose faeces in sensitive dogs, and may provide us with important opportunities for new management strategies.

THE PATHOPHYSIOLOGY OF CANINE NON-SPECIFIC DIETARY SENSITIVITY Introduction Dietary sensitivity is widely recognised in dogs and cats as a cause of dermatological, gastrointestinal, or more uncommonly respiratory, disease. Such adverse reactions are a clinically abnormal response to an ingested food or food additives, and can be divided into food hypersensitivity and food intolerance. Hypersensitivity is synonymous with food allergy and has an immunological basis while intolerance results from idiosyncratic, metabolic, pharmacologic, or toxic responses to foods. Dogs that produce loose stools, or have diarrhoea when fed certain foods are commonly recognised in veterinary practice. Although some owners make the association between the food and the occurrence of signs without veterinary advice, other patients are subjected to gastrointestinal investigations with no conclusive outcome. These owners describe their dogs as having ‘sensitive digestive systems’. We have recognised a similar phenomenon, which we have termed ‘non-specific dietary sensitivity’(DS), in a small

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percentage of dogs at the WALTHAM Centre for Pet Nutrition. Previous studies have shown that sensitive dogs are healthy on clinical examination and have no abnormalities on routine hematology and blood biochemistry panels. Serum trypsin-like immunoreactivity, and folate and cobalamin concentrations are well within normal limits for their base population,and there are no significant abnormalities in small intestinal absorptive function or permeability when tested by differential sugar absorption. These results indicate that the poor faecal quality in these dogs was not due to changes in pancreatic or small intestinal function, but likely involved alterations in one or more of colonic motility, transit, or absorptive capacity.

Levels of serum and mucosal immunoglobulins (IgG, IgM, IgA, IgE) were measured to determine whether there was an underlying inflammation using canine specific ELISA. The four groups were compared by Multifactoral ANOVA and significance assumed at p<0.05.

Results The faecal consistency of the DS dogs fed diet B was significantly poorer than diet A. Sensitive dogs appear to represent one end of a continuum in digestive function, whereby they consistently produce looser faeces than the control animals at the other end of the continuum.

Aim The purpose of the studies presented here was to investigate possible causes of poor faeces quality in sensitive dogs. We investigated the immuno-physiological mechansisms underlying DS.

Histology On diet B, the histological appearance of colonic mucosa in control dogs was healthy with no disruption to the crypt architecture and normal levels of immune cells within the lamina propria. In DS dogs, the mucosa displayed a lymphocytic-plasmacytic infiltrate with disruption to the crypt architecture.

Methods All aspects of animal husbandry and procedures used in this study were in accordance with the United Kingdom Home Office regulations. Groups of dietary sensitive and control dogs of various breed, age and sex were compared during an 8 week crossover design trial. Two standard diets were fed: one that produced relatively good faeces quality in all dogs and a diet that was associated with loose faeces in the sensitive, but not the healthy controls. All defecations were scored by trained assessors using the 17-point Waltham Faeces Scoring Index. Grade 1 represented dry crumbly faeces and grade 5 represented diarrhoea. Intermediate points were scored to the nearest quarter. Colonic samples were obtained endoscopically and subjected to structural analysis by an independent histopathologist. Colonic electrolyte absorption was measured using dialysis bags in vivo, and water uptake from the colonic crypts measured in vitro using digital confocal microscopy. Additional colon samples were cultured for 24 hours in sterile conditions. The production of inflammatory mediators (PGE2 and NO) were measured in the culture media and standardised against the protein content of the sample.

Water and electrolyte transport On diet B, Na+ absorption in vivo was significantly reduced (p<0.05, ANOVA) in sensitive dogs (-39.2 ± 6.4 mM.hr) compared to controls (-52.3 ± 6.76 mM.hr), as was Cl- (sensitive -48.2 ± 4.64 versus controls -59.8 ± 7.1 mM.hr, p<0.05). In sensitive dogs the FITC fluorescence intensity within the crypt lumen was reduced compared to control dogs (control 62.6 ± 7.5 versus sensitive 27.4 ± 3.6 D intensity.30 mins, p<0.05 ANOVA), indicating a reduction in crypt water uptake.

Inflammatory Mediators The production of pro-inflammatory eicosanoids (PGE2, TXB2) and nitric oxide was significantly increased in DS dogs compared to controls (Table 1).

Table 1 - Mucosal pro-inflammatory mediator and nitric oxide production. Controls

Sensitive

Parameter

Diet A

Diet B

Diet A

Diet B

PGE2 (ng/mg protein)

42 ab

30 a

78 b

146 c

TXB2 (ng/mg protein)

13 a

16 a

15 a

27 b

NO (uM/mg protein)

24 ab

14 b

20 b

Different letter denotes a significant difference assumed at p<0.05.

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Table 2 - Mucosal immunoglobulin production. Controls

Sensitive

Parameter

Diet A

Diet B

Diet A

Diet B

IgA (ug.mg protein)

27 a

25 a

26 a

46 b

IgG (ug/mg protein)

13 a

14 a

IgE (ng/mg protein)

591 a

954 ab

387 a

1483 b

Different letter denotes a significant difference assumed at p<0.05.

Serum and mucosal Immunoglobulins Serum IgG concentrations in the sensitive dogs were significantly higher (p<0.05) than control dogs (Control - 18.0 mg/ml versus sensitive - 47.8 mg/ml). This increase in serum IgG levels was not reflected in the intestine (Table 2). A significant increase (p<0.05) in mucosal IgA was identified in the sensitive panel compared to controls (Table 2), whereas serum levels were similar. Levels of mucosal IgE were significantly higher in sensitive dogs fed Diet B compared to Diet A (Table 2). The percentage of serum Ig binding to various dietary components was investigated by ELISA and the sensitive panel were found to have significantly (p<0.05) higher levels of wheat specific IgE compared with control dogs (Control - 0.77% ver sus sensitive - 2.64%). There was no significant difference in Ig binding to any other dietary component tested.

Summary of Results Numerous immunological and physiological parameters in sensitive dogs were significantly different from healthy controls. To summarise: Canine DS was associated with • loose faecal consistency. • mild lymphocytic-plasmacytic colitis. • reduction in colonic water and electrolyte transport function. • change in the inflammatory status of the colon, in particular the release of pro-inflammatory eicosanoids and nitric oxide. • increased colonic IgA production. • increased serum IgG and produce higher levels of serum IgE antibody specific for wheat protein compared to control dogs.

oxide and IgA. The inflammatory response leads to a reduction in the absorptive function of the colon, resulting in loose faecal consistency. This study has shown that variations in faecal character in dogs fed different diets are related to changes in colonic transport function, and that water absorption is a major determinant of faeces quality. Changes in the absorption of NaCl in the present study were associated with decreased salvage of water from the colonic crypts. The results support the hypothesis that deterioration in faecal character is a consequence of reduced absorptive function, and that this effect is exaggerated in dogs with non-specific dietary sensitivity. We also found that more substantial changes in transport function, as seen in the sensitive dogs, were associated with disruption of crypt microstructure, although the origin of this damage were not determined. This study has demonstrated that sensitivity is associated with a mild lymphocytic-plasmacytic colitis and an ‘active’ inflammatory response. Levels of pro-inflammatory eicosanoids and the free radical nitric oxide were significantly higher in sensitive dogs, as was mucosal IgA. The release of PGE2 and NO may contribute to the alteration in colonic transport function, causing dissipation of electrolyte concentration gradients across the colonic mucosa and failure of crypt water uptake. These physiological changes resulted in the passing of loose faeces in these dogs. To conclude, dietary sensitivity is associated with a mild inflammation, which actively involves the release of pro-in flammatory eicosanoids, nitric oxide and IgA in the gut. The inflammatory response leads to a reduction in the absorptive function of the colon, resulting in loose faecal consistency. This work has provided an important advance in our understanding of the mechanism of loose faeces in sensitive dogs, and may provide us with important opportunities for new management strategies.

Related References Discussion The aim of this study was to advance our understanding of the pathophysiology of dietary sensitivity. Previous investigations demonstrated that the poor faecal quality in these dogs was not due to changes in pancreatic or small intestinal function (Rolfe et al). The present study showed that sensi tivity is associated with a mild inflammation which actively involves the release of pro-inflammatory eicosanoids, nitric

Rolfe VE, Adams C, Smith VV, Butterwick RB & Batt RB (2000). Pathophysiology of canine NSDS. Gastroenterology 118(4), 5224. Halff M, McNeill L,Adams C & Rolfe VE (2000). Changes in serum and colonic immunoglobulin production in dogs with NSDS. Gastroenterology 118(4), 6122. McNeill L, Vallance C,Adams C & Rolfe VE (2000). Diarrhoea is associated with colonic inflammation in NSDS dogs. Gastroenterology 118(4), 6179. Rolfe VE,Edon G, Hare J, Butterwick RM & Batt RM. Characterisation of non-specific dietary sensitivity in dogs and evaluation of pancreatic and small intestinal function. (Submitted for publication).

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Medicina preventiva e diagnosi precoce delle malattie oncologiche nell’animale giovane adulto ed anziano Giorgio Romanelli DMV, Diplomato ECVS - Libero professionista, Milano

Le malattie tumorali sono la causa più comune di morte nei nostri animali da compagnia, ancora di più che nell’uomo dove le malattie cardiovascolari detengono questo triste primato. Pur sapendo che l’età di picco dell’insorgenza tumorale è di 10.5 anni, è necessario impostare sin dai primi mesi di vita una sor veglianza attiva sulle forme neoplastiche atta ad un loro precoce riconoscimento e tr attamento. Purtroppo in medicina veterinaria è difficile parlare di diagnosi precoce vista la scarsità di esami biochimici e strumentali che sono invece oramai la norma nella specie umana (PAP test, mammografia, sangue occulto fecale, misurazione di marker tumorali); si deve invece tendere ad una diagnostica precoce e ad una prevenzione per così dire a larga fascia.

ANIMALE GIOVANE da 0 ad 1 anno di vita La reale incidenza di forme neoplastiche nell’animale giovane è di circa 1.5/100.000. estremamente più bassa rispetto a quella nel soggetto di 10-11 anni che si calcola attorno a 84/100.000. Mentre la maggior parte dei tumori dell’adulto sono di derivazione epiteliale, i tumori dell’animale giovane sono prevalentemente di derivazione mesenchimale. Le neoplasie più comuni nell’animale giovani sono l’istiocitoma cutaneo, il linfangiosarcoma, il linfoma,l’osteosarcoma, il fibrosarcoma indifferenziato orale, i tumori embrionari ed i tumori dell’SNC. Nel gatto i tumori più comuni sono quelli di origine linfatica.

Prevenzione • Test e vaccinazione per FeLV • Nel gatto, attenzione estrema al sito di iniezione di vaccini e farmaci • Gonadectomia prepubere L’ovarioisterectomia eseguita prima del primo calore oltre ad eliminare totalmente la possibilità di tumori ovarici ed uterini, riduce allo 0.5% la possibilità di insorgenza di neoplasie mammarie. La castrazione elimina il rischio di tumori al testicolo.

Diagnosi precoce Anche nell’animale giovane, non escludere mai le forme tumorali dal diagnostico differenziale ed attuare tutte le misure atte a diagnosticarle

ANIMALE ADULTO (da 1 a 7 anni di vita nel gatto e nei cani di piccola taglia, da 1 a 5 anni nel cane di grossa taglia) ed ANIMALE ANZIANO Con l’avanzare dell’età la possibilità di crescita tumorale aumenta fino ai 10-11 anni per poi decrescere fino alla fine della vita

Prevenzione Nel gatto adottare quanto suggerito dalla Feline Vaccine Associated Sarcomas Task Force sull’uso e le modalità di somministrazione dei vaccini ed annotare il punto di iniezione del vaccino annuale per non praticare consecutivamente due inoculazioni nella stessa posizione Attuare tutte le procedure diagnostiche corrette in caso di formazione di nodulo post-iniettivo se: • Persiste per 3 mesi dopo l’iniezione • È maggiore di 2 centimetri in diametro • Aumenta di dimensioni 1 mese dopo l’iniezione

Diagnosi precoce Ad ogni visita clinica controllare accuratamente il cavo orale, i testicoli, le ghiandole mammarie e la cute ed insegnare al proprietario le manovre corrette per poterlo fare periodicamente a casa. Cavo orale: i tumori della bocca sono comuni e maligni nella maggior parte dei casi. Controllare con maggiore a ttenzione la parte aborale e le tonsille. Mammella: circa il 60%, nel cane, ed il 90%, nel gatto, dei tumori mammari sono maligni. La prognosi è anche dipendente dalle dimensioni. Cute: circa il 20%, nel cane, e l’80%, nel gatto, delle neoformazioni cutanee sono maligne. Ancora una volta la prognosi è anche dipendente dalle dimensioni. Tutte le neoformazioni cutanee vanno sottoposte ad ago aspirazione Nell’animale porre attenzione particolare a tutti i sintomi che possano essere provocati da una forma tumorale, soprattutto carico dell’apparato respiratorio e digerente

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REGOLE GENERALI DI DIAGNOSTICA TUMORALE (IN OGNI ETÀ) • Non escludere mai una forma neoplastica in alcun so ggetto di qualsiasi età • Tutte i tumori devono essere considerati maligni fino a che un esame citologico e/o istologico non dimostra il contrario • Non adottare mai l’atteggiamento aspettiamo e vediamo se cresce • Inviare tutto ciò che si asporta ad un laboratorio di istologia veterinaria per un esame istologico e non gettarlo • In caso di neoplasie multiple sullo stesso soggetto, prendere nota dei siti di escissione che devono corrispondere nella risposta • Non emettere prognosi senza una diagnosi • In caso di dubbio chiedete informazioni al patologo • Non esitare a ripetere la biopsia • Trattare i tumori quando sono di piccole dimensioni • Tutto quello che cresce sopra o dentro una animale deve essere diagnosticato prima di poterlo considerare benigno • Eseguire una biopsia preoperatoria tutte le volte che il risultato può influenzare il tipo di trattamento • Ogni volta che un’ ago aspirato risulta non diagnostico, ripeterlo o passare ad un esame bioptico

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Diagnosi, trattamento e prevenzione del tromboembolismo arterioso felino Roberto A. Santilli Dr Med.Vet., D.E.C.V.I.M.-C.A. (Cardiology), Libero Professionista, Samarate (Varese)

Andrea Volpe Dr Med.Vet., Libero Professionista, Roma

Riassunto Il tromboembolismo arterioso (T.E.A.) è una grave complicanza che occorre in molti gatti con malattie cardiache, an che se raramente è presente in soggetti cardiologicamente sani.11,27 Il T.E.A. rappresenta una condizione ischemica cau sata da un’ostruzione acuta dei vasi sanguigni da parte di un aggregato piastrinico. L’aggregato piastrinico, o embolo, origina da un punto distante del sistema circolatorio (atrio sinistro) e viaggia nei vasi sanguigni fino al punto dell’oc clusione. L’origine dell’embolo è un trombo, un largo aggregato di fibrina e piastrine adese alle pareti vascolari. I pun ti di più frequente embolizzazione nel gatto sono la triforcazione aortica (90%), le arterie renali, mesenterica craniale, cerebrali, polmonari e brachiali. I segni clinici associati a questo tipo di patologia variano in base alla localizzazione dell’embolo.11,28 Il tromboembolismo arterioso è una complicazione comune della cardiomiopatia ipertrofica, della re strittiva e delle forme non classificate, mentre un tempo, quando era più frequente, della cardiomiopatia dilatativa se condaria a carenza di taurina. 11,28 Raramente è possibile riscontrare il T.E.A. anche in gatti con ipertiroidismo.21,22

1- EZIOPATOGENESI

b- Alterazioni circolatorie

In generale la formazione del trombo risulta dalla concomitante presenza delle seguenti condizioni costituenti la triade di Wirchow28: a) Esposizione del tessuto vascolare subendoteliale; b) Alterazioni circolatorie; c) Aumento della coagulabilità.

L’iperaggregabilità piastrinica, secondaria alle alterazioni circolatorie, è il principale fattore predisponente la formazione di trombi nelle cardiomiopatie feline. La stasi e la turbolenza circolatoria, presenti nelle camere cardiache dilatate, determinano l’insorgenza di fenomeni trombotici. Queste alterazioni circolatorie sono talvolta evidenziabili con un esame ecocardiografico che mostra la presenza dell’ecocontrasto spontaneo in atrio sinistro, a testimonianza di un aumento delle dimensioni camerali e di una riduzione della velocità del flusso.

a- Esposizione del tessuto vascolare subendoteliale La formazione del trombo si può verificare se una lesione dell’endocardio, solitamente atriale sinistro, permette l’esposizione del collagene subendocardico, inducendo adesione, aggregazione piastrinica e attivazione del sistema intrinseco della coagulazione. Le piastrine attivate rilasciano adenosina di fosfato (ADP), serotonina e trombossano A2, i quali promuovono un’ulteriore aggregazione piastrinica e vasocostrizione. La fibrina, che rappresenta il prodotto finale della cascata coagulativa, polimerizza all’interno dell’aggregato piastrinico dando luogo alla formazione di un trombo che aderisce alle pareti vascolari.

c- Aumento della coagulabilità Il gatto già in condizioni fisiologiche presenta un’alta reattività piastrinica che aumenta notevolmente alla presenza di esposizioni del collagene subendocardico o di alterazioni circolatorie. L’alta reattività piastrinica nel gatto è causata dal maggior volume dei trombociti, dall’elevato contenuto in serotonina degli stessi e dalla loro intensa aggregazione in risposta agli stimoli serotoninergici.

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Diversi studi hanno valutato il sistema coagulativo e i fattori predisponesti il tromboembolismo arterioso in gatti sani e con cardiomiopatie. Alte concentrazioni plasmatiche di omocisteina e basse concentrazioni di vitamina B 12 e arginina rappresentano fattori di rischio per lo sviluppo di aterosclerosi coronaria e cerebrale e di malattie vascolari periferiche, a causa dei danni ossidativi all’endotelio vascolare, alterazione del potenziale trombotico, aumento della coagulabilità e diminuzione della produzione di ossido nitrico (N.O.).6 Tali alterazioni dell’omocisteina8 e della vitamina B126 sono state rilevate in gatti con cardiomiopatia e/o T.E.A.. La concentrazione di vitamina B12 ha una correlazione inversamente proporzionale con le dimensioni dell’atrio sinistro. 6 Come unico precursore del NO, la riduzione plasmatica dell’arginina, può giocare un ruolo determinante nella patogenesi del tromboembolismo. Essa induce, infatti, una diminuzione della concentrazione del N.O. con una conseguente assenza dell’effetto vasodilatatore e antiaggregante di quest’ultimo.6 Recenti ricerche hanno dimostrato, tuttavia, che i cani e i gatti con cardiomiopatie e in gatti con T.E.A. presentano in realtà un aumento e non una riduzione dell’ossido nitrico.3,7 Tra i parametri coagulativi valutati in corso di cardiomiopatie feline i più importanti sono le attività dell’AT-III e del plasminogeno. I gatti con malattie cardiache acquisite hanno mostrato un aumento dell’attività dell’AT-III. Questo indica una maggiore capacità d’inibire la trombina e le altre proteasi seriche (VIIa, IXa, Xa e XIa) diminuendo, così, i rischi di complicazioni tromboemboliche, anche se le alterazioni emodinamiche possono sopraffare questo potenziale meccanismo protettivo. L’attività del plasminogeno è diminuita nei gatti cardiomiopatici, così come la retrazione del coagulo in corso di disfunzione ventricolare sinistra.24 Infine le piastrine dei gatti che ricevono propranololo o diltiazem mostrano un marcato aumento della reattività nei confronti del collagene24, anche se in studi precedenti il propranololo da solo o in associazione con l’aspirina non determinava un aumento dell’aggregazione piastrinica in risposta al collagene, all’ADP o all’adrenalina. 30 La sintomatologia rilevata in corso di Tea è dovuta essenzialmente ad un’inibizione del circolo collaterale a causa di sostanze vasocostrittrici (Serotonina, Trombossano A2) liberate dall’embolo. La serotonina oltre ad inibire il circolo collaterale attraverso la contrazione della muscolatura liscia dei vasi, induce aggregazione piastrinica e promuove la formazione ed il rilascio di trombossano A2. Quest’ultimo è una prostaglandina prodotta e rilasciata dalle piastrine in risposta a diversi stimoli (collagene, trauma, ADP, serotonina). Esso riveste un ruolo d’estrema importanza sull’attivazione, il rilascio e l’aggregazione piastrinica ed un inteso effetto vasocostrittore.27,28,32 In seguito ad un evento tromboembolico a carico della triforcazione aortica, l’apporto di sangue ai muscoli ed ai nervi degli arti posteriori è molto ridotto. In un modello sperimentale tale perfusione è ridotta al 23% 72 ore dopo l’embolizzazione.28 Nei casi clinici di tromboembolismo aortico è dimostrata la comparsa di una neuropatia ischemica le cui manifestazioni iniziali sono una riduzione della velocità di conduzione nervosa e del potenziale d’azione. Il danno

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ischemico a carico delle fibre nervose può variare da diversi gradi di demielinizzazione, a degenerazione assonale. La rimielinizzazione occorre in un periodo da due a quattro settimane dopo l’episodio ischemico acuto. Un aumento nella velocità di conduzione nervosa e del potenziale d’azione in un periodo di tre settimane, è ben correlato con un grado di recupero degli arti posteriori. Nei gatti la rigenerazione degli assoni dei nervi peroneo e tibiale è presente due mesi dopo l’evento tromboembolico. 28 Il tromboembolismo aortico causa un danno ischemico anche ai muscoli degli arti posteriori (tibiale craniale, gastrocnemio)34. Le alterazioni istologiche sono caratterizzate da vari gradi di necrosi localizzata. Le fibre muscolari meno seriamente lesionate sono in grado di rigenerare mentre le fibre necrotiche sono sostituite da tessuto cicatriziale.28

2- PRESENTAZIONE CLINICA La maggior parte dei gatti con T.E.A. è di razza domestica con una lieve predisposizione del sesso maschile, è inoltre presente una cardiopatia sottostante, che nel 90% delle volte rimane subclinica fino all’evento tromboembolico.22 Tra i rilievi anamnestici di più frequente riscontro il più caratteristico è l’insorgenza improvvisa di paresi o paralisi del treno posteriore con vocalizzi e sospetto di lesioni traumatiche.11 All’esame clinico spesso sono presenti soffi cardiaci e/o ritmi di galoppo. Molti gatti presentano inoltre segni clinici riferibili alla patologia cardiaca sottostante quali tachipnea, dispnea, ipotermia e al tromboembolismo quali polso femorale assente (78%)22 o debole, muscoli gastrocnemi contratti e dolenti con perdita della funzione motoria, arti freddi con letto ungueale pallido o cianotico. Alcuni gatti mantengono la capacità di muovere la coda, altri perdono la capacità di muovere gli arti posteriori a partire dai fianchi, mentre altri ancora perdono solo la capacità di muovere gli arti distalmente al ginocchio o al garretto. Questi ultimi possono estendere e flettere le articolazioni coxo-femorali camminando sulle ginocchia.11 La perdita della sensibilità cutanea occorre abbastanza precocemente e segue il quadro di perdita motoria; alcuni gatti perdono la sensibilità cutanea di sotto al ginocchio, mentre altri presentano una perdita che coinvolge tutto il treno posteriore. Il riflesso patellare manca in alcuni gatti mentre rimane inalterato in altri. Il riflesso anale è solitamente normale così come la funzionalità vescicale. Alcuni soggetti possono presentare ritenzione urinaria, ma la vescica solitamente può essere facilmente svuotata per compressione manuale esterna. 11 Dopo l’evento tromboembolico acuto ha inizio il processo di trombolisi. In alcuni soggetti con trombi di piccole dimensioni, la trombolisi è rapida e completa permettendo la ripresa funzionale degli arti in poche ore. In altri casi se il trombo è di grosse dimensioni e l’attività trombolitica è modesta, si ha una perdita permanente del flusso con paralisi permanente. Tra questi due estremi ci sono gatti che recuperano la funzionalità degli arti lentamente ma sviluppano fenomeni di necrosi muscolare e cutanea che richiedono un’accurata pulizia chirurgica ed in rari casi l’amputazione dell’arto.11 L’embolo, oltre che la trifor-

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cazione aortica, può occludere altre arterie sistemiche determinando sintomatologie diverse secondo il distretto interessato. L’embolizzazione bilaterale delle arterie renali causa un’insufficienza renale acuta, dell’arteria mesenterica craniale un’ischemia intestinale fatale, delle arterie cerebrali disfunzioni del sistema nervoso centrale, delle arterie polmonari insufficienza respiratoria e dell’arteria brachiale paresi degli arti anteriori.28

3 - DIAGNOSI La diagnosi di tromboembolismo aortico si basa sulla presenza dei classici segni clinici sopraindicati, uniti ai rilievi di laboratorio e strumentali atti a svelare il tipo e la prognosi della patologia cardiaca sottostante e delle alterazioni conseguenti al fenomeno tromboembolico. La metodica angiografica consente di valutare l’entità del processo embolico e la vascolarizzazione collaterale, anche se questo studio richiede una preventiva stabilizzazione del paziente. L’ecografia addominale può visualizzare il trombo all’interno dell’aorta e il Doppler a codice di colore valutare la compromissione del flusso. 11 Gli esami strumentali che permettono di diagnosticare le cardiomiopatie sottostanti includono le radiografie del torace, l’elettrocardiogramma e l’ecocardiografia. I radiogrammi del torace rivelano cardiomegalia nel 90% dei casi e segni d’insufficienza cardiaca nel 70%.22 La maggior parte dei gatti con T.E.A. ha delle alterazioni elettrocardiografiche riferibili ad ingrandimento ventricolare sinistro e a disturbi della conduzione. I ritmi di più frequente riscontro sono il ritmo sinusale e la tachicardia sinusale.22 All’ecocardiografia le più comuni cardiomiopatie sono la cardiomiopatia ipertrofica (60%) e le forme non classificate (25%). 22 Nei rimanenti casi sono presenti le forme restrittive, dilatative o tireotossiche. Tra le alterazioni biochimiche ritroviamo aumenti della ALT, della AST e della glicemia. Le variazioni dei parametri epatici sono riveribili a necrosi muscolar e, mentre la glicemia aumenta in seguito allo stress. L’azotemia e la creatinina sono spesso elevate, probabilmente in seguito ad una riduzione della perfusione renale o all’embolizzazione delle arterie renali. In uno studio di N.J. Laste e N.K. Harpster è stato rilevato un caso d’iperkalemia, mentre l’ipocalcemia era presente in 20 dei 53 casi esaminati. Nell’uomo l’ipocalcemia è stata descritta come un evento transitorio in corso di rabdomiolisi traumatica correlata ad un massiccio danno muscolare. L’ipercolesterolemia è stata riscontrata in molti pazienti, mentre modici squilibri elettrolitici ed acido-basici sono stati ritrovati in un numero esiguo di casi e imputabili a disidratazione, vomito, minor consumo di cibo ed acqua e somministrazione di diuretici. L’esame emocromocitometrico può evidenziare una neutrofilia matura ed una linfopenia secondari ai fenomeni di stress. 22 Le diagnosi differenziali da considerare in presenza di una paralisi improvvisa del treno posteriore includono oltre al tromboembolismo aortico, eventi traumatici, tumori pr imari o metastatici, processi infiammatori, protrusione dei dischi intervertebrali ed infarti fibrocartilaginei.33,35

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4 - INCIDENZA E SOPRAVVIVENZA MEDIA DEL T.E.A. Secondo alcuni ricercatori il T.E.A. si manifesta in più del 48% dei soggetti cardiopatici,6 con un’incidenza pari al 25% nella cardiomiopatia dilat at iva, del 50% nella cardiomiopatia ipertrofica, del 25% nella cardiomiopatia res t ri t t iva e del 15% nella cardiomiopatia a bande moderatrici. 28 Altri autori riportano invece lo sviluppo di T.E.A. nel 13% dei casi clinici di cardiomiopatia ipert ro fica felina, mentre nel 41% dei casi sottoposti ad un’analisi necroscopica.14 Lo studio più ampio di tromboembolismo aortico distali riporta su 63 gatti che il 57,1% presentava una cardiomiopatia ipertrofica, il 4,8% una cardiomiopatia ipertrofica secondaria a ipertiroidismo, il 27% una cardiomiopatia intermedia, il 6,3% una cardiomiopatia restrittiva e il 3,2% una cardiomiopatia dilatativa.22 In uno studio di Atkins la sopravvivenza mediana di 61 gatti con cardiomiopatia ipertrofica è risultata essere di 732 giorni.26 Essa non è stata influenzata dall’età al momento della diagnosi, dalla razza, dal peso o dal sesso. Al contrario i segni clinici sono risultati importanti nella determinazione della prognosi. I gatti con una frequenza cardiaca minore di 200 battiti/minuto sono sopravvissuti più a lungo rispetto a quelli con una frequenza cardiaca maggiore o uguale a 200 battiti/minuti. I soggetti senza segni clinici hanno avuto una sopravvivenza maggiore rispetto a quelli sintomatici, mentre i gatti con insufficienza cardiaca hanno avuto una sopravvivenza mediana di 92 giorni e quelli con T.E.A. di 61 giorni. Tutti i gatti con tromboembolismo e il 60% di quelli con insufficienza cardiaca sono morti entro sei mesi dal momento della diagnosi. Altri valori prognostici negativi in corso di cardiomiopatia ipertrofica sono rappresentati dall’estensione e dal grado d’ipertrofia, dall’ingrandimento atriale sinistro e dall’assenza del movimento sistolico anteriore.20 Da un altro studio è emerso che solo il 37% dei gatti con cardiomiopatia e tromboembolismo aortico distale sono sopravvissuti alla fase acuta. Dei ventidue gatti cardiopatici sopravvissuti quattro sono stati trattati con aspirina e diciotto con warfarin, la sopravvivenza media è risultata pari a 11,5 mesi, con alcuni soggetti ancora in vita a due anni dall’episodio iniziale; il 50% dei pazienti trattati ha presentati un ulteriore episodio tromboembolico. 22 L’utilizzo dell’acido acetilsalicilico ha dimostrato un ricorrenza di fenomeni trombotici pari al 50 27 – 7511% entro 2 – 6 mesi 21, anche se uno studio del New York State College ha registrato una sopravvivenza per più di 18 mesi senza ulteriori episodi tromboembolici in cinque gatti trattati con questo farmaco.28 L’uso del warfarin sodico come terapia profilattica nelle tromboembolie aumenta i tempi di sopravvivenza da pochi giorni a 78 mesi, con il 56% che sopravvive per più di sei mesi.21 Tromboembolismi ricorrenti sono stati documentati comunque anche nei gatti trattati con warfarin (43,5%)21, ma in percentuale minore rispetto alla profilassi con aspirina dopo terapia con t-PA11,27 (50 – 75%).

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5- CASISTICA PERSONALE

d- Sopravvivenza media

a- Incidenza delle diverse cardiomiopatie

- Gruppo 1: gatti con T.E.A. accertato

L’analisi è stata effettuata su 141 gatti con cardiomiopatia riferiti al nostro centro dal 01-01-1996 al 23-09-2000. Le diverse cardiomiopatie risultavano così distribuite: • 50,3% cardiomiopatia ipertrofica di cui il 64,8% era in forma ostruttiva • 15,6% cardiomiopatia restrittiva • 15,6% cardiomiopatia tireotossica • 13,5% cardiomiopatia ipertensiva • 2,8% cardiomiopatia dilatativa • 1,4% cardiomiopatia ischemica • 0,7% cardiomiopatia tachicardia-indotta. Dal campione totale sono stati selezionati 85 gatti poi suddivisi in tre gruppi: 1) Con almeno un episodio certo di T.E.A.; 2) con episodi sospetti di T.E.A. (zoppie, debolezza periodica sul treno posteriore); 3) a rischio di T.E.A., in base ai parametri ecocardiografici (rapporto atrio sinistro/Aorta > 2,autocontrasto spontaneo atriale). La maggior parte dei gatti compresi in questi gruppi attuava una profilassi aspirinica, fatta eccezione dei soggetti con cardiomiopatia tireotossica ed ipertensiva ed alcuni soggetti con proprietari poco disponibili. Un ultimo gruppo di gatti includeva soggetti in terapia aspirinica indipendentemente dai parametri sopraindicati. Di questi ottantacinque gatti, sedici sono stati persi al follow-up

b- Incidenza del T.E.A. L’incidenza del T.E.A. nel nostro campione di gatti è risultata pari al 23,2% con un totale di sedici gatti con almeno un episodio tromboembolico. Di questi sedici gatti due hanno avuto una trombosi a livello dell’arto anteriore destro, uno ha avuto un primo episodio sul treno posteriore seguito da una trombosi all’arto anteriore destro e da un successivo episodio tromboembolico riguardante l’aorta distale; undici hanno avuto una trombosi delle iliache, uno una trombosi iliaca parziale e uno una trombosi dell’arto posteriore sinistro. Durante il periodo di studio si sono verificati due casi di T.E.A. in un soggetto con cor triatriatum sinister ed in un soggetto senza cardiopatie sottostanti. L’incidenza del T.E.A. nelle diverse cardiomiopatie sui 69 gatti considerati è stata la seguente: • nel 46,7% dei casi di cardiomiopatia ipertrofica • nel 22,7% dei casi di cardiomiopatia ipertrofica ostruttiva • nel 26,6% dei casi di cardiomiopatia restrittiva

c- Percentuale delle diverse cardiomiopatie nei 16 gatti con T.E.A. La percentuale delle diverse cardiomiopatie nei 16 gatti con T.E.A. è la seguente: • 43,7% di cardiomiopatia ipertrofica • 31,2% di cardiomiopatia ipertrofica ostruttiva • 25% di cardiomiopatia restrittiva

Escludendo dal calcolo della sopravvivenza media i soggetti sottoposti subito ad eutanasia e quelli morti nella fase acuta della malattia; assumendo come tempo di sopravvivenza quello fino al 31/10/00 e quello relativo al momento in cui non si sono avute più notizie per quelli persi al followup, la sopravvivenza media è stata pari a 17,25 mesi.

- Gruppo 2: gatti con zoppie o debolezza periodica treno posteriore Dei 7 gatti presi in esame, con le caratteristiche sopra riportate, in 3 era stata segnalata nell’anamnesi una zoppia a livello del treno posteriore, in 1 una zoppia a livello dell’arto anteriore destro, in 2 una debolezza periodica sul treno posteriore ed in 1 una zoppia sul posteriore insorse nei 20 giorni intercorrenti tra la diagnosi e l’eutanasia per chilotorace; di questi 7 gatti 3 sono ancora in vita, 2 sono stati persi al follow-up e 2 sono morti. La sopravvivenza media, assumendo come tempo di sopravvivenza quello fino al 31/10/00, è stata pari a 15,3 mesi.

- Gruppo 3: gatti con parametri ecografici a maggior rischio di Tea Dei 65 gatti presi in esame, con le caratteristiche sopra riportate, 4 hanno avuto un episodio tromboembolico successivamente. Escludendo dal calcolo della sopravvivenza media i gatti deceduti o sottoposti ad eutanasia subito dopo la diagnosi, quelli persi al follow-up ed assumendo come tempo di sopravvivenza quello fino al 31/10/00, il risultato medio è stato pari a 10,5 mesi per i gatti senza fenomeni embolici e pari a 5,9 mesi per quelli con fenomeni di T.E.A. successivi.

e- Follow-up Dei 16 gatti con T.E.A. 7 sono stati sottoposti ad eutanasia immediatamente dopo l’evento tromboembolico, 2 sono morti nella fase acuta della malattia,2 sono stati persi al follow-up, 5 sono ancora in vita di cui uno ha episodi ricor renti di trombosi all’arto anteriore destro ed uno a distanza di circa 9 mesi dal primo episodio di paresi sul treno posteriore ha avuto una trombosi all’arto anteriore destro seguita, a pochi giorni di distanza, da una trombosi a carico dell’aorta distale con successiva eutanasia. Dei rimanenti 69 gatti, 16 sono stati persi al follow-up mentre 8 sono ancora vivi, le cause di morte nei rimanenti 45 sono state le seguenti: • Morte per causa ignota 26,7% • Eutanasia per causa ignota 17,8% • Edema polmonare alveolare 17,8% • Morte improvvisa 11,1% • Neoplasia 6,7% • Sincope 4,4% • Insufficienza renale cronica 4,4% • Eutanasia per insufficienza cardiaca refrattaria 4,4% • Morte per insufficienza cardiaca congestizia 2,2% • Lipotimia 2,2% • Insufficienza renale acuta anurica 2,2%

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6- TRATTAMENTO DEL T.E.A. Il trattamento del tromboembolismo aortico è un argomento di dibattito. La rimozione chirurgica dell’embolo è raccomandata da alcuni autori; la maggior parte delle pubblicazioni recenti raccomanda riposo in gabbia con trattamento medico di supporto e prevenzione delle recidive.28

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L’uso del catetere di Fogarty nel gatto richiede ulteriori indagini. La cateterizzazione di un’arteria femorale felina embolizzata è difficoltosa a causa del suo piccolo lume e l’immobilizzazione del gatto richiede solitamente una pesante sedazione o anestesia generale, aumentando così la percentuale di rischio in pazienti cardiopatici.

b- Trattamento medico a- Trattamento chirurgico L’embolectomia è il trattamento chirurgico usato nel tromboembolismo aortico felino. 28 La rimozione dell’embolo dall’aorta addominale caudale è una procedura più comunemente riportata. L’aorta addominale caudale è raggiunta attraverso un’incisione ventrale e viene temporaneamente occlusa insieme alle arterie iliache interne ed esterne e all’arteria mediana sacrale. Un’incisione trasversale o longitudinale è praticata sull’arteria all’altezza dell’embolo. Il trombo è rimosso attraverso un forcipe fine e le legature sono temporaneamente sciolte, permettendo al flusso ematico di rimuovere ogni residuo di coagulo attraverso l’arteriotomia. Nell’uomo questa tecnica è stata abbandonata a causa dell’alto tasso di mortalità (>50%) correlato al fatto che la maggior parte dei pazienti presentava una grave compromissione del sistema cardiovascolare. Nel gatto il tasso di mortalità non è stato determinato ma, poiché la maggior parte dei pazienti felini con tromboembolismo presenta una cardiomiopatia non stabilizzata, i rischi di un’anestesia generale e di una chirurgia addominale sono alti. Attualmente la maggior parte degli emboli a carico dell’aorta addominale caudale negli uomini viene rimossa attraverso l’uso del catetere di Fogarty introdotto attraverso un’arteriotomia femorale bilaterale. Il palloncino posto all’estremità del catetere è fatto passare cranialmente all’ostruzione aortica, una volta superato l’embolo è insufflato e il catetere tirato distalmente. L’embolo viene spinto dal palloncino a livello dell’incisione femorale, dove viene estratto. L’analgesia è ottenuta attraverso premedicazione ed anestesia locale. Gravi complicazioni, non correlate all’anestesia, sono state riportate nei pazienti umani sottoposti a questo tipo d’intervento in seguito alla riperfusione degli arti inferiori. La rivascolarizzazione delle zone ischemiche può determinare la mobilizzazione di alcuni metaboliti come l’acido lattico, il potassio e gli ioni idrogeno che si sono riversati nello spazio interstiziale in seguito alla rottura di cellule ne crotiche. Altri danni da riperfusione sono causati dall’improvviso rilascio di sangue intrappolato negli arti con successiva depressione miocardica, ridistribuzione in circolo dei fattori della coagulazione attivati e di coaguli che si sono formati all’interno delle vene che possono embolizzare a livello polmonare ed infine dalla mioglobinemia e dalla mioglobinuria con danno renale. Nell’uomo il tasso di mortalità associato all’embolectomia con il catetere di Fogarty è del 10-25%; tuttavia, come nei pazienti felini, i pazienti umani con rigidità e cianosi degli arti sono considerati ad alto rischio di complicazioni letali. In uno studio di umana è stato riportato che l’81% dei soggetti gravemente colpiti muore dopo embolectomia28.

Gli obiettivi del trattamento medico sono rappresentati da cure iniziali di supporto durante la crisi ischemica acuta, ripristino del flusso ematico agli arti e prevenzione di ulteriori episodi embolici. Durante la fase acuta è di fondamentale importanza il supporto cardiovascolare, l’alleviamento del dolore ed il riposo in gabbia.28 Lo stress da embolizzazione può causare scompenso cardiovascolare in gatti con cardiomiopatia sottostante. Alcuni soggetti possono andare incontro ad edema polmonare, versamento pleurico, ipotermia o shock cardiogeno. Ossigenoterapia, fluidoterapia con attento monitoraggio al sovraccarico di fluidi, diuretici e nutrizione forzata possono essere necessari come supporto iniziale, dato che nella fase acuta del tromboembolismo queste terapie di supporto sono più importanti della terapia trombolitica stessa. Se le condizioni cliniche del paziente lo permettono bisognerà diagnosticare il tipo di cardiomiopatia sottostante attraverso indagini elettrocardiografiche, radiografiche ed ecocardiografiche al fine di stabilire una terapia specifica ed emettere una prognosi precisa. In caso di cardiomiopatia ipertrofica sarà preferibile evitare di somministrare propranololo a favore del diltiazem; infatti, sebbene entrambi abbiano un effetto inotropo negativo determinando una diminuzione della frequenza cardiaca e migliorando la funzione diastolica, il propranololo promuove la contrazione della muscolatura liscia con conseguente vasocostrizione mentre il diltiazem determina vasodilatazione.28 Tra i B-Bloccanti in cardiologia felina trova largo impiego l’atenololo, che oltre alla sua azione B1- selettiva, riduce la reattività piastrinica nei confronti dell’ADP riducendo la possibilità di fenomeni tromboembolici, com’è stato dimostrato in uno studio su gatti ipertiroidei con disfunzione ventricolare sinistra secondaria alla tireotossicosi.24 La neuropatia ischemica determina nei gatti una forte dolorabilità agli arti durante le prime 12-24 ore. Il movimento e la palpazione dei muscoli tendono ad esacerbare il dolore. La somministrazione di 0,05-0,15mg/kg ogni 6 ore IM o IV di ossimorfone o l’inoculazione IV di butorfanolo alle dosi di 0,1mg/kg o 0,02-0,4mg/kg IM o SC da ripetere ogni 4 ore è consigliata al fine di ottenere una buona analgesia.11 Le proprietà analgesiche del butorfanolo sono 5 volte superiori a quelle della morfina e i suoi effetti deprimenti a livello del sistema respiratorio la eguagliano; di conseguenza bisogna essere molto cauti nell’utilizzare questi farmaci in pazienti con edema polmonare o versamento pleurico. L’acepromazina (0,05-0,1 mg/kg IV) può essere utilizzata come ansiolitico in quei gatti che continuano ad apparire angosciati nonostante la somministrazione degli analgesici, ponendo attenzione al fatto che le sue proprietà ipotensive non peggiorino la già compromessa perfusione del

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treno posteriore.11,13 Infine gli arti interessati dovranno essere mantenuti al caldo e protetti da possibili traumatismi vista l’assenza di sensibilità. La durata del ricovero dei gatti con embolo a sella può essere ridotta attraverso la lisi rapida del coagulo o l’anticipazione dello sviluppo di un circolo collaterale. In medicina umana la tecnica più comunemente usata per il trattamento del tromboembolismo è la ter apia con enzimi trombolitici. I trombi intravascolari, nei soggetti sani e malati, sono dissolti dal sistema fibrinolitico composto dal plasminogeno e dagli attivatori ed inibitori del plasminogeno. Gli attivatori del plasminogeno sono enzimi che catalizzano la conversione del plasminogeno in plasmina, la quale idrolizza la fibrina e il fibrinogeno in modo da dissolvere e prevenire la formazione di trombi intravascolari.27 Gli attivatori convenzionali sono rappresentati dalle streptochinasi ed urochinasi le quali convertono sia il plasminogeno presente nel sistema circolatorio che quello legato alla fibrina in plasmina. La plasmina, essendo una proteasi sierica non specifica, determina una degradazione di numerose proteine presenti in circolo come il fibrinogeno,i fattori della coagulazione, il plasminogeno e l’attivatore stesso somministrato. La degradazione del fibrinogeno circolante determina un aumento nel plasma dei prodotti di degradazione della fibrina, che sono dei potenti anticoagulanti. Quindi l’attivazione del plasminogeno circolante, la produzione dei prodotti di degradazione della fibrina, e la diminuzione dei fattori della coagulazione aumentano quello che viene definito lo stato di proteolisi sistemica incrementando i rischi di sanguinamento. Gli effetti negativi della streptochinasi e dell’urochinasi non possono essere disgiunti dagli effetti terapeutici desiderati.13,27 In uno studio sperimentale è stata dimostrata l’inefficacia di una dose di carico di 90.000 UI di streptochinasi, somministrate per infusione endovenosa lenta in 20-30 minuti, seguita da una dose endovenosa di mantenimento pari a 45.000 UI/h nell’arco di 180 minuti nel tentativo di ottenere una riperfusione degli arti posteriori.27,29 L’insuccesso della terapia con str eptochinasi da un punto di vista funzionale, malgrado quest’ultima sia in grado di realizzare una riduzione o addirittura una completa risoluzione del trombo aortico, è da imputare all’azione vasocostrittrice esercitata dalle sostanze vasoattive, come la serotonina e il trombossano A2, liberate dalle piastrine attivate. Secondo alcuni autori la somministrazione di una dose minore per un periodo più prolungato può essere più appropriata per il trattamento del tromboembolismo aortico, essendo la somministrazione per 180 minuti un intervallo di tempo troppo breve per ottenere la lisi completa del coagulo.11,13 In tutti i casi il protocollo terapeutico riportato in letteratura prevede la somministrazione di 90.000UI IV nella prima ora seguite da 45.000 UI/h IV per non più di 5 ore monitorando il K +, la creatinina almeno ogni 4 ore, l’aPTT e il PT.28,29 Sebbene sia difficile giudicarne l’efficacia, alcuni casi gravi hanno tratto beneficio da questo approccio terapeutico.11 Una valida alternativa potrebbe essere rappresentata dagli attivatori tissutali del plasminogeno (t-PA). I t-PA sono delle proteine presenti in tutti i mammiferi che possono essere sintetizzate in laboratorio ed utilizzati come agenti trombolitici. I t-PA hanno una bassa affinità per il plasminogeno circolante e la dose necessaria per determinare la lisi

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del coagulo non è in grado né di attivare il plasminogeno circolante né d’indurre uno stato di proteolisi sistemica.13,27 Inoltre i t-PA ed il plasminogeno hanno un’alta affinità per la fibrina all’interno dei trombi; in questo modo entrambi si legano ad essa in stretta vicinanza l’uno all’altro potenziando la conversione del plasminogeno in plasmina nel sito di maggior interesse. La piccola frazione plasmina che entra nel sistema circolatorio è neutralizzata dall’alpha2–antiplasmina circolante. In base ad esperienze cliniche la posologia riportata in letteratura è da 1 a 10 mg/kg IV totali, somministrati alla velocità di 0,25-1 mg/kg/h.13 Studi clinici eseguiti in gatti con tromboembolismo aortico hanno dimostrato un’elevata capacità trombolitica dei t-PA con riduzione del tempo di riperfusione e rapida ripresa alla deambulazione. Il 43% dei soggetti trattati sopravvivono alla terapia e camminano entro 48 ore dalla presentazione e l’angiogramma, eseguito dopo trattamento, dimostra la risoluzione dell’occlusione vascolare.27 Tuttavia il 50% dei gatti va incontro a morte durante la terapia.13,27 Le cause di mortalità sono rappresentate dall’iperkaliemia (71%), insufficienza cardiaca congestizia (14%) e morte improvvisa secondaria ad una trombosi coronaria acuta in partenza da un trombo primario presente nell’atrio sinistro.27 L’alta incidenza dell’iperpotassiemia, accompagnata da acidosi metabolica, dipende dal fatto che prodotti metabolici di scarto quali l’acido lattico e il potassio si accumulano nell’interstizio e nello spazio vascolare delle regioni poste distalmente al trombo. In seguito alla riperfusione degli arti queste sostanze sono trasportate dal sistema venoso nella circolazione sistemica fino a raggiungere il cuore causando effetti deleteri. I soggetti che sopravvivono alla terapia con t-PA, come già detto in precedenza, mostrano segni di aumento della funzione neuromuscolare e della capacità deambulatoria entro due giorni dalla presentazione, in contrasto con le 1-6 settimane necessarie per vedere segni analoghi di miglioramento in gatti che vanno incontro a risoluzione spontanea. Il monitoraggio elettrocardiografico e la frequente valutazione clinica del paziente, accompagnata da ripetuti controlli della potassiemia e dell’acidosi metabolica, dovrebbero essere usati per rilevare l’inizio degli squilibri biochimici. Quando si sviluppa iperkaliemia è necessario intraprendere una ter apia aggressiva con bicarbonati somministrati con o senza calcio gluconato. Tuttavia, spesso, l’iperpotassiemia e l’acidosi possono evolvere indipendentemente dall’inizio della terapia, portando a morte il paziente.13 Visti gli alti costi del farmaco, l’elevata mortalità (50%)13,27, l’alta incidenza di sindromi da riperfusione, la ritrombosi nonostante prevenzione con aspirina nel 5075%11,27 dei soggetti e il risultato simile ottenibile, anche se con tempi di recupero più lunghi (entro 6 settimane)27, con l’aspirina, la terapia con t-PA non è ancora consigliabile.11 Un altro farmaco utilizzato nel tromboembolismo aortico felino è l’eparina. Questo farmaco non è efficace per determinare la lisi del trombo, ma possiede proprietà anticoagulanti che si manifestano attraverso il legame con l’antitrombina III e la conseguente inattivazione dei fattori II e Xa. Affinché ciò sia possibile, l’eparina non frazionata deve essere costituita da almeno diciotto unità saccaridiche per l’inattivazione del fattore II e da cinque unità per l’inattivazione del fattore Xa. Grazie alla sua struttura molecolare, co-

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stituita da una media di 45 unità saccaridiche per catena, l’eparina non frazionata complessata con l’antitrombina III riesce a legare con successo sia il fattore Xa che il fattore II inattivandoli.12 L’eparina, quindi, è efficace nel prevenire la formazione del coagulo ma non è in grado di dissolvere trombi già formati. La somministrazione di eparina può prevenire l’allargamento dell’embolo attraverso l’inibizione della formazione di ulteriori coaguli sul trombo preesistente, favorendo un più rapido istaurarsi di un circolo collaterale. Sebbene diverse dosi di eparina siano state proposte nel trattamento del T.E.A., la posologia più indicata sembra essere quella che prevede la somministrazione di 200-300 UI/kg ogni 6-8 ore, a patto che non si faccia uso di agenti trombolitici.13 L’eparina può essere somministrata per via sottocutanea o IV. Un bolo IV iniziale può essere seguito da un infusione continua o da una somministrazione sottocutanea. Molta attenzione deve essere riservata al sito d’inoculo evitando scrupolosamente di somministrare il farmaco nella metà caudale del corpo, poiché oltre a causarne un mancato assorbimento, si potrebbe indurre un’infezione in zone prive di flusso e quindi non in grado di garantire un buon funzionamento delle difese immunitarie. Quando l’eparina è usata come unico farmaco anticoagulante la dose di 200 UI/kg ogni 6 ore raramente alterare in maniera significativa la cascata coagulativa.13 La terapia con eparina è continuata fino al momento della dimissione dall’ospedale e poi il suo uso viene monitorato attraverso il confronto del tempo di tromboplastina parziale attivata (aPTT) basale ed i rispettivi valori giornalieri dopo l’inizio della terapia con eparina. L’aPTT sotto eparina dovrebbe essere almeno 1,5 volte il valore basale.11 Secondo Kittleson la terapia migliore prevede la somministrazione di eparina sodica ad una dose iniziale di 220 UI/kg IV, seguita da una dose di mantenimento di 70200 UI/kg SC ogni 6 ore di eparina calcica. La dose deve essere scelta in base all’aPTT. Come terapia parallela è consigliabile utilizzare farmaci vasodilatatori che possono migliorare il flusso sanguigno collaterale in corso di tromboembolismo aortico. Un efficace vasodilatatore deve antagonizzare la riduzione del circolo collaterale indotto dalle sostanze vasoattive liberate dalle piastrine durante il fenomeno tromboembolico. L’ipotensione associata all’uso di alcuni vasodilatatori periferici ne limita l’impiego per la possibilità di compromettere il sistema cardiovascolare e ridurre ulteriormente il flusso di sangue agli arti già scarsamente irrorati. L’uso dell’acepromazina, che determina una marcata vasodilatazione attraverso un’inibizione α-adrenergica, non è consigliato da molti autori.13 I calcio-antagonisti producono vasodilatazione attraverso l’inibizione della contrazione calcio-dipendente della muscolatura liscia, è inoltre motivo di discussione la loro capacità d’inibire l’aggregazione piastrinica, infatti in uno studio sperimentale condotto su gatti sani è stato dimostrato che il diltiazem non inibisce l’aggregazione piastrinica né potenzia l’azione dell’aspirina mentre nell’uomo tale inibizione può avvenire attraverso diversi meccanismi.19 Questo gruppo di farmaci, come già detto, è da preferire al propranololo in corso di tromboembolismo in gatti con cardiomiopatia ipertrofica. Studi sperimentali hanno dimostrato l’efficacia dell’indometacina nel prevenire la vasocostrizione nelle zone di-

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stali all’embolo se somministrata prima di indurre l’ostruzione arteriosa. Purtroppo non è chiaro se l’indometacina sia in grado di migliorare il circolo collaterale se somministrata, successivamente all’evento tromboembolico.11

7- PROGNOSI La prognosi a breve termine del T.E.A. è buona per i gatti senza insufficienza cardiaca congestizia (I.C.C.) al momento della diagnosi, mentre è considerata riservata nei soggetti con T.E.A. e I.C.C. associate. Una delle più comuni cause di morte nelle prime 24 ore è l’eutanasia. In uno studio, circa il 30% dei gatti con tromboembolismo acuto muoiono durante la fase iniziale dell’ospedalizzazione e circa il 35% è sottoposto ad eutanasia. La prognosi a lungo termine per i soggetti che superano la fase acuta è altamente variabile con gatti che sopravvivono dai 3 ai 30 mesi. Il tempo medio di sopravvivenza è di circa 10-12 mesi.22 In un precedente studio retrospettivo di 74 gatti con cardiomiopatia ipertrofica, nove soggetti che avevano sviluppato tromboembolismo mostrarono una sopravvivenza mediana di 61 giorni e nessuno visse per più di 6 mesi. 26 L’esito più favorevole dei casi descritti da N.J. Laste e N.K. Harpster con tutta probabilità è attribuibile all’utilizzo profilattico del warfarin sodico come agente anticoagulante. La prognosi individuale dipende comunque dalla gravità dell’evento embolico, dal grado d’ischemia, dalla presenza di aree infartuali a livello di organi addominali, dalla gravità della malattia cardiaca sottostante e dal grado d’insufficienza cardiaca concomitante. La prognosi a lungo termine per il recupero della funzionalità degli arti dipende o dall’abilità del sistema fibrinolitico del gatto o dal successo delle terapie instaurate. Molte variabili biologiche determinano o meno la spontanea riperfusione del treno posteriore. Il 50% dei soggetti recuperano l’uso degli arti posteriori senza ulteriori problemi mentre altri sviluppano complicazioni come lesioni cutanee, gangrena e contrattura muscolare. La maggior parte dei gatti sviluppa un ulteriore evento tromboembolico giorni o mesi dopo il primo evento di T.E.A..11,13,,21,22,27

8- PROFILASSI a- Aspirina L’aspirina è il farmaco più usato nella prevenzione del T.E.A. nell’uomo e nel gatto, essa inibisce la funzione e l’aggregazione piastrinica attraverso il blocco della produzione piastrinica di trombossano A2. L’aspirina inibisce l’attività della ciclossigenasi piastrinica, l’enzima necessario per la conversione dell’acido arachidonico in endoperossidasi, la quale a sua volta è convertita in trombossano A2 per opera della trombossano sintetasi. Grazie alla diminuzione degli effetti vasocostrittori del trombossano A2, l’aspirina permette al sangue di superare l’ostruzione aortica attraverso il circolo collaterale. Gli effetti inibitori di questo farmaco sulla ciclossigenasi piastrinica sono irreversibili, in questo modo le piastrine presenti nel torrente circolatorio sono rese incapaci per tutta la dura-

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ta della loro permanenza in circolo di produr re trombossano A2. Diversamente a quanto accade a livello piastrinico, l’aspirina ha effetti reversibili sulla ciclossigenasi presente a livello dell’endotelio vascolar e. La ciclossigenasi endoteliale catalizza la conversione dell’acido arachidonico in endoperossidasi, il quale a sua volta, è convertito in prostaciclina per opera della prostaciclina sintetasi. La prostaciclina è un potente inibitore dell’aggregazione piastrinica e svolge un ruolo di primo piano nella prevenzione dell’aggregazione piastrinica spontanea all’interno dei vasi sanguigni. Poiché l’inibizione della ciclossigenasi endoteliale persiste per meno di 24 ore, la somministrazione di aspirina ogni 3 giorni permette la sintesi di prostaciclina mentre inibisce in modo continuativo la produzione di trombossano A2. I gatti hanno una scarsa tolleranza all’acido acetilsalicilico a causa del ridotto metabolismo epatico di questa molecola. Reazioni tossiche quali anoressia, emesi, letargia e morte si possono verificare a dosi pari a 25 mg/kg tre volte al giorno. La dose richiesta per inibire l’aggregazione piastrinica è pari a 25 mg/kg ogni tre giorni.28,31 Questa posologia permette anche la sintesi di prostaciclina fra le due somministrazioni del farmaco. Alcuni autori raccomandano l’uso profilattico dell’aspirina in tutti quei casi in cui ci sia un moderato ingrandimento dell’atrio sinistro. 13 Sfortunatamente 5027 – 75%11 dei gatti in terapia con acido acetilsalicilico vanno incontro ugualmente a fenomeni tromboembolici.

b- Acido eicosapentanoico e acido docosaesaenoico Un approccio potenzialmente utile nella gestione dei gatti predisposti al tromboembolismo è la somministrazione degli acidi grassi n-3 poliinsaturi a lunga catena quali lo eicosapentanoico (EPA, 20:5 n-3) e il docosaesaenoico (DHA, 22:6 n-3), che sono presenti abbondantemente nei pesci e nei mammiferi marini. Numerosi studi biochimici, fisiologici e clinici in cardiologia umana hanno dimostrato gli effetti vasodilatatori, antischemici ed antiaggreganti di questi acidi grassi. In seguito ad una integrazione dietetica gli acidi grassi n-3 competono con l’acido arachidonico per entrare a costituire le membrane fosfolipidiche riducendo i livelli tissutali di quest’ultimo. Quando a livello piastrinico viene attivato il metabolismo degli eicosanoidi gli EPA si sostituiscono all’acido arachidonico come substrato per la ciclossigenasi, determinando l’inibizione della produzione di trombossano A2 e la sintesi di trombossano A3 inattivo. Al con trario la produzione di prostaciclina I 2 da parte dell’endotelio vascolare non viene ridotta in maniera sostanziale ed in aggiunta viene sintetizzata prostaciclina I3 che mantiene l’attività antiaggregante. Diversamente dagli altri mammiferi, i gatti non sono in grado di convertire l’acido linoleico in acido arachidonico a livello epatico, motivo per cui la fonte di quest’ultimo è essenzialmente di natura alimentare. In base a ciò ci si dovrebbe aspettare che la somministrazione di EPA e DHA comporti una riduzione significativa del rapporto n-6/n-3 nel plasma e nelle membrane piastriniche determinando una riduzione dell’aggregazione piastrinica e delle trombosi. Tale aspettativa viene disattesa dai risultati di uno studio eseguito su gatti sani il quale ha dimostrato che la

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somministrazione di alte dosi di acidi grassi n-3 purificati (EPA, DHA) una volta al giorno non prolunga il tempo di sanguinamento buccale né inibisce l’aggregazione piastrinica in gatti clinicamente normali.12 Risulta quindi improbabile che una simile somministrazione di EPA e DHA possa diminuire la trombogenesi in gatti con malattie cardiovascolari. Pertanto la somministrazione giornaliera di acidi grassi n3 non è raccomandata per la gestione di questi pazienti. Tali risultati sono inaspettati e suggeriscono studi addizionali per valutare altre variabili quali intervallo tra dosi e contenuto di acidi grassi n-6 nella dieta. Una più frequente somministrazione di acidi grassi n-3 purificati o un’alimentazione continua con diete ad alto contenuto di acidi grassi n-3 rimane un mezzo potenzialmente efficace d’inibizione della funzione piastrinica in gatti predisposti al tromboembolismo.

