CompanionQuarterly vol27 no4 December 2016 by Companion Quarterly

COMPANION QUARTERLY â&#x20AC;&#x201C; Official Newsletter of the Companion Animal Veterinarians Branch of the NZVA

Companion Quarterly

OFFICIAL NEWSLETTER OF THE COMPANION ANIMAL VETERINARIANS BRANCH OF THE NZVA Volume 27, No. 4 | December 2016

VOLUME 27 NO 4 DECEMBER 2016

Collecting ceresbrospinal fluid

A South Island case of leptospirosis

In-clinic safety around dogs

Displacement of protein-bound drugs

Pimobendan for treatment of feline HCM

Volume 27 | No. 4 | December 2016 ISSN No. 2463-753X EXECUTIVE COMMITTEE 2016 cas@vets.org.nz

CONTENTS

President

Helen Beattie

Companion Quarterly

Operations Manager Rochelle Ferguson

Treasurer

Aimee Brooker

Committee Members Warren Stroud John Munday Catherine Watson Toni Anns Natalie Lloyd Pauline Calvert

EDITORAL COMMITTEE Sarah Fowler (Editor) Genevieve Rogerson Angus Fechney Christine Moloney (Advertising) Janice Thompson Simon Clark

Address for submitting copy/ correspondence

2 Editorial 4 Highlights from CAS Executive Meeting

8 CAV Noticeboard 10 CAV News Update 14 What is your diagnosis? Brianna Dalbeth

Sarah Fowler 66 Callum Brae Drive, Rototuna, Hamilton 3210 T (H) 07 845 7455 | M 027 358 4674 E sarah.fowler@gmail.com

16 Collecting cerebrospinal fluid –

Advertising Manager

20 Tips for in-clinic safety around

Christine Moloney 25 Manchester St, Feilding T 06 323 6161 | F 06 323 6179 E christine.moloney@totallyvets.co.nz

NZVA website www.nzva.org.nz CAV website www.cas.nzva.org.nz

do it my way? Boyd R Jones

dogs Dr Elsa Flint

24 Displacement of protein bound drugs: a pharmacological review Liz Shackleton

32 Use of pimobendan for the treatment of hypertrophic cardiomyopathy in a cat ZL Kamsma

The whole of the content of the Companion Quarterly is copyright, The Companion Animal Veterinarians Branch of the NZVA (CAV) and The New Zealand Veterinary Association (NZVA) Inc.

38 Not your usual yellow dog: A

case of leptospirosis in a South Island dog Angela Wright

Cover photograph

Courtesy of Jade Hackney and shows her 4-year-old dog Rook, after climbing Mt Sunday (Canterbury) with his rucksack on.

Newsletter design and setting Penny May T 021-255-1140 E penfriend1163@gmail.com

Disclaimer The Companion Quarterly is a non peer reviewed publication. It is published by the Companion Animal Veterinarians Branch of the NZVA (CAV), a branch of the New Zealand Veterinary Association Incorporated (NZVA). The views expressed in the articles and letters do not necessarily represent those of the editorial committee of the Companion Quarterly, the CAV executive, the NZVA, and neither CAV nor the editor endorses any products or services advertised. CAV is not the source of the information reproduced in this publication and has not independently verified the truth of the information. It does not accept legal responsibility for the truth or accuracy of the information contained herein. Neither CAV nor the editor accepts any liability whatsoever for the contents of this publication or for any consequences that may result from the use of any information contained herein or advice given herein. The provision is intended to exclude CAV, NZVA, the editor and the staff from all liability whatsoever, including liability for negligence in the publication or reproduction of the materials set out herein.

10 44

43 Erratum 44 Honest placebos Allan Bell

45 Conference report: Highlights from the Australian and New Zealand College of Veterinary Scientists Science Week conference Dr Pru Galloway

50 Conference report: Veterinary Dental Forum Angus Fechney

53 Companion Animal Health

Vets in Stress Programme

24 Hour Freephone Confidential Counselling Service

Foundation Update

What's your diagnosis? The answers

0508 664 981 Helps you solve personal and work problems, including: Relationship problems Drug and alcohol issues Work issues Change Stress Grief

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

EDITORIAL

Cats, dogs, and politicians It’s perhaps been a little bit of induction by fire in to the CAVs president’s role – timing has aligned with two significant, topical and fairly emotive issues; cat control and dangerous dogs. And in fact, these topics have had to fit in around me racing off to Perth to bike for 30 minutes around Rottnest Island on time trial bike, juggling a couple of fabulous children, working fulltime, studying part time to gain my Animal Welfare Inspector’s warrant (tick that box!), and dealing with “a few emails” (Pieter Verhoek!!) as part of the CAVs executive. As a high country farmer’s daughter, I did not see my career in Persians and Labradoodles, education, nor the SPCA. Rather, I saw farm cats and huntaways. But my journey thus far has been interesting and challenging, and as always, has many topics that I’m keen to get my figurative teeth into. Firstly, the National Cat Management Strategy Group released their document for a second round of consultation. I’ve been at the table with the group from the outset, and it’s fair to say have learned a lot and re-evaluated my position on issues contained therein. Overall, the feedback regarding the strategy is largely positive. One issue that has caused some conjecture is the idea of trap, neuter and return (TNR) for stray (not feral) cats – that is, cats living around human habitation, whether they are social or unsocial. This was an issue about which I had to re-position myself, and now fully understand and endorse its use as a short-to-medium term management tool. Understanding why this is important and getting the support of our profession is critical to the success of any cat management for New Zealand. The key to my re-positioning was developing an understanding that the TNR must be managed, and targeted (mtTNR). That means that cats in a specific area, are caught, health checked, de-sexed, distance identified (e.g. ear tip), vaccinated and microchipped. They are then returned to a managed colony – that means someone, or a group of people, have to agree to supervise, manage and monitor these cats. Immigration is prevented and colony managers assist with feeding, care and addressing health issues for these cats. And yes – there are people who are prepared to do this, and perceive a relationship with many of these colony cats. This has been proven to reduce numbers of stray cats over time. Random, non-targeted, un-managed TNR has not, and neither has trap and destruction. There are quite simply too many other cats in the surrounding areas that in-fill the cleared area, in a very short (weeks to months) period of time. It is evident that mtTNR is a necessity. The details of exactly how this would work (e.g. where records are kept) are to be determined. But I am in no doubt, that in order to achieve Predator Free 2050, managed, targeted TNR will needs to be part of the toolbox, in appropriate areas.

