Compendium Equine | May 2009 by davidpsu

VOLUME 4 NUMBER 4 MAY 2009

3 CE Contact Hours | CompendiumEquine.com | Peer Reviewed

Vol 4(4) May 2009

COMPENDIUM EQUINE CONTINUING EDUCATION FOR VETERINARIANS®

Oral Joint Health Supplements Abstract Thoughts g

PAGES 145–192

Inﬂammation and Infertility in Mares Clinical Snapshot

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Refereed Peer Review

FREE

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Federal law restricts this drug to use by or on the order of a licensed veterinarian. For use in horses only. Do not use in horses intended for food.

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Job #: 1227-36939 Size: 8 x 10.75 Publications:

Version: 1 IO 11007 Compendium Equine

4/29/09 4:19:51 PM

Scale

1” =

1”

Last Saved By:

jim_walsh

Trim Size:

8” x 10.75”

Studio Artist:

Jim Walsh

Bleed Size:

8.25” x 11”

Art Director:

Dudley Burt

Live Area:

7” x 9.75”

Print Production:Susan Boyer

Built @ 100%

Output @ None

Color: 4C Pantone Colors:

Links: BHC_AH_SM_4C.ai (32%), Legend Reduced Content BS_041409.eps, Legend_wTag_K.ai (112.34%), GettyImages_78457396_Jumper_4C_R1_HR.tif (CMYK; 298 ppi; 102%)

B:11”

S:9.75”

So choose the only FDA-approved I.V. joint therapy for equine noninfectious synovitis.

T:10.75”

Both depend on which therapy you choose.

May 2009 Vol 4(4)

CompendiumEquine.com | Peer Reviewed | Free CE

The AAEP’s Media Partnership Program is composed of an esteemed group of industry-leading media outlets dedicated to providing resources and education, through the AAEP, to veterinarians and horse owners to improve the health and welfare of horses. Mission Statement: Compendium Equine is dedicated to providing essential and accurate clinical and professional information to beneﬁt equine practitioners, their profession, and their patients. Compendium Equine: Continuing Education for Veterinarians is free to veterinarians practicing in the United States. To sign up, go online to CompendiumEquine.com or call 800-426-9119, option 2. US subscriptions: $35 for 1 year. International subscriptions: Canadian and Mexican subscriptions (surface mail): $40 for 1 year. Other foreign subscriptions (surface mail): $135 for 1 year. Payments by check must be in US funds drawn on a US branch of a US bank only; credit cards are also accepted. Change of Address: Please notify the Circulation Department 45 days before the change is to be effective. Send your new address and enclose an address label from a recent issue. Selected back issues are available for $8 (United States and Canada) and $10 (foreign) each (plus postage).

EXECUTIVE EDITOR Tracey L. Giannouris, MA 800-426-9119, ext 52447 | tgiannouris@vetlearn.com

PUBLISHED BY

MANAGING EDITOR Kirk McKay 800-426-9119, ext 52434 | kmckay@vetlearn.com SENIOR EDITOR Robin A. Henry 800-426-9119, ext 52412 | rhenry@vetlearn.com ASSOCIATE EDITOR Chris Reilly 800-426-9119, ext 52483 | creilly@vetlearn.com ASSISTANT EDITOR Benjamin Hollis 800-426-9119, ext 52489 | bhollis@vetlearn.com VETERINARY ADVISERS Dorothy Normile, VMD, Chief Medical Officer 800-426-9119, ext 52442 | dnormile@vetlearn.com Amy I. Bentz, VMD, DACVIM, Professional Services Manager 800-426-9119, ext 52389 | abentz@vetlearn.com SENIOR ART DIRECTOR Michelle Taylor 267-685-2474 | mtaylor@vetlearn.com ART DIRECTOR David Beagin 267-685-2461 | dbeagin@vetlearn.com OPERATIONS Marissa DiCindio, Director of Operations 267-685-2405 | mdicindio@vetlearn.com Elizabeth Ward, Production Manager 267-685-2458 | eward@vetlearn.com SALES & MARKETING Joanne Carson, National Account Manager 267-685-2410 | Cell 609-238-6147 | jcarson@vetlearn.com Boyd Shearon, Account Manager 913-322-1643 | Cell 215-287-7871 | bshearon@vetlearn.com Lisa Siebert, Account Manager 913-422-3974 | Cell 215-589-9457 | lsiebert@vetlearn.com CLASSIFIED ADVERTISING Liese Dixon, Classified Advertising Specialist 800-920-1695 | classifieds@vetlearn.com | www.vetclassifieds.com

Published nine times per year by Veterinary Learning Systems, a division of MediMedia, 780 Township Line Road, Yardley, PA 19067. Copyright © 2009 Veterinary Learning Systems. All rights reserved. Printed in the USA. No part of this issue may be reproduced in any form by any means without prior written permission of the publisher. Compendium Equine: Continuing Education for Veterinarians (ISSN 15595811) is published nine times per year by Veterinary Learning Systems, 780 Township Line Road, Yardley, PA 19067. Periodicals postage paid at Morrisville, PA 19067-9998, and additional mailing ofﬁces. POSTMASTER: Send address changes to Compendium Equine, 780 Township Line Road, Yardley, PA 19067.

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May 2009 Vol 4(4)

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EDITORIAL BOARD Michelle Henry Barton, DVM, PhD, DACVIM The University of Georgia Internal Medicine

EDITOR IN CHIEF James N. Moore, DVM, PhD Department of Large Animal Medicine College of Veterinary Medicine The University of Georgia Athens, GA 30602 706-542-3325 Fax 706-542-8833 jmoore@uga.edu

Gary M. Baxter, VMD, MS, DACVS Colorado State University Acupuncture, Surgery Jim Belknap, DVM, PhD, DACVS The Ohio State University Soft Tissue Surgery Bo Brock, DVM, DABVP (Equine) Brock Veterinary Clinic, Lamesa, Texas Surgery Noah D. Cohen, VMD, MPH, PhD, DACVIM (Internal Medicine) Texas A&M University Internal Medicine Norm G. Ducharme, DVM, MSc, DACVS Cornell University Large Animal

Compendium Equine is a refereed journal. Articles published herein have been reviewed by at least two academic experts on the respective topic and by the editor in chief.

146

Raymond J. Geor, BVSc, MVSc, PhD, DACVIM Michigan State University Metabolism, Nutrition, Endocrine-Related Laminitis Katharina Lohmann, MedVet, PhD, DACVIM (Large Animal) University of Saskatchewan Large Animal Robert J. MacKay, BVSc, PhD, DACVIM (Large Animal) University of Florida Large Animal Rustin M. Moore, DVM, PhD, DACVS The Ohio State University Surgery Debra Deem Morris, DVM, MS, DACVIM East Hanover, New Jersey Internal Medicine P. O. Eric Mueller, DVM, PhD, DACVS The University of Georgia Soft Tissue and Orthopedic Surgery

Susan C. Eades, DVM, PhD, DACVIM (Large Animal) Louisiana State University Large Animal

Elizabeth M. Santschi, DVM, DACVS The Ohio State University Surgery

Earl M. Gaughan, DVM, DACVS Littleton Large Animal Clinic Littleton, Colorado Surgery

Nathaniel A. White II, DVM, MS, DACVS Virginia Polytechnic Institute and State University Surgery

Any statements, claims, or product endorsements made in Compendium Equine are solely the opinions of our authors and advertisers and do not necessarily reï¬&#x201A;ect the views of the Publisher or Editorial Board.

We’re for saving lives.

NEW EquiRab™ the first rabies vaccine designed specifically for the horse. We’re for recommending rabies protection for every horse, every year. For following the AAEP core vaccine guidelines. For preventing a fatal disease and your exposure to it. With low reaction rates and a 14-month DOI, EquiRab is the only rabies vaccine made specifically for the horse. Recommend EquiRab to your clients. Because like you, we’re for not taking chances with a horse’s life.

We’re for the horse. P.O. Box 318 • 29160 Intervet Lane • Millsboro, Delaware 19966 • intervetusa.com • 800.521.5767 EquiRab is a trademark of Intervet Inc. or an affiliate. ©2008 Intervet Inc. All rights reserved. 35961-EquiRabVet-05/09-FP4C-CE

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www.equirab.com

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May 2009 Vol 4(4)

Features 166

❯❯ Kim A. Sprayberry Learn what you need to know about the diagnosis, treatment, monitoring, and prognosis of this important lung disease.

CompendiumEquine.com | Peer Reviewed | Free CE

177

Each CE article is accredited for 3 contact hours by Auburn University College of Veterinary Medicine.

Feature Pleuropneumonia

FREE

CE Feature Oral Joint Health Supplements: Chemistry, Pharmacology, and Administration Guidelines ❯❯ Stacey Oke The use of oral joint health supplements in the equine industry continues to increase, often without veterinary consultation. This article can help you convey to your clients more appropriate means of administering these supplements.

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The Final Diagnosis My Buddy Mahoot ❯❯ Bo Brock This small-town veterinarian recalls an expensive all-nighter in a big city, but it wasn’t as fun as it sounds.

Departments 150 CompendiumEquine.com 151

Calendar C

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Compendium Equine: Continuing Education for Veterinarians®

Clinical Snapshot 156 Flaking and Crusting Skin on an American Paint Gelding

185 Blepharospasm in a Paint Horse Gelding ❯❯ Amber L. Labelle and Carrie B. Breaux

158 Abstract Thoughts Inﬂammation and Infertility in Mares: How Irritating! ❯❯ David J. Hurley and James N. Moore

189 Index to Advertisers 189 Classiﬁed Advertising

❯❯ Adam Stern and Timothy Snider

162 A Rapidly Growing Mass on a Quarter Horse Mare ❯❯ Robin Fontenot, Pat McCoy, and Ann Rashmir-Raven

Clinical Snapshot PAGE 185

This is my horse

™

Soft N Shiney is just a great little mare. We got her as a 2-year - old and it was clear right away that she was gonna be a real prospect. She made the finals at Snaffle Bit and started the next year with a top 10 finish at the Derby in Stephenville. It was after that we first noticed the soreness in her coffin joints and suspensories. We rested her for a while, but she wasn't improving. So about a month later, we started her on Platinum, hoping for the best. It was amazing how fast she started to feel - and look - better. We worked her into the fall, and by year's end she was giving me the same effort she did as a 3-year - old. She placed fourth at her first derby back. Stepping up, like I knew she could. In my line of work, preventing injuries is key. That's why I've put the whole barn on Platinum Performance. And Shiney, she gets the Platinum Performance CJ.

robbie boyce, 2006 Reserve World’s Greatest Horseman 2007 Intermediate Snaffle Bit Futurity Champion Platinum Performance™ Client since 2002 , 5-year-old bay mare, NRCHA Snafﬂe Bit Futurity Finalist Owned by Singleton Ranches

FIND THE SOLUTION TO YOUR HORSE’S NEEDS – DISCOVER YOUR PLATINUM!

Platinum Performance™ Complete Joint contains:

To ﬁnd the right Platinum Performance™ nutritional

Platinum Performance™The Ultimate Equine Wellness and Performance Formula to support the total health of every horse

solution for your horse, and to learn about the science behind the supplements call 1-800-553-2400, visit www.ThisIsMyPlatinum.com and speak with your

ASU-Avocado/Soy Unsaponifiables counter inﬂammation, protect and rebuild cartilage Ortho-Chon™ II HAAdvanced therapeutic joint support formula

equine veterinarian. To keep his horses healthy and performing, Robbie feeds the horses in his barn , and he feeds Shiney Platinum Performance™ CJ, Platinum Performance™ our Complete Joint formula. © 2008 platinum performance, inc.

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May

CompendiumEquine.com

2009 Vol 4(4)

WEB EXCLUSIVES

CE ARTICLES WEB EXCLUSIVE

VIDEOS

Earn 3 free contact hours for each CE article. SEARCHABLE ARCHIVES

Search all content since Compendium Equine’s launch in 2005. CE CONFERENCE CALENDAR

❯❯ Head Shaking Videoss Head shaking is one of the most difﬁcult problems to diagnose because of the great diversity of causes. Watch videos of typical and photic head shaking.

Check the online version to ﬁnd events that aren’t listed in the journal. NEWS BITS

❯❯ White Paper on Equine Plasma and Serum Products ❯❯ Veterinary Workforce Shortage ❯❯ AAEP Recommendations for Protecting Racehorses

150

E-NEWSLETTERS

❯❯ EquineMail helps you prepare for questions from your clients by highlighting the latest topics from popular publications for horse owners. In addition, links to related content in Compendium Equine are provided. ❯❯ Compendium Equine EXTRA provides a preview of, and access to, the latest issue of Compendium Equine. Breaking news and Web-exclusive content is included. For both monthly e-newsletters, sign up for free at CompendiumEquine.com. CONTACT US

❯❯ E-mail your questions, suggestions, comments, or letters to the editor: editor@CompendiumEquine.com

CE Calendar July 18–24 31st Bain Fallon Memorial Lectures Twin Waters Resort Sunshine Coast, Queensland, Australia Phone 02 9280 0922 Fax 02 9211 7601 E-mail eva@infosalons.com.au Web eva.org.au

July 19–21 AAEP Focus on the Foot and Practice Management Seminar Columbus, Ohio Web aaep.org

August 6 3rd Annual Hambletonian Continuing Education Wet Labs for Equine Veterinarians Meadowlands Racetrack East Rutherford, New Jersey Phone 973-240-7471 E-mail gordon@ﬁrstchoicemarketing Web ﬁrstchoicemarketing.us

August 7–8 Florida Association of Equine Practitioners 2nd Annual Promoting Excellence Foot/Farrier Symposium Orlando, Florida Web faep.net

August 26–30 Focus on the Equine Spine: Thoracolumbar Region

(polysulfated glycosaminoglycan)

stimulates cartilage repair and reverses traumatic joint dysfunction

Within 48 hours the hyaluronic acid (HA) in the synovial fluid nearly doubles after a single injection.* Recommended dose: 5 mL every 4 days for 7 treatments intramuscularly.

Colorado State University College of Veterinary Medicine and Biomedical Sciences Fort Collins, Colorado Phone 970-297-1273 E-mail tiffany.banﬁeld@colostate.edu

August 27–30 Veterinary Thermal Imaging Seminar The Ohio State University Columbus, Ohio Phone 800-458-8890 Web veteldiagnostics.com

September 4–5 International Focus Stiﬂe Course 2009 Congress Center

To learn about the wear-and-repair of joints go to www.adequan.com. Or call 800-974-9247 for a free video.

Keep joints in healthy balance

Halle Münsterland, Münster/Westfalen Phone 0049 2504-933212 Fax 0049 2504-7929 E-mail berger@tierklinik-telgte.com Compiled by Benjamin Hollis; send listings to bhollis@vetlearn.com.

May 2009 | Compendium Equine

Only Adequan® i.m.