9- NUOVE PROSPETTIVE TERAPEUTICHE a- Eparina frazionata (LMWH) L’eparina non frazionata (UFH) produce il suo effetto anticoagulante legandosi all’antitrombina III e inibendo la trombogenesi primariamente con l’inattivazione dei fattori II e Xa. L’eparina frazionata (LMWH), a causa della sua struttura molecolare (in media quindici unità saccaridiche per catena con meno del 50% delle LMWHs con 18 unità saccaridiche per catena necessarie per permettere l’inattivazione del fattore II), ha una più alta attività antifattore Xa rispetto a quella antifattore II con un rapporto antifattore Xa/II pari a 2:1-4:1.10,12 A causa dei diversi metodi di scomposizione, le LMWHs sono una classe eterogenea di composti con differenze in peso molecolare, farmacocinesi ed attività antitrombotica ed anticoagulante, motivo per cui ciascun composto deve essere considerato individualmente al momento di selezionare un prodotto e una dose per un suo uso specifico. Perciò ciascuna LMWH deve essere considerata un’entità distinta che può essere usata soltanto ad un dosaggio ottimizzato per una specifica indicazione. In modelli sperimentali animali e in varie prove cliniche è stato evidenziato che le LMWHs rilasciano un inibitore del percorso del fattore tissutale (TFPI) sia dopo la somministrazione endovenosa sia sottocutanea. La somministrazione ripetuta di LMWHs produce effetti antitrombotici progressivamente più pronunciati. Nondimeno le risposte emorragiche restano variabili e sono dipendenti dal prodotto come hanno dimostrato studi su primati dove la misura del rilascio di TFPI in seguito a somministrazione IV o SC è specifica del prodotto. Tali studi hanno anche dimostrato l’importanza di questo inibitore per le azioni delle LMWHs.Altre azioni farmacologiche dell’eparina a basso peso molecolare includono il rilascio del plasminogeno tissutale (t-PA), l’inibizione del rilascio di molecole di adesione intracellulare e vascolare, la diminuzione dei livelli circolanti del fattore di von Willebrand e la modulazione del flusso sanguigno, motivo per cui le analisi convenzionali usate per l’eparina, come i test anti-Xa, anti-IIa e di anticoagulazione globale non riescono né a misurare né a quantificare queste azioni. La farmacocinesi prevedibile e la più lunga emivita dell’LMWH rappresentano la ragione della sua facilità d’uso,

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rendendone possibile la somministrazione 1 o 2 volte al giorno senza monitoraggio di laboratorio.10 In veterinaria l’utilizzo della LMWH può rappresentare un valido metodo per la cura e la profilassi del tromboembolismo aortico felino. Ricercatori della Tufs University hanno recentemente valutato l’uso di dalteparin in gatti sani. Una dose di 100 UI/kg/die per via sottocutanea è stata raccomandata, monitorando l’attività dell’antifattore Xa e l’aPTT (le molecole con meno di 18 unità saccaridiche delle LMWHs non sono in grado di inibire la trombina esercitando effetti trascurabili sull’aPTT). Non è stata data nessuna conferma, tuttavia, dell’efficacia. Una considerazione importante nei gatti a rischio di tromboembolismo è rappresentata dal fatto che l’LMWH ha un minor effetto inibitorio sull’attivazione piastrinica indotta dal collagene, rispetto all’UFH. In relazione al fatto che i gatti presentano una maggior predisposizione ai fenomeni trombotici rispetto alle altre specie a causa della loro iperaggregabilità piastrinica, può essere necessario associare una terapia antiaggregante alla LMWH. È inoltre importante sottolineare che l’antidoto utilizzato per neutralizzare l’attività antitrombotica dell’eparina non frazionata è rappresentato dalla protamina solfato. Essa, infatti, può neutralizzare l’attività anti-II rapidamente e completamente; mentre inverte solo parzialmente (40-70%) l’attività anti-Xa. Poiché le LMWH producono la maggior parte del loro effetto anticoagulante attraverso l’inibizione del fattore Xa, l’efficacia della protamina nella loro in attivazione sarà limitata, richiedendo la somministrazione di plasma fresco in caso di g rave sanguinamento.10

b- Eptifibatide Il percorso finale comune all’aggregazione piastrinica e alla trombosi coinvolge l’attivazione della funzione recettoriale del complesso glicoproteico (GP) IIb-IIIa piastrinico (αIIbβ3). Tale funzione GP IIb-IIIa è altamente regolata: su piastrine non stimolate, la GP IIa-IIIb ha una bassa affinità per le proteine adesive solubili, ma dopo l’attivazione piastrinica essa diventa un recettore per il fibrinogeno e per il fattore di vonWillebrand. Il legame di questi fattori a molecole singole di GP IIb-IIIa su piastrine adiacenti porta alla formazione di aggregati piastrinici e trombi coronarici. La GP IIb-IIIa rappresenta quindi un bersaglio terapeutico più razionale e fino a poco tempo fa inesplorato.17 L’eptapeptide ciclico sintetico Eptifibatide (INTEGRILIN; COR therapeutics,South San Francisco, CA/Schering-Plough, Kenilworth, NJ), è uno degli inibitori della GP IIb-IIIa valutato in modo più esteso ed ha già mostrato caratteristiche di eccellente efficacia e sicurezza nella prevenzione di complicazioni ischemiche dell’angioplastica e nella gestione di trombosi coronariche in corso di sindrome ischemica coronarica acuta nell’uomo.4,5,15-18 Esso è un inibitore specifico della GP IIb-IIIa, e poiché la distribuzione del suo complesso è ristretta alle piastrine e ai loro precursori, l’azione farmacologia dell’eptifibatide è limitata a queste cellule, permettendo il suo ampio uso nella clinica. Sia studi preclinici che clinici hanno dimostrato che l’eptifibatide è un potente inibitore dell’aggregazione piastrinica con un rapido inizio d’azione e solo mo-

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desti effetti sulle misure del tempo di sanguinamento. Inoltre l’effetto antitrombotico dell’eptifibatide è prontamente reversibile. La rapida dissociazione di questa molecola dalla Gp IIb-IIIa e la sua clearance relativamente rapida, permettono un pronto ripristino della funzione piastrinica e dell’emostasi normale in seguito all’interruzione della sua infusione endovenosa. L’eliminazione è sia renale sia extrarenale ed è direttamente proporzionale al peso ed inversamente proporzionale all’età. In base a studi clinici l’inibizione dell’aggregazione piastrinica si verifica entro 15 minuti dalla somministrazione del farmaco e, a dosaggi appropriati,l’inibizione è mantenuta per tutta la durata dell’infusione endovenosa. L’eptifibatide è eliminata rapidamente (1 o 2 ore) e la funzione piastrinica è ripristinata entro 2-4 ore dal termine del trattamento. La mancanza di risposta anticorpale, che è spiegata molto facilmente dalle piccole dimensioni di questa molecola, potrebbe essere un’importante considerazione nei pazienti che richiedono la somministrazione ripetuta di un inibitore del recettore GP IIb-IIIa e in quelli con storia sconosciuta. La struttura del peptide ciclico rende, infine, l’eptifibatide resistente alle proteasi del plasma ed aumenta la sua biodisponibilità. In medicina veterinaria campioni di sangue sono stati prelevati da due gatti sani e trattati con PPACK per prevenire la coagulazione. L’eptifibatide è stata aggiunta al sangue in cinque differenti concentrazioni, compreso un campione di controllo, e l’aggregazione piastrinica è stata misurata in vitro. Il risultato finale è stato un’inibizione dell’aggregazione piastrinica in vitro nel sangue felino da parte delle due concentrazioni maggiori di eptifibatide. Questa classe di farmaci può,quindi, fornire un effettivo metodo di prevenzione del tromboembolismo aortico in gatti cardiopatici. Ulteriori valutazioni della farmacocinesi, efficacia e tossicità sono necessarie .

c- Warfarin Il Warfarin sodico è una miscela racemica di due stereoisomeri (R e S) presenti in quantità approssimativamente uguali. Il Warfarin racemico di solito si somministra per via orale, ma è disponibile anche per iniezione endovenosa. Il farmaco possiede un’alta biodisponibilità e viene rapidamente assorbito dal tr atto gastrointestinale, raggiungendo le massime concentrazioni plasmatiche molto velocemente (uomo: <90 min; gatto: <2 ore).14 Esso circola nel sangue primariamente legato alle proteine del plasma (uomo e gatto: 99%; cane: 93%)14, principalmente albumine, e si accumula velocemente nel fegato dove svolge il suo effetto biologico e viene metabolizzato principalmente ad opera del sistema citocromo P-450. Malattie epatiche e/o farmaci che inibiscono o inducono questo sistema enzimatico possono potenzialmente influenzare la farmacocinetica del farmaco. Il warfarin produce i suoi effetti anticoagulanti attraverso l’inibizione dell’interconversione ciclica della vitamina K epossido in vitamina KH2, impedendo la _-carbossilazione dei residui di acido glutammico dei fattori della coagulazione vitamina K-dipendenti (II, VII, IX e X) e delle proteine anticoagulanti C ed S. Il fattore procoagulante VII scompare per primo poiché possiede l’emivita biologica più breve (cane 6,2 ore; uomo 6 ore)9,14. L’emivita della proteina C an-

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ticoagulante è simile a quella del fattore VII. I fattori II, IX e X hanno emivita rispettivamente di 41, 13,9 e 16,5 ore nel cane.14 La differente emivita tra i fattori procoagulanti ed anticoagulanti determina un transitorio stato di ipercoagulabilità che è ben documentato nell’uomo nella fase iniziale della terapia con warfarin. La diminuzione della concentrazione sierica dei fattori IX e X, primariamente responsabile degli effetti antitrombotici, si verifica dai 4 ai 6 giorni dopo l’inizio della terapia nei pazienti umani.21 Poiché la concentrazione della proteina C diminuisce rapidamente, i pazienti possono andare incontro ad uno stato di ipercoagulabilità per i primi 3-4 giorni. L’eparina somministrata per via SC esplica la sua azione antitrombotica indipendentemente dal meccanismo sopra riportato e andrebbe somministrata in concomitanza con il warfarin per i primi 2-5 giorni di terapia.14,21 In base ad uno studio in medicina umana di Hirsh, Dalen et al. gli effetti antitrombotici del warfarin sono da imputare primariamente ad una riduzione della protrombina (fattore II) e forse del fattore X, più che ad una riduzione dei fattori VII e IX. Viene quindi consigliato di sovrapporre l’eparina al warfarin nel trattamento dei pazienti con malattie trombotiche fino a che il livello di protrombina viene abbassato al range terapeutico. Dato che il fattore II ha un’emivita di circa 60 ore nell’uomo, è necessaria una sovrapposizione di almeno 4 giorni per ottenere questo risultato.9 Numerosi farmaci influenzano l’azione del warfarin nell’uomo9,25 e presumibilmente anche nel gatto.21 La maggior parte di essi riduce l’assorbimento intestinale o altera la clearance del warfarin. Altri interferiscono con l’azione del warfarin alterando i fattori della coagulazione o la funzione piastrinica. Prima di utilizzare il warfarin occorre quindi conoscere i possibili rischi derivati dalla somministrazione o dalla sospensione di farmaci in soggetti in terapia anticoagulante facendo ricorso ad un più frequente monitoraggio dei tempi di coagulazione. Nell’uomo è ben documentato che malattie epatiche e disfunzioni tiroidee influenzino la risposta al warfarin. Sono necessari ulteriori studi per stabilire se stati febbrili, I.C.C. ed altri stati patologici aumentano l’effetto del warfarin o di altri anticoagulanti orali in alcuni pazienti.1 Il warfarin è usato nei pazienti umani per il trattamento delle trombosi di vene profonde, per la prevenzione delle trombosi post-operatorie, per prevenire complicazioni tromboemboliche nella sostituzione delle valvole cardiache, nelle malattie valvolari e nella fibrillazione atriale. In veterinaria l’alta incidenza di episodi ricorrenti di tromboembolismo in gatti trattati con aspirina in associazione con l’esito spesso fatale di tali fenomeni, ha rappresentato l’impulso per l’utilizzo del warfarin come alternativa. Inizialmente il warfarin era somministrato solo ai gatti ricoverati in seguito ad un evento tromboembolici, oggi se ne consiglia l’usa a scopo profilattico in tutti i soggetti con un rapporto in M-mode atrio sinistro/aorta >2.0 o in caso di autocontrasto spontaneo nelle camere atriali anche in assenza di precedenti eventi tromboembolici.21,22 In passato si raccomandava di valutare il grado di anticoagulazione facendo riferimento al tempo di protrombina (P.T.) ed avendo cura che esso fosse da 1,3 a 1,6 volte il valore normale dopo somministrazione di warfarin. A causa della variabilità delle tromboplastine commerciali usate per

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l’esecuzione del test, oggi si ritiene più corretto standardizzare il P.T. utilizzando il rapporto internazionale di normalizzazione (INR).9,14,21 Questo rapporto esprime il P.T. come se fosse determinato usando la preparazione internazionale di riferimento di tromboplastina di cervello umano. In questo modo il P.T. può essere comparato sia tra laboratori diversi che in diversi momenti in uno stesso labor atori. L’I.N.R. è calcolato in base alla seguente formula: INR= (PT del paziente/PT di controllo)ISI dove l’ISI rappresenta l’indice di sensibilità individuale della tromboplastina usata nell’analisi del P.T.. L’ISI riflette la rispondenza di una data tromboplastina alla riduzione dei fattori della coagulazione vitamina K-dipendenti in rapporto alla preparazione internazionale di riferimento. I produttori di tromboplastina forniscono l’ISI di ciascun gruppo prodotto. Da ciò si comprende il rischio di attuare un’anticoagulazione inappropriata non usando l’INR nel monitoraggio del paziente. È inoltre molto importante sapere che diversi lotti di una stessa marca di tromboplastina possono avere ISI diversi. L’uso di tromboplastine con ISI basso (<1,2) aumenta la sensibilità dell’INR, infatti, si è visto che una tromboplastina “non rispondente” (ISI elevato) porta a un prolungamento del P.T., per una data riduzione di fattori della coagulazione vitamina K-dipendenti, minore rispetto ad una tromboplastina più rispondente.9 Le tromboplastine variano nella loro rispondenza agli effetti anticoagulanti del warfarin in base al loro tessuto di origine, al contenuto di fosfolipidi, e al metodo di preparazione. L’I.N.R. raccomandato per la prevenzione del tromboembolismo arterioso felino, estrapolando questo valore da studi di umana, è compreso tra 2,0 e 3,0.14,21 Tali studi han no confermato che una terapia a basse dosi di warfarin con un I.N.R. compreso tra 2,0 e 3,0 è efficace nella prevenzione del tromboembolismo e meno rischiosa al fine delle complicazioni emorragiche rispetto ad una terapia ad alte dosi con un INR > di 3. La dose di warfarin consigliata nel gatto per ottenere un I.N.R. tra 2,0 e 3,0 è risultata pari a 0,5mg ogni 2421 ore per os (0,25mg/die nei gatti di piccola taglia) e nei primi 4-6 giorni occorre associare la somministrazione di 200 UI/kg SC tre volte al giorno di eparina calcica. Il monitoraggio è eseguito una volta al giorno, fino a due giorni dopo la sospensione dell’eparina, per assicurarsi che sia stato raggiunto il grado di anticoagulazione desiderato prima delle dimissioni del paziente. Una volta a casa la frequenza viene ridotta a due volte a settimana per 2 settimane, poi una volta a settimana per un periodo che varia da alcune settimane a due mesi ed infine ogni 6-8 settimane.21 Un cambiamento nella marca del warfarin utilizzato o nella somministrazione di altri farmaci richiede una temporanea intensificazione dei monitoraggi. L’esperienza di Harpster e Baty nella gestione di un gruppo di gatti con gravi malattie cardiache con la terapia anticoagulante, ha mostrato chiaramente che il warfarin non è un farmaco innocuo. Su 25 gatti trattati col warfarin per prevenire il tromboembolismo arterioso, il 20% ha sviluppato almeno un episodio emorragico, fatale in 2 casi.14,21 È inoltre emerso che esiste una considerevole variabilità nel dosaggio richiesto al fine di avere la risposta terapeutica de-

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siderata e il suo raggiungimento più o meno rapido. Le complicazioni di sanguinamento vanno da perdite minori (gengivali o lesioni orali) ad epistassi, perdite da lesioni cutanee, ematuria o anche sanguinamento cavitario accompagnato da debolezza, collasso o morte improvvisa. Gravi complicazioni vengono generalmente evitate eseguendo un attento monitoraggio dell’INR. 21

Bibliografia 1.

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Demirkan K, Stephens MA, Newman KP, et al. (2000). Response to warfarin and other anticoagulants: effects of desease states. South Med J 93(5):448-455 Dowers KL, Bright JM (2000). Anti-aggregatory effects of a GPIIb/IIIa antagonist on feline platelet function. Proc. 18th ACVIM 712,Seattle,WA Freeman LM,McMichael M, De Laforcade A,et al. (2000). Elevated nitric oxide in cats with cardiomyopathy. Proc. ESVIM Congress 78 Kleiman NS, Lincoff AM, Flaker GC, et al. (2000). Early percuta neous coronary intervention,platelet inhibition with eptifibatide, and clinical outcomes in patients with acute coronary syndromes. Circulation 101:751-757 Mark DB, Harrington RA, Lincoff AM, et al. (2000). Cost-effectiveness of platelet glicoprotein IIb/IIIa inhibition with eptifibatide in patients with non-ST-elevation acute coronary syndromes.Circulation 101:366-371 McMichael MA, Freeman LM, Selhub J, et al. (2000). Plasma homocysteine, B vitamins, and acid concentrations in cats with cardiomyopathy and arterial thromboembolism. J Vet Intern Med 14: 507-512 Rush JE, Freeman LM (2000). Congestive heart failure:a chronic inflammatory disease? Proc. ESVIM Congress 34-36 Hohenhaus AE (1999). Evaluation of plasma homocysteine concentration in CM cats with CHF and TEA. 17th ACVIM Forum 715 Hirsh J, Dalen JE,Anderson DR, et al. (1998). Oral anticoagulants. Mechanism of action, clinical effectiveness, and optimal ther apeutic range. Chest 114(5):445S-469S Huang JN, Shimamura A (1998). Low molecular weight heparins. Hemat/Oncol Cl North Am 12(6): 1251-1281 Kittleson MD, Kienle DK (1998). Thromboembolic disease. A Textbook of Small An Card Med: 540-551 Quader MA, Stump LS, Sumpio BE (1998). Low molecular weight heparins:current use and indications. J Am Coll Surg 187(6): 641-658 Rush JE (1998). Therapy of feline hypertrophic cardiomyopathy. Vet Clin North Am 28(6): 1459-1479 Smith SA (1998). Warfarin therapy in small animal patients. What we do know and what we do not know. Proc. 16th ACVIM: 440-442 Harrington RA (1997). Design and methodology of the PURSUIT trial: evaluating eptifibatide for acute ischaemic coronary syndromes. Am J Cardiology 80(4A):34B-38B

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IMPACT-2 Investigators (1997). Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-2. The Lancet 349: 1422-1428 Phillips DR, Scarborough RM (1997). Clinical pharmacology of eptifibatide. Am J Cardiology 80(4A): 11B-20B Tcheng JE (1997). Impact of eptifibatide on early ischaemic events in acute ischaemic coronary syndromes: a review of the IMPACT II trial. Am J Cardiology 80(4A): 21B-28B Behrend EN, Grauer GF, Greco DS, et al. (1996). Comparison of the effects of diltiazem and aspirin on platelet aggregation in cats. J Am Animal Hosp 32: 11-18 Fox PR, Liu S , Maron BJ (1995). Echocardiographic assessment of spontaneously occurring feline hypertrophic cardiomyopathy. Circulation 92:2645-2651 Harpster NK, Baty CJ (1995). Warfarin therapy of the cat at risk of thromboembolism. C V T 12: 868-873 Laste NJ, Harpster NK (1995). A retrospective study of 100 cases of feline distal aortic thromboembolism: 1977-1993. J Am Anim Hosp 31:492-500 Bright JM, Sullivan PS, Melton SL, et al. (1994). The effects of n-3 fatty acid supplementation on bleeding time, plasma fatty acid composition, and in vitro platelet aggregation in cats. J Vet Intern Med 8(4): 247-252 Welles EG, Boudreaux MK, Crager CS, et al. (1994). Platelet function and antithrombin, plasminogen,and fibrinolytic activities in cats with heart disease. Am J Vet Res 55(5): 619-627 Wells PS, Holbrook AM, Crowther NR, et al. (1994). Interactions of warfarin with drugs and food. Ann Intern Med 121: 676-683 Atkins CE, Gallo AM, Kurtzman ID, et al. (1992). Risk factors, clinical signs,and survival in cats with a clinical diagnosis of idiopathic hypertrophic cardiomyopathy. J Am Vet Med Assoc 201: 613-618 Pion PD (1988). Feline aortic thromboemboli and potential utility of thrombolytic therapy with tissue plasminogen activator. Vet Clin North Am 18(1): 79-86 Flanders JA (1986). Feline aortic thromboembolism. Comp Continuing Education 8(7):473-484 Killingsworth CR, Eyster GE,Adams T, et al. (1986). Streptokinase treatment of cats with esperimentally induced aortic thrombosis. Am J Vet Res 47(6): 1351-1359 Allen DG, Johnstone IB, Crane S (1985). Effects of aspirin and pr opanolol alone or in combination on haemostatic determinants in the healthy cat. Am J Vet Res 46(3): 660-663 Greene CE (1985). Effects of aspirin and propanolol on feline platelet aggregation. Am J Vet Res 46(9): 1820-1823 Schaub RG, Gates KA, Roberts RE (1982). Effect of aspirin on collateral blood flow after experimental thrombosis of the feline aorta. Am J Vet Res 43(9):1647-1650 Nafe LA (1981). Feline paraparesis. Vet Med/Small 76(12): 17591762 Griffiths IR, Duncan ID (1979). Ischaemic neuromyopathy in cats. Veterinary Record 104: 518-522 Swaim SF, Shields RP (1971). Paraplegia in the cat:etiology and differential diagnosis. Vet Med/Small Anim Clinician 66(8): 787-792

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Selezione del paziente con displasia dell'anca attraverso l'analisi di casi clinici Aldo Vezzoni Med. Vet., Dipl. ECVS, Libero professionista, Cremona

Nella selezione del paziente con displasia dell'anca, per poter suggerire il trattamento sia conservativo che chirurgico più adeguato per ogni singolo caso, occorre seguire un protocollo clinico d'indagine diagnostica che permetta un'inquadramento preciso della condizione patologica presente. 1 Questo protocollo prevede: ❑ una valutazione ortopedica completa del soggetto, che tenga presente le patologie più frequenti in ciascuna razza (BOA - breed oriented approach) e che permetta un'accurata diagnosi differenziale con altre patologie; essa serve, inoltre, per inquadrare il problema "anca" nell'insieme di eventuali altre patologie concomitanti a carico dello stesso arto o di altri arti; ❑ una valutazione attenta del portamento del cane, sia da fermo che in movimento, per evidenziare la distribuzione dei carichi ed eventuali atteggiamenti antalgici; ❑ una valutazione morfologica e funzionale dell'anca nel cane in sedazione profonda, per evidenziare segni di lassità articolare, mediante il test di Ortolani e di Bardens e la valutazione degli angoli di riduzione e di sublussazione, per valutare l’ampiezza dei movimenti articolari ed eventuali segni di artrosi (crepitio articolar e, dolore, fibrosi articolare); ❑ una valutazione radiografica dell’anca mediante le proiezioni necessarie per definire la morfologia articolare e poter esprimere una prognosi e definire un piano terapeutico; oltre alla proiezione ventro-dorsale ad arti estesi e paralleli, considerata come proiezione standard, può render-

si utile una proiezione ad arti flessi (a rana), una proiezione DAR, una proiezione con distrazione delle anche ed una proiezione latero-laterale. Nella selezione del paziente con displasia dell’anca occorre anche considerare gli strumenti terapeutici disponibili, da poter poi scegliere in funzione di ciascun caso clinico: ❑ trattamento conservativo (esercizio controllato, riduzione del peso, FANS); ❑ trattamento chirurgico preventivo (sinfisiodesi pubica, triplice osteotomia pelvica, osteotomia intertrocanterica, acetaboloplastica); ❑ trattamento chirurgico di salvataggio (protesi totale d’anca, ostectomia della testa e del collo del femore); ❑ trattamento chirurgico palliativo (PIN- miotenectomia del muscolo pettineo, tenectomia del muscolo ileopsoas, nevrectomia di superficie della capsula articolare mediale). Nella selezione del paziente con displasia dell’anca per la scelta del trattamento più indicato, occorre considerare anche i seguenti parametri: ❑ età ❑ peso e carattere ❑ attese funzionali ❑ determinazione ed affidabilità del proprietario Seguendo il protocollo descritto, si prendono in considerazione diversi casi clinici relativi a cani di diversa età affetti da displasia dell’anca, per i quali si espone l’iter diagnostico seguito, le considerazioni effettuate, i trattamenti instaurati ed i risultati conseguiti.

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Diagnosi di artrosi nel cane: visita ortopedica ed approccio orientato alla razza Aldo Vezzoni Med. Vet., Dipl. ECVS, Libero professionista, Cremona

L'approccio diagnostico ortopedico orientato alla razza (BOA, breed oriented ap p ro a ch) premette di focalizzare immediatamente la ricerca delle patologie osteo-articolari più frequenti in ciascuna razza, offrendo la possibilità al clinico di operare secondo delle priorità, con minor dispendio di tempo e d'indagini diagnostiche. Consente anche, in virtù della sospettabilità delle varie patologie in ciascuna razza, di operare delle diagnosi precoci, prima dell'instaurarsi di gravi degenerazioni art ro s i ch e, e di facilitare le diagnosi differenziali in presenza di patologie concomitanti. Seguendo quest'approccio e considerando le razze canine più diffuse e con problemi ortopedici più frequenti, proponiamo un algoritmo diagnostico per il cane Pastore Tedesco, i Retrievers ed il cane Corso, mentre altre razze verranno considerate dagli altri relatori. Nel cane Pastore Tedesco le articolazioni bersaglio più frequentemente colpite da patologie sono: ❑ articolazione dell'anca ➨ displasia dell'anca ❑ articolazione del gomito ➨ displasia del gomito (UAP - FCP) ❑ articolazione del ginocchio ➨ OCD, rottura LCA (cane adulto/anziano) Nei cani Retrievers le articolazioni bersaglio più frequentemente colpite da patologie sono: ❑ articolazione dell'anca ➨ displasia dell'anca ❑ articolazione del gomito ➨ displasia del gomito (FCP - OCD) ❑ articolazione del ginocchio ➨ lussazione rotulea, rottura LCA (cane giovane/adulto) ❑ articolazione del garretto ➨ OCD Nel cane Corso le articolazioni bersaglio più frequente mente colpite da patologie sono: ❑ articolazione dell'anca ➨ displasia dell'anca ❑ articolazione del gomito ➨ displasia del gomito (UAP - FCP) ❑ articolazione del ginocchio ➨ OCD, rottura LCA (cane giovane/adulto) ❑ articolazione della spalla ➨ OCD

Nell'approccio diagnostico delle patologie osteo-articolari frequenti in queste razze, prendiamo in considerazione un breve inquadramento di ciascuna patologia (in cosa consiste e come si manifesta clinicamente) e la procedura diagnostica più indicata.

DISPLASIA DELL'ANCA: ❑ in cosa consiste: malformazione articolare a carico dell'acetabolo (bordo dorsale inclinato dorsalmente) e/o della testa e collo femorali (valgismo, anteversione) che si determina durante lo sviluppo, caratterizzata da una mancanza di congruenza articolare e da lassità capsulare; la distribuzione dei carichi ponderali su superfici limitate dell'articolazione provoca una degenerazione della cartilagine sottoposta all'eccessivo carico ed un rimodellamento osseo della testa del femore e dell'acetabolo; la degenerazione della cartilagine e l'esposizione dell'osso subcondrale scatenano il processo degenerativo artrosico. ❑ come si manifesta: nei casi gravi la sublussazione della testa femorale può provocare nei cani in accrescimento (5-8 mesi di età) microfratture del bordo acetabolare dorsale ed erosione della parte dorso-mediale della testa femorale, cause di infiammazione articolare e di dolore, più evidenti clinicamente quando sono monolaterali con zoppia di 2° e 3° grado; nei casi bilaterali le manifestazioni cliniche sono meno evidenti, ma può esserci una difficoltà ad alzarsi da seduto, l'andatura appare incerta, con utilizzo contemporaneo di entrambe le zampe posteriori durante il galoppo (andatura a coniglio), scarsa resistenza alla corsa. Nei cani adulti e anziani le manifestazioni cliniche sono quelle tipiche di un processo artrosico cronico, con rigidità e dolore a freddo e dopo sforzo, limitazioni funzionali e scarsa resistenza alla fatica. ❑ procedura diagnostica: nei casi particolarmente gravi la diagnosi precoce può essere effettuata già dopo il 3°-4° mese di età mediante un esame radiologico del bacino in posizione ventro-dorsale con arti posteriori estesi, paralleli ed intraruotati fino ad ottenere la centratura delle rotule nelle troclee femorali; in questi casi l'acetabolo appare appiattito e la testa femorale sublussata

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o lussata. Nei casi invece di displasia da leggera a grave, la diagnosi precoce può essere eseguita con maggior attendibilità al 6° mese di età, quando sono più facilmente evidenziabili le alterazioni morfologiche dei capi articolari, l'incongruenza articolare e la lassità articolare. Per una valutazione morfologica accurata, utile per una corretta formulazione prognostica e per un eventuale programma terapeutico cor rettivo, occorre un esame radiografico con la proiezione vetrodorsale ad arti estesi, la proiezione ventrodorsale ad arti flessi (a rana) utile per la valutazione del riempimento acetabolare, la proiezione DAR con evidenziazione del bordo dorsale dell'acetabolo e della sua inclinazione. Per la valutazione della lassità articolare, oltre all'evidenziazione dell'incongruenza, è utile eseguire una proiezione con distrazione delle anche ottenuta con un apposito distanziatore, per valutare l'indice di distrazione (DI) di ogni anca: il DI permette di formulare una prognosi sull'evoluzione della displasia nelle forme apparentemente più lievi.

DISPLASIA DEL GOMITO (UAP): ❑ in cosa consiste: la displasia del gomito è una malformazione articolare che si determina durante lo sviluppo, con mancata congruenza articolare a causa di una crescita asincrona di radio ed ulna e/o di una alterazione elittica dell'incisura semiluna re dell'ulna; l'incongruenza articolare determinatasi comporta un sovraccarico ed un'eccessiva sollecitazione di alcune strutture articolari, ed in particolare del processo cronoideo mediale dell'ulna e del condilo mediale dell'omero nella FCP (frammentazione del processo coronoideo dell'ulna) e nella OCD (osteocndrosi dissecante) del condilo mediale dell'omero, quando la crescita del radio è inferiore a quella dell'ulna, del processo anconeo dell'ulna (UAP, mancata unione del processo anconeo) quando la crescita del radio è superiore a quella dell'ulna e dell'incisura semilunare dell'ulna quando questa assume una forma elittica. La concentrazione delle forze di carico su queste strutture articolari determina una degenerazione della cartilagine articolare coinvolta, modificazioni strutturali dell'osso sottostante e lo sviluppo di osteo-artrosi. Nella UAP, in particolare, si determina la mancata fusione della fisi di accrescimento del processo anconeo che avviene normalmente attorno al quarto mese di età, quando una crescita più rapida del radio rispetto all'ulna in questo periodo della crescita trasmette, tramite il condilo omerale, una spinta al processo anconeo che, non essendo ancora fuso con l'ulna, si stacca da essa. Un eventuale ritardo nel processo di ossificazione encondrale (osteocondrosi) della fisi di accrescimento del processo anconeo può contribuire alla debolezza strutturale del processo ed al suo distacco in seguito alle sollecitazioni meccaniche articolari. In questa patologia, l'incongruenza articolare da radio più lungo può variare da un grado minimo ad un g rado elevato con dislocazione craniale del condilo omerale ad opera del capitello radiale; con la crescita successiva quest'incongruenza può sia diminuire che aumentare, od anche invertirsi, determinandosi in tal caso una situazione con radio più corto che provoca una sollecitazione ed una sofferenza del processo coronoideo mediale dell'ulna (FCP).

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❑ come si manifesta: l'insorgere della UAP determina un risentimento algico che si manifesta con una zoppia di 1° o di 2° grado all'età di cinque mesi, talvolta subdola e sottostimata sia dal proprietario che dal veterinario curante. La persistenza della zoppia, il portamento dell'arto in posizione antalgica con il gomito in fuori ed il carpo in atteggiamento valgo, conducono poi alla diagnosi radiologica. La patologia bilaterale determina una sintomatologia più subdola e meno appariscente, causa spesso di diagnosi tardive, con artrosi ormai avanzata. La sinto matologia, anche nel cane adulto, è proporzionale al grado di artrosi determinatasi che, a sua volta, è correlata al grado di incongruenza articolare rimasta. ❑ procedura diagnostica: il sospetto diagnostico nasce ogni qual volta un cucciolo di razza predisposta a UAP presenta una zoppia od un portamento non corretto dell'arto anteriore; la vista clinica evidenzia algia alla palpazione profonda del gomito ed alla sua iperflessione ed iperestensione, con ectasia sinoviale laterale, a livello del muscolo anconeo, nei casi più avanzati. La diagnosi richiede un esame radiografico in proiezione medio-laterale con gomito flesso (30-45°), che permette l'evidenziazione completa del processo anconeo, ed una proiezione sagittale, utile per valutare il grado d'incongruenza articolare tra radio ed ulna. Il grado d'incongruenza articolare può essere ulteriormente indagato con una proiezione medio-laterale neutra (100-120°), valutando lo scalino tra il capitello radiale ed il processo coronoideo laterale dell'ulna. Devono essere radiografati entrambi i gomiti, sia per rilevare la presenza di una patologia bilaterale, spesso presente, sia per avere una conferma della fusione avvenuta nel processo controlaterale sano. I soggetti molto giovani (sotto i cinque mesi d'età) e con mancata fusione bilaterale dei processi anconei, devono essere rivalutati radiograficamente ad intervalli di due settimane per seguirne l'evoluzione. La linea di minor radiodensità che separa il processo anconeo dalla metafisi ulnare, in caso di fusione in atto, tenderà a diventare sempre meno appariscente, mentre in caso di mancata unione diventerà più ampia e più radiotrasparente. In base all'aspetto radiografico la UAP nel cane giovane può essere classificata in tre gradi: nel 1° la linea di separazione non ha una radiotrasparenza completa ed il processo appare in posizione normale, nel 2° la linea di separazione ha una zona di radiotrasparenza completa, ma il processo appare ancora in posizione normale, nel 3°, oltre alla zona di radiotrasparenza completa, che appare più ampia, si osserva un riassorbimento osseo del processo con erosioni del suo profilo ed il processo appare spostato prossimalmente rispetto alla sua sede. Nei soggetti adulti e non trattati, il processo anconeo distaccato può andare incontro ad un processo di decalcificazione nei casi di incongruenza marcata con dislocazione prossimale, oppure rimanere calcificato ed unito all'ulna da fibrocartilagine nei casi con incongruenza articolare più lieve od assente.

DISPLASIA DEL GOMITO (OCD): ❑ in cosa consiste: processo di osteocondrosi localizzato alla cartilagine articolare della superficie mediale e distale del condilo omera-

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le. L'osteocondrosi consiste in una ritardata ossificazione encondrale, dovuta ad un insieme di fattori sia genetici che ambientali (crescita rapida, alimentazione, equilibrio ormonale), che, provocando un ispessimento della cartilagine, può determinare la sofferenza e la morte dei condrociti più distanti dalla superficie articolare e dal liquido sinoviale, il distacco della cartilagine dall'osso subcondrale, la sua fissurazione e formazione di un lembo di cartilagine staccata (OCD). Il distacco della cartilagine ispessita è sollecitato dal carico e dai microtraumi, e poiché nel gomito il condilo mediale appare quello maggiormente sollecitato quando l'incongruenza articolare comporta un sovraccarico ponderale tra il processo coronoideo mediale dell'ulna ed il condilo mediale, la lesione si verifica generalmente a questo livello. L'esposizione dell'osso subcondrale in ambito sinoviale scatena una serie di meccanismi reattivi che portano all'infiammazione ed all'artrosi. ❑ come si manifesta: l'OCD del gomito determina un notevole risentimento algico, caratteristico di tutte le OCD, che si manifesta con zoppia di 1° e 2°, risparmio dell'arto ed atteggiamento antalgico (carpo valgo) in stazione. ❑ procedura diagnostica: il sospetto diagnostico di displasia del gomito nasce ogni qual volta un cucciolo di razza predisposta presenti una zoppia a carico dell'arto anteriore e la vista clinica evidenzi algia alla palpazione profonda ed ai movimenti passivi del gomito. La diagnosi eziologica, ed in particolare di OCD, viene raggiunta con un esame radiografico eseguito con due proiezioni, una medio-laterale in posizione neutra (100°120°) ed una sagittale antero-posterior e. La lesione si presenta come un difetto del profilo osseo del condilo mediale, riassobimento osseo subcondrale nelle lesioni iniziali e sclerosi ossea in quelle più croniche, e con l'evidenziazione, talvolta, del lembo cartilagineo staccato.

OCD DEL GINOCCHIO: ❑ in cosa consiste: processo di osteocondrosi localizzato alla cartilagine articolare della superficie laterale e distale del condilo femorale. Il distacco della cartilagine ispessita è sollecitato dal carico e dai microtraumi, e poiché nel ginocchio il condilo laterale appare quello maggiormente sollecitato, la lesione si verifica generalmente a questo livello e nella parte più distale, quella più sottoposta al carico. L'esposizione dell'osso subcondrale in ambito sinoviale scatena una serie di meccanismi reattivi che portano all'infiammazione ed all'artrosi. ❑ come si manifesta: l'OCD del ginocchio determina un notevole risentimento algico, soprattutto nelle fasi iniziali, con ectasia sinoviale ed ispessimento periarticolare del ginocchio. Ne risulta una zoppia di 2° o 3°, talvolta imputata alla displasia dell'anca, se concomitante. Nei casi di patologia bilaterale, di frequente riscontro, la manifestazione può essere più subdola, ma generalmente la gravità delle lesioni è diversa e pertanto quella più grave richiama maggiormente l'attenzione.

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❑ procedura diagnostica: il sospetto diagnostico nasce ogni qual volta un cucciolo di razza predisposta ad OCD del ginocchio presenti una zoppia dell'arto posteriore; la vista clinica evidenzia algia alla palpazione profonda del ginocchio ed ai movimenti passivi, con ectasia sinoviale ed ispessimento periarticolare; il legamento tibio-rotuleo non appare più isolabile in maniera netta alla palpazione ed comparto mediale dell'articolazione appare particolarmente ispessito. L'esame radiografico permette di evidenziare la lesione, che appare come un difetto nel profilo dell'osso subcondrale od una sua diminuzione di densità; sono necessarie una proiezione mediolaterale del ginocchio ed una proiezione sagittale antero-posteriore con l'articolazione posta a 90°, in modo che il fascio radiogeno risulti tangente alla lesione nella parte più distale del condilo. In una proiezione sagittale antero-posteriore con arto in estensione la lesione potrebbe risultare oscurata dal profilo osseo normale più craniale.

OCD DEL GARRETTO: ❑ in cosa consiste: processo di osteocondrosi localizzato alla cartilagine articolare del bordo trocleare mediale (più frequente) e laterale (meno frequente) della troclea astragalica. Il distacco della cartilagine ispessita è sollecitato dal carico e dai microtraumi, e nell'articolazione tibio-astragalica determina una grave perdita di superficie articolare con incongruenza. L'esposizione dell'osso subcondrale in ambito sinoviale, oltre all'incongruenza articolare, scatenano tutta una serie di meccanismi reattivi che portano all'infiammazione ed all'artrosi che può risultare particolarmente invalidante. ❑ come si manifesta: l'OCD del garretto determina un notevole risentimento algico, con ectasia sinoviale ed ispessimento periarticolare dell'articolazione, soprattutto sul lato mediale. Ne risulta rapidamente una notevole diminuzione della flessione del garretto, che, nelle fase iniziali, viene portato in iperestensione come atteggiamento antalgico per scaricare la pressione sulla parte articolare colpita. Nelle forme croniche il garretto va incontro ad anchilosi con una grande limitazione dell'ampiezza dei movimenti. ❑ procedura diagnostica: il sospetto diagnostico deriva dall'evidenziazione dell'ispessimento periarticolare e dalla limitata flessione passiva del garretto in un cane in accrescimento appartenente ad una delle razze predisposte ad OCD del garretto. La diagnosi viene accertata mediante un esame radiografico in grado di evidenziare la perdita del profilo articolare della troclea astragalica, il lembo cartilagineo distaccato ed i segni di artrosi; sono indicate tre proiezioni, una medio-laterale neutra, un'antero-posteriore in estensione completa (utile per visualizzare la componente più caudale della traclea astragalica) ed un'antero-posteriore in flessione (sky-line) che permetta di togliere la sovr apposizione del calcaneo con la parte mediale della troclea astragalica e di visualizzarne anche la componente più prossimale.

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DISTORSIONE E ROTTURA DEL LCA: ❑ in cosa consiste: in diverse razze si verifica spontaneamente la distorsione e la rottura completa del legamento crociato anteriore (LCA) del ginocchio, non associate ad eventi traumatici, ma come risultato di uno squilibrio nella biomeccanica di quest'articolazione nei cani di taglia grande e gigante con scarsa angolatura degli arti posteriori. Nei soggetti predisposti, la distorsione del LCA, risultante da un continuo stress del le gamento, può verificarsi già durante l'accrescimento e culminare nella sua rottura completa tra il 1° ed il 2° anno di vita. Anche in cani appartenenti a razze non costituzionalmente predisposte alla rottura spontanea del LCA, un eccessivo incremento ponderale nell'età adulta può comportare una modificazione dell'angolatura del ginocchio, mantenuto in estensione per meglio sopportare il maggior peso, che ugualmente provoca a lungo andare la distorsione e la rottura spontanee del LCA. In tutti questi casi l'inclinazione del plateau tibiale associata ad un portamento eretto del ginocchio gioca un ruolo biomeccanico fondamentale nell'esercitare un continuo stress sul legamento crociato: la sua inclinazione rispetto alle forze di carico trasmesse a terra dal condilo femorale comporta una continua spinta in avanti della tibia durante il carico ponderale che viene contrastata principalmente dal legamento crociato anteriore finché va incontro a distorsione e rottura. Il cedimento del LCA comporta anche lo schiacciamento e la lacerazione del corno posteriore del menisco mediale, dovuto allo scivolamento in avanti della tibia ed alla sua compressione da parte del condilo femorale. ❑ come si manifesta: nei soggetti predisposti alla distorsione/rottura precoce del LCA, la sintomatologia può essere inizialmente poco appariscente, particolarmente quando la lesione interessa entrambi gli arti; man mano la lesione progredisce ed aumenta il dolore articolare, il cane ne presenta le tipiche manifestazioni con rigidità a freddo, facile affaticabilità, zoppia dopo sforzo. Nella posizione da seduto il cane non flette completamente il ginocchio e porta il calcaneo lateralmente e cra-

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nialmente alla tuberosità ischiatica, invece che a contatto della stessa, come farebbe normalmente un cane con ginocchio sano (test da seduto positivo). Alla palpazione del ginocchio si evidenzia un ispessimento periarticolare più evidente medialmente e a livello della troclea femorale; anche il legamento patellare appare ispessito. Nei casi di rottura completa del LCA la sintomatologia subisce un improvviso peggioramento e la palpazione del ginocchio nei casi recenti mostra il segno del cassetto positivo, che invece può diventare negativo nei casi cronici per l'imponente fibrosi periarticolare che in seguito si sviluppa. ❑ procedura diagnostica: il sospetto diagnostico stimolato dalla sintomatologia e dalla palpazione del ginocchio viene approfondito attraverso un accurato esame radiografico: sono indicate una proiezione medio-laterale con il ginocchio mantenuto a circa 120°-140° (moderata estensione), con i condili sovrapposti, eseguita con un basso carico di kV per poter evidenziare i tessuti molli periarticolari. Con una esposizione corretta si deve poter identificare il legamento patellare. In caso di sofferenza del LCA e del menisco mediale, si evidenzia un aumento di densità del grasso infrapatellare, testimonianza dell'aumento di vascolarizzazione della sinovia infiammata, uno spostamento caudale delle fasce muscolari caudali all'articolazione, testimonianza di un ispessimento della capsula articolare posteriore, segni di osteo-artrosi che nei casi iniziali si localizzano sull'estremità della rotula e del plateau tibiale. Questa proiezione permette anche di escludere lesioni da OCD. Per evidenziare radiologicamente il cedimento del LCA, occorre una seconda proiezione medio-laterale del ginocchio nella stessa angolazione della precedente, ma esercitando un'iperflessione del garretto senza modificare l'angolo del ginocchio: in questo modo si esegue il Test di compressione tibiale, per la spinta esercitata dalla tibia contro il condilo femorale. In caso di cedimento anche parziale del LCA, la tibia subirà uno spostamento craniale rispetto alla proiezione neutra, per effetto della sua spinta sul piano inclinato del plateau tibiale, misurabile radiologicamente.

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Artrosi e chirurgia tradizionale: dalla prevenzione al salvataggio Aldo Vezzoni Med. Vet., Dipl. ECVS, Libero professionista, Cremona

La biomeccanica di un’articolazione normale presuppone un’uniforme distribuzione dei carichi ponderali su tutta la superficie articolare affinché la cartilagine li possa sopportare senza soffrirne; la cartilagine articolare può sopportare un carico massimo di 1 kg per mm, oltre il quale va incontro a fenomeni degenerativi. La riduzione della superficie articolare attiva, sottoposta cioè al carico, che si verifica quando l’articolazione diventa incongruente, come in caso di displasia e in caso di fratture articolari malconsolidate, sottopone la sua cartilagine ad un eccessivo sforzo che porta inevitabilmente alla sua degenerazione con condromalacia, fissurazione ed erosione. La biomeccanica di un’articolazione normale presuppone anche che le strutture di contenimento articolare, come la capsula, i legamenti e, nel ginocchio, i menischi, non vengano sollecitati continuamente, ma servano solo per tenere compatta ed in allineamento l’articolazione ed evitarne movimenti superiori a quelli fisiologici. L’alterazione della biomeccanica articolare conseguente a difetti morfologici o post-traumatici può comportare una continua sollecitazione delle strutture periarticolari fino al loro cedimento. Risultato comune di tutte le condizioni in cui la biomeccanica articolare risulta alterata è lo sviluppo di una degenerazione articolare di tipo artrosico con dolore cronico e funzionalità ridotta. La chirurgia può essere efficacemente utilizzata per cor reggere le alterazioni della biomeccanica articolare prima dello sviluppo o dell’aggravamento dell’artrosi, come chirurgia preventiva, come anche può essere utilizzata, con tecniche diverse, per salvare delle articolazioni rese ormai inutilizzabili da un’artrosi invalidante. L’obiettivo della chirurgia preventiva, in caso d’alterazioni della biomeccanica articolare, è quello di migliorare la distribuzione del carico ponderale su una superficie articolare più vasta, migliorando in questo modo la biomeccanica stessa dell’articolazione, prima dello sviluppo di un’artrosi irreversibile. La chirurgia preventiva è in grado anche di modificare la biomeccanica articolare per eliminare sollecitazioni continue ed eccessive delle strutture periarticolari prima che si verifichi il loro cedimento. L’obiettivo della chirurgia di salvataggio, quando ormai si è già instaurata un’artrosi garve, è di poter garantire comunque la funzionalità dell’arto, oltre che di eliminare o ridurre il dolore articolare quando il trattamento conservativo non è più in grado di fornire una qualità funzionale ed un controllo del dolore accettabili.