Secondly, dangerous dogs. A lot of background work has happened since the NZVA roadshows, where criticism was heard about a lack of NZVA voice on this issue, perhaps rightly so. Silence was a conscious decision – it was realised that a complete re-dress of NZVA dog policy was required, and that our approach needed to be more 3-dimensional. Indeed, that meant embracing the human, animal and the environmental aspects that all contribute to dogs biting. All the expectations of furore around the cat strategy document were a little sidelined by Associate Minister Upston’s announcement about dog control. Whilst she has been fully informed and briefed regarding the science and research around breed specific legislation, her proposal reflected none of this. CAVs and NZVA are pursuing further communications and proffering advice, with the intention of the Government position being fair and reasonable, and informed by science. The article “Recent developments on the Dangerous Dog Issue” covers this off in more detail. Frustrations run high, when logic, reason and evidence are disregarded – the core of what we do and know as a profession. This is another example of where the veterinary profession bridges the triad of people, animal and the environment, and are capable of offering sound positioning because of this. Managing political agendas may fall outside of all of those contributing factors! Helen Beattie, CAV President. l

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

WORKING TO PROMOTE AND SUPPORT COMPANION ANIMAL PRACTICE IN NEW ZEALAND

Highlights from the CAV Executive Committee meeting August 2016

New committee officers

In the first meeting following the AGM, the officers for the coming year are appointed. Brendon Bullen was thanked for his contribution to the committee and Helen Beattie was unanimously elected to be the new President. Rochelle Ferguson remained as Secretary, and Aimee Brooker will continue to serve as the Treasurer.

NZKC brachycephalic breeding initiative

The NZKC are looking at a scheme to improve the welfare of brachycephalic dogs through selective breeding based on a model currently used by the UK kennel club. We have signalled our support to them on this initiative.

Vaccination policy

The NZVA vaccination policy (reviewed in 2014) will need to be reviewed again in light of the WSAVA vaccination guidelines released earlier this year. Key changes are: • Puppy and kitten vaccination schedules starting earlier at 6–8 weeks and continuing every 2–4 weeks to 16 weeks of age, • The recommendation of a booster or titre test at 6–12 months of age, instead of one year after the primary series finished, • A change in the FIV vaccination classification from ‘not recommended’ to a ‘non-core vaccine.’

Pet insurance

The promotion of pet insurance in general terms to the public was discussed and we have agreed to look at this as a project for 2017.

Disaster preparedness

The committee were given a presentation by Steve Glassey on this topic. He detailed learnings from past disasters such as Hurricane Katrina and the Queensland bush fires that showed the intrinsic link between keeping people safe and having an acceptable evacuation plan in place for their animals.

3 Have a pet carrier for each animal (labelled) 4 Have a muzzle and leash for each dog 5 Download the new Red Cross HAZARD APP for notifications 6 Always evacuate with your pet and evacuate early 7 Family plans – Pets are members of the family – include pets when making plans for alternate accommodation, or have an alternative person to send the pets on to. 8 Getaway kits – make sure to have extra pet food and water, pet photos to help with reuniting, vaccination cards and any medications.

Veterinary clinic disaster preparedness

• Have a plan • Know your hazards and building standard • Develop mutual aid agreements with other clinics or businesses • Know how to operate remote call diversion and data access after hours • Make checking microchips part of routine checks and collect out of region contact details • Participate in Get Ready week – involve clients

Greyhound welfare committee

NZVA has been invited to join the Greyhound Racing New Zealand (GRNZ) Welfare Committee. This committee is chaired by Dr Jim Edwards. It is charged with ensuring that “all greyhounds in New Zealand are protected and promoted by the adoption and development of sound animal welfare standards and practices.” The committee ensures the recommendations from GRNZ’s welfare review are implemented. The SPCA and National Animal Welfare Advisory Committee (NAWAC) are also advisors to this committee. While the committee holds reservations about the welfare of racing greyhounds, it was thought that we would be more likely to positively influence their welfare by being at the table, along with the SPCA and NAWAC. Rochelle Ferguson was appointed as the NZVA/CAV advisor to the GRNZ Welfare Committee. l

8 pet- and people-saving tips

1 Microchip, microchip, microchip – with an “out of region” contact for the second contact. 2 Have an out of region contact details on ID tag also

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

The CAV Noticeboard Hill’s Pet Nutrition/CAV Educating the Educators Scholarship This scholarship provides assistance for veterinary educators to attend advanced level continuing education events outside New Zealand, in exchange for articles, reports and presentations on their area of interest. Through this partnership, we recognise the importance in supporting our leading veterinarians’ participation in international conferences to ensure they remain up to date, and disseminate this knowledge to the wider CAV membership. This scholarship is open to both CAV members and non-members. Successful applicants are usually specialists in their field but we also support those who have developed advanced skills in a specialist area.

If you would like to partner with us to improve the knowledge of NZ veterinarians, then see our website, or contact cav@vets.org.nz for application forms and a list of the terms and conditions. Applications are usually considered at the end of March and September each year. We have $10,000 per annum to grant and are very keen to have this resource utilised to support and promote companion animal veterinarians. We are very grateful to Hill’s Pet Nutrition as the principle sponsor along with support we receive from the Institute of Veterinary, Animal and Biomedical Sciences and VetLearn.

G SCH RAN OL TS & AR SH Ava IPS ilab CAV le to me mb ers

CAV/CAHF Project Grant 2016 The Companion Animal Health Foundation is a charitable trust that acts as the research funding arm for CAV. Funding applications from CAV members are invited in March and September for research projects that will enhance companion animal health and welfare.

WINNER

See the CAHF website (www.healthypets. org.nz) to find out how we are supporting projects on elbow dysplasia, bone marrow sampling techniques and FIV prevalence. Any queries on how to make an application or donate contact Rochelle Ferguson (CAV Operations Manager) on cav@vets.org.nz

Article of the Issue

“Feline orofacial pain syndrome”

Nikki Frost

September 2016 | Volume 27 (3) | Pages 32–37

EYEVET Services Limited

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

CAV NEWS UPDATE

Recent developments on the dangerous dog issue Since reviewing the NZVA dangerous dog position statement in August, CAV have made a submission to the Department of Internal Affairs (DIA) on managing dangerous dogs and met with them to discuss it further. We have involved ourselves in this issue since as veterinarians we believe it is important that New Zealand society continues to enjoy the benefits of having dogs in our lives, people are kept safe from dog aggression, and the welfare needs of dogs are also met with any proposed changes to dog control law. Following on from this, during the New Zealand Institute of Animal Management conference in September, the Associate Local Government Minister, Louise Upston announced a new national action plan, intended to reduce the risk and prevent harm from dog attacks. The plan contains some of the initiatives detailed in our submission, such as support for community education and better consistency in dog control approaches between local authorities. There has also been ongoing discussion about owner licensing (albeit limited to classified dog owners only). Unfortunately, the new plan did not address the problems that the NZVA raised with the current classification system in the Dog Control Act. The current classifications include breedspecific legislation and acts as a barrier to effective dog control.