151

There are no known contraindications to the use of intramuscular PSGAG in horses. Studies have not been conducted to establish safety in breeding horses. WARNING: Do not use in horses intended for human consumption. Adequan® i.m. brand Polysulfated Glycosaminoglycan (PSGAG). Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Each 5 mL contains 500 mg Polysulfated Glycosaminoglycan. Brief Summary Indications: For the intramuscular treatment of non-infectious degenerative and/or traumatic joint dysfunction and associated lameness of the carpal and hock joints in horses. LUITPOLD PHARMACEUTICALS, INC. Animal Health Division, Shirley, NY 11967. See product package insert for full prescribing information. *Burba DJ, Collier MA, Default LE, Hanson-Painton O, Thompson HC, Holder CL: IN VIVO KINETIC STUDY ON UPTAKE AND DISTRIBUTION OF INTRAMUSCULAR TRITIUM-LABELED POLYSULFATED GLYCOSAMINOGLYCAN IN EQUINE BODY FLUID COMPARTMENTS AND ARTICULAR CARTILAGE IN AN OSTEOCHONDRAL DEFECT MODEL. The Journal of Equine Veterinary Science 1993; 696-703. Concentrations of Adequan i.m. in the synovial fluid begin to decline after peak levels are reached at 2 hours; then remain constant from 24 hours post injection through 96 hours. © 2008 Luitpold Animal Health. Adequan® is a registered trademark of Luitpold Pharmaceuticals, Inc. AHD 85201, Iss. 2/08 CE

Guest Editorial ❯❯ C. A. Tony Bufﬁngton, DVM, MS, PhD, DACVN, The Ohio State University

Some People Use Data Like Drunks Use Lampposts: More for Support Than Illumination* There’s an old joke, one variation of which is

A drunk loses the keys to his house and is looking for them under a lamppost. A policeman comes over and asks what he’s doing. “I’m looking for my keys,” he says. “I lost them over there.” The policeman looks puzzled. “Then why are you looking for them all the way over here?” “Because the light is so much better.” We humans are a complicated bunch. We evolved as a social species living in small groups with a strong dominance hierarchy, and we seem to retain far more of the attributes necessary for survival in such groups than we might admit (or imagine). We have used emotion—our feelings about what happens to us—to guide our behavior for many millennia. Very recently (within the past 1000 years or so), another method of understanding what is happening to us has emerged. We call this method the scientific method. The scientific method has helped us construct a more reliable, consistent, and externally valid representation of the world. The method developed with the recognition that personal and cultural influences affect our perceptions and interpretations *Reprinted with permission from Compendium of observed phenomena. It relies on agreed-upon 2009;31(2):55-56. procedures and criteria to minimize emotional

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influences when developing a “map” of reality, while remaining cognizant that the map is not the territory. I think of the scientific method as a strategy to separate what I know from what I think (or feel) I know. The scientific method generally comprises four consecutive, essential steps: observation, hypothesis, experiment, and conclusion. The conclusion also commonly provides the observation for the next cycle of the method. Importantly, the scientific method disproves hypotheses about observations. It permits conclusions to be drawn, theories tested, and knowledge acquired in an evolutionary process wherein weak, mistaken, and limited hypotheses are cast aside, leaving those with the greatest explanatory power—until something with greater explanatory power comes along. The scientific method uses data for illumination, whereas our ancient drives for acquisition of resources (safety, food, sex, power, etc.) may motivate the use of data for support. And while our heritage may not permit us to escape the emotions associated with our actions (for example, eight of the Ten Commandments prohibit behaviors), we may at least come to better recognize their presence. Instances wherein data are used more for support than for illumination do occur in veterinary medicine, often when the emotional drive for

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Guest Editorial resources conflicts with the rational presentation of data. As in other areas of our lives, money and power are common sources of this conflict, especially in relationships between commercial and academic entities. For example, I have had data “embargoed” because a corporate sponsor did not like what they showed and have been pressured to include or exclude certain data during “sponsored” talks. My experiences are not unique; withholding of key contrary data by medical companies has been reported prominently in the media. Scientific and medical societies have become so concerned that many now require speakers to disclose all relationships with commercial enterprises, including their own. Restriction of data also occurs within the scientific and medical communities—in a slightly different fashion, but for the same reasons. For example, intense competition for ever-scarcer research funding has led some investigators to conduct only “safe” experiments, which risks reporting only results that support more funding. Even universities now aggressively market data to the press, ignoring or minimizing their limitations in an effort to gain status and resources. This state of affairs recently motivated the US National Institutes of Health to revise its proposal review standards to help return research to the “high risk, high payoff” enterprise it must be. Both scientific and emotional approaches provide important assistance in navigating our world. The challenge is in recognizing how they interact and overlap. The following are a few examples of the myriad situations that may raise SHARE YOUR COMMENTS our index of suspicion Have something to say about this that data are being used editorial or topic? Let us know: for support (emotional reasons) rather than E-MAIL editor@CompendiumEquine.com illumination (scientific FAX 800-556-3288 ones): The presenter generated the data (most of us love our data like children, making objectivity impossible). The presenter relies on clinical experience or testimonial support as adequate evidence to support his or her claims. Vague summaries of results are presented, or results are published outside the peer-reviewed literature (e.g., abstracts), reported without explanation, or declared to be “on fi le.” Single studies of small samples are provided.

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Statistics are absent or confusing, or their “significance” does not match their clinical relevance. Reports of results do not clearly describe the limitations, present in all studies, that influence the interpretability of the study. Acceptance of the data results in gain to the presenter, often at others’ expense. We also must recognize our own conscious and unconscious responses to presentations of data; after all, we share the emotional heritage of the presenter. Although our response to the presentation of information may be conscious, most information (maybe 95%) transmitted to our brains is perceived, processed, and acted on emotionally, outside of consciousness. Our own history and attitudes toward the subject and the presenter, the context in which the data are presented, and our expectations of the utility of the data and their interpretation toward our own ends all influence our receptivity or resistance to the information. These reactions can lead to our practicing, as Isaacs and Fitzgerald1 put it, eminence-, vehemence-, eloquence- (or elegance-), providence-, diffidence-, nervousness-, or (particularly for surgeons) confidence-based medicine, as opposed to evidence-based medicine. Fortunately, we can monitor our unconscious responses by using our emotional reactions for their diagnostic value. When we experience strong positive or negative feelings during the presentation of data, we can decide whether our response is to the content of the presentation or to other factors. In a way, this is where evidence-based medicine starts: our efforts to identify and interpret data. And although evidence-based medicine has its detractors and limitations, at its best, it provides a useful tool to guide one’s thinking about the utility of data in situations pertinent to one’s practice. Data represent information, and we may be the preeminent information-gathering species; after all, we have millions of years of experience with using information for support. Given that we have been using it for illumination for only 1000 years or so, maybe we are doing pretty well with our new skill already and can even improve with practice. Reference 1. Isaacs D, Fitzgerald D. Seven alternatives to evidence based medicine. BMJ 1999;319:1618.

Compendium Equine: Continuing Education for Veterinarians® | May 2009 | CompendiumEquine.com

compendium ad 2009 vet conference.pdf

3/31/09

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PURINA

V E T E R I N A RY C O N F E R E N C E O c t o b e r 2 - 4, 2 0 0 9

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CMY

Join over 250 leading equine veterinarians from across the U.S. and 100 of the top senior equine veterinary students. The 10th annual Purina Equine Veterinary Conference will be held in St. Louis, Missouri, October 2nd - 4th. This program will feature top clinicians, practice management consultants and nutritionists presenting the latest information in their respective field of expertise.

It also will include a job fair mixer that will enable senior equine students to network with equine practices from across the nation. Registration, travel and lodging are complimentary from Purina to equine practitioners and senior students.

This Course submitted for 16 hours of Continuing education credit in jurisdictions which recognize AAVSB's RACE approval.

Millennium Hotel 200 South 4th Street St. Louis, MO 63102 Please visit equinevetnutrition.com for more information or call 1-800-227-8941 Please register early as seating is limited.

Clinical Snapshot Oral Paste for Horses and Foals NADA 141-123, Approved by FDA Caution Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Description Chemical name: 5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl]sulfinyl]-1H-benzimidazole. Empirical formula: C17H19N3O3S. Molecular weight: 345.42. Structural formula: H3C

OCH3 CH3 O

OCH3 H

How Supplied GASTROGARD® (omeprazole) Paste for horses contains 37% w/w omeprazole and is available in an adjustable-dose syringe. Each syringe contains 2.28 g of omeprazole. Syringes are calibrated according to body weight and are available in boxes of 7 units or 72 units. Storage Conditions Store at 68°F – 77°F (20-25°C). Excursions between 59°F – 86°F (15-30°C) are permitted. Indications For treatment and prevention of recurrence of gastric ulcers in horses and foals 4 weeks of age and older. Dosage Regimen For treatment of gastric ulcers, GASTROGARD Paste should be administered orally once-a-day for 4 weeks at the recommended dosage of 1.8 mg omeprazole/lb body weight (4 mg/kg). For the prevention of recurrence of gastric ulcers, continue treatment for at least an additional 4 weeks by administering GASTROGARD Paste at the recommended daily maintenance dose of 0.9 mg/lb (2 mg/kg). Directions For Use • GASTROGARD Paste for horses is recommended for use in horses and foals 4 weeks of age and older. The contents of one syringe will dose a 1250 lb (568 kg) horse at the rate of 1.8 mg omeprazole/lb body weight (4 mg/kg). For treatment of gastric ulcers, each weight marking on the syringe plunger will deliver sufficient omeprazole to treat 250 lb (114 kg) body weight. For prevention of recurrence of gastric ulcers, each weight marking will deliver sufficient omeprazole to dose 500 lb (227 kg) body weight. • To deliver GASTROGARD Paste at the treatment dose rate of 1.8 mg omeprazole/lb body weight (4 mg/kg), set the syringe plunger to the appropriate weight marking according to the horse’s weight in pounds. • To deliver GASTROGARD Paste at the dose rate of 0.9 mg/lb (2 mg/kg) to prevent recurrence of ulcers, set the syringe plunger to the weight marking corresponding to half of the horse’s weight in pounds. • To set the syringe plunger, unlock the knurled ring by rotating it 1/4 turn. Slide the knurled ring along the plunger shaft so that the side nearest the barrel is at the appropriate notch. Rotate the plunger ring 1/4 turn to lock it in place and ensure it is locked. Make sure the horse’s mouth contains no feed. Remove the cover from the tip of the syringe, and insert the syringe into the horse’s mouth at the interdental space. Depress the plunger until stopped by the knurled ring. The dose should be deposited on the back of the tongue or deep into the cheek pouch. Care should be taken to ensure that the horse consumes the complete dose. Treated animals should be observed briefly after administration to ensure that part of the dose is not lost or rejected. If any of the dose is lost, redosing is recommended. • If, after dosing, the syringe is not completely empty, it may be reused on following days until emptied. Replace the cap after each use. Warning Do not use in horses intended for human consumption. Keep this and all drugs out of the reach of children. In case of ingestion, contact a physician. Physicians may contact a poison control center for advice concerning accidental ingestion. Adverse Reactions In efficacy trials, when the drug was administered at 1.8 mg omeprazole/lb (4 mg/kg) body weight daily for 28 days and 0.9 mg omeprazole/lb (2 mg/kg) body weight daily for 30 additional days, no adverse reactions were observed. Precautions The safety of GASTROGARD Paste has not been determined in pregnant or lactating mares. Clinical Pharmacology Mechanism of Action: Omeprazole is a gastric acid pump inhibitor that regulates the final step in hydrogen ion production and blocks gastric acid secretion regardless of the stimulus. Omeprazole irreversibly binds to the gastric parietal cell’s H+, K+ ATPase enzyme which pumps hydrogen ions into the lumen of the stomach in exchange for potassium ions. Since omeprazole accumulates in the cell canaliculi and is irreversibly bound to the effect site, the plasma concentration at steady state is not directly related to the amount that is bound to the enzyme. The relationship between omeprazole action and plasma concentration is a function of the rate-limiting process of H+, K+ ATPase activity/turnover. Once all of the enzyme becomes bound, acid secretion resumes only after new H+, K+ ATPase is synthesized in the parietal cell (i.e., the rate of new enzyme synthesis exceeds the rate of inhibition). Pharmacodynamics: In a study of pharmacodynamic effects using horses with gastric cannulae, secretion of gastric acid was inhibited in horses given 4 mg omeprazole/kg/day. After the expected maximum suppression of gastric acid secretion was reached (5 days), the actual secretion of gastric acid was reduced by 99%, 95% and 90% at 8, 16, and 24 hours, respectively. Pharmacokinetics: In a pharmacokinetic study involving thirteen healthy, mixed breed horses (8 female, 5 male) receiving multiple doses of omeprazole paste (1.8 mg/lb once daily for fifteen days) in either a fed or fasted state, there was no evidence of drug accumulation in the plasma when comparing the extent of systemic exposure (AUC0-∞). When comparing the individual bioavailability data (AUC0-∞, Cmax, and Tmax measurements) across the study days, there was great inter- and intrasubject variability in the rate and extent of product absorption. Also, the extent of omeprazole absorption in horses was reduced by approximately 67% in the presence of food. This is evidenced by the observation that the mean AUC0-∞ values measured during the fifth day of omeprazole therapy when the animals were fasted for 24 hours was approximately three times greater than the AUC estimated after the first and fifteenth doses when the horses were fed hay ad libitum and sweet feed (grain) twice daily. Prandial status did not affect the rate of drug elimination. The terminal half-life estimates (N=38) ranged from approximately one-half to eight hours. Efficacy Dose Confirmation: GASTROGARD® (omeprazole) Paste, administered to provide omeprazole at 1.8 mg/lb (4 mg/kg) daily for 28 days, effectively healed or reduced the severity of gastric ulcers in 92% of omeprazole-treated horses. In comparison, 32% of controls exhibited healed or less severe ulcers. Horses enrolled in this study were healthy animals confirmed to have gastric ulcers by gastroscopy. Subsequent daily administration of GASTROGARD Paste to provide omeprazole at 0.9 mg/lb (2 mg/kg) for 30 days prevented recurrence of gastric ulcers in 84% of treated horses, whereas ulcers recurred or became more severe in horses removed from omeprazole treatment. Clinical Field Trials: GASTROGARD Paste administered at 1.8 mg/lb (4 mg/kg) daily for 28 days healed or reduced the severity of gastric ulcers in 99% of omeprazoletreated horses. In comparison, 32.4% of control horses had healed ulcers or ulcers which were reduced in severity. These trials included horses of various breeds and under different management conditions, and included horses in race or show training, pleasure horses, and foals as young as one month. Horses enrolled in the efficacy trials were healthy animals confirmed to have gastric ulcers by gastroscopy. In these field trials, horses readily accepted GASTROGARD Paste. There were no drug related adverse reactions. In the clinical trials, GASTROGARD Paste was used concomitantly with other therapies, which included: anthelmintics, antibiotics, non-steroidal and steroidal anti-inflammatory agents, diuretics, tranquilizers and vaccines. Diagnostic and Management Considerations: The following clinical signs may be associated with gastric ulceration in adult horses: inappetence or decreased appetite, recurrent colic, intermittent loose stools or chronic diarrhea, poor hair coat, poor body condition, or poor performance. Clinical signs in foals may include: bruxism (grinding of teeth), excessive salivation, colic, cranial abdominal tenderness, anorexia, diarrhea, sternal recumbency or weakness. A more accurate diagnosis of gastric ulceration in horses and foals may be made if ulcers are visualized directly by endoscopic examination of the gastric mucosa. Gastric ulcers may recur in horses if therapy to prevent recurrence is not administered after the initial treatment is completed. Use GASTROGARD Paste at 0.9 mg omeprazole/lb body weight (2 mg/kg) for control of gastric ulcers following treatment. The safety of administration of GASTROGARD Paste for longer than 91 days has not been determined. Maximal acid suppression occurs after three to five days of treatment with omeprazole. Safety • GASTROGARD Paste was well tolerated in the following controlled efficacy and safety studies. • In field trials involving 139 horses, including foals as young as one month of age, no adverse reactions attributable to omeprazole treatment were noted. • In a placebo controlled adult horse safety study, horses received 20 mg/kg/day omeprazole (5x the recommended dose) for 90 days. No treatment related adverse effects were observed. • In a placebo controlled tolerance study, adult horses were treated with GASTROGARD Paste at a dosage of 40 mg/kg/day (10x the recommended dose) for 21 days. No treatment related adverse effects were observed. • A placebo controlled foal safety study evaluated the safety of omeprazole at doses of 4, 12 or 20 mg/kg (1, 3 or 5x) once daily for 91 days. Foals ranged in age from 66 to 110 days at study initiation. Gamma glutamyltransferase (GGT) levels were significantly elevated in horses treated at exaggerated doses of 20 mg/kg (5x the recommended dose). Mean stomach to body weight ratio was higher for foals in the 3x and 5x groups than for controls; however, no abnormalities of the stomach were evident on histological examination. Reproductive Safety In a male reproductive safety study, 10 stallions received GastroGard Paste at 12 mg/kg/day (3x the recommended dose) for 70 days. No treatment related adverse effects on semen quality or breeding behavior were observed. A safety study in breeding mares has not been conducted. For More Information Please call 1-888-637-4251 and please visit our web site at www.gastrogard.com. Marketed by: Merial Limited Duluth, GA 30096-4640 Merial Limited, a company limited by shares registered in England and Wales (registered number 3332751) with a registered office at PO Box 327, Sandringham House, Sandringham Avenue, Harlow Business Park, Harlow, Essex CM19 5QA, England, and domesticated in Delaware, USA as Merial LLC. US Patent: 4255431 and 5708017 Copyright © 2005 Merial Limited. All rights reserved. Rev. 08-2005

Particularly intriguing or difﬁcult cases

Case Presentation #1 ❯❯ Adam Stern, DVM ❯❯ Timothy Snider, DVM, PhD, DACVP Oklahoma State University

A 20-year-old American Paint gelding presented to the Oklahoma State University College of Veterinary Med icine with a history of f laking and crusting skin as well as recent weight loss. Physical examination revealed marked crusting of all areas of the body, including the neck, trunk, and prepuce. In addition, there was multifocal alopecia, marked scaling, and edema of the ventral abdomen

and the extremities. A photograph of the prepuce (A) is provided. No other clinical abnormalities were noted on examination. Full-thickness skin biopsy specimens were obtained. 1. What is the diagnosis? 2. Where does this lesion com-

monly appear? SEE PAGE 163 FOR ANSWERS AND EXPLANATIONS.