La chirurgia preventiva dell’artrosi nel cane riguarda diverse articolazioni e condizioni patologiche: ❑ articolazione dell’anca: nelle alterazioni morfologiche displasiche dell’acetabolo, ed in particolare del suo bordo dorsale; in caso di displasia dell’anca esso può essere eccessivamente inclinato dorsalmente e costituire un piano inclinato che provoca la sublussazione della testa del femore e la distensione della capsula articolare. L’intervento di triplice osteotomia del bacino (TPO), di cui la tecnica più diffusamente utilizzata è quella descritta da B. Slocum, permette di modificare l’inclinazione del bordo dorsale dell’acetabolo portandolo in posizione più orizzontale, in modo tale da contenere la testa del femore ed evitarne la sublussazione dorsale. L’intervento di TPO è indicato quando il cane è ancora in crescita e le modificazioni artrosiche non si sono ancora instaurate; la crescita residua permetterà una miglior congruenza tra le due componenti articolari che , grazie all’intervento di TPO, ritornano ad essere in stretto contatto e limiterà enormemente l’evoluzione artrosica. In situazioni più gravi, con artrosi già instaurata, ma sempre nel cane in accrescimento, trova indicazione l’intervento di plastica acetabolare; la tecnica descritta da B. Slocum di DARacetaboloplastica, consiste nel trapianto d’osso cortico-spongioso sul bordo dorsale dell’acetabolo e sulla capsula articolar e, al disotto del muscolo gluteo profondo, finalizzato a favorire la formazione di un nuovo bordo dorso-laterale dell’acetabolo in grado di trasmettere il carico ponderale sulla testa del femore, anche se non è in grado di evitare un certo grado di degenerazione artrosica. Quando la diagnosi d’eccessiva inclinazione dorsale dell’acetabolo può essere effettuata molto precocemente, tra il terzo ed il quarto mese d’età, è indicato l’intervento di sinfisiodesi pubica; la fusione chirurgica della sinfisi pubica provoca una trazione ventrale sugli acetaboli e pertanto una maggior inclinazione ventrale del loro bordo dorsale. Nelle alterazioni morfologiche displasiche a carico della componente femorale, con valgismo e/o anteversione del collo del femore, la testa del femore non si articola cor rettamente con l’acetabolo, ma gravita solo sul suo bordo craniolaterale, con un’eccessiva concentrazione dei carichi su una superficie limitata; in questi casi, peraltro poco frequenti r ispetto alle situazioni displasiche da alterata morfologia dell’acetabolo, trova indicazione l’intervento d’osteotomia va-

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rizzante intertrocanterica descritta da W.Prieur. Con quest’intervento si determina un varismo del collo del femore e si corregge la sua anteversione, in modo da direzionare la testa del femore verso il centro dell’acetabolo e quindi ridistribuire uniformemente i carichi ponderali. ❑ articolazione del gomito: nelle alterazioni morfologiche di tipo displasico del gomito e nelle chiusure premature delle fisi d’accrescimento di radio ed ulna. Nella displasia del gomito, per l’asincronia di crescita tra radio ed ulna, può verificarsi un sovraccarico del processo anconeo che porta alla sua mancata fusione con l’ulna (UAP), oppure un sovraccarico del processo cornoideo mediale dell’ulna che porta alla sua frammentazione (FCP). In questi casi, un’intervento d’osteotomia dinamica dell’ulna (DUO) permette il ripristino di una migliore congruenza articolare, particolarmente se eseguita quando l’accrescimento è ancora in corso e le modificazioni artrosiche sono ancora limitate; la DUO può essere eseguita prossimalmente oppure distalmente, in funzione dei diversi gradi d’incongruenza e delle diverse condizioni patolo giche. Lo stes so trattamento può correggere le incongruenze articolari provocate dalla chiusura prematura delle fisi d’accrescimento di radio ed ulna. La UAP e la FCP associate all’incongruenza articolare richiedono, oltre all’intervento di DUO necessario a ripristinare la congruenza articolare, anche un intervento indirizzato a trattare la lesione intra-articolare determinatasi a livello del coronoideo mediale, con la rimozione artroscopica od artrotomica dei frammenti staccati, od a livello del processo anconeo con la sua fissazione con vite a compressione nei casi recenti e la sua rimozione nei casi cronici. ❑ articolazione del ginocchio: nelle alterazioni della crescita che comportano valgismo del ginocchio con lussazione laterale della rotula o varismo del ginocchio con lussazione mediale della rotula, nelle modificazioni della biomeccanica articolare del ginocchio con eccessiva azione dell’inclinazione del plateau tibiale sul legamento crociato anteriore (LCA) e sul menisco mediale. Nelle lussazioni della rotula, conseguenti a valgismo ed a varismo del ginocchio, trovano indicazione interventi d’allineamento dell’arto mediante osteotomie correttive che permettano alle linee di forza di riposizionare la rotula nella troclea femorale. Quando la deviazione assiale è inferiore a 20°, come indicazione di massima, è sufficiente una trasposizione della cresta tibiale, mentre quando è superiore occorre eseguire un’osteotomia cuneiforme del femore. Oltre all’intervento d’allineamento osseo, nella lussazione della rotula occorre intervenire anche sui tessuti molli periarticolari con il rilascio delle componenti in tensione e la sovrapposizione del retinacolo e della capsula articolare distesi. In caso d’eccessiva spinta craniale della tibia per azione del piano inclinato del plateau tibiale, dovuta ad un appiombo dell’arto posteriore poco angolato oppure ad un plateau tibiale particolarmente inclinato (oltre 24°), con distorsione precoce del LCA e lesione meniscale, trova indicazione l’intervento d’osteotomia livellante del plateau tibiale (TPLO) descritta da B. Slocum. All’intervento di TPLO si associa generalmente il rilascio del settore posteriore del menisco mediale, per evitarne la compressione e lesione da parte del condilo

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femorale. Nei cani ancora in crescita, in cui già si manifestano segni di sofferenza del LCA e del menisco mediale per un’elevata inclinazione del plateau tibiale, è indicato arrestarne la crescita della sua parte craniale mediante l’inserimento di una vite; l’arresto di crescita che ne deriva provoca un livellamento del plateau tibiale generalmente sufficiente a riequilibrare le forze intra-articolari e ad alleviare la trazione sul LCA. ❑ tutte le articolazioni: nelle incongruenze articolari conseguenti a fratture intraarticolari; in questi casi si rendono necessari interventi d’osteosintesi ricostruttiva che permettano un perfetto raffronto delle superfici articolari fratturate ed il ripristino di una corretta congruenza articolare. La chirurgia di salvataggio, quando l’artrosi nel cane ha già provocato una compromissione funzionale grave dell’articolazione coinvolta, riguarda diverse articolazioni e condizioni patologiche: ❑ articolazione dell’anca: nelle degenerazioni artrosiche gravi conseguenti a displasia dell’anca, a lussazioni croniche della testa del femore, a fratture intra-articolari mal consolidate, a processi articolari settici o degenerativi. In questi casi, per ripristinare una funzionalità articolare ottimale ed eliminare il dolore, è indicata la protesi totale d’anca (THR), che può essere sia cementata che non cementata. Il perfezionamento della tecnica protesica e dei materiali d’impianto hanno permesso di ridurre enormemente le complicazioni, tanto che oggi la THR rappresenta il trattamento d’elezione per l’artrosi invalidante dell’anca. L’alternativa alla THR, quando motivazioni di tipo economico o la presenza di controindicazioni (sepsi, eccessive alterazioni morfologiche, cani troppo piccoli per gli impianti protesici disponibili) ne precludano l’impiego, è rappresentata dall’ ostectomia della testa e del collo femorali (FHNO). Se eseguito correttamente e con una precoce riabilitazione post-operatoria, quest’intervento consente un buon recupero funzionale con la conservazione di circa il 60-70% dell’ampiezza dei movimenti articolari e la riduzione del dolore. L’efficacia dell’intervento è maggiore nei cani più leggeri e minore in quelli più pesanti. Quando la sintomatologia non è tale da richiedere un intervento drastico come la THR o la FHNO, trova indicazione l’intervento di mio-tenectomia del muscolo pettineo, tenectomia del muscolo ileopsoas e nevrectomia della capsula articolare mediale (PIN) descritto da P. Montavon. Quest’intervento è in grado di migliorare l’abduzione e l’estensione del femore, di ridurre la tensione sulla capsula articolare e di desensibilizzarla; l’efficacia è però limitata nel tempo ed è pertanto considerato un intervento palliativo. ❑ articolazione del gomito: nelle degenerazioni artrosiche gravi conseguenti a displasia del gomito, a fratture intra-articolari mal consolidate, a processi articolari settici o degenerativi. In questi casi, quando il trattamento conservativo non è più in grado di permettere una qualità della vita accettabile, per ripristinare una funzionalità articolare ottimale ed eliminare il dolore, è

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indicata la protesi totale di gomito (TER), cementata, che dopo diversi anni di sperimentazione (M. Conzemius, J-F. Bardet), diventerà presto disponibile anche in ambito clinico. L’alternativa è costituita dall’artrodesi, che però nel gomito offre dei risultati funzionali estremamente scarsi, pur essendo in grado d’eliminare il dolore articolar e. ❑ articolazione del ginocchio: nelle degenerazioni artrosiche gravi conseguenti a lussazioni croniche della rotula, a gravi processi di osteocondrosi, a rotture croniche del LCA, a fratture intra-articolari mal consolidate, a processi articolari settici o degenerativi. In questi casi, quando il trattamento conservativo non è più in grado di permettere una qualità della vita accettabile, per ripristinare una funzionalità articolare ottimale ed eliminare il dolore, sarebbe indicata la protesi totale di ginocchio (TKR), cementata, che dopo diversi anni di sperimentazione (T. Turner, J-F. Bardet, potrebbe diventare presto disponibile anche in ambito clinico. In alternativa, e limitatamente alla rottura cronica del LCA, la TPLO è in grado di migliorare la funzionalità articolare e di arrestare l’evoluzione artrosica, permettendo un carico articolare più confortevole. L’alternativa alla TKR, in tutti gli altri casi, è costituita dall’artrodesi del ginocchio, che consente un discreto risultato funzionale oltre all’eliminazione del dolore. ❑ articolazione della spalla: nelle degenerazioni artrosiche gravi conseguenti a lussazioni croniche dell’omero, a gravi processi d’osteocondrosi, a fratture intra-articolari mal consolidate, a processi articolari settici o degenerativi. In questi casi, quando il trattamento conservativo non è più in grado di permettere una qualità della vita accettabile, per ripristinare una buona fun-

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zionalità articolare e ridurre il dolore è indicata l’ostectomia della testa dell’omero e della glena scapolare, descritta da D. Piermattei. In alternativa, o come prima indicazione nei cani più pesanti, l’artrodesi scapolo-omerale offre un buon risultato funzionale e l’eliminazione del dolor e. ❑ articolazioni del carpo e del tarso: nelle degenerazioni artrosiche gravi conseguenti a lussazioni croniche, a fratture intra-articolari mal consolidate, a processi articolari settici o degenerativi. In questi casi, quando il trattamento conservativo non è più in grado di permettere una qualità della vita accettabile, l’artrodesi totale o parziale del carpo o del tarso offrono un buon risultato funzionale e l’eliminazione del dolore. In conclusione, vista la complessità degli interventi di salvataggio funzionale e la loro limitata efficacia in molti casi, comunque indicati quando l’artrosi ha raggiunto gradi altamente invalidanti, sono invece particolarmente indicati gli interventi preventivi che permettono un arresto od una riduzione dell’evoluzione artrosica. Gli interventi di tipo preventivo richiedono però una diagnosi precoce essendo molto ristretto il tempo utile per poter invertire la tendenza artrosica ed essendo limitato al periodo della crescita. Occorre pertanto una particolare attenzione da parte del veterinario clinico nel considerare le razze a rischio e nell’effettuare in questi cani una visita ortopedica di routine a sei mesi di età. Per evitare, inoltre, che le situazioni artrosiche non corrette degenerino al punto tale da diventare gravemente invalidanti, è necessario che venga attuato un trattamento conservativo adeguato che si protragga per tutta la vita del cane, con un controllo rigoroso del peso, un’attività fisica regolare, ma non eccessiva, ed un impiego oculato di FANS e di condroprotettori.

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Capire l’emogasanalisi: una semplice interpretazione Fabio Viganò Med. Vet., Libero professionista, Milano

INTRODUZIONE Scopo del presente lavoro è illustrare un metodo di facile comprensione dell’emogasanalisi. Nel passato, la pratica dell’emogasanalisi era di pertinenza di ospedali o centri di ricerca ben attrezzati, per eseguirla era necessario utilizzare apparecchiature molto complesse che richiedevano una manutenzione ed una calibrazione costante, inoltre i costi elevati di acquisto e mantenimento che una tale tecnologia implicava ne limitava l’uso. Le complicazioni che portavano con sé tali strumenti ne aveva reso l’utilizzazione limitata e l’interpretazione dei dati forniti patrimonio di poche persone. Compresa l’importanza di dover eseguire l’emogasanalisi anche quando il personale addetto non era presente e la necessità di avere i risultati in tempi brevi, ha stimolato la ricerca a produrre macchine sempre più semplici ma altrettanto affidabili. Oggi sono disponibili strumenti palmari in grado di fornire dati paragonabili a quelli ottenibili con macchine più complesse e sofisticate1. L’emogasanalisi è l’unico esame che ci permette di stabilire lo stato acido base del paziente e l’efficienza dell’apparato cardiopolmonare nello scambiare ossigeno con l’ambiente. Un’alterazione del pH ematico modifica le reazioni chimiche che avvengono nella cellula, una insufficiente ossigenazione è responsabile di una ridotta produzione di energia cellulare.

FISIOLOGIA Come fare a quantificare lo stato acido base in un mezzo come quello ematico? La risposta è semplice, basterebbe immergere la sonda di un comune piaccametro e misurare lo stato di acidità o basicità del sangue. Tutto ciò sarebbe molto meno costoso e molto più semplice. Il problema è che così facendo non raccoglieremmo nessuna informazione riguardante la causa che ha prodotto l’alterazione e la funzionalità dell’apparato cardiorespiratorio. Ai fini terapeutici è importante comprendere quali sono le specie chimiche coinvolte che hanno prodotto lo squilibrio acido base e se i dati misurati corrispondono alla sintomatologia del paziente. Le specie chimiche maggiormente coinvolte nell’equilibrio acido base sono l’acqua e l’anidride carbonica. L’anidride carbonica in presenza di acqua forma acido carbonico, ma la reazione è molto lenta, quando invece è presente l’anidrasi carbonica (ubiquitaria nell’organismo), allora la ve-

locità aumenta notevolmente tanto da renderla istantanea, tale equilibrio può essere così sintetizzato: CO2 + H2O – H 2CO3 (form. n.1) Maggiore sarà la concentrazione di anidride carbonica (CO2) disciolta nell’acqua, maggiore sarà la concentrazione di acido carbonico (H 2CO3). La reazione evidenzia una specie chimica acida (H2CO3) la quale ha una sua costante di dissociazione (pKa). La pKa, in sintesi, indica la tendenza a dissociarsi in idrogenioni (H+) e ioni bicarbonato (HCO3-). Il suo equilibrio è rappresentato dalla seguente formula: H2CO3 – H + + HCO3(form. n.2) L’aumento della concentrazione di idrogenioni è responsabile di una diminuzione del pH, l’aumento della concentrazione di ioni bicarbonato è responsabile di un aumento del pH. Il pH è la misura logaritmica della concentrazione di ioni idrogeno (H+). La misura logaritmica inverte il segno della concentrazione potendo generare una incomprensione. Può venire spontaneo pensare che se aumenta la concentrazione di idrogenioni il pH aumenta perché esso misura la concentrazione di idrogenioni; invece il pH diminuisce! Il problema risiede nel fatto che se misurassimo la concentrazione di una specie chimica come l’H+ ci ritroveremmo a fare i conti con numeri piccolissimi e tanti zeri (esso è presente in ragione di qualche decina di nanoequivalenti = 0,0000001 mEq/L) che renderebbero i calcoli molto complessi. Anche utilizzando i nanoequivalenti avremmo altre difficoltà interpretative perché ad una variazione del pH non corrisponde sempre una esatta variazione dei nanoequivalenti. Il pH è una misurazione logaritmica e si calcola con la seguente formula: [ HCO3- ] pH = 6,1 + lo g __________ 0,03 PCO2 comunemente conosciuta con il nome di HendersonHasselbach. Dall’equazione si possono riconoscere le due molecole maggiormente coinvolte nell’equilibrio acido base: il bicarbonato (HCO 3-) e l’anidride carbonica (CO 2).

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Osservando l’equazione si possono comprendere alcuni concetti importanti: ad un aumento dell’anidride carbonica si verifica una riduzione del pH, mentre ad un incremento del bicarbonato si ha un aumento del pH. In altre parole è come se dicessimo che ad incrementi della CO 2 (dovuti a difficoltà respiratorie oppure ad incrementi nella sua produzione) l’acidità nell’organismo tende ad aumentare, mentre una sua diminuzione tende a farla ridurre. Allo stesso modo un aumento della concentrazione dell’HCO3- tende ad aumentare il pH ed una sua diminuzione tende a far ridurre il pH. Nell’organismo però le cose non sono così semplici. Ogni semplificazione porta con sé l’esclusione di alcune componenti che in situazioni particolari diventano invece molto importanti. Vediamo ora di comprendere cosa succede in vivo. Se uniamo le formule numero uno e due sopra esposte avremo un’idea più completa di quanto accade nella realtà: CO2 + H2O – H 2CO3 – H+ + HCO3(form. n.4) La logica di tali fenomeni si spiega con l’azione della legge di massa, la quale afferma che i prodotti a destra ed a sinistra dell’equazione devono rimanere costanti o meglio in equilibrio, se si verifica un aumento di una componente, l’altra, per bilanciare deve aumentare anch’essa. Per esempio se aumenta l’H2CO3 si ha un corrispondente aumento della CO2. Di fatto un aumento dell’HCO3- provoca un aumento della produzione di acido carbonico (H2CO3) spostando l’equilibrio verso sinistra, un aumento dell’acido carbonico è responsabile di un incremento della produzione di CO2, perciò se il paziente è in grado di ventilarsi efficacemente eliminerà con la respirazione l’eccesso di CO2, se invece la capacità ventilatoria è ostacolata (o la gittata cardiaca è ridotta) avremo un incremento della CO2, la conseguenza è una riduzione pH ematico responsabile di un’acidosi respiratoria paradossa2. Questo rappresenta uno dei problemi più comuni nella terapia dell’acidosi quando si utilizza il bicarbonato di sodio (NaHCO3). Se è somministrato in quantità eccessive o se il paziente ha una ventilazione inefficace o gravemente ostacolata, oppure quando la gittata cardiaca è ridotta, possiamo compromettere un equilibrio già sbilanciato. A questo punto diventa molto importante somministrare il bicarbonato di sodio sotto stretto monitoraggio emogasanalitico (ogni 5 minuti) per prevenire aggravamenti della sintomatologia. Allo stesso modo un aumento della CO2 sposta l’equilibrio verso destra, aumentando la produzione di acido carbonico che deve essere compensata da una aumento della produzione di bicarbonato perché consumato dall’acido prodotto. Un esempio caratteristico di questa situazione è la ritenzione di anidride carbonica per una malattia dello spazio pleurico (es. pneumotorace, emotorace). In genere entro 12 ore i reni devono iniziare a compensare la perdite di bicarbonato aumentandone la ritenzione a livello di tubulo prossimale, diversamente si realizza uno squilibro a favore della CO2 con aumento dell’acido carbonico ed una riduzione del pH ematico. Un’altra sorgente di acidi è costituita da quelli prodotti durante il metabolismo degli amminoacidi e più comune-

mente conosciuti come “acidi fissi”. Essi non possono essere eliminati dai polmoni. Questi acidi sono tamponati dal bicarbonato prodotto a livello del tubulo prossimale renale oppure sono eliminati come NH4+ a livello dei tubuli collettori renali.

EMOGASANALISI, MATERIALI E METODI Che cosa è? È la misurazione del pH e dei gas disciolti nel sangue. Il pH come abbiamo visto in precedenza è misurato su scala logaritmica per semplificare i calcoli mentre i gas disciolti sono misurati come pressione parziale espressa in millimetri di mercurio (mmHg) o in Kilopascal (kPa). Il fattore di conversione da mmHg a kPa è 0,133. La pressione parziale dell’ossigeno nel sangue arterioso viene indicata come paO2, mentre la pressione parziale della CO2 come paCO2. Perché è necessario eseguire l’emogasanalisi? I motivi sono stati precedentemente esposti, vediamone ora un esempio. Se riceviamo un paziente che è tachipneico, tachicardico e cianotico come possiamo sapere quale è il suo pH ed il suo stato di ossigenazione e ventilazione? Egli potrebbe avere due problemi completamente differenti. Potrebbe avere un innalzamento del pH ematico, una riduzione della paCO2 ed una riduzione della paO2, perché affetto da una insufficienza respiratoria acuta. Lo stesso paziente potrebbe avere un pH diminuito, un aumento della paCO 2 ed una modesta riduzione della p a O2, in questo caso il paziente è affetto da un pro bl e m a p revalentemente ve n t i l at o rio mentre il primo soffriva di ipossia. La diagnosi nel primo caso aveva documentato una insufficienza respiratoria specificando che il problema principale era dovuto all’ipossia (diminuita paO2) e quantifi c at o la gravità dell’anormalità nei gas scambiati con l’ambiente. Nel secondo caso si è potuto documentare una insufficienza respiratoria, specificando che il problema principale era dovuto alla ventilazione (paCO2 elevata) e quantificato la gravità del processo morboso 2. L’emogasanalisi serve allora per differenziare se i deficit di ossigenazione sono prevalentemente ventilatori o di ossigenazione e per distinguerli da disturbi acido-base di origine metabolica. Essa dovrebbe essere eseguita in ogni paziente affetto da una grave malattia così da poter trattare disturbi acido-base che mettono in pericolo di vita il paziente e per stabilire la capacità dei polmoni di portare l’ossigeno al sangue. Dalla formula di Henderson-Hasselbach (n.4) abbiamo visto che gli idrogenioni e l’anidride carbonica sono parte del sistema tampone del bicarbonato, misurando i primi due possiamo calcolare il bicarbonato e l’eccesso di basi (BE). Misurando e calcolando queste componenti otteniamo tutti i dati necessari per interpretare lo stato acido base e ventilatorio del paziente. I valori normali misurati nel cane e nel gatto (differenti laboratori possono avere intervalli diversi, in base alla metodica utilizzata) sono:

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Tabella 1 CANE

GATTO

Arterioso Range

Arterioso

Venoso Range

Venoso

Arterioso Range

Arterioso

Venoso Range

Venoso

7,4

7,35 – 7,45

7,40

7,32 – 7,50

7,39

7,24 – 7,45

7,36

7,28 – 7,41

CO2

35 – 45

35,3

33 - 50

25 – 37

40,8

33 - 45

HCO3-

22 - 27

22,3

18 - 26

15 – 22

22,4

18 - 23

80 - 110

107

96 – 118

39,1

35 - 45

-2 - +2

c 2,5

-2 - +2,5

+2,5

-2 - +2,5

12 – 20

12 - 18

TCO2

23 – 29

15 - 20

SO2

> 90

A-a

10 - 20

Eseguendo le misurazioni è possibile calcolare anche l’eccesso od il deficit di basi (BE). Oltre al bicarbonato esistono altre basi contenute nel sangue, quella contenuta in maggior quantità è l’emoglobina. Quando si ha un aumento degli acidi fissi, la quantità di basi totali presenti nel sangue diminuisce in proporzione all’aumento degli acidi, così anche la concentrazione di bicarbonato diminuisce3. Negli stati di alcalosi metabolica invece il bicarbonato, aumenta, in altre parole è come se dicessimo che ad ogni aumento o diminuzione di bicarbonato si verifica un aumento od una diminuzione di tutte le basi presenti nel sangue. Perciò la misurazione delle basi presenti nel sangue è una misurazione più accurata della sola determinazione dello ione bicarbonato. Per poterla misurare è necessario conoscere la concentrazione di emoglobina, se consideriamo 15 g/dl come valore normale della quantità di emoglobina presente nel sangue e 20 c 4 mEq/L la concentrazione normale di bicarbonato è possibile stabilire l’eccesso od il deficit con la seguente for mula: BE = BB normale – BB misurate (form. n. 5) Dove BB indica le basi tampone (Buffer Base), il cui valore normale è di circa 48 mEq/L (se si assume l’emoglobina normale pari a 15 g/dl). I valori normali di BE (Base Excess) sono compresi tra c 2 mEq/L. Quando i valori misurati sono positivi e maggiori di 2, significa che vi è un eccesso di basi e che probabilmente anche il bicarbonato è aumentato, se il valore è negativo e maggiore di due indica che vi è una carenza di basi e che il bicarbonato dovrebbe essere diminuito, potendo generare una incomprensione perché si afferma che l’eccesso di basi è ridotto. Alcuni infatti affermano che in tali casi siamo di fronte ad un deficit di basi anche se il simbolo BE indica

un eccesso di basi. Generalmente il bicarbonato costituisce circa la metà del valore di BE. Il valore di BE può variare a seconda del laboratorio utilizzato per l’emogasanalisi, ciò dipende se il BE è calcolato nel sangue o nel liquido extracellulare, valutare la formula utilizzata e fare i calcoli necessari può essere complicato e distrae l’attenzione dal problema principale. In alcuni casi l’alterazione del valore può essere normale ed anzi indicare un buona risposta da parte dell’organismo. Per esempio un paziente che soffre di un’acidosi respiratoria cronica potrà avere un BE superiore alla norma per tamponare l’aumento della CO2 presente nel sangue, in questi casi avere un BE elevato non è un riscontro patologico ma costituisce la risposta naturale ad un alterato equilibrio acido-base. Un altro dato che è importante misurare, quando si valuta lo stato acido base è l’anion gap (AG). Per problemi di elettroneutralità i cationi e gli anioni presenti nel sangue devono essere pari. I cationi si distinguono in: misurati, come il sodio (Na+) ed il potassio (K+), e non misurati (UC) in quanto contenuti in quantità inferiore come il calcio (Ca++) ed il magnesio (Mg++). Anche gli anioni seguono la stessa sorte, si distinguono perciò in misurati, come il cloro (Cl-)ed il bicarbonato (HCO 3-), e non misurati (UA) come le proteine, i fosfati ed i solfati presenti nel sangue. Tale equilibrio è regolato dalla seguente equazione: (Na++ K +) + UC + = (Cl - + HCO3-) + UA(form. n 6) Perciò se volessimo misurare la differenza tra cationi ed anioni dovremmo cambiare i termini dell’equazione nel seguente modo: AG = [(Na++ K+) + UC +] - [(Cl- + HCO3-) + UA-] (form. n 7)

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L’AG o deficit di anioni è calcolato sottraendo ai cationi misurati gli anioni misurati, semplificando ulteriormente la formula: AG = (Na ++ K+) - (Cl- + HCO3-) (form. n 8) In condizioni normali i cationi sono più nu m e rosi degli anioni e sono compresi tra i 12 ed i 20 mmol/L. Quando aumentano gli anioni minori il bilancio elettrolitico deve ri m a n e re inva ri at o , quindi gli anioni maggi ori (Cl- + HCO3-) devono diminuire producendo un aumento dell’AG. Tipici esempi di aumento degli anioni minori sono: l’acidosi lattica, la chetoacidosi, l’insufficienza renale con aumento di solfati e fosfati, l’uremia, l’avvelenamento da gli cole etilenico e da salicilati. L’acidosi metabolica con AG normale è tipica dell’insufficienza renale o della diarrea, in corso di queste malattie si verificano spesso perdite di bicarbonato con aumento compensatorio dello ione cloro (perché il bilancio elettrolitico deve rimanere invariato), tanto da essere identificate come acidosi ipercloremiche. Quindi una volta identificata un’acidosi metabolica, il calcolo dell’AG diventa importante per identificarne la causa.

INTERPRETAZIONE DELL’EMOGASANALISI, RISULTATI L’interpretazione dell’emogasanalisi non è semplice e deve sempre tenere conto delle condizioni cliniche del paziente, a volte può essere necessario eseguire una radiografia per confermare il sospetto, altre volte può essere necessario ricontrollare i parametri vitali (frequenza cardiaca respiratoria, temperatura corporea, tempo di riempimento capillare, misurazione della pressione arteriosa ecc.) e rivalutare il processo morboso in atto alla luce dei risultati ottenuti. Come prima cosa è necessario identificare l'origine del campione, se è arteriosa, venosa o mista (artero-venosa). I campioni di origine arteriosa devono avere una percentuale di saturazione maggiore del 90%, i campioni di provenienza venosa hanno una percentuale di saturazione dell’emoglobina infe ri o re, generalmente campioni con un contenuto pari od inferiore al 75% sono di origine venosa

o mista. Le misurazioni devono essere lette con il seguente ordine cronologico: 1) il pH. Quando è inferiore a 7,35 si ha acidemia, quando è maggiore di 7,45 abbiamo alcalemia. Il termine acidosi ed alcalosi indicano la tendenza di un processo a realizzare il disturbo, sia esso un’acidemia od un’alcalemia. 2) paCO2 quando è maggiore di 45 abbiamo un’acidosi respiratoria e quando è inferiore a 35 abbiamo un’alcalosi respiratoria. 3) HCO3-, quando è inferiore a 20 con un BE – 5: acidosi, se è >20 ed un BE > 5 abbiamo un’alcalosi A questo punto dobbiamo identificare il disturbo prima rio. Per poterlo riconoscere è necessario innanzitutto identificare l’alterazione del pH, se siamo di fronte ad un’acidosi oppure ad un’alcalosi. Per poterlo fare basta controllare gli intervalli indicati nella tabella n. 1. Quindi controlliamo il valore della paCO 2, se è alterata nella stessa direzione allora il problema sarà respiratorio. Ad esempio se un paziente ha un pH inferiore ai livelli normali (acidosi) ed un aumento della paCO2 (acidosi respiratoria) il disturbo primario sarà dovuto ad una insufficienza ventilatoria. Se invece in presenza di acidemia avremo una riduzione del bicarbonato il disturbo primario è metabolico. Lo stesso metodo si può applicare pH maggiori del normale (alcalosi), se il bicarbonato è aumentato avremo una componente metabolica come disturbo primario, se invece la paCO2 è diminuita il disturbo primario è respiratorio. Identificato il disturbo primario dobbiamo verificare se la compensazione messa in atto dall’organismo è dell’entità attesa o differente. Se la risposta del paziente è proporzionata significa che sta cercando di correggere l’alterazione con i propri meccanismi compensatori, se invece la risposta è inadeguata la malattia non è sotto controllo e può causare alterazioni incompatibili con la vita. Squilibri non compensati sono facili da identificare perché il valore alterato riguarda un solo parametro, il bicarbonato per l’alcalosi metabolica e la paCO 2, per la componente respiratoria. Nella maggior parte dei pazienti il pH costituisce la guida per identificare il disturbo primario perché il parametro alterato nella stessa direzione indica il disturbo primario in quanto l’organismo non compensa mai in eccesso. Le normali compensazioni nei nostri pazienti sono:

Tabella 2 DISTURBO PRIMARIO

ALTERAZIONE

COMPENSAZIONE

Acidosi metabolica Alcalosi metabolica

Riduzione HCO 3- di 1 mEq/L Aumento HCO 3- di 1 mEq/L

Riduzione paCO2 di 0,7 mmHg Aumento paCO 2 di 0,7 mmHg

Acidosi resp. Acuta Acidosi resp. Cronica

Aumento paCO2 di 1 mmHg Aumento paCO 2 di 1 mmHg

Aumento HCO3- di 0,15 mEq/L Aumento HCO 3- di 0,35 mEq/L

Alcalosi resp. Acuta Alcalosi resp. Cronica

Riduzione paCO2 di 1 mmHg Riduzione paCO2 di 1 mmHg

Riduzione HCO3- di 0,25 mEq/L Riduzione HCO 3- di 0,55 mEq/L

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Identificato il disturbo primario e valutata l’entità della compensazione, si osserva l’AG, per comprendere se l’acidosi è dovuta a molecole (es. acido lattico) prodotte da una delle malattie sopra citate. Infine se vogliamo valutare la funzionalità dell’apparato respiratorio dobbiamo controllare il gradiente alveolo-arterioso. Tale parametro indica la capacità dei polmoni di trasportare l’ossigeno dall’aria ambiente al sangue e si calcola con la seguente formula: A-a = (150-1,25 x paCO 2) - paO2 (form. n 9) Nella prima parte dell’equazione si misura la pressione parziale dell’ossigeno nell’aria ambiente (PAO 2), infatti moltiplicando la FiO2 (aria ambiente è 0,21) che corrisponde alla percentuale di ossigeno nell’aria inspirata per la pressione barometrica sottratta del vapore acqueo (Pb-PH2O) otteniamo la frazione di aria che contiene ancora l’anidride carbonica la quale va divisa per il quoziente respirat o ri o . Va l o ri superi o ri a 15 mmHg stanno ad indicare mal attie polmonari pare n chimali. Il A-a diventa quindi i m p o rtante per compre n d e re la gravità di alcune malattie polmonari (es. polmonite), s t ab i l i re la terap i a , o ss e rva rne l’efficacia e va l u t a re il decorso del pro c e s s o morboso.

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Esempio n. 3 - Acidosi respiratoria Segnalamento: gatto,maschio comune europeo,14 anni, 4 kg Anamnesi: difficoltà respiratoria ed asma cronica. Emogasanalisi: pH 7,25 paCO2: 70 paO2: 59 HCO3: 24 BE: - 4 Commento: il paziente presenta una acidosi respiratoria (pH ridotto, paCO2 aumentata ) non compensata (bicarbonato normale).

Esempio n. 4 - Alcalosi respiratoria Segnalamento: cane, femmina, meticcio, 2 anni, 20 kg Anamnesi: investimento automobilistico, frattura femore destro, shock traumatico compensato. Emogasanalisi: pH 7,50 paCO2: 25 HCO3: 22 BE: + 1 Commento: il paziente presenta una alcalosi respiratoria da dolore (pH aumentato, paCO2 ridotta) non compensata (il bicarbonato è normale perché in dolore è insorto due ore prima).

Esempio n. 5 - Acidosi respiratoria compensata

Esempio n. 1 - Acidosi metabolica Segnalamento: cane, maschio, cocker spaniel, 4 mesi, 5kg Anamnesi: diarrea emorragica e vomito, perdita di peso, shock settico scompensato Emogasanalisi: pH 7,2 paCO2: 32 HCO3: 11 BE: -15 Commento: il paziente presenta una acidosi metabolica (pH, bicarbonato e BE ridotti) che cerca di compensare con una alcalosi respiratoria (diminuzione della paCO2)

Segnalamento: gatto,maschio comune europeo, 3 anni, 5 kg Anamnesi: sospetto trauma ottuso addominale, ernia diaframmatica, shock traumatico compensato. Emogasanalisi: pH 7,37 paCO2: 59 HCO3: 40 BE: + 10 Commento: il paziente presenta una acidosi respiratoria da insufficienza ventilatoria ostruttiva (pH diminuito, paCO2 aumentata) compensata (bicarbonato aumentato).

CONCLUSIONI Esempio n. 2 - Alcalosi metabolica Segnalamento: Cane femmina, meticcio, 7 anni, 35 kg Anamnesi: vomito incoercibile, grave disidratazione (89%), shock ipovolemico scompensato. Emogasanalisi: pH: 7,71 paCO2: 55 HCO3: 42 BE: 18 Commento: il paziente è affetto da una alcalosi metabolica (pH aumentato) con tendenza a compensare attraverso una acidosi respiratoria (paCO2 aumentata).

Il metodo interpretativo sopra illustrato è una esemplificazione della valutazione emogasanalitica, esistono differenti altri approcci, come quello non tradizionale od altri che sfruttano il particolare comportamento di alcune specie chimiche, nomogrammi e tabelle. Le difficoltà nello sfruttare tali metodi risiedono nella necessità di conoscere alcuni fondamenti di biochimica la cui comprensione richiede uno studio approfondito e particolareggiato della materia. Utilizzando il metodo sopra esposto possiamo invece riconoscere le alterazioni principali dell’equilibrio acido base e respiratorie, fornendo anche al medico veterinario non specializzato una chiave di interpretazione dell'emogasanalisi.

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Bibliografia

2. 3.

MR Raffe, Drandall, C. Kulas, J Laber, L Faudskor, V Pe rm a n , SA Sanderson, CA Osborne. Validation of a point of care chemistry and blood gas analysis. Proceedings fifth International Veterinary Symposium Ve t e ri n a ry Emergency and Critical care Society, 1996

4. 5.

BA Shapiro, WT Peruzzi, R Tamplin. Clinical application of blood gases, Mosby ’94 L. Martin. All you really need to know and to interpret arterial blood gases. Lea and Febiger Philadelphia ’92 BD Rose, Clinical physiology of acid base and electrolyte disorders. 4th edition, Mac Graw-Hill Inc. New York, 1994 S. Di Bartola, Fluid therapy in small animal practice 2nd edition, Saunders Philadelphia, 2000

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Pitfalls in the diagnosis and treatment of difficult gastrointestinal disorders Trucchi e tranelli nella diagnosi e nel trattamento delle pi첫 difficili malattie gastrointestinali

Michael D. Willard DVM, MS, Dipl ACVIM, Professor, Texas A&M University

Anytime you are faced with a patient not responding to therapy, there are 3 main considerations. Either you have the wrong diagnosis, the right diagnosis but the wrong treatment, or the right diagnosis and right treatment but an owner that does not comply with what you tell them to do. Most of the time, failure to respond to therapy leads one to look for bigger and better drugs. However, incorrect diagnosis is probably by far the most common cause of failure to respond to therapy. The first consideration is whether the test results you have are accurate or inaccurate. Artifacts occur even in the best laboratories. There are three main questions to ask: a) does the result fit the animal?, b) does the result fit other lab results?, and c) are there any other artifacts on the panel? Unless strict quality control is being practiced, it is easy to have major artifacts from in-house laboratories. The next consideration is the sensitivity and specificity of the test. Some tests are renown for poor sensitivity and/or specificity (e.g., changes in serum cobalamin and folate concentrations are specific for small intestinal bacterial overgrowth, but have poor sensitivity). If you are having a very difficult time with a case, it is often best to start over and repeat previously performed tests (to be sure the results are consistent and there are no artifacts). In fact, I will repeat some of my own work ups if I am having a problem. The overriding characteristic of common diseases is that they appear commonly. It is usually far cheaper and far more diagnostic to recheck and look for a common disease that you have missed or overlooked than it is to look for a rare disease. A major problem seems to arise when we already have the diagnose Aconfirmed@ histologically. I have seen more errors related to histopathologic diagnosis (actually misdiagnosis) than anything else. Many mistakes relative to intestinal biopsies fall into one or more of the following categories: a) not taking good tissue samples (i.e., too small, too superficial, too much artifact), b) not taking enough samples from a given site, and c) not sampling enough sites throughout the alimentary tract. There are two basic ways to biopsy intestines: endoscopy and surgery. Endoscopic biopsy can be accomplished with a rigid or a flexible scope. Rigid scopes retrieve much better tissue samples than flexible scopes; however, they can only be used for obtaining tissue from the descending colon. When I use flexible scopes, I prefer those with a 2.8 mm biopsy channel. These scopes have larger outer diameters (usually 9.0-9.4 mm) than scopes with 2.0 mm channels, but

can be used in almost all dogs and most cats. I recommend using fenestrated, ellipsoidal forceps with a serrated edge and preferably without a needle. At least 5 excellent quality tissue samples should be obtained from each site. After obtaining the tissue sample, carefully remove it from the biopsy forceps with a needle and gently spread it out on a tissue cassette sponge so that the lumenal side (i.e., in small intestinal samples this would mean the side with the villi) is oriented upwards and the sample is no longer folded. The samples are allowed to adhere to the sponge, but are not allowed to dry out. Small intestinal mucosa is much more delicate than colonic or gastric mucosa. The sponge with the tissue samples is promptly placed in formalin. Clinicians occasionally express concern that lymphomas may "hide" in the deeper layers of the intestinal or gastric mucosa, and the endoscopist may only obtain overlying mucosa that has a reactive, lymphocytic-plasmacytic infiltrate. If the operator is using an instrument with a 2.8 mm biopsy channel, this should not be a problem because we routinely obtain full thickness of the mucosa (i.e., from the tips of the villi down to and including muscularis mucosa). Endoscopy seems to provide the correct answer in over 90% of cases. I biopsy as much of the alimentary tract as possible. Animals with large bowel diarrhea should have the colon, ileum, and cecum biopsied. Those patients with small bowel diarrhea should have the stomach, duodenum, jejunum (if your endoscope will reach that far), ileum, and colon sampled (you may have both large and small bowel diarrhea present but only perceive the small bowel disease because the patient is losing weight. Histopathologic evaluation is the final consideration. Just because a pathologist has made a diagnosis does not mean that you have an answer you can trust. Gastrointestinal pathology is a difficult area, and unless the pathologist is working in it routinely and receiving feedback on the diagnoses made (e.g., treating for this disease did or did not help), it is easy for the person to make substantial mistakes. Never hesitate to call your pathologist to discuss the case. The first question is how good of a sample you sent them. You next need to find out is if the histopathologic lesions they are seeing are sufficient to explain the clinical signs you are seeing. If the answer is equivocal, you might need to keep looking for the answer. Finally, do not hesitate to ask for a second opinion on the histopathology slide if you are dealing with a difficult case.

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Feline hepatic disease Epatopatie nel gatto

Michael D. Willard DVM, MS, Dipl ACVIM, Professor, Texas A&M University

One of the more common questions diagnosticians ask themselves is whether or not the liver is diseased in a particular patient. Unfortunately, the most common signs of hepatic disease (i.e., anorexia, lethargy, depression, intermittent vomiting, weight loss) are commonly seen in other diseases as well. A high ALT and/or SAP shows that there is hepatic disease, but normal values do not eliminate hepatic disease. Hepatic function tests (i.e., serum albumin, serum urea nitrogen, serum bile acids) are simply another way of trying to determine if the liver is diseased. You can have significant hepatic disease without an increased serum bile acid concentration (significant hepatic disease may have lesser increases if it has just begun and there is not yet a marked loss of hepatic function), and sometimes animals have major increases in serum bile acid concentrations but have hepatic disease that is clinically insignificant (e.g., vacuolar or hydropic change). If the other lab tests tell you that there is what appears to be a clinically significant hepatic disease present (e.g., the animal has hepatobiliary icterus), there is usually no advantage in measuring serum bile acids. Major points to remember: a normal ALT and SAP does not rule out hepatic disease, and the magnitude of the increase in the ALT and SAP does not have prognostic or diagnostic implications. There is usually no reason to measure serum bile acids when the serum is icteric because you already know that they will be significantly increased . Considering the shape and size of the liver may also help answer this question. The two main considerations are a) is there evidence of focal hepatic disease (i.e., is there a mass) and b) is the liver larger or smaller than normal? If either of these are present, then there is again evidence of hepatic disease. Finally, ultrasonography may reveal changes in the hepatic parenchyma that show that there is something abnormal occurring in the liver. Major points to remember: if the liver is clearly smaller than normal and there is not some obvious reason to look for acquired hepatic disease, you should consider the possibility of a portosystemic shunt, even if the dog is middle-aged or older. Also, not all dogs with severe microhepatia will have cirrhosis or a portosystemic shunt. Once hepatic disease has been documented, the next question is whether the hepatic disease appears to be clinically significant or not. Said another way, is the disease in the liver the cause of the animal's problems, or is the disease in the liver caused by whatever is making the animal sick? This is an important consideration, and one that is not always too easy to answer. If there is evidence of hepatic in-

sufficiency (e.g., hypoalbuminemia, low BUN, hypocholesterolemia, significant increases in serum bile acid concentrations, icterus), then it is likely (not guaranteed, but likely) that the liver is the cause of the animal's disease. Markedly small livers (i.e., microhepatia) are usually considered evidence of important hepatic disease. Microhepatia is typically caused by atrophy secondary to shunting of blood or scarring. Idiopathic hepatic atrophy occasionally occurs, ostensibly due to chronic exposure to some toxin. However, this is a poorly defined entity and we do not know what to do for it except remove the "toxin". Focal masses or enlargement in the liver are particularly worrisome and should always be noted as being potentially important. Evidence of chronicity (e.g., hepatic enzymes increased for weeks) is considered to denote potentially significant hepatic disease. If the patient is asymptomatic or mildly symptomatic except for biochemical abnormalities, it is usually appropriate to first wait and see whether these biochemical abnormalities persist or worsen. However, if the ALT remains increased (even if it is a minor increase) for weeks,the patient should be considered to have significant disease until proven otherwise. If a breed that is recognized to be at risk for hepatic disease (e.g., Cocker spaniel) has changes that might be due to hepatic disease, it should be investigated now as opposed to later. Finally, if there is no other explanation for the animal's problems, then it is appropriate to consider the liver the likely cause. The next question is whether there are any obvious or likely reasons for the hepatic disease. Hyperadrenocorticism and drugs are two particularly common causes that are often (not always, but often) relatively easy to spot. If there is an apparently obvious cause, then it may be dealt with first (e.g., stop administering the drug, perform a low-dose dexamethasone suppression test). If the animal is too ill to take a chance on guessing correctly that something is an obvious cause, or if there is not an obvious cause, then the next question is whether or not to biopsy the liver. In general, the answer to this question should be "yes". Focal hepatomegaly (i.e., a hepatic mass) almost always indicates the need for a hepatic biopsy because it suggests a tumor, granuloma, cyst, or abscess. However, it may be something that is extremely benign, such as a regenerative nodule. Generalized hepatomegaly may be due to any num-

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ber of problems. Unfortunately, generalized hepatomegaly is nonspecific: it is commonly seen in animals with mild, moderate, severe, and insignificant hepatic disease. Major points to remember: very large hepatic masses may be extremely benign and curable. In fact, if the hepatic mass is very large, malignancy might be a bit less likely than if the mass were smaller (i.e., a malignancy would probably have killed the patient before the mass became that large). Persistent increases in hepatic enzymes are a very reasonable indication for hepatic biopsy. Even if the dog or cat is clinically normal, persistent elevations of ALT or SAP should be investigated, which usually means biopsying the liver. Explain to the client that you hope you will find nothing of significance. However, it is better to diagnose severe hepatic disease before it causes severe clinical signs (which is when you can usually do more to treat and control it) than after the patient is so ill that it can longer compensate for the hepatic disease (which is when you usually cannot do as much with your therapy as you wish you could). Also,do not be fooled into thinking that you can predict whether or not the hepatic disease will be significant based upon the hepatic enzymes. Most of us have seen a lot of dogs that have increased SAPs that were found on routine blood screening when the ALT, GGT, and bilirubin concentrations were normal (along with the rest of the panel except perhaps for an increased cholesterol). These are typically older dogs which are otherwise normal. After adrenal gland testing to eliminate hyperadrenocorticism, we tend to want to ignore the increased SAP because these dogs almost invariably have some sort of vacuolar hepatopathy which is clinically insignificant. However, the important word is Aalmost@. Dogs like this can also have clinically important disease that needs to be diagnosed. It does not happen often, but it is 100% for those that do that such diseases. There are basically four techniques for obtaining hepatic biopsies: a) fine needle aspiration for cytology, b) core needle (e.g., a Tru-Cut used with ultrasound or during laparoscopy), c) clam shell forceps (usually used at laparoscopy), and d) wedge (obtained surgically). Fine needle aspiration can be done on dogs or cats. A 25 to 23 gauge needle is blindly advanced into the liver via abdominal puncture. As long as the needle goes straight into the liver and straight out, there is minimal risk of hemorrhage, even if other organs are punctured. However, I have seen one animal almost exsanguinate from such a procedure. If the animal is a clinical bleeder or has a platelet count < 20,000/ul, then one must consider whether the possible benefits outweigh the risks of this procedure. The main advantages of fine needle aspiration are a) it is easy and b) it is relatively safe. If the animal is tractable, anesthesia or sedation are not necessary. The main disadvantages of fine needle aspiration are a) it does not reveal architecture of the liver (i.e., it will not reveal whether regeneration nodules or atrophy are present) and b) it can easily miss vitally important disease (e.g., it will not reveal fibrosis and may miss many infiltrative diseases, even when they are extensive). A good example of the latter occurs in cats with possible hepatic lipidosis. Simply finding hepatocytes with vacuoles, while diagnostic for lipidosis, does not eliminate other hepatic disease (e.g., cholangiohepatitis or lymphosarcoma) and does

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not necessarily ensure that the lipidosis is severe enough to cause the clinical signs seen in the patient. In general, fine needle aspiration is best done immediately before a core needle biopsy. If the cytologic diagnosis is definitive (i.e., lymphosarcoma, histoplasmosis, bacterial infection, carcinoma), then the core needle procedure is canceled. However, if the fine needle aspiration is not definitive, then the core needle procedure is performed. Major point to remember: you can almost never eliminate a diagnosis (even lymphosarcoma) because it was not found with a fine needle aspirate. Fine needle aspirates only Acount@ if they are positive for cells that cannot be considered normal under any circumstance (e.g., neoplastic cells, Histoplasma capsulatum). Core needle biopsy is usually performed with a Tru-Cut (or one of its modifications such as the Monopty or Biopty) or a Menghini or a Vim-Silverman needle. While these needles can be used blindly, they are usually used in conjunction with ultrasonography or laparoscopy. It is preferable to use these needles with such guidance because the possibility of complications is substantially more with this procedure than with a fine needle aspiration (e.g., you can puncture the posterior vena cava or gall bladder with a 25 gauge needle and probably have no complications; the same cannot be said about taking a 14 gauge piece out of the same organs). As before, you need to have serious justification for performing this procedure on animals that are clinically bleeding and those with platelet counts < 20,000/ul. In general, if the animal appears to have substantial risk for hemorrhage due to bleeding tendencies, I prefer to perform a laparotomy or laparoscopy so that I can not only monitor for hemorrhage, but do something about it if it is excessive. The advantages of core needle biopsy are a) you obtain a piece of tissue large enough to determine architecture, b) you can diagnose infiltrative diseases that were previously missed by fine needle aspiration, c) both ultrasound and laparoscopy provide enough guidance to make this a relatively safe technique. The main disadvantages are a) you cannot easily monitor for post procedure hemorrhage if you use ultrasound guidance, except by monitoring the animal closely and b) it is very easy to obtain samples that are too small, too fragmented, or too few to be diagnostic. Said another way, while this is an excellent technique and is routinely diagnostic when performed correctly, there are a lot of good ways of doing this wrong and obtaining useless samples. First, you must remember that one pass with such a needle generally allows you to sample approximately 1/50,000th of the liver. Therefore, you need to take at least 2 and preferable 3 adequate sized samples with such a needle. It is best if they are from different lobes of the liver. It is very important that each sample is at least 15 mm and preferably 20 mm long. You need a sample this long in order to have sufficient tissue to find abnormalities such as bridging fibrosis, which is necessary for diagnosing cirrhosis. Finally, you should always use the largest gauge needle that can safely be used in the patient. Small gauge needles can easily miss "spotty" lesions whereas larger gauge needles are more likely to fine lesions. Contrary to what is said, these needles can usually be reused many times. However, once they become excessively dull, they will not obtain samples of the length desired and must be discarded. In general, you will need to use the cut-

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ting needles (e.g., Tru-Cut) instead of the aspiration needles (e.g., Menghini) when biopsying fibrotic tissue. Major point to remember: you want at least 2 and preferably 3 cores, each 20 mm long, from the largest gauge instrument that you can safely use in a particular patient. If possible, use a nee dle that obtains a 14 gauge core. Once you obtain a core needle sample of hepatic tissue, it is easy to handle it roughly and fragment it. The best way to handle the tissue is to take the needle that has the tissue still in it and carefully place the tip of the needle and the undisturbed tissue in formalin until the hepatic tissue partially fixes (usually 3-5 min). Then one can very carefully tease it out with the tip of a 25 gauge needle. This necessitates using another needle to obtain the next biopsy. Major points to remember: do not place core needle biopsies of hepatic tissue on gauze because this will usually cause more artifact. If you wish to mount the biopsy on something, place it on cardboard or Teflon before putting it in formalin. Do not allow the tissue sample to dry out before it is fixed. A real question is whether ultrasound or laparoscopy is the best means to guide core needles. While ultrasound seems very useful for most procedures, some malignancies are miliary and cannot be detected with ultrasound. Laparoscopy is sometimes better at guiding core needles when there are small, focal malignancies of the liver (unless the tumor is buried within the parenchyma, in which case ultrasound is probably better). Major point to remember: while ultrasound is an excellent technique, it cannot detect all infiltrative lesions (especially miliary ones). Clam shell biopsy forceps may be used in conjunction with laparoscopy. The advantage of such biopsy is that one can visualize the lesion or area to be biopsied (which may help if there are miliary lesions that cannot be found with ultrasound). The main disadvantage of this technique is that it is easy to obtain a very superficial tissue sample of the liver. The superficial aspects of the liver has a lesser blood supply and has substantially more fibrosis than the deeper parenchyma. This means that it is easy for the pathologist to incorrectly conclude that there is pathologic fibrosis or even cirrhosis when in fact there is no such disease in the patient. Done correctly, this is an excellent way to obtain hepatic tissue for histopathology. Be sure to explore the liver first and to take biopsies from at least 2 or 3 different hepatic lobes. Major point to remember: the best approach is probably to perform ultrasonography and then obtain biopsies with laparoscopy. This approach is more expensive, but offers more likelihood of finding the cause of the hepatic disease, especially when it is not uniformly distributed throughout the liver. Wedge biopsies are taken during surgery. The main advantages are a) they are the largest and often the most diagnostic (assuming that there is not a deep, focal lesion that cannot be detected during surgery -- which is why it is always preferable to ultrasound livers before any type of biopsy) and b) if you have a patient that is a clinical bleeder or is at risk for bleeding (i.e., has clinically significant thrombocytopenia), you can use electrocautery, gelfoam, etc. to help ensure that all bleeding is under control before you close the abdomen. The main disadvantages of wedge biopsy are a) you seldom need to perform surgery to obtain diagnostic

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biopsies, b) you can still miss lesions deep in the hepatic parenchyma, and c) surgical biopsy taken after the patient has been anesthetized for a long time can contain neutrophils under the capsule. This may suggest focal suppurative hepatitis when in fact there is no such disease present. Heavy sedation may do the same. Major points to remember: surgery is seldom needed to obtain good, diagnostic hepatic samples if care is taken to perform the biopsies correctly. Even if you do obtain the biopsies at surgery, it is still best to obtain biopsies from at least two different liver lobes. Icteric animals should be determined to have either hemolytic disease or hepatobiliary tract disease. To do this, you should first measure the hematocrit. If the hematocrit is within the reference range or reasonably close, it is extremely doubtful that hemolysis is responsible for icterus, especially if the serum bilirubin is persistently > 3 mg/dl. Check reticulocyte numbers and RBC morphology, especially looking for Heinz bodies and haemobartonella in cats and for spherocytes and autoagglutination in dogs. Occasionally one will find schistocytes, suggestive of micr ovascular angiopathy (i.e., disseminated intravascular coagulation). If there is no evidence of regenerative anemia, Heinz bodies, or haemobartonella, hemolysis probably does not need to be further considered. However, if the hematocrit < 20%, one should probably recheck the CBC in 2-5 days to see if a regenerative response has developed. It might be that the patient has had a sudden episode of hemolysis but had not yet developed the regenerative response when you first examined it. Major points to remember: conjugated (direct) and unconjugated (indirect) bilirubin measurements are useless. Although uncommon, it is possible to have hemolytic icterus with a PCV > 25%, which is why you should look for Heinz bodies, reticulocytes, spherocytes, and autoagglutination. If hemolysis is eliminated as the cause for icterus, then it must be due to hepatobiliary disease. The next question is whether the animal has hepatic parenchymal disease or extrahepatic biliary tract obstruction. Abdominal ultrasonography is the best tool to distinguish the two. Any anorexic animal will have a large gall bladder. Obstruction is diagnosed by finding dilated tortuous bile ducts (a large gall bladder simply means that the patient has not eaten recently, you must see the dilated bile ducts before you diagnose biliary tract obstruction). Distinguishing between hepatocellular and biliary tract disease will help you determine whether your next step will be to biopsy the liver by some percutaneous technique (i.e., for hepatocellular disease), or perform an abdominal exploratory surgery (biliary tract disease not due to pancreatitis). Major point to remember: clients must always be warned that some patients with hepatic disease (even those with chronic, apparently "stable" hepatic disease) may acutely decompensate and die after a hepatic biopsy. This is particularly true after abdominal surgery, but can also occur after anesthesia for laparoscopy. Coagulation function should be checked prior to any biopsy procedure. There seems to be poor correlation between which animals have poor clotting function (as determined by clotting times) and which ones will bleed excessively after biopsy. In general, I only wor ry if the animal is significantly thrombocytopenic or is bleeding clinically after venipuncture or other procedures. I prefer the mucosal

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bleeding time as opposed to any of the clotting times. If there seems to be clinically significant bleeding, I recommend exploratory surgery using electrocautery so that all cut surfaces can be examined and cauterized if necessary. Others prefer using laparotomy and applying gel foam to persistently bleeding biopsy sites. Some clinicians will automatically give most dogs with significant hepatic disease subcutaneous injections of vitamin K1. While this usually is not helpful, every once in a while you find a patient for whom it makes a major difference in clotting; therefor e, it is reason able although it is not likely to help. Major point to remember: watch the patient closely for 3-4 hours after the biopsy procedure to see if there is any evidence of hypovolemia, suggesting significant hemorrhage. An increased PT and/or PTT is not necessary a good reason to avoid hepatic biopsy.