Current classifications under the Dog Control Act 1996

Under the Dog Control Act 1996, there are two categories of classified dogs – ‘menacing’ and ‘dangerous.’

Dogs are automatically classified as ‘menacing’ if they belong to a breed or type listed on Schedule 4 of the Dog Control Act (this includes the American pit bull type). To compound matters, there is no scientifically validated method to determine if a dog is an American pit bull terrier type (see sidebar). Identification is based solely on a visual appraisal by an animal control officer, while this is cost-effective and immediate, it has also been shown to be inaccurate and inconsi (Voith et al. 2013) stent. The NZVA does not support identification of unregistered breeds and/or crossbreeds on the basis of 'visual assessment’ due to the lack of scientific correlation between genetic makeup and physical characteristics (Australian Veterinary Association 2012). Dogs can also be classified as ‘dangerous’ in New Zealand based on their actions. This classification does not account for the context or severity of the incident. This means that the same restrictions are applied to a dog that has rushed aggressively at their gate causing a fright, as to one that has chased and bitten someone multiple times without provocation. The NZVA would like the dangerous classification divided into ‘potentially dangerous’ and ‘dangerous’ categories. These

Source: pixabay/com

would be based on the context of the incident and any provocation, with increasingly stringent restrictions applied depending on category assigned. Mandatory behaviour testing by suitably qualified assessors should also be applied to all classified dogs (at the owner’s expense), and a rehabilitation pathway developed for the ‘potentially dangerous’ dogs. Owners of a classified dog would also be subject to further restrictions such as being over 18 years of age, subject to criminal background checks and tested for their ability to handle the dog.

Proposed ban on re-homing pit bulls

The Minister’s recent announcement also extended the breedspecific focus of dog control legislation to ban the re-homing of pit bull types. This policy appears to be based on a poor understanding of dog bite statistics (Hussain 2006) and a disregard for the scientific evidence showing that breed bans do not effectively reduce dog bite injuries to people (Patronek et al. 2010).

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

Pit bull types are a breed of choice for ‘irresponsible’ owners, their over representation in dog bite “statistics” reflects their popularity in the victim’s community and reporting biases. Controlled studies have not shown them to be disproportionately dangerous (American Veterinary Medical Association Animal Welfare Division 2014). Any dog that has been raised in the wrong environment by an irresponsible owner poses a risk to society. To focus on pit bull types alone is a gross oversimplification, wastes precious resources and reduces the effectiveness of dog control laws.

The next steps

Unfortunately, if the Minister continues to pursue her current agenda, it will result in a major loss of support amongst key stakeholders. We recently attended a meeting with the Minister where she was not prepared to look at the literature on this issue or entertain any changes to the government’s plan. The SPCA has started a petition against the ban on rehoming pit bulls that has attracted a high level of support. Other animal welfare groups have also indicated that they intend to oppose this aspect of the new plan. The Minister plans to introduce the legislation into the House in February and the NZVA will make a submission that includes the international research that clearly shows no support for breed-specific legislation reducing or preventing dog bite injuries. The way forward to manage this issue is not to ban breeds, but for communities to implement policies that hold all dog owners responsible for the humane care, custody, and control of their dogs, regardless of breed or appearance. It requires a multifactorial approach, focusing on improved ownership and husbandry practices, better understanding of dog behaviour, education of parents and children regarding safety around dogs, and consistent enforcement of sensible dangerous dog control laws (National Canine Research Council 2014). For further information on this issue the NZVA have prepared a position description available on our website: http://www.nzva.org.nz/default. asp?page=policydangerousdogs or see the summary printed in the November issue of Vetscript.

References

American Veterinary Medical Association Animal Welfare Division. Literature review on the welfare implications of the role of breed in dog bite. Retrieved from https://www.avma.org/KB/Resources/ LiteratureReviews/Pages/The-Roleof-Breed-in-Dog-Bite-Risk-andPrevention.aspx, Americal Veterinary Medical Association, 2014 Australian Veterinary Association. Dangerous dogs – a sensible solution: Policy and model legislative framework. Retrieved from http://www.ava.com.au/ sites/default/files/AVA_website/pdfs/ Dangerous%20dogs%20FINAL.pdf, St Leonards, NSW, Australian Veterinary Association Ltd 2012 Hussain S. Attacking the dog-bite epidemic: Why breed-specific legislation won't solve the dangerous-dog dilemma. Fordham Law Review 74 2847. Retrieved from http://ir.lawnet.fordham.edu/flr/ vol74/iss5/7, 2006 National Canine Research Council. Breed-specific legislation is on the decline. Retrieved from http://www. nationalcanineresearchcouncil.com/ news/breed-specific-legislation-decline, National Canine Research Council, 2014

Olson KR, Levy JK, Norby B, Crandall MM, Broadhurst JE, Jacks S et al. Inconsistent identification of pit bulltype dogs by shelter staff. The Veterinary Journal 206, 197–202, 2015 Patronek G, Slater M, and Marder A. Use of a number-needed-to-ban calculation to illustrate limitations of breed-specific legislation in decreasing the risk of dog bite-related injury. Journal of the Americal Veterinary Medical Association 237, 788–92. 2010 Simpson R, Simpson K, and VanKavage L. Rethinking dog breed identification in veterinary practice. Journal of the American Veterinary Medical Association 241, 1163–6, 2012 Specialist Diagnostic Services Ltd. BITSA – Frequently Asked Questions. Retrieved from http://www.bitsa.com. au/faq.php?fid=10, Specialist Diagnostic Services, Heidelberg, VIC, Australia. Voith V, Trevejo R, Dowling-Guyer S, Chadik C, Marder A, Johnson V, Irizarry K. Comparison of visual and DNA breed identification of dogs and inter-observer reliability. American Journal of Sociological Research 3, 17–29, 2013 l

The problem with pit bulls…

At the heart of the breed specific legislation is the problem of identifying exactly what is a pit bull. The American pit bull is not a registered breed outside of the United States and in New Zealand it is referred to as a ‘type’ not a ‘breed.’ In New Zealand American pit bull types are assigned as such based solely on visual inspection. Being identified as a pit bull type in New Zealand has serious implications for dogs and their owners. Pit bull types are listed in Schedule 4 of the Dog Control Act 1996 and are automatically classified as ‘menacing’ and subject to restrictions. This process of visual identification is fraught with error – particularly when dealing with dogs of mixed breeding. When scientifically analysed, the visual identification of mixed dog breeds, has shown them to have less sensitivity and specificity than a coin toss (Olson et al. 2015). A recent study in 2012 compared the results of breed identification made on the basis of visual inspection with the results of DNA analysis of breed. The major breed determined on the basis of visual inspection matched the predominant breed identified by means of DNA analysis in only 25% of cases (Voith et al. 2013). Because pit bulls are sourced from a range of bull breeds, genetic tests to determine if a dog is a pit bull are unreliable (Simpson et al. 2012). The BITSA test, available in New Zealand, through Gribbles Veterinary Pathology, cannot identify American pit bulls. The BITSA product is an informative genetic service to give owners an insight into their dogs breed ancestry. They do not authorise or permit the test to be used to legally verify a dog’s breed, obtain official papers, or serve as evidence of a pedigree dog (Specialist Diagnostic Services Ltd). The NZVA does not support veterinarians being used to identify unregistered breeds and/or crossbreeds on the basis of 'visual assessment only' because of the inconsistencies (highlighted by recent research) in visual breed identification. The term “mixed-breed” should be used rather than guessing at a dog’s breed by visual inspection when classifying a dog in veterinary practice.