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Challenge your colleagues with a particularly intriguing or difficult case in Clinical Snapshot. Submit your photo(s) along with a brief case description, at least one test question, and detailed answers to each question posed. Each published submission entitles you to an honorarium of $100. For more details, call 800-426-9119, extension 52434, or e-mail editor@CompendiumEquine.com.

®GASTROGARD is a registered trademark of the AstraZeneca Group of Companies.

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FPO The best treatment for EGUS may be a dose of reality. Equine Gastric Ulcer Syndrome (EGUS) caan easily become a reality for today’s horse. In fact, the majority of your clients’ racing and non-racing competittive horses could already be sufffering in silence with gastric ulcers.1,2 Clients come to o you for knowledge and tools they can’t get anywhere else. Training. Experience. Diagnosis. Approved treatment. You havee the power to make the solution n for EGUS this simple. Unique respon nse. Only GASTROGARD® (omeprazole) is FDA-approved to treeat gastric ulcers. Unique ability.. Only you have the ability to prrovide diagnoses and GASTTROGARD. For information and EGUS educational tools, taalk with your Merial Sales Represeentative today. Or call 1-888--MERIAL-1.

Response.Ability. CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian. GASTROGARD is indicated for the treatment and prevention of recurrence of gastric ulcers in horses and foals 4 weeks and older. In efﬁcacy trials, no adverse reactions were observed. Safety in pregnant or lactating mares has not been determined. DO NOT USE IN HORSES INTENDED FOR HUMAN CONSUMPTION. KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN. Mitchell RD. Prevalence of gastric ulcers in hunter/jumper and dressage horses evaluated for poor performance. Association for Equine Sports Medicine. September 2001. Murray MJ. Endoscopic appearance of gastric lesions in foals: 94 cases (1987-1988). J Am Vet Med Assoc 1989;195(8):1135-1141.

See Page 156 for Product Information Summary

Abstract Thoughts Highlighting scientiﬁc articles with important information relating to equine diseases

Inﬂammation and Infertility in Mares: How Irritating! Column Editors ❯❯ David J. Hurley, PhD ❯e-mail djhurley@uga.edu ❯❯ James N. Moore, DVM, PhD The University of Georgia

CriticalPo nt Inﬂammatory problems in areas of the body other than the reproductive tract may result in fertility problems in mares.

TO LEARN MORE Take CE Tests More full-text articles Watch video You can find it in our archives at

CompendiumEquine.com 158

ABSTR ACT *

Low-volume uterine flush (n = 401) was performed in 308 infertile mares to diagnose endometritis. Mares evaluated were either barren after three or more breedings or had two or more unsuccessful embryo recovery attempts during consecutive cycles. Culture results were compared with cytological and histological findings, efflux clarity, and pH to substantiate that the micro-organisms recovered were truly pathogens. Cytological specimens were evaluated for presence of epithelial and inflammatory cells, bacteria, yeast, and debris. Endometrial biopsies (n = 110) were examined for the presence of neutrophils in the stratum compactum. Microorganisms were recovered in 282/401 (70%) of low-volume flushes; E. coli was most frequently isolated (42.2%), followed by β hemolytic Streptococcus (37.6%). Efflux clarity of 318 flushes was clear (n = 109), cloudy (n = 149), or mucoid (n = 60). Isolation of micro-organisms was highly associated with cloudy and mucoid effluxes (P < 0.001), debris on cytological specimens (P < 0.001), increased efflux pH (P < 0.003), and neutrophils on endometrial biopsy (P < 0.01). E. coli was associated with debris on cytological smear (P < 0.002), whereas β hemolytic Streptococcus was associated with increased efflux pH (P < 0.002). Using the presence of neutrophils in a tissue specimen as the ‘‘best standard’’ for diagnosing endometritis, the sensitivity of flush culture was 0.71 and for flush cytology was 0.8, whereas the specificity was 0.86 and 0.67, respectively. Neutrophils in uterine flushes under-reported inflammation; only 86/282 positive cultures were positive on cytology. The clinical estimate of a contaminated (false positive) flush culture was 11%, if a false positive was defined as positive culture with clear efflux and no debris or neutrophils on cytology (26/228). In conclusion, a low-volume uterine flush was a rapid, accurate method for identifying mares with chronic endometritis. When micro-organisms were recovered, endometritis was confirmed by efflux clarity, pH and cytological findings of debris, bacteria, or neutrophils. E. coli was most commonly isolated, and it appeared to differ in pathogenicity from β hemolytic Streptococcus.

COM MEN TA RY Infertility in mares is a signiﬁcant economic problem for horse owners, as it often necessitates several attempts to breed affected mares. As a result, horse owners and veterinarians become frustrated and feel powerless. The cascade of events involved in mare fertility is complex and discontinuous. A mare must cycle through a complex series of steps to produce *Reprinted verbatim from LeBlanc MM, Magsig J, Stromberg AJ. Use of a low-volume uterine ﬂush for diagnosing endometritis in chronically infertile mares. Theriogenology 2007;68:403-412; © 2007, with permission from Elsevier.

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Abstract Thoughts

CriticalPo nt Based on the lack of identiﬁcation of bacteria in 30% of chronic infertility cases reported by LeBlanc et al, we postulate that some infertile mares have occult infections of the reproductive tract and other mares have inﬂammatory problems elsewhere in the body.

an ovum. These steps are influenced by many factors: some arise from within the reproductive tissue; others may be produced remotely. Once the ovum has matured and been released, another complex series of events leads to fertilization and, eventually, development of the fertilized ovum into a multicellular structure capable of implanting into a “prepared” uterine wall. Preparation of the uterine wall is also a complex process influenced by many factors that may be produced locally or in other parts of the body. Failure at any of the steps or poor coordination of the steps leads to infertility. Infertility in mares is strongly associated with infection and inflammation of the uterus. Inflammation of the uterus is generally assumed to be associated with uterine infection. We recommend the LeBlanc et al article for several reasons. First, the investigators compared results of using low-volume uterine flush versus uterine tissue biopsy to recover microbial, cytologic, and histologic evidence of infection. While bacterial infections in the uterus are clearly important to development of infertility, no bacteria were recovered from 30% of chronically infertile mares in the study. This fi nding suggests that other inflammatory problems may be worth considering as underlying causes of mare infertility. A strong correlation was previously identified between failure of mares to conceive and either isolation of Streptococcus organisms on uterine culture or evidence of coliform bacteria on uterine cytology.1 Similarly, Escherichia coli and β-hemolytic Streptococcus were most commonly isolated from the mares in the LeBlanc et al study. Each of these “families” of bacteria is associated with induction of significant and strong inflammation in the reproductive tract. Each induces strong production of inflammatory cytokines and lipid mediators associated with the inflammatory response, including cytokines that alter breeding efficacy.2 In addition, lipopolysaccharide and tumor necrosis factor α had direct effects on ovarian cell function in vitro and in vivo.

In cattle, infections at sites other than the reproductive tract negatively affect fertility. For example, mastitis reduces fertility in dairy cattle, apparently due to the effect of inflammatory cytokine and prostaglandin concentrations on embryonic mortality; these cytokines are produced in response to mammary gland infection.3 Similarly, Hansen et al3 postulate that any source of systemic inflammation in cows could lead to infertility by a variety of routes, including interference with follicular development, preventing formation of the corpus luteum or implantation of the embryo, or with development of a viable embryo. These effects of inflammation are exerted through the many inflammatory mediators, many of which have overlapping actions or counteract some of the factors that regulate development of the ovum and interactions between the embryo and uterus. In other words, inflammatory problems in areas of the body other than the reproductive tract may result in fertility problems in mares. Based on the lack of identification of bacteria in 30% of chronic infertility cases reported by LeBlanc et al, we postulate that some infertile mares have occult infections of the reproductive tract and other mares have inflammatory problems elsewhere in the body. Thus, it seems prudent to relax our focus on the uterus and consider what might be going on somewhere else. As the Little River Band said, “There are so many paths up the mountain, nobody knows all the ways.”4 Thus, our understanding of all factors surrounding fertility is based on many contradicting positions from different scientific approaches to the problem.

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References 1. Riddle WT, LeBlanc MM, Stromberg AJ. Relationship between uterine culture, cytology and pregnancy rates in a Thoroughbred practice. Theriogenology 2007;68:395-402. 2. Willams EJ, Sibley K, Miller AN, et al. The effect of Escherichia coli lipopolysaccharide and tumor necrosis factor alpha on ovarian function. Am J Reprod Immunol 2008;60:462-473.

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3. Hansen PJ, Soto P, Natzke RP. Mastitis and fertility in cattle: possible involvement of inﬂammatory or immune activation in embryonic mortality. Am J Reprod Immunol 2004;51:294-301. 4. Shorrock G, Jones I. So many paths [song title]. Sleeper Catcher [album]. 1978.

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Clinical Snapshot Case Presentation #2

â?Żâ?Ż Robin Fontenot, DVM â?Żâ?Ż Pat McCoy, DVM, MS, DACVT â?Żâ?Ż Ann Rashmir-Raven, DVM, MS, DACVS Mississippi State University

A 22-year-old, gray Quarter horse mare presented with a rapidly growing, ulcerated, yellow mass on the ventral aspect of the tail (A). The mass had been present for several months but recently began to grow rapidly. In addition, multiple small, darkly pigmented, hairy masses were present on the ventral aspect of the tail, around the rectum, on the anus, on the perineum, and over the left parotid gland. 1. What is the most likely diagnosis regarding the large mass on the ventral aspect of the tail? 2. What are the treatment options for this lesion? SEE PAGE 164 FOR ANSWERS AND EXPLANATIONS.

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We invite the submission of clinical and laboratory research manuscripts in small animal, large animal, and comparative medicine, including pathophysiology, diagnosis, treatment, and prognosis. Prospective, retrospective, and corroborative studies are all welcome. Submitted articles are scheduled to be published 90 to 120 days after acceptance. Contact Cheryl Hobbs, 800-426-9119, ext 52408, or e-mail chobbs@vetlearn.com.

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Clinical Snapshot Answers and Explanations Case Presentation #1 B

We Don’t Just Build Hyperbaric Chambers... SEE PAGE 156 FOR CASE PRESENTATION.

1. Based on clinical examination and

histopathologic evaluation of the skin, a diagnosis of pemphigus foliaceus was made. Histologic examination of the lesion (B) revealed characteristic individual and clustered acantholytic keratinocytes (arrows) surrounded by neutrophils; neither fungi nor yeast were identiﬁed with special stains. Pemphigus foliaceus is an autoimmune skin disease in which antibodies are directed against desmosomes within stratiﬁed squamous epithelium. The glycoprotein desmoglein 1 is the major pemphigus foliaceus antigen in dogs with pemphigus foliaceus, but this has not been proven in horses. Clinically, horses with the disease can present with pustules, bullae, vesicles, alopecia, crusts, erosions, or scaling. Systemic signs (e.g., fever, depression, anorexia, weight loss, lethargy) have been reported.1 The differential diagnosis for pemphigus foliaceus includes ectoparasites, dermatophy tosis, food hypersensitivity, bacterial folliculitis, and

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epitheliotropic lymphoma. Several reports in the literature discuss treatment options.1 2. Primary skin lesions of pemphigus foliaceus in horses commonly occur on the face, neck, and extremities. Uncommonly affected areas include the prepuce, mammary glands, mucosal surfaces (esophagus and lips), and coronary bands.2

REFERENCES 1. Scott DW, Miller WH. Equine Dermatology: Immune-Mediated Disorders. St. Louis: Saunders; 2003: 483-490. 2. Zabel S, Mueller RS, Fieseler KV, et al. Review of 15 cases of pemphigus foliaceus in horses and a survey of the literature. Vet Rec 2005;157:505-509.

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Clinical Snapshot Answers and Explanations Case Presentation #2 SEE PAGE 162 FOR CASE PRESENTATION.

1. The clinical presentation of an aged

gray horse with a lesion in this location makes a diagnosis of equine melanoma likely. However, the history of rapid growth and the lesion’s yellow color suggest atypical melanoma. Biopsy of the mass revealed a malignant melanoma. Histologic examination indicated variation in nucleus size and melanin content and a high mitotic index (B). 2. Malignant melanomas should be treated aggressively due to their tendency to be locally aggressive, rapidly growing, and metastatic. Multimodal therapy is recommended for these aggressive tumors. This patient underwent wide surgical resection with implantation of cisplatin-containing biodegradable beads at the surgical margins. Cisplatin-containing beads require fewer repeat treatments, which is a distinct advantage over cisplatin intratumoral injections. The mare was prescribed perioperative procaine penicillin and received a tetanus toxoid vaccination. __Additional treatment options for equine melanomas include cryotherapy, medical treatment with cimetidine, and autogenous vaccination. Six years before presentation, the owner administered cimetidine therapy for 1½ years to treat the few small melanomas on the tail and the large melanoma over the parotid. The owner discontinued therapy because the tumors did not change. __This mare had no sign of tumor recurrence at a 5-month recheck (C). However, additional reevaluation will be necessary to accurately assess tumor recurrence and longterm prognosis.

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Histologic examination revealed mitotic figures (black arrows), nuclei of various sizes (white arrows), and melanin in cytoplasm of a tumor cell (arrowhead). (Hematoxylin–eosin stain; magnification: ×400) C

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Pleuropneumonia* ❯❯ Kim A. Sprayberry, DVM, DACVIM Hagyard Equine Medical Institute Lexington, Kentucky

At a Glance Diagnostic Criteria Page 166

Chest-Tube Placement Page 170

Treatment Recommendations Page 171

Assessment of Pleural Fluid Samples Page 172

Therapeutic Agents and Dosages Page 173

Prognosis Page 174

Although the terms pleuritis and pleuropneumonia are often used interchangeably, pleuropneumonia is preferred because this disease in horses typically involves underlying viral or bacterial infection of the lung parenchyma with subsequent extension to the pleurae. The pleural response to inflammation is transudation or exudation of fluid into the pleural space, resulting in accumulation of a sometimes marked volume of effusion. Other causes of fluid in the pleural space include neoplastic effusion, transudation of fluid secondary to acute or severe hypoalbuminemia, and penetrating thoracic wounds. Although some forms of pleurisy in humans involve, and are restricted to, the pleural membranes, infectious pleuritis unassociated with a primary pulmonary infection is rare in horses. Pleural inflammation in horses usually develops secondary to bacterial infection, but mycotic, mycoplasmal, nocardial, and metacestodal infections have been identified. Penetrating thoracic wounds that lead to infection of the parietal pleura are an exception, but the assumption that a horse with pleuritis has concurrent underlying pneumonia is correct in most instances.