FELINE HEPATOBILIARY DISEASES Adverse drug reactions may cause mild to fatal hepatic disease. They can be due to almost any drug (e.g., acetaminophen, diazepam, cimetidine). Whenever there is any doubt as to whether a particular drug might be responsible for hepatic disease in a patient, stop administering it and observe the results. You need to be aware that it may take days or longer for the effects of a drug-induce hepatopathy to resolve. Main point to remember:almost any drug might be responsible for abnormal hepatic enzymes in a given patient. The healthier the patient is, the more inclined we are to wait and see what happens after stopping the drugs. The sicker the patient is, the quicker we are to biopsy, just in case there is something more significant that we need to eliminate now. Hepatic lipidosis is due to anorexia and subsequent protein deficiency which causes hepatocellular fat accumulation, especially in obese cats which mobilize large amounts of fat when they become anorexic. The classic history is that of a fat cat which for some reason stopped eating and then began to lose weight. Next it begins to vomit and usually become icteric. However, not all obese cats have lipidosis and not all cats with lipidosis are obese. Most cats with clinically significant lipidosis have an increased SAP. Increased serum bilirubin concentrations are very common, but not invariable. The ALT is usually normal or it may be slightly increased. The GGT is usually normal despite the high SAP, which is supposedly unique to the cat with lipidosis (e.g., cats with other hepatic diseases causing icterus usually have a high GGT). However, finding a high SAP and a normal GGT does not reliably diagnose idiopathic hepatic lipidosis. Ultimately, you must have a hepatic biopsy in order to know that you have hepatic lipidosis and if there is any other underlying hepatic disease which may have caused the lipidotic. Diagnosis is often made with only cytologic examination of a fine needle aspirate, but it might be best to obtain a core biopsy in case cholangiohepatitis or lymphosarcoma or FIP are also present. You may diagnose lipidosis but miss cholangitis or lymphosarcoma if you just do a fine needle aspirate of the liver. Most cats with symptomatic hepatic lipidosis have hepatomegaly. Major points to remember: just because an icteric cat is or was obese is not sufficient ground to diagnose lipidosis, and fine needle aspirates may mislead

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you by missing other hepatic diseases such as cholangitis or lymphosarcoma which can have a multifocal infiltrative pattern in the hepatic parenc hyma. When hepatic lipidosis is diagnosed, adequate nutrition must be supplied. Some cats that are fed via tube start vomiting. This is probably a reflection of the hepatic disease, and not simply due to the feeding technique. Metoclopramide or cisapride may be useful to stimulate gastric emptying in these cats. Sometimes one must carefully administer small amounts of food frequently for 1-3 weeks (or more) before the vomiting stops. In these animals, it may be useful to constantly drip a liquid diet into the stomach (much like an IV infusion) at a low rate so as to provide nutrition without stimulating vomiting. We routinely feed a gruel made from feline p/d and do not supplement it. Clinicare can be used, but there are some data to suggest that it needs supplemental protein added. Other individuals have supplemented such diets with arginine (1000 mg/day), taurine (500 mg/day), and carnitine (250-500 mg/day), in an effort to improve hepatic metabolism. There is currently some thought that it may be advantageous to add L-citrulline to the enteral diet. Adding B-complex vitamins is reasonable, as is supplementation of vitamin K 1 if there are coagulopathies. Ursodeoxycholic acid (a hydrophilic bile acid mentioned below) is also reasonable. The cat should be fed 30-40 kcal/lb/day. This means that most cats will receive approximately 200-300 kcal/day. You should generally start feeding small amounts (e.g., 10 ml q 4-6 hours) and take 2-5 days to work up to the desired amount. If you overfill the stomach initially, you may induce vomiting. In some severe cases, we will hook up an IV bag that has been filled with the enteral diet and attach it to the feeding tube. In this way, we can "drip" the diet into the cat's stomach by constant rate infusion in an effort to avoid overfilling the stomach and inducing vomiting. If the patient is not doing well (e.g., cannot keep down the food you administer), you need to look for other diseases. One report suggested that concurrent pancreatitis is a reason why some of these patients do not recover. There are some preliminary data that suggest that finding ascites or severe hemorrhagic tendencies may mean that pancreatitis is likely to also be present. Major points to remember: cats with lipidosis can have ascites and marked abnormalities on coagulation profiles and still not have pancreatitis. Also, it is absolutely inappropriate to simply treat seriously lipidotic cats with valium or cyproheptadine (i.e., appetite stimulants); once they are seriously ill you need to also provide special nutritional supplementation. Cats with severe hepatic lipidosis that are not responding to therapy may have concurrent pancreatitis. Cholangitis-cholangiohepatitis may be caused by different mechanisms, including but not limited to bacteria and the immune system. Therefore, it is important to clearly identify and define this disease because different types have different recommended therapies. Patients with intense neutrophilic infiltrates from which bacteria are not cultured should be treated aggressively with cefazolin (my first choice), amoxicillin and/or metronidazole. If the animal is very ill and I believe that I must get any infection under control right NOW, I may use a combination of enrofloxacin and amoxicillin. It is especially helpful to culture bile or hepatic

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parenchyma from these animals as we occasionally find an organism that is resistant to the commonly used antibiotics. B-vitamin supplementation is also used in many of these animals. Ursodeoxycholic acid is safe and may also be helpful but does not seem to be as necessary as in lymphocytic versions. Although it is rare, check to see if there is evidence of biliary tract disease (e.g., stones) which may have caused the problem in the first place. There is also some thought now that many of these patients have an underlying inflammatory bowel disease which allowed bacteria to gain access to the portal blood and be filtered out by the liver. If too many bacteria are being filtered out, then an infection in the liver can be established. The important aspects of this connection are 1) if you find suppurative cholangitis, you should probably biopsy the intestines to see if there is concurrent inflammatory bowel disease and 2) if you treat a cat for inflammatory bowel disease with immunosuppressive drugs and it becomes ill (and especially if it becomes icteric or febrile), you need to look for cholangitis-cholangiohepatitis caused by the immunosuppressive therapy. The long-term prognosis of cats with suppurative cholangitis-cholangiohepatitis is usually good, if you can bring the infection under control. Major point to remember: in cats there may be a connection between suppurative cholangiohepatitis and intestinal disease. For most patients with lymphocytic infiltrates in and around the bile ducts, corticosteroids (1 mg prednisolone/lb/ day) and nutritional modification are the most useful therapies. Antibiotics may be used, but seldom are effective by themselves. Ursodeoxycholic acid (10 mg/kg, sid) may be tried as it can protect hepatocytes from hepatotoxic hydrophobic bile acids. Remember that lymphocytic cholangitis may produce an abdominal effusion that is a perfect mimic of that expected with FIP. These two diseases can be difficult to distinguish at times, a hepatic biopsy being the only way to discern between them. The prognosis of cats with lymphocytic cholangitis-cholangiohepatitis is more guarded than with suppurative cholangiohepatitis. In some cats that

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do not respond well to prednisolone, there is recent evidence that methotrexate might help. However, this drug has many side effects (e.g., myelosuppression, anorexia, vomiting) and there is no justification for using this drug unless you have a histopathologic diagnosis. Major point to remember: cholangitis-cholangiohepatitis is probably more common than many people realize and it is crucial that you know what type is present in order to treat the patient properly. Hepatic lymphosarcoma may cause icterus. A reasonably high number of animals with hepatic lymphosarcoma and other hepatic tumors do not have any detectable abnormalities in the ALT or SAP. The FeLV test may be negative in these patients. Major point to remember: many animals with hepatic lymphosarcoma have normal ALT and SAP. Hepatic cystadenoma is another tumor found in cats. This tumor may appear large and "obviously fatal" during exploratory surgery. However, biopsy usually is definite and reveals it to be the clinically insignificant lesion that it is. Major point to remember: never euthanatize a cat with an obviously fatal lesion until you see the histopathology report. Hepatic cysts are potentially fatal for the same reason that cystadenomas can be fatal (i.e., they can lead to inappropriate euthanasia). Hepatic cysts must be understood to be different than polycystic disease. The latter affects the liver and kidney and usually results in fatal renal failure. Benign hepatic cysts rarely cause any problem to the patient, until the veterinarian gets involved. These cysts appear to be large masses (there may be one or several) in the liver and may be the size of very large eggs. They are usually found during abdominal palpation, when imaging the liver, or at surgery. They are usually smooth and thereby distinguishable from other masses, but this is not invariable. Major point to remember: these cysts are usually found when the patient has some other hepatic disease (e.g., cholangiohepatitis). Do not be so amazed at the size of the cyst that you forget to biopsy BOTH the cyst and the noncystic hepatic tissue. The latter is usually where the diagnosis that will ultimately help cure the patient will be found.

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Chronic vomiting that is difficult to diagnose or treat Vomito cronico di difficile diagnosi e trattamento

Michael D. Willard DVM, MS, Dipl ACVIM, Professor, Texas A&M University

Distinguish vomiting from regurgitation: The first decision to be made is whether an animal is vomiting or regurgitating. Just as there are reliable ways to distinguish regurgitation from vomiting, there are inaccurate and misleading methods. The time of the episode relative to eating is not informative. Pets may vomit or regurgitate minutes to hours after eating. Furthermore, the amount of food or fluid expelled is not helpful in distinguishing vomiting from regurgitation. Most food that has been either vomited or regurgitated will appear partially digested (i.e., there are a lot of little pieces of food mixed with water and mucus). Even when food is vomited after having been in the stomach, gastric dysfunction may have prevented digestion. Food regurgitated from the esophagus is typically expelled as an unformed pile of apparently "semi-digested" food mixed with water. The most reliable indications that the patient is truly vomiting are a) obvious prodromal signs, b) dry heaves and/or vigorous abdominal retching, or c) finding bile (i.e., bright yellow or bright green fluid) or digested blood (i.e., coffee grounds) in the vomitus. If these indicators are not found, that does not eliminate vomiting. Some animals that appear to be regurgitating (i.e., have none of these abnormalities) are in fact vomiting. The best next step in such animals may be to obtain plain Âą contrast thoracic radiographs. If a barium contrast esophagram is performed, it must be done correctly in order to assuredly determine whether esophageal disease is or is not present. Always use barium (NOT hypertonic iodide contrast agents) unless there is evidence of esophageal perforation (i.e., pneumothorax, pneumomediastinum, or pleural effusion). If a contrast series with liquid barium is not helpful, then mix the liquid barium with canned food and repeat the series so as to detect partial strictures. Physical examination may also help distinguish vomiting from regurgitation. Occasionally the esophagus is so dilated and flaccid that it can be seen expanding and collapsing near the thoracic inlet as the animal breathes (much like a bellows). A particularly nice trick is to test the expelled material with a urine dipstick. If the pH of the material that the animal spit out is < 5 or if bile is present, then the material has been vomited. Otherwise, it has probably been regurgitated. Do not trust the reaction for blood. It is invariable positive and does not help distinguish vomiting from regurgitation. Once you have decided that an animal is vomiting gastric or intestinal contents as opposed to regurgitating esophageal contents, the next step is to determine if there is blood in the vomitus. If there is hematemesis, you will be able to consid-

erably limit your list of rule outs. The next major consideration is whether the vomiting is acute or chronic. Most dogs and cats that have acute vomiting but do not have an obvious acute abdomen (that is to say, do not have abdominal pain or shock or sepsis) usually have some form of self-limiting gastroenteritis, although foreign objects and intussusception are possible (and parvovirus must always be considered in younger dogs). Appropriate supportive and/or symptomatic therapy is usually sufficient for such patients. Chronic vomiting (i.e., that which has been occurring for at least 2-3 weeks) is rarely self-limiting, and indicates the need for a more aggressive diagnostic approach. Differential diagnoses for animals that have chronic vomiting: Most patients with chronic vomiting that is not due to motion sickness have either a) alimentary tract obstruction, b) peritoneal or gastrointestinal inflammation, or c) any of several extra-alimentary tract (i.e., "systemic") diseases. Occasionally, there are other causes such as CNS dysfunction, but these causes are genuinely rar e. Gastric outlet obstruction may be caused by foreign objects, tissue proliferation, malpositioning of the stomach, or may be iatrogenic (i.e., due to poorly preformed surgery, especially pyloromyotomies). Contrary to what is suggested in some texts, you cannot diagnose or eliminate gastric outlet obstruction based upon the presence or absence of a hypokalemic, hypochloremic, metabolic alkalosis. The specific diseases causing gastric outlet obstruction that are more difficult to diagnose or that are easy to misdiagnose include antral mucosal hypertrophy, gastric carcinoma, spontaneously resolving partial gastric dilatation-volvulus and iatrogenic obstruction due to poor sur gical technique. Gastric antral mucosal hypertrophy grossly (especially through an endoscope) can look like an ugly adenocarcinoma. Gastric antral mucosal hypertrophy is usually found in older, small-breed dogs (the same signalment that is so suggestive of gastric tumor). However, mucosal hypertrophy has a much better prognosis because surgery (i.e., pyloroplasty, not pyloromyotomy) is curative. It is hard to differentiate gastric antral mucosal hypertrophy from cancer based upon gross appearance, but mucosal hypertrophy tends to be softer than infiltrative cancers (however, this is not always the case). Therefore, appropriate (i.e., deep enough and large enough) biopsy is always indicated before suggesting euthanasia, no matter how obvious the diagnosis appears. Major point to remember: do not make a microscopic diagnosis without a microscope 6 always biopsy and wait for cytology or histopathology before suggesting a per-

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manent "solution". This is a disease that looks exactly like cancer and is found in older dogs (just like cancer); but, it is curable. Gastric malignancies are infiltrative lesions that may be proliferative and/or ulcerative. Chow chows seem to have an inappropriately high incidence of these tumors. These lesions usually have a very poor prognosis unless they are diagnosed very early. Unfortunately, these tumors are rarely diagnosed early because the most common clinical sign of gastric tumors (and for almost all gastric disease for that matter) is usually anorexia, not vomiting. The problem is that when an older animal does not want to eat was well as it used to eat, it is often attributed to the pet's "getting along in years". Subsequently, nothing much is done until the problem is severe or the animal is losing significant weight or the animal starts vomiting. This means that these animals are often not given aggressive diagnostic work ups early in the course of the disease, which is when the clinician would have the best chance of curing the disease. Gastric foreign objects are common and are usually responsible for vomiting, anorexia, and/or abdominal discomfort when they are present. However, the mere presence of a foreign object in the stomach does not guarantee that it is causing that animal's clinical signs. I have seen dogs that had foreign objects in their stomachs for months without any problems what-so-ever. If there is any doubt about whether a particular foreign body is causing vomiting (e.g., some cloth that is not obstructing the pylorus or causing a liner foreign body effect, biopsy the gastric and duodenal mucosa while you are removing the foreign object so that you have tissue samples for histopathology in case the animal continues to vomit after you have removed the object. If you decide to remove the foreign object with endoscopy, be sure that you radiograph the patient immediately before the procedure because some objects will sit in the stomach (or for that matter, in the small intestines) for days and "decide" to move the night before you do the endoscopy. Bones of incredible size can disappear within 24 hours of exposure to gastric acid; give them a chance to go on their own instead of cutting or pulling them out. Linear foreign objects have some unique aspects. Everyone knows that you need to look under the tongue of every vomiting cat for such linear foreign objects. In particular, cats which have a painful lingual frenulum (due to the foreign object cutting into the area) and cats which simply resent having the underside of their tongue examined (which seems to be most cats where I work) cannot be adequately examined without chemical restraint. One mg ketamine/lb given IV and the use of a mosquito hemostat will allow you to inspect this area adequately. If you find a linear foreign object caught under the tongue in a patient that has only been sick for a day or two, you can try cutting the object at the base of the tongue and seeing if it will pass through the intestines without causing any further problem. Monitor the patient carefully; if it does not improve substantially within 24-36 hours, you probably need to suggest surgery. Remember that linear foreign objects can also lodge at the pylorus, in which case there will be nothing to see under the tongue. If a linear foreign object is found endoscopically, it is appropriate to try to remove it with the scope, if it has only

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been there for a few days. This is done by passing the tip of the endoscope into the duodenum and trying to grab the foreign object near its end. In that manner, one may be able to pull the object into the stomach and then remove it. Be extremely reluctant to grab the object near the pylorus and pull. If the object has only been present for 2-3 days, it might be worth a try, depending upon the nature of the linear foreign object. If the foreign object is relatively broad and seems unlikely to readily cut into and perforate the intestine, you might try pulling; however, do not pull too hard. Its not worth the chance of perforating. On the other hand, if the foreign object has been there for several days or if the foreign object seems to be relatively thin and could easily cut through the intestine, do not pull at all. Chronic linear foreign objects in dogs may present differently than most clinicians are aware. We have seen a few dogs that have had massive intestinal involvement with linear foreign objects that had minimal vomiting and even became normal for a few days to weeks before becoming symptomatic again. Major points to remember: not all foreign objects cause clinical signs and not all linear foreign objects cause expected clinical signs (i.e., vomiting). Second, do not refrain from anesthetizing a cat in order to adequately look under its tongue . Idiopathic gastric hypomotility is a diagnosis of exclusion. It seems to occur infrequently, but no one really knows how common it is. There is no anatomic obstruction of the gastric outflow tract, but these patients typically vomit undigested food hours after being fed. Barium contrast radiographs document lack of gastric emptying. Surgery and/or endoscopy fails to reveal an anatomic gastric outflow obstruction. Remember that inflammation anywhere in the abdomen may produce gastroparesis; therefore, be careful in making this diagnosis lest an occult inflammatory lesion be ignored. Metoclopramide is often used to help empty the stomach and prevent vomiting, but some patients are refractory to this treatment. Cisapride (0.25-0.5 mg/kg bid to tid) may be ef fective in stimulating gastric motility when therapy with metoclopramide fails. Erythromycin is also an excellent prokinetic agent for the stomach. However, the prokinetic dose of erythromycin is 1 mg/kg, about 1/5th to 1/10th the antimicrobial dose. Major point to remember: it is crucial to truly eliminate other causes of gastric hypomotili ty, such as inflammatory disease and partial obstruction. Bilious vomiting syndrome is a situation in which otherwise normal animals vomit bile, usually in the morning, shortly after getting up. This appears to be some sort of gastroduodenal reflux syndrome. Feeding the dog just before it goes to sleep, or sometimes giving a prokinetic (e.g., metoclopramide or cisapride or erythromycin) usually solves the problem. Extra-alimentary tract (i.e., "systemic") diseases that especially must be considered in dogs and cats that are vomiting are: 1) renal failure, 2) adrenal hypofunction, 3) hypercalcemia, 4) diabetic ketoacidosis, 5) acute pancreatitis, 6) hepatic inflammation/hypofunction, 7) feline hyperthyroidism, 8) feline heartworm disease (which might simply be due to ear ly congestive heart failure), and 9) pyometra. Alimentary tract inflammation can be the most difficult of the three main categories to diagnose. You cannot rely on

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CBC's or radiographs or ultrasonography; you need appropriate biopsies in order to make this diagnosis. Gastric spirochetes have recently received a lot of attention as a cause of gastric inflammation. They were first discovered in the gastric mucosa of animals and people before the turn of the century. They were considered a nonpathogenic novelty then and were re-discovered in apparently healthy dogs in the 1960's. However, a little over a decade ago, investigators in Australia suggested a causal relationship between these bacteria and human gastritis/ulceration. Today, there is strong evidence that Helicobacter pylori is responsible for most of the peptic ulcers diagnosed in people, as well as non-ulcer dyspepsia in many others. Helicobacter pylori has also been suggested as a predisposing cause of human gastric carcinoma and there are multiple reports of biopsy "proven" gastric lymphosarcoma completely regressing after eliminating resident Helicobacter with antibiotic therapy. Veterinarians have a vested interest in the work on this bacteria because of 2 main questions: a) Do dogs and cats also develop disease due to this bacteria? and b) Can this bacteria be transmitted from dogs and cats to people? Diagnosis of gastric Helicobacter infection is usually obtained by cytology, urease testing of gastric mucosa, and/or histopathology of gastric mucosal biopsies. I find that histopathology is usually more than adequate, if the pathologist looks for the organisms. Cytology (which is actually a bit more sensitive than biopsy) is performed on gastric mucosal biopsy samples or on cytology samples obtained with endoscopic brushes. Slides can be stained with new methylene blue or Diff Quick or various other techniques. Done correctly, cytology appears to be as or more sensitive than culture. Cytologic preparations made from brush techniques performed endoscopically tend to be less sensitive than preparations made from mucosal biopsies. Histopathology is reasonably sensitive. Currently, either silver stains (e.g., Warthin-Starry) or Giemsa stains are used; however, experienced pathologists routinely find the organisms in sections stained with routine H&E. Urease testing may be performed by placing a gastric mucosal biopsy on appropriate agar. There are test kits available (e.g., CLO test, Trimed Specialties Inc, Lenexa, KS) which, when a gastric mucosal sample is placed on them, will indicate the presence of urease (and by implication, Helicobacter pylori) within 2-3 hours. In people, this test has been reported by some as having a sensitivity of 90-98% and a specificity of close to 100%. One may use less expensive tubes of agar designed for detecting urease in other species of bacteria for the same purpose. Although there is currently a serologic test for He licobacter infection in people, there is not such a validated test for dogs or cats. Treatment in people has involved a variety of combinations of drugs. Because the bacteria live below the mucus layer, in vitro sensitivities do not always translate into in vivo efficacy. In general, Helicobacter pylori tends to develop resistance quickly when only one drug is used. Currently, approximately 30% of strains are resistant to metronidazole. Certain other factors (i.e., short period of treatment, poor compliance, prior therapy with omeprazole) seem to be associated with an increased incidence of therapeutic failure.

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The classic triple therapy (metronidazole, bismuth subsalicylate, and tetracycline for 2 weeks) had success rates of 90% (success being defined as eradication of the organism). However, up to 30% of the human patients receiving triple therapy have adverse effects which lead to noncompliance. The macrolides may be the most effective antibiotics for this infection. There are anecdotal reports of erythromycin working well as a single agent in some cats and dogs. Recently, clarithromycin and azithromycin (new macrolides) have been used with apparently good success in infected people. The currently recommended dose of azithromycin appears to be 5 mg/kg sid for cats and 10-40 mg/kg sid for dogs. Azithromycin seems to have fewer side effects (especially vomiting) than erythromycin, but is probably as or more effective. Use of omeprazole to eliminate gastric acidity seems to make the antibiotics more effective. Omeprazole is, in people at least, distinctly more effective for helping to eliminate Helicobacter infections than either cimetidine or famotidine. Combinations of omeprazole, azithromycin, and metronidazole seemingly only need to be given for 7-12 days to effect a cure in people and it is implied (although not proven) that dogs and cats similarly require shortened treatment times. A more fundamental question is, "When should we treat animals with upper gastrointestinal signs for Helicobacter infections? Current experience suggests that one cannot rely upon the presence or absence of gastric inflammatory infiltrates to be able to determine the clinical significance of the presence of Helicobacter. One study found that cats that were not vomiting were just a likely to have these spirochetes and gastric inflammation as were cats that were not vomiting. Dr Guyer found that approximately 30% of vomiting cats and 30% of normal cats had both inflammatory gastric infiltrates and Helicobacter. Likewise, approximately 30% of vomiting cats and 30% of normal cats had neither inflammation nor Helicobacter in their stomachs. Because of our inability to look at a gastric biopsy and determine if the bacteria are responsible for the clinical signs. our current approach is to first determine if there are any other potential causes for the vomiting in the patient. If there is another potential cause that looks as or more likely to be causing the vomiting, we often treat it first. If this treatment does not work; or, if there is no other identifiable cause of vomiting, then one may treat for gastric Helicobacter and see if the patient responds. I believe it is also reasonable (although not particularly likely to succeed) to treat vomiting dogs and cats for Helicobacter gastritis before proceeding with more aggressive diagnostics such as endoscopy. However, if the animal is particularly ill or is losing a lot of weight, I recommend the diagnostics first. A harder question to answer is whether cats belonging to people with Helicobacter-associated disease should be treated to try to eliminate what may have been the source of the human infection. Cur rently, no one really knows how much risk infected dogs and cats are for people. While Helicobac ter heilmannii is distinctly less common as a human pathogen than is H. pylori, a study of 125 people with H. heilmannii infection found that 70.3% of them had contact with pets, compared to 37% of the control population. Thus animals may be a reser voir for this particular species of He -

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licobacter. However, at the time of this writing, it is still not clear how most people become infected with Helicobacter pylori. Therefore, it is vastly premature to state that dogs or cats are a major risk factor for people. We will need to wait on the research. Major points to remember: simply finding spirochetes in the stomach does not mean they are causing disease (many clinically normal dogs and cats have spirochetes -- sometimes in large numbers and sometimes with inflammation -- in their gastric mucosa); you are probably going to have to treat the infection and see how the pet responds. Finally, even if the pet responded, we still are not positive that Helicobacter sp was causing the problem. Even assuming that this is the problem, be aware that there are good data that these bacteria can "return" and re-infect the patient; this has been shown in cats. Abdominal epilepsy (a.k.a. psychomotor seizures) seems rare, but can cause intractable vomiting in a particular patient. So far, it seems like dogs but not cats are affected. It causes vomiting due to stimulation of the medullary vomiting center by the cerebral cortex and/or higher centers of the brain. It should be suspected when the other major causes of

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chronic vomiting (i.e., extra-alimentary tract diseases, alimentary obstruction, peritoneal or alimentary inflammation) have been eliminated. Behavioral change is not expected or even common in these patients. There may be seizures, but most of the cases I have seen have not had seizures or cranial nerve defects. Abnormal electroencephalograms are often detectable, but it is hard to interpret EEGs. The CSF fluid analysis is usually normal. CT scan or MRI are sometimes helpful. The disease can sometimes be treated successfully with anticonvulsants (e.g., phenobarbital or primidone), which gives us another method of trying to identify the disease. If all else has failed, one may start the dog on a therapeutic trial of phenobarbital. One mg/lb twice daily is a reasonable starting point, although the dosage may need to be adjusted based upon therapeutic drug monitoring results. Major point to remember: when you truly have eliminated everything else, try treating for CNS disease. However, be prepared to measure phenobarbital concentrations to be sure that failure to respond is due to the vomiting being caused by some other disease and not due to inadequate absorption of the correct medication.

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Diagnosing and stopping aintractable diarrhea in dogs and cats Come bloccare e diagnosticare la “diarea intrattabile” nel cane e nel gatto

Michael D. Willard DVM, MS, Dipl ACVIM, Professor, Texas A&M University

BASIC APPROACH TO CHRONIC DIARRHEA Chronic diarrhea (i.e., that which persists > 2-3 weeks) usually necessitates a systematic diagnostic approach, even if the diagnostics used are dietary trials. The first question in the patient with chronic diarrhea is whether the patient has an obvious problem such as parasites or an obviously poor diet. Please note that at this time we are not talking about dietary allergy or intolerance. Giardiasis in particular can be occult and responsible for chronic, severe enteritis. It is cost-effective to perform at least 3 fecal flotation and direct exams at 48-hour intervals. Zinc sulfate is a particularly good flotation media to use to look for giardia. There are also an ELISA and an IFA available that find giardia antigen in the feces. If parasites cannot be found, then a therapeutic trial with metronidazole (50 mg/kg/day) is reasonable before proceeding to more aggressive and expensive diagnostics. I prefer to treat with metronidazole for 10-12 days and bath the dogs 1 or 2 times during this time to help remove giardia cysts form their hair coat to minimize the chance of reinfection. Albendazole (25 mg/kg bid for 2 days) and fenbendazole (regular dose as used for helminths administered for 5 days) have been found to be useful in eliminating giardia and there are some data suggesting that oral neomycin is also effective. Furazolidone is useful in cats and kittens because it comes as a liquid suspension which makes administration easier, especially for clients. The next question is whether the patient has large intestinal disease or small intestinal disease. Note that diarrhea is due to increased fecal water. Small bowel disease may have minimal or no diarrhea if the colon can absorb enough water to make the feces firm or solid. It is only when the colon's water absorbing capacity is exceeded that diarrhea occurs. Even when small bowel disease does cause diarrhea, the weight loss from nutrient malabsorption may precede diarrhea by months. Weight loss, especially in the face of a reasonable appetite, suggests nutrient loss from the small intestine. Remember that some patients with severe small intestinal disease will be anorexic. This is probably the most important area to look at in differentiating large bowel from small bowel disease . Any animal with significant small intestinal disease should have loss of weight or condition. Any

animal with chronic diarrhea and no loss of weight or condition has large bowel disease. However, some animals with severe large bowel disease will have weight loss, but these usually also have hematochezia, mucus, and/or marked tenesmus.

SMALL INTESTINAL DISEASE Once small intestinal disease is diagnosed, the next question is whether there is a protein-losing enteropathy (PLE) or not. Check the serum albumin concentration (NOT the total protein) to make this determination. At this point, the approach to canine and feline chronic diarrhea tends to diverge, due to the fact that they tend to have different diseases.

DOGS WITH CHRONIC SMALL BOWEL DIARRHEA If the patient has PLE, then you need to skip down to that section. If the patient does not have PLE, the next step is to eliminate maldigestion. Maldigestion principally means exocrine pancreatic insufficiency (EPI). Cats rarely develop exocrine pancreatic insufficiency, and they are often obviously steatorrhic with a greasy hair coat. I have yet to see classic steatorrhea in a dog with EPI. You need to use the TLI test to establish the diagnosis; all the other tests (including fat absorption test and therapeutic trials with pancreatic enzymes) have so many false positive and false negative results that they are essentially untrustworthy. Major points to remember: enzyme replacement therapy for EPI will not work in all patients; therefore, you need to establish a diagnosis of EPI with certainty using the TLI test (especially in almost any German shepherd). Failure to use the TLI may mean that you wrongly decide that EPI is not present and go on to unnecessary, costly tests (e.g., intestinal biopsy). Most of the cases of EPI I have seen have been referred for endoscopy and biopsy because EPI was "eliminated" after the animal did not respond to enzymatic supplementation. Conversely, incorrectly diagnosing exocrine pancreatic insufficiency in a dog that does not have that disorder results in prescribing expensive enzyme supplements

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that are not needed. Dogs may have EPI and not respond to pancreatic enzyme replacement because a) the enzyme product is poorly effective, b) the diet is too high in fat, and c) the dog also has antibiotic responsive enteropathy. Sometimes you need to address all of these issue before the dog will respond. Once maldigestion is eliminated, then malabsorptive diseases must be considered. Malabsorptive small intestinal disease is a common cause of diarrhea. However, a substantial number of dogs (and cats) with malabsorptive small intestinal disease have normal stools despite severe intestinal pathology. This is especially true in cats because they conserve water better than dogs. Small intestinal disease is a major concern in any animal with weight loss despite a normal (and especially an increased) appetite. If the appetite is decreased, one should still explore the possibility of small intestinal disease. In particular, explore the history to find out if the appetite was normal when the problem first began (a strong indication of small intestinal disease or hyperthyroidism). Major points to remember: many animals with severe, life-threatening weight loss due to small intestinal disease do not have diarrhea. The most common causes of malabsorptive disease in dogs are probably parasites (e.g., giardiasis), antibiotic responsive enteropathy, and dietary intolerance/allergy. Inflammatory bowel disease, lymphoma, and fungal infections are important, but are not the most common causes (at least not in the authors practice areas). Once parasites, protein-losing enteropathy, and maldigestion are eliminated (i.e., you have determined that the patient has a non-PLE malabsorptive disease), the question is whether to recommend therapeutic trials or a major diagnostic work up. If the patient can tolerate a possible delay of 4-8 weeks without undue risk, then therapeutic trials are reasonable. If therapeutic trials are performed, they must be designed such that even if they fail, useful information is obtained and the clinician is further ahead than previously. Always ask yourself: "If this therapy fails, will I really know more about what the patient probably has, or will I be as confused as I was before treating it?". An elimination diet is often useful for non-protein-losing malabsorptive disease. There is no such thing as a commercial diet which is an appropriate elimination diet (i.e., is hypoallergenic and appropriate to look for non-allergic intolerance) for all dogs. We often see cases in which the right thing was done (i.e., an elimination diet was used); but, it was done in such a poorly planned or implemented fashion that the effort was wasted. One must carefully investigate the history and see what the patient has eaten in the past. However, even when you have determined what dietary ingredients the patient has previously been exposed to, it is sometimes difficult to find a diet that works for that particular patient. In some cases, all of our well-planned hypoallergenic diets fail but a chance try at some commercial brand works. When starting the patient on an elimination diet, a homemade diet strongly recommends itself over commercial diets. Although there are excellent commercial diets, homemade elimination diets may be superior when one is first trying to determine if the diarrhea will respond to a diet. If feeding a home-made elimination diet resolves the problem,

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then one can switch to a completely balanced, more convenient, commercially prepared diet. An elimination diet must be used for an absolute minimum of 3-4 weeks (and possibly 6-8) before its efficacy can be accurately determined. If the diet seems to be effective (i.e., weight gain plus resolution of diarrhea) then continue it for at least another 3-4 weeks to be sure that it was the diet that made a difference and the patient is not having a transient impr ovement due to whatever. Major point to remember: poorly constructed dietary trials are a major cause of therapeutic failure. Many chronic small intestinal problems can be resolved with a well-designed therapeutic trial. Antibiotics are reasonable therapy for chronic small intestinal malabsorptive disease, because antibiotic-responsive enteropathy (ARE) is a re l at ively common problem in dogs. This is a syndrome in which there are excessive numbers of bacteria in the upper small intestine AND the host responds to them in such a manner as to cause intestinal dysfunction. These bacteria are not usually obligate pathogens, but rather contaminants which are not eliminated from the upper small intestines. The signs they produce, if any, depend upon which bacteria are present and how the host responds to them. Anaerobic bacteria are often more pathogenic than aerobic bacteria. The relationship of this syndrome to inflammatory bowel disease, if any, is uncertain. Antibiotic-responsive enteropathy (previously called small intestinal bacterial overgrowth can be hard to diagnose. Because of the potential difficulty in diagnosing this disease, empirical therapy is often chosen instead of diagnostic tests. The obvious drawback to this approach is that the patient may have another disease which predisposed it to the bacterial overgrowth. Oral aminoglycosides are poor choices of antibiotics to treat ARE because anaerobic bacteria (which are often the more important type present) are resistant to aminoglycosides. Tetracycline is often effective, and tylosin powder has also been useful. Some clinicians like metronidazole; however, I have not been impressed with the efficacy of this drug for ARE. Regardless of which drug is used, such a trial should be performed for at least 2 weeks before a decision is made as to its efficacy. Not only do you need to eliminate the infection, but you must also allow the intestines to heal. Major point to remember: it may be a good idea to routinely treat all dogs with chronic small intestinal disease for ARE, even if you have histologic evidence of IBD or other disease. At this time, there is no easy, readily available "gold standard" for the diagnosis of ARE. Cobalamin and folate concentrations are often used to look for ARE; however, they are uncertain sensitivity and specificity. The bottom line is that I will treat for ARE in almost every dog with non-PLE malabsorptive disease; there is nothing I will see on the cobalamin and folate determinations that will change that. If a therapeutic trial will be done, it is usually a good idea to use a hypoallergenic diet and antibiotic therapy initiall y. If the patient responds, you can later stop one or the other and figure out which is the important aspect of therapy. If the patient is so sick that you cannot chance a 2-6 week therapeutic trial that may fail; or if the owners insist upon

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obtaining a diagnosis, then tests are the next step. If, based upon history, physical examination, laboratory data and/or radiographs, you are sure that the small intestine is involved, then the best next step is usually intestinal biopsy. Intestinal biopsy may be accomplished two ways: endoscopy and surgery. CBC,serum chemistry profile, and urinalysis are useful and may point out systemic manifestations of the disease which will aid in correctly diagnosing and prognosing the problem (e.g., hypoalbuminemia due to histoplasmosis), but are also useful as a preanesthetic work up before endoscopy. Ultrasound is useful to look for enlarged mesenteric lymph nodes or focal intestinal/gastric lesions, which may suggest a tumor (e.g., alimentary lymphoma or carcinoma) is present. However, animals with severe IBD may also have mesenteric lymphadenopathy. If the nodes are clearly enlarged, it may be helpful to aspirate them percutaneously with ultrasound guidance. It may also help you decide whether to perform endoscopy or laparotomy when biopsying intestines (i.e., if there is an obvious lesion where an endoscope cannot reach, it is best to perform laparotomy instead of endoscopy). In contrast, abdominal radiographs (plain or contrast) are rarely helpful and are seldom cost-effective.

HYPOALBUMINEMIA Severe hypoalbuminemia (i.e., < 2 gm/dl) in an animal with diarrhea suggests a protein-losing enteropathy (PLE). If severe, exudative cutaneous disease, protein-losing nephropathy, and hepatic insufficiency are eliminated, then PLE is a reasonable tentative diagnosis. Contrary to what the textbooks say, PLE may be associated with a low, normal or increased serum globulin concentration. Inflammatory bowel disease and intestinal lymphoma are the most common causes of canine PLE, although intestinal lymphangiectasia is the disease most people associate with PLE. Protein-losing enteropathy is rare in the cat, but when it happens it is often due to inflammatory bowel disease or alimentary lymphoma. Gastrointestinal ulceration may also be responsible, but that is uncommon. While one may symptomatically treat a patient with PLE, it is far preferable to obtain a definitive diagnosis because PLE tends to be caused by severe disease. Furthermore, the different causes of PLE have different treatments and different prognoses. There is some increased risk of dehiscence of intestinal incisions when the serum albumin is < 1.5 g/dl. Endoscopic biopsies alleviate this risk, but they may not always provide the diagnosis. If full thickness biopsies are obtained during celiotomy, serosal patch grafting minimizes the risk of suture line leakage. A nonabsorbable or a poorly absorbable suture (PDS) should also be used. Intestinal lymphangiectasia is more common in textbooks than in patients, at least in our practice. It seems to be more common in Yorkshire terriers and Soft-Coated Wheaten terriers, but may occur in any breed. Therapy for intestinal lymphangiectasia revolves around an ultra-low fat diet. Using elemental diets (e.g., Vivonex) is very helpful in these patients. Sometimes corticosteroids are also useful as lipogranulomas may form in the intestines, further impeding

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lymphatic flow. However, be aware that some of the causes of PLE are made much worse by corticosteroids (e.g., histoplasmosis). If the serum albumin is very low (e.g., < 1.3 gm/dl), a plasma transfusion may be needed while waiting to see what effect the diet will have. However, it is difficult to increase serum albumin concentrations by transfusing PLE patients. This is because approximately half of the albumin you administer will end up going into the interstitial compartment and only about half will remain in the vascular compartment. I've given as much as two units of plasma to a 15 lb dog in order to raise the serum albumin from 1.0 gm/dl to 1.8 gm/dl.

CATS WITH CHRONIC SMALL BOWEL DIARRHEA The differentials for cats with chronic small intestinal disease tend to be different than what is found in dogs. Parasites are possible, but are generally not as common as in dogs. Exocrine pancreatic insufficiency is quite rare in cats. Antibiotic-responsive enteropathy does not appear to be as common in cats as it is in dogs. Dietary problems are seen and should be kept on the list of differentials. However, infiltrative bowel diseases, specifically inflammatory bowel disease and lymphoma, are much more common in cats than in dogs. These differences affect the order that things are done in cats with chronic small bowel diarrhea, compared to dogs with chronic small bo wel diarrhea. Of all the chronic intestinal problems recognized in cats, inflammatory bowel disease (IBD) has probably had the most press. In general, clinical signs of small bowel IBD are usually considered to be vomiting and diarrhea while large bowel disease primarily causes hematochezia with or without diarrhea. However, the clinical signs of IBD can be vague and nondescript. IBD can cause anorexia (with or without diarrhea), weight loss, or icterus secondary to a suppurative cholangitis caused by bacteria that probably originate from the intestines. Therefore, one needs to be diagnostically aggressive, which means being willing to sometimes biopsy intestines even when the clinical signs do not clearly point to that organ. If a non-hyperthyroid patient is losing weight despite a reasonable appetite, of if other common causes of weight loss have been eliminated in a patient with a poor appetite, endoscopy of the small intestines should be considered. If the cat has hematochezia, one should biopsy the large intestines even if there is no diarrhea. One should never feel bad about biopsying intestines only to find that they are normal. Inflammatory bowel disease is defined by finding inflammatory infiltrates in the intestine but being unable to attribute them to a specific cause. Said another way, IBD is idiopathic intestinal inflammation. For example, if there are inflammatory infiltrates in the intestines and they subside when the patient is fed an elimination diet, then that cat had dietary intolerance or allergy, not IBD. Since IBD is a diagnosis of exclusion, it is crucial to be sure that all known causes have been eliminated. If we have eliminated all known causes of the intestinal inflammation, then by defini-

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tion we only have symptomatic therapy available. This is the case when we diagnose IBD. If we can find an underlying cause for the intestinal inflammation, the chances of successfully treating the disease are substantially improved because we can then directly address the problem instead of just trying to deal with the signs. Furthermore, if we can treat the underlying disease, we may avoid using anti-inflammatory drugs that may have substantial side-effects, or at least be able to use smaller doses than usual. The cause of feline IBD is unknown, but can reasonably be hypothesized to be due to exposure of the intestine to antigens which results in an influx of inflammatory cells such as lymphocytes. If dietary intolerance or allergy is present but never identified (either because it did not respond to a poorly constructed elimination diet, or because more time was needed to respond to an elimination diet than was allot ted by the clinician), then IBD will be erroneously diagnosed. The length of a dietary trial is very important. In general, most clinicians believe that if a patient is going to respond to an elimination diet, it will do so within 3-4 weeks. While this appears to often be true, some dogs with cutaneous manifestations of dietary allergy require weeks or months to have their clinical disease resolve once the offending allergen is eliminated. The same might be true of some cats with exaggerated intestinal inflammatory responses to allergens. Therefore, it seems reasonable that any cat suspected of having IBD or any cat that has been diagnosed as having IBD should receive, in addition to the typical symptomatic anti-inflammatory drugs, a carefully designed elimination diet which will hopefully treat any here-to-fore unidentified dietary intolerances. We recommend use of elimination diets even when they were previously unsuccessful in the hope that they may at least allow use of lower doses of the anti-inflammatory drugs.. There are several types of IBD in cats and they are named for the predominant type of cell infiltrating the mucosa. Lymphocytes and plasma cells are the cells most commonly found infiltrating the intestines; hence, lymphocytic-plasmacytic enteritis (LPE) is the most common fo rm of feline small intestinal IBD. Occasionally, eosinophils, neutrophils, and/or macrophages are also found in greater or lesser numbers. If many macrophages are seen (i.e., gra nu l o m atous disease) one should consider the possibility that there might be an underlying neoplasia (e. g. , lymphoma). This is not always the case, but occasionally occurs. I often start treating cats with LPE with an elimination diet, metronidazole, and prednisolone. Metronidazole seems to have immunomodulatory properties that help treat some forms of IBD. Metronidazole is sometimes as or more effective than prednisolone, especially with LPC. Using prednisolone in conjunction with metronidazole seems to improve results. The dose of metronidazole used for IBD is usually 10-15 mg/kg bid. Cats that are infected with FeLV or FIV can be at increased risk for infection; these can often be treated successfully with metronidazole alone. Likewise, cats with diabetes mellitus should not receive steroids as these drugs may cause insulin resistance. In both of these cases, one should initially use metronidazole without prednisolone, to see if it will be adequate. Adverse reactions to

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metronidazole are rare when used at this dose and we do not hesitate to use it for weeks or even months. If CNS toxicity (e.g., seizures, convulsions,disorientation, weakness) occurs due to metronidazole, withdrawal of the drug will usually be associated with clinical remission within 24-48 hours. Vomiting may occur as a minor side effect of metronidazole; if it occurs, it can usually be dealt with quickly by stopping the drug for a day or two and then administering it with food. Chlorambucil (Leukeran) is another cytotoxic drug that can be used. This alkylating agent is much less dangerous than cyclophosphamide and may be safer than azathioprine. It is sometimes useful for the cat with LPE that does not respond to diet,prednisolone, and metronidazole. There is limited experience with this drug in cats with IBD, but it seems that it should be administered with prednisolone. There are at least two methods of administering chlorambucil to cats. In the first method, the initial dose is 2 mg of chlorambucil/M2 of body surface area given daily for 4-7 days. The dose is then decreased to 1 mg/M2 daily for 7 days. If the clinical signs are lessening, one then starts to administer the drug daily, but only every other week. It is common for these patients to develop anemia (PCV = 18-22%). The second method is to g ive large cats (i.e., > 7 lbs) 2 mg twice weekly and smaller cats (i.e., < 7 lbs) 1 mg twice weekly. If a clinical response will occur, it should be seen in 4-6 weeks, after which time the drug may be slowly tapered to the lowest effective dose. CBC's should be monitored periodically or anytime the cat seems to feel bad. Lymphoma is usually the most common form of gastrointestinal malignancy found in the cat. Furthermore, the alimentary form of lymphoma is often the most common form identified, although this finding varies from location to location. Most alimentary lymphomas are FeLV negative which is not surprising when you consider that most alimentary lymphomas are believed to be of B-cell origin. The most common signs of intestinal lymphoma are similar to that found for IBD while gastric lymphoma may present with anorexia as the sole complaint. Thickened intestinal loops may be found, but are not invariable. There are no CBC or serum chemistry profile findings that are diagnostic for or strongly suggestive of alimentary lymphoma. Chylous abdomen is rarely found in cats, but when present may be associated with various neoplasms, including lymphoma. Abdominal radiographs rarely show a solitary mass. Abdominal ultrasound may reveal thickened intestines and/or enlarged mesenteric lymph nodes. Neither of these findings diagnose lymphoma or eliminate IBD; however, marked mesenteric lymphadenopathy seems to be more common in lymphoma than in IBD. There are some instances in which an apparently correct diagnosis of IBD is latter followed by a diagnosis of intestinal lymphoma. It is suspected that in some patients, LPE may be a preneoplastic disorder. The frequency of this occurrence is unknown; the point is that one should not hesitate to rebiopsy a patient if the disease (e. g. , IBD) does not respond to apparently ap propriate therapy. This concept works in "reverse" also. We have just documented a cat in which lymphoma was diagnosed twice over 9 months and the patient was ultimately found to only have IBD.

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SELECT SPECIFIC LARGE BOWEL DISEASES OF DOGS AND CATS Clostridial colitis is a very important disease in the dog, but we are not sure how important or common it is in the cat. It is caused by toxigenic strains of Clostridium perfringens. However, even when a toxigenic strain of Clostridium perfringens is established in the colon, it does not generally produce disease unless the bacteria are sporulating. Toxigenic strains upregulate the amount of enterotoxin produced when they sporulate, and it is this toxin (i.e., enterotoxin A) which damages the colonic epithelium and produces diarrhea. Diagnosing clostridial colitis is not as easy as it was a few years ago. One cannot relia bly diagnose clostridial colitis by finding spores in the feces (via fecal cytology) or by performing quantitative cultures for Clostridium perfringens. Looking for fecal spores is an especially easy screening procedure, and the spores can be detected with a variety of stains. However, just as the disease can wax and wane unexpectedly, the presence and number of spores may likewise change. Biopsy is not that helpful; there may or may not be histologic changes in the colonic mucosa in animals with clostridial colitis. Besides, the histologic lesions seen with clostridial colitis are nonspecific, and cannot be reliably differentiated from IBD or dietary allergy/intolerance. We used to think that the most definitive method of diagnosing clostridial colitis was to assay the feces for the presence of toxin, using a reversed passive latex agglutination test. However, this last method is relatively expensive and is no more sensitive or specific than other tests. Therefore, we now treat for the disease and observe the clinical response. While this approach can cause a problem when there are two things happening concurrently (e.g., clostridial colitis PLUS dietary intolerance), it seems to be one of the best ways to diagnose clostridial colitis. Major point to remember: response to amoxicillin or tylosin may be one of the best ways to presumptively diagnose clostridial colitis. However, clostridial colitis may occur concurrently with dietary intolerance or allergy in some patients and you may need to treat both. There is an acute form of clostridial colitis (usually nosocomial) in which previously normal hospitalized patients suddenly have a "blow out" of acute, bloody diarrhea but are otherwise essentially normal. There also seems to be a chronic form in which the patients have relentless, mucoid stools (+ hematochezia). The latter patients may have inflammatory colonic disease, but often have histologically normal colonic mucosa. In general, all tests (except those directed at finding the bacteria or its toxin) are essentially normal. Rarely, there is historic evidence of conta gion between dogs, or even between dogs and people. Unless one is aware of this disease, these patients will usually be diagnosed as having idiopathic large bowel diarrhea (i.e., "irritable bowel syndrome"). There is a very rare form of intestinal clostridial disease that seems similar to the "Pig-Bel" described in people. If there is overgrowth of Clostridium perfringens and the patient is eating a diet which has substantial antiprotease activity, there may be systemic signs or even death from the bacterial enterotoxins. This disease is not currently definitively described in dogs, but something like it probably exists.

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Tylosin is an antibiotic that seems to be consistently effective against Clostridium perfringens which a major cause of large bowel disease in dogs, at least in Michigan and Texas. This is a wettable powder that is used to treat poultry. Tylosin should be used for at least one week and preferably two before any judgment is made as to its usefulness. The dose is 10-40 mg/kg bid, but approximately 1/16th of a teaspoon two times per day in the food for cats and small dogs (i.e., less than 7 kg), 1/8th teaspoon two to three times per day for medium dogs (i.e., 7 to 15 kg), and 1/4 teaspoon two to three times per day for larger dogs (i.e., > 15 kg) is safe, effective, and easier to remember. Some patients will need treatment for the rest of their lives while others can be slowly weaned off the drug. Tylosin tends to have an unpleasant taste and needs to be mixed into the food. Amoxicillin and clavamox are also effective in animals with clostridial colitis. Many animals with chronic clostridial colitis that require antimicrobial therapy can be well controlled with one treatment of amoxicillin every 2-3 days. Metronidazole is very effective against anaerobic bacteria in general, but metronidazole is inconsistently effective in animals with clostridial colitis, possibly because metronidazole does not reliably achieve therapeutic levels throughout the feces. Some dogs with clostridial colitis respond to fiber supplementation, which makes sense because fiber will usually remain relatively intact until it reaches the colon where it may have profound effects on the microenvironment of the colonic bacterial flora. Such an impact on the fecal microenvironment may make Clostridium perfringens quit sporulating, which causes the diarrhea to stop. See below under "Irritable bowel disease" for more discussion on fiber supplementation. While some patients with clostridial colitis will respond adequately to a high fiber diet, others may seemingly require indefinite tylosin therapy. However, in these latter patients, one may be able to control the disease by administering the drug once every two to three days. The goal is not necessarily to eradicate Clostridium perfringens from the animal; rather, it is to prevent the bacteria from elaborating and releasing the enterotoxin. The preferred long term therapy of clostridial colitis is to maintain the animal on a high fiber diet which controls signs. Ostensibly, the high fiber component alters the microflora and/or environment such that spore are not produced and the bacteria, even if present, do not cause disease. Irritable bowel syndrome (IBS) is the name given to the situation in which a patient has chronic diarrhea (usually large bowel) but no organic lesions can be found despite an appropriate diagnostic work up (i.e., idiopathic diarrhea). In people, IBS means much more, including have abdominal discomfort. Therefore, you must understand that we are using this term differently than physicians. Saying that the dog or cat has idiopathic large bowel diarrhea is simply to say that we have not yet recognized the cause. There is bound to be some cause, and until we identify it, we will continue to use the term IBS. Major point to remember: IBS is a diagnosis of exclusion and you must be certain that you have in fact excluded everything else. However, it is far preferable to determine that the patient responds to fiber supplementation early in the work up rather than do everything and then try adding fiber.

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Many patients diagnosed as having IBS seem to respond to dietary fiber supplementation. In these patients, it is uncertain whether the fiber is aiding the animal's fight against the disease process or if the fiber is simply "soaking" up excessive water and making the stool appear more normal. The dose of fiber or bulking agent to add to the diet is empirical, but approximately one tablespoon of metamucil or coarse wheat bran per can of food is a useful starting point. If this amount is tolerated, the dosage can be gradually increased or decreased as needed. Not all types of fiber have similar effects. The old distinction between soluble and insoluble is overly simplistic. If fiber will be used, you must remember that some animals respond best to one type of fiber while others respond best to another type. In fact, we have seen some animals become markedly worse when one type of fiber was used, only to respond well when that type was replaced with a second type. For example, in some cases, addition of metamucil to a diet will make the problem worse while a commercial diet supplemented with another form of fiber will be beneficial. There is some thought that using both soluble and insoluble types simultaneously may be the most physiologic manner to supplement fiber. Two weeks is usually adequate to see if the patient will respond to a fiber-supplemented diet, although 4-8 may be necessary before a patient responds beneficially to a hypoallergenic or elimination diet. It is important to realize that fiber will not help all types of chronic large bowel disease. A few patients clearly do better on a low residue diet, especially if the problem is due to dietary intolerance and/or food allergy. Major point to remember: too much metamucil may cause excessive amounts of feces which is interpreted by the client as more diarrhea. Dietary intolerance is more common than many suspect, especially in cats with chronic large bowel disease. You cannot count on finding eosinophils in the colonic mucosa; most patients with dietary intolerance have minimal histologic changes or have nonspecific lymphocytic and/or plasmacytic and/or eosinophilic infiltrates. Because the histologic findings are nonspecific, it is often preferable to try elimination diets prior to performing colonoscopy, as you can rarely definitively diagnose dietary intolerance from the biopsy. The biggest problem in these patients is finding an effective diet. In this area in particular, we often see cases in which the right thing was done (i.e., an elimination diet was used), but was done in such a poorly planned or implemented fashion that the effort was wasted. Most of the time, all that is needed is to carefully investigate the history and see what the patient has eaten in the past. However, sometimes it is difficult to find a diet that is "right" for a particular patient. This might be because you do not know if the problem is an allergy or an non-allergic intolerance. The former can be guessed at by looking at former diets while the latter is impossible to predict. In some cases, all of our well-planned

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hypoallergenic diets failed but a chance try at some commercial brand worked. Major point to remember:it is easy to do a poor job of trying a hypoallergenic diet and make the client so discouraged with dietary therapy that they end up requesting costly work ups when a good dietary trial done at the beginning would have wor ked. Also, if you do a thorough work up and do not find a reasonable cause of the diarrhea, it is probably a dietary intolerance or allergy and you will have to simply try diet after diet until you finally find the right one. Metronidazole is useful to modulate the immune system in some patients. It is used at a dose of 10-15 mg/kg bid for these patients. It may, but does not have to be combined with prednisolone in patients with IBD because it is often effective as a sole agent, especially some cats with IBD and concurrent FIV or FeLV infection. I have seen at least one dog with a chronic purulent colitis that responded better to metronidazole than to azulfidine. I do not know how to predict which dogs and cats will respond to metronidazole and which will not. Therefore, it often must be used and the results evaluated. In some patients (especially cats),CNS signs may occur due to accumulation of metronidazole levels. If seizures occur, support the patient and withdraw the drug. Generally, the patient's signs will disappear quickly as the serum drug levels diminish. Major point to remember: when used at the 15-20 mg/kg bid dose, metronidazole can usually be used for extremely long periods of time with little or no risk of CNS disease . The most important question is, "What do you do when you do all of these things and the dog or cat still has diarrhea?" "Intractable" large bowel diarrhea is usually due to a common, treatable cause that can be controlled with appropriate therapy, but that has been misdiagnosed and/or mismanaged. In most cases you do not need some newer, more powerful, drug. Careful consideration of the patient's prior drug administrations, previous diets, the client's compliance, and a careful review of prior diagnostic procedures will usually reveal that other less aggressive and less dangerous therapies are effective once the problem has been better defined. It is common to ultimately find that diet will partially or completely resolve the problem, once the correct diet is found. If you are convinced that your therapies have been excellent and carried out correctly, you should not hesitate to repeat your diagnostic work up. Look again for giardia and do not hesitate to rebiopsy the colon, being sure that you examine the entire colon and probably the ileum as well. Such a work up may reveal another, previously unsuspected problem or a second disease that has occurred since you diagnosed the first disease. Major point to remember: you should not hesitate to consider the possibility that you have the wrong diagnosis in patients who are not responding to apparently appropriate therapy, even if you have previously obtained multiple colonic biopsies.

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Gastrointestinal hemorrhage Emorragia gastrointestinale

Michael D. Willard DVM, MS, Dipl ACVIM, Professor, Texas A&M University

Significant hemorrhage from the gastrointestinal tract usually manifests as hematemesis, hematochezia, melena, or anemia. Ulceration/erosion are usually the first considerations for hematemesis; however, there are other important considerations. Many mistakes are typically made in patients with hematemesis. First, digested blood does not always look like blood; it usually looks like Acoffee grounds@. Many people therefore do not recognize hematemesis. Second, it is not appropriate to automatically administer H-2 receptor antagonists and carafate to every dog that has some blood in its vomitus, especially if endoscopy is contemplated (administering carafate makes it very difficult to find ulcers). It is best to first consider the possible causes of hematemesis. Coagulopathies are uncommon causes of hematemesis; but,they have important ramifications when they occur. A platelet count and a measure of clotting function (e.g., activated clotting time, one-stage prothrombin time, mucosal bleeding time) are indicated in animals with substantial blood loss. A dog may have a coagulopathy causing hematemesis despite not having evidence of hemorrhage elsewhere, even after venipuncture. Hematemesis necessitates a slightly different approach because some rule-outs become more likely while others become much less likely. There are 3 major reasons for an animal to vomit blood: coagulopathy, swallowing blood from elsewhere, and gastrointestinal ulceration/erosion (GUE). The most common causes of GUE that are also the easiest to check for are mast cell tumor, drug administration and "stress". Drugs are a very important cause of GUE in the dog. While there is some controversy whether all corticosteroids are ulcerogenic, most clinicians agree that high doses of dexamethasone have the potential for significant gastric erosion. Prednisolone by itself is not ulcerogenic unless it is used in very high doses (e.g., > 2-3 mg/lb/day), and even then it is not particularly bad. However, there is no doubt about the danger of nonsteroidal anti-inflammatory drugs in dogs. All NSAIDs (including carprofen) have the potential to cause devastating GUE, and some of these non-steroidal drugs are renowned for their toxic effects (i.e., indomethacin and naproxen). Ibuprofen is also particularly ulcer ogenic in the dog because it undergoes an enterohepatic circulation. Some of the newer NSAIDs (carprofen) have much less potential for causing GUE than the older drugs; however, you can get GUE if you used excessive doses or use the drug at the wrong time (e.g., when the patient is experiencing shock or poor perfusion to the alimentary tract). Flunixin is a particu-

larly dangerous drug from the standpoint of causing GUE. It is extremely potent and can be devastating if combined with steroids like dexamethasone. While able to cause significant ulceration and bleeding all by themselves, the ulcerogenic potential of NSAIDs is particularly augmented by other factors, especially concurrent administration of another NSAID or a corticosteroid, and hypoperfusion of the alimentary tract. Even though many dogs tolerate such combination therapy, you need to realize that you are "walking on thin ice". Most of the dogs treated with such drugs have endoscopically visible erosions, hemorrhages, and ulcers. However, they do not evidence signs to the owner. None-the-less, it is easy for a previously asymptomatic animal to suddenly begin vomiting blood or to perforate and develop peritonitis. Finally, there is tremendous between-dog variation in the response to NSAID's. I have seen a dog almost bleed to death because of a small dose of aspirin used in post-heartworm therapy, while most dogs would tolerate a much larger dose with impunity. Major point to remember: NSAID's must be considered in any dog with GUE that is not obviously due to some other cause. Stress, when mentioned as a cause of ulcers, specifically refers to hypovolemic or septic shock (usually but not always obvious from history and/or physical examination). Neurogenic shock can also be responsible. Poor perfusion is often most severe in the gut, making it particularly susceptible to ulceration. Mast cell tumors may look like any (and I mean literally "any") skin lesion. In particular, they can perfectly mimic the appearance and feel of lipomas, such that the only way to distinguish them from lipomas is by aspirate cytology. When these tumors degranulate, they release histamine which causes gastric acid hypersecretion. This can result in severe ulceration, especially just inside or just beyond the pylorus. There are other causes of GUE which are a little more involved to diagnose. A major cause of GUE in the dog appears to be hepatic failure. A good example of such disease is hepatic cirrhosis. Anytime I have a dog with hepatic disease that suddenly becomes clinically worse (especially if it becomes encephalopathic), I look for GUE. Bleeding into the intestine counts as a high protein meal and predisposes to hepatic encephalopathy in these patients. Hepatic disease may cause disseminated intravascular coagulopathy which can cloud the picture when trying to determine the cause of hematemesis. It is noteworthy that coagulopathies rarely cause hematemesis by themselves.