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

What is your diagnosis? THE QUESTIONSâ&#x20AC;Ś BRIANNA DALBETH, BVSc, Zoetis VSG Small Animal Medicine & Surgery Intern

An 80 kg, 3-year-10-month-old male neutered Leonberger dog was presented to the referring veterinarian for right forelimb lameness. He was treated conservatively with non-steroidal anti-inflammatory medications for 10 days, however the owner noted no improvement. One week after completing the non-steroidal antiinflammatory medications, a swelling was identified over his distal radius. Radiographs of the right antebrachium were performed (Figure 1). He was then treated with clindamycin, 10 mg/kg, orally every 12 hours for 14 days; minimal clinical improvement was noted and he was then referred to a specialist practice for further work-up and treatment. On presentation to the specialist, the dog was ambulatory with a moderate, consistent, weight-bearing right forelimb lameness at a walk. Physical examination revealed a firm, painful mass on the medial aspect of the distal right radius. Mucus membrane colour and capillary refill time were normal. Thoracic auscultation and abdominal palpation revealed no abnormalities. No other orthopaedic abnormalities were noted on examination. 1 What are your radiographic findings? 2 What are your differential diagnoses? 3 What further diagnostic tests would you perform? 4 For the most likely diagnosis, what treatment options are available? l

Answers revealed on page 54.

Figure 1. Figure 1. (A) cranio-caudal, and (B) medio-lateral radiographs of the right antebrachium

Contact current address: College of Veterinary Medicine, University of Georgia Athens, Georgia, USA. Email: bnd54974@uga.edu

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

FEATURE ARTICLE

Collecting cerebrospinal fluid – do it my way? This is the last in our series of 12 review articles from Emeritus Professor Boyd Jones which were funded from proceeds of WSAVA 2013

BOYD R JONES ONZM, BVSc,

FACVSc, DECVIM-Ca

Collection of cerebrospinal fluid (CSF), for me, has similar resonance to the Frank Sinatra song ‘I did it my way’. I use a technique similar to, but not the same as, most textbook descriptions and it is easy. There are chapters or sections on CSF collection in small animal neurology books, journal papers and ‘how to’ books (Walmsley and Alleman 2011; Lowrie 2013). All of them work but here are my comments and advice on a simplified and complication-free CSF collection procedure in the dog and cat.

Why should I collect CSF?

You might think collection of CSF for analysis could be useful in all cases of neurological disease but it is not. You must select cases correctly to get the best reward. CSF analysis can determine whether inflammatory disease is present or sometimes another cause: neoplastic, degenerative, traumatic etc. The results of the analysis must be interpreted with the history, clinical signs and other findings (imaging, biochemistry etc).

What cases are right for CSF collection? The following might indicate that CSF analysis could be helpful: l Focal or generalised pain (especially head and neck pain): particularly in younger dogs, suggests meningoencephalomyelitis (MEM). MEM, including granulomatous meningoencephalomyelitis (GME) and steroid-responsive meningitis-arteritis (SRSM), can occur concurrently with, or as a sequela to, many inflammatory and infectious diseases. MEM should be suspected in dogs with pyrexia, neck pain, low head carriage and lethargy. Clinical signs frequently wax and wane. Contact: IVABS, Massey University, Palmerston North

l Multifocal CNS disease: if neurological

examination supports multifocal or diffuse CNS disease this can be characteristic of diffuse neoplastic or inflammatory disease. l Where systemic inflammatory disease is present along with neurological signs: pyrexia of unknown origin is an indication if CNS signs are present and even when not, as some meningeal conditions can be subclinical. l Myelography: myelography is indicated to determine the site of possible spinal cord compression or swelling. Always collect CSF before the contrast agent is administered. Ideally the CSF analysis should be completed before the myelogram. In some institutions this is routine; probably not in general practice. l Think CSF collection at the onset of the condition or if signs are progressing. Think of CSF as ‘blood’ draining the CNS. Don’t wait until all other tests are done or medications have been administered if you think CSF analysis is indicated. Do it now!

Should I undertake the procedure?

If you have experience it is easy. Collecting CSF can result in iatrogenic injury to the brain or spinal cord if not done properly. You need to weigh up whether you will undertake the procedure or maybe administer, say, glucocorticosteroids, which can obviously influence any future diagnostic investigations. You may wish to refer to an experienced clinician to undertake the CSF tap.

When is CSF collection not indicated or advised?

l When the veterinarian is inexperienced

in the technique – case for referral.

l Atlanto-axial instability due to

developmental abnormalities or head trauma in small breeds. Remember you have to flex the head on the neck – a bad move (and potentially a lethal one!) if there is an atlanto-axial problem. Radiograph first if you are unsure.

l Increased intracranial pressure: clinical

signs will give some indication of increased pressure – altered mentation, somnolence, head pressing, altered pupil size (pinpoint, anisocoria, dilated), abnormal (delayed) motor function. MRI can confirm whether signs are associated with increased pressure: flattening of cerebral gyri, herniation of the caudal cerebellum into the foramen magnum, compression of the caudal cerebrum under the tentori cerebelli and compression of the midbrain.

What do I need?

Anaesthesic: The animal must be anaesthetised for the procedure and must be intubated. You have to be quick because the animal will have its neck flexed and the endotracheal tube will be kinked or obstructed during flexion of the head to position for the tap. Hair on the head is clipped from the occiput to a line across the wings of the atlas. The skin is prepared as for surgery. Many authors recommend surgical gloves but I don’t think that is required as the procedure can be undertaken as a ‘no touch’ technique – only the needle hub and stylet hub are handled. A sterile drape or swab is useful so that, if need be, you can remove the stylet from the hub and place it on the drape/swab and then replace it to continue. A spinal needle: 1½” (3.8 cm), plastic hub, 20 gauge (or 22 gauge for small dogs and cats). The light-weight plastic hub is important especially with small dogs and cats as it will not move if you let go of the hub. Also, 20 gauge needles are preferred over finer gauge needles as you have a better ‘feel’ and they do not flex or bend easily. For very big dogs (e.g. Rottweilers or great Danes) a 20 gauge 2½” (4.4 cm) needle is more suitable. You can use a standard hypodermic needle for small patients (Lowrie 2015) but I don’t advise this option. Collection vials: plastic preferred, have them ready with tops loosened before you start! A plain tube and an EDTA tube (in case blood is present) are suitable. There

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

are now many diagnostic tests performed on CSF, not just a total and differential cell count (e.g. serology, microbiology, PCR analysis etc) so make sure you have the correct containers. CSF samples should be processed for cytology or preserved within 30 minutes of collection. You can arrange immediate shipment to the diagnostic laboratory or add one drop of buffered 5% formalin or 1 drop of autologous serum to 0.25 ml of CSF (Walmsley and Alleman 2011) if shipment is delayed. Remember to split your sample so that you have an aliquot without any additives! Check with your lab to ensure any additive will still allow suitable analysis by the method they use for cell count and analysis.