Diagnostic Criteria No sex predisposition. The disease most commonly affects adult horses but can also affect foals and yearlings. Medical history often includes recent land transport, air transport, or residence at a show or sales venue where large numbers of horses commingled. Other events commonly associated with pleuropneumonia in horses include recent general anesthesia, tracheal intubation, or surgery (especially procedures involving the upper airway). Continuing training or competition while being treated for low-grade signs of respiratory tract infection. Disruptions in routine, such as a recent increase in training intensity or competition stress. Inﬂuenza is a known precedent of pleuropneumonia. Diagnosed most commonly in racehorses, likely because horses in race training or competition are young and the most frequently exposed to various combinations of the above risk factors. Some horses develop pleuropneumonia despite having no identiﬁable risk factors.

Physical Examination Findings

TO LEARN MORE Pulmonary and Systemic Fungal Infections (June 2008) Pathogenesis of Staphylococcus aureus Pneumonia (Winter 2006) *Updated by the author and reprinted with permission from Standards of Care: Equine Diagnosis and Treatment 2002;2.2:1-5, 10.

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Fever, lethargy, and inappetence; owners may report that the horse has recently lost weight. High heart and respiratory rates (>40 bpm and >16 respirations/min, respectively); toxic vascular injection pattern in oral mucous membranes and sclerae. Anxious facial expression with overall depressed demeanor; nostrils may be ﬂared at rest. Nasal discharge is variable and not always detected; when observed, discharge can be odorless or fetid.

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Pleuropneumonia Signs of thoracic pain (pleurodynia) may be evident, including grunting during the chest wall’s ventilatory excursions and standing with elbows abducted. Thoracic auscultation reveals dullness ventrally; lung sounds heard dorsally may vary from normal to abnormal according to the distribution of underlying pulmonary disease. Friction rubs may be auscultated initially; however, development of effusion separates visceral and parietal pleurae, eliminating some abnormal sounds. Percussion of thorax reveals easily distinguished horizontal line below which dullness and absence of resonance are obvious. Affected horses often ﬂinch or grunt at the examiner’s efforts to percuss the chest and may try to evade contact. Coughing, if present, is typically soft, moist, and deep. Ventral edema often develops below the thorax; this ﬁnding is common when pleural effusion is voluminous. Stiff, stilted gait in forelimbs. Reluctance to walk and signs of pain may be exacerbated when the horse is asked to turn, similar to signs of laminitis. This results from the horse’s attempt to minimize rib movement. Severe cases of pleuropneumonia may cause laminitis. Signs of colic may result from referred pain from the thorax to visceral structures or impaction secondary to hypovolemia and reluctance to defecate.

FIGURE 1

Ultrasonogram of the right hemithorax in a 2-year-old Thoroughbred with effusive pleuropneumonia. The diaphragm (arrowhead) and liver can be seen on the right side of the image, and lung tissue buoyed by pleural fluid (yellow circle) is evident on the left side of the diaphragm. Most of the lung in this image has normal reverberation artifact (blue circle), denoting healthy, aerated tissue; the atelectatic lung margin is easily seen (long arrows), along with the pericardiodiaphragmatic ligament (yellow arrow), which should not be mistaken for fibrin. This is a normal structure but can be detected only when there is sufficient pleural fluid to surround and highlight it. FIGURE 2

Other Diagnostic Procedures Ultrasonography is the initial imaging modality of choice. Ultrasonography noninvasively and promptly confirms the presence of pleural effusion and distinguishes between unilateral and bilateral pleural effusion. Ultrasonography is very helpful for determining the optimum site of drain-tube placement (BOX 1). Pleuropneumonia is recognized as anechoic to echogenic fluid accumulated in the pleural cavity. The fluid volume is often sufficient to buoy lung lobes while causing hydraulic compression and atelectasis along the ventral margin (FIGURES 1 AND 2). The pulmonary tissue usually has an abnormal appearance that may involve abscess formation, broad to coalescing comet-tail artifacts, early organization of fibrin and fluid into pockets that will become abscesses, adhesions to

Ultrasonogram of the left hemithorax in a yearling Thoroughbred ﬁlly. The diaphragm (arrowhead) is to the left. The volume of lung that has undergone compression atelectasis (circle on left) is larger than that in Figure 1; air-filled bronchi or gas pockets (circle on right) can be seen in the compressed pulmonary tissue floating in pleural fluid.

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Pleuropneumonia

CriticalPo nt It is helpful to culture both pleural fluid and tracheal fluid because pleural fluid does not always yield bacterial growth and because isolates cultured from airways differ from those cultured from pleural fluid in many instances.

parietal and diaphragmatic pleurae, or homogeneous infiltrative patterns (FIGURE 3). In aggravated or severe cases, exuberant fronds of fibrin may be seen emanating from pleural surfaces and undulating in the fluid or forming thick tethering adhesions between the lung and the chest wall. Also commonly imaged is collapsed or hepatized lung tissue containing pockets of gas that can represent islands of aerated alveoli be gas elaborated by anaerobes (FIGURE 4). Radiography is useful in detecting pulmonary lesions in deeper, more axial tissue planes that do not communicate with the pleural surface (e.g., lesions associated with deep parenchymal abscesses, interstitial infiltration, pulmonary edema, or peribronchial infiltration). Thoracocentesis: yields pleural fluid for bacterial culture and cytologic analysis (BOX 2). Fluid can be collected via cannula or from the placed chest tube. Transtracheal aspiration should be performed at admission, ideally before administration of antimicrobials, and samples submitted for culture and cytology. It is helpful to culture both pleural fluid and tracheal fluid because pleural fluid does not always yield bacterial growth and because isolates cultured from airways differ from those cultured from pleural fluid in many instances.

FIGURE 3

Ultrasonogram of the right hemithorax in a yearling Thoroughbred colt. Note the thick bilayered accumulation of fibrin adherent to the parietal pleura (circle) and the large volume of anechoic fluid (brackets) separating the chest wall from the surface of the abnormal lung.

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Blood culture is a useful ancillary diagnostic aid for increasing the odds of isolating causative pathogens and for determining whether an equine patient is septic.

Laboratory Findings Complete Blood Count and Serum Biochemistry Blood work frequently reveals inﬂammatory changes such as neutrophilia, with or without a left shift, and hyperproteinemia secondary to hyperﬁbrinogenemia and hyperglobulinemia; some horses are also hypovolemic at evaluation, which exacerbates high serum protein values. Blood values in horses in the peracute or subacute stages of infection with bacterial sepsis may reveal leukopenia, neutropenia, hypoproteinemia, hemoconcentration, and azotemia.

Chest-Tube Placement BOX 1

1. Sedate the patient and aseptically prepare the area of tube placement as determined by ultrasonography. 2. Block the skin and chest wall with anesthetic solution at the site of tube placement. 3. With sterile technique, make a fullthickness stab incision using a scalpel. 4. Insert the chest drain or cannula into the incision and carefully advance it into the pleural cavity. The depth markers on the ultrasonographic image can be used to determine how far the trocar must penetrate before reaching the pleural cavity. 5. Have sterile forceps available to clamp onto the tube if positive flow of pleural fluid stops. Aspiration of air into the tube can lead to pneumothorax. 6. Secure chest tube in place using a Chinese finger-trap suture and affix a Heimlich valve (or a condom) over the end of the drain and secure with electrical tape. 7. The drain should be left indwelling only if the patient can be visually monitored frequently. This is especially important in foals. When the fluid exiting the drain becomes minimal, the tube may be ready to remove; serial ultrasonography can help determine removal.

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Pleuropneumonia With chronicity, the leukocyte count and ﬁbrinogen concentration may be within reference range or may be high.

Serial monitoring and control of secondary complications that can result from the disease process or develop as iatrogenic problems associated with interventional measures.

Analysis of Pleural Fluid and Tracheal Aspirate Assessment of ﬂuid samples (BOX 2; FIGURE 5). Wright’s staining should be performed and ﬂuid cytologically assessed to determine whether the effusion is neoplastic. Tracheal aspirate should undergo Gram staining, aerobic and anaerobic culture and sensitivity testing, and cytologic analysis.

Summary of Diagnostic Criteria History of recent transport, upper respiratory tract viral infection, surgery, anesthesia, or intubation. Painful cough, fever, and possible nasal discharge. Auscultation of dullness in the ventral portion of the thorax, with normal or abnormal lung sounds dorsally; fluid line can often be established via auscultation or percussion. Inflammatory changes in routine blood work results (e.g., complete blood count). Ultrasonographic demonstration of hypoechoic to anechoic fluid in one or both pleural cavities.

Differential Diagnosis Neoplastic effusion. Transudation of ﬂuid into intracavitary location secondary to low oncotic pressure (from protein-losing enteropathy or nephropathy). Penetrating chest wound. Hemothorax. Pulmonary hydatidosis.

Removal of Pleural Fluid In horses with substantial volumes of effusion (e.g., 10 to 20 L), establishing drainage and removing the fluid is necessary, in addition to administering antimicrobials and other medications. Administration of antimicrobials alone will not result in a successful outcome in horses with pleural effusion. Insertion of a teat cannula into the pleural space is effective for sampling and removing fluid if the volume is modest and there is little or no fibrin in the fluid to obstruct the cannula. If pleural effusion is removed by cannulization, it must often be repeated daily or multiple times before antimicrobial treatment effectively controls the underlying infection, thereby curtailing the inflammatory mechanisms that drive production of effusion. An indwelling chest tube is a more efficient conduit for removing a large volume of pleural fluid. However, rapid removal of effusion may lead to circulatory collapse and shock because of third-space effects; intravenous replacement fluids should be administered before and during drainage of pleural fluid.

CriticalPo nt Acute, mild pleuropneumonia may be managed successfully with antimicrobials and antiinﬂammatories, and affected horses may recover with no need for invasive procedures, protracted treatment, or monitoring. Even horses with mild disease should be prescribed at least 30 days of rest from training or any form of induced exercise.

FIGURE 4

Treatment Recommendations Initial Treatment Acute, mild pleuropneumonia may be managed successfully with antimicrobials and antiinﬂammatories, and affected horses may recover with no need for invasive procedures, protracted treatment, or monitoring. Even horses with mild disease should be prescribed at least 30 days of rest from training or any form of induced exercise. Principles guiding treatment of complicated pleuropneumonia include: Removal of effusion and inﬂammatory material from pleural space as needed. Arrest of underlying bacterial infection by administering broad-spectrum antimicrobials.

Ultrasonogram of the right hemithorax in a 3-year-old colt in race training. The atelectatic lung contains pockets of white echoes corresponding to gas (circle). Inflammatory debris and adhesions on the pleural surface of the lung and on the chest wall and diaphragm (arrows) are evident.

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Pleuropneumonia A Heimlich valve (or a condom with the end snipped off) must be afﬁ xed to the end of the tube to avoid pneumothorax. An indwelling large-bore tube (e.g., a 20- to 32-French trocar catheter) enables constant egress of effusion and exudate, which is facilitated by lung excursions during inspiration and expiration. In some instances, a drain placed in one hemithorax will drain both sides of the chest because of the perforated conformation of the caudal part of the mediastinum in horses. With chronicity, the pores become plugged FIGURE 5

or fi lled with inflammatory debris, and the two hemithoraces may not communicate. In this instance, a tube must be placed in each hemithorax to remove all fluid. Whether a cannula or larger-bore tube is placed, the instrument should be situated in the middle of the selected intercostal space to avoid the vein–artery–nerve bundles that course along the caudal aspect of each rib. The lateral thoracic vein must be avoided in its course along the ventral aspect of the thorax. Once placed and secured, chest tubes may be left indwelling until substantial drainage ceases. Tubes are typically left in situ for 2 to 3 days but, because of the risk of acute pneumothorax, should not be left indwelling if the horse cannot be monitored around the clock. It is not unusual for ultrasonography to reveal reaccumulation of pleural fluid several days after removal of a drainage tube; in this instance, a new tube should be placed, optimally by ultrasound guidance. Because this scenario is common, it should be included in the estimate to the owner at the outset of treatment.

Controlling Underlying Bacterial Infection Frequently isolated aerobes: β-hemolytic Streptococcus spp. Actinobacillus spp. Pasteurella spp. Escherichia coli. Klebsiella pneumoniae.

Assessment of Pleural Fluid Samples BOX 2

A trocar catheter in the right hemithorax of a horse with pleuropneumonia. The catheter can be either sutured in place using a Chinese finger-trap suture and left indwelling for 1 to 3 days or removed once the fluid in the pleural space has been removed. If the catheter is left indwelling, a Heimlich valve (or a condom) should be affixed to the end with electrical tape to serve as a one-way valve that conducts fluid but prevents retrograde aspiration of air.

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Assessment of pleural ﬂuid samples collected during thoracocentesis should include aerobic and anaerobic bacterial culture and sensitivity testing as well as determination of protein concentration (<2.5 mg/dL is normal) and nucleated cell numbers (<5000 [some references cite <10,000] cells/μL is normal). The latter two indices indicate whether effusion is exudative or transudative in nature and, combined with values of L-lactate dehydrogenase (>1000 U/L is high), glucose (<40 mg/dL is low), and pH (<7.1 is low), offer prompt empiric determination of septic effusion until culture results are available.

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Pleuropneumonia Anaerobes: Bacteroides spp (common). Peptostreptococcus spp (common). Clostridium spp (uncommon). Broad-spectrum antimicrobials (TABLE 1) should be administered as soon as fluid samples have been obtained from the transtracheal aspirate and pleural space. If a horse has been treated with antimicrobials at the time of admission and is physiologically stable, I may recommend withdrawing the treatments and delaying these procedures for 24 hours to maximize the likelihood of microbial growth from fluid samples. In more compromised horses, the procedures are performed at admission regardless of previous treatment. Combination of a β-lactam drug (e.g., penicillin, ampicillin, ceftiofur) and an aminoglycoside (e.g., gentamicin) or a fluoroquinolone (e.g., enrofloxacin) is common. If anaerobic involvement is suspected (e.g., a fetid odor to the horse’s breath or sonographic detection of gas in pleural fluid), metronidazole is often added to the treatment regimen due to potential anaerobic resistance (e.g., from Bacteroides spp) to penicillin as a result of β-lactamase production. Therapeutic choices are augmented or revised on the basis of culture and sensitivity results. Most pleuritis infections are mixed, and drug monotherapy is rarely effective. Intravenous treatment with antimicrobials is typically continued for 7 to 14 days and then followed by long-term oral administration. The decision to change to orally administered antimicrobials should be made on the basis of a positive response to treatment, manifested by resolution of drainage from chest tubes or by serial sonographic imaging to confirm absence of effusion. Selection of oral antimicrobials should be based on culture and sensitivity results; repeated culturing of pleural or tracheal fluid is recommended when effusion continues despite treatment or when fever persists. Tri methoprim–sulfamethoxazole, chloramphenicol, rifampin, doxycycline, and enrofloxacin may be useful in horses with pleuropneumonia. As with any horse receiving antimicrobials, colonic disturbance is a potential complication of treatment; therefore, the

horse’s appetite and fecal consistency should be closely monitored during treatment. Treatment with NSAIDs is also indicated to relieve pyrexia and pain; flunixin meglumine, phenylbutazone, and ketoprofen are commonly used for the first week of treatment or longer. Narcotics such as butorphanol tartrate can effectively augment the analgesic effect of NSAIDs, but long-term administration of these drugs can cause constipation, especially in horses that are not drinking adequately and are reluctant to defecate because of chest-wall pain. Administration of corticosteroids is not indicated in horses with pleuropneumonia, despite the antiinflammatory effects of these drugs. TABLE 1

Therapeutic Agents and Dosages

Drug

Dose

Sodium ampicillin

15–30 mg/kg IV q8h

Potassium penicillin G

20,000–50,000 IU/kg IV q6h

Procaine penicillin G

20,000–50,000 IU/kg IM q12h

Ceftiofur

2.2–5 mg/kg IV or IM q12h

Ceftazidime

20–50 mg/kg IV q12h

Gentamicin sulfate

6.6 mg/kg IV or IM q24h or 8 mg/kg IV for initial dosea

Amikacin sulfate

21–23 mg/kg IV or IM q24ha

Enroﬂoxacin

5.5 mg/kg IV q24h; 7.5 mg/kg PO q24h or 4 mg/kg PO q12h

Metronidazoleb

10–25 mg/kg PO q6–12hc or 15–25 mg/kg PO q6hd

Trimethoprim–sulfamethoxazole

30 mg/kg PO q12h

Doxycycline HCl

5–10 mg/kg PO q12–24h

Chloramphenicol palmitate

40 mg/kg PO q6–8h

Rifampin

5–10 mg/kg PO q12h

Phenylbutazone

2.2–4.4 mg/kg IV or PO q12h

Flunixin meglumine

0.5–1.1 mg/kg IV or IM q12h

Butorphanol tartrate

0.01–0.02 mg/kg IV or IM q6–12h

Adjust as needed based on therapeutic drug monitoring and determination of peak and trough concentrations.