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Renal failure is associated with gastrin accumulation, gastric erosion, and poor platelet function. It is uncommon that large GUE occur due to renal failure, but it is seen from time to time. Inflammatory bowel disease may be associated with GUE, especially in the dog. It appears that this is not as common as IBD without ulceration, but it does occur. Therefore, anytime GUE is found during endoscopy, the stomach and duodenum should be biopsied. Occasionally, hypoadrenocorticism may be responsible for severe hematemesis, but this situation does not seem to be common. Severe neurologic disease may also be responsible; but, as these patients are often treated aggressively with corticosteroids, it is difficult to establish cause and effect. Heavy metal intoxication might also cause hematemesis, but this seems uncommon. Gastrinomas are typically small pancreatic tumors which produce large quantities of gastrin, a hormone which causes gastric acid secretion much like insulin causes cells to take up glucose. Since the gastric mucosa is stimulated to grow, ulceration typically occurs in the duodenum instead of the stomach. Esophageal ulceration may also occur if there is gastroesophageal reflux of the highly acidic gastric contents. Measurement of serum gastrin concentrations may be diagnostic. However, anything which causes gastric distention or renal failure can produce increased fasting serum gastrin concentrations. Treatment with H-2 antagonists has been rewarding although unexpectedly large doses and/or newer, stronger preparations (e.g., omeprazole) may be necessary. Major points to remember: consider gastrinoma in any older dog that has vomiting, weight loss, and diarrhea of unknown origin, you usually need to measure serum gastrin concentrations to diagnose gastrinoma, the ulcers are usually found in the duodenum (not the stomach), and esophagitis is common. If the patient is exsanguinating or if the patient has not responded to 5-7 days of "appropriate" medical therapy for the ulceration, it is reasonable to surgically resect the ulcer ated area. However, it is usually wise to perform gastroduodenoscopy before the surgery to be sure that you find all of the sites of ulceration. It is very easy to fail to detect an ulcer at surgery, and endoscopy usually allows one to easily find all areas of ulcer ation. If the patient is not exsanguinating and has not had 5-7 days of appropriate medical therapy, then medical therapy is typically indicated. Adequate fluid therapy is important in the dehydr ated or poorly perfused patient because mucosa probably cannot heal well if it is not well perfused. If there is significant gastroduodenal reflux of bile, metoclopramide or cisapride may be helpful in preventing bile from entering and/or staying in the stomach and augmenting the ulcerogenic process. Cimetidine, ranitidine, and famotidine are now available as "over-the-counter" (i.e., OTC) preparations and all are good medications for decreasing the gastric hydrogen ion concentration. Cimetidine (5-10 mg/kg) needs to be given 34 times per day if you are really serious about decreasing gastric acid secretion. However, famotidine (0.5 mg/kg) on ly needs to be given once or twice daily. In most patients, cimetidine is more than adequate to allow healing of gastric ulcers. However, the OTC preparations are all oral and some

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patients are vomiting so vigorously that they must receive parenteral medication. Ranitidine (2.2 mg/kg) is usually effective if given twice daily and is my favorite injectable H-2 antagonist. However, it will cause vomiting if given as an IV bolus. Side-effects of the H-2 antagonists are rare but may include diarrhea, drug eruption, hyperpyrexia, thrombocytopenia, granulocytopenia, and CNS problems including seizures. We believe we have seen dogs in which ranitidine was responsible for large bowel diarrhea and for seizures. The primary value of the H-2 antagonists is in treating existing ulcers and erosions. They can be somewhat helpful in preventing some types of ulcers, but this is not true with all types of ulcers. There is no value to routinely administering the H-2 antagonists when treating animals with high doses of prednisolone. The only exception might be when treating dogs with severe immune-mediated hemolytic anemia that have low PCV's and hence a somewhat anoxic gastric mucosa. This is a clinical impression and is not documented. Ranitidine and nizatidine also have prokinetic activity, which may help some patients. Omeprazole and lanosprazole are the most effective inhibitors of gastric acid secretion we have available. Omeprazole is available as Prilosec7. It is from a class of drugs called proton pump inhibitors (PPI). We rarely use omeprazole because of its expense and the fact that the H-2 receptor antagonists seem quite adequate except in some animals with gastrinomas and those with esophagitis due to gastroesophageal reflux. The dose of omeprazole is 0.7-1.5 mg/kg sid, although I have often used it at up to 2 mg/kg bid in patients with severe reflux esophagitis or gastrinomas. Very rarely, an H-2 antagonist will work better than omeprazole; be prepared to experiment in your difficult cases. Major point to remember: omeprazole seems to be most useful for treating gastrinomas, gastroesophageal reflux, and Helicobacter infections. Sucralfate seems to be extremely effective in protecting those areas which are already ulcerated and helping them heal. The only common side-effect is constipation. There is minimal absorption from the intestines, but it does have the capacity for adsorbing other drugs (e.g., enrofloxacin, cimetidine). While carafate is effective in treating ulcers, it is not always effective in preventing ulceration. In patients with severe hematemesis and anemia, we sometimes us a large "loading" dose to help stop potentially life-threatening blood loss. This may mean giving 3-6 grams initially and then decreasing the dose to 1 gram tid to qid. My major problem with this drug is that it must be given orally, which does not always work in vomiting dogs. Sometimes you may dissolve the table in water or buy the suspension and have less problem with that being vomited. Major point to remember: try to avoid giving this drug at the same time as other drugs. Although it is usually acceptable, sometimes it causes problems with the absorption of the other drug. If there is no apparent reason for hemorrhage in the esophagus, stomach, or duodenum, one should consider whether the blood may be originating from the respiratory tract. Bleeding respiratory lesions can result in large amounts of blood being swallowed and then vomited. Therefore, if gastroduodenoscopy is fruitless, bronchoscopy should be performed.

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Any number of colonic lesions may cause hematochezia (as opposed to melena from upper alimentary hemorrhage). Colonic mucosal disease usually produces obvious diarrhea, and hematochezia occurs because of the severity of the lesion. However, some patients have relatively normal stools associated with hematochezia. Most cats with this combination have colonic inflammatory bowel disease; however, dogs usually have rectal lesions (e.g., polyps, tumors). Anal

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sac disease can also cause these findings. Thorough, repeated digital rectal examination is often more rewarding initially than endoscopy in such dogs. Digital rectal examination often finds lesions missed by proctoscopy. If there is no evidence of a rectal lesion, then endoscopy is appropriate. However, flexible endoscopy is suggested (as opposed to rigid) because the next most likely site of disease is the ileocolic valve, especially intussusceptions of this structure.

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Canine/feline pancreatitis Pancreatite nel cane e pancreatite nel gatto

Michael D. Willard DVM, MS, Dipl ACVIM, Professor, Texas A&M University

CANINE PANCREATITIS Canine pancreatitis usually presents with signs of vomiting and anor exia. Abdominal pain is frequently present, but it is easy to miss during physical examination. Fever is one of the least common signs. If acute pancreatitis is associated with or due to pancreatic carcinoma (rare), you may also see a dog that has widespread subcutaneous fat necrosis causing sterile abscesses that are typically painful and cause cutaneous discoloration. Most cases of canine pancreatitis are related to either ingestion of fat or lipemia associated with diabetic ketoacidosis. Trauma and drugs can also cause canine pancreatitis. Drugs that are suspected of causing pancreatitis in people and animals include acetaminophen, aminosalicylic acid, asparaginase, azathioprine, cimetidine, corticosteroids, danazol, estrogens, furosemide, metronidazole, nitrofurantoin, piroxicam, ranitidine, sulfasalazine, sulfonamides, tetracycline, and thiazides. Major point to remember: while vomiting is the most common sign of pancreatitis in the dog, some dogs (especially those with hepatic abscesses) may have relatively mild, intermittent vomiting and continue to eat a reasona ble amount of food. There is no readily available biochemical test that has good positive or negative predictive value. Canine TLI is probably better than amylase and lipase, but is still not as sensitive or specific as desired. We have seen dogs with pancreatitis that had normal serum TLI's. Serum lipase and amylase activities are insensitive and nonspecific for pancreatitis. Dogs with acute pancreatitis and even pancreatic abscesses have had normal serum lipase activities. We have also identified dogs with drastically increased serum lipase activities that have intestinal foreign objects or gastritis, but no gross evidence of acute pancreatitis. Lipase is produced by the canine gastric mucosa which explains why inflammation or damage to the stomach can result in excessive serum lipase activity. Blockage of the main pancreatic duct due to swelling due to inflammation,an intrapancreatic granuloma, or an abscess that subsequently blocks the pancreatic duct may cause extrahepatic biliary tract obstruction with a notable increase in serum alkaline phosphatase and serum bilirubin. In fact, pancreatitis is probably the most common cause of extrahepatic biliary tract obstruction in the dog. However, while the triad of vomiting, abdominal pain, and icterus is consistent with acute pancreatitis (as well as many other diseases), relatively few dogs with acute pancreatitis evidence these changes. Furthermore, there are reasons besides acute pancreatitis for this triad of signs (e.g., cholangi-

tis-cholangiohepatitis). Ultrasonographic evaluation of the abdomen (discussed below) is particularly helpful in these patients. Major point to remember: serum amylase and lipase are absolutely unreliable in looking for canine pancreatitis; they have false positive and false negative results too frequently to be of use in diagnosing pancreatitis. CBC's often show an inflammatory leukogram, but 1) this is a relatively nonspecific finding and may be due to any number of problems and 2) not all animals with acute pancreatitis have a notable leukocytosis. Major point to remember: there are no findings on CBC, profile, or urinalysis that definitively diagnose or definitively eliminate pancreatitis. Plain abdominal radiographs help eliminate other diseases which may mimic acute pancreatitis. Not finding evidence of other abdominal disease (such as a foreign object) is helpful in eliminating obstruction and narrowing the list of differential diagnoses. Occasionally, one will find radiographic signs which specifically suggest acute pancreatitis: A sentinel loop (i.e., a dilated, air-filled segment) in the descending duodenum, lack of serosal detail in the upper right abdominal quadrant, lateral displacement of the descending duodenum on the ventro-dorsal projection, a mass medial to the descending duodenum (on the ventro-dorsal projection) and/or a mass just behind the liver and just below the pylorus (on the lateral projection) are suggestive of pancreatitis. These findings are only meaningful if present; many dogs and cats with acute pancreatitis do not have these radiographic findings. Major point to remember: radiographs may tell you that there are changes consistent with pancreatitis and also eliminate other diseases (e.g., foreign object, obstruction) that can mimic pancreatitis. Abdominal ultrasonography often finds abnormalities that suggest or are consistent with pancreatitis. One may sometimes detect hypoechogenicity in the region of the pancreas that is due to inflammation. At other times, a thickened pancreas may be found. One of the most diagnostic findings is a pancreatic mass. Evidence of extrahepatic biliary tract obstruction (which requires seeing dilated bile ducts, not just a big gall bladder) is very suggestive of pancreatitis. Major point to remember: ultrasonography (performed by an accomplished operator) is probably the best (i.e., the most sensitive and most specific) and the fastest test for pancreatitis in the dog (but not necessarily the cat). Surgical diagnosis of pancreatitis is, fortunately, uncommon in the dog. However, if surgery is performed on a dog with possible pancreatitis, one should note the following points: A pancreas may look normal and still have inflam-

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matory infiltrates. You need to biopsy it to know for sure what is happening. Never simply look at what appears to be an obviously neoplastic mass in the pancreas and make a diagnosis without biopsying it. In the dog, pancreatitis is much more common than pancreatic carcinoma. It is important that you obtain a deep biopsy (you must get deeper than the superficial necrotic surface). Cytology is a useful procedure for making a presumptive diagnosis; however, I have seen at least one case in which cytology of a pancreatic mass was read out as carcinoma by two accomplished cytologists and yet multiple biopsies all came back as necrotic pancreatitis. Major points to remember: there appears to be more risk of causing iatrogenic pancreatitis with surgery in the dog than in the cat. Maintaining excellent mesenteric perfusion and performing the surgery with reasonable care and good technique minimizes the risks. However, it seems that biopsy is seldom needed to diagnose pancreatitis in the dog, which is perhaps different than what happens in the cat. Chronic, recurrent pancreatitis (i.e., chronic pancreatitis with intermittent, relatively mild recurrences) can be very challenging to diagnose. Dogs with episodic vomiting due to recurrent bouts of pancreatitis may not have any other signs of disease, and they invariably are admitted to your clinic for a work up after the last bout has run its course or is on the mend. Episodes of vomiting and anorexia due to recurrent pancreatitis can be random and unpredictable. In such patients, the previously mentioned diagnostics may be attempted, especially when acute exacerbations occur. Upper gastrointestinal barium contrast radiographs may rarely reveal duodenal abnormalities (e.g., dilatation, stricture) which suggest that recurrent bouts of acute pancreatitis have caused scarring of the pancreas which in turn have compromised the maximum size of the duodenal lumen. Major points to remember: strict adherence to an ultra-low fat diet and observation of the animal's response may be the only way to presumptively prove that recurrent pancreatitis is responsible for clinical signs. Abdominal ultrasonography is another excellent method to try to diagnose this smoldering disease process. If these two approaches fail, surgical biopsy of the pancreas may be necessary for diagnosis. Therapy for acute pancreatitis principally consists of nothing per os plus aggressive IV fluid therapy. Subcutaneous administration of fluids is clearly inferior for all but the mildly affected animals. This symptomatic management is often suf ficient, even in dogs in which a pancreatic granuloma has temporarily blocked the main bile duct. Adequate pancreatic circulation is probably necessary for healing of the damaged tissue; therefore, unless the patient has congestive heart failure or oliguric renal failure, it is far better to provide a little too much fluid rather than a little too little fluid. Remember that the abdominal viscera is not "first in line" to receive circulation when the patient is dehydrated, as most dogs with pancreatitis are when they come to your office. Remember that obese and fat dogs (which describes a lot of dogs with pancreatitis) do not have skin tenting when they are dehydrated. Likewise, although you might expect dry, tacky oral mucus membranes, a nauseated animal may be salivating enough to make the mucus membranes moist even though it is dehydrated. If the dog is not eating or drinking and is vomiting, it is dehydrated regardless of how

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it looks on physical examination. Major point to remember: the most common therapeutic errors are to start feeding the dog too soon, to underestimate dehydration, and to underestimate ongoing losses via vomiting. One should monitor the serum albumin concentration during fluid therapy in these patients. If the serum albumin concentration decreases significantly, then the plasma oncotic pressure likewise decreases which diminishes the effective perfusion of cells at the capillary level. Since perfusion is so critical to treating dogs with pancreatitis, one should become concerned whenever the serum albumin concentration falls below 2.0 gm/dl. The most common error in administering plasma is to administer too little to significantly raise the plasma albumin concentration. Remember that half of the albumin that you administer will end up in the interstitial compartment instead of the intravascular compartment. Hetastarch is probably helpful since it will improve plasma oncotic pressure and help microcirculation in patients that are becoming hypoproteinemic. Administration of plasma might also restore circulating protease inhibitors. Although this intuitively makes sense, this approach has also not been proven to be efficacious. Major point to remember: do not wait too long to administer plasma or hetastarch and be sure to check the serum albumin concentration after administering plasma to be sure that you have accomplished your goal. Total parenteral nutrition seems to be very useful in our patients with severe disease. We have not performed a double-blinded trial, but we seem to lose very, very few of the animals that we treat with this modality. However, it is expensive and labor-intensive. Alternatively, one might try using an enterostomy tube that is placed well below the level of the duodenum. We do not know if such therapy is effective, but it would be a reasonable approach in a patient that seems to need special nutritional therapy. Beyond withholding food and fluid therapy, almost everything else imaginable has been tried (even radiation), but nothing else has been found that is consistently effective. Antibiotics have been used to prevent infection of the inflamed pancreas which is supposed to be "fertile ground" for infection. Drugs designed to decrease pancreatic secretion have been disappointing, which is not surprising when one considers that acute pancreatitis may be associated with pancreatic hyposecretion instead of hypersecretion. Corticosteroids probably should not be used unless the patient is in severe shock due to the pancreatitis and you are desperate to reduce inflammation. Even then, the usefulness of steroids in these patients is unproven. Steroids are probably best used as a one-time or twice only therapy in these patients, but future work remains to confirm or deny this. Although it would seem to be helpful to treat early DIC (which can probably make acute pancreatitis worse),heparin therapy has not been shown to be useful in treating acute pancreatitis. Major points to remember: you cannot substitute antibiotic, parasympatholytics, steroids, and antiemetics for good fluid therapy and withholding all oral intake. Watch the serum albumin concentration and consider total parenteral nutrition. Analgesics can be very useful in animals with substantial abdominal pain. This does not mean that every patient with pancreatitis needs analgesics; the simplest way to determine

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if analgesics are needed is to ask yourself if you would want them if you were the patient. Whether or not to perform surgery on a dog with pancreatitis is probably one of the hardest therapeutic decisions in small animal internal medicine. Strict guidelines cannot be given, but some basic principals may be suggested. In general, one must realize that unless an abscess, pseudocyst, and/or an obstructed gall bladder with a bacterial infection are found, surgery will probably not benefit the patient (and may even be detrimental -- anesthesia is usually associated with some decrease in visceral perfusion unless great care is taken to maintain circulation). Ultrasonography should find most lesions that would be benefitted by surgery, except perhaps for widespread necrosis. If one is uncertain whether or not a cyst or abscess might be present and might be responsible for appropriate medical therapy being ineffective, one may reasonably decide to explore the area surgically. However, this decision should be based on the finding that 5-7 days of excellent, supportive medical management has been unsuccessful. That is why it is important to provide the best possible medical management when first confronted with the patient with suspected acute pancreatitis. I will usually try aggressive medical therapy for 5-8 days, depending upon how quickly the patient is decompensating. If I have not indication that optimal medical therapy is helping after 7-9 days, then I will seriously consider surgery. If a pseudocyst or abscess is not found, lavaging the area and resecting obviously necrotic tissue might help the patient, but this is uncertain. In people, there are conflicting data as to whether daily lavage of the pancreas and surrounding area is helpful or not. One might also consider putting in an enterostomy tube that enters the jejunum well below the level of the duodenum. Major point to remember: excellent medical therapy performed initially may seem to be more expensive, but will ultimately save money when the patient has severe disease and these difficult decisions must be made . Prognosis is difficult to predict. Hyperbilirubinemia is not necessarily a poor prognostic sign; pancreatic granulomas causing icterus due to obstruction of the bile duct often resolve if the patient receives appropriate supportive therapy. Hypocalcemia (used to prognosticate in people) is infrequently found in dogs and cannot be used to predict the outcome. In general, a patient with a pancreatic abscess has a guarded to poor prognosis, although some patients survive. Finding a degenerative left shift and/or a marked thrombocytopenia (probably due to DIC) are not known to be prognosticators, but one intuitively fears that a poor outcome is more likely.

FELINE PANCREATITIS Feline pancreatitis tends to have different causes, clinical signs, means of diagnosis,and treatments than what is found in canine pancreatitis. While dietary fat, trauma, and drugs (e.g., azathioprine) appear to be the principle causes of canine pancreatitis, feline pancreatitis can be caused by herpes virus infection, feline infectious peritonitis, toxoplasmosis, organophosphate intoxication, trauma, hepatobiliary infections, drugs (e.g., acemannan) and certain flukes (e.g., Eury-

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trema procyonis and Amphimerus pseudofelineus). It may seemingly occur after anesthesia or sedation in some cats. In other cases it appears to be idiopathic. There is no the clear association with dietary fat, as is seen in dogs. The preliminary observation has been made that Siamese cats may be at increased risk for pancreatitis. There is no evidence of a correlation of a diagnosis of feline pancreatitis with obesity. In fact, many cats diagnosed with pancreatitis have been underweight. Finall y, there is no obvious age or sex predilection. It seems that some cats have a triad of IBD, hepatitis, and pancreatitis. In such cases, the question is whether the pancreas is the cause of the problem or the effect of the problem. Major point to remember: cats have different causes of pancreatitis than dogs have. The clinical signs of pancreatitis in cats are much more varied than in dogs. While most dogs demonstrate anorexia and vomiting, affected cats may evidence just anorexia and/or just weight loss, both with or without vomiting. Icterus may or may not occur. In one experimental study, cats with pancreatitis induced by infusion of oleic acid into the pancreatic duct evidenced depression, transient fever, rare or no vomiting, and abdominal discomfort during abdominal palpation. In a retrospective study of 40 cats with naturally occurring pancreatitis, the three most common signs in 32 cats with pancreatic necrosis were lethargy to the point of being moribund (100%),partial to complete anorexia (84-97%), and dehydration (92%). Hypothermia, not fever, was the next most common sign (68%) and only 35% were found to be vomiting. Other clinical signs included abdominal pain (25%), abdominal mass (23%), diarrhea (15%), and dyspnea(15%). When acute pancreatitis occurs in cats with hepatic lipidosis, abdominal effusion (which may only be detected with ultrasonography) seems to be relatively common. However, personal experience has shown that this is not necessarily a sensitive or specific finding. Approximately 1/3 of cats with pancreatitis also have intestinal pathology and 42% have interstitial nephritis. Occasionally, thrombosis and/or petechiation will also be seen. Finally, affected cats that are depressed and dehydrated may become constipated. In one report, feline pancreatitis seemed to follow a two-stage course. First there was a chronic illness composed of weight loss, anorexia, and lethargy, with or without vomiting. Next, there was a sudden decompensation which was noted by finding the animal going into shock. However, this state of shock was not necessarily associated with a classic acute abdomen evidencing abdominal pain. Major point to remember: pancreatitis in cats may have extremely vague clinical signs and vomiting is often absent. At times is seems to present with clinical signs that are strongly suggestive of primary hepatic disease . Feline pancreatitis can be relatively difficult to diagnose, not only because the clinical signs can be so vague, but because there is little or no consistency in clinical pathology findings. Although elevated serum lipase activities have been shown to be relatively consistent and diagnostic in cats with experimental pancreatitis, this has not been the case in cats with spontaneous pancreatitis. In general, serum amylase and lipase activities in sera from cats with spontaneous pancreatitis are usually normal. In one study of 32 cats with naturally-occurring pancreatic necrosis, the most common

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laboratory findings were hypocalcemia (45%), hypokalemia (56%), increased BUN (57%), hyperglycemia (64%), hypercholesterolemia (64%), increased ALT (68%), increased SAP (50%), and hyperbilirubinemia (64%). It is noteworthy that only 30% had a leukocytosis while 15% had leukopenia. Major point to remember: cats with pancreatitis may have clinical pathology findings suggestive of hepatic disease. Feline TLI might (??) be helpful if it is substantially increased over normal (i.e., > 300); however, a normal finding or a modest increase (e.g., 100-200) does not eliminate pancreatitis. Be sure that the TLI is designed for use in the cat as opposed to the dog. Dr. David Williams at Texas A&M University (409-845-9053) is the only investigator currently able to offer this test in the cat. Abdominal radio graphs and ultrasonography are useful if they reveal suggestive abnormalities. Ultrasonographic abnormalities may include masses, hypoechoic areas in the pancreas, and/or dilated bile ducts. However, although the specificity of these findings for pancreatitis is believed to be high, the sensitivity of radiography and ultrasonography for detecting feline pancreatitis appears to be poorer than what is seen in the dog. In general, ultrasound appears to probably be more useful at finding pancreatitis in dogs which have a relatively large organ compared to cats. Biopsy of the pancreas appears to be a sensitive and specific means of diagnosing feline pancreatitis. Biopsy may be performed during exploratory laparotomy or laparoscopy. Many times, obvious gross findings suggestive of pancreatitis may be seen (e.g., hyperemia, saponification of fat, diffusely firm, adhesions, hemorrhage). However, we do not know how reliably one can detect pancreatitis by the gross appearance of the pancreas. I have a friend who has twice diagnosed pancreatic carcinoma after biopsying a grossly normal pancreas in a cat. In general, it appears that if the cat is well-perfused and reasonable care is taken to prevent the pancreas from drying out or from being excessively manipulated, the chance of iatrogenic pancreatitis is relatively minimal. If there are numerous adhesions, take care so that the pancreatic biopsy is deep enough to ensure that underlying pancreatic tissue is obtained, and not just overlying saponification and adhesions. A pancreatic carcinoma may have attendant inflammation which is superficial to the malignant cells. Major point to remember: pancreatic biopsy should be considered in cats with vague disorders that might be consistent with pancreatitis (which is almost any sick cat). Therapy for feline pancreatitis is aided by finding and treating the underlying cause, whenever possible. However, a substantial number of affected cats seemingly have idiopathic pancreatitis. Coincident diseases, such as diabetes mellitus, should be treated when they are present. One needs to replace fluid and electrolyte deficits as well as maintain

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them. Healing of a damaged pancreas is probably dependent upon there being adequate perfusion; therefore, one should be relatively aggressive in administering fluids. If the patient is becoming hypoproteinemic, either plasma or a colloid (e.g., hetastarch) should be considered to maintain normal fluid mechanics at the level of the capillary. Administration of plasma may also replace protease inhibitors that are used up by binding to proteases that escape into the blood. Release of such proteases is thought to be one mechanism which can result in acute death in some patients. Plasma may also replace clotting factors that are consumed if disseminated intravascular coagulation is occur ring. Antibiotics have been used in cats with pancreatitis. The majority of cases of feline pancreatitis are sterile. However, occasional cats have septic pancreatitis; therefore, administration of antibiotics is reasonable. There is some evidence that acute pancreatitis renders the pancreas more susceptible to infection from bacteria that enter the blood as well as those that translocate through the colonic wall. One study found that cefotaxime (a third generation cephalosporin) significantly reduced the incidence of pancreatic infection in cats that had experimentally-induced pancreatitis and infusion of E. coli into the pancreatic duct. Major point to remember: as in dogs, it is doubtful that antibiotics will cure the pancreatitis, but they may still be useful to prevent a secondary infection. Corticosteroids have also been used in these patients, ostensibly to decrease inflammation. Although steroids can cause hyperlipasemia and/or hyperamylasemia, it is doubtful that they often cause overt pancreatitis. There is the concern that steroids might allow pancreatitis to persist or worsen, but there are no data that strongly support that suspicion. A clinical observation by some clinicians is that selected patients seem to be benefitted be steroids, especially if the steroids are used for a limited time early in the course of the disease. In contrast to the dog, it is not clear that feeding low fat foods is beneficial during or after the acute episodes. However, IF the cat is vomiting, food should probably be withheld until vomiting ceases. None-the-less, I will feed the cat as soon as it will hold down food. Starving a cat seemingly does little or no good, and may cause major problems. It seems reasonable to feed low fat foods on the chance that fat is important in some cats with pancreatitis, but I would not delay feeding in order to use a low fat diet (e.g., if you can start NE feeding with a liquid diet, do so instead of waiting a day or two to have an E-tube or G-tube placed). In animals with protracted vomiting, parenteral nutrition is advantageous, albeit expensive. Antiemetics may be used if vomiting is severe; chlorpromazine is usually the most effective one although metoclopramide may be helpful in some patients.

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Procedure diagnostiche per la diagnosi precoce delle malattie renali Andrea Zatelli Med. Vet., Libero professionista, Reggio Emilia

Il glomerulo, il tubulo, l’interstizio e la componente vascolare possono essere interessati da processi patologici di varia intensità ed eziologia che ne determinano la distruzione attraverso incontrollati meccanismi infiammatori. L’evoluzione della patologia renale è legata a fattori individuali e coinvolge parametri istologici e funzionali che devono essere valutati concomitantemente al fine di raggiungere una diagnosi istologica e funzionale che ci permettano, quando possibile, di instaurare una terapia mirata il più precocemente possibile. Le alterazioni istologiche e funzionali dipendono da localizzazione, tipo ed intensità del danno. Da un punto di vista istologico riconosciamo tre stadi evolutivi della patologia renale: 1) fase iniziale caratterizzata da infiltrazione cellulare ed essudazione; 2) fase cro nica caratterizzata da infiltrazione di macrofagi e monociti, nonché da vari gradi di infiltrazione cellulare parenchimale; 3) fase cronica avanzata caratterizzata da sclerosi e fibrosi d’organo. L’evoluzione infiammatoria della patologia renale è legata alla attivazione ed al rilascio di molecole biologicamente attive e procede in parallelo con l’evoluzione istologica, condizionandola e venendone condizionata. Da un punto di vista infiammatorio sono riconoscibili quattro stadi evolutivi, caratterizzati da markers cellulari (MC) e markers molecolari (MM): 1) iniziale contraddistinto dalla presenza di piastrine e PMN (MC) e fattori del complemento (C3c), 5-LO, IL-4,10, 13 e MAC (MM); 2) croni co iniziale caratterizzato da proliferazione parenchimale, macrofagi e TH1 (MC) e da IL-1, 2, 6, 8, TNF-α, 15-LO, PDGF e TGF-β (MM); 3) cronico avanzato con MC sovrapponibili a quelli identificabili nella fase cronica iniziale e con proteine della matrice come MM; 4) fase fibrotica nella quale prevalgono fibrosi e sclerosi. Allo stato attuale la biopsia è la metodica in grado di consentire l’identificazione della patologia in atto attraverso uno studio anatomopatologico in microscopia ottica convenzionale, immunoistochimico e , quando possibile, in micr oscopia elettronica. Una diagnosi patologica deve comprendere anche la stadiazione della stessa per fornire dei fattori diagnostici e prognostici corretti; a tale proposito proponiamo la seguente stadiazione delle glomerulonefriti membranose, membranoproliferative e mesangiali.

GN MESANGIALE Sulla base della classificazione di Churg e Sobin per la GN a depositi mesangiali di IgA (GN di Berger), al fine di monitorare la progressione della malattia renale, viene effettuata una valutazione semiquantitativa (range 0-4) dei seguenti parametri morfologici osservabili in microscopia ottica convenzionale: − ispessimento della matrice mesangiale − ipercellularità mesangiale − sclerosi mesangiale − aderenze flocculo-capsulari − presenza di semilune (epiteliali e/o fibrose)

GN MEMBRANOSA In patologia umana, per questa forma di GN viene a tutt’oggi utilizzata la classificazione originale di Ehrenreich e Churg del 1968, comprendente 4 stadi istologici; è ammesso da tutti gli autori che gli stadi della malattia, da I a IV, rappresentano fasi successive del processo patologico, per cui con il passare del tempo, pazienti con lesioni istologiche di tipo I e II tendono ad evolvere verso quadri istologici di tipo III e IV. Al fine di monitorare la progressione della malattia renale viene effettuata una valutazione semiquantitativa (range 0-4) dei seguenti parametri morfologici osservabili in microscopia ottica convenzionale: − presenza di spikes e depositi intramembranosi − ispessimento delle membrane basali dei capillari glomerulari − sclerosi del flocculo

GN MEMBRANO-PROLIFERATIVA Per questa forma di GN (definita anche GN mesangiocapillare), non esistono in patologia umana criteri di stadiazione universalmente riconosciuti; tuttavia lo studio di biopsie ripetute nel tempo, ha dimostrato variazioni del quadro morfologico, con progressione del danno glomerulare (estensione delle lesioni della parete capillare, accentuazione nodulare del mesangio, sclerosi glomerulare).

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Al fine di monitorare la progressione della malattia renale viene effettuata una valutazione semiquantitativa (range 0-4) dei seguenti parametri morfologici osservabili in microscopia ottica convenzionale: − lobulazione del flocculo − essudazione glomerulare (presenza di elementi infiammatori) − doppi contorni delle membrane basali dei capillari glomerulari − sclerosi del flocculo − presenza di semilune (epiteliali e/o fibrose) L’evoluzione istologica ed infiammatoria della patologia sono correlate ad una involuzione funzionale che dipende dalla localizzazione e dalla entità della lesione. Molti clinici utilizzano la concentrazione sierica della creatinina come metodo di valutazione della funzionalità renale. In realtà la creatinina sierica è un pessimo indicatore di funzionalità renale ed un suo aumento oltre i limiti di normalità è da correlare ad un danno parenchimale che coinvolge una percentuale variabile dal 70% all’80% dei nefroni. La metodica elettiva per lo studio della funzionalità renale è rappresentata dalla determinazione del Tasso di Filtrazione Glomerulare (TFG). Misurare il TFG è spesso laborioso anche se rappresenta un passaggio obbligato per la valutazione della funzionalità renale in pazienti che hanno una creatininemia sierica nel range elevato di normalità. Molti clinici, per la determinazione del TFG, utilizzano la clearance della creatinina endogena; questa metodica, benché semplice, non è attendibile nel gatto e nel cane di sesso maschi le (ha la capacità di secernere e riassorbire questo marker endogeno a livello tubulare). La concentrazione sierica di creatinina è inoltre influenzata dalla massa muscolare, dallo stato muscolare e dall’età. Il test della clearance della creatinina endogena dovrebbe quindi essere interpretato in base alle condizioni del singolo paziente ed effettuato esclusivamente nelle cagne. Le metodiche utilizzabili per il calcolo del TFG si basano sull’utilizzo dell’inulina come marker di filtrazione glomerulare o sulla scintigrafia renale. La determinazione del TFG mediante inulina è attendibile ed a basso rischio anche se presenta lo svantaggio di lunghi tempi, ospedalizzazione del paziente e molteplici prelievi ematici da effettuare; rispetto alla tecnica scintigrafica ha lo svantaggio di determinare la clearance renale totale del paziente. La metodica migliore per lo studio della funzionalità renale è rappresentata dalla scintigrafia renale. L’applicazione della me-

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dicina nucleare in questo campo si è dimostrata, rispetto alle altre metodiche utilizzate, attendibile, sicura, veloce e comparativamente non dispendiosa. La scintigrafia renale con 99mTecnezio acido-DTPA offre inoltre la possibilità di valutare con un unico esame la funzionalità di ogni singolo rene. L’ecotomografia renale è un esame utile, non dispendioso, veloce e sicuro che ogni nefrologo dovrebbe effettuare tempestivamente al paziente nefropatico. Il Dott. O’Neil di Atlanta ha scritto con un po’ di ironia che sono essenzialmente tre i motivi perché l’esame ecografico non venga effettuato ad un paziente nefropatico: 1) non avere le mani; 2) non avere la vista; 3) non avere il paziente. La possibilità di non possedere un ecografo non viene contemplata in quanto è possibile riferire il paziente presso un centro attrezzato. L’ecografia renale in corso di insufficienza renale acuta e/o cronica è utile per uno studio morfologico, strutturale, vascolare ed offre possibilità di indirizzo diagnostico nei casi di litiasi, calcificazione, ostruzione con idronefrosi, nelle patologie focali o diffuse correlate a masse e non (infarto renale), nell’identificazione di forme cistiche singole (semplici, complicate) o multiple, nelle pseudocisti, negli ematomi, negli ascessi sottocapsulari. L’ecografia renale è inoltre utile per l’esecuzione di metodiche diagnostiche miniinvasive quali le procedure bioptiche, le pielografie translombari, le centesi per campionature destinate ad esami citologici e/o colturali. Molte patologie renali risultano trattabili se diagnosticate con tempestività e molte “insufficienze renali acute rite nute risolte” evolvono liberamente da un punto di vista infiammatorio ed istologico perché la patologia in atto spesso non viene diagnosticata e trattata portando un paziente affetto da insufficienza renale acuta ad essere un paziente affetto da insufficienza renale cronica. Ricordiamo le nozioni di insufficienza renale cronica ed acuta accettate dalla Società Internazionale di Nefrologia: “La nozione di insufficienza renale cronica implica che il filtrato glomerulare è ridotto in maniera irreversibile. Questa definizione è usata in maniera estensiva includendo anche una compromissione lieve del filtrato glomerulare. L’evidenza della cronicità è fornita da misure cliniche mul tiple del filtrato glomerulare che ne documentano la ridu zione stabile o un declino più o meno graduale nel tempo. La nozione di insufficienza renale acuta implica un de clino rapido della funzione renale che si è stabilito in un ar co di tempo variabile da poche ore a settimane, potenzial mente reversibile”.

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Trattamento in fase precoce delle malattie renali Andrea Zatelli Med. Vet., Libero professionista, Reggio Emilia

La terapia delle malattie renali in fase precoce prevede due passaggi fondamentali: 1. terapia eziologica: riconoscere ed eliminare lo stimolo antigenico o la causa eziologica risulta di fondamentale importanza per il blocco e/o l’involuzione del processo patologico glomerulare e/o interstiziale su base antigenica (ad es. le glomerulopatie paraneoplastiche risolvono dopo resezione della massa neoplastica). In diversi casi il riconoscimento dell’eziologia risulta impossibile e, di conseguenza, l’unica terapia attuabile è quella antinfiammatoria. Il riconoscimento ed il trattamento della causa risulta di fondamentale importanza anche nelle patologie renali che non riconoscono una base antigenica quali quelle su base emodinamica (ipertensive o ipotensive), neoplastica primara o metastatica, tossica e/o farmacologica, ostruttiva, litiasica, compressiva, secondaria a patologie sistemiche (es. ipercalcemia, diabete etc.);

2. terapia antinfiammatoria: è diretta alla modulazione del sistema immunitario che attraverso meccanismi umorali e cellulari determina l’evoluzione e la pr ogressione della patologia. Attualmente questo tipo di terapia si rivolge a meccanismi infiammatori locali. Una attenzione particolare meritano alcune patologie con presentazione acuta quali la Necrosi Tubulare Acuta (NTA) e la Nefrite Interstiziale Infiltrativa Acuta (NIIA) per la frequenza con cui si presentano in modo particolare nella specie canina; una diagnosi di certezza (mediante biopsia) di NTA o NIIA consente il trattamento della patologia in circa il 70 % dei casi con follow up positivo e restituzio ad integrum. Nel caso di NTA o NIIA spesso la terapia mirata viene attuata durante un iniziale periodo (10-15 giorni) di trattamento emodialitico che consente il mantenimento del paziente in condizioni fisiologiche ottimali.

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COMUNICAZIONI LIBERE e COMUNICAZIONI DALLE AZIENDE

Le comunicazioni sono elencate in ordine alfabetico secondo il cognome dell’autore presentatore.

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TRATTAMENTO CHIRURGICO DELLA SINDROME DI WOBBLER NEL CANE CON DISTRAZIONE ED INSERZIONE INTERVERTEBRALE DI METILMETACRILATO. RISULTATI A BREVE E LUNGO TERMINE IN 8 CASI Adamo P. Filippo* Dipl. ECVN, Cherubini G., Mocavero A., Terrana M. *Libero professionista, Bagni di Tivoli (ROMA) Introduzione. Il trattamento chirurgico rappresenta potenzialmente la cura per la Spondilo Mielopatia Cervicale Caudale (SMCC), comunemente conosciuta come sindrome di Wobbler. Nelle varie tecniche chirurgiche esiste una significante morbidità e mortalità. Le numerose tecniche chirurgiche proposte evidenziano la variabilità del tipo di lesione e nessuna delle tecniche chirurgiche è universalmente riconosciuta come unica valida. Obiettivo. Verificare la tecnica di distrazione vertebrale con inserzione di metilmetacrilato e fusione descritta da Dixon. Materiali e metodi. Il nostro studio comprende 8 casi con compressione dinamica ventrale. Le razze interessate erano 6 Dobermann, 1 Weimaraner e un Pastore Tedesco, età da 6 a 11 anni. Dei 6 Dobermann in 5 la lesione era a livello di C6-C7 ed in uno a C5-C6, nel Pastore Tedesco e nel Weimaraner a C5-C6. Tutti i soggetti avevano vari gradi di atassia e tetraparesi, un caso era tetraplegico tre giorni prima e migliorato a tetr aparesi dopo terapia cortisonica. Tutti i casi sono stati trattati chirurgicamente seguendo la tecnica di Dixon con ventral slot parziale, distrazione vertebrale, creazione di un difetto osseo nei due corpi vertebrali adiacenti, inserzione di metilmetacrilato in forma liquida e trapianto di spongiosa omerale. Al termine della chirurgia veniva eseguita una radiografia di controllo per valutare il posizionamento del metilmetacrilato ed il grado di distrazione vertebrale. In tutti casi è stato applicato un corpetto rigido per due mesi, ospedalizzazione per due settimane, valutazione radiografica dopo un mese, due mesi e sei mesi in anestesia generale. In tutti i casi si è valutato il recupero post-operatorio, i risultati clinici a breve termine (6-7 mesi) ed in quattro casi a lungo termine (2-3 anni). Infine i risultati ottenuti sono stati paragonati a quelli di altre tecniche. Risultati e discussione. In un caso il metilmetacrilato non correttamente posizionato si era dislocato ventralmente con parziale collasso dello spazio intervertebrale, tale evento non influiva sulle condizioni cliniche. In tutti i casi al controllo radiografico a due mesi e sei mesi si è osservata notevole proliferazione ossea ventralmente allo spazio intervertebrale con assenza di fusione ventrale delle due vertebre. Nelle radiografie in distrazione lineare si osservava il permanere di un certo grado di mobilità dello spazio intervertebrale. Tutti i soggetti hanno ben tollerato il corpetto rigido. In tutti i casi il recupero post-operatorio è stato eccellente e si è osservato un progressivo recupero delle condizioni neurologiche rispetto a quelle pre-operatorie. Nei quattro ca si ad un follw-up medio di 26 mesi non si sono osservati segni clinici di recidiva. Paragonando questa tecnica con altre tecniche abbiamo osservato gli stessi vantaggi riportati nella distrazione con chiodi o viti e cemento e con viti e rondella + fusione: rapida decompressione spinale, rapida decompressione radici nervose, nessuna manipolazione spinale, trattamento di lesioni multiple; vantaggi aggiuntivi includono: assenza di possibile danno iatrogeno spinale e del collasso dei piatti vertebrali e manualità chirurgica più semplice. Come svantaggio è da considerare la necessità di un corpetto rigido che risultava comunque essere ben tollerato. Nei nostri casi nel follow-up a lungo termine non si osservava clinicamente l’effetto domino, è possibile che la conservata mobilità dello spazio intervertebrale impedisca un carico esagerato di forze sullo spazio intervertebrale adiacente. Conclusioni. Nel trattamento della SMCC la tecnica descritta da Dixon sembra essere molto promettente soprattutto per la minore incidenza dell’effetto Domino, sarà comunque necessario verificarne l’efficacia su un numero maggiore di casi.

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TRATTAMENTO CHIRURGICO DI TRE MENINGIOMI CEREBRALI DELLA FOSSA CRANICA ANTERIORE NEL GATTO Adamo P. Filippo* Med. Vet., Dipl. ECVN, Cherubini G., Terrana M., Mocavero A., Cantile C. *Libero professionista, Bagni di Tivoli (ROMA) Introduzione. I meningiomi sono i tumori cerebrali più comuni nel gatto, la loro localizzazione è prevalentemente sopratentoriale, a volte sono presenti in forma multipla, generalmente non sono infiltranti ed hanno di solito un comportamento biologico benigno. La lenta crescita tumorale è responsabile del carattere subdolo e progressivo della sintomatologia clinica. I segni neurologici dipendono dalla localizzazione del tumore. Nei tumori della fossa cranica anteriore le alterazioni neurologiche sono frequentemente caratterizzate da cambio di comportamento, cambio della personalità, deficit della visione, cammino compulsivo e movimenti di maneggio. Materiali e metodi. Vengono qui descritti tre casi di meningioma cerebrale parieto-occipitale nel gatto integrando i dati clinici e di laboratorio con le immagini TC pre e post contrastografiche cerebrali. Tutti i soggetti sono stati sottoposti a terapia chirurgica. I gatti erano tutti di razza comune europea, di sesso femminile, sterilizzati e di età rispettivamente di 16 anni, 12 e 11 anni Esame neurologico. Le alterazioni neurologiche comuni in tutti casi erano stato del sensorio stuporoso, atassia locomotoria, cammino compulsivo, movimenti di maneggio, deficit propriocettivi controlaterali alla sede della lesione e diminuzione della visione. In un caso il gatto aveva smesso di fare le fusa da due mesi e aveva iniziato da due settimane a lanciare urla improvvise immotivate. Localizzazione neuroanatomica. In due casi le alterazioni riscontrate all’esame neurologico consentivano una localizzazione intracranica nel cervello anteriore di destra ed in un caso nel cervello anteriore di sinistra. Indagini diagnostiche. Le indagini diagnostiche sono consistite in esami ematologici, delle urine, sierologici per FIP, FeLV, FIV e Toxoplasmosi, misurazione della pressione venosa periferica e TC cerebrale. Di valore diagnostico in tutti i casi è risultato l’esame TC cerebrale. La TC pre-contrastografica ha rivelato in tutti e tre i casi aree di calcificazioni intralesionali. La TC dopo contrasto ha evidenziato una lesione con impregnazione omogenea, a margini ben limitati; in due casi in area cortico-occipitale destra ed in un caso cortico-occipitale sinistra. L’indagine TC suggeriva in tutti i casi una diagnosi presuntiva di meningioma. Terapia. Tutti i casi sono stati trattati chirurgicamente attraverso un approccio rostrotentoriale standard. Risultati e discussione. In due casi è stato possibile asportare completamente la lesione, in un caso la massa aveva invaso ed oltrepassato il tentorium cerebellum ed aveva aderenze con il seno sagittale mediano. In quest’ultimo caso nella fase di risveglio si è verificato un progressivo deterioramento delle condizioni cliniche, midriasi, assenza del riflesso pupilare diretto e consensuale e arresto respiratorio. I segni neurologici facevano presupporre la presenza di una lesione progressiva pontino-mesencefalica. Nei due gatti sopravvissuti la TC con mezzo di contrasto post-operatoria rilevava la completa asportazione macrosco pica della lesione. In un gatto la TC di controllo dopo sei mesi mostrava assenza di recidive. Nei due gatti sopravvissuti il recupero delle alterazioni comportamentali avveniva in pochi giorni, mentre la persistenza dei disturbi della visione nell’occhio controlaterale alla lesione risultava persistente. Conclusioni. I meningiomi cerebrali del gatto hanno delle peculiari caratteristiche pre e post-contrastografiche in TC. Per le loro caratteristiche nel gatto, i meningiomi cerebrali localizzati in zone chirurgicamente accessibili possono essere facilmente asportati ed offrire una prognosi favorevole.

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UN CASO DI FISTOLA RETTO VAGINALE ASSOCIATA AD ATRESIA ANI IN UN GATTO COMUNE EUROPEO Allievi Graziano* Med. Vet., Olivieri Massimo** Med. Vet. *Libero professionista, Rovello Porro (CO) **Libero professionista, Samarate (VA) L'evenienza di una fistola rettogenitale è rara nel gatto e di solito associata a condizioni di anus imperforatus o di atresia ani. Dal momento che solitamente la fistola è di modeste dimensioni, solo materiale fecale liquido o semiliquido è in grado di passare attraverso questa. Nei pochi casi riportati in letteratura è segnalato che, normalmente, il tempo di sopravvivenza di quei soggetti è breve (4-5 mesi), e che spesso possono associarsi infezioni ascendenti delle vie urinarie. Ne consegue che, in questi casi, è necessario attuare precocemente una profilassi antibiotica, nonché programmare l'intervento chirurgico non appena le condizioni cliniche generali lo consentano. Le possibili opzioni chirurgiche sono due: la prima prevede di chiudere primariamente la fistola e di effettuare uno stoma nel punto in cui avrebbe dovuto trovarsi lo sfintere anale; in alternativa nei soggetti molto piccoli sarebbe teoricamente possibile, per ridurre i tempi operativi e i rischi anestesiologici, stadiare l'intervento in due tappe separate: una prima di creazione dello stoma e una seconda di chiusura della fistola. Letizia faceva parte di una cucciolata di gattini europei che a 45 giorni di vita è stata portata presso la nostra struttura per una visita di routine. L'anamnesi riferiva che la gattina aveva continuamente diarrea ed era incapace di controllare la defecazione. Alla visita clinica veniva rilevato che Letizia, oltre ad essere di dimensioni nettamente inferiori rispetto ai fratelli, non aveva lo sfintere anale, e che feci liquide uscivano dalla vulva. Uno studio contrastografico permetteva di confermare la diagnosi di fistola retto-vaginale e di atresia ani. Poiché le condizioni cliniche di Letizia erano critiche e il suo peso di soli 320 grammi, si decise con i proprietari di portarla alle condizioni per poter effettuare una correzione chirurgica dell'anomalia. È stata instaur ata quindi una dieta iperdigeribile liquida e una profilassi antibiotica con amoxicillina 20 mg/kg per bocca ogni 12 ore. All'età di 3 mesi e con un peso di 520 grammi, in condizioni cliniche non ancora ottimali, la gattina è stata sottoposta ad intervento chirurgico. Letizia è stata indotta con una miscela di diazepan e ketamina e mantenuta in anestesia con isofluorano. Eseguita un'incisione circolare nel punto in cui avrebbe dovuto trovarsi naturalmente lo sfintere anale, sono stati scollati i tessuti sottostanti fino a reperire il retto. Praticata un'incisione circolare anche nella parte terminale del retto, si procedeva a suturarlo alla cute con conse guente formazione di uno stoma del diametro di circa 1 cm. Si decideva invece di non cercare al momento la fistola vaginorettale per chiuderla sia perché le condizioni anestesiologiche non erano ottimali, sia perché si faceva affidamento sul fatto che, essendo piccola e non venendo più alimentata, potesse chiudersi spontaneamente. Dopo l'intervento Letizia fu ancora alimentata con cibi iperdigeribili e, non appena le feci divenivano troppo solide, veniva somministrato Lattulosio per os al dosaggio di 0,5 mg/kg per facilitare la defecazione. I controlli successivi evidenziarono una scomparsa delle feci dalla vulva, urine limpide, condizioni cliniche generali ottimali, un controllo della defecazione progressivamente migliorata e, dopo circa 3 mesi, il raggiungimento di un peso di 2,5 kg. Non è stato possibile ottenere una conferma radiografica dell'avvenuta obliterazione della fistola rettovaginale poiché Letizia è deceduta in seguito alle lesioni riportate in un'aggressione da parte di un cane.

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LA MIRINGOPLASTICA E TIMPANOPLASTICA,VIA TRANSMEATALE NELLE PERFORAZIONI TIMPANICHE DEL CANE Arcelli Rolando Med. Vet., Bellezza E. Med. Vet., Di Meo A. Med. Vet., Moriconi F. Med. Vet. Dip. Pat. Diagn. e Cli., Università degli Studi di Perugia Introduzione. La ricostruzione chirurgica della membrana timpanica per via transmeatale, in seguito a perforazioni post-traumatiche, è stata l’oggetto del nostro studio. Molte patologie acute e croniche del condotto uditivo esterno (c.u.e.) del cane hanno alla base una perforazione del timpano di natura traumatica dovuta perlopiù a corpi estranei, a traumi ottusi trasmessi dall’esterno o dall’interno come si può verificare accidentalmente durante l’esecuzione di visite otologiche. Obiettivi. Mettere a punto una tecnica che permetta il ripristino dell’integrità della membrana in quei casi dove questo non si verificherebbe sponteneamente per perdite di sostanza superiori al 40% o nei casi di perforazioni croniche. Materiali e metodi. La nostra casistica è costituita da 11 cani di razza e taglia diverse. Di questi, sette presentavano lesioni di limitate dimensioni della membrana paracentrale mentre gli altri avevano la rottura quasi completa. Le otoscopie come tutte le chirurgie sono state eseguite con coni da otoscopia adeguati, interposti fra microscopio operativo ed orecchio del paziente . Nel primo gruppo, dopo aver cruentato i margini della lesione con un uncino, abbiamo impiegato del gel poroso di fibrina (gelita), modellandolo con le forbici, per ottenere un disco dello stesso diametro della membrana timpanica. Questo disco è stato compresso con pinze anatomiche per ridurre il suo spessore iniziale a circa 0,1 mm ed è stato fatto progredire attraverso il cono dell’otoscopio fino ad adagiarlo sul timpano. Nel secondo gruppo abbiamo eseguito una timpanoplastica tipo I (class. secondo Wullstein). Questa prevede la sostituzione della membrana danneggiata con diversi materiali che ricreino, dopo opportuna vascolarizzazione, un nuovo timpano. Abbiamo eseguito sempre per via transmeatale, un’incisione posteriore della cute del c.u.e. da ore 6 ad ore 12, a distanza di circa 8-9 mm dall’anulus, impiegando un bisturi curvo e del diametro di 2 mm. Successivamente abbiamo scollato la cute del condotto dalla nostra incisione fino al timpano, creando così una tasca idonea all’inserimento dell’innesto. La cavità timpanica è stata riempita di materiale riassorbibile (gelita), allo scopo di sostenere l’innesto ed impedirne l’adesione alla parete mediale della cassa. Abbiamo quindi modellato il materiale da tr apiantare per ottenere un disco di dimensioni superiori al timpano originale e posizionato in prossimità dell’incisione. La parte centrale è stata adagiata al di sopra del materiale residuo timpanico (over lay). Risultati e conclusioni. Negli animali sottoposti al primo intervento si è avuta chiusura della perforazione, normalizzazione dell’aspetto anatomico della membrana, scomparsa del quadro sintomatologico. In questo caso il disco posto sopra la membrana, funge da guida per una rapida ed uniforme cicatrizzazione. I soggetti sottoposti al secondo intervento oltre ad una completa attenuazione del quadro sintomatologico, presentavano, all’esame microscopico, una buona vascolarizzazione della neo membrana, discreta linearità, ed ottima stabilità. La scelta di una procedura rispetto all’altra dipende da dimensioni e sede della lesione e dalla sua cronicità. La miringoplastica di prima istanza, intervento più breve e di più facile esecuzione, può essere eseguito con successo solo in caso di lesioni di limitate estensioni dove l’aspetto dei margini della ferita non lascia presuppor re una guarigione spontanea della stessa.

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CARCINOMA RENALE COME PROBABILE CAUSA DI IPOGLICEMIA IN UN CANE Battaglia Luca* Med. Vet., Petterino Claudio** Med. Vet. *Libero professionista, Cavriago RE **Istituto di Patologia ed Igiene Veterinaria, Facoltà di Medicina Veterinaria di Padova Introduzione. L’ipoglicemia è una sindrome paraneoplastica da tempo riconosciuta e descritta sia nella letteratura umana che veterinaria: l’insulinoma, neoplasia delle cellule beta degli isolotti pancreatici, determina una ipoglicemia da aumento specifico di secrezione di insulina, mentre, numerose altre neoplasie sia di origine epiteliale (carcinoma epatocellulare, epatoma), sia di origine mesenchimale (leiomiosarcoma, emangiosarcoma), determinano ipoglicemia attraverso la secrezione di fattori cosiddetti insulino-simili. Sono descritte in medicina umana numerose manifestazioni paraneoplastiche conseguenza di neoplasie renali ma scarsi contributi pervengono dalla letteratura veterinaria. Caso clinico. Un cane meticcio, femmina sterilizzata, di anni 11 è stato riferito presso la nostra struttura a causa di una sintomatologia prevalentemente neurologica, associata ad una ipoglicemia persistente. Alla visita clinica il cane manifestava scialorrea, tremori, debolezza generalizzata, “head pressing”, iporiflessia spinale. L’anamnesi riferiva una insorgenza graduale dei sintomi con peggioramento marcato negli ultimi sette giorni. Veniva, inoltre, segnalata polidipsia e poliuria ed un miglioramento della sintomatologia dopo i pasti. Fu eseguito un prelievo di sangue per determinare rapidamente la glicemia che risultava inferiore a 40 mg/dl. Oltre agli esami emato-sierologici di base (emocromocitometrico, profilo epato-renale, protidogramma e status elettrolitico) sono state valutate l’insulinemia e le fruttosamine. L’insulina ematica, con un valore di 1,5 mU/ml (intervallo di riferimento 3-13 mU/ml) rendeva poco probabile l’iperproduzione della stessa da parte di una neoplasia delle cellule beta del pancreas. Gli altri parametri ematologici presi in considerazione non indirizzavano verso patologie specifiche. Infusioni endovenose di sol. glucosata al 5% permettevano una temporanea attenuazione della sintomatologia. La determinazione della glicemia a 4 ore dal pasto si manteneva, dopo ripetuti controlli, inferiore a 50 mg/dl. Si effettuarono indagini ecografiche e radiologiche che evidenziarono una massa retroepatica coinvolgente il rene destro (apprezzabile anche alla palpazione). Il rene sinistro non presentava particolari atipie. Erano altresì repertabili aspetti radiologicamente compatibili con metastasi a livello polmonare. Il proprietario accordò come ultima indagine l’esame citologico della neoformazione effettuato tramite ecoguida. La citologia risultò compatibile con neoplasia, pur non permettendo una chiara identificazione del comportamento biologico del tumore stesso. Ulteriori accertamenti venivano negati. La terapia proposta fu basata sulla somministrazione di glucorticoidi e sulla somministrazione dei pasti diverse volte durante il giorno per mantenere la glicemia entro livelli compatibili con la vita. Dopo venticinque giorni dalle dimissioni il cane fu sottoposto ad eutanasia a causa del grave scadimento delle condizioni generali. L’esame necroscopico rivelò una massa di circa 7 cm di diametro coinvolgente la parte caudale del rene destro e numerosi noduli localizzati sia al polmone destro che sinistro. Macroscopicamente altri organi non erano coinvolti. L’esame istologico effettuato sul rene destro e sui noduli polmonari permise di emettere una diagnosi di carcinoma renale tubular e, associato a nefrite interstiziale con metastasi a livello polmonare.