Positioning for cerebromedullary cistern collection

Correct position of the head is essential! Take time to get the animal in the correct position: in right lateral recumbency for a right handed collector and vice versa if left handed. You may need to use a foam pad under the neck and sometimes between the forelegs, to bring the vertebral column level. If you stand at the table edge bring the legs towards you, over the edge of the table. Push the forelimbs backwards with your right hip. If you are right handed, take hold of the head with your left hand; thumb on the left dorsocranial wing of the atlas and forefinger (or another finger) on the occipital crest. Flex the head at right angles to the neck. Now with your needle in your right hand lean over the patient and insert the needle midline midway between these two points (Figure 1). You will push the needle towards yourself on a line parallel to the muzzle and table top, directed at the ramus of the mandible. With the head held firmly in your left hand you can appreciate the pressure from the needle and hold the head steady without other assistance. Such a grip allows for total control over needle advancement. If you are left handed, reverse this procedure.

capsule and fascial planes. If you feel altered resistance, you can withdraw the stylet and see if fluid flows from the hub of the needle. If not, replace the stylet and advance the needle again. The textbook ‘pop’ as you enter the cistern almost never happens; don’t believe it! Once the needle is in the subarachnoid space, remove the stylet and let CSF run from the needle hub into the collection vials. Always loosen the lid/stopper before you start. Do not aspirate CSF from the needle. Collect about 1 ml of CSF or more from a large dog. If the CSF pressure is elevated, CSF will flow rapidly from the needle. Collect your sample, remove the needle and extend the head. When you withdraw the needle, grip the shaft between the thumb and forefinger at skin level. This will give you the exact depth of the cistern for the size of the patient. Record it for the next time. After you have collected CSF from animals of different sizes you will have some appreciation of how deep the cistern is from the skin surface: 8–10 mm in a cat or small dog and about 34 mm in a Labrador.

What if I hit bone?

You are in the wrong position. If you hit bone of the skull, step the needle backwards and then advance into the cistern. If you have hit C1 remove the needle and insert again at a more cranial site and check the direction of the needle.

What if I get blood?

You are off midline and have hit a major vessel. You may have advanced the needle ‘off midline’ or the animal is not positioned correctly. You can replace the stylet or get a new needle, reposition the patient and try again. You may collect CSF contaminated with blood. A concurrent haemogram might aid interpretation of the CSF cell count if this occurs.

What if I insert the needle too far?

This can happen, particularly in small dogs or cats, and it can cause brainstem damage. You may get a change in heart and respiratory rates at the time, and, on recovery from anaesthesia, signs of opisthotonus/paresis/tetraplegia/CNS and cranial nerve deficits. Full recovery is rare and you have some explaining to do to the owner!

Can I collect CSF from the lumbar subarachnoid space?

Figure 1. A diagrammatic representation of the atlanto-occipital junction with the key landmarks indicated. Line A is from the dorsal spinous process of the axis (C2) to the occipital crest. Line B marks the atlanto-occipital space cranial to the anterior border of the atlas. The site for insertion of the spinal needle is where the two lines intersect. (Reproduced with permission from Lowrie, M. How to…. perform a CSF tap. Companion, the membership magazine of the BSAVA, June 2010)

For larger dogs rest the lateral part of the right hand along the neck; the needle insertion is mostly a finger wrist movement with the hand fixed. For small dogs and cats this step is not as easy as there is no room to rest the right hand. You can feel the resistance as the needle is advanced slowly. Varying degrees of resistance are encountered as the needle is advanced through ligamentum nuchae, atlanto-occipital joint

Yes you can but it is technically more difficult and you often do not get a suitable CSF sample. A 2½” spinal needle is suitable. The needle is inserted between L5 and L6 and passes through the interarcuate ligament, dorsal meninges and spinal cord to enter the ventral subarachnoid space. There is often a detectable twitch of the tail or legs as the needle is advanced till bone on the ventral vertebral canal is reached. Remove the stylet to see if CSF flows; if not, withdraw the needle a short (0.5 mm) distance. The jugular veins can be occluded which may assist CSF flow by raising CSF pressure. Lumbar collection is most often undertaken when myelography is indicated. See Lowrie (2010) or several current neurology textbooks for more details. I would not select a lumbar tap if I wanted to ensure I obtained a CSF sample.

Acknowledgement

Joe Mayhew’s comments and suggestions in preparation of this article were appreciated and helpful.

References

Lowrie M. How to perform a CSF tap. In: How To: Collected Articles from BSAVA Companion. Goodfellow M (Ed.). Pp 12–5. Wiley, Chichester, UK, 2013 Walmsley H and Alleman AR. Clinical Pathology. In: BSAVA Manual of Canine and Feline Neurology, 3rd ed, Platt S and Olby N (eds). pp 43–53, BSAVA, Gloucester, UK, 2011 l

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

FEATURE ARTICLE

Tips for in-clinic safety around dogs DR ELSA FLINT, MSc (hons),

BVSc, MANCVS, PhD

Going to the veterinary clinic is often stressful for both dogs and owners. Ideally we would like all our canine patients to have attended puppy school at the clinic and to have developed a positive association by doing so. Unfortunately this is not always the case and we often have to see dogs that are fearful and so try to avoid being handled, becoming aggressive when they cannot escape. Some dogs are comfortable with their owners present in consultation but become very aggressive in cages. This is due to feeling trapped and vulnerable in a strange and stressful situation. Dogs in pain may be difficult to handle and will understandably bite to protect themselves. In addition to fearful dogs and dogs in pain, we sometimes have to deal with dogs that have been

kept as guard dogs and never socialised. Often these dogs have had no training and the owners have no control over them. These are even more challenging.

Fearful dogs in consultation In the waiting room

Consider the ambience in the waiting room. This period before entering the consultation room can be a time to chill out and relax or a time to wind up to the point of panic. To help create a positive experience:

• Play relaxing background music – • •

•

• Staff should be friendly and welcoming without being intrusive. Putting the owner at ease can often help the dog to relax. Treats should be available on the desk for owners to offer their dogs or for the staff to do so should the dog be confident enough to accept these.