Metronidazole can be given rectally, with some loss in availability and absorption, in equine patients with ileus or other forms of gastrointestinal tract failure. At higher dosages, horses can develop depression, ataxia, and anorexia.

In: Robinson NE, Sprayberry K, eds. Current Therapy in Equine Medicine. 6th ed. Philadelphia: WB Saunders; 2008.

Sweeney RW, Soma LR, Woodward CB, Charlton CB. Pharmacokinetics of metronidazole given to horses by intravenous and oral routes. Am J Vet Res 1986;47(8):1726-1729.

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Pleuropneumonia Monitoring and Controlling Complications Serial blood monitoring and sonographic imaging should be conducted frequently during the initial treatment period to ensure response to therapy. Complications associated with pleuropneumonia include those that develop as a result of the disease process (e.g., laminitis) or therapeutic measures (such as development of pneumothorax or cellulitis of the thoracic wall). Ideally, horses with pleuropneumonia are hospitalized during the initial treatment phase, when instrumentation with indwelling pleural drains and intravenous catheters is necessary. Access to a facility where diagnostic ultrasonography is available and personnel are on duty to recognize and respond to problems is a critical factor in patient outcome.

CriticalPo nt Many horses with pleuropneumonia can have a favorable prognosis for survival if appropriate treatment and intervention are provided.

Complications Associated with the Disease Process Bronchopleural fistula formation (and secondary pneumothorax) due to lung tissue necrosis leading to communication between the airways and pleural space. Development of fibrinous interpleural adhesions. Development of pulmonary abscesses and loculation of fluid into multiple noncommunicating cells. Forward dissection and organization of empyema into cranial mediastinal abscess. Pericarditis. Laminitis.

Iatrogenic Complications Cellulitis at chest-tube insertion sites. Development of pneumothorax from leakage of air around or into indwelling tubes. Antimicrobial-induced colitis. Immune-mediated anemia secondary to administration of β-lactam drugs or enroﬂoxacin. Jugular phlebitis or thrombosis at catheter site.

Additional Treatment Measures Trocarization of pulmonary or extrapulmonary abscesses. Lavage of pleural cavity may be necessary to remove inspissated material, eliminate ﬂuid dead space and large microbial populations, and help prevent adhesion formation between the visceral and parietal pleurae. Thoracostomy or use of the “finger-hole” technique may aid in draining exudate or

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accumulated fibrinous material. Before such a defect is created in the thoracic wall, it must be determined whether the mediastinum has become imperforate (by plugging and f illing of the communicating pores) so that the resultant pneumothorax will not affect both hemithoraces. This can be facilitated by placing a trocar catheter and leaving it open to aspirate air for brief periods in order to determine whether the horse remains stable with the other lung inflated. Otherwise, the horse is not a candidate for thoracostomy. Surgical thoracotomy or rib resection can be performed in aggravated cases in which response to treatment is poor or lavage of the pleural cavity through an indwelling tube or thoracostomy opening is insufficient. The same considerations mentioned for pneumothorax apply. Trocarization and drainage of cranial mediastinal masses may be necessary to manage abscesses that compromise cardiovascular function by compressing the cardiac chambers (especially the right ventricular outflow tract) or great vessels.

Prognosis Once pleuropneumonia has been diagnosed, recommendations regarding treatment should be made with candid discussion of the protracted course of treatment; expenses associated with hospitalization, medications, and monitoring; and likelihood for development of sequelae and necessary treatment. Many horses with pleuropneumonia can have a favorable prognosis for survival if appropriate treatment and intervention are provided. The prognosis for survival in horses with pleuropneumonia is largely related to the persistence of a treating veterinarian who is experienced in diagnostic ultrasonography, pleurocentesis, and placing pleural drainage tubes. Complications and sequelae of the infection or of treatment must be addressed promptly and sometimes repeatedly. Although clients must decide whether the horse’s value justiﬁes the expense and longterm commitment to provide care, it is possible to have a positive outcome. Referral of the horse to a referral care center for initial conﬁrmation, instrumentation, and treatment is often the most tenable course of action, with the horse discharged as soon as feasible

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Pleuropneumonia to the owner’s care and referring veterinarian’s supervision for long-term follow-up monitoring and treatment.

Favorable Criteria

Horse tolerates chest-tube manipulation, medication, and ancillary care procedures and does not develop secondary laminitis.

Unfavorable Criteria

Positive response to treatment: resolution of fever and substantial decrease in or cessation of pleural ﬂuid production.

Pleural effusion continues despite administration of broad-spectrum antimicrobials. Development of anaerobic infection. Development of necrotizing or gangrenous pneumonia. Development of laminitis. Horse is intractable or intolerant of handling, conﬁ nement, or frequent medical intervention. SEE RECOMMENDED READING ON NEXT PAGE.

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Pleuropneumonia

Recommended Reading Bertone JJ. Flagrant and covert pleuropneumonia–cases. Proc West Vet Conf 2003. Byars TD, Becht JL. Pleuropneumonia. Vet Clin North Am Equine Pract 1991;7:63-78. Chaffin MK, Carter GK. Equine bacterial pleuropneumonia, part 1: epidemiology, pathophysiology, and bacterial isolates. Compend Contin Educ Pract Vet 1993;15:1642-1650. Chaffin MK, Carter GK, Byars TD. Equine bacterial pleuropneumonia, part 3: treatment, sequelae, and prognosis. Compend Contin Educ Pract Vet 1994;16:1585-1589. Chaffin MK, Carter GK, Relford RL. Equine bacterial pleuropneumonia, part 2: clinical signs and diagnostic evaluation. Compend Contin Educ Pract Vet 1994;16:362-378. McFarland D, Mann KA, Harmon BG, et al. Pleural effusion secondary to aberrant metacestode infection. Compend Contin Educ Pract Vet 1994;16:1032-1039. Seltzer KL. Prognosis for return to racing after recovery from infectious pleuropneumonia in Thoroughbred racehorses: 70 cases (1984–1989). JAVMA 1996;208:1300-1301. Smith BP. Large Animal Internal Medicine. 4th ed. Philadelphia: Elsevier Health Sciences; 2008. Sprayberry KA, Byars TD. Equine pleuropneumonia. Equine Vet Educ 1999;11:290-293. Sweeney CR. Pleuropneumonia. In: Smith BP, ed. Large Animal Internal Medicine. 3rd ed. St Louis: Mosby; 2002:500-504. Wilkins PA. Lower airway diseases of the adult horse. Vet Clin North Am Equine Pract 2003;19(1):101-121.

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CE Article 1

3 CE CREDITS

Oral Joint Health Supplements: Chemistry, Pharmacology, and Administration Guidelines ❯❯ Stacey Oke, DVM, MSc* Rolling Thunder Scientiﬁc Acton, Ontario, Canada

At a Glance Glucosamine Page 178

Chondroitin Sulfate Page 179

Glucosamine/Chondroitin Sulfate Combination Products Page 180

Avocado/Soybean Unsaponiﬁable Extracts Page 181

Avocado/Soybean Unsaponiﬁable Extract/ Glucosamine/Chondroitin Sulfate Combination Products Page 182

Methylsulfonylmethane Page 182

Other Ingredients Page 183

*Dr. Oke is a freelance medical writer for Nutramax Laboratories, Inc.

Abstract: Oral joint health supplements are popular in the equine industry despite, in many cases, a lack of understanding of the chemistry, pharmacology (particularly safety), and appropriate dosages of these products among owners and trainers. The most popular ingredients include glucosamine, chondroitin sulfate, and methylsulfonylmethane; however, a multitude of alternative supplements, including cetyl myristoleate, hyaluronic acid, ester-C, devil’s claw, yucca, garlic, and avocado/soybean unsaponiﬁable extracts, are also widely available. In this article, the most up-to-date information regarding the chemistry, pharmacokinetics (primarily absorption), safety, and dosing of oral joint health supplements is relayed in a practical manner. This information can help clinicians educate clients regarding the use of supplements to ensure that horses derive as much beneﬁt as possible.

omplementary and alternative medical therapies, including the use of oral nutritional supplements, have become increasingly popular in the veterinary community, particularly the equine industry.1 Among these, joint health supplements are ubiquitously employed.1 Oral joint health supplements are popular not only because of the high incidence of osteoarthritis (OA; degenerative joint disease) in the equine population but also because of limitations of conventional medical treatment. Despite the widespread availability and administration of oral nutritional supplements, these products are not considered to be drugs by the FDA. As a result, nutritional supplements, including equine oral joint health supplements, are poorly regulated and typically lack important pharmacologic information, such as absorption, distribution, metabolism, excretion, recommended dosages, and safety information. This dearth of basic scientiﬁc information makes it challenging for practicing veterinarians to identify quality oral joint health supplements. Comprehensive reviews have been published regarding the medical management of equine OA2 and the use of nutraceuticals in horses with OA 3 (both of these reviews

include an up-to-date description of the pathophysiology of OA) as well as future OA management strategies.4 Together, these lay an excellent foundation for this discussion, which focuses on the rationale for the administration of various oral joint health supplements, including glucosamine, chondroitin sulfate, methylsulfonylmethane (MSM),

TO LEARN MORE

Osteochondrosis: Etiologic Factors CE

Article #2

Osteochondrosis: Etiologic Factors Stacy A. Semevolos, DVM, MS, DACVS Oregon State University

Alan J. Nixon, BVSc, MS, DACVS Cornell University

ABSTRACT: Osteochondrosis is a disease of articular cartilage development and is a major source of lameness in young horses, leading to decreased athletic potential. Osteochondrosis involves abnormal differentiation and ossification of articular cartilage during development, resulting in a weakened cartilage matrix and subsequent cartilage flap formation within the joint. This disease is multifactorial, with nutrition, growth rate, hereditary factors, and trauma playing important roles. In addition, aberrant local signaling to the chondrocytes in the deep layer of the articular-epiphyseal cartilage complex is believed to underlie the development of this disease. steochondrosis constitutes a complex of cartilage aberrations, collectively known as developmental orthopedic diseases in horses, including osteochondritis dissecans of the joints (Figure 1), physitis, collapse of cuboidal bones in the carpus and hock, and cervical vertebral malformation.1 Osteochondrosis develops as the result of focal or multifocal defects in cartilage differentiation and endochondral ossification. Dyschondroplasia is used synonymously with osteochondrosis to describe the disease in horses,2 but dyschondroplasia really represents a more generalized metabolic disorder of endochondral ossification that affects the entire skeleton from the early stages of development.3 The definitive cause of osteochondrosis has not been identified, despite many studies of this disease in horses and other species. The consensus is that osteochondrosis is multifactorial and • Take CE tests likely the result of a combina• See full-text articles tion of metabolic derangeCompendiumEquine.com ments. Nutrition, hereditary

COMPENDIUM: EQUINE EDITION

158

factors, biomechanical trauma, and molecular aberrations have all been implicated in the etiopathogenesis of osteochondrosis.2

NUTRITION The impact of nutrition on the development of osteochondrosis has been studied extensively during the past 15 years. High planes of nutrition coupled with rapid growth rates are associated with an increased incidence of osteochondrosis.4–6 In addition, weanlings with a high glucose and insulin response to concentrates may be predisposed to osteochondrosis,7 and weanlings that have adapted to high glycemic feeds may show changes in insulin sensitivity.8 Other nutritional factors that may be involved in the etiopathogenesis include low copper, calcium, or selenium levels and high phosphorus, zinc, or molybdenum levels.9–13 Copper supplementation of mares during pregnancy may help decrease the prevalence of osteochondrosis.13,14 As a result of altered nutritional practices to reduce growth rates and balance the mineral content of feed, the incidence of osteochondroMay/June 2007

159

sis in foals and yearlings has been significantly reduced. Despite these altered practices, however, the disease complex remains at an incidence plateau of approximately 10%.15 In addition, osteochondrosis has been identified in feral horses not receiving high levels of nutrition.16

GENETIC INFLUENCE The possibility of a familial tendency for osteochondrosis has been described, particularly in Standardbreds and Swedish Warmbloods.17–19 In these breeds, the incidence of osteochondrosis is significantly greater in offspring of stallions with osteochondrosis of the hock than in offspring of stallions without the disease.19 Heritability estimates of up to 0.52 also support genetic influence as an important factor in osteochondrosis.20 In further support of heritability as an etiologic factor, research21 shows that inherent growth rate is a major determinant in the development of femoropatellar osteochondrosis in horses. Based on this study,21 greater weight gains during the third and fifth months of life appear to have the most influence on the development of osteochondrosis. The same study 21 did not report a gender influence on the prevalence of osteochondrosis. However, others have reported22 a male predominance:

Figure 1. Osteochondrotic lesion (arrow) of the

femoropatellar joint in a yearling quarter horse. The cartilage of the lateral trochlear ridge of the distal femur remains attached to adjacent cartilage but has partially separated from the underlying subchondral bone.

foal decreases significantly from 5 to 11 months of age, suggesting that lesion healing may occur naturally during this 6-month period. Based on this study,23 biomechanical forces appear to play an important role in the location

Rapid growth rates and factors that lead to rapid growth, including genetic and environmental influences, predispose young horses to osteochondrosis. twice the number of males underwent surgery for femoropatellar osteochondrosis than did females.

BIOMECHANICAL FACTORS Environmental conditions such as access to exercise have been investigated to determine their effects on the manifestation of osteochondrosis. In one study, three groups of foals were compared: those confined in stalls, those turned out to pasture, and those confined in stalls but galloped daily.23 Although the addition of exercise did not significantly affect the number of osteochondrotic lesions, it did affect their location and severity. Compared with other affected foals, foals confined in stalls tended to have more severe lesions, and the femoral condyles were more often affected. In contrast, exercised foals tended to have lesions involving the lateral trochlear ridge of the femur. The results of this study23 indicate that the number of osteochondrotic lesions per May/June 2007

and severity of osteochondrotic lesions. Other investigators24 also suggest that biomechanical forces play an important role in causing the detached cartilage flaps associated with osteochondritis dissecans by initiating separation at the chondro-osseous junction, where the matrix is already weakened.

MOLECULAR ALTERATIONS The biochemical phenomena that precede the weakened matrix associated with osteochondrosis have only recently been studied.25–28 There is little doubt that some abnormality in matrix production and assembly is at the core of the development of osteochondrosis. It is likely that aberrant signaling to the chondrocytes of the prehypertrophic or hypertrophic layers of the articular–epiphyseal cartilage complex may result in delayed chondrocytic differentiation and matrix calcification and the subsequent development of osteochondrosis. Figure 2 COMPENDIUM: EQUINE EDITION

Osteochondrosis: Etiologic Factors (May/June 2007) Abstract Thoughts—Trouble Doing the Locomotion? It May Be an Inside Job (March/April 2007) Related content on

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FREE CE Oral Joint Health Supplements

FIGURE 1

+ Glutamine

+ Acetyl CoA

+ Galactose + sulfate

+ Glucuronate

Glucuronate + sulfate

Iduronate + sulfate

CriticalPo nt Glucosamine is a water-soluble amino monosaccharide that is a fundamental building block for articular cartilage.