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POLIEDRICITÀ SINTOMATOLOGICA IN CORSO DI PKD FELINA; ESPERIENZA CLINICA IN DUE GATTI PERSIANI Beccati Massimo* Med. Vet, Giretto Daniela** Med. Vet. *Libero professionista, Capriate S.G. (BG) **Libero Professionista, Bordighera (IM) Introduzione. La sindrome del rene policistico (PKD) rappresenta una patologia degenerativa progressiva, di frequente riscontro nel gatto Persiano e razze correlate. Tale sindrome, dopo un decorso clinico solitamente asintomatico o comunque paucisintomatico, culmina in un quadro di insufficienza renale cronica, divenendo solo allora clinicamente manifesta. Nella nostra esperienza si descrivono due presentazioni clinico-anatomopatologiche insolite della PKD, caratterizzate nel primo caso da una sintomatologia esclusivamente oftalmica, mentre nel secondo caso da una dilatazione addominale a seguito di pseudocisti perirenale. Materiali e metodi. Un gatto Persiano femmina, di 10 anni, viene portato alla nostra attenzione, per un problema oftalmico rappresentato da una variazione di colore delle iridi e da una midriasi bilaterale associata ad una diminuzione del visus. Il soggetto non presentava alcun sintomo sistemico. L’esame oftalmologico ha indotto a sospettare una coroidopatia su base ipertensiva, confermata, poi, da indagini specifiche (analisi ematochimiche , doppler, rx, ecocardiografia). La successiva ecografia addominale ha evidenziato una nefromegalia bilaterale con un parenchima renale scompaginato da numerose neoformazioni a carattere cistico, ascrivibili a PKD, identificata quale causa primaria dell’ipertensione sistemica. Il paziente è stato, ed è tuttora, gestito terapeuticamente con amlodipina besilato (0,625 mg/die) ed è andato incontro ad un recupero della funzionalità visiva. Nel secondo caso, un gatto Persiano femmina di 8 anni, è stato portato alla visita clinica per una improvvisa (a parere del proprietario) dilatazione addominale, associata a poliuria, polidipsia, disidratazione ed anoressia. L’iter diagnostico improntato su indagini emato-urochimiche e radiologiche, ha deposto per una forma di insufficienza renale cronica in corso di PKD. In partico lare, l’esame ecografico dell’addome, ha messo in risalto la presenza di una g rossa neoformazione addominale a carattere cistico strettamente adesa al rene destro (rivelatasi in sede autoptica una pseudocisti perirenale); inoltre, in ambedue i reni, così come nel fegato, erano presenti strutture cistiche di dimensioni variabili. Discussione. Come l’analoga patologia descritta in ambito umano (ADPKD 1), la PKD felina è diagnosticabile fin dai primi mesi di età, grazie all’ausilio ecografico. Nel gatto Persiano e razze correlate, viene trasmessa geneticamente, in modo autosomico dominante. I sintomi clinici ad essa correlati, insorgono tardivamente (7-8 anni), e sono solitamente riconducibili a quelli di una insufficienza renale cronica aspecifica. Sebbene in corso di ADPKD nell’uomo la presenza di lesioni cistiche a livello epatico e/o ipertensione sistemica (come unico sintomo) siano relativamente frequenti, in medicina felina segnalazioni di questo tipo sono riportate sporadicamente. Nonostante l’eventuale precocità della diagnosi, la progressione della degenerazione renale è inevitabile, a dispetto delle terapie di supporto, volte alla gestione delle manifestazioni correlate. La patogenesi delle formazioni cistiche non è a tutt’o ggi completamente nota; tra i differenti meccanismi chiamati in causa vanno annoverati la proliferazione dell’epitelio tubulare e l’inversione di polarità, con traslocazione della Na/K ATPasi di membrana, delle stesse cellule tubulari; inoltre, nell’uomo, è stata recentemente sottolineata, a questo proposito, l’importanza dell’apoptosi cellulare caspasidipendente.

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ALTERAZIONI COAGULATIVE IN CORSO DI MIELOMA MULTIPLO NEL CANE ED INTERESSE AD UNA NUOVA METODICA PER LO STUDIO DELLA FUNZIONALITÀ PIASTRINICA Bertoldi Antonio Med. Vet., Furlanello TommasoMed. Vet., Caldin Marco Med. Vet. Liberi professionisti, Padova Introduzione. In corso di mieloma multiplo sono descritti fenomeni emorragici, anche se vi sono pochi dati riguardo alla loro eziopatogenesi. Nel caso che verrà descritto, l’utilizzo di una nuova metodica per la funzione piastrinica ha permesso di svelare l’origine della grave coagulopatia. Descrizione del caso clinico. In data 28-06-00 è stato visitato un cane meticcio maschio, di 10 anni d’età. Il proprietario riferiva di una profusa emorragia gengivale, insorta il giorno precedente dopo una detartrasi e di una dolorabilità osteoarticolare presente da circa due mesi, non imputabile ad alcuna causa apparente. All’esame fisico era presente pallore delle mucose e dolorabilità ossea alla palpazione. I principali dati patologici provenienti dagli esami di laboratorio erano anemia scarsamente rigenerativa (3,85 x 106/µl, riferimento 5,70-8,80; IR 0,4), neutropenia (2,66 x103/µL, rif. 3,9-8,0), iperazotemia (89 mg/dl, rif. 15-45), ipercalcemia totale (13,3 mg/dl, rif. 8,0-12,0), ipoalbuminemia (1.3 g/dl rif. 2,6-3,8) ed iperglobulinemia (9,8 g/dl, norm. 2,64,5). L’elettroforesi proteica presentava un picco monoclonale nelle beta-globuline. Nelle urine era presente proteinuria grave, con rapporto proteine/creatinina urinaria di 3.0 (rif. < 0.4). Il profilo coagulativo presentava allungamento del aPTT (19.6 sec., rif. 12,4-16,6) e diminuzione dell’ATIII (45%, rif. 80-120). PT, FDPs, D-dimeri della fibrina e fibrinogenemia erano compresi negli intervalli di riferimento. La causa del grave sanguinamento non era quindi giustificata dai dati sopra riportati, indici esaurienti dell’emostasi secondaria (plasmatica) ma non della emostasi primaria (piastrinica), ad eccezione della conta piastrinica, che era nella norma. Per lo studio della funzionalità piastrinica veniva utilizzata una nuova metodica di laboratorio (PFA-100, Dade Behring, USA), recentemente validata nella specie canina (Callan et al., ACVIM Proceedings, pag. 737, 2000), che utilizza campioni di sangue intero reso incoagulabile con sodio citrato 3,8%. Il campione prelevato dal paziente prima descritto presentava un tempo di aggregazione piastrinica di 183 sec. (rif. 55-86). Questo risultato permette di riconoscere in una piastrinopatia la causa del sanguinamento buccale. I dati provenienti dalla patologia clinica evidenziavano la presenza di una bicitopenia e di una paraprotidemia monoclonale , che imponevano l’esecuzione di un esame cito-istopatologico del midollo emopoietico e dei test sierologici per le principali malattie batteriche trasmesse da zecche (Rickettsia rickettsii, Ehrlichia canis ed ehrlichiosi granulocitaria) e per leishmaniosi. La valutazione del midollo riportava la presenza di una popolazione plasmacellulare, monomorfa (circa 50% rispetto alla popolazione mielo/eritroide), mentre gli esami sierologici erano negativi. Radiogaficamente inoltre venivano notate le caratteristiche lesioni ossee, prevalentemente a carico dei corpi vertebrali. La diagnosi conclusiva era di mieloma multiplo. Il paziente è stato trattato con prednisone, melphalan e ciclofosfamide ed è vivente al 30-1000. La valutazione con il PFA-100, in data 17-10-00, riportava un tempo di aggregazione piastrinica di 85 sec. Commenti e conclusioni. Le alterazioni coagulative in corso di disprotidemia secondaria a mieloma multiplo sono state ampiamente descritte in medicina umana, ma più raramente in ambito veterinario. Nel nostro caso il sanguinamento era legato ad una grave disfunzione piastrinica, come dimostrato dall’utilizzo di questa nuova metodica diagnostica. Il test inoltre può essere utilizzato sia per la diagnosi delle trombocitopatie che per il monitoraggio della patologia. A nostra conoscenza è questo il primo utilizzo del test in un caso di mieloma multiplo.

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ABLAZIONE PARZIALE DELL’OSSO PENIENO NEL TRATTAMENTO DELL’OSTRUZIONE URETRALE Bobbio Roberta*, Tommasini Degna Matteo, Rolla Edoardo *Centro veterinario Gregorio VII - Roma Introduzione. La litiasi uretrale costituisce una delle cause più comuni di ostruzione parziale o completa dell’uretra del cane maschio. Più frequentemente i calcoli uretrali si localizzano caudalmente all’osso del pene o a livello di incisura ischiatica, dove l’uretra subisce un restringimento anatomico. Nella femmina la presenza di uroliti, generalmente, non è associata a fenomeni ostruttivi; il condotto uretrale, infatti, si presenta più breve, con diametro maggiore e più distensibile rispetto al maschio. L’estrema variabilità di composizione dei diversi tipi di uroliti (struvite, ossalato di calcio, urato d’ammonio, cistina, silice), derivante da vari meccanismi eziopatogenetici (predisposizione di razza, fattori dietetici, UTI, ipercalciuria, iperossaluria, iperuricosuria, aumento di escrezione degli urati) rende essenziale la tipizzazione degli stessi al fine di impostare un adeguato protocollo medico non solo a scopo terapeutico ma anche per evitare recidive. L’intervento chirurgico deve essere preso in considerazione qualora costituisca l’unica possibilità di risolvere l’ostruzione. Le tecniche tradizionali includono l’uretrotomia, da preferirsi in sede prescrotale, e l’uretrostomia scrotale associata a orchiectomia. Nel primo caso le complicazioni più frequenti sono rappresentate da fenomeni emorragici durante la minzione, sieromi, ascessi in corrispondenza della sutura e stenosi; nel secondo caso si possono manifestare infezioni ascendenti delle basse vie urinarie, reazioni locali, infiltrazione d’urina attraverso la sutura e più raramente fenomeni stenotici. Obiettivo. Gli Autori propongono l’ablazione longitudinale parziale dell’osso penieno nel trattamento chirurgico di fenomeni ostruttivi derivanti da litiasi uretrale. Materiali e metodi. L’intervento è stato effettuato in due cani. Nel primo caso si trattava di uno Shih-Tzu, di 10 anni, maschio, intero, con ostruzione uretrale parziale. L’esame radiografico ha evidenziato la presenza di calcoli nell’uretra peniena ed in vescica. Il cateterismo e l’idropulsione non sono stati sufficienti a ripristinare la pervietà del lume uretrale. Si è proceduto all’asportazione, mediante ossivora, di una porzione laterale della doccia peniena, nei suoi due terzi più caudali, al fine di permettere la distensione dell’uretra, mantenendone comunque il supporto scheletrico e l’integrità anatomica. L’ablazione parziale dell’osso penieno ha permesso, tramite idropulsione, il passaggio degli uroliti uretrali in vescica per una definitiva rimozione mediante cistotomia. L’esame dei calcoli ha evidenziato la presenza di fosfato e ossalato di calcio. Il secondo paziente sottoposto all’intervento è stato un Rottweiler di 9 anni, maschio, intero, con uroperitoneo da rottura vescicale e ostruzione uretrale totale. L’idropulsione si è dimostrata inefficace per rimuovere il calcolo responsabile dell’ostruzione. L’ablazione parziale dell’osso del pene, praticata nel suo terzo più caudale, ha consentito all’uretra di dilatarsi permettendo l’eliminazione dell’urolita tramite la breccia vescicale. Risultati e discussione . In entrambi i casi, i controlli eseguiti a distanza di 5 e 10 giorni dall’intervento hanno dimostrato un pieno recupero della normale attività di minzione. L’ablazione parziale dell’osso penieno presenta una minor invasività rispetto all’uretrotomia, riducendo il rischio di stenosi e di emorragie post operatorie. L’intervento comporta, tuttavia, una certa difficoltà di esecuzione e si pensa possa predisporre l’osso del pene a fratture; l’accoppiamento viene sconsigliato. L’uretrostomia scrotale costituisce l’intervento di prima scelta in corso di ostruzione uretrale nonostante comporti il rischio di infezioni e la castrazione dell’animale. Conclusioni. La presenza di concrezioni minerali localizzate nel lume uretrale può rappresentare un pericolo per la vita dell’animale qualora sia la causa di ostruzione totale dell’uretra. L’obiettivo principale della terapia è quello di ripristinare la pervietà delle vie urinarie mediante cateterismo ascendente, idropulsione e conseguente cistotomia; qualora la tecnica conservativa fallisca, è indispensabile ricorrere all’intervento chirurgico. Nonostante la nostra casistica sia limitata, l’ablazione parziale dell’osso del pene viene proposta per la sua scarsa invasività; i risultati sembrano incoraggianti e le complicanze post operatorie limitate.

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UN CASO DI MENINGIOMA MALIGNO INTRACRANICO IN UN CANE Bogoni Paolo* Med. Vet., Rovesti Gian Luca** Med. Vet. Dipl. ECVS *Libero professionista, Ghedi, (BS) **Libero professionista, Cavriago, (RE) Introduzione. I meningiomi rappresentano, nel cane e nel gatto, una delle neoplasie più frequenti del SNC seconda solo ai tumori gliali maligni. Sono tumori mesenchimali che derivano dell’alterato sviluppo di cellule aracnoidali delle meningi. I meningiomi intracranici spesso sono di tipo benigno (80%), al contrario di quelli extracranici che solitamente sono maligni. L’età media in cui si sviluppa la neoplasia è di 7 anni (range da 16 mesi a 14 anni). Secondo alcuni autori le razze più colpite sono quelle dolicomorfe, secondo altri meticci, boxer, barboncino, pastore tedesco e scozzese. I meningiomi intracranici sono per lo più localizzati a livello della base, in particolare a ridosso del chiasma ottico o della sella turcica, della falce cerebrale, o sulla convessità; mentre quelli extracranici soprattutto a livello orbitale e paranasale. Caso clinico. Un cane, meticcio, maschio, età 9 anni, presentato per sospetto di glaucoma bilaterale, in terapia con pilocarpina 1% 1 goccia bid . Alla visita si evidenziava assenza del riflesso di minaccia a carico dell’occhio destro (normale a sx), PLR diretto e consensuale negativo a destra, PLR diretto e consensuale positivo a sinistra, midriasi relativa a destra, IOP 29 mm Hg a destra e 18 mm Hg a sinistra, STT 22 mm/min a destra e 17 mm/min a sinistra, modesto esoftalmo a destra. Escludendo una leggera iperemia congiuntivale e nucleosclerosi senile del nucleo bilaterale, non si evidenziavano altre alterazioni. L’esame del fondo dell’occhio non evidenziava alterazioni. Non erano presenti deficit neurologici. Gli esami ematici evidenziavano una leucocitosi con spostamento a sinistra, e alcuni parametri biochimici alterati. L’ERG si presentava normale, escludendo quindi, patologie retiniche o SARD. Abbiamo sottoposto il soggetto a RMN, in bianco e con mezzo di contrasto, in anestesia generale evidenziando la presenza di una neoformazione nella sella turcica a ridosso dell’ipofisi, più estesa a destra delle dimensioni di 1,48 cm di lunghezza e 0,98 cm di larghezza, che determinava compressione sul chiasma ottico. Visto il sospetto diagnostico di neoplasia e la localizzazione, il proprietario ha optato per una terapia conservativa basata su cortisonico a dosaggi antinfiammatori e antibiotici eseguiti per 20 giorni. Il soggetto ha riacquisito la visione, a destra il PLR diretto e consensuale è tornato positivo, come anche la IOP. A distanza di 30 giorni dalla sospensione della terapia gradualmente la sintomatologia iniziale si ripresen tava. Si decise di riprendere la terapia iniziale mantenendo il cortisonico in via continuativa. Dopo 75 giorni il soggetto iniziò a peggiorare, con la comparsa di deficit visivi sempre maggiori sino ad arrivare alla completa assenza di visus; inoltre divenne gradualmente aggressivo e sempre più letargico. Il cane venne sottoposto ad eutanasia e all’esame autoptico si è evidenziata una massa di color grigio chiaro a ridosso dell’ipofisi, staccata dalle strutture cerebrali. L’esame istopatologico ha stabilito che la massa era un meningoma maligno. Discussione. I meningiomi intracranici si presentano solitamente come masse uniche, a lenta e progressiva crescita. La sintomatologia che determinano è diversa a seconda delle zone che vanno a comprimere. La osteolisi concomitante che a volte si osserva è legata alla compressione esercitata dalla massa sul calvarium. La terapia per il meningioma è rappresentata dalla asportazione o dalla citoriduzione chirurgica e dalla terapia radiante, usate singolarmente o in combinazione. La terapia radiante in medicina umana r appresenta un trattamento significativo in neoplasie non trattabili chirurgicamente, nelle recidive e soprattutto nelle forme maligne. L’uso di corticosteroidi e di anticonvulsivanti ha solo uno scopo palliati vo.

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UN CASO DI MYASTHENIA GRAVIS ACQUISITA IN UN GATTO Bonfanti Ugo Med. Vet. Libero professionista, Milano La myasthenia gravis (MG) acquisita è una patologia immunomediata che colpisce l’apparato neuromuscolare; consiste, in particolare, in un’inefficiente trasmissione neuromuscolare secondaria a deplezione immunomediata dei recettori nicotinici per l’acetilcolina (AChR) a livello della membrana postsinaptica della giunzione neuromuscolare stessa. Il caso riportato descr ive una forma di MG acquisita in un gatto. Un gatto, comune europeo, femmina di 5 anni e del peso di 1,9 kg, è stato riferito presso la nostra clinica per un consulto; il soggetto, che non si alimentava da 5 giorni, si presentava in decubito laterale, manifestava evidente depressione del sensorio, grado di disidratazione pari all’8%, atrofia muscolare diffusa, pelo opaco e furfuraceo, modesta scialorrea e scolo nasale mucopurulento; stimolato a camminare, effettuava con estrema difficoltà solo alcuni passi alla fine dei quali tendeva a riassumere posizione seduta o decubito laterale; in questa occasione risultava particolarmente evidente una manifesta ventroflessione del collo. Dal punto di vista anamnestico la proprietaria riferiva improvvisa e progressiva debolezza generalizzata, difficoltà ad alimentarsi (disfagia), rigurgito, oltre a dimagramento progressivo. Alla visita neurologica, l’esame dei nervi cranici permetteva di evidenziare la riduzione dei riflessi palpebrale e corneale, ed il test di Schirmer testimoniava modesta riduzione della produzione lacrimale . Effettuato un prelievo di sangue dalla vena giugulare, al gatto è stato posizionato un catetere endovenoso in una vena cefalica al fine di somministrare, mediante pompa ad infusione, una soluzione composta da destrosio con elettroliti al 10%, soluzione aminoacidica all’8,5%, acqua per preparazioni iniettabili e cloruro di potassio (nutrizione parenterale parziale o periferica - PPN). È stata inoltre intrapresa un terapia antibiotica a base di amoxicillina ed acido clavulanico. Con il sangue prelevato è stato effettuato un esame emocromocitometrico, un profilo biochimico completo, misurata la creatinkinasi, la tiroxina libera (fT4) ed accertata l’eventuale presenza di malattie virali o protozoarie in atto o pregresse (FIP, FeLV, FIV e Toxoplasmosi). Le uniche alterazioni riportate consistevano in una modesta ipergammaglobulinemia ed ipotrigliceridemia. Sono state successivamente eseguite lastre di collo, torace ed addome: evidente un modesto megaesofago dei primi due terzi dell’organo, assenza di masse craniali al cuore, e rilevante meteorismo ed atonia dell’apparato gastroenterico. Effettuati, inoltre, esame ecografico dell’addome ed ecocardiografia che sono risultati assolutamente normali. È stato, infine, inviato il siero per la titolazione degli anticorpi contro i recettori per l’acetilcolina al “Comparative Neuromuscular Laboratory” presso la “University of California” San Diego, USA (Dr. D. Shelton); il titolo è risultato pari a 6,39 nmol/l (valori normali nel gatto inferiori a 0,3 nmol/l), da considerarsi diagnostico di m yasthenia gravis (MG) acquisita. È stata quindi intrapresa una terapia corticosteroidea a dosi immunosoppressive, ritenuta più tollerata rispetto all’impiego di farmaci anticolinesterasici. La titolazione degli anticorpi contro i recettori per l’acetilcolina è considerata diagnostica di myasthenia gravis (MG) acquisita nel cane e nel gatto; a dif ferenza del cane , la MG nel gatto è considerata una malattia estremamente rara, i cui sintomi (debolezza muscolare generalizzata, megaesofago, disfagia, assenza del riflesso palpebrale) sono spesso associati, in questa specie, a timoma. La terapia verte sull’utilizzo di farmaci anticolinesterasici (poco maneggevoli nel gatto) o sull’utilizzo di cortisone a dosaggio immunosoppressivo.

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RILIEVI PATOLOGICI RISCONTRATI ALL’ESAME FISICO E CON ESAMI DI LABORATORIO PRE-OPERATORI IN UNA POPOLAZIONE DI CANI E GATTI DA SOTTOPORRE AD ABLAZIONE DEL TARTARO Borghi Maria, Furlanello TommasoMed. Vet., Caldin Marco Med. Vet. Liberi professionisti, Padova Obiettivo. Valutare l’incidenza di rilievi patologici evidenziati dall’esame fisico e da indagini emato-chimiche-urinarie in cani e gatti da sottoporre ad ablazione del tartaro, al fine di determinare l’utilità di questi ultimi come atto preliminare alla procedura stessa. Popolazione considerata ed indagini di laboratorio. Nel periodo compreso tra Ottobre 1998 e Ottobre 2000 sono stati considerati 18 cani e 10 gatti, di età compresa tra 2 e 16 anni, di entrambi i sessi, da sottoporre ad ablazione del tartaro. L’odontopatia era stata riscontrata durante visite di controllo/profilassi vaccinali, oppure segnalata dai proprietari. Non considerando l’odontopatia, l’anamnesi non presentava informazioni degne di nota. Oltre all’esame fisico, tutti i soggetti venivano sottoposti, come valutazione pre-operatoria, ai seguenti esami di laboratorio: esame emocromocitometrico completo, integrato da misurazione della VES, profilo coagulativo, profilo biochimico con elettroforesi proteica e profilo urinario. Risultati. L’esame fisico riportava reperti patologici in 6 cani su 18 (stato di nutrizione insufficiente n.=5, soffio cardiaco mitralico n.=1, neoformazione cutanea n.=1) e in 5 gatti su 10 (stato di nutrizione insufficiente n.=2, ipertermia n.=1, dermatopatia n.=1, congiuntivite monolaterale n.=1). Le alterazioni riscontrate negli esami di laboratorio sono presentati nella tabella sot tostante. Esami di laboratorio Esame fisico Esame emocromocitometrico Profilo coagulativo Profilo biochimico Elettroforesi proteica Profilo urinario

Cani (n.=18)

Gatti (n.=10)

6 (33.3%) 18 (100%) 13 (72.2%) 17 (94.4%) 6 (33.3%) 6 (33.3%)

5 (50%) 8 (80%) 6 (60%) 8 (80%) 5 (50%) 7 (70%)

Conclusioni. I risultati degli esami di laboratorio erano frequentemente alter ati in animali ritenuti sani dai proprietari e con rilievi patologici all’esame fisico spesso aspecifici. I rilievi patologici presentano maggiore incidenza rispetto ad una popolazione di animali ritenuti sani sia dal punto di vista anamnestico che all’esame fisico, da sottoporre a terapie chirurgiche programmate (Caldin et al.,Atti del 40° Congresso Naz. SCIVAC, pag. 138, 2000). Ciò può essere spiegato dall’età spesso avanzata dei soggetti considerati e dalla presenza di uno stato di flogosi gengivale cronica, spesso complicata da infezioni batteriche. Considerato inoltre che l’ablazione del tartaro richiede l’anestesia generale, di una durata solitamente superiore a un’ora e un’inevitabile batteriemia, seppur temporanea, si può concludere che i pazienti da sottoporre a tale procedura, pur routinaria nella medicina veterinaria dei piccoli animali, devono essere considerati a particolare rischio anestesiologico. Inoltre, gli esami di laboratorio hanno permesso un approccio globale più corretto al singolo paziente per evitare l’aggravarsi di stati patologici, trattare eventuali patologie già presenti e stabilire quale procedura medica sia prioritaria per il benessere del soggetto.

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RIDUZIONE DI UNA FRATTURA MANDIBOLARE IN UN CANE CON L’USO DI RESINA ACRILICA ANCORATA A FILI IN ACCIAIO Brusa Franco, Med. Vet. Libero professionista, Massa Lombarda (RA) In un cane Dobermann di circa 2 anni si è verificata una frattura traumatica del corpo della mandibola destra: tale frattura si estende obliquamente iniziando dallo spazio tra canino e 1° premolare e procedendo in direzione ventro - distale. Si presenta completa, non scheggiosa, non esposta, ma di non agevole riduzione data la presenza delle voluminose radici dentali in questa razza canina e considerato il fatto che sia il peso della parte rostrale dell'arcata mandibolare sia l'occlusione stessa e le forze masticatorie tendono a dislocare i capi ossei. Previa anestesia generale inalatoria si è proceduto a ridur re la frattura con l'ausilio di un filo in acciaio del diametro di 0,4 mm, che è stato ancorato al periostio in posizione immediatamente mesiale al canino inferiore, e successivamente fatto passare attraverso un foro di adeguata misura, praticato nell'osso mandibolare tra il 2° ed il 3° premolare, facendo attenzione a non interessare le radici dei medesimi denti. Il filo è stato sagomato ad "8" per fornire una migliore stabilità, ed il nodo stretto a sufficienza per ottenere un buon allineamento dei due monconi. Un secondo filo in acciaio del medesimo diametro è stato ancorato al periostio nello spazio interprossimale tra il 4° premolare ed il 1° molare, ed allacciato a formare un anello posizionato verticalmente: la funzione di questo espediente è quella di fornire un ancoraggio distale per la resi na che verrà usata per conferire stabilità alla riduzione della fr attura, non essendo tale materiale dotato di adesione chimica con i denti; nella parte rostrale invece l'ancoraggio è garantito dal sottosquadro fornito dagli elementi dentali presenti a questo livello. Si è proceduto quindi a distribuire una colata di resina acrilica su tutta l'emiarcata destra, avendo cura di raffreddare bene l'impianto durante la polimerizzazione per i ben noti effetti esotermici. L'impianto, una volta consolidato, è stato rifinito con frese per eliminare gli eccessi di resina e consentire una masticazione confortevole per il paziente; si è dimostrato ottimamente stabile e ben tollerato dall'animale. È stato consigliato al proprietario di distribuire periodicamente gel alla clorexidina 0,12% nel cavo orale per abbattere, per quanto possibile, la carica batterica. Dopo circa 5 settimane, previa anestesia generale iniettiva endovenosa e radiografia di controllo, sono stati rimossi l'impianto in resina ed i fili metallici. L'occlusione è risultata perfetta, così come il consolidamento della frattura, senza alcun danno per gli elementi dentali; unico effetto collaterale due inevitabili decubiti, di piccolissime dimensioni, a livello labiale e sul pavimento buccale, assolutamente insignificanti e spontaneamente guariti in nel giro di un paio di giorni.

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ANESTESIA GENERALE CON PROPOFOL E PROPOFOL/ISOFLUORANO NEL CANE: STUDI ELETTROENCEFALOGRAFICI (EEG) Bufalari Antonello Med. Vet. PhD, R. Arcelli Med. Vet., M. Pepe Med. Vet., * R. Gialletti Med. Vet., F. Moriconi Med. Vet. Dip. di Pat., Diagn. e Clin. Vet., Sezione di Chirurgica e Radiodiagnostica, Università di Perugia *Dip. di Scienze Veterinarie, Università di Camerino Introduzione. La valutazione del grado di analgesia e del livello di anestesia tradizionalmente si basa sull’interpretazione dei segni neuromuscolari durante l’anestesia generale. I principali agenti anestetici (endovenosi o inalatori), causano una transitoria e reversibile depressione del SNC che è dose-dipendente ed è accompagnata da una concomitante riduzione dell’attività elettrica corticale. La possibilità di effettuare un esame elettroencefalografico in corso di anestesia consentirebbe di valutare, in modo particolare, l’entità della depressione elettrica cer ebrale indotta dall’anestetico. Obiettivi. Scopo di questo lavoro è quello di poter confrontare le modificazioni dell’attività cardiorespiratoria e cerebrale in due gruppi di cani anestetizzati mediante propofol e propofol/isofluorano. Materiali e metodi. Sono stati utilizzati 12 cani meticci, di peso ed età uniformi, suddivisi in due gruppi. In tutti i soggetti, l’induzione dell’anestesia è stata ottenuta mediante un bolo unico di propofol (6,6 mg/kg, ev). Per il mantenimento dell’anestesia (30 minuti), nel primo gruppo (gruppo PP) è stata impiegata una pompa ad infusione per la somministrazione di dosi ripetute di propofol (1,1 mg\kg), nel secondo è stata impiegata una miscela di ossigeno e isofluorano (gruppo PI). Durante l’anestesia sono stati monitorati i principali parametri cardiopolmonari. Per la determinazione della profondità dell’anestesia e del grado di analgesia si è ricorsi a valutazioni soggettive quali l’osservazione dei segni clinici dell’anestesia e delle reazioni motorie alla compressione della coda mediante una pinza intestinale tipo Doyen, ed oggettive quali l’analisi dell’attività elettrica cerebrale attraverso l’esame di due parametri: lo Spettro di Frequenza (SF) e l’Amplitudine Totale (AT). Risultati e discussione. In entrambi i gruppi, i principali parametri cardiopolmonari sono rimasti entro i valori fisiologici per tutta la durata dell’anestesia e le differenze tra i due gruppi non sono risultate significative. Il rispetto dei parametri fisiologici è di particolare importanza in quanto le modificazioni del flusso ematico cerebrale indotte da eventuali condizioni di ipercapnia, ipossia o ipotensione arteriosa potrebbero determinare una modificazione dell’attività metabolica neuronale e, conseguentemente, un’alterazione delle risposte elettroencefalografiche. Significative, invece, sono risultate le differenze nei tempi di risveglio tra i due gruppi con un più rapido recupero per i cani del gruppo PP. Dall’analisi dell’esame elettroencefalografico si nota che i valori di AT nel gruppo PP, pur registrando bassi valori in assoluto (< 150 µV), sono risultati statisticamente più elevati rispetto al gruppo PI a 2’, 5’ e 30’. Anche i valori dello SF sono risultati significativamente superiori nel g ruppo PP a 20’, 25’ e 30’. Da ciò si può evincere che l’associazione propofol/isofluorano deprime l’attività elettrica corticale in modo più efficace rispetto al solo propofol, sebbene in entrambi i gruppi non ci sia stato alcun tipo di risposta neuromotoria allo stimolo dolorifico indotto. Inoltre, l’evidente riduzione della AT e dello SF unitamente all’assenza di risposte agli stimoli algici e alla stabilità dei principali parametri cardiorespiratori riscontrati nel gruppo PI, dimostra che i soggetti di questo gruppo hanno raggiunto un livello di anestesia più profondo di quello raggiunto dai cani del g ruppo PP. Conclusioni. L’analisi della attività elettrica corticale in corso di anestesia può risultare un importante parametro oggettivo per la valutazione della profondità dell’anestesia e del grado di analgesia.

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UTILIZZO DI UNA PLACCA DI PROTEZIONE SAGOMATA DOPO LA RIDUZIONE CHIRURGICA DELLA PALATOSCHISI CONGENITA IN UN BULLDOG INGLESE DI 3 ANNI Calzolari Davide*, Med.Vet., Dario Cattaneo§, Odontotecnico * Libero professionista, Pavia § Studente in odontoiatria, Pavia Introduzione. L'origine della palatoschisi congenita è riconducibile ad una mancata o incompleta unione, in corrispondenza della linea mediana, delle due metà del palato duro è di quello molle. Le fissurazioni palatine semplici o duplici, totali o parziali mettono in rapporto il cavo orale con le cavità nasali. 1 Obiettivi. Lo scopo del nostro lavoro è di risolvere chirurgicamente la schisi del palato duro e molle, secondo la tecnica di Von Langenbeck2, eliminandone gli effetti collaterali legati alla deiscenza della ferita e velocizzandone la guarigione con una placca di protezione ancorata al palato. Materiali e metodi. “Sandrone” (fig. 1), bulldog inglese maschio di tre anni è stato portato presso la Clinica Veterinaria Città di Pavia con una grave palatoschisi congenita. La preparazione del paziente ha incluso: 1) tre radiografie toraciche 2) un emocromo, un profilo biochimico e l'esame completo delle urine. 3) una coltura batteriologica con antibiogramma tramite un tampone sterile posto attraverso la schisi nelle cavità nasali. La terapia antibiotica ha avuto inizio 72 h. prima della seduta anestesiologica. Il paziente è stato premedicato con atropina solfato 0,02 mg/kg e diazepan 0.1 mg/kg I.V., indotto con penthotal sodium 20 mg/kg I.V., intubato e mantenuto in anestesia con una miscela di isofluorano e ossigeno; posizionato in decubito dorsale (fig. 4), lo stetoscopio esofageo e il tracheotubo sono stati assicurati saldamente alla mandibola. Il monitor ci ha permesso di controllare il ritmo e la frequenza cardiaca e respiratoria, mentre una soluzione di ringer lattato è stata somministrata lentamente, per via endovenosa. Tramite due portaimpronta è stato possibile riprodurre l'impronta dell'arcata mandibolare, mascellare (fig. 5) e del palato (fig. 6), utilizzando alginato (figg. 7, 8 e 9). Da questa è stato ricavato un calco in gesso (fig. 10). È stata quindi realizzata una placca in resina per protesi sagomata che aderisse perfettamente al palato duro (fig. 11 e 12) e quindi fosse in grado di proteggerlo da qualsiasi tipo di insulto. La seconda seduta anestesiologica non ha subito mutamenti rispetto alla precedente. L'unica eccezione ha riguardato il lavaggio delle cavità nasali. La terapia chirurgica è stata eseguita secondo la tecnica di Von Langenbeck 2 (fig. 13), che consiste nell’incisione dell’estremità del difetto palatale seguito dalle elevazioni e slittamento dei due flaps insieme sopra il difetto; due incisioni liberatorie si eseguono in prossimità delle arcate dentali per diminuire la tensione. È necessario rispettare in questo caso il decorso delle arterie palatine. Terminata la stessa abbiamo installato la placca di protezione (figg. 11 e 12) capace di adattarsi precisamente al palato e di incastrarsi ad incisivi, premolari e molari superiori e fissata con composito fotopolimerizzante. Nei giorni successivi il paziente è stato alimentato con piccoli dadini di carne cruda; la terapia antibiotica è proseguita per 10 giorni. Il 12° giorno dopo l'intervento è stata tolta la placca senza la necessità di alcun tipo di anestesia. La sutura era perfettamente cicatrizzata, con abbondante tessuto di granulazione neoformato. Risultati. Il follow up è stato fissato a 20, 40, 90, 180 e 360 giorni. Nessun problema si è manifestato ad eccezione di una leggera rinite sierosa con car atteri di cronicità. Conclusioni. L'installazione della placca sagomata ha permesso una guarigione rapida senza la deiscenza della ferita, tipico effetto collaterale. Di contro si sono rese necessarie due sedute anestesiologiche e la collaborazione di un odontotecnico; i costi hanno quindi subito un notevole rialzo. Bibliografia 1. Jurkiewicz, M.J., and Bryant, D.L.: Cleft lip and palate in dogs: A progress report. Cleft Palate J. 5:30-36, 1968. 2. Howard DR: Palate. In: Bojrab MJ, ed. Current Techniques in Small Animal Surgery, 2nd ed. Philadelphia: WB Saunders, 1983: 109-113. 3. Böhning, R.H., Dehoff, W.D., McElhinney, A., and Hofsfra, P.C.: Pharyngostomy for maintenance of the anorectic animal. J. Am. Vet. Med. Assoc. 156:611-615, 1970.

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TROMBOSI PORTALE NEL CANE: TRE CASI Sergio Fanfoni* Med.Vet., Hans Ulrich Zeyen* Med.Vet., Tommaso Furlanello**Med.Vet., Marco Caldin** Med.Vet. *Libero professionista, Roma; **Libero professionista, Padova Introduzione. La trombosi della vena porta è un evento raramente diagnosticato ante mortem nel cane. La patogenesi della trombosi riconosce tre cause predisponenti, note con il nome di “triade di Virchow”: stati di ipercoagulabilità, stasi vascolare e danni all’endotelio vascolare. In letteratura veterinaria le cause più frequentemente riportate sono dirofilariosi cardiopolmonare, endocarditi batteriche, lesioni secondarie all’installazione di cateteri endovenosi, sindromi nefrosiche , pancreatiti, insufficienza cardiaca, iperadrenocorticismo, anemie emolitiche immunomediate e neoplasie epatiche. Obiettivo. Valutare come lo studio doppler dei flussi venosi addominali e il coagulogramma siano fondamentali per raggiungere una diagnosi in vita di tale patologia. Materiali e metodi. Nel periodo compreso tra Giugno 1999 e Settembre 2000 sono stati visitati tre cani, riferiti per varie alterazioni cliniche (vedi oltre). Oltre all’esame fisico, in ognuno dei soggetti sono stati eseguiti l’esame emocromocitometrico, il profilo biochimico, il profilo urinario, il profilo coagulativo e l’esame eco grafico bidimensionale e doppler dell’addome. Risultati e discussione Caso n° 1: Cane meticcio m., di 8 anni, portato alla visita per comparsa di ascite e melena. Il soggetto era in trattamento da due mesi per la presenza di un’anemia emolitica immunomediata con prednisone (2,2 mg/kg/die). Il cane presentava inoltre sieropositività nei confronti di Ehrlichia canis. L’esame emocromocitometrico riportava grave anemia con sferocitosi e note di displasia eritroide. Nel profilo coagulativo era positivo il dosaggio degli FDPs, con aumento delle concentrazioni dei D-dimeri plasmatici e diminuzione dell’antitrombinemia. L’esame ecografico bidimensionale evidenziava la presenza di più trombi a carico della vena porta e dei vasi splenici. A causa delle scadenti condizioni generali, il proprietario richiese l’eutanasia. L’esame autoptico ha confermato la presenza dei trombi già visualizzati ed inoltre ha permesso di visualizzarne altri, occludenti i vasi mesenterici. La causa della trombosi era presumibilmente l’anemia immuno-mediata e/o il trattamento cronico con corticosteroidi. Caso n° 2: Greyhound maschio, di 6 anni, riferito per la comparsa di un versamento addominale, preceduto da diarrea. Nel profilo biochimico si notava grave ipoalbuminemia. Il profilo urinario presentava spiccata proteinuria. Il liquido ascitico era un trasudato puro. Il coagulogramma mostrava aumento dell’aPTT, presenza di FDPs ed aumentata concentrazione dei D-dimeri, con diminuzione dell’ATIII plasmatica. L’esame ecografico evidenziava un voluminoso trombo portale, posto cranialmente allo sbocco di una vena splenica. Sono state eseguite biopsie renali ed epatiche, con conseguente diagnosi di grave glomerulopatia ed epatopatia secondaria all’ipossia cronica. A Ottobre 2000 il cane è vivente. Caso n° 3: Dogue de Bordeaux, m., 5 anni di età, portato alla visita per un episodio di vomito e dilatazione acuta dell’addome . L’esame fisico mostrava una marcata splenomegalia. Gli esami di laboratorio hanno evidenziato lieve iperglobulinemia, ipercolesterolemia, allungamento di aPTT e PT, aumento della concentrazione plasmatica di FDPs e D-dimeri, con diminuzione dell’antitrombinemia. All’ecografia si evidenziava la presenza di un voluminoso trombo portale. L’eziopatogenesi dello stato trombotico è ignota. A Ottobre 2000 il paziente è vivente. Conclusioni. Come testimoniato dai casi sopra descritti, le trombosi portali si possono presentare in seguito a varie patologie. Il rilevamento ecografico del trombo nel lume vascolare e la conseguente ipertensione portale, la presenza di FDPs plasmatici e l’aumentata concentrazione di D-dimeri sono gli unici rilievi costanti nel corso di tale patologia.

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INFEZIONI CONCOMITANTI IN CANI SIEROPOSITIVI PER RICKETTSIA RICKETTSII: STUDIO SIEROLOGICO SU 802 CASI Furlanello Tommaso* Med. Vet., Caldin Marco* Med. Vet., Lubas George** Med. Vet., Brigato Luca*Dott. Biol. *Libero professionista, Padova **Università di Pisa Premessa. Una elevata incidenza di sieroconversioni per Rickettsia rickettsii, l’agente eziologico della Febbre Maculosa delle Montagne Rocciose (Rocky Mountain Spotted Fever, RMSF), in cani provenienti dal territorio italiano è stata recentemente segnalata dal nostro gruppo di lavoro (Furlanello et al., Proc. 10th ESVIM Congr, 115, 2000). Da questo iniziale studio sierologico appariva degna di interesse la frequenza di concomitanti sieropositività tra RMSF ed altre malattie batteriche trasmesse da zecche e Leishmaniosi. In questa nota sono riportate la prevalenza di infezioni concomitanti a RMSF in un più ampio numero di casi. Materiali, metodi e risultati. Nel periodo compreso tra il 31-07-99 e il 30-09-00 sono stati esaminati 802 sieri ottenuti da cani residenti nell'intero territorio italiano. I sieri erano stati inviati al Labor atorio Privato d’Analisi Veterinarie “San Marco” a fini clinici-diagnostici e presumibilmente provenivano da cani affetti da uno stato patologico che i clinici referenti consideravano ascrivibile ad una o più infezioni trasmesse da zecche, appartenenti alla famiglia delle Rickettsiaceae (Rickettsia rickettsii [RMSF], Ehrlichia canis [Canine Monocytic Ehrlichiosis, CME], Ehrlichia granulocitaria [Canine Granulocytic Ehrlichiosis/Human Granulocytic Ehrlichiosis, CGE/HGE]) o da Leishmania infantum. Le indagini sierologiche sono state effettuate con la metodica dell’immunofluorescenza indiretta, utilizzando materiali e procedure validate nella specie canina e commercialmente disponibili. Per RMSF venivano dosati gli anticorpi delle classi IgG e/o IgM, per CME, CGE e Leishmaniosi era realizzabile solo il dosaggio delle IgG. Il titolo diluitivo minimo per considerare il soggetto sotto indagine positivo è di 1:80 per tutte le patologie sopra indicate. I risultati di maggiore interesse sono presentati nella tabella sottostante . Infezioni e classi anticorpali RMSF IgG+CME RMSF IgG+RMSF IgM + CME RMSF IgG+CGE/HE RMSF IgG+Leishmaniosi RMSF IgG+CME+CGE RMSF IgG+CME+CGE + Leishmaniosi

N° campioni

N° campioni positivi

696 201 182 277 168 33

308 (44.2 %) 99 (49.2 %) 130 (71.4 %) 156 (56.3 %) 67 (39.8 %) 7 (21.2 %)

Commenti e conclusione. Risulta di grande interesse una così elevata incidenza di infezioni concomitanti, mai riportata prima d’ora nella specie canina. Ricordando poi che non è prevista cross-reattività tra gli agenti infettivi esaminati, la sieropositività può certamente non esprimere uno stato di malattia in atto, ma comunque riferisce di un avvenuto contatto con l’agente eziologico. È nostra opinione che infezioni concomitanti possono essere all’origine di stati patologici atipici, cronici e di difficile trattamento. L’influenza, presumibilmente negativa, di infezioni multiple, sulle capacità immunitarie degli animali sieropositivi dovrebbe essere oggetto di studi approfonditi, vista la frequenza del fenomeno. Infine dovrebbero essere considerate le implicazioni per la salute umana di infezioni batteriche recentemente segnalate in Italia, quali la RMSF (o un’infezione correlata antigenicamente) e la CGE, da considerare gravi zoonosi trasmesse da zecche . Ringraziamenti. Si ringrazia il Sig. Filippo Tognin per la raccolta e l’elaborazione dei dati.

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TECNICA DI TETTOPLASTICA ACETABOLARE (DORSAL ACETABULAR RIM ARTHROPLASTY O DARTHROPLASTY) SECONDO SLOCUM NEL TRATTAMENTO DELLA DISPLASIA DELL’ANCA DEL CANE. ESPERIENZA IN 15 CASI TRATTATI Gilardini Raffaele Med. Vet. DVM, Beghelli Annalisa DVM Liberi professionisti, Voghera Introduzione. La tettoplastica acetabolare proposta da Slocum per il trattamento della displasia d’anca nel cane consiste nella fissazione di osso prelevato dall’ala dell’ileo sopra la capsula articolare e sul bordo acetabolare, al fine di costituire un supporto dorsale per la testa del femore e prevenire il dolore generato dalla trazione della capsula articolare sul bordo acetabolare dorsale (Dorsal Acetabular Rim o DAR). Attraverso le vie di accesso caudo-laterale all’anca e laterale all’ala dell’ileo mediante separazione delle fibre della muscolatura glutea, si prelevano dall’ala dell’ileo diverse listelle di osso cortico-spongioso di dimensioni appropriate. Le listelle vengono poi suturate, in numero da una a quattro (a seconda del grado di lussazione) sulla capsula articolare, in corrispondenza del punto più alto della testa del femore. Una listella viene appoggiata dorsalmente all’acetabolo per costituire il limite dorsale sotto la muscolatura glutea. Lo spazio tra le listelle suturate alla capsula e quella posta sotto la muscolatura glutea viene riempito da osso spongioso appoggiato su fori eseguiti attorno all’acetabolo e coperto da altre listelle di osso cortico-spongioso. Alcuni punti di sutura tra il muscolo gluteo profondo ed il tendine dell’otturatore interno ricoprono l’impianto prevenendone la migrazione. Materiali e metodi. Le 16 anche displasiche (9 soggetti in tutto) da noi trattate, presentavano diverso grado di osteoartrosi e riempimento acetabolare più o meno accentuato, con cartilagine articolare presumibilmente integra. Clinicamente i soggetti trattati presentavano sintomi variabili quali dolore all’estensione forzata dell’articolazione dell’anca, zoppia di grado variabile, scarsa resistenza e zoppia dopo l’attività fisica, segno di Ortolani. Sono stati eseguiti esami radiografici subito dopo l’intervento, dopo due e quattro mesi e poi in tempi variabili fino a 18 mesi (per i primi soggetti trattati) con proiezioni ventro-dorsale classica e DAR view. La valutazione clinica è stata eseguita in tutti i soggetti a dieci giorni, a due mesi, quattro mesi dall’intervento e appena prima della stesura del seguente lavoro. Risultati. I radiogrammi hanno permesso in tutti i casi la valutazione dell’aspetto dell’impianto osseo ed il grado di copertura della testa del femore. Da un punto di vista clinico sono stati valutati il dolore all’estensione dell’anca, la presenza di zoppia, la prova di Ortolani in anestesia, ed al proprietario è stato consegnato un questionario sulla resistenza all’esercizio fisico e sulla presenza di dolore o zoppia dopo l’esercizio. Complessivamente tutti i soggetti trattati hanno evidenziato un miglioramento decisivo evidenziato con maggior tolleranza all’estensione forzata dell’anca ed all’esercizio e scomparsa delle zoppie dopo 4-6 mesi dal trattamento. Nessuna complicazione si è evidenziata durante o dopo l’intervento tranne un deficit propriocettivo di grado moderato in un soggetto, regredito spontaneamente nel giro di 45 giorni e riferibile ad una probabile neurapraxia del nervo ischiatico. Conclusioni. La tettoplastica acetabolare di Slocum è una tecnica adottata recentemente presso la nostra struttura per il trattamento della displasia d’anca nei soggetti che non hanno più i requisiti per essere trattati con una Tripla Osteotomia Pelvica e non sono sufficientemente gravi da richiedere una Protesi Totale di Anca. I soggetti operati hanno ben tollerato l’intervento e mostrato beneficio subito dopo la chirurgia, probabilmente per la denervazione subita dalla capsula articolare durante l’esecuzione della via di accesso. Il miglioramento clinico è più evidente dopo 4 -6 mesi dal trattamento chirurgico.

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UVEITE FACOCLASTICA DA ENCEPHALITOZOON CUNICULI NEL CONIGLIO Giordano Cristina* Med. Vet., Vercelli Antonella* Med. Vet., Weigt Anne§ VMD *Libero professionista, Torino § VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA Introduzione. L’uveite lente-indotta può essere causata dalla perdita di proteine denaturate della lente in caso di catar atta ipermatura (PLU o uveite facolitica) o da una improvvisa esposizione a normali proteine della lente a seguito della rottura della sua capsula (PCU o uveite facoclastica). Quest’ultima può insorgere in seguito a ferite penetranti o a chirurgia intraoculare. In letteratura sono stati descritti casi di PCU nel coniglio, senza anamnesi o evidenza istologica di trauma oculare, il cui agente responsabile è stato individuato in un microsporidio, Encephalitozoon cuniculi. Clinicamente l’infiammazione causata da PCU è progressiva e spesso intrattabile. I cortisonici locali e i midriatici hanno poco o nessun effetto nel corso della malattia e la rimozione chirurgica della lente con la facoemulsificazione, se non effettuata in fasi molto precoci, può risultare difficile od impossibile a causa dell’ostruzione della pupilla da parte di materiale granulomatoso. Tali casi, conducono quasi sempre all’enucleazione. Obiettivo. Scopo di questo studio è stato di rilevare con varie metodiche la presenza dell’Encephalitozoon cuniculi in 4 casi di uveite piogranulomatosa non traumatica nel coniglio. Materiali e metodi. I casi descritti sono stati sottoposti alla visita oftalmologica e ad esami sierologici per la determinazione della presenza di E. cuniculi. Nei casi 1-2-3 si è dovuto ricorrere all’enucleazione monolaterale; gli occhi enucleati sono stati fissati in formalina, inclusi in paraffina e le sezioni ottenute colorate con ematossilina ed eosina e colorazione di Gram. Il caso 4 è attualmente in terapia medica. Risultati e discussione. All’esame istologico dei casi 1-2-3 si è dimostrata la presenza organismi Gram positivi ritenuti identificabili con E. cuniculi. Istologicamente in tutti gli occhi la caratteristica prevalente è stata la rottura della capsula della lente e la presenza di infiammazione di tipo misto intorno alla zona di rottura. Conclusioni. L’encephalitozoonosi è stata descritta in letteratura umana ed è particolarmente problematica nei soggetti immunodepressi. Nel coniglio l’encefalitozoonosi spesso evolve in forma asintomatica. L’albendazolo è stato utilizzato per trattare con successo pazienti affetti da AIDS con microsporidiosi disseminata causata da E. cuniculi. La combinazione di albendazolo orale e corticosteroidi è stata efficacemente utilizzata anche nel coniglio in casi di PCU. Secondo alcuni autori la facoemulsificazione rappresenta il trattamento più efficace per i conigli con PCU, sebbene possano esserci recidive. In quasi tutti i casi da noi trattati l’elevato costo della procedura chirurgica e la g ravità dei segni oculari hanno portato all’enucleazione .

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PRESENZA DI MOLTEPLICI MASSE GENGIVALI IN QUATTRO GATTI Gracis Margherita, DVM, Dipl. AVDC, Dipl. EVDC Dept. of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA - USA Quattro gatti, tre di razza comune americana ed uno persiano, furono presentati al Servizio di Odontostomatologia dell’Ospedale Veterinario dell’Università della Pennsylvania per la valutazione di molteplici masse gengivali a carico di tutti i denti, ad eccezione dei canini superiori. Il caso #1 era un gatto randagio maschio, castrato, di circa 6 anni di età, le cui masse gengivali si erano ripresentate dopo escissione chirurgica (gengivectomia) avvenuta un anno prima; il caso #2 era una gatta sterilizzata di circa 9 anni di età le cui masse erano state rimosse chirurgicamente già in tre precedenti occasioni; il caso #3 era un gatto maschio castrato di circa 18 mesi di età; il caso #4 era una femmina sterilizzata, di razza persiana e di circa 6 anni di età. Le masse apparivano di aspetto infiammato e di consistenza friabile, e coprivano la gran parte delle corone dentali. I tessuti gengivali intorno ai canini superiori erano solo infiammati, mentre quelli delle zone edentule apparivano normali. I linfonodi mandibolari erano leggermente ingrossati. I gatti apparivano altrimenti in buono stato di salute e la visita clinica e gli esami di laboratorio (emocromocitometrico, profilo biochimico, test per FIV e FeLV) non evidenziarono altre anomalie. Le masse gengivali, rimosse dopo estrazione di alcuni (caso #3 e #4) o tutti i denti (caso #1 e #2), furono esaminate istologicamente. Nel primo caso la diagnosi fu di sarcoma odontogenico a cellule fusate, nel secondo e nel quarto di epulidi fibromatose, e nel terzo di gengivite spongiotica cronica iperplastica. In tutti i casi, l’escissione chirurgica in concomitanza ad estrazione dentale ed alveoloplastica risultò curativa. Le cause di iperplasia gengivale sono genetiche, traumatiche, farmacologiche ed ormonali. Mentre i cani di razza Boxer sembrano essere geneticamente predisposti allo sviluppo di iperplasia gengivale, questa predisposizione non è riconosciuta in nessuna razza felina. Le più comuni cause traumatiche comprendono le lesioni da riassorbimento odontoclastico e la malattia parodontale; solitamente, tuttavia, queste patologie causano iperplasia localizzata e non generalizzata. Anche la malocclusione dentale può causare traumatismi ed iperplasia dei tessuti gengivali: in questi gatti l’occlusione era normale. I farmaci in grado di causare iperplasia gengivale sono l’aspirina, la ciclosporina A, i calcio antagonisti, alcuni anticonvulsivanti e la vitamina A. Nessuno di questi composti era stato mai somministrato ai gatti oggetto di questo lavoro. Nella donna e nelle pecore, inoltre, è noto il ruolo degli ormoni sullo sviluppo di iperplasia gengivale durante la gravidanza: tuttavia due dei gatti erano maschi e la femmina era sterilizzata. La classificazione dei tumori di origine dentale è tuttora controversa. Quella attualmente accettata, di Kramer et al. (1992), è una versione revisionata della classificazione della World Health Organization di Pindborg et al. (1971), in cui i tumori sono raggruppati in base ai tessuti di origine. Le epulidi fibromatose sono attualmente classificate tra i tumori originanti dall’ectomesenchima dentale (con o senza tessuto epiteliale) e definite come fibromi odontogenici periferici. Il numero delle masse nei casi qui descritti è alquanto insolito. I casi riportati presentavano similarità cliniche significative e la terapia chirurgica risultò in una guarigione completa in tutti i pazienti. Tuttavia, la diagnosi istologica era diversa. L’eziologia delle masse gengivali di questi gatti rimane sconosciuta. La bibliografia è disponibile su richiesta.