•

Bocelli is good if you want classical, Jack Johnston for easy listening. Have Adaptil diffusers going in the waiting room and consult rooms and in the kennel and prep areas. Have a toy box available for young dogs in particular to take interest in. Ensure these are washed between uses. Ensure that any dogs admitted for surgery are pre medicated on admission and so are quickly settled. There is nothing more unnerving for a dog than hearing a distressed conspecific crying in the kennels. If a nervous dog has urinated or defaecated in the waiting room clean the area thoroughly. If this has not happened but the dog has been clearly distressed, mopping the floor will help to remove stress pheromones.

Source: pixabay/com

Contact: 094157173, e.flint@xtra.co.nz Animals with Attitude Behaviour Clinic

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

• If an animal has bled onto the floor make sure the blood is properly cleaned up.

In the consultation room

Greet the owner initially and ignore the dog unless it voluntarily approaches you. Do not shut the door immediately. Look at the file and get ready for the consultation then quietly close the door. Ask the owner to release the dog from the lead and allow the dog to explore while you discuss the history. Watch the dog during this time. If the dog approaches you allow it to sniff your feet and legs and speak gently to it without making eye contact or attempting to touch it. Offer a treat. If the dog will not accept it from your hand drop the treat on the floor. If the treat is eaten you know the dog is starting to relax. When you are ready, call the dog to you and ask it to sit for a treat. Progress to a down, ask for shake or paw if the dog is familiar with these commands. Doing this puts the dog at ease. Now you can gently progress with your examination. When you get to abdominal palpation, taking the temperature or, examining a sore limb, ask the owner to cuddle the dog while you do so. They can distract with treats if the dog is happy to take these. Always touch the dog in an area that you do not expect to be painful before progressing to an affected area. Don’t just identify the affected limb for example and immediately start to manipulate.

If at any stage the dog the dog attempts to struggle free of its owner say NO firmly without shouting and just keep your hands still on the dog’s body. Once it settles tell it it is good in a light voice and continue. If you have to do a potentially painful procedure such as examining sore ears, shaving a deep pyoderma or examining a broken nail use sedation. Medetomidine/butorphanol combination is useful for most of these procedures. It is rapid acting given IM and will make the whole experience much better and safer for you and the owners. If the procedure can be delayed (e.g. vaccination) ask the owners to return with the dog at least twice weekly for 2–4 weeks to visit the clinic. During these visits the dog should receive treats and attention from your or the staff and should then go home. After the first social visit sit in the waiting room with owner and dog and reward the dog for approaching as you are chatting to the owner. At the next visit see if you can gently pat the dog. Once you feel confident that the dog is no longer fearful and is amenable to handling you can reschedule an official appointment.

When you have finished the examination verbally praise the dog and reward it with a treat.

Owners will generally love you for this as it shows how much you care. Some clinic managers may not as time is money, however in my opinion this approach pays dividends in PR.

Dogs that growl and snap

Injections

If not, and the procedure must be done that day, give the owner a muzzle to put on the dog while it is still outside and then ask them to bring it into the consult room again.

Have the injection in your pocket, have the owner cuddle the dog and/or feed treats, stroke the dog and while tenting the skin move your fingers on the tented area so that the dog is distracted when you GENTLY introduce the needle.

If the dog starts to panic when you try to examine it, take dog and owner outside and see if the dog is more amenable outside.

Ask them to cuddle the dog while you start to touch it gently on the side. Gradually massage the dog on both sides and then progress to your examination site.

Many dogs are needle shy so never approach a dog with the syringe in your hand.

NEVER inject with a needle that you have used to draw up with through a rubber stopper as this will have blunted the needle. Always use a new one.

Cage-aggressive dogs

If you do not know a dog and it needs to be hospitalised leave a lead attached to its collar. If the dog has been fine to handle before going into the cage but becomes aggressive within avoid making eye contact with the dog or approaching the cage face on. If you have to stand nearby turn sideways. Talk softly to the dog as you pass. Some of these dogs will settle if a staff member sits near the cage for a while and gently talks to the dog without making eye contact. Others will not relax until out of the cage. When you need to get the dog out, shut all the connecting doors, pick up the lead open the cage and use the cage door to protect yourself. Let the dog walk out of the cage and then walk with it away from the cage before handling it.

Dogs that are unhandlable

Dogs that come in snarling and frothing (hopefully already muzzled) and need a procedure should be swiftly restrained by experienced staff and given butorphanol with/without medetomidine or if requiring a surgical procedure a standard premed replacing acepromazine with butorphanol. When these dogs are hospitalised a trailing lead should be attached to their collar at all times. When they are due to go home, let the owner get them out of the cage. Discuss the benefits of referral to a veterinary behaviourist. If you can access it, Trazodone given at 5 mg/kg two hours before subsequent visits can be very helpful. This is now a section29 drug but can be compounded by Optimus laboratories. You are within your rights to refuse to handle an aggressive dog that the owner cannot control and recommend that they get help to modify its behaviour provided of course that the dog is not in need of urgent veterinary care due to serious illness or injury. l

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

FEATURE ARTICLE

Displacement of protein bound drugs: a pharmacological review LIZ SHACKLETON, MVB (Hons1), MANZCVS (Pharmacology)

Introduction

Many of our commonly used veterinary medicines are classified as highly protein bound compounds, and the question of the clinical impact of the displacement of these protein bound drugs continues to be raised in clinical practice. A large body of literature generated in the last 30 years including the now classic overview by Benet and Hoener (2002) highlights that for most drugs, changes in plasma protein binding have little clinical relevance (Rolan, 1994; Trainor 2007). Despite this, the topic of drug-drug interaction via protein binding displacement appears to resurface periodically, with concern being raised and the information subsequently rediscovered. This is likely due in part to the drawn-out process involved in updating textbooks, teaching materials and regulatory review processes, and the message therefore failing to fully reach the wider veterinary community. Therefore this review will discuss; 1 Pharmacokinetics and binding of drugs to plasma proteins. 2 Where did concern regarding protein binding and drug-drug interaction arise? 3 The evidence that changes in plasma protein binding have little clinical impact for most drugs and most situations (and exceptions to this rule). Drugs exhibit various degrees of protein binding and the threshold above which a compound is considered to be highly protein bound are variously described as >90% (Ascenzi et al. 2014), with others stating >80% (Booth 2011) Contact: elizabeth.shackleton@merck.com

and >95% (Papich 2016). As a practical example, the drugs listed in Table 1 may be classified as highly protein bound. These drugs are used commonly, many concurrently, and some in our critically ill patients. This illustrates the actual clinical impact that changes in plasma protein binding of drugs could potentially have. Table 1. Commonly used highly protein bound drugs