Biosynthetic pathway of various glycosaminoglycans, including keratin sulfate and chondroitin sulfate, which are the “building blocks” for healthy articular cartilage.

and avocado/soybean unsaponiﬁable (ASU) extracts, either alone or in combination products, to horses with OA. This article examines the chemistry of articular cartilage and some oral joint health supplement components and presents the most up-to-date and relevant pharmacologic information available. This should allow practicing equine veterinarians to remain current with the ever-increasing information regarding oral joint health supplements and to facilitate product, formulation, and dosing decisions.

Glucosamine Glucosamine is a water-soluble amino monosaccharide that is a fundamental building block for articular cartilage.5,6 As illustrated in FIGURE 1, glucosamine is integral to the synthesis of various glycosaminoglycans (i.e., large molecules

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comprising repeating disaccharide units), including chondroitin sulfate and keratin sulfate (FIGURE 2). In turn, these glycosaminoglycans are incorporated into proteoglycans, which are large molecules composed of a protein core and at least one glycosaminoglycan molecule that is covalently attached.7,8 Perhaps the most well-known proteoglycan is aggrecan (FIGURE 3), which provides compressive stiffness to articular cartilage by swelling and hydrating the framework of collagen ﬁbrils.7,8 Glucosamine is commercially available in three main forms: glucosamine hydrochloride, glucosamine sulfate, and N-acetyl- D glucosamine (FIGURE 4). The hydrochloride and sulfate forms are both salts that stabilize glucosamine following its large-scale production.9 The pKa of glucosamine is 6.91 at 98.6°F (37°C), which means that in the acidic stomach

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Oral Joint Health Supplements CE FIGURE 2 Chemical structure of two predominant glycosaminoglycans in equine articular cartilage.

Chondroitin sulfate C (chondroitin 6-sulfate) and chondroitin sulfate A (chondroitin 4-sulfate).

environment, dissolution of the salts generates glucosamine free base5,6 (FIGURE 4). The freebase form is thought to be absorbed and ultimately incorporated into various biosynthetic pathways, including the synthesis of cartilage glycosaminoglycans as described in FIGURE 1. While all glucosamine salts are believed to generate glucosamine free base in the stomach, not all glucosamine salts deliver comparable amounts of glucosamine free base. Ninety-nine percent–pure glucosamine hydrochloride delivers approximately 80% glucosamine free base, whereas glucosamine sulfate delivers 50% to 60%.9–11 Thus, if an oral joint health supplement contains 12 g of glucosamine hydrochloride, the horse is actually being fed 9.6 g of glucosamine free base. Likewise, if 12 g of glucosamine sulfate per serving is administered, the horse is receiving 6 to 7.2 g of glucosamine free base. Glucosamine is widely regarded as safe. Even after oral administration of very high levels of glucosamine (>5000 mg/kg), no mortality was noted in mice or rats.12 Adverse events associated with administration have not been reported in horses.13,14 In human trials, such as a study by Reginster et al,15 primary complaints included gastrointestinal (GI) effects (i.e., abdominal pain, diarrhea, dyspepsia), but fatigue, headache, vertigo, depressed mood, and allergic episodes were also reported; however, there were no signiﬁcant differences in the reporting of adverse events between the treatment and placebo groups. In late 2004 and early 2005, two separate

Keratin sulfate.

studies conducted by the research groups of Du13 and Laverty,14 respectively, reported that glucosamine hydrochloride was absorbed in horses following intravenous or oral administration via nasogastric intubation. Laverty et al14 reported a mean bioavailability of 5.9% following oral administration at a dose of 20 mg/kg (approximately 10 g) in eight horses, whereas Du et al13 identiﬁed a mean bioavailability of 2.5% after the administration of 125 mg/kg (approximately 56 g for an average horse [990 lb; 450 kg], which is ﬁvefold to tenfold higher than typical doses) of glucosamine hydrochloride.

Chondroitin Sulfate Chondroitin sulfate is a highly sulfated disaccharide polymer (FIGURE 2). Like glucosamine, chondroitin sulfate is a basic building block of articular cartilage and highly variable in terms of molecular weight, source, degree of sulfation, and purity.3,16 Chondroitin sulfate is an expensive ingredient and, therefore, is frequently criticized in terms of failing to meet label claims.17 Like glucosamine, chondroitin sulfate is generally considered safe because the LD50 in mice is >10,000 mg/kg.18 Adverse events related to the administration of chondroitin sulfate alone have not been reported in horses. In the human literature, chondroitin sulfate– related adverse events are typically mild and include GI and unspeciﬁed “musculoskeletal and connective tissue” complaints, although no difference between treatment and placebo groups was noted.19

CriticalPo nt Perhaps the most well-known proteoglycan is aggrecan, which provides compressive stiffness to articular cartilage by swelling and hydrating the framework of collagen ﬁbrils.

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Du et al13 reported a bioavailability of 22% for a low-molecular-weight chondroitin sulfate product after orally administering 3 g via nasogastric intubation. This study indicates that this particular low-molecular-weight chondroitin sulfate is absorbed systemically at this dose. Most equine oral joint health supplement products recommend 0.5 to 2.4 g of various forms and purities of chondroitin sulfate, although a select few recommend up to 3.6 g; however, without further clinical trials in horses, the effective dose is still unknown.

Glucosamine/Chondroitin Sulfate Combination Products

CriticalPo nt Chondroitin sulfate is a highly sulfated disaccharide polymer.

Few studies have evaluated the effect of the combination of glucosamine and chondroitin sulfate in treating equine OA. Hanson and colleagues20 identified a beneficial effect in horses with navicular syndrome after the administration of 9 g of glucosamine hydrochloride and 3 g of chondroitin sulfate daily for 8 weeks. Similarly, while being treated with glucosamine/chondroitin sulfate, 25 horses with degenerative joint disease experienced significant improvement in lameness in the first 2 weeks, which remained level for the following 4 weeks.21 The doses used in this study

were 5.4 g of glucosamine hydrochloride and 1.8 g of chondroitin sulfate twice per day in horses weighing less than 1199 lb (545 kg) and 7.2 g of glucosamine hydrochloride and 2.4 g of chondroitin sulfate twice per day in horses heavier than 1199 lb (545 kg).21 Improved stride characteristics were noted in 20 veteran horses that were administered 2 to 4 g of purified chondroitin sulfate, 5 to 10 g of glucosamine hydrochloride, and 500 mg to 1 g of N-acetyl- D -glucosamine PO for 12 weeks.22 In terms of safety, horses administered five times the recommended maintenance dose (i.e., 18 g of glucosamine hydrochloride and 6 g of chondroitin sulfate daily for 35 days) experienced no clinically significant changes in physical, hematologic, or serum biochemical parameters.23 In an in vivo study by Lippiello and colleagues,24 the effect of glucosamine and chondroitin sulfate in combination was superior to that of either agent alone using a rabbit instability model of osteoarthritis. The synergistic activity of glucosamine and chondroitin sulfate was also reported by Homandberg et al25 while assessing the effectiveness of this combination to protect cartilage from proteoglycan loss caused by exposure to fibronectin

FIGURE 3

Keratin sulfate–rich region Chondroitin sulfate–rich region

Hyaluronic acid

Random chondroitin sulfate attachment region

Clustered chondroitin sulfate attachment region

Chemical structure of aggrecan—a large proteoglycan molecule responsible for providing compressive stiffness by swelling and hydrating the framework of collagen fibrils.

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Oral Joint Health Supplements CE FIGURE 4 Chemical structures of the common forms of glucosamine.

2 + 2Na (or K) + SO4 Glucosamine hydrochloride.

Glucosamine sulfate.

N-Acetyl-D-glucosamine.

Glucosamine free base.

fragments when added to bovine cartilage cultures (which are known to stimulate cytokines and matrix metalloproteinases).25 This study revealed that the combination of glucosamine and chondroitin sulfate at physiologically relevant concentrations synergistically reversed ﬁbronectin fragment–induced cartilage damage and promoted proteoglycan synthesis.25

Avocado/Soybean Unsaponifiable Extracts Unlike information regarding glucosamine and chondroitin sulfate, the history of how ASU extracts were discovered to be potential disease modifiers for OA is unclear. Nonetheless, ASU extracts have been studied in human OA for the past decade and have just recently been introduced to the North American equine industry. ASU extracts are produced by isolating the oils from avocados and soybeans, collecting the unsaponifiable fractions (i.e., the oils that remain after hydrolysis and do not

form soaps), and combining these unsaponified oils in various ratios (1:2 is typical).26 In humans, 300 mg of ASU (4.6 mg/kg per 143-lb [65-kg] person) PO per day appears to be the standard recommended dose. No LD50 or pharmacokinetic/pharmacodynamic information was identified while preparing this article. As summarized in a systematic review of four human clinical trials, the adverse effects associated with ASU extract administration were infrequent and mild.26 The predominant complaints were related to the GI system and were reported with equal frequency in the treatment and placebo groups.26 In horses, the safety of ASU (in combination with glucosamine and chondroitin sulfate) was evaluated in 20 horses during an 84-day period using a randomized, blinded, and placebo-controlled study.27 No significant changes in complete blood counts, serum biochemistry parameters, body weight, or physical examination findings were noted.

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CriticalPo nt ASU extracts are produced by isolating the oils from avocados and soybeans, collecting the unsaponiﬁable fractions (i.e., the oils that remain after hydrolysis and do not form soaps), and combining these unsaponiﬁed oils in various ratios (1:2 is typical).

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Reported in vitro mechanisms of action and the beneficial effects of ASU in welldesigned clinical trials conducted in humans spurred the evaluation of ASU in horses.28 In a blinded and placebo-controlled clinical trial, 16 horses underwent surgical induction of an osteochondral defect in one middle carpal joint on day 0.28 Horses were randomly divided into two groups: the ASU extract group was administered the supplement mixed with molasses, while the placebo group received only molasses from day 0 to 70. Beginning on day 14, all horses were exercised on a treadmill five times weekly until completion of the study. Outcome measures included clinical evaluation, radiography, serum and synovial fluid analyses, gross and histologic examination, and assessment of the articular cartilage matrix. Results indicated that induction of the osteochondral defect resulted in a significant increase in joint pain and disease. While treatment with ASU extracts did not have an effect on pain or lameness, a significant reduction in the degree of articular cartilage erosion and synovial hemorrhage was observed. In addition, there was a significant increase in glycosaminoglycan synthesis by articular cartilage compared with the placebo group. The administered dose used in this study could not be calculated based on the published information; however, the authors specifically stated that no adverse effects were noted and the product was easily administered to horses when it was mixed with a small volume of molasses. This study, which is the only in vivo veterinary trial published to date to evaluate the efficacy of ASU extracts, concluded that while this product did not ameliorate clinical signs of OA, a disease-modifying effect was noted compared with placebo-treated horses. 28 Therefore, the authors suggested that it may be best to combine ASU extracts with clinical sign–modifying agents in clinical practice.

sold in combination with glucosamine and chondroitin sulfate. With the use of an in vitro equine chondrocyte and osteoblast model activated with interleukin [IL] 1β or tumor necrosis factor–α to express the inflammatory mediators cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2), a glucosamine/chondroitin sulfate/ASU extract combination product was evaluated for its antiinflammatory properties.29 This study found that the combination product down-regulated both COX-2 and PGE2. Furthermore, pretreatment of the cultures before cytokine activation profoundly inhibited COX-2 and PGE2 production compared with activated levels in the control cultures.29 Au et al30,31 determined that the glucosamine/chondroitin sulfate/ASU extract combination profoundly inhibited the expression of COX-2 in equine chondrocytes and human fibroblasts, the chemokines IL-8 and monocyte chemoattractant protein 1 in human chondrocytes, some cytokines (tumor necrosis factor–α, IL-1β), inducible nitric oxide synthase, and mitogen-activated protein kinase 14 (also known as p38) in monocytes or macrophages. Inhibition of expression with the use of a glucosamine/ chondroitin sulfate/ASU extract combination in equine and human chondrocytes and monocytes/macrophages was better than that seen with the use of glucosamine or chondroitin sulfate alone. The manufacturer-recommended dose of ASU extracts in the available product is 2100 mg per two level scoops (32.2 g of product), which is equivalent to approximately 5 mg/kg for a 990-lb (450-kg) horse.

Methylsulfonylmethane

Avocado/Soybean Unsaponiﬁable Extract/ Glucosamine/Chondroitin Sulfate Combination Products

Considering the popularity of methylsulfonylmethane (MSM), there is exceedingly little information regarding its chemistry, pharmacology, efﬁcacy, and mechanism(s) of action or safety, particularly in the veterinary literature. MSM is an organosulfur molecule (CH3SO2CH3) naturally found in foods such as fruit, alfalfa, corn, tea, coffee, and milk32 and is metabolized in the body from dimethyl sulfoxide (DMSO).33

The ASU extract product used in the equine clinical trial described above contained only ASU extracts and will not be made available in the United States.a At present, the only ASU extract product available in North America is

a Personal communication with Dr. David Frisbie, Gail Holmes Equine Orthopaedic Research Center, Department of Clinical Sciences, College of Veterinary Medicine and Biological Sciences, Colorado State University (May 2006).

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Oral Joint Health Supplements CE The rationale for administration is twofold. First, MSM is a sulfur-containing molecule that can be used by the body to synthesize various connective tissues.33 Second, because MSM is related to DMSO, which has been used in managing musculoskeletal disorders, many users believe that MSM is therefore also advantageous for musculoskeletal pain, including that associated with OA. To date, only two human clinical trials involving MSM have been conducted, both of which reported improvements in pain, mobility, and swelling.33,34 Doses of 1.5 and 6 g/day PO of MSM were administered without major adverse events. Minor patient-reported adverse events included bloating, constipation, indigestion, fatigue, de creased concentration, insomnia, and headache, but no difference between the incidences of these signs existed between the treatment and placebo groups.33 MSM is considered safe: the LD50 is >20 mg/ kg in mice.35 No pharmacologic information exists in the human literature, but Horváth et al36 found that no adverse events or mortality occurred in rats when 2 g/kg PO of MSM was administered once, and no postmortem gross or renal histologic changes were noted following administration of 1.5 g/kg PO for 90 days. Typical recommended dosages of MSM in equine supplements range from 5 to 10 g/day PO. Kim et al33 used 6 g/day (approximately 90 mg/kg; divided into 3 g q12h) in humans. Extrapolating from the human dose, it is possible that horses can be safely supplemented with higher amounts of MSM than the currently recommended 5 to 10 g/day; however,

this suggestion should be conﬁrmed in controlled clinical trials.

Other Ingredients In addition to the compounds discussed above, a medley of other ingredients are commonly found in equine oral joint health supplements, including ester-C, hyaluronic acid or sodium hyaluronate, cetyl myristoleate, yucca, garlic, and a variety of amino acids, vitamins, and herbs. Many of these compounds are based on structural elements of articular cartilage and therefore may predominantly serve as precursor molecules. Considering that glucosamine and chondroitin sulfate have proven to possess numerous additional mechanisms for promoting joint health, it will be interesting to observe how the use of other supplements will evolve. This is certainly an area worthy of further research.

Conclusion The use of oral joint health supplements in the equine industry continues to increase, often without veterinary consultation. This article can help practicing equine veterinarians better convey to their clients more appropriate means of using oral joint health supplements.

SHARE YOUR COMMENTS Have something to say about this topic? Let us know: E-MAIL editor@CompendiumEquine.com FAX 800-556-3288

CriticalPo nt Considering the popularity of methylsulfonylmethane, there is exceedingly little information regarding its chemistry, pharmacology, efﬁcacy, and mechanism(s) of action or safety, particularly in the veterinary literature.