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USO DI UN FLAP DI MUCOSA VOMERALE E DI UNA MEMBRANA BIOLOGICA NELLA RIDUZIONE CHIRURGICA DI UN DIFETTO PALATALE CONGENITO Gracis Margherita, DVM, Dipl. AVDC, Dipl. EVDC Dept. of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA - USA Un cucciolo di cane di razza Cocker Spaniel, maschio venne presentato a circa 4 mesi di età al Servizio di Odontostomatologia dell’Ospedale Veterinario dell’Università della Pennsylvania per la valutazione di un difetto congenito di palatoschisi e cheiloschisi bilaterale. L’esame clinico confermò la presenza di fissurazioni bilaterali che partivano a livello della papilla incisiva, si dirigevano obliquamente tra il terzo incisivo laterale ed il canino e terminavano a livello del piano nasale. Circa 2 cm della porzione mediana del labbro superiore, al di sotto del tartufo, era mancante. Il difetto palatale continuava sulla linea mediana caudalmente alla papilla incisiva per un tratto di circa 1,5 cm. La dentizione era mista: in particolare i primi e secondi incisivi superiori permanenti erano in fase di eruzione, mentre numerosi denti decidui erano ancora presenti. Alcuni degli incisivi erano localizzati sulla linea di incisione per i flap mucosali necessari alla riduzione dei difetti congeniti. Fu quindi presa la decisione di estrarre tutti gli incisivi superiori e rimandare l’intervento di chiusura della schisi fino a guarigione delle aree di estrazione. Questa decisione fu anche basata sulle ottime condizioni fisiche del cane e l’abilità dei proprietari di nutrirlo senza problemi nonostante la presenza delle fistole oro-nasali. I difetti palato-labiali vennero poi ridotti chirurgicamente nell’arco di tre sedute, quando il cucciolo aveva tra i 6 ed i 9 mesi d’età. Il difetto mediano del palato secondario fu ripar ato con l’utilizzo di un flap di mucosa che copriva l’osso vomere, visibile attraverso l’area di schisi. Innanzitutto la mucosa palatale venne incisa a tutto spessore lungo il margine del processo palatale dell’osso mascellare che delimitava il difetto. La mucosa venne poi scollata per un breve tratto dall’osso sottostante in maniera tale da facilitare la sutura finale. La mucosa del vomere fu quindi incisa longitudinalmente dal punto più caudale della fissurazione fino all’osso incisi vo, per poi continuare attorno ad esso, a destra e a sinistra, per circa 1 cm e quindi trasversalmente per circa 4-5 mm. I lembi vennero delicatamente sollevati con un elevatore periostale, e i due flap di mucosa vomerale di destra e di sinistra vennero posizionati tra il processo osseo e la mucosa palatale del lato corrispondente in maniera tale che la faccia epiteliale dei flap pavimentasse la cavità nasale. Una membrana biolo gica venne quindi posizionata a coprire l’osso vomere e i flap mucosali. La mucosa vomerale, la membrana biologica e la mucosa palatale vennero infine suturate con punti a U orizzontali. I difetti labiali vennero ridotti con flap di mucosa buccale. Sei mesi dopo l’ultimo intervento, il cane continua a condurre vita normale. I difetti del palato primario o secondario causano lo sviluppo di fistole oro-nasali che possono compromettere le possibilità di sopravvivenza di un cucciolo. Per questo motivo è bene ridurre i difetti chirurgicamente entro i primi mesi di vita. L’età minima consigliata per l’intervento, tuttavia, è circa tre mesi, quando il rischio anestesiologico è minore e i tessuti hanno raggiunto uno sviluppo volumetrico f avorevole. I principi della chirurgia palatale includono: a) preservazione dell’irrorazione sanguigna dei flap; b) supporto osseo al di sotto della linea di sutura; c) assenza totale di tensione lungo la linea di sutura. Numerose sono le tecniche suggerite per la riduzione chirurgica dei difetti palatali, quali la tecnica di scorrimento, il flap ad “U” (split palatal U-flap), la tecnica di Von Langenbeck (doppio flap riposizionato medialmente), la tecnica dei flap sovrapposti (overlapping flap technique), ecc. Il flap di mucosa vomerale è spesso utilizzato in chirurgia neonatale per la chiusura di difetti palatali mediani. La bibliografia è disponibile su richiesta.

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FALSAGRAVIDANZA NELLA CAGNA: RISCONTRI CLINICI DI TERAPIA CON AGOPUNTURA Groppetti Debora Med. Vet., Pecile Alessandro Med. Vet. PhD, Cremonesi Fausto Med. Vet. Prof. Pat. Riprod. Istituto di Clinica Ostetrica e Ginecologica Veterinaria dell’Università degli Studi di Milano Introduzione. La falsagravidanza (FG) nella cagna va considerata come una condizione parafisiologica legata al particolare ciclo estrale di questa specie. Infatti, tutte le cagne non gravide in fase diestrale sono in condizione di FG ma solo alcune mostrano sintomi clinicamente evidenti quali,alterazione del comportamento, ipertrofia del parenchima mammario ed eiezione lattea. Con il susseguirsi dei cicli tale sintomatologia è di solito ricorrente, con tendenza al peggioramento delle manifestazioni cliniche e predisponendo, nel lungo termine, all’insorgenza delle neoplasie mammarie. Sebbene l’eziologia della FG sia ancora incerta, le manifestazioni cliniche sembrano correlate, durante la seconda metà della fase diestrale, ad un aumento della concentrazione di prolattina responsabile della preparazione, induzione e mantenimento della secrezione lattea e delle manifestazioni comportamentali di tipo materno e a concomitante calo del progesterone. Obiettivo. Utilizzare la terapia agopunturale per la cura della FG, valutando i risultati clinici e i livelli ematici di prolattina e progesterone. Materiali e metodi. 14 cagne con FG, di diversa razza, di età compresa tra i 10 mesi e gli 8 anni, sono state trattate con agopuntura (AP) nei punti 23 BL, 6 SP, 41 GB, 1 CV, 4 CV, 17 CV, per 2-6 volte a distanza di 24-48 ore per 5-15 minuti, a partire dal primo giorno in cui è comparsa eiezione lattea fino ad un massimo di 10 giorni. Altre 3 cagne sono state impiegate come controllo e non sottoposte ad AP. I sintomi sono stati valutati clinicamente in gradi di intensità, con riferimento alle alterazioni comportamentali, alla eiezione lattea e alla ipertrofia mammaria e in funzione del tempo. In tutti gli animali si sono effettuati prelievi di sangue a tempi prestabiliti. I dosaggi ormonali sono stati eseguiti mediante un kit RIA per il progesterone (DSL-3900 activeTM progesterone coated-tube RIA kit) ed allestendo un dosaggio RIA per la prolattina. Risultati e discussione. Dei soggetti sottoposti ad AP, 13 hanno avuto remissione della sintomatologia in 7-10 giorni dall’inizio della FG e della terapia. In un caso si è osservata la persistenza della eiezione lattea per un periodo sovrapponibile a quello delle cagne del gruppo di controllo. In queste ultime si è attesa la remissione spontanea dei sintomi che si è verificata molto più tardi, 30-45 giorni dall’inizio della FG. La risposta più rapida al nostro trattamento con AP è stata il ripristino del normale comportamento, quindi la scomparsa dell’eiezione lattea ed infine la riduzione del parenchima mammario. I risultati endocrini evidenziano: 1) la conferma della diminuzione del progesterone in corrispondenza dell’inizio della FG 2) il variabile comportamento della prolattina che tende comunque a decrescere con l’attenuazione della sintomatologia. Conclusioni. L’AP si è rivelata una valida alternativa alle classiche terapie farmacologiche. Tra i vantaggi citiamo la mancanza di effetti collaterali, la possibilità di evitare la somministrazione di farmaci e la rapida remissione dei sintomi. Ringraziamenti. Dr. Parlow, direttore del “National Hormone & Pituitary Program”, California, per aver fornito gli immunoreagenti per la titolazione della prolattina.

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IPERCALCEMIA ASSOCIATA AD UN EMANGIOSARCOMA IN UN CANE: PRIMA SEGNALAZIONE Furlanello TommasoMed. Vet., Ledda Gianluca Med. Vet., Caldin Marco Med. Vet. Liberi professionisti, Padova Introduzione. In numerosi stati neoplastici può comparire una condizione di ipercalcemia, per la produzione di fattori paratormone simili e/o per altri meccanismi eziopatogenetici. A nostra conoscenza l’ipercalcemia maligna è stata associata a patologie linfo e mieloproliferative e tumori solidi con o senza metastasi ossee, mentre mancano segnalazioni riguardo all’emangiosarcoma. Descrizione del caso clinico. In data 30-08-00 è stato ammesso alla visita un cane bullmastiff maschio, di 6 anni di età. L’anamnesi riferiva disoressia, dimagramento e poliuria-polidipsia, comparsa da circa un mese e di progressiva gravità. Alla visita veniva confermata l’estrema magrezza del soggetto e si notava un evidente stato di disidratazione. I principali dati patologici provenienti dagli esami di patologia clinica erano iperazotemia (278 mg/dl, intervallo di riferimento: 15-45), ipercreatininemia (6,88 mg/dl, rif.: 0,75-1,30), ipercalcemia (12,8 mg/dl, rif: 8,0-12,0) e iperfosforemia (8,9 mg/dl, rif.: 2,5-4,7). Inoltre risulta elevata la ferritinemia (685 ng/ml, rif.: 84-120), a fronte di normale sideremia. Il peso specifico urinario era 1,011. Come approfondimento per l’ipercalcemia veniva dosato il calcio ionico venoso, che si presentava aumentato (1,67 mmol/l, rif.: 1,131,32). Il paratormone plasmatico risultava fortemente diminuito (0,1 pmol/l, rif.: 0,10-1,10). Lo stato di ipercalcemia veniva considerato quindi causa dell’uremia, e provocato dalla presenza di un fattore plasmatico PTH-simile, ipotizzando così una eziologia neoplastica. L’esame radiografico del torace rivelava una maggiore visualizzazione dell’albero respiratorio, possibile conseguenza del deposito di sali di calcio. L’esame radiografico dell’addome evidenzia una perdita di dettaglio dell’area epatica, con aumentata radio-opacità caudalmente allo stomaco. Tale quadro, all’esame ecografico, si manifestava come una massa disomogenea tipo “complex”, a carico del parenchima epatico. Entrambi i reni presentavano i diverticoli pelvici iperecogeni e coni d’ombra distali riferibili ad aree calcifiche. La massa sopra descritta veniva campionata mediante biopsia eco-guidata e la diagnosi istopatologica dei frammenti esaminati era di emangiosarcoma. Nonostante la fluidoterapia e l’uso di farmaci ipocalcemizzanti (corticosteroidi, furosemide, calcitonina) avesse portato ad una remissione dell’ipercalcemia, l’uremia manifestava un’ulteriore progressione e il giorno 06-09-00 il cane veniva sottoposto ad eutanasia per scadimento delle condizioni generali. L’esame autoptico permetteva un ulteriore campionamento della massa, dei linfonodi prescapolari (unici a presentare modesta ipertrofia), del midollo emopoietico e di entrambi i reni. La massa veniva nuovamente classificata come emangiosarcoma e unici rilievi patologici provenivano dalla corticale renale, affetta da grave nefrite interstiziale, necrosi e calcificazione dell’epitelio tubulare. Commenti e conclusioni. L’ipercalcemia è una grave sindrome paraneoplastica e deriva dalla produzione di un fattore PTH-simile da parte del tessuto neoplastico in caso di linfomi, adenocarcinomi ed altre neoplasie, tra le quali non era però compreso l’emangiosarcoma. Il caso sopra descritto manifesta invece, per la prima volta, la probabile secrezione, da parte della neoplasia, di una proteina ad azione PTH-simile, che ha generato ipercalcemia e secondariamente una grave insufficienza renale. In questo caso il dosaggio del calcio ionico e del PTH sono risultati indispensabili per la valutazione del paziente. È degna di nota l’i perferritinemia, da considerare marker neoplastico. Ringraziamenti. Si ringrazia il Dott. Ferdinando Zanin per aver riferito il caso.

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MIELODISPLASIA NEL CANE: DESCRIZIONE DI TREDICI CASI CLINICI Caldin Marco Med. Vet., Furlanello TommasoMed. Vet., Loewer Sabine Med. Vet. Liberi professionisti, Padova Introduzione e presentazione dei casi clinici. La sindrome mielodisplastica comprende una serie di turbe delle cellule staminali del midollo emopoietico, a patogenesi complessa, che portano ad alterata proliferazione e maturazione (emopoiesi inefficace). Verrano presentati 13 casi di mielodisplasia raccolti nel periodo compreso tra Aprile 1998 e Luglio 2000. I cani erano di entrambi i sessi, sia meticci che di razza, di età compresa tra 9 mesi e 10 anni. In tutti sono stati eseguiti esame fisico, esame emocromocitometrico, profilo biochimico, coagulativo, urinario. Sono stati inoltre eseguiti altri esami di laboratorio, secondo quanto suggerito dai r eperti raccolti per ogni singolo caso. I dati principali provenienti dall’esame emocromocitometrico sono raccolti nella tabella. Alla lettura dello striscio erano presenti in ognuno una o più alterazioni della morfologia eritrocitaria, quali anisocitosi, macrocitosi, microcitosi, dacriocitosi, schistocitosi, presenza di Corpi di Howell-Jolly, punteggiature basofile, codocitosi. L’esame citopatologico ed istopatologico del midollo emopoietico,proveniente dall’ala dell’ileo, veniva eseguito in tutti i casi, presentando sempre alterazioni compatibili con mielodisplasia.

Interv. di rif.to Caso 1 Caso 2 Caso 3 Caso 4 Caso 5 Caso 6 Caso 7 Caso 8 Caso 9 Caso 10 Caso 11 Caso 12 Caso 13

RBC

WBC

Gran.Neutr.

Stima Piastr.

5.7-8.8 (x 10 6/µl)

0-1

5.2-13.9 (x 103/µl)

3.9-8.0 (x 10 3/µl)

Adeg.

4.4 5.2 5.7 4.8 3.3 5.8 2.8 3.5 1.9 3.9 1.13 6.08 5.69

1.4 ND ND ND 3.0 ND 0.1 5.1 0.6 ND 0.05 ND ND

15.8 2.1 4.3 5.7 6.5 18.2 22.9 23.9 6.6 11.8 22.4 2.8 4.9

12.1 1.2 3.2 4.2 5.5 13.1 12.5 19.8 4.1 8.9 18.8 2.2 3.0

Aum. Adeg. Adeg. Adeg. Adeg. Inadeg. Aum. Inadeg. Adeg. Adeg. Adeg. Inadeg. Inadeg.

La mielodiplasia era associata o causata dalle seguenti patologie: sieropositività a Rickettsia rickettsii (casi 1, 2, 3 e 12) e contemporaneamente a Ehrlichiosi granulocitaria [CGE] (3 e 12) o a insufficienza epatica cronica (5). Il caso 10 presentava anemia emolitica e sieropositività per CGE. Il caso 4 era affetto da linfoma multicentrico, in chemioterapia. Per i casi 7 e 11 si sospettava uno stato leucemico, rispettivamente megacarioblastico e mieloide acuto. I casi 6 e 8 presentavano complicazioni successive ad ovarioisterectomia terapeutica. Il caso 9 era affetto da iperadrenocorticismo con pregressa terapia con lysodren. Per il caso 13 non era evidente alcuna patolo gia concomitante. Commenti e conclusioni. La mielodisplasia è descritta infrequentemente in medicina veterinaria, ma la nostra raccolta di casi dimostra che la sindrome può presentarsi in seguito a patologie comuni, quali neoplasie, infezioni batteriche trasmesse da zec che, complicazione di terapie chirurgiche ed altre, oppure isolatamente, come forma primaria. Se la sindrome mielodisplastica viene riconosciuta, e l’attenta valutazione microscopica dello striscio ematico appare a questo fine indispensabile, è possibile approntare ulteriori piani diagnostici e ter apeutici, migliorando la gestione di casi altrimenti di difficile risoluzione.

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CLINICA E DIAGNOSTICA DI 2 CASI DI CISTI ARACNOIDEE INTRACRANICHE NEL CANE Lotti Donatella Med. Vet., Dottore di Ricerca in Medicina Interna - Libero professionista, Torino Arachnoid cysts (AC) can be congenital infrequent lesions that arise during development from a splitting and duplication of the arachnoid membrane; this splitting results in the formation of a cyst filled with cerebrospinal fluid. AC can also be acquired. There are very few reports of this lesion in domestic animals; to our knowledge, only six cases have been described in dogs and one in a cat. Clinical features, follow-up and magnetic resonance imaging (MRI) of intracranial intra-arachnoid cyst in two adult, male, small breed dogs are described. Case # 1, a 6.5 year-old, male, West highland white terrier was presented with cluster seizures since the age of 4 years, while case # 2, a 7 year-old, male, Pekingese dog was referred with acute behavioral alter ations and personality changes. In case #1 the physical and neurological exam were normal, and the signs were compatible with a forebrain dysfunction and with hepatic encephalopathy. In case # 2 the physical examination was normal. The neuroexam was normal except for a left rear limb delayed proprioception, compatible with a right forebrain lesion. The complete blood cell count and serum biochemistry were normal except for the ALP value, and post-prandial bile acid in case #1. Hepatic ultrasonography resulted normal in both dogs. MRI and eventually cerebrospinal fluid analysis were proposed in both dogs. In both cases MRI revealed an arachnoid cyst located in the quadrigeminal cistern: the signal intensity of the fluid-filled cyst was compatible with the contents being CSF fluid. Neither the cystic contents nor the wall were enhanced by contrast. In case #1 MRI showed a hypoplasia of corpus callosum and a partial absence of the septum pellucidum. The ventricular system was dilated, symmetrical and in axis in case #1 and asymmetric in case #2. Both dogs received only medical treatment: case #1 was started with KBr and phenobarbital and for the first two weeks with dexamethasone. The post-prandial bile acid level had returned to normal while ALP is currently increased. Case#2 was treated with dexamethasone and complete remission of clinical signs was obtained. Discussion. Previous reported canine cases occurred in three dogs aged 6-7 months and in three aged 4-7 years. The dogs presented in this paper are 6.5 and 7 years old. Seven of the eight canine cases, including the two in this report, occurred in small breed dogs and six out the eight affected dogs were male. In veterinary reports all the cysts were localized in the posterior fossa: the AC was located in the quadrigeminal cistern in the two dogs presented in this paper. Human AC can be associated with other anomalies such as the corpus callosum agenesis as in case #1 of this report. Hydrocephalus is present in 30 – 60% of patients with arachnoid cysts. In previously reported cases three dogs had ventriculomegaly; in both dogs of this paper ventriculomegaly was present. In human the most common clinical signs and symptoms are headache, nausea or vomiting, lethargy, seizures… In animals the most common clinical sign is seizures, but it is difficult to relate them to the cysts. In human medicine the treatment is medical or surgical. Of the six previously reported dogs, two were euthanised, two had a fenestration and anticonvulsant therapy and two were treated for seizures. The two dogs reported here had only medical treatment. The follow-up is 32 an 20 months respectively. Case #1 has now been free from seizures for 18 months, while case # 2 had one recurrence which resolved once more time with dexamethasone: he is not currently receiving any treatment. Further cases are necessary to confirm the apparent prevalence of AC in small breed, male dogs and to establish whether the onset of clinical signs is more frequent in young or adults dogs, whether the most frequent location is the quadrigeminal cistern and if there is a correlation between seizures and the cysts. References. Unpublished for lack of space, can be requested to the Author.

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CORREZIONE DI UN DOTTO ARTERIOSO PERVIO IN UNA TIGRE (PANTHERA TIGRIS) Maraldi Gianluca Med. Vet., Bertoldi Antonio Med. Vet., Furlanello Tommaso Med. Vet., Caldin Marco Med. Vet., Novello Lorenzo Med. Vet. Liberi professionisti, Padova Introduzione. Il dotto arterioso pervio è il difetto cardiaco congenito più comune nel cane ed è segnalato anche nel gatto. Nel caso che descriviamo questo difetto è stato diagnosticato e poi corretto chirurgicamente in una tigre (Panthera tigris). Descrizione del caso clinico. In data 16-05-00 è stato ammesso alla visita un cucciolo di tigre (nato in Italia da genitori detenuti dai proprietari), maschio, di un mese di età. L’anamnesi riferiva dispnea, abbattimento e vomito da circa 24 ore. Poiché l’alimentazione del cucciolo era a base di latte ricostituito e di alimenti pronti del commercio destinati ai felini, il proprietario avanzava l’ipotesi si trattasse di una polmonite ab ingestis. Alla visita il felino si presentava in scadenti condizioni di salute, con spiccata magrezza. All’auscultazione veniva rilevata la presenza di un murmure respiratorio normale ed un soffio cardiaco continuo irradiantesi su tutti i focolai. Radiogrammi di torace ed addome risultavano nella norma. L’esame ecocardiografico bidimensionale metteva in evidenza un sovraccarico volumetrico del ventricolo sinistro, mentre all’esame doppler era evidente un flusso turbolento nell’arteria polmonare principale, compatibile con dotto arterioso pervio. In data 08-06-00 si è proceduto alla correzione chirurgica del dotto arterioso pervio. Non essendo stato possibile, malgrado alcuni tentativi, ottenere subito un accesso vascolare stabile il paziente è stato tranquillizzato con acetilpromazina per via intramuscolare e, dopo 15 minuti, fentanil e ketamina sempre per via intramuscolare. Ottenuto un accesso vascolare, l’anestesia è stata indotta con la sequenza midazolam, atropina, alfentanil e propofol per via endovenosa ed è stata mantenuta con propofol, fentanil ed atracurio per via endovenosa in perfusione continua (TIVA Total Intra Venous Anaesthesia). Il paziente è stato ventilato meccanicamente per tutta la durata dell’anestesia con una miscela aria-ossigeno (FiO 2 0,5-1,0) con circuito semichiuso. Per il controllo del dolore perioperatorio si sono utilizzati mepivacaina intercostale prima dell’accesso chirurgico, ketamina a basso dosaggio in perfusione continua, mepivacaina intrapleurica in unica somministrazione alla chiusura del torace, ketorolac in unica somministrazione endovenosa lenta al termine della chirurgia. L’analgesia postoperatoria è stata valutata per 36 ore con la scala a punteggio di Mathews. È stata effettuata la toracotomia con accesso laterale a livello del quarto spazio intercostale sinistro con tecnica simile a quella descritta per il cane. Dopo aver retratto il nervo vago il dotto è stato isolato ed è stata effettuata una doppia legatura in seta. All’esame ecocardiografico di controllo, eseguito ad un mese di distanza dall’intervento, non era più visualizzabile il flusso turbolento in arteria polmonare ed era inoltre scomparso il sovraccarico volumetrico a carico del ventricolo sinistro. Al 30.10.00 l’animale è in ottimo stato di salute ed il suo sviluppo corporeo risulta normale. Commenti e conclusioni. Questo caso appare degno di nota essendo,a nostra conoscenza, il primo caso documentato di malformazione genetica cardiaca nella tigre (dotto arterioso pervio), documentata ecocardiograficamente e cor retta con successo. La terapia chirurgica ha permesso di mantenere in vita un animale appartenente ad una specie a rischio d’estinzione, anche se la possibile ereditabilità della malformazione dovrebbe precluderne la carriera riproduttiva. Ringraziamenti. Si ringraziano il Dott. Sergio Fanfoni per la consulenza cardiologica e il Dott. Piero Laricchiuta per la collaborazione fornita nella gestione del paziente.

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LINFOMA A LOCALIZZAZIONE SPINALE NEL CANE: SEGNALAZIONE DI UN CASO Maraldi Gianluca*, Furlanello Tommaso*Med. Vet., Caldin Marco* Med. Vet., Baroni Massimo** Med. Vet. *Libero professionista, Padova **Libero professionista, Monsummano Terme (PT) Introduzione. La comparsa di una paraparesi progressiva fino alla paraplegia, in un cane anziano di media taglia, può far sospettare principalmente una patologia compressiva a carico del midollo spinale, sia essa di natura discale che neoplastica. Meno probabili, in sede diagnostica differenziale, risultano lesioni di tipo infiammatorio o degenerativo. Nel presente lavoro viene descritto un caso clinico in cui, l’applicazione di un corretto protocollo diagnostico, ha consentito il raggiungimento della diagnosi e la conseguente formulazione di un’idonea terapia. Descrizione del caso clinico. In data 30-08-00 è stato ammesso alla visita un cane meticcio femmina ovariectomizzata, di 8 anni di età e di 23 kg di peso. L’anamnesi riferiva progressiva debolezza del treno posteriore e incontinenza urinaria. Gli esami di laboratorio, eseguiti alla comparsa della sintomatologia, tre settimane prima, denunciavano leucocitosi con neutrofilia matura e modesta tossicità. Il cane aveva ricevuto una terapia antibiotica a base di enrofloxacina ed amoxicillina più acido clavulanico senza ottenere alcun miglioramento. Alla visita il cane si presentava paraplegico, con vescica repleta e l’esame neurologico consentiva una localizzazione neuroanatomica della lesione compresa tra i segmenti midollari T3 e L3. La lesione appariva clinicamente di tipo monofocale. Il dolore superficiale era assente, mentre era ancora presente la dolorabilità profonda. Uno studio radiologico del rachide toraco-lombare non metteva in evidenza alcuna lesione ossea. Veniva quindi eseguito uno studio mielografico, preceduto dalla raccolta lombare del liquido cefalo-rachidiano (CSF). La mielografia metteva in evidenza una irregolare distribuzione del mezzo contrasto a livello del corpo vertebrale di T12. L’esame del CSF presentava una elevata cellularità, caratterizzata da una popolazione uniforme di elementi linfoidi d’aspetto blastico. Tale reperto permetteva la formulazione di una diagnosi di linfoma a localizzazione spinale intradurale. La chemioterapia prescelta, frutto di un compromesso tra la necessità di un’azione antitumorale e alcune limitazioni imposte dai proprietari, comprendeva un’associazione tra doxorubina (30 mg/mq ogni 3 settimane IV) e prednisone (1 mg/kg q24h PO). Il cane presentava un’ottima risposta già alla prima somministrazione di antiblastico, con ripresa delle capacità motorie dopo 48h. In data 30-10-00 la remissione era mantenuta, con ottime condizioni generali e in assenza di manifestazioni di tossicità alla doxorubicina. Commenti e conclusioni. Questo caso appare degno di nota essendo non frequente nel cane la localizzazione spinale intradurale, neoplasia viceversa relativamente frequente a livello spinale extradurale. È da notare che solo un corretto approccio diagnostico, eseguito senza la contemporanea o precedente somministrazione di terapia sintomatica, ha consentito di raggiungere la diagnosi e di mettere in atto una terapia di immediato successo. Infatti anche una sola somministrazione di corticosteroidi, di così frequente quanto erronea esecuzione nella pratica ambulatoriale, avrebbe quasi sicuramente negativizzato l’esame del CSF, escludendo ogni possibilità diagnostica. È infine interessante il riconoscimento,tramite gli esami di patologia clinica, di uno stato infiammatorio sistemico. Tale quadro era compatibile con uno stato linfomatoso ma non con altri quadri di patologia compressiva come, per esempio, una lesione di natura discale . Ringraziamenti. Si ringrazia il Dott. Stefano Mirko Barnes per aver riferito il caso.

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UN CASO DI TROMBOEMBOLISMO AORTICO NEL CANE IN SEGUITO AD IPERADRENOCORTICISMO Migliorini Francesco Med. Vet., Gaglio Paolo Med. Vet., Ruggiero Pietro Med. Vet. Liberi professionisti, Roma Caso clinico. Un cane meticcio, maschio, di anni 12 è sottoposto a visita perché da una settimana presenta diarrea, abbattimento sensoriale e zoppia ingravescente ad un arto posteriore. L’anamnesi remota e quella recente sono scarne a parte il riferimento di poliuria, polidipsia e polifagia da alcuni mesi. All’esame fisico l’arto posteriore destro appare sottratto all’appoggio, freddo al termotatto, dolente. Non è possibile percepire il polso femorale destro. A seguito del sospetto diagnostico di tromboembolismo arterioso il cane è sottoposto ad un approfondimento diagnostico comprendente esame emocromocitometrico, profilo biochimico, profilo emostatico ed esame delle urine completo. Valutati i dati anamnestici e il quadro clinico si effettua anche la titolazione del cortisolo basale e dopo stimolazione con ACTH. Viene effettuato un esame ecotomografico addominale, che conferma la presenza di un trombo occludente quasi completamente il lume dell’aorta addominale per un tratto di circa 5 cm fino all’insorgenza delle aa. iliache esterne. Si riscontra anche un aumento significativo del volume di entrambe le ghiandole sur renali, e una lesione nodulare iperecoica a carico del polo craniale del surrene destro. All’esame ecocardiografico è evidente ipertrofia miocardica concentrica e simmetrica del ventricolo sinistro e un’immagine riferibile ad un trombo, del diametro massimo di circa 1 cm, adeso alla parete atriale sinistra. Durante le procedure diagnostiche e, nonostante la terapia analgesica, la sintomatologia dolorifica del cane peggiora, spingendo i proprietari ad optare per l’eutanasia. All’esame necroscopico è confermata la presenza del trombo a carico del segmento distale dell’aorta addominale , le ghiandole surrenali appaiono asimmetriche e aumentate di volume e vengono sottoposte ad esame istopatologico; si evidenzia incremento degli spessori del setto interventricolare e della parete posteriore del ventricolo sinistro. I risultati degli esami ematobiochimici e del test ormonale sono compatibili con iperadrenocorticismo; il profilo emostatico suggerisce una sindrome da ipercoagulabilità con diminuzione significativa dei livelli di antitrombina III; l’esame istologico delle ghiandole surrenali testimonia un’iperplasia diffusa delle corticali e una iperplasia nodulare a carico del surrene destro. Conclusioni. Il tromboembolismo aortico nel cane non è un’evenienza comune e può essere una complicanza della sindrome di Cushing. La trombosi arteriosa è di solito secondaria a uno o alla combinazione di più fattori predisponenti: 1. Danno all’endotelio vascolare; 2. Stasi o turbolenza ematica; 3. Stato di ipercoagulabilità. L’ipertensione e la tendenza agli episodi di sepsi in corso di iperadrenocorticismo possono essere causa di danno endoteliale. L’aumento della pressione sistemica in corso di sindrome di Cushing può causare anche un danno glomerulare, responsabile della perdita di antitrombina III e del conseguente stato di ipercoagulabilità unitamente all’aumento dei fattori V, VIII, IX, X, del fibrinogeno e del plasminogeno. Nel nostro caso il sospetto diagnostico di tromboembolismo aortico è confermato dall’esame ecografico, e la patogenesi viene chiarita dagli esami ematobiochimici e dal test ormonale. L’ipertrofia concentrica miocardica documentata all’ecografia e all’esame necroscopico possono essere conseguenza dell’ipertensione sistemica e/o di una miocardiopatia ipertrofica primaria. Il reperto ecocardiografico del trombo intraatriale conferma lo stato di ipercoagulabilità del paziente.

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L’IMPIEGO DELLA CICLOSPORINA NEL TRATTAMENTO DELLE FISTOLE PERIANALI DEL CANE: ESPERIENZE PRELIMINARI Mussi Daniela A.* Med.Vet., Mortellaro Carlo M.** Med.Vet. *Libero professionista, Desio (MI) **Professore Ordinario di Patologia Chirurgica - Istituto di Clinica Chirurgica e Radiologia Veterinaria, Facoltà di Medicina Veterinaria, Università degli Studi di Milano Introduzione. Con il termine fistole perianali del cane s’intende un’infiammazione cronica aspecifica delle ghiandole perianali. L’adenite, sterile all’esordio, evolverebbe in una infezione cronica, necrotizzante e piogranulomatosa, responsabile della progressiva distruzione degli elementi ghiandolari e della comparsa di ulcere e tragitti di varia estensione e profondità, con possibile coinvolgimento dei tessuti anali, perirettali e perineali. Il Pastore tedesco sembra essere maggiormente predisposto a questa patologia. I trattamenti sintomatici, medici e/o chirurgici, hanno garantito risultati variabili e non infrequenti complicanze: recidiva, incontinenza e stenosi anale. Oggi, sebbene l’eziopatogenesi rimanga ancora non chiarita, gli studi si orientano verso una eziologia di tipo immuno-mediata. Obiettivo. Sono proposte le esperienze degli Autori nell’impiego della ciclosporina per il trattamento di fistole perianali di varia gravità, non complicate da stenosi anale. Materiali e metodi. Lo studio ha incluso 11 cani con fistole perianali di estensione tra 45° e 360°, non complicate da stenosi, accompagnate da lambimento frequente della regione perianale, tenesmo, dischezia ed ematochezia. Si richiedeva un profilo ematologico di base con protidogramma da ripetersi ogni 30 giorni ed una valutazione ogni 2 settimane mediante ispezione, palpazione e fotografia della regione perianale. In 4 casi si è effettuato un controllo della ciclosporinemia (riferimento: 400-600 ng/ml). La ciclosporina (5 mg/kg PO ogni 12 ore) è stata somministrata in associazione con metronidazolo (15 mg/kg PO ogni 12 ore) per 14 giorni, quindi da sola allo stesso dosaggio fino al raggiungimento di un grado di miglioramento stabile prossimo al 95%; infine alla dose di 2,5-3 mg/kg PO ogni 12 ore per 6 settimane. Laddove il grado di miglioramento non raggiungeva la completa guarigione si è proceduto a fistolectomia e sacculectomia bilaterale. Risultati. Sono stati inclusi 10 cani Pastore tedesco, di cui 2 incroci, ed 1 incrocio Setter: 5 maschi interi, 6 femmine (3 ovariectomizzate), di età media di 7,3 anni e peso medio di 32,1 kg. Al 14° giorno di terapia, scomparsi tutti i sintomi, il miglioramento delle lesioni variava tra il 50 ed il 100%. Un miglioramento stabile prossimo al 95% era ottenuto in 4-23 settimane. Trascorse le altre 6 settimane, per il residuare di 1-2 lesioni fistolose puntiformi, 5 cani erano sottoposti a fistolectomia e sacculectomia bilaterale: essi sono attualmente liberi da malattia (4,5-18 mesi); per altri 2 casi non si era ottenuto il consenso del proprietario alla chirurgia: il loro quadro clinico è attualmente stabile. Un cane, esente da malattia da 7 mesi, è stato soppresso per l’insorgenza di mielopatia degenerativa. I rimanenti 3 soggetti sono attualmente esenti da malattia (6,5-7,5 mesi). In 4 cani la cicatrizzazione delle lesioni è stata “esuberante” con comparsa di proliferazioni similpolipoidi diffuse. Due cani sono stati sottoposti a mastectomia (adenocarcinoma). Conclusioni. La ciclosporina ha consentito di ridurre (a volte con rapidità stupefacente) estensione e profondità delle lesioni, permettendo o una remissione totale (soprattutto per i casi meno gravi) o una che, seppur incompleta, ha concesso il ricorso ad una chirurgia meno demolitiva. Purtroppo i suoi costi, soprattutto per la lunghezza trattamento, ne limitano fortemente le possibilità d’impiego. Un più lungo follow-up ed una più ampia casistica sono inoltre imprescindibili per una completa valutazione del farmaco, in particolare per un suo impie go esclusivo.

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INUSUALE PRESENTAZIONE DI INFEZIONE DA TOXOPLASMA GONDII NEL GATTO, CON LESIONE SIMIL NEOPLASTICA NEL CAVO ORALE Nespolo Sandro* Med. Vet., Furlanello Tommaso** Med. Vet., Masserdotti Carlo*** Med. Vet., Mechelli Luca**** Med. Vet., Caldin Marco** Med.Vet. *Libero Professionista, Treviso **Libero professionista, Padova ***Libero professionista, Salò (BS) ****Dipartimento di Scienze Biopatologiche Veterinarie, Università di Perugia Premessa. La comparsa di una neoformazione nel cavo orale in un gatto anziano, affetto da un progressivo stato di malattia porta solitamente il clinico a sospettare la comparsa di uno stato neoplastico. In questo caso l'approfondimento cito-istopatologico ha portato ad una diagnosi di differente natura. Descrizione del caso clinico. È stato portato alla visita un gatto europeo maschio, castrato, di dieci anni d'età con deviazione a destra della lingua a causa della comparsa di una neoformazione sottomucosale, alla base della lingua, del diametro di circa due centimetri, che poteva essere descritta come una ranula. Il gatto era sottoposto a terapia steroidea (prednisone 10 mg/die) da circa due settimane a causa di una grave anemia non rigenerativa, ad eziologia ignota ed associata a mielofibrosi, come testimoniato da un precedente esame cito-istopatologico del midollo emopoietico. Il gatto è stato considerato esente da infezioni da retrovirus per la ripetuta negatività degli appositi accertamenti diagnostici. Considerando il segnalamento, l’anamnesi e l’esame fisico, si poteva sospettare uno stato neoplastico e veniva eseguito un ago aspirato della massa, ottenendo una cellularità mista, formata prevalentemente da cellule c.d. rotonde, a volte con aspetto istiocitario. I nuclei erano dismetrici a profilo rotondeggiante, ma fortemente alterato da numerose ed irregolari indentature membranarie. Associati si osservavano numerosi globi basofili anucleati, assimilabili a corpi linfoghiandolari. I linfonodi regionali ipsilaterali risultavano moderatamente ingranditi e venivano anch'essi campionati riportando, oltre alla popolazione linfoide residente, la medesima popolazione riscontrata nella lesione antecedente. Si sospettava quindi uno stato proliferativo di cellule c.d. rotonde, e primariamente uno stato linfomatoso. Si riteneva comunque indispensabile l'esame istopatologico della massa, che veniva campionata tramite biopsia incisionale. L'esame istopatologico del tessuto linguale evidenziava un'area di tessuto connettivo muscolare profondo, con aspetti flogistici di tipo necrotico-granulomatoso. All'interno di tale area erano presenti istiociti, cellule epitelioidi e macrofagiche contenenti numerosi corpiccioli di forma rotondeggiante, ovalare o falciforme, polarmente basofili e Feulgen positivi, per lo più intracellulari, di circa 1-3 µ di lunghezza, morfologicamente riferibili a trofozoiti. Nello stesso focolaio erano presenti pseudocisti intracellulari contenenti 10-15 elementi parassitari (tachizoiti). Alcune fibrocellule muscolari mostravano fenomeni di rabdomiolisi accanto ad eventi rigenerativi ed alcune di esse contenevano tipiche "cisti terminali" di 25-100 µ di lunghezza, con aggregati di numerosi bradizoiti circondati da una membrana PAS positiva. La valutazione dei preparati con metodica PCR confermava l'origine infettiva da Toxoplasma gondii. Il g atto veniva sottoposto a terapia con clindamicina, ma lo scadimento delle condizioni generali e l'impossibilità dell'assunzione di alimenti portava il proprietario a richiederne l'eutanasia. Conclusioni. Il caso sopra descritto appare degno di nota perché riporta una infezione da Toxoplasma con localizzazione tissutale, che aveva indotto una flogosi reattiva tale da presentarsi come una possibile neoformazione sia dal punto di vista fisico che cito-patologico. In mancanza di un esame istopatologico sarebbe stato impossibile emettere la diagnosi corretta. La grave soppressione midollare potrebbe avere una qualche relazione con l'infezione cronica. Infine si ignora se la terapia steroidea possa aver favorito la progressione dell'infezione.

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THE EVOLVING STONE AGE – AN ITALIAN PERSPECTIVE Stevenson Abigail E. (BSc. GIBiol), Hynds Waring K. (AIAT), Markwell Peter J. (BSc, BvetMed, MRCVS), Kasidas G.P. (BSc., PhD), Pedrick Toi P. (BSc., DVM) Mowbray, Leicestershire, UK Urolithiasis continues to be an important clinical problem in dogs and cats. Effective management of urolithiasis largely depends upon identification and manipulation of factors contributing toward the initial urolith formation. This process, in turn relies upon accurate identification of the type of urolith formed. This study details the analysis of uroliths surgically removed and analysed from cats and dogs in Italy. Uroliths removed from 47 cats and 181 dogs in Italy between January, 1999 and November, 2000, were analysed quantitatively by infra-red spectroscopy and photo-acoustic detection. The majority of feline uroliths analysed were found to be composed (> 70% of the mineral component) of struvite (68% of all uroliths analysed), with calcium oxalate comprising 9% (Table 1). Ammonium urate/uric acid occurred more commonly than either calcium oxalate or calcium phosphate. In contrast, the majority of canine uroliths were composed of either calcium oxalate (41%) or struvite (41%), (Table 2). A further 11% were ammonium urate/uric acid, with calcium phosphate and cystine each comprising 4% of the total. In cats, 58% of all uroliths were found in males across all age ranges. Canine uroliths composed of struvite, calcium oxalate, calcium phosphate were found in both sexes (as were mixed uroliths), although struvite was more common in females, while uroliths containing calcium (oxalate or phosphate) were found more commonly in males. In both species, struvite was the only mineral type found in patients less than one year old. The majority of feline uroliths were found in domestic shorthaired cats, although 22% of struvite, 25% of ammonium urate/uric acid, and 50% of calcium oxalate uroliths were found in Persians. 3% of struvite uroliths were also found in Siamese and Angora cats. Eighteen different breeds of dog presented with struvite urolithiasis, including the Yorkshire terrier (11% of struvite uroliths), shih tzu (20%), German shepherd (5%), and chow chow (4%), although 33% of struvite uroliths were found in crossbreed dogs. Eighteen breeds also presented with calcium oxalate uroliths with 31% found in the Yorkshire terrier, and 13% in the shih tzu. 83% of all ammonium urate/uric acid uroliths were found in Dalmatian dogs, while no breed predisposition was noted for dogs with cystine uroliths. In the past struvite has been the most common mineral type identified in feline and canine uroliths. Recently, however, an increase in the prevalence of calcium oxalate has been noted at two stone analysis centres within the US, implying that this mineral type may now be more common than struvite. This also appears to be the case in dogs within Italy, although the reasons behind this increase as yet remain unclear. In contrast however, struvite uroliths still remain the most common mineral type encountered in cats within Italy. Interestingly, ammonium urate/uric acid uroliths were more prevalent in cats than calcium oxalate uroliths, for reasons yet to be identified .

Table 1 - Quantitative analysis of uroliths surgically removed from cats within Italy Mineral

Struvite Calcium oxalate Ammonium urate/uric acid Calcium phosphate Cystine Mixed*

% (& no.) of total analysed 68 (32) 9 (4) 13 (6) 6 (3) 0 (0) 4 (2)

% found in male female 60 100 100 67 0 40

<1.0

40 0 0 33 0 60

7 0 0 0 0 0

% found in age range (years) 1.1 – 5.0 5.1 – 10.0 10.1+ 43 25 100 33 0 67

32 25 0 67 0 33

18 50 0 0 0 0

Table 2 - Quantitative analysis of uroliths surgically removed from dogs within Italy Mineral

Struvite Calcium oxalate Ammonium urate/uric acid Calcium phosphate Cystine Mixed*

% (& no.) of total analysed 33 (60) 41 (74) 10 (18) 4 (7) 4 (8) 8 (14)

% found in male female 38 89 95 86 100 81

62 11 5 14 0 19

<1.0 3 0 0 0 0 0

% found in age range (years) 1.1 – 5.0 5.1 – 10.0 10.1+ 39 11 78 33 29 7

46 58 22 50 71 64

12 31 0 17 0 29

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IMPIEGO DI COLLAGENE LIOFILIZZATO STERILE IN ORTOPEDIA E TRAUMATOLOGIA DEI PICCOLI ANIMALI, 55 CASI Vezzoni Aldo Med. Vet. SPCPA Dipl. ECVS, Petazzoni Massimo** Med. Vet, Olivieri Massimo Med. Vet ***, Baroni Ermenegildo Med. Vet.**** * Libero professionista, Cremona **Libero professionista, Mulazzano (Lo) ***Libero professionista, Samarate (Va) ****Libero professionista, Rovigo Introduzione. Per molti anni il mondo medico-scientifico ha studiato il modo di trovare un materiale adatto per sostituire i tessuti nelle lesioni con perdita di sostanza. A tale scopo, in passato, è stata impie gata una ampia gamma di materiali quali osso, cartilagine, metalli di diverso tipo, ceramica, polimeri di metacrilato, ecc. ma nessuno di questi materiali ha tuttavia soddisfatto le caratteristiche necessarie di un trapianto ideale ad impiego universale quali biocompatibilità, biodegradabilità capacità di essere sostituito da nuovo tessuto, assenza di immunogenicità, adeguata malleabilità e assenza di interferenza con la riparazione dei tessuti. Il collagene, invece, sembrerebbe soddisfare tutte queste caratteristiche. Obiettivo del presente lavoro è quello di individuare le applicazioni di collagene eterologo equino liofilizzato, sotto forma di feltro o di polvere, in traumatologia ed ortopedia dei piccoli animali. Materiali e metodi. 55 pazienti (vedi tabella a pagina seguente) sono stati selezionati per l’applicazione di un impianto di collagene eterologo equino sotto forma di feltro o di polvere. Tutti i pazienti erano animali di proprietà e da compagnia. Al momento dell’applicazione è stata compilata una scheda per la raccolta del segnalamento, dei dati anamnestici, del tipo di patologia, del tipo di applicazione e la forma di collagene applicata - polvere o feltro e le dimensioni di quest'ultimo. A 14 giorni dall’applicazione è stato eseguito il primo controllo clinico per verificare l’eventuale presenza di rigetto, di eventuali fistole, e/o di infezioni. L'ultimo controllo clinico e/o radiografico è stato eseguito come riportato in tabella con una media di circa tre mesi dall'applicazione dell'impianto. Risultati. Delle 55 applicazioni, 9 volte è stata impiegata la forma in polvere e 46 volte il feltro; 13 volte l’impiego di collagene è servito per colmare perdita di sostanza a carico della cute e/o dei tessuti molli sottostanti, 5 volte per colmare perdite di sostanza a carico di strutture teno-legamentose e 32 volte per colmare perdite di sostanza a carico dei tessuti osteocartilaginei. In 6 casi il collagene è stato impiegato anche come tampone emostatico intrachirurgico. In nessun caso si sono verificati fenomeni clinici di rigetto o di infezione a carico delle applicazioni. Discussione e conclusioni. Numerose sono state le applicazioni a conferma della versatilità d’impiego delle due forme di collagene utilizzate. Gli autori hanno riscontrato una certa difficoltà nell’applicazione del collagene in feltro se inumidito o imbibito da soluzioni fisiologiche od organiche in quanto il feltro stesso diventa leggermente colloso e ciò ne impedisce una precisa applicazione. Questa difficoltà è stata ben superata con l’applicazione del materiale su tessuti asciutti. Il collagene in feltro si è rivelato utile per il mantenimento in sede dei trapianti di osso spongioso nelle osteosintesi. Il feltro collagene può essere tagliato agevolmente con un paio di forbici o spezzato manualmente per essere adattato nelle più diverse situazioni. L’impianto di collagene, impiegato come matrice a riempimento di “difetti” a carico di tessuti molli o di tessuti osteocartilaginei e come tampone emostatico, è risultato di notevole aiuto in numerosi interventi di pertinenza ortopedica e/o traumatologica. Ulteriori studi comparativi dovranno essere eseguiti per la valutazione delle proprietà del collagene eterologo a confronto con quelle del trapianto di osso spongioso utilizzato a riempimento di difetti a carico del tessuto osseo. La bassa immunogenicità del collagene impiegato ha consentito di ottenere una alta biocompatibilità e conseguentemente nessun caso di rigetto da parte degli organismi ospite.

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SPECIE

RAZZA

SESSO

ETÀ

PESO

PATOLOGIA

APPLICAZIONE

(kg) 1 2

CANE CANE

3 4 5

FORMA

FOLLOW-UP

COLLAGENE

(giorni) 30 21

BARBONE NANO BRACCO ITALIANO

Fs M

5A 3A

4 23

LUSSAZIONE COXOFEMORALE FERITA LACERO-CONTUSA

PLASTICA CAPSULA ARTICOLARE MEDICAZIONE FERITA

FELTRO FELTRO

CANE

CANE CORSO

TPLO OSTEOTOMIA LIVELLANTE IL PIATTO TIBIALE

DIFETTO OSSEO

FELTRO

180

CANE CANE

COLLIE COLLIE

M M

3A 5A

27 34

FERITA INFETTA METACARPI LUSSAZIONE COXOFEMORALE

MEDICAZIONE FERITA EMOSTASI

FELTRO FELTRO

21 60

CANE

DOBERMANN

SLOT VENTRALE CERVICALE C6-C7

EMOSTASI

FELTRO

7 8

CANE CANE

GOLDEN RETRIEVER GOLDEN RETRIEVER

M M

7M 7M

28 21

OSTECTOMIA DISTALE ULNA OSTECTOMIA DISTALE ULNA

DIFETTO OSSEO DIFETTO OSSEO

FELTRO FELTRO

60 180

CANE

INCROCIO

10A

NECROSI ISCHEMICA DA BENDAGGIO

MEDICAZIONE FERITA

FELTRO

10 11

CANE CANE

INCROCIO INCROCIO

F F

10M 14A

15 9

OSTEOSINTESI RADIO E TIBIA FERITA DA MORSO REGIONE AVAMBRACCIO

DIFETTO OSSEO MEDICAZIONE FERITA

FELTRO FELTRO

70 21

CANE

INCROCIO

ARTRODESI ARTICOLAZIONE GOMITO

DIFETTO OSSEO

POLVERE

CANE

INCROCIO

FERITA DA MORSO REGIONE GOMITO

MEDICAZIONE FERITA

FELTRO

14 15

CANE CANE

INCROCIO INCROCIO

F F

6A 6A

8 8

OSTEOSINTESI TIBIA LUSSAZIONE COXOFEMORALE DORSALE BILATERALE

DIFETTO OSSEO PLASTICA CAPSULA ARTICOLARE

FELTRO FELTRO

101 21

CANE

INCROCIO

OSTEOSINTESI TIBIA

DIFETTO OSSEO

FELTRO

126

17 18

CANE CANE

INCROCIO INCROCIO

M M

10A 11A

12 18

SLOT CERVICALE OSTEOSINTESI RADIO

DIFETTO OSSEO DIFETTO OSSEO

FELTRO POLVERE

30 112

CANE

INCROCIO

12M

ARTRODESI ARTICOLAZIONE TARSO

DIFETTO OSSEO

FELTRO

120

20 21

CANE CANE

INCROCIO INCROCIO

M M

15A 1A

10 10

FERITE DA MORSO SOLCOPLASTICA TROCLEA FEMORALE

MEDICAZIONE FERITA DIFETTO OSTEOCARTILAGINEO

FELTRO FELTRO

120 60

CANE

INCROCIO

REVISIONE ARTRODESI GOMITO

DIFETTO OSSEO

FELTRO

23 24

CANE CANE

INCROCIO INCROCIO

M M

6M 7A

17 26

OSTEOSINTESI OMERO OSTEOSINTESI METAFISI DISTALE FEMORE

DIFETTO OSSEO DIFETTO OSSEO

POLVERE FELTRO

84 80

CANE

INCROCIO

TPLO OSTEOTOMIA LIVELLANTE IL PIATTO TIBIALE

EMOSTASI

FELTRO

CANE

INCROCIO

TPLO OSTEOTOMIA LIVELLANTE IL PIATTO TIBIALE

EMOSTASI

FELTRO

27 28

CANE CANE

LABRADOR RETRIEVER LABRADOR RETRIEVER

F F

14M 6M

30 20

DAR ARTROPLASTICA OSTECTOMIA DISTALE ULNA

DIFETTO OSSEO DIFETTO OSSEO

FELTRO FELTRO

150 56

CANE

LABRADOR RETRIEVER

OSTECTOMIA DISTALE ULNA

DIFETTO OSSEO

FELTRO

30 31

CANE CANE

LABRADOR RETRIEVER LABRADOR RETRIEVER

Fs M

1,5A 7M

27 23

DAR ARTROPLASTICA TRIPLICE OSTEOTOMIA PELVICA

DIFETTO OSSEO DIFETTO OSSEO

FELTRO FELTRO

285 56

CANE

LABRADOR RETRIEVER

TRIPLICE OSTEOTOMIA PELVICA

DIFETTO OSSEO

FELTRO

33 34

CANE CANE

PASTORE BELGA PASTORE TEDESCO

M F

2,5A 10A

26 31

ESTRAZIONE DENTE CANINO INVESTIMENTO - FERITA LACERO-CONTUSA

DIFETTO OSSEO MEDICAZIONE FERITA

FELTRO FELTRO

21 120

CANE

PASTORE TEDESCO

OSTEOSINTESI UAP CON VITE A COMPRESSIONE

DIFETTO OSSEO

POLVERE

36 37

CANE CANE

PASTORE TEDESCO PASTORE TEDESCO

Fs Fs

12A 2A

36 30

LUSSAZIONE COXOFEMORALE VENTRALE OSTEOSINTESI RICOSTRUZIONE FEMORE

PLASTICA CAPSULA ARTICOLARE DIFETTO OSSEO

FELTRO FELTRO

56 308

CANE

PASTORE TEDESCO

INVESTIMENTO - FERITA LACERO-CONTUSA

MEDICAZIONE FERITA

FELTRO

136

CANE

ROTTWEILER

1,5A

SINDESMORRAFIA TIBIO-ROTULEO

PERDITA DI SOSTANZA LEGAMENTO

POLVERE

40 41

CANE CANE

SCHNAUTZER SCHNAUTZER

F M

4,5A 10A

14 32

FERITA LACERO-CONTUSA CARPO NEOPLASIA OSSEA

MEDICAZIONE FERITA EMOSTASI

FELTRO FELTRO

21 14

CANE

SCHNAUTZER

LUSSAZIONE COXOFEMORALE DORSALE

PLASTICA CAPSULA ARTICOLARE

FELTRO

43 44

CANE CANE

SETTER INGLESE TERRANOVA

M M

7M 8M

17 48

DAR ARTROPLASTICA DAR ARTROPLASTICA

AMALGAMA TETTO ACETABOLARE DIFETTO OSSEO

POLVERE FELTRO

56 245

CANE

YORKSHIRE TERRIER

2,2

ALLINEAMENTO TIBIA

MEDICAZIONE FERITA

POLVERE

46 47

CANE GATTO

YORKSHIRE TERRIER COMUNE EUROPEO

M Fs

8A 2A

5 3,5

EMILAMINECTOMIA OSTEOSINTESI METAFISI DISTALE FEMORE

EMOSTASI DIFETTO OSSEO

FELTRO FELTRO

30 155

GATTO

COMUNE EUROPEO

OSTEOSINTESI

DIFETTO OSSEO

FELTRO

150

49 50

GATTO GATTO

COMUNE EUROPEO COMUNE EUROPEO

M M

3A 5M

3,7 2,5

FERITA INFETTA REGIONE LOMBARE FERITA LACERO-CONTUSA CARPO

MEDICAZIONE FERITA MEDICAZIONE FERITA

FELTRO FELTRO

30 21

GATTO

COMUNE EUROPEO

4,5

SALTER HARRIS I FEMORE DISTALE

DIFETTO OSSEO

FELTRO

180

GATTO

COMUNE EUROPEO

3,5

OSTEOSINTESI TIBIA

DIFETTO OSSEO

POLVERE

252

53 54

GATTO GATTO

COMUNE EUROPEO PERSIANO

Mc Mc

5A 1A

5 3,5

OSTEOSINTESI TIBIA OSTEOSINTESI TIBIA

DIFETTO OSSEO DIFETTO OSSEO

POLVERE FELTRO

42 34

GATTO

COMUNE EUROPEO

FERITA LACERO CONTUSA

MEDICAZIONE FERITA

FELTRO

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CONDROMA TRACHEALE: DIAGNOSI E TRATTAMENTO PER – ENDOSCOPICO Petroccia Giovanni Med.Vet. Libero professionista, Roma Introduzione. Nello studio delle patologie dell’albero respiratorio, l’endoscopia rappresenta un importante mezzo diagnostico, tramite l’utilizzo di telecamera e proiezione su video delle immagini acquisite, è possibile gestire con maggiore praticità l’endoscopia operativa. Obiettivo. Documentare la minima invasività della gestione endoscopica di un caso di condroma tracheale, sia da un punto di vista diagnostico, ma anche terapeutico. Materiali e metodi. (Viene di seguito presentato il caso clinico riferibile ad un cane Rottweiler maschio sottoposto ad accertamenti clinico-diagnostici in seguito alla presenza di grave sintomatologia respiratoria). Cico, Rottweiler, maschio di 8 anni di età, viene portato alla visita per una sintomatologia respiratoria grave, caratterizzata da dispnea con rumore sia inspir atorio che espiratorio, con tendenza ad aggravarsi con la minima eccitazione. L’anamnesi remota riferiva che inizialmente il paziente presentava anche tosse e aveva ricevuto un trattamento sintomatico che mitigava solamente i sintomi principali. I primi segni clinici si erano manifestati 2 mesi prima e le indagini precedentemente eseguite comprendenti esami ematochimici e le radiografie del torace nei due decubiti laterali e in decubito dorsale, non avevano rilevato alterazioni di sorta. A fronte della progressione dei segni clinici e della mancata risposta a un trattamento sintomatico, abbiamo consigliato una tracheo-broncoscopia. (La scelta di un esame diagnostico collaterale non deve essere consigliata per la mancata regressione dei sintomi in base a terapie ex juvantibus). La tipologia dei disturbi clinici e la scarsa sensibilità diagnostica dell’esame radiografico per quanto attiene ad eventuali lesioni intraluminali ha consigliato l’impiego di una indagine strumentale broncoscopica diretta. Il paziente è stato premedicato con Diazepam, l’anestesia generale è stata indotta con Propofolo per via endovenosa e proseguita poi per via inalatoria tramite intubazione orotracheale mediante Isoflorane. Posto il paziente in decubito destro, si è proceduto a intubazione selettiva del bronco principale di sinistra, sotto visione endoscopica, a mezzo di un broncoscopio flessibile , diametro 6 mm. La tracheoscopia evidenziava, in corrisponenza del tratto intratoracico della trachea alla distanza di 40 cm dagli incisivi, una massa rotondeggiante a larga base di impianto, biancastra che occupava il 90% del lume tracheale. La biopsia escissionale è stata condotta sotto guida endoscopica, inizialmente con endoscopio flessibile di 6 mm di diametro, poiché ha permesso l’uso della pinza o ansa diatermo per polipectomia attraverso il canale di servizio dell’endoscopio, asportando gran parte della massa occupante il lume tracheale. Successivamente l’intervento è stato completato con un endoscopio rigido o telescopio di Hopkins del diametro di 4 mm e di una forbice diatermo per chirurgia endoscopica, l’impiego di quest’ultimo strumento è avvenuto per via parendoscopica. Il tutto con l’ausilio di una videocamera e di un video dedicato. L’istologia dimostrava un quadro compatibile con una diagnosi di condroma tracheale, o di condrosarcoma low grade. Le condizioni del paziente miglioravano immediatamente dopo la chirurgia endoscopica e il proprietario rifiutava quindi una resezione chirurgica della lesione tracheale. Il paziente è stato poi ricondotto alla nostra attenzione 8 mesi dopo la rimozione della massa, a causa di una recidiva dei segni clinici. La tracheoscopia effettuata in quell’occasione evidenziava una massa simile a quella precedentemente asportata, ma molto più distale, in corrispondenza della biforcazione o carena tracheale a circa 3 cm dal bronco principale di sinistra, del diametro di circa 2 cm, di colore biancastro. La sede della precedente biopsia escissionale risultava rivestita da una mucosa tracheale normale e non erano evidenti recidive della massa. Il proprietario ha negato l’autorizzazione per una biopsia della nuova lesione e ha chiesto l’eutanasia del paziente. Risultati e discussione. La tracheoscopia ha permesso di diagnosticare la patologia tracheale e di dare sollievo alla sintomatologia con un intervento di breve durata e con una minima invasione chirurgica. La video endoscopia ha reso più agevole la rimozione della massa. In seguito alla diagnosi istologica, il paziente avrebbe richiesto una resezione chirurgica della porzione di trachea interessata dalla neoplasia. Le migliori condizioni respiratorie avrebbero consentito una gestione anestesiologica meno rischiosa, tuttavia il proprietario ha rifiutato l’intervento chirurgico. La rimozione per-endoscopica della massa, se pur da considerarsi unicamente una biopsia escissionale, è risultata in una palliazione dei segni clinici per 8 mesi. La recidiva a 8 mesi era attribuibile a una seconda lesione distale rispetto alla lesione primaria che potrebbe rappresentare una seconda lesione primaria,una metastasi, o il risultato della manipolazione della massa durante la biopsia escissionale. La differenziazione istologica tra un condroma e un condrosarcoma low grade può non essere sempre univoca, come nel caso in esame. Conclusioni. L’endoscopia è un esame complementare importante in un paziente affetto da patologie respiratorie, soprattutto a fronte della negatività degli accertamenti ematochimici e radiografici. In questo caso l’endoscopia ha permesso sia di raggiungere una diagnosi istologica della patologia in esame, ma anche di ottenere la palliazione della sintomatolo gia respiratoria per 8 mesi. Nella valutazione di un paziente con sintomatologia tracheale è importante includere nella lista delle diagnosi differenziali anche le neoplasie tracheali.