Anaesthetics Propofol Midazolam Thiopentone Benzodiazepines Cardiac drugs Pimobendan Frusemide Amiodarone Prazosin Antimicrobials Doxycycline Cloxacillin Cefazolin Cefovecin Ceftriaxone Ketoconazole Itraconazole Others Maropitant NSAIDs (an exception is aspirin which is 45% protein bound in dogs; Gupta 2007) Isoxazoline compounds (e.g. afoxolaner, fluralaner, sarolaner) Glipizide Leukotriene receptor antagonists (e.g. montelukast, zafirlukast)

Pharmacokinetics and plasma protein binding Once absorbed into the circulation, a drug undergoes distribution in the body where it may undergo several fates; accumulation (e.g. aminoglycosides in the proximal convoluted tubules of the kidney), transfer to storage sites (e.g.

lipophilic drugs in fat depots) or transfer to sites where the drug is subsequently metabolised/excreted (e.g. the liver and kidneys). A number of components can transport drugs around the body. Plasma proteins are the primary means of transport for most drugs. As most drugs exist in the form of either weak acids (e.g. penicillins) or weak bases (e.g. morphine) they may bind albumin or alpha glycoproteins (AGP) respectively. Lipoproteins may also play a role in the transport of very lipophilic drugs. Red blood cells (rbc) play an important role in transport of certain molecules such as lead. The lymphatic system may also contribute to the transport of highly lipophilic drugs and is a route experiencing ongoing transformation in our understanding of its function from â&#x20AC;&#x2DC;sewer to subwayâ&#x20AC;&#x2122;. Recent studies have investigated its potential use as a route for improved delivery of oral drugs and in chemotherapy to reduce non-specific organ toxicities (Zhang and Lu 2014). Albumin is the most abundant plasma protein and is a single monomeric non-glycosylated protein. It has many binding sites, most of which are not saturable. Some chemicals may bind up to 25 molecules for every molecule of albumin and there are nine binding sites for fatty acids. However, two major sites exist in human albumin that bind drugs, one of which has a counterpart in dogs (Kaneko et al. 2007). By contrast, AGP is a less abundant plasma protein and has a single binding site for which binding is saturable.

Binding forces and displacement

Drugs may bind to proteins (including plasma proteins, especially albumin and AGP, and their target receptors) by a number of methods which are summarised in Table 2. Most drugs bind to plasma proteins by reversible forces (governed by the Law of Mass Action).

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

A key concept in protein binding relative to drug action is that of free drug concentration – that is the concentration of drug not bound to proteins (see Figure 1). The free concentration of a drug (in contrast to total drug concentration) at the site of action predominantly influences drug occupation of the target site and therefore drug effect. In the absence of active transporters for uptake/efflux, the free drug concentration will be equal in all compartments that are in steady-state equilibrium (this however is not usually the case). A high degree of protein binding can contribute to prolonging a drug’s half-life in the body, such as that reported with some of the newer systemically acting ectoparasiticides.

Table 2. Types of bonds between drugs and proteins

Bond Type Covalent bonds

Comments Non-reversible: the drug cannot dissociate until the protein degrades. However only a small proportion of total dose of a drug will be in a covalently bound state.

Examples • Cisplatin binding to rbc • Binding of a metabolite of omeprazole to the gastric acid secretory pump • Binding of penicillin to bacterial cell walls

Non-covalent bonds

Reversible process – allows the drug to dissociate (sometimes at an extremely low rate if bond is strong e.g. cefovecin)

Most drugs

• Ionic bonds

Electrostatic interaction between oppositely charged ions on the drug and the protein. Van der Waals forces involve weak interactions between the nucleus of one atom and the electrons of another atom. Two non-polar molecules come together to exclude water

Charged molecules e.g. sodium fluoride

• Hydrophobic bonds

Figure 1. Free and protein bound drug fractions

How tightly a drug binds to plasma protein is measured by the dissociation constant or K[diss]. The lower the K[diss], the more tightly the drug binds. Most drugs remain in equilibrium between free and protein bound state until they dissociate or reversibly bind to another tissue or molecule to which it has a higher binding affinity at which time a new equilibrium is established. Therefore a change in a drug’s protein bound state can occur when the drug encounters; 1 A protein with binding sites of greater affinity for the drug. 2 A higher concentration of proteins with lower affinity. 3 Alterations in K[diss] e.g. pH, temperature changes, pathological states. Drug distribution relies on bound drug dissociating from the plasma protein that is carrying it. Drug displacement may also occur following interaction/ competition with other drugs competing for the same plasma protein binding site or competition from endogenous substances (e.g. bilirubin, fatty acids). For lowly protein bound

drugs, displacement may result in minor increases in free drug concentration. Concern has historically arisen about displacement of drugs that are highly protein bound, resulting in much greater rises in free drug concentration with potential for greater free drug effect. However the evidence to date suggests there are few scenarios that result in clinically significant impact and these are discussed further below.

How did concern regarding protein-binding interactions arise?

The idea that drug-drug interactions from protein binding displacement could result in adverse impact was proposed in three human clinical papers on anticoagulants and antidiabetic drugs published in the 1960s. A study of warfarin treatment by Fox (1964) documented marked increases in prothrombin times in patients concurrently taking phenylbutazone. Christensen et al. (1963) reported severe hypoglycaemia in patients taking tolbutamide and sulphonamides together. The clinical impact observed was attributed to plasma protein displacement leading to increased plasma concentration of free drug, although other authors proposed different mechanisms as responsible (Brodie 1965; Tillement et al. 1973).

Lipophilic drug interaction with the lipid of biological membranes

In the third paper, a follow up to the initial warfarin study, Aggeler et al. (1967) conducted an in vitro proteinbinding experiment, which revealed that phenylbutazone displaced warfarin from its binding site. These in vitro results were then extrapolated to the in vivo drug interactions observed in the previous studies. A smoking gun hypothesis emerged – increased free fraction of drug in plasma was responsible for the clinical impact observed. In reality and following reviews by a number of authors (Mac Kichan 1989; Sansom et al 1995), the actual cause was later assigned to changes in the metabolic clearance of the drug and not from changes in protein binding. However, as changes in protein binding can alter pharmacokinetic parameters in some exceptions, concern persisted regarding the potential for adverse clinical impact for highly protein bound drugs.

Changes in plasma protein binding have little clinical relevance for most drugs (and exceptions) As an example; we administer drug 1 (which is highly plasma protein bound) and the free concentration of drug 1 is available to bind the receptor and therefore exert the effect of this drug.