References 1. Packaged Facts. Publishing Division of MarketResearch.com; May 2005. 2. Goodrich LR, Nixon AJ. Medical treatment of osteoarthritis in the horse—a review. Vet J 2006;171:51-69. 3. Trumble RN. The use of nutraceuticals for osteoarthritis in the horse. Vet Clin North Am Equine Pract 2004;34:7-38. 4. Frisbie DD. Future directions in treatment of joint disease in horses. Vet Clin North Am Equine Pract 2005;21:713-724, viii. 5. Wright IM. Oral supplements in the treatment and prevention of joint disease: a review of their potential application in the horse. Equine Vet Educ 2001;13:135-139. 6. Kelly GS. The role of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease. Alt Med Rev 1998;3:27-39. 7. Palmer JL, Bertone AL. Joint structure, biochemistry and biochemical disequilibrium in synovitis and equine joint disease. Equine Vet J 1994;26:263-277. 8. Brama PA, TeKoppele JM, Bank RA, et al. Inﬂuence of site and age on biochemical characteristics of the collagen network of equine articular cartilage. Am J Vet Res 1999;60:341-345.

9. Russell AS, Aghazadeh-Habashi A, Jamali F. Active ingredient constituency of commercially available glucosamine sulfate products. J Rheumatol 2002;29:2407-2409. 10. Zhou JZ, Waszkuc T, Mohammed F. Single laboratory validation of a method for determination of glucosamine in raw materials and dietary supplements containing glucosamine sulfate and/or glucosamine hydrochloride by high-performance liquid chromatography with FMOC-Su derivatization. J AOAC Int 2004;87:1083-1092. 11. Deal CL, Moskowitz RW. Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate, and collagen hydrolysate. Rheum Dis Clin North Am 1999;25:379-395. 12. Anon. Glucosamine sulfate monograph. Alt Med Rev 1999;4: 193-195. 13. Du J, White N, Eddington ND. The bioavailability and pharmacokinetics of glucosamine hydrochloride and chondroitin sulfate after oral and intravenous single dose administration in the horse. Biopharm Drug Dispos 2004;25:109-116. 14. Laverty S, Sandy JD, Celeste C, et al. Synovial ﬂuid levels and serum pharmacokinetics in a large animal model following treatment with oral glucosamine at clinically relevant doses. Arthritis

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Rheum 2005;52:181-191. 15. Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulfate on osteoarthritis progression: a randomized, placebo-controlled clinical trial. Lancet 2001;357:251-256. 16. Volpi N. Analytical aspects of pharmaceutical grade chondroitin sulfates. J Pharm Sci 2007;Jul 13 [Epub ahead of print]. 17. Boothe DM. Balancing fact and ﬁction of novel ingredients: deﬁnitions, regulations and evaluation. Vet Clin North Am Small Anim Pract 2004;34:7-38. 18. Anon. Science Lab.com Chondroitin Sulfate Materials Safety Data Sheet (MSDS). Accessed August 2007 at www.sciencelab. com/xMSDS-Chondroitin_sulfate_sodium_salt-9923462. 19. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 2006;354:858-860. 20. Hanson RR, Brawner WR, Blaik MA, et al. Oral treatment with a nutraceutical (Cosequin) for ameliorating signs of navicular syndrome in horses. Vet Ther 2001;2:148-159. 21. Hanson RR, Smalley LR, Huff GK, et al. Oral treatment with a glucosamine-chondroitin sulfate compound for degenerative joint disease in horses. Equine Pract 1997;19:16-22. 22. Forsyth RK, Brigden CN, Northrop AJ. Double blind investigation of the effects of oral supplementation of combined glucosamine hydrochloride (GHCL) and chondroitin sulfate (CS) on stride charac-

teristics of veteran horses. Equine Vet J Suppl 2006;36:622-625. 23. Kirker-Head CA, Kirker-Head RP. Safety of an oral chondroprotective agent in horses. Vet Ther 2001;4:345-353. 24. Lippiello L, Woodward J, Karpman R, et al. In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate. Clin Orthop Rel Res 2000;381:229-240. 25. Homandberg GA, Duo D, Ray LM, et al. Mixtures of glucosamine and chondroitin sulfate reverse fibronectin fragment mediated damage to cartilage more effectively than either agent alone. Osteoarthritis Cartilage 2006;14:793-806. 26. Ernst E. Avocado-soybean unsaponifiables (ASU) for osteoarthritis: a systematic review. Clin Rheumatol 2003;22:285-288. 27. Kettenacker RA, Friffin D. Safety profile evaluation of an equine joint health supplement containing avocado/soybean unsaponifiables (ASU), glucosamine, chondroitin sulfate and methylsulfonylmethane (MSM). Proc Am Acad Vet Pharmacol Ther 2007. 28. Kawcak CE, Frisbie DD, McIlwraith CW, et al. Evaluation of avocado and soybean unsaponifiable extracts for treatment of horses with experimentally induced osteoarthritis. Am J Vet Res 2007;6:598-604. 29. Au AY, Au RY, Rashmir-Raven AM, Frondoza CG. Downregulation of cyclooxygenase-2 expression and prostaglandin-E2 production in equine chondrocytes and osteoblasts by avocado soybean unsaponifiables, glucosamine, and chondroitin sulfate. Proc Equine Sci Soc 2007. REFERENCES CONTINUE ON PAGE 185.

3 CE CREDITS

CE TEST 1

This article qualifies for 3 contact hours of continuing education credit from the Auburn University College of Veterinary Medicine. Subscribers may take individual CE tests online and get real-time scores at CompendiumEquine.com. Those who wish to apply this credit to fulfill state relicensure requirements should consult their respective state authorities regarding the applicability of this program. 1. Aggrecan, a proteoglycan, provides a. a scaffolding for bony remodeling. b. compressive stiffness to articular cartilage. c. a and b d. none of the above 2. Glycosaminoglycans in articular cartilage a. serve as building blocks for proteoglycans such as aggrecan. b. include chondroitin sulfate. c. are typically sulfated. d. all of the above 3. Glucosamine is commercially available as a. a sulfate form. b. a hydrochloride form. c. N-acetyl-D-glucosamine. d. all of the above 4. A few research trials involving a glucosamine/chondroitin sulfate combination product have a. shown a beneficial effect in treating horses with degenerative joint disease. b. shown that these products do not have a beneficial effect. c. demonstrated significant changes in clinical measurement (e.g., physical,

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hematologic, and serum biochemical parameters). d. none of the above 5. Oral joint health supplements are popular in the equine industry due to a. the high incidence of osteoarthritis. b. widespread availability of the products. c. interest in complementary and alternative therapies. d. all of the above 6. Typical adverse events associated with glucosamine administration in horses include a. gastrointestinal upset (vomiting and diarrhea). b. lameness. c. urticaria. d. none of the above (No adverse events in horses have been reported.) 7. Which statement regarding MSM is correct? a. It is a well-studied product, which explains why it is so widely used. b. It is popular but does not work. c. It is popular, but further research must be conducted to evaluate its efﬁcacy. d. It is not used in horses; only its metabolite, DMSO, is safe.

8. Glucosamine is integral to synthesis of a. keratin sulfate. b. chondroitin sulfate. c. a and b d. none of the above 9. Which statement regarding studies of ASU extract use is correct? a. No studies have evaluated its use in horses. b. Kawcak et al28 did not find any benefit to using it. c. It appeared to improve signs of pain and have a disease-modifying effect. d. While it did not improve signs of pain, it appeared to have disease-modifying properties. 10. The use of ASU extracts in horses a. has not been reported. b. is associated with serious adverse effects, according to the only clinical trial reported to date. c. can effectively protect articular cartilage from trauma in performance horses. d. may be beneficial in horses with OA, particularly if it is combined with clinical sign–modifying agents.

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Clinical Snapshot Case Presentation #3

❯❯ Amber L. Labelle, DVM ❯❯ Carrie B. Breaux, DVM, MVSc, DACVO*

A 10-year-old Paint horse gelding presented to the Veterinary Teaching Hospital at the University of Illinois Urbana-Champaign with recurrent blepharospasm in the left eye. Ophthalmic examination of the right eye revealed a visual, comfortable globe with no ocular abnormalities and an intraocular pressure of 17 mm Hg. Examination of the left eye revealed moderate blepharospasm and epiphora, mild conjunctival hyperemia, and a miotic pupil with positive direct and consensual (left eye to right eye) pupillary light reflexes. Few keratic precipitates were noted in the ventral cornea, with mid-stromal blood vessels extending from the limbus toward *Dr. Breaux discloses that she has received ﬁnancial beneﬁts from Animal Eye Consultants, Chicago, Illinois.

Courtesy of Erica Tolar, DVM, DACVO

University of Illinois Urbana-Champaign

the axial cornea. There was marked discoloration of the iris, with a yellow hue to the normally blue iris surface, multifocal iris hemorrhages, and moderate aqueous ﬂare. The vitreous was also grossly discolored with a greenish-yellow hue. The fundic examination results were normal. Intraocular pressure in the left eye was 7 mm Hg. No ﬂuorescein stain uptake was noted

in either eye. Image A shows the left eye at presentation. 1. What is your diagnosis? 2. What is the most likely etiology? 3. What are the two most common blinding sequelae of this disease? 4. What is the signiﬁcance of multifocal iris pigmentation? SEE PAGE 186 FOR ANSWERS AND EXPLANATIONS.

Oral Joint Health Supplements: Chemistry, Pharmacology, and Administration Guidelines REFERENCES CONTINUED FROM PAGE 184.

30. Au RY, Au AY, Rashmir AM, et al. Pro-inflammatory gene expression in chondrocytes and monocyte/macrophages is inhibited by the combination of avocado soybean unsaponifiables, glucosamine, and chondroitin sulfate. Proc Vet Orthop Soc 2007;57. 31. Au R, Au A, Rashmir-Raven A, Grondoza CG. Inhibition of proinflammatory gene expression in chondrocytes, monocytes, and fibroblasts by the combination of avocado soybean unsaponifiables, glucosamine, and chondroitin sulfate. Proc FASEB 2007. 32. Richmond VL. Incorporation of methylsulfonylmethane sulfur into guinea pig serum proteins. Life Sci 1986;39:263-268.

33. Kim LS, Axelrod LJ, Howard P, et al. Efﬁcacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthritis Cartilage 2006;14:286-294. 34. Usha P, Naidu M. Randomised, double-blind, parallel, placebocontrolled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Invest 2004;24:353-363. 35. Parcell S, Cand ND. Sulfur in human nutrition and applications in medicine. Alternative Med Rev 2002;7:22-44. 36. Horváth K, Noker PE, Somfai-Relle S, et al. Toxicity of methylsulfonylmethane in rats. Food Chem Toxicol 2002;40:1459-1462.

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Clinical Snapshot Answers and Explanations Case Presentation #3 SEE PAGE 185 FOR CASE PRESENTATION.

1. The most likely diagnosis is equine

recurrent uveitis. 2. Equine recurrent uveitis is a com-

mon syndrome involving recurrent and persistent intraocular inflammation. Although the definitive etiology of this disease remains controversial, it is commonly accepted that some inciting factor initiates an inflammatory cascade, resulting in a self-perpetuating autoimmune attack on the uveal tract. Possible inciting causes include systemic infection with Leptospira spp, trauma, a systemic inflammatory disease, and systemic neoplasia. A hereditary component to the disease is suspected in Appaloosa horses.1 3. The two most common sequelae resulting in blindness are cataract and retinal detachment.1 Image B shows the affected eye after 1 year of topical antiinflammatory treatment using flurbiprofen 0.03% ophthalmic solution. No active intraocular inflammation is present. Image C shows the presence of an incipient anterior and posterior cortical cataract (arrow) that has formed in response to previous episodes of uveitis (the pupil has been dilated with 1% tropicamide solution). 4. Multifocal iris pigmentation is a manifestation of preexisting heterochromia irides, which is often observed in Paint horses and is unrelated to equine recurrent uveitis.

Reference 1. Gilger BC. Equine Ophthalmology. St. Louis: Elsevier Saunders; 2005:285-322.

SHARE YOUR PICTUREPERFECT CASES IN CLINICAL SNAPSHOT

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The Final Diagnosis ❯❯ Bo Brock, DVM, DABVP (Equine), Brock Veterinary Clinic | Lamesa, Texas

My Buddy Mahoot

“S

mall town, Texas” must be tattooed on my forehead. This trip to a big city started out with the ominous feeling I had on many other trips. After some connecting ﬂight problems, my plane finally arrived at 11:00 PM, just 30 minutes after the last shuttle to my hotel. Translation: I had to get a taxi and was about to be ﬂeeced. I approached the only taxicab outside the airport and asked, knowing the pain was about to come, “How much to downtown?” It sounded like the driver said, “$49,” but I could actually see downtown from the airport. Don’t you think a $50 cab ride should at least take you somewhere you can’t see?

Don’t you think a $50 cab ride should at least take you somewhere you can’t see?

TO LEARN MORE The Final Diagnosis gives readers a chance to share their wondrous, weird, or legendary cases or anecdotes. E-mail submissions (no more than 1500 words) to jmoore@uga.edu. CompendiumEquine.com

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After conﬁrming that it was, in fact, going to cost $49, I sighed and got in. As we started off, the driver spoke with a heavy accent. I picked up a few words here and there and grunted in agreement whenever he paused and looked at me in the rearview mirror. The nameplate on the back of the driver’s seat read “Mahoot”; his last name had approximately 27 letters and seemed hungry for vowels. As our oneway conversation progressed, I learned that Mahoot was a new father. Mahoot Jr had been born the previous morning, which, I ﬁgured, may have contributed to the cost of the trip to downtown. When I told Mahoot I was a veterinarian going to a convention about horses, he was speechless, the conversation ended, and he turned on a CD that sounded a lot like breeding cats.

With a few minutes to myself, I decided to call home to check in. The funny thing about my cell phone is you’d think it would work great in a city with millions of people. Unfortunately, the connection was a lot like it is at home in Lamesa: it was good in spots and then fizzled out. I got through once, but the signal died. As we approached my hotel, I found only two $50 bills in my wallet. I wasn’t about to part with both of them, so I gave Mahoot one and told him to keep the change. Heck, it might teach him for overcharging the small-town guy. The hotel looked fine, and sleep sounded wonderful after a day stuck in airports, especially because I had a 7:00 AM meeting the next morning. However, as I unpacked, I realized my cell phone was missing. It must have dropped out in the cab ... of a guy whom I just tipped a buck! A bit frantic, I called my cell phone from the hotel room phone. After five rings, Mahoot answered, “Taxicab service.” What? I’d been out of the cab for 15 minutes, and Mahoot was answering my cell phone like it was his personal pager! “Uh, Mahoot, you are talking on my cell phone. It must have dropped out of my coat while I was in your cab.” The reception wasn’t good, and Mahoot kept repeating, “Taxicab service.” Then the service died completely, leaving me wishing I had given Mahoot both fifties. When I tried calling again a few minutes later, Mahoot answered and said he would bring the phone to the hotel in an hour—at 1:00 AM. So I took a shower and went to the lobby to wait. At 2:00 AM, Mahoot still hadn’t arrived. I was faced with a dilemma—go back to my room to

Compendium Equine: Continuing Education for Veterinarians® | May 2009 | CompendiumEquine.com

The Final Diagnosis call him again, risking the chance of missing him, or sit there and hope. At 3:00 AM, I was pacing the lobby to stay awake. The only person in sight was the woman working the registration counter, and she must have thought I was a small-town idiot who had been taken by a taxicab driver. At 3:30 A M , I went to my room and called Mahoot, who answered, “Taxicab service,” just like before. I politely asked when he was going to bring me my phone, and he answered, “In an hour,” just like before. At 5:05 AM, Mahoot pulled in front of the hotel. As I approached his cab, he rolled down the window and asked, “How much phone worth to you?” Before I could answer, he let me know, in no uncertain terms, that he had to drive all the way back from the airport just for me and that the phone was worth at least the price of another fare from the airport to the hotel. My pockets were empty as Mahoot pulled away from the hotel, and I was left there rubbing my forehead, hoping some of that “Small town, Texas” would come off. But all wasn’t lost—at least I had my phone and time to eat breakfast before the meeting started.