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IPERTENSIONE SISTEMICA IN CANI AFFETTI DA GLOMERULONEFRITE DOVUTA A LEISHMANIOSI: MODIFICAZIONI CARDIOVASCOLARI IN CORSO DI TERAPIA CON BENAZEPRIL Poggi Marco* Med. Vet., Borgarelli Michele** Med. Vet. Dipl. ECVIM-CA (Cardiology), Bussadori Claudio*** Med. Vet. Dipl. ECVIM-CA (Cardiology) *Libero professionista, Imperia **Libero professionista, Avigliana (To) ***Libero professionista, Milano Introduzione. La leishmaniosi canina appare spesso associata a glomerulonefrite che rappresenta una delle cause più frequenti di ipertensione sistemica in medicina veterinaria. Tra i meccanismi fisiopatologici responsabili dell’ipertensione nel corso di glomerulonefrite, i più importanti riguardano l’attivazione del sistema renina angiotensina aldosterone (SRAA), l’aumento del liquido extracellulare (LEC), la diminuita secrezione da parte del rene dei sistemi antiipertensivi renali (prostaglandine, chinine e bradichinine). Le alterazioni cardiache, conseguenti a ipertensione, sono legate all’ipert ro fia concentrica ventricolare sinistra in risposta all’aumento del post carico (sovraccarico pressorio). Tale condizione conduce ad una alterata funzione diastolica. Lo studio ecocardiografico Doppler dei flussi transmitralici si è dimostrato sia nell’uomo che negli animali un metodo sensibile per lo studio non invasivo della funzione diastolica. Obiettivo. Lo scopo di questo lavoro è quello di descrivere le modificazioni ecocardiografiche, nel corso del trattamento con benazepril, in cani con glomerulonefrite da leishmaniosi e ipertensione sistemica. Materiali e metodi. Cinque soggetti affetti da leishmaniosi (diagnosticata con sierologia immuno-fluorescenza >1/160 o diagnosi parassitologica diretta) sono stati inclusi nel presente studio, tutti i soggetti dovevano inoltre rispondere ai seguenti criteri: età superiore a sei mesi, consenso informato, Leishmaniosi in fase stabile con insufficienza renale, creatinemia compresa tra 1,6 e 3,9 peso specifico urine < 1015 e proteinuria > 500 mg/dl, pressione sistemica sistolica > 160 mmHg (metodo Doppler). I cani sono stati assegnati su base random ad uno dei due seguenti gruppi terapeutici: gruppo 1 è stato somministrato benazepril 0,25 mg/kg (n= 2), gruppo 2 controllo (n=3). Lo studio è stato eseguito in doppio cieco. I controlli sono stati effettuati ai giorni 0 – 7 – 15 – 30 – 60 – 90 sono stati eseguiti misurazione della pressione sistemica, esame emocromocitometrico, elettroforesi ed esame urine completo con sedimento rapporto proteinuria creatinuria, creatinemia, urea ed elettroliti, ai giorni 0 – 90 sono stati eseguiti eco doppler renale, esame ecocardiografico Doppler ed urocoltura. Risultati e discussione. Le tabelle 1 e 2 riportano i valori della pressione sistemica e i valori ecocardiografici eco Doppler rispettivamente per i soggetti del gruppo 1 e 2. Entrambi i cani appartenenti al gruppo 1 presentavano disfunzione diastolica, mentre al termine dello studio si osserva tendenza all’aumento del rapporto E/A. Un solo soggetto del gruppo 2 (caso n°3) presentava disfunzione diastolica, mentre tutti i casi del gruppo 2 presentavano diminuito rapporto E/A alla visita gg. 90. In entrambi i soggetti del gruppo 1 si osserva inoltre diminuzione della massa ventricolare sinistra. I risultati preliminari di questo lavoro suggeriscono l’efficacia del benazepril nel rallentare l’ipert ro fia cardiaca e nella normalizzazione della funzione diastolica nei soggetti affetti da ipertensione sistemica, conseguente a nefropatia. B i bl i ografia. La bibliografia è a disposizione presso gli autori. Ringraziamenti. Il presente lavoro è stato reso possibile grazie al contributo di Novartis Animal Health. Tabella 1 - Gruppo 1 soggetti sottoposti a terapia con benazepril Caso 1 Visita g 0

Caso 1 Visita g 90

Caso 2 Visita g 0

Caso 2 Visita g 90

14 170 9,5 33,5 10 20,9 38 75 0,63 0,74 0,85 83

14 162 7,8 39,4 8,7 25,8 34 71 0,69 0,7 0,98 154

57 180 12,5 40 12,3 29,9 28 121 0,34 0,48 0,7 137

62 178 10,3 40 12,1 27,1 32 106 0,39 0,43 0,9 124

Peso (kg) BPs (mmHg) IVSd (mm) LVd (mm) PWd (mm) LVs (mm) SF (%) LVM (gr.) Ve (m/s) Va (m/s) E/A dt E (msec)

Tabella 2 - Gruppo 2 soggetti sottoposti a terapia con placebo

Peso (kg) BPs (mmHg) IVSd (mm) LVd (mm) PWd (mm) LVs (mm) SF (%) LVM (g) Ve (m/s) Va (m/s) E/A dt E (msec)

Caso 3 V. g 0

Caso 3 V. g 90

Caso 4 V. g 0

Caso 4 V. g 90

Caso 5 V. g 0

Caso 5 V. g 90

33 215 10,1 38,2 11,1 29,4 23 95 0,46 0,59 0,77 105

30 191 10,9 39,9 11,4 32,5 19 106 0,39 0,43 0,90 114

28 176 9,1 38,9 8,7 19,9 49 78 0,75 0,46 1,63 NA

28 171 9,2 38,7 11,1 26,4 32 91 0,52 0,58 0,90 102

31 163 11,5 38,9 13 29,6 24 116 0,63 0,56 1,1 NA

30 170 10,5 41,8 12 29,1 30 111 0,49 0,69 0,71 119

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PARAMETRI FISIOLOGICI NELL'OFTALMOLOGIA DEI RAPACI Puddu Gianluigi DVM PhD, Petruzzi Valentino DVM, Professor Facoltà Medicina Veterinaria di Sassari Introduzione. Nell'ambito dell'oftalmologia aviare l'approccio clinico è complicato spesso dall'assenza in bibliografia di parametri fisiologici importanti per una corretta valutazione della funzionalità dell'apparato visivo. Scopo del lavoro. Gli Autori si propongono di quantificare 2 importanti parametri fisiologici quali Schirmer Tear Test (STT) e pressione intraoculare (IOP) nei rapaci, classe che conta diverse centinaia di specie. Materiali e metodi. Sono state impiegate 21 poiane adulte (Buteo buteo) con peso medio di 722,7 g, 20 gheppi adulti (Falco tinnunculus) con peso medio di 230 g e 16 barbagianni adulti (Tyto alba) con peso medio di 420 g. Sono stati indagati i seguenti parametri: 1) Valutazione quantitativa della secrezione lacrimale. Sono state utilizzate a questo scopo strisce sterili dello Schirmer Tear Test (Schering Plough). Ogni striscia era posta, mediante una pinza, nel centro del fornice congiuntivale della palpebra inferiore per 60''; allo scadere del tempo veniva letto il valore corrispondente. 2) Tonometria. La tonometria è stata valutata mediante il tonometro per applanazione (Tono-Pen XL, Mentor Opthalmics). La IOP è stata valutata dopo 60'' dall'instillazione topica di un anestetico locale (Novesina 0,4%, Novartis). La rilevazione è stata effettuata toccando con leggerezza la cornea, lateralmente, 5 mm dal limbo per ridurre al minimo il movimento di escursione della membrana nittitante che, normalmente, è stimolato dall'avvicinarsi dello strumento all'occhio. Risultati. La IOP media rilevata nelle poiane è stata di 21,66 (± 3,48) mm di Hg, con un range compreso tra 16 e 29 mm di Hg. Nei gheppi la IOP media è stata di 11,65 (± 2,78) mm di Hg con un range compreso tra 24 e 7 mm di Hg. Nei barbagianni la IOP media è stata di 9,95 (± 2,19) mm di Hg, con un range compreso tra 13 e 6 mm di Hg. Il valore medio del test di Schirmer nelle poiane è risultato di 16,16 (± 3,61) mm/minuto con valori minimi di 10 e massimi di 23 mm/min. Nei gheppi il valore medio è stato di 5,7 (± 1) mm/min, con minimi e massimi rispettivamente di 8 e 5 mm/min. Nei barbagianni il valore medio dello STT è stato di 5,5 (± 0,5) mm/min, con range di 5 e 7 mm/min. Discussione. Parametri come la IOP sono influenzati da diversi fattori: emodinamici, tono dei muscoli extraoculari, farmaci anestetici, retrazione da parte dei muscoli retrattori del bulbo. Nella nostra esperienza abbiamo avuto modo di osser vare che alcuni protocolli anestesiologici, come per esempio l'associazione tiletamina-zolazepam, non hanno indotto variazioni significative sia nella IPO sia nella quantità di lacrime prodotte. Per quanto attiene alla valutazione dello STT, la scarsa secrezione lacrimale registrata nei rapaci notturni, con valori più bassi rispetto ai rapaci diurni, trova verosimilmente motivazione anatomica nell'assenza della gh. della terza palpebra in questa specie; per quanto riguarda i gheppi, la riduzione della produzione lacrimale, potrebbe essere dovuta alle ridotte dimensioni dell'occhio di questi animali e quindi alla conseguente ridotta dimensione della gh. della terza palpebra e del suo secreto.

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EFFETTO MIDRIATICO DI SOSTANZE PARASIMPATICO-LITICHE E CURARIFORMI NEL BUTEO BUTEO Puddu Gianluigi DVM PhD, Petruzzi Valentino DVM, Professor Facoltà Medicina Veterinaria di Sassari Introduzione. È noto che negli uccelli l'iride è composta principalmente da fibre muscolari striate, con una percentuale variabile e non ancora definita nelle varie specie, di fibre non striate. Pertanto le sostanze simpaticomimetiche e parasimpaticolitiche comunemente usate per la dilatazione pupillare degli occhi dei mammiferi sono inefficaci negli uccelli, nei quali sono invece prevalentemente usate per lo scopo sostanze che bloccano le giunzioni neuro-muscolari come i farmaci curarosimili. Scopo del lavoro è di comparare l'effetto midriatico di sostanze parasimpaticolitiche e curariformi applicate localmente nel Bu teo buteo e di valutarne gli eventuali effetti secondari locali e/o sistemici. Materiali e metodi. Sono state impiegate 21 poiane adulte. Gli animali sono stati suddivisi random in tre gruppi di sette soggetti. Non è stata adottata nessuna contenzione chimica. I prodotti testati sono soluzioni commerciali di vecuronio bromuro (a) (4 mg/ml), sol. salina sterile (0,9%) e atropina solfato 1% (b) (10 mg/ml). Ai soggetti del gruppo A sono state applicate 2 gocce di vecuronio per 3 volte ad intervalli di 15 minuti. Ai soggetti del gruppo B ogni 7,5 minuti erano somministrate alternativamente, per 3 volte, 2 gocce di vecuronio e 2 gocce di atropina. Ai soggetti del gruppo C infine ogni 7,5 minuti, per 3 volte, era somministrato vecuronio in quantità di 2 gocce. Sull'occhio di controllo, venivano applicate con la stessa cadenza dei farmaci testati 2 gocce di sol. salina sterile. Le osservazioni sulla variazione del diametro pupillare erano valutate successivamente, ad intervalli di 15 minuti, per la durata di 250 minuti. Risultati. Gruppo A: gli effetti farmacologici sono stati lenti e la dilatazione completa non è stata ottenuta in 4 dei 7 soggetti testati. Gruppo B: in 6 dei 7 soggetti si è avuta una dilatazione pupillare completa. Gruppo C: la completa dilatazione della pupilla non è stata raggiunta in 3 dei 7 soggetti. Su tutti gli animali testati non sono stati evidenziati effetti collaterali locali o sistemici. Conclusioni. L'applicazione topica di vecuronio bromuro sia ad intervalli di 15' che di 7,5' ha determinato effetti midriatici non costanti. Massima midriasi non è stata raggiunta, infatti, in più della metà dei soggetti del gruppo A ed in 3 soggetti del gruppo C. Risultati più costanti garantisce l'associazione atropina + vecuronio con la quale in 6 soggetti su 7, si è raggiunta la dilatazione pupillare massima per un lasso di tempo sufficientemente lungo. Il migliore effetto midriatico ottenuto con l'associazione potrebbe essere il risultato del sommarsi dell'azione parasimpaticolitica dell'atropina sulle fibre muscolari lisce e di blocco neuromuscolare del vecuronio sulle fibre striate. L'assenza di effetti collaterali, sia locali sia sistemici, segnalati in altre sperimentazioni, vanno verosimilmente attribuiti alla scarsa dose di farmaco assorbito. L'instillazione topica di vecuronio bromuro e atropina risponde alle esigenze di midriasi per esami oftalmici di routine negli occhi degli uccelli.

(a) Norcuron, Organon Teknica. (b) Atropina 1%,Allergan.

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MALFORMAZIONE BILATERALE DEL GOMITO IN UN GATTO Rossi Federica DMV, SRV, Specialista in radiologia veterinaria, Vignoli Massimo DMV, SRV, Terragni Rossella*** DMV Liberi professionisti, Sasso Marconi (BO) Introduzione. La letteratura veterinaria segnala alcune malformazioni congenite degli arti anteriori nel gatto: vengono descritti casi di polidattilia, sindattilia, sinfalangismo, agenesia o ipoplasia del radio, dislocazioni congenite della testa del radio, fusione carpale, sinostosi radio-ulnare. L'obiettivo del presente lavoro è di descrivere l'aspetto clinico e radiografico di un gatto affetto da una malformazione congenita bilaterale del gomiti, mai riportata, in base alle nostre conoscenze, dalla letteratura. Caso clinico. Un gatto Europeo, maschio, di 9 mesi veniva portato alla visita presso l'Ambulatorio Veterinario dell'Orologio per un consulto radiografico. L'anamnesi riportava il mancato utilizzo, fin dalla nascita, dell'arto anteriore sinistro durante la deambulazione; l'animale viveva in casa e non erano mai stati riportati traumi. Clinicamente era evidente un accorciamento dell'avambraccio sinistro e la mano veniva mantenuta in atteggiamento di extrarotazione di circa 90°; i movimenti di flessione ed estensione dell'articolazione del gomito sinistro erano ridotti, ma le manualità non evocavano dolore. L'esame obiettivo non evidenziava altre anormalità. Il gatto veniva sottoposto, previa sedazione profonda, all'esame radiografico di tutte le articolazioni dello scheletro appendicolar e, inoltre del bacino e del cranio. Entrambi gli arti anteriori presentavano una malformazione , che risultava più grave a sinistra, caratterizzata da una deviazione in senso craniale della porzione prossimale dell'ulna. A sinistra era inoltre presente la sublussazione prossimale del radio, un rilevante accorciamento di tutto l'avambraccio, la sinostosi radio-ulnare e la rotazione di 90° del carpo e della mano. A destra si rilevava anche una deviazione mediale della diafisi del radio, mentre la rotazione della mano risultava di minima entità. Le altre articolazioni si presentavano radiologicamente normali. Il controllo dopo 3 mesi dalla prima visita metteva in evidenza un miglioramento clinico del gatto nell'utilizzo dell'arto anteriore sinistro, mentre il follow up radiografico mostrava una situazione sostanzialmente invariata. Nonostante la presenza della malformazione, la funzionalità degli arti anteriori veniva considerata soddisfacente, quindi non veniva effettuato l'intervento chirurgico di osteotomia correttiva inizialmente ipotizzato. Discussione. La presenza della malformazione fin dalla nascita, la bilateralità dell'anomalia, seppur di gravità diversa, e le ca ratteristiche radiografiche consentono di inquadrare il presente caso clinico nell'ambito delle malformazioni congenite del gomito. L'esame radio grafico completo ha permesso di verificare la adeguata mineralizzazione dello scheletro ed il normale sviluppo scheletrico del gatto in base all'età, e non ha evidenziato segni radiografici riferibili ad eventi traumatici recenti. Tra le malformazioni congenite articolari riportate dalla letteratura nel cane e nel gatto, il presente caso presenta alcune analogie radiografiche con l'agenesia o ipoplasia del radio, di cui dalla letteratura conosciamo una decina di casi; la bibliografia medica riporta inoltre diversi casi di sinostosi radio-ulnare congenita, che nel nostro caso è presente in una delle due articolazioni. Le cause che vengono imputate nella genesi di tali malformazioni comprendono fattori genetici e ambientali teratogenetici, attivi durante le prime settimane di vita fetale (traumi o compressioni intrauterine, malattie, terapie o carenze nutrizionali materne); nel nostro caso, le informazioni ottenute riguardo i genitori ed i fratelli non hanno riferito altre situazioni di anormalità a carico dello scheletro.

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PLANNING PREOPERATORIO COMPUTER-ASSISTITO NEL TRATTAMENTO DELLE FRATTURE E DELLE DEVIAZIONI ASSIALI DI RADIOULNA MEDIANTE FISSATORI ESTERNI Rovesti Gian Luca* Med. Vet. dipl. ECVS, Cannavale A.** Med. Vet., Passaro C.** Med. Vet. *Libero professionista, Cavriago (RE) **Medical Media Production, Napoli Introduzione. Un planning preoperatorio accurato è di fondamentale importanza nel trattamento delle fratture e delle deviazioni assiali di radio e ulna nel cane mediante fissatori esterni, sia lineari che circolari. Lo scopo di questo studio è quello di verificare se un’opera multimediale interattiva sia utile in questa fase per il chirurgo meno esperto. Materiali e metodi. Un’opera multimediale interattiva è stata realizzata in collaborazione con uno studio specializzato in computer grafica 3D. Sono state ottenute sezioni assiali dell’avambraccio di cani normali in Risonanza Magnetica Nucleare (RMN). Ciascun arto è stato suddiviso in 20 segmenti da 21 linee di scansione, con la più prossimale e la più distale in corrispondenza delle superfici articolari del radio a livello del gomito e dell’articolazione radiocarpica. In ciascuna sezione sono state identificate le strutture vascolonervose, e quelle di interesse chirurgico sono state evidenziate graficamente per una loro migliore visualizzazione. Per ciascuna sezione assiale sono mostr ate le vie di infissione suggerite per i fili e le fiches filettate; la loro direzione è chiarita dal riferimento goniometrico che circonda l’immagine della sezione. È possibile esaminare in maniera interattiva i modelli 3D dei fissatori, sia per quanto riguarda il trattamento delle fratture che delle deviazioni assiali. È anche possibile esaminare un modello 3D dell’avambraccio con le strutture vascolonervose e la base ossea, con e senza il fissatore esterno montato, in modo da potere meglio apprezzare i rapporti fra il fissatore e le strutture anatomiche, e fra le diverse strutture anatomiche. Ad una resident in chirurgia, senza una esperienza specifica nel montaggio di fissatori esterni in qualità di primo chirurgo, è stato chiesto di applicare dei fissatori esterni, sia lineari che circolari, in configurazione standard per il trattamento di fratture mediodiafisarie, ad ambedue gli avambracci di 3 cadaveri di cane non congelati per ciascun tipo di fissatore, per un totale di 6 montaggi per i lineari e 6 per i circolari, dopo averle consentito di studiare l’opera multimediale per una settimana. Ciascun fissatore è poi stato rimosso, lasciando in posizione le fiches o i fili, e il tragitto di questi è stato seguito dissezionando i tessuti dell’arto, verificando se fosse stata danneggiata qualche struttura vascolonervosa. Risultati. In nessuno dei preparati esaminati sono stati osservati danni a strutture vascolari o nervose. In alcuni casi il passaggio dei fili o delle fiches risultava molto vicino ad alcune strutture, ma questo è stato considerato come proprio delle particolari caratteristiche anatomiche di quel distretto, e non come errore tecnico. È stato compilato un questionario da parte della resident relativo all’utilizzo dell’opera multimediale. Gli aspetti descritti come quelli maggiormente utili sono rappresentati dalle sezioni assiali con le indicazioni per l’infissione dei fili e delle fiches, e i modelli 3D con le strutture vascolonervose di interesse chirurgico, con e senza fissatore montato. Questi ultimi hanno consentito una migliore comprensione dell’anatomia regionale e dei rapporti fra le strutture. Discussione. I problemi della didattica in campo chirurgico sono molteplici, soprattutto legati alla difficoltà di fare eseguire procedure complesse su pazienti clinici a chirurghi meno esperti. Per quanto riguarda specificamente l’utilizzo dei fissatori esterni, non è sempre facile comprendere i rapporti tridimensionali fra strutture anatomiche e struttura del fissatore. Per questo motivo è sembrata utile la realizzazione di un’opera che, mediante sofisticate tecniche di modellazione 3D, potesse consentire al chirurgo di manipolare il fissatore, ruotandolo in tutte le direzioni e ingrandendo i dettagli di interesse come se fosse nelle mani dell’esaminatore. La realizzazione dell’atlante di anatomia assiale si è rivelata particolarmente utile per la comprensione dell’anatomia regionale livello per livello, pur in considerazione delle differenze individuali e di quelle legate alle differenti tipologie nel cane. Il fatto che in nessuno dei 12 montaggi realizzati si sia verificato il danneggiamento di strutture vascolonervose importanti è significativo per la possibilità che questo tipo di approccio allo studio dell’applicazione dei fissatori esterni si riveli particolarmente efficace per quanto riguarda l’apprendimento dei principi relativi ai “corridoi sicuri” da parte dei chirurghi meno esperti.

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ESPERIENZE PRELIMINARI NELL’APPLICAZIONE DEI PRINCIPI DI TRAZIONE TRANSCHELETRICA NEL CANE Rovesti Gian Luca* Med. Vet. dipl. ECVS Libero professionista, Cavriago (RE) Introduzione. La trazione scheletrica non è una metodica abitualmente applicata in chirurgia veterinaria. Il suo utilizzo è stato descritto per procedure chirurgiche specifiche in maniera aneddotica, ma manca uno studio sistematico del suo utilizzo. Lo scopo di questo lavoro è quello di studiarne l’applicazione in modo ripetibile per la chirurgia dello scheletro appendicolare del cane. Materiali e metodi. Sono stati utilizzati dieci cadaveri di cane non congelati, senza lesioni apparenti o conosciute a carico dello scheletro appendicolare. Per l’applicazione della trazione intraoperatoria è stato utilizzato un tavolo operatorio veterinario Ergomed 99 (Med Matrix, S. Prospero, Modena, Italia). Per ogni cadavere sono stati studiati i posizionamenti per l’esecuzione della trazione di omero, radioulna, femore e tibia. L’ancoraggio del corpo del cane al tavolo è stato eseguito con le cinghie di ritenzione apposite, e la trazione mediante la barra di trazione micrometrica. L’ancoraggio dell’arto alla barra di trazione è stato eseguito o mediante cinghiette o mediante staffa di trazione, assicurata mediante un filo transcheletrico. Eseguito il posizionamento, è stata esercitata la trazione per verificare la stabilità della configurazione. Ciascun segmento osseo è stato a questo punto aggredito chirurgicamente nella sua porzione mediodiafisaria, la trazione è stata allentata e l’osso è stato sezionato mediante sega oscillante. La trazione è stata ripristinata, verificandone l’assialità, intesa come la tendenza dei monconi ossei ad allinearsi secondo un asse longitudinale fisiologico. Risultati. Per ogni segmento sono stati definiti due punti: un punto di opposizione e uno di ancoraggio per la trazione. Il punto di opposizione (PO) è quello che impedisce la traslazione del corpo del paziente, mentre quello di ancoraggio (PA) è quello che consente l’applicazione della forza di trazione all’arto. Omero: decubito sul lato controlaterale, PO sterno, PA staffa con filo transcheletrico applicato nella zona sopracondilica. Radioulna: decubito sul lato omolaterale, PO sterno, PA cinghia applicata nella zona carpo-metacarpica. Femore: decubito sul lato controlaterale, PO area inguinale, PA staffa con filo transcheletrico applicato nella zona sopracondilica. Tibia: decubito dorsale, PO area perineale con appoggio popliteo, PA cinghia applicata nella zona tarso-metatarsica. Per quanto riguarda l’assialità della trazione, non ha presentato particolari problemi per radioulna e tibia; in questi segmenti l’elemento determinante è rappresentato dalla corretta altezza a cui si posiziona il PA. Per omero e femore i problemi sono stati maggiori, in quanto, oltre all’altezza del PA, si è rivelata fondamentale la posizione dell’asta di trazione in senso craniocaudale, vista la tendenza dell’omero a subire una deviazione in recurvato e quella del femore in procurvato quando la trazione è esercitata perpendicolarmente all’asse longitudinale del corpo in corrispondenza di spalla e anca rispettivamente. Discussione. La trazione scheletrica è applicata da secoli in chirurgia ortopedica umana quale importante strumento di riduzio ne delle fratture. È ovvio che la collaborazione da parte del paziente ne estende l’applicazione anche ai periodi pre e postoperatori, così come le indicazioni rispetto al suo utilizzo in veterinaria. Data la frequenza con cui, in sede intraoperatoria, si avverte la necessità di applicare forze tese a distrarre e riallineare i monconi di frattura porta a ritenere che una tecnica di trazione scheletrica praticabile e ripetibile potrebbe essere di g rande utilità anche in chirurgia veterinaria. I punti salienti per la definizione di questa tecnica sono stati ritenuti il decubito del paziente, l’applicazione delle forze di ritenzione del corpo con meto di che non arrechino danni ai tessuti e in punti che non creino stasi circolatoria a causa della compressione, e l’applicazione della trazione in punti appropriati per ottenere il riallineamento del segmento osseo oggetto della trazione. Inoltre il segmento deve essere trazionabile senza che le forze applicate danneggino strutture adiacenti, e in particolar modo quelle articolari prossimali e distali. Questo può essere ottenuto non applicando forze transarticolari nel caso in cui le forze muscolari da vincere siano di grande entità, come è nel caso di omero e femore. L’uso della staffa di trazione consente di applicare la trazione prossimalmente alle articolazioni.

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QUATTORDICI CASI DI DEFORMITÀ ANGOLARI NEL CANE CORRETTE MEDIANTE LA TECNICA DI ILIZAROV Rovesti Gian Luca Med. Vet. dipl. ECVS, Schmidt K. Med. Vet., Margini A. Med. Vet. Libero professionista, Cavriago (RE) Introduzione. Le deformità angolari sono causate da molteplici fattori, fra cui i traumi, specialmente a carico delle cartilagini di accrescimento, le patologie metaboliche, la predisposizione genetica e la scorretta riduzione di fratture. Per questa patologia sono stati proposti diversi metodi di trattamento, ciascuno con vantaggi e svantaggi. Lo scopo di questo studio è quello di valu tare retrospettivamente il protocollo terapeutico e i risultati ottenuti in cani trattati per un problema di deviazione assiale mediante la tecnica di Ilizar ov. Materiali e metodi. Sono state esaminate le cartelle cliniche dei cani trattati presso l’Ambulatorio Veterinario Associato “M. E. Miller” mediante la tecnica di Ilizarov, e 14 arti in 12 cani avevano i requisiti per essere inclusi nello studio. Per il trattamento della deformità sono stati utilizzati 2 sistemi: lo Small Bone Fixator (SBF) e il Multiplanar C-Fix (MCF). L’età media dei cani al momento del tr attamento era 12 mesi (range, da 5 a 24; SD 5,5), e il peso medio era 24 kg (range, da 5 a 50; SD 12). I segmenti trattati sono stati 10 radioulna (4 destri, 6 sinistri) e 4 tibie (3 destre, 1 sinistra); i problemi iniziali erano carpo valgo supinato (8), piede supinato con accorciamento dell’arto anteriore (1), piede posteriore supinato (3), tarso valgo (1), e carpo varo supinato (1). Le cause della deformità erano fratture delle cartilagini di accrescimento (5), problemi di tipo genetico (5), congenito (3), e di origine non determinata (1). La deviazione in valgo preoperatoria media era di 24° (range, da 6 a 40; SD 10), il supinato medio era 41° (range, da 25 a 70; SD 14), il procurvato medio era 21° (range, da 2 a 40; SD 12), e soltanto un cane aveva un varo di 45°. La lunghezza media preoperatoria del segmento trattato era 14,1 cm (range, da 10 a 18.7; SD 3.3). Risultati. Il sistema SBF è stato usato in 11 casi, l’MCF in 1 caso, e costruzioni ibride con ambedue i componenti in 2 casi. I livelli di fissazione erano da 3 a 5, e il diametro dei fili di Kirschner andava da 1 a 1,5 mm, a seconda della taglia del cane e della localizzazione del filo. Sono state utilizzate fiches da 3 e 4 mm, e tutti gli impianti erano ibridi. La distrazione è di solito iniziata 3 giorni dopo la chirurgia, e il tempo medio per il riallineamento clinico è stato di 18 giorni (range, da 7 a 27; SD 8). Il tempo medio di trattamento, considerato come il tempo dalla chirurgia alla rimozione dell’impianto, è stato di 74 giorni (range, da 49 a 107; SD 19). In dodici casi si sono manifestate complicazioni minori, rappresentate da sierosità prodotta in corrispondenza dei fili o delle fiches (12), la necessità di correggere una deviazione assiale senza AG (2), una contrattura in flessione del carpo (2), rottura di fili (2), e dolore intenso durante il periodo di distrazione (1). Cinque casi hanno manifestato complicazioni maggiori con la necessità di modifiche dell’impianto in AG (3), rottura di fili con la necessità di sostituirli in AG (1), e contrattura in flessione del carpo (1); 4 pazienti hanno avuto sia complicazioni minori che maggiori, ed alcuni più di una complicazione minore. Il valgo medio PO era di 5° (range, da 0 a 16), il varo residuo nell’unico cane con questa deviazione era di 10°, e il supinato medio era 2° (range, da 0 a 10). La lunghezza media del segmento trattato era 16 cm (range, da 10,5 a 23,5; SD 4,3). I risultati sono stati giudicati come eccellenti in 12 casi (86%) per l’esito funzionale, e come buoni in 2 (14%). Il giudizio estetico era eccellente in 10 (71%), buono in 3 (22%), e mediocre nel restante. Discussione. Le deviazioni assiali e l’allungamento degli arti sono considerate indicazioni specifiche per la tecnica di Ilizarov, in quanto si possono effettuare correzioni sui 3 piani, effettuando anche l’allungamento dell’arto interessato se ve ne sono le condizioni. La tecnica inoltre consente di effettuare ulteriori correzioni nel periodo postoperatorio. Nella nostra casistica la metodica si è dimostrata molto efficace, e si può concedere pieno carico nel periodo PO, riducendo al minimo l’atrofia muscolare e il tempo di recupero funzionale. Durante l’allungamento dell’arto vengono stirate le strutture vascolonervose, con conseguente dolore, in alcuni casi anche intenso, che di solito può essere controllato con analgesici ed antiinfiammatori. La tecnica richiede comunque una lunga curva di apprendimento, e la stretta collaborazione del proprietario è tassativa per il raggiungimento dei risultati prestabiliti.

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TECNICHE OPERATIVE ARTROSCOPICHE Rovesti Gian Luca* Med. Vet. dipl. ECVS, Fadiga G.** Med. Vet. *Libero professionista, Cavriago (RE) **Libero professionista, Casalecchio (BO) Introduzione. L’artroscopia veterinaria ha avuto in questi ultimi anni una discreta diffusione, grazie agli innegabili vantaggi che presenta dal punto di vista diagnostico rispetto ad altre metodiche più invasive. Mentre dal punto di vista diagnostico sono stati proposti diversi protocolli, sia per quanto riguarda gli accessi che la classificazione delle patologie, non altrettanto è stato fatto per quanto riguarda le possibilità chirurgiche artroscopiche. Lo scopo di questo lavoro è quello di esaminare le caratteristiche e le indicazioni dello strumentario e delle tecniche attualmente disponibili. Materiali e metodi. Sono state studiate le caratteristiche dello strumentario artroscopico per chirurgia intraarticolare disponibile commercialmente, ed è stata verificata la letteratura sull’argomento presente in veterinaria. Sono poi stati revisionati tutti i video registrati durante le procedure artroscopiche eseguite presso le strutture degli autori, selezionando quelle nelle quali era stata eseguita una procedura chirurgica artroscopica di qualsiasi tipo. Sono infine state confrontate le metodiche di trattamento e lo strumentario utilizzato per le lesioni rilevate con quelle descritte in letteratura. Risultati. Rispetto allo strumentario disponibile commercialmente e comunemente usato in artroscopia umana, quello veterinario è molto ridotto sia per tipologia sia per indicazioni. Gli strumenti si possono dividere in 3 categorie: quelli per uso manuale, quelli motorizzati e quelli che trasferiscono energia termica ai tessuti (coagulatori e vaporizzatori). I più utilizzati in veterinaria sono quelli manuali, perché caratterizzati da costi di acquisto e gestione inferiori, ma anche perché rappresentano le basi delle manualità chirurgiche artroscopiche, quali la presa, il taglio e la trazione o la pressione. Quelli motorizzati sono caratterizzati dalla capacità di ripetere molto velocemente azioni ripetitive, abbreviando in maniera consistente i tempi nel caso di azioni selezionate. Sono indicati in caso di asportazione di tessuti o della loro toelettatura. Gli strumenti a trasferimento di energia termica sono indicati per controllare le emorragie intraarticolari e nel caso di tessuti da vaporizzare, cioè da coartare o da dissolvere a seconda delle potenze e dei tempi utilizzati. Lo studio delle registrazioni delle procedure cliniche ha mostrato come non sia sempre ovvia la scelta dello strumento più indicato per una situazione specifica, in quanto la previsione del risultato di una manovra o di una tecnica richiede una curva di apprendimento piuttosto lunga. Inoltre l’apprendimento delle tecniche di triangolazione fra ottica e strumentario chirurgico, così come la scelta dei portali appropriati, condiziona in maniera determinante l’esecuzione di queste manovre. Anche la interazione fra le mani che operano sugli strumenti e occhio e cervello del chirurgo che ricevono gli impulsi e le informazioni da un monitor, cioè da un punto diverso da quello nel quale si svolge l’azione chirurgica, richiede un’impostazione completamente diversa da quella a cui la maggior parte dei chirurghi è abituata. In letteratura veterinaria sono stati trovati riferimenti molto scarsi a queste problematiche, e per alcune tecniche, quali la vaporizzazione, soltanto cenni della sua esistenza, senza alcuna indicazione. Discussione. Come per la maggior parte delle metodiche in corso di evoluzione, anche per l’artroscopia operativa veterinaria sono attualmente più consistenti i dubbi delle certezze assodate. Di questa situazione è testimonianza diretta la scarsità delle informazioni reperibili in letteratura, soprattutto per le tecniche più recenti, ma non solo. Molte delle procedure riportate in artroscopia umana e fattibili in veterinaria, come dimostrato dalla loro esecuzione su casi clinici, sono spesso menzionate in maniera aneddotica, ma senza il necessario consolidamento, capace di farle divenire metodiche di riferimento per situazioni standard. La g rande disponibilità tecnologica attuale è solo in piccola parte proponibile in veterinaria, in parte per ragioni di costo eccessivamente elevato per la situazione veterinaria, ed in parte per le dimensioni di molti strumenti, di solito pensati per articolazioni decisamente più spaziose, quali quelle umane. Questi elementi fanno sì che al momento attuale molte tecniche chirurgiche artroscopiche siano più affidate alla inventiva personale del chirurgo che ad un approccio teoricamente prestabilito.

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INDAGINE PRELIMINARE SULLA LEPTINA NELLA SPECIE CANINA Saleri Roberta Med.Vet., Grasselli Francesca Med.Vet., Tamanini Carlo Med.Vet. Prof. Istituto di Fisiologia Veterinaria, Facoltà di Medicina Veterinaria, Università di Parma Introduzione. La leptina, scoperta nel ratto da Zhang e coll. (Nature 372: 425-432; 1994), è un ormone secreto principalmente dagli adipociti in grado di “informare” l’organismo del livello delle sue riserve lipidiche. La sua azione si realizza attraverso il legame con uno specifico recettore ipotalamico ed è diretta all’inibizione della sintesi e del rilascio del neuropeptide Y, che stimola l’assunzione del cibo e riduce la termogenesi. Proprio questi sono i motivi che fanno della leptina un nuovo possibile marker fisiopatologico dei disordini del peso corporeo ed un valido mezzo nel trattamento dell’obesità nella specie umana; nonostante questa patologia rappresenti uno dei principali disturbi nutrizionali e metabolici anche nella specie canina, mancano a tutt’oggi informazioni sulla leptina in questa specie. Obiettivo. Lo scopo di questo lavoro è stato di indagare le caratteristiche della secrezione della leptina nella specie canina, determinandone i profili plasmatici durante le ore diurne in femmine adulte normopeso. Materiali e metodi. In questo studio sono state utilizzate 12 cagne di taglia grande, d’età compresa fra i due ed i cinque anni, in buone condizioni fisiche e con peso normale. Tutti gli animali sono stati sottoposti a prelievi ematici dalla vena cefalica dell’avambraccio ad intervalli di 30 minuti per 12 ore; per un periodo di 6 ore i prelievi sono stati effettuati ogni 15 minuti. I campioni di sangue (1 ml) sono stati raccolti in tubi pretrattati con EDTA e subito centrifugati a 1800×g: il plasma è stato stoccato a –20°C fino alla determinazione dei livelli di leptina, estradiolo 17-ß (E2), progesterone (P4) ed ormone luteinizzante (LH). Il dosaggio della leptina è stato realizzato mediante kit EIA messo a punto per la specie umana (Cayman Chemical); la determinazione di E2 e P4 è stata realizzata mediante RIA modificato da Grasselli et al., (Anim. Reprod. Sci. 32:153-161; 1993) e quella dell’LH mediante ELISA eterologo modificato (Saleri et al., Reprod. Dom. Anim. 33:27-32; 1998). Risultati e discussione. In tutti i soggetti, che si trovavano in una condizione di anestro stagionale [E2< 0,77 pg/ml; P4 = 0,3±0,01 ng/ml; LH: valori basali = 3,4± 0,21 ng/ml; pulsatilità = 0,13 pulses/ora], la concentrazione basale (media±ES) di leptina è stata 1,77±0,1 ng/ml; un solo animale ha presentato livelli di leptina nettamente inferiori (0,88±0,02 ng/ml). Abbiamo r ilevato un andamento pulsatile dell’ormone con una frequenza di 1 pulse/2 ore e con un’altezza media del picco di 3,46±0,21 ng/ml. I prelievi effettuati ogni 15 minuti non hanno evidenziato alcuna variazione ulteriore nella pulsatilità dell’ormone. Conclusioni. La leptina viene oggi considerata in medicina umana come uno dei maggiori regolatori endogeni del complesso sistema responsabile del controllo del peso corporeo. Nel cane mancano indicazioni sulla leptina e sulle sue caratteristiche di secrezione, benché l’obesità costituisca senza dubbio un frequente riscontro clinico. Questo studio dimostra la possibilità di quantificare la leptina anche nel cane, grazie alla sua elevata omologia (>80%) con quella umana. I dati qui riportati, in linea con quanto già noto nel ratto e nell’uomo, rendono plausibile un’applicazione della leptina come parametro attendibile delle performances fisiche e metaboliche anche in questa specie, analogamente a quanto già avviene in quella umana. Ringraziamenti. Gli autori desiderano ringraziare il signor Luigi Rimoldi per aver messo a disposizione gli animali.

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EFFICACIA DI UN PRODOTTO PER USO OTOLOGICO CONTENENTE GENTAMICINA, CLOTRIMAZOLO E BETAMETASONE NELLA TERAPIA DELLE OTITI ESTERNE DEL CANE Scarampella F.§ Dip. ECVD, Noli C.§ Dip. ECVD, Cevidalli A.E.*Med. Vet § Studio Dermatologico Veterinario, Milano * Schering-Plough Animal Health, Segrate Introduzione. L'eziologia dell’otite esterna del cane è multifattoriale. Vi sono fattori primari, quali i corpi estranei, le malattie allergiche e l’acaro auricolare Otodectes cynotis; fattori predisponenti, tra cui la conformazione anatomica dell’orecchio; e fattori perpuetuanti, tra i quali sono frequenti le infezioni batteriche e/o da lieviti. I microrganismi coinvolti più spesso sono i lieviti, in particolare Malassezia pachydermatis, e/o i batteri Staphylococcus intermedius, Staphylococcus aureus, streptococchi, Pseudomonas spp., Proteus spp., E. coli e altri. La terapia dell’otite esterna si basa sull'identificazione e correzione, ove possibile, delle cause primarie e predisponenti, e sull'uso di preparazioni topiche antibatteriche e/o antifungine, a cui spesso è associato un cortisonico al fine di disinfiammare la cute del condotto e alleviare la sintomatologia dolorosa o pruriginosa. Recentemente è stato immesso sul mercato italiano un nuovo prodotto otologico veterinario a base di gentamicina, clotrimazolo e betametasone valerato (Otomax ) che ha il vantaggio di agire sia sulla Malassezia, sia sui batteri, siano essi gram positivi o gram negativi. Obiettivo. Gli autori presentano i risultati di una ricerca in cui è stata valutata l'efficacia di questo prodotto in campo, con uno studio multicentrico che ha coinvolto 12 cliniche veterinarie su tutto il territorio italiano. Materiali e metodi. Centoquarantadue cani con otite mono- o bilaterale, di prima insorgenza o ricorrente, sono stati trattati con una sospensione oleosa contenente gentamicina, clotrimazolo e betametasone valerato, ogni 12 ore per 7 giorni e valutati clinicamente, citologicamente e con colture batteriche e antibiogrammi prima e dopo il trattamento. Non era permessa nel corso dello studio la somministrazione di altri preparati antibiotici, antimicotici, cortisonici, antistaminici e antinfiammatori non steroidei per via locale e generale. Risultati e discussione. Le variazioni dei parametri clinici esaminati (fastidio, eritema, edema, quantità, odore e colore dell'essudato), sono state valutate statisticamente mediante il test non parametrico di Wilcoxon per dati appaiati. Tutti i parametri considerati sono migliorati significativamente (P< 0,01) in seguito al trattamento. La valutazione soggettiva dell'efficacia del trattamento da parte degli sperimentatori ha riportato risultati eccellenti o buoni nell'89% dei casi, discreti nell'11% e insufficienti nell'1% dei casi. Citologicamente si è osservata una diminuzione della presenza di lieviti e batteri. Il miglioramento clinico e citologico non sembra essere influenzato dal tipo di germe coinvolto o dalla cronicità o ricorrenza dell'otite. La combinazione della gentamicina, del clotrimazolo e del betametasone valerato in un veicolo innovativo potrebbe rappresentare quindi una soluzione molto interessante al problema otite esterna, associando un’ottima attività antibatterica ed antifungina ad ampio spettro ad una attività antiinfiammatoria persistente fra una somministrazione e l'altra. In conclusione questo studio ha mostrato come il prodotto testato rappresenti una efficace terapia in corso di otite esterna del cane, in presenza di Malassezia e/o batteri. Ringraziamenti. Gli autori desiderano ringraziare la Schering-Plough per aver reso possibile questo studio e gli sperimentatori Dr.Francesco Albanese, Dr.Francesco Basso, Dr.Fabrizio Fabbrini, Dr.Ivan Fileccia, Dr.ssa Franca Galeotti, Dr.Francesco Ghiani, Dr.Federico Leone, Dr.ssa Erica Romano, Dr.ssa Silvia Schiavi, Dr.ssa Antonella Vercelli per averne preso parte.

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42° Congresso Nazionale SCIVAC

FIBROSARCOMA DELLA CAVITÀ ORALE IN UN CANE DI DIECI MESI (CASO CLINICO) Paolo Squarzoni Libero professionista, Molinella (BO) Il trattamento dei tumori della cavità orale è una pratica chirurgica che coinvolge spesso i veterinari che si occupano di odontostomatologia. I dati riportati in letteratura riferiscono statistiche attendibili su età, taglia e sesso degli animali colpiti dalle varie forme neoplastiche. A volte però il veterinario si può trovare di fronte a soggetti molto giovani con tumori nella cavità orale; in questi casi solo un iter diagnostico scrupoloso può evitare di confondere queste neoplasie con neoformazioni di altra natura (ascessi, granulomi, ecc.). Viene qui descritto il caso clinico di un pastore tedesco meticcio, di sesso maschile, del peso di circa 40 kg, di 10 mesi d'età. Il soggetto veniva sottoposto alla nostra attenzione da un collega; l'anamnesi riferiva che la proprietaria del cane aveva rilevato circa 30-40 giorni prima una massa di colore rosso nella porzione distale sinistra della mascella, la quale, una volta asportata dal veterinario curante , era rapidamente ricresciuta. Il soggetto, dopo accurata visita clinica, veniva anestetizzato e sottoposto a radiografie del cranio in diverse proiezioni e a biopsia escissionale. Mentre le radiografie mostravano anomalie di modesta entità e del tutto aspecifiche, l'esame istologico segnalava la presenza di un fibrosarcoma. Veniva quindi proposta ed eseguita una maxillectomia distale: la porzione di mascella asportata, nuovamente sottoposta ad indagine istologica, riferiva "margini puliti"; i linfonodi loco-regionali non coinvolti e i follow-up sono sino ad oggi soddisfacenti. Questo, come altri casi clinici, insegna a non ignorare ipotesi diagnostiche raramente segnalate in letteratura, ma ad indagare accuratamente sino a giungere ad una diagnosi precisa. Il caso clinico viene presentato con fotografie, radiografie e completo di follow-up.

UTILIZZO DI UNA PINZA “CREA BRACKETS” AUTO COSTRUITA IN ORTODONZIA VETERINARIA Paolo Squarzoni Libero professionista, Molinella (BO) I trattamenti ortodontici in medicina veterinaria si avvalgono di diversi sistemi atti a correggere occlusioni errate: apparecchi con molle o viti ad espansione, piani inclinati, bande, brackets, ecc. I brackets (attacchi diretti) rivestono un’importanza particolare perché possono essere sfruttati per molteplici utilizzi quali: sostegno per archi, attacco per elastici, ritenzione di colate in resina epossidica qualora manchi il sottosquadro fornito dai denti, ecc. Questo, assieme al basso costo e al fatto che non è necessario ricorrere ad un laboratorio odontotecnico, fa sì che il loro impiego in ortodonzia sia molto importante. L’adesione di brackets alle corone dentali è affidata a collanti appositi che, in presenza di una perfetta complementarità delle superfici che vanno a contatto, si distendono in un sottile strato uniforme; quest’ultimo, una volta indurito, garantisce la perfetta adesione del bracket alla corona. Purtroppo in veterinaria, dobbiamo accontentarci di brackets preparati per la medicina umana ed è, quindi, molto raro trovare un attacco che si adatti perfettamente alla corona da trattare. Il collante, non distribuendosi uniformemente, riempirà le lacune tra dente ed attacco e l’adesione dei brackets non sarà garantita perché il collante, una volta indurito, è molto fragile e, se presente in strati spessi tende a rompersi. In alternativa ai collanti specifici per attacchi, si possono usare compositi fotoindurenti; questi, anche se hanno spessore variabile, raramente si fratturano perché sono sufficientemente elastici. Spesso si assiste, però, al distacco del composito dal bracket, mentre non si nota quasi mai il distacco del composito dalla corona, perché si tratta di materiali progettati per aderire in maniera specifica al dente. Da questa considerazione, è nata l’idea di costruire una pinza che dia una forma predefinita ad un po’ di composito posto sulla corona dentale per essere poi fotopolimerizzato, formando così un attacco utile alle applicazioni ortodontiche. In questo modo si evita la perdita dell’attacco dal collante , perché è il collante stesso a diventare attacco. L’esposizione tratterà gli aspetti pratici dell’utilizzo di questa tecnica cercando di indicarne il suo corretto uso e i limiti delle possibili applicazioni.

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STUDIO RETROSPETTIVO DELLE NEOPLASIE PALPEBRALI NEL CANE E NEL GATTO Vercelli Antonella Med. Vet., Giordano Cristina Med. Vet. Libero Professionista, Torino Introduction. Eyelid neoplasias are a relatively common clinical entity in dogs but are rare in cats. Sebaceous gland tumors in dogs are the most frequently reported eyelid tumor representing 82,1% of the eyelid neoplasms in one study. So far in literature sebaceous neoplasms were classified in adenomas and carcinomas thus not considering the simple hyperplasia or the locally invasive form described as sebaceous epithelioma that has a malignant histologic aspect with a high mitotic rate due to its prominent basal cells component but has shown to have a good prognosis Purpose. The aim of this study was to analyze retrospectively 201 canine and 22 feline eyelid neoplasms and to differentiate sebaceous neoplasia according to the dermatologic classification of cutaneous sebaceous tumors: benign forms (hyperplasia and adenoma), locally invasive forms (sebaceous epithelioma) and highly malignant forms (carcinoma). Methods. Tissues were fixed in 10% formalin and stained with hematoxylin and eosin. Correlation between the histological findings and breed, sex, age and location was performed . Results. In dogs benign tumors (93%) were more prevalent then malignant forms (6,9%), the breeds more frequently represented were German Sheperd, Cocker Spaniel, Poodle and Boxer; the average age of dogs with eyelid tumors was 7,7 years. Sebaceous gland tumors were most frequently encountered, comprising 70,1% of all canine eyelid tumors. Compared to previous study (15,3% and 2%) the percentage of adenocarcinoma was 1,9%. Follow up in dogs showed no recurrence of sebaceous epitheliomas after surgical exision. In cats the most frequently encountered eyelid tumor was squamous cell carcinoma (54,5%) followed by sebaceous adenoma (13,6%) and lymphosarcoma (9%). Average age was 9,4 years. Conclusion. Sebaceous neoplasms are the most prevalent eyelid tumor types in dogs and benign forms (sebaceous adenoma, hyperplasia and epithelioma) are more prevalent than malignant forms (adenocarcinoma). Squamous cell carcinoma is the most prevalent eyelid tumor type in cats. In this animal, due to the high incidence of SCC, biopsy of the lesions before surgical excision is strongly recommended.

42° Congresso SCIVAC Multisala - Milano 1-4 marzo 2001

Elenco degli autori Graziano Allievi Rolando Arcelli Ermenegildo Baroni Massimo Baroni Luca Battaglia Massimo Beccati Annalisa Beghelli E. Bellezza Antonio Bertoldi David Biller Roberta Bobbio Paolo Bogoni Dea Bonello Ugo Bonfanti Alessandro Bonioli Dawn Boothe Michele Borgarelli Maria Borghi Luca Brigato Franco Brusa Antonello Bufalari Claudio Bussadori Marco Caldin Davide Calzolari Margherita Cammarata Parodi A. Cannavale Dario Cattaneo Alberto Cevidalli G. Cherubini Davide Chiavegato Fabrice Clerfeuille Massimo Colosio Stefano Comazzi Fausto Cremonesi Michael Davidson Gino D’Agnolo Stephen DiBartola Mauro Di Giancamillo A. Di Meo G. Fadiga Sergio Fanfoni Bernard F. Feldman Antonio Ferretti Adamo P. Filippo Antonella Fioravanti Richard B. Ford

Theresa F. Fossum Tommaso Furlanello Paolo Gaglio Claudio Genchi R. Gialletti Raffaele Gilardini Cristina Giordano Daniela Giretto Cecilia Gorrell Margherita Gracis Francesca Grasselli Debora Groppetti Massimo Gualtieri Timothy Hackett Edward J. Hall Jens Häggström Philippe R. Hennet Waring K. Hynds G. P. Kasidas Thomas Kern Laura Kramer Clarence Kvart Gianluca Ledda Sabine Loewer Donatella Lotti George Lubas S. Malegori Gianluca Maraldi Carlo Masserdotti Luca Mechelli Francesco Migliorini R. Marcolongo A. Margini Peter J. Markwell F. Moriconi Alda Miolo Carlo Maria Mortellaro A. Mocavero Daniela Mussi F. Nerucci Sandro Nespolo Chiara Noli Lorenzo Novello Gregory K. Ogilvie Massimo Olivieri

Robert R. Paddleford Saverio Paltrinieri C. Passaro Alessandro Pecile P. Toy Pedrick M. Pepe Massimo Petazzoni Giovanni Petroccia Valentino Petruzzi Claudio Petterino Guido Pisani Stefano Pizzirani Marco Poggi Wilma Ponti Gianluigi Puddu Vivien Rolfe Edoardo Rolla Giorgio Romanelli Federica Rossi Gianluca Rovesti Pietro Ruggiero Roberta Saleri Roberto Santilli Marco Scandone F. Scarampella K. Schmidt Valentina Spagnolo Paolo Squarzoni Abigail E. Stevenson Carlo Tamanini Attilio Tarducci M. Terrana Rossella Terragni C. Tofi Matteo Tommasini Degna Aldo Vezzoni Antonella Vercelli Fabio Viganò Massimo Vignoli Anne Weigt Michael Willard Andrea Zatelli Hans Ulrich Zeyen

Supervisione Scientifica Enrico Febbo, Med Vet Aldo Vezzoni, Med Vet, Dipl ECVS

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ATTI CONGRESSUALI 42° CONGRESSO NAZIONALE SCIVAC

Ideazione e realizzazione Enrico Febbo, Med Vet