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American Association of Equine Practitioners Bayer Animal Health BET Pharm Boehringer Ingelheim Vetmedica, Inc

CE Meetings Legend BioRelease Meloxicam LA Surpass and Hyvisc

191 Inside front cover 175 192, Inside back cover

Dandy Products, Inc Dechra Veterinary Products Equine Oxygen Therapy, LLC Freedom Health, LLC Intervet/Schering-Plough Animal Health

Padding and Flooring irap Therapy Hyperbaric Treatment Succeed Equine Fecal Blood Test EquiRab PreveNile We’re for the Horse. We’re for You. Adequan i.m. Compounding Pharmacy GastroGard IMRAB Platinum Performance Equine Veterinary Conference Triple Crown Training Formula MYLAB Ultrasound, UMS 900, TERAVET T3000 Veterinary Therapeutics

162 187 163 Back cover 147 159 168–169 151 176 156, 157 161 149 155 165 153 162

Luitpold Pharmaceuticals, Inc Meds for Vets Merial Platinum Performance, Inc Purina Mills Triple Crown Nutrition, Inc Universal Ultrasound Veterinary Learning Systems

Looking for new team members? Reach over 16,100 total qualified subscribers1 — plus the virtually unlimited Internet audience — with your classified ad in Compendium Equine. Reserve your space today! Toll-free: 800-920-1695 Email: CompendiumEquineClassifieds@vetlearn.com Web: www.VetClassifieds.com/placeanad Fax: 201-231-6373

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NADA 141-186, Approved by FDA Veterinary Package Insert

Surpass® (1% diclofenac sodium) Topical Anti-Inflammatory Cream For Use in Horses Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Description: Surpass® topical cream contains 1% diclofenac sodium. Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class. The chemical name for diclofenac is sodium [o- (2,6-dichloroanilino)phenyl]acetate. The empirical formula is C14H10Cl2NNaO2 and the molecular weight is 318.13. Surpass topical cream contains 1% diclofenac sodium in a base composed of Phospholipon 90H, propylene glycol, alcohol (5.94%), vitamin E acetate, benzethonium chloride and purified water in the Wisdom® liposomal formulation. Indications: Surpass topical cream is indicated for the control of pain and inflammation associated with osteoarthritis (OA) in tarsal, carpal, metacarpophalangeal, metatarsophalangeal and proximal interphalangeal (hock, knee, fetlock and pastern) joints in horses. Dosage and Administration: Always provide the Client Information Sheet with the prescription. Dosage: Apply a five-inch (5”) ribbon of Surpass topical cream twice daily over the affected joint for up to ten days. Administration: Wear rubber gloves to prevent absorption into the hands. Rub the cream thoroughly into the hair covering the joint until it disappears. Contraindications: Surpass topical cream is contraindicated in animals with known hypersensitivity to diclofenac. Warnings: Not for horses intended for human consumption. User Safety: Keep out of reach of children. Not for human use. Consult a physician in case of accidental ingestion by humans. Wear gloves to prevent absorption into the hands. Direct contact with the skin should be avoided. If contact occurs, the skin should be washed immediately with soap and water. Animal Safety: For topical use in horses only. Owners should be advised to observe for signs of potential drug toxicity (see Information for Owner or Person Treating Animal and Adverse Reactions). Precautions: Exceeding the recommended dosage or treating multiple joints may increase plasma concentrations of diclofenac (see Animal Safety). The systemic effects of excess diclofenac doses that exceed the recommended label amount and duration have not been evaluated. Horses should undergo a thorough history and physical examination before initiation of NSAID therapy. Appropriate laboratory tests should be conducted to establish hematological and serum biochemical baseline data before and periodically during administration of any NSAID. Owners should be advised to observe for signs of potential drug toxicity (see Information for Owner or Person Treating Animal). Treatment with Surpass cream should be terminated if signs such as inappetence, colic, fecal abnormalities, anemia or depression are observed. As a class, NSAIDs may be associated with gastrointestinal and renal toxicity. When NSAIDs inhibit prostaglandins that cause inflammation, they may also inhibit prostaglandins that maintain normal homeostatic function. These anti-prostaglandin effects may result in clinically significant disease in patients with underlying or preexisting disease more often than in healthy patients. Patients at greatest risk for renal toxicity are those that are dehydrated, on concomitant diuretic therapy, or those with renal, cardiovascular and/or hepatic dysfunction. Studies to determine the effect of Surpass topical cream when administered concomitantly with other drugs have not been conducted. Since many NSAIDs possess the potential to induce gastric ulceration, concomitant use of Surpass cream with any other anti-inflammatory drugs, such as other NSAIDs and corticosteroids, should be avoided. Drug compatibility should be monitored closely in patients receiving adjunctive therapy. The safety of Surpass cream has not been investigated in breeding, pregnant or lactating horses, or in horses under one year of age. Adverse Reactions: During the field study, one diclofenac-treated horse developed colic on day four of the study and responded to symptomatic treatment. One placebo-treated horse exhibited mildly jaundiced mucous membranes on day five. Adverse reactions during the safety study included a gastric ulcer in one horse that received 5.6X the recommended dosage, diarrhea and uterine discharge in one horse that received 2.8X the recommended dosage, and weight loss in four of the six horses in the 5.6X dosage group. To report suspected adverse reactions, to obtain a Material Safety Data Sheet or for technical assistance, call 1-866-638-2226. Information for Owner or Person Treating Animal: Owners should be advised of the potential for adverse reactions and be informed of the clinical signs associated with NSAID intolerance. Adverse reactions may include: weight loss, colic, diarrhea, or icterus. Serious adverse reactions associated with this drug class can occur without warning and, in rare situations, result in death. Owners should be advised to discontinue NSAID therapy and contact their veterinarian immediately if signs of intolerance are observed. The majority of patients with drug-related adverse reactions recover when the signs are recognized, drug administration is stopped, and veterinary care is initiated. Clinical Pharmacology: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties. The mechanism of action of diclofenac, like other NSAIDs, is believed to be associated with the inhibition of cyclooxygenase activity. Effectiveness: In a controlled field study, 82 horses with osteoarthritis were treated with Surpass topical cream (42 horses) or placebo (40 horses). Lameness examinations were performed in horses with osteoarthritis associated with the tarsal, carpal, metacarpophalangeal, metatarsophalangeal and proximal interphalangeal joints. Investigators were masked to treatment. Investigators and owners were instructed to apply the test article over the affected joint twice daily (BID) for five days. Actual doses received by individual horses were calculated using tube weight measurements. The mean dose applied during the study was 73 mg per application. Average lameness scores showed statistically significant improvement following treatment with Surpass topical cream. One diclofenac-treated horse developed colic and responded to symptomatic treatment on day four of the study. Day five bloodwork for the horse that colicked showed decreases in RBC, Hb and HCT, with an increase in PMNs, compared to pretreatment values. One placebotreated horse exhibited mildly jaundiced mucous membranes on day five. No other adverse reactions were noted during the study. Animal Safety: A controlled safety study was conducted with Surpass topical cream. Four groups of six healthy adult horses received 0, 0.6, 1.7 or 2.8X the recommended daily dose for twenty-eight days. The daily dose was divided into two applications on day one of the study. For the remainder of the study, the entire daily dose was given at one time on 0, 1, 3 or 5 joints (tarsal, carpal, metacarpophalangeal, metatarsophalangeal, and proximal interphalangeal joints), depending on the dosage group. The control group of six horses was shamdosed by rubbing the joints daily for twenty-eight days. An additional study group evaluated six horses that received 5.6X the recommended daily dose of Surpass topical cream distributed over five joints on a single day. This dose group was observed for fourteen days without additional treatment. Clinical examinations, hematology, serum chemistry, synovial fluid analyses, gross necropsy and histopathology were performed. At necropsy, one horse in the 5.6X group had a glandular gastric ulcer. A horse in the 2.8X group had diarrhea and uterine discharge throughout the study. Four of the six horses in the 5.6X group lost weight during the study. Dose-dependent increases in diclofenac plasma concentrations were detected in horses in the 1.7X and 2.8X treatment groups. Storage Information: Store at up to 25°C (77°F). Protect from freezing. How Supplied: Surpass topical cream is white to pinkish-white and is packaged in 124-gram trilaminate tubes. Surpass and Wisdom are registered trademarks of Boehringer Ingelheim Vetmedica, Inc. Manufactured for: Boehringer Ingelheim Vetmedica, Inc., St. Joseph, MO 64506 U.S.A. Manufactured under U.S. Patent Nos. 4,937,078 and 6,936,273. © 2009 Boehringer Ingelheim Vetmedica, Inc. All Rights Reserved. 449801L-00-0901 Revised 01/2009 Code 449811

+\YLVF

11 mg/mL (hyaluronate sodium) STERILE INJECTION For intra-articular injection in horses only. DESCRIPTION: Hyvisc® (hyaluronate sodium) is a clear, colorless, viscous fluid contained in a 5 mL disposable syringe, as a single 2 mL dose. Chemically, hyaluronic acid is a high molecular weight mucopolysaccharide composed of repeating di-saccharide units, each unit consisting of D-glucuronic acid and N-acetylD-glucosamine. Each mL of Hyvisc® Injection contains 11 mg of hyaluronate sodium and 8.47 mg of sodium chloride, U.S.P., in sterile water for injection, U.S.P., q.s. ACTIONS: Hyaluronate sodium is a natural constituent of connective tissue and synovial fluid in both man and animals. In synovial fluid, hyaluronate sodium confers viscoelastic as well as lubricating properties (1-2). In connective tissue, hyaluronate sodium specifically interacts with cartilage proteoglycans to form stable aggregates (3-5). The mechanism of action by which exogenous hyaluronate sodium exerts its therapeutic effect in arthritic joints is not known at this time. INDICATIONS: Hyvisc® (hyaluronate sodium) Injection is recommended for the treatment of joint dysfunction in horses due to non-infectious synovitis associated with equine osteoarthritis. CONTRAINDICATIONS: There are no known contraindications to the use of Hyvisc® (hyaluronate sodium) Injection. WARNINGS: Not for use in horses intended for food. Hyvisc® (hyaluronate sodium) Injection must not be administered intravascularly. ADVERSE REACTIONS: In the clinical trial with Hyvisc® (hyaluronate sodium) Injection, a mild, transient post-injection inflammatory response in the joint was reported in 12% of the cases treated. There were no other side effects. DOSAGE AND ADMINISTRATION: The recommended dose of Hyvisc® (hyaluronate sodium) Injection is 2 mL (22 mg) given to horses intra-articularly in small and medium-sized joints (carpal, fetlock). In larger joints (hock), the dosage is 4 mL (44 mg). Treatment may be repeated at weekly intervals for a total of three treatments. As with any intra-articular injection, aseptic technique is used. The following are suggested use directions regardless of the type of joint to be treated. 1. Carefully diagnose each case using routine methods. The origin of lameness should be pinpointed to be within a specific joint or joints (e.g., lameness is localized to a specific joint using intra-articular anesthesia). Radiographs or other diagnostic aids should not reveal recent fractures or other serious abnormalities which would suggest a poor prognosis. 2. Aseptically remove as much synovial fluid from the afflicted joint as can be easily withdrawn. 3. Remove tip cap from the Hyvisc® syringe and inject through a sterile needle, 20 gauge or larger. 4. Inject a single 2 mL dose (one syringe) of Hyvisc® into each joint to be treated; if the joint being treated is the hock joint, inject 4 mL (two syringes). Since Hyvisc® is a viscous fluid, care should be exercised on injection so as not to dislodge the needle from the syringe. 5. Two or four days of rest or light exercise is recommended before resumption of normal activity. Improvement of joint function should be seen within one to two weeks after Hyvisc® Injection. As with any intra-articular injection, a mild inflammatory response (tenderness, heat and swelling) may be seen in the joint following the Hyvisc® Injection. This response is self-limiting, but may last from two to five days after treatment. If inflammation is excessive or severe, the possibility of infection should be considered and appropriate antibiotic therapy instituted. CAUTION: Federal Law restricts this drug to use by or on the order of a licensed veterinarian. Used or partially used syringes should be crushed and disposed of in an appropriate landfill. Do not use if numerous small air bubbles are present throughout the solution. STORAGE: Store under refrigerated conditions. Protect from freezing and avoid excessive heat. HOW SUPPLIED: Hyvisc® (hyaluronate sodium) Injection, 11 mg/mL, is available in 2 mL prefilled, disposable syringes individually packaged. SAFETY MARGIN IN HORSES: In toxicity studies of Hyvisc® (hyaluronate sodium) Injection in horses, intra-articular doses at one, three, and five times the recommended dose once weekly for three consecutive weeks did not result in any drug related local or systemic toxic effects. The mild transient post-injection inflammatory response observed within the joints of some horses was qualitatively and quantitatively similar to that detected in the physiologic saline injected controls. In a reproductive study in mares, 16 mL of Hyvisc® (10 mg/mL) injected intramuscularly or subcutaneously once or twice during the second or third stage of pregnancy resulted in no adverse effects on the mares or newborn foals. REFERENCES: 1. Radin, E.L. et al: Annals of the Rheumatic Diseases, 30: 322325, (1971). 2. Swann, D.A. et al: Annals of the Rheumatic Diseases, 33: 318326, (1974). 3. Hardingham, T.E. and H. Muir: Biochemical et Biophysica Acta, 279: 401-405, (1972). 4. Hascall, V.C. and D. Heingard: Journal of Biological Chemistry, 249: 423-433, (1974). 5. Brandt, K.D. et al: Arthritis and Rheumatism, 19: 1308-1314, (1976). Hyvisc® registered trademark of Anika Therapeutics, Inc. Manufactured by: Anika Therapeutics, Inc. Woburn, Massachusetts 01801 U.S.A. Distributed by: Boehringer Ingelheim Vetmedica, Inc. St. Joseph, MO 64506 U.S.A.

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JOINT HEALTH

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THE CHOICE IS UP TO YOU.

SURPASS® is a trusted name for effective FRQWURO RI SDLQ DQG LQÁDPPDWLRQ DVVRFLDWHG with osteoarthritis in hock, knee, fetlock and pastern joints in horses.

i ® combines Hyvisc bi hi high h molecular l l weight i ht with extremely low levels of extraneous protein, offering your horse a pure, dependable treatment for joint dysfunction.

Boehringer Ingelheim Vetmedica Inc. is proud to provide the veterinarian with these two distinct Joint Health Management products. 1-866-638-2226 WWW.BI-VETMEDICA.COM

As with any prescription medication, prior to use, a veterinarian should review the medical history of the horse and perform a physical examination. Observe for signs of potential drug toxicity. As a class, nonsteroidal anti-inﬂammatory drugs may be associated with gastrointestinal and renal toxicity. Consult full package insert for information regarding use.

In the clinical trial, as is common with intra-articular injection, a mild inﬂammatory response was observed post-injection. Care should be taken to ensure aseptic technique. There are no known contraindications to the use of Hyvisc. Surpass® is a registered trademark of Boehringer Ingelheim Vetmedica, Inc. © 2008 Boehringer Ingelheim Vetmedica, Inc. All rights reserved

See Page 192 for Product Information Summary

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Now available. SUCCEED® is a registered trademark and Equine Fecal Blood Test™ and SmartSignal™ are trademarks of Freedom Health, LLC. © 2009. All Rights Reserved. PATENT PENDING. Murray MJ (1994), “Gastric ulcers in adult horses”, Comp Cont Educ Pract Vet; 16: pp. 792-794, 797. McClure SR, Glickman LT, Glickman NW (1999) “Prevalence of gastric ulcers in show horses”, J Am Vet Med Assoc; 215: pp. 1130–1133. Michell RD (2001), “Prevalence of gastric ulcers in hunter/jumper and dressage horses evaluated for poor performance”, in Proceedings. Annual Meeting of the Association of Equine Sports Medicine 2001; pp. 74-77. 4 Pelligrini FL (2005), “Results of a large-scale necroscopic study of equine colonic ulcers”, J Equine Vet Sci; 25 (3): pp. 113-117. 1 2 3