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

We then administer drug 2 (which is also highly protein bound) which encounters the same plasma protein and competition for the same binding site occurs. Drug 1 is displaced from the plasma protein. Therefore will the increased concentration of free drug 1 result in more drug effect? In reality, a number of systemic mechanisms exist to buffer rises in free drug concentration and potential increased free drug effect for most drugs (Figure 2). These are: 1 The amount of drug 1 displaced in the presence of drug 2 is made equally available to both the receptor at the site of action and for redistribution in the body, with redistribution acting as a buffer. 2 Free drug attachment to the receptor does not occur instantaneously, but often occurs simultaneously with the drug redistribution process. 3 Once free drug 1 has been redistributed; it also becomes available for elimination which acts as an additional buffer.

short time frame between drug achieving concentration at the site of action and the drug exerting effect on the body). There are very few clinically relevant examples of this, as most drugs do not exhibit very rapid equilibration times and therefore any change in drug effect is delayed relative to the plasma concentration. Holford and Benet (1995) use warfarin as a clinical example to demonstrate the delay in drug effect that occurs relative to plasma concentration. Warfarin acts rapidly on the enzyme epoxide reductase, however the anticoagulant effect of the drug is delayed up to 14 hours. This is because the anticoagulant effect is a result of decreased amounts of the prothrombin complex of clotting factors (2, 7, 9, 10 and anticoagulant proteins C, S) which is governed by the half-life of the complex and the time taken for clotting factors to reach their new steady state plasma concentration in addition to the activity of epoxide reductase. Another example is morphine, which has rapid plasma pharmacokinetics (i.e. the time course of absorption, distribution, metabolism and excretion) but has slow blood-brain equilibration, which offsets an immediate drug effect. Exceptions where potential clinical impact may be seen are listed in Table 3. Table 3. Scenarios where drug protein binding changes may result in clinically relevant effect

Figure 2. Influence of reversible interactions (including plasma proteins) on drug action at the primary action site. Adapted from Goldstein 1949.

Therefore in most situations, the increase in free drug concentration is temporary, unsustained and subject to rapid redistribution and elimination. Benet and Hoener (2002), and many others outline the limited number of scenarios when protein binding changes may have significant clinical impact. These scenarios include drugs with a narrow therapeutic index and high extraction ratio given rapidly parenterally (e.g. lignocaine I/V). These are drugs that are rapidly and extensively cleared from the body and this clearance is primarily dependent on hepatic blood flow. Another scenario is narrow therapeutic index drugs administered orally with very rapid pharmacokinetic-pharmacodynamic equilibration time (very 28

Scenario Low therapeutic index drugs with low clearance rate and small volume of distribution

Example phenytoin

Comment Increases in free drug concentration and variation to the dosing interval may result in clinical impact

Drugs with high clearance rates administered rapidly IV

lidocaine

Increased clearance does not occur as both free and bound drug are already available for elimination. Therefore clinically significant interaction is possible where drugs are highly protein bound. However practically few examples of this actually exist.

Authors have published useful algorithms for assessing the clinical significance of potential protein binding displacement interactions (e.g. Rolan 1994). An adapted example is provided in Figure 3. Since the situations in which changes in protein binding result in actual clinical effects are rare, dose adjustments in clinical practice to account for drug-drug interaction are not required for most drugs. However assessment of protein binding remains a critical consideration in new drug development. For example, when applying animal pharmacokinetic/ pharmacodynamic models to humans, species variation in protein binding of the drug being studied is a key consideration. Protein binding assessment is also critical in dose determination studies of drugs with a narrow therapeutic index such as the aminoglycosides, where dose adjustment is based on therapeutic drug monitoring (which often assesses only total dose rather than free drug fraction).

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

Figure 3. Decision tree for determining potential protein binding interactions between two highly protein bound drugs. Adapted from Rolan 1994.

Conclusion

Despite ongoing concern raised in practice about displacement of protein bound drugs, a large body of evidence indicates that there is seldom an adverse clinical impact for most drugs. Whilst anticipating protein bound drug displacement remains an important element of drug development, for most drugs in practice no adjustments in dosing regimens should be necessary except in the very rare cases discussed above.

Acknowledgements

I would like to thank Stephen Page for his input to this review.

References

Ascenzi P, Fanali G, Fasano M, Pallotini V, Tressa V. Clinical relevance of drug binding to plasma proteins. Journal of Molecular Structure 1077, 4–13, 2014 Benet L, Hoener B. Changes in plasma protein binding have little clinical relevance. Clinical Pharmacology and Therapeutics 71, 115–21, 2002 Boothe DM. Factors affecting drug distribution. Small Animal Clinical Pharmacology and Therapeutics 2nd Edtn. 34–71, WB Saunders, Philadelphia, USA, 2011 Brodie BB. Displacement of one drug by another from carrier or receptor sites. Proceedings of the Royal Society of Medicine 58, 946–55, 1965 Christensen LK, Hansen JM, Kristensen M. Sulphaphenazoleinduced hypoglycaemic attacks in tolbutamide treated diabetics. The Lancet 2, 1298–1301, 1963 Fox SL. Potentiation of anticoagulants caused by pyrazol compounds. Journal of the American Medical Association 188, 320–321, 1964 30

Goldstein A. The interaction of drugs and plasma proteins. Journal of Pharmacology and Experimental Therapeutics 2, 102–65, 1949 Gupta RC. Veterinary Toxicology: Basic and Clinical Principles 1st Edtn. 455–458, Academic Press, London, UK, 2007 Holford NH, Benet LZ. Pharmacokinetic and pharmacodynamics: dose selection and the time course of drug action. Basic and Clinical pharmacology 12th Edtn. 6. Pp 33–47, Lange Medical, New York, USA, 1995 Kaneko, K, Fukuda H, Giam Chuang VT, Yamasaki K, Kawahara K, Nakayama H, Suenaga A, Maruyama T, Otagiri M. Subdomain IIIA of dog albumin contains a binding site similar to site II of human albumin. Drug Metabolism & Disposition 36, 81–6, 2007 MacKichan JJ. Protein binding drug displacement interactions fact or fiction? Clinical Pharmacokinetics 16, 65–73, 1989 Papich M. Saunders Handbook of Veterinary Drugs: Small and Large animal 4th Edtn. 296–297, WB Saunders, Philadelphia, USA, 2016 Rolan PE. Plasma protein binding displacement interactions – why are they still regarded as clinically important? British Journal of Clinical Pharmacology 37, 125–8, 1994 Sansom LN, Evans AM. What is the true clinical significance of plasma protein binding displacement interactions? Drug Safety 12, 227–33, 1995 Trainor GL. Plasma protein binding and the free drug principle: recent developments and applications. Annual Reports in Medicinal Chemistry 31, 489–502, 2007 Tillement JP, Zini R, Mattei C, Singlas E. Effect of phenylbutazone on the binding of vitamin K antagonists to albumin. European Journal of Clinical Pharmacology 6, 15–8, 1973 Zhang XY, Lu WY. Recent advances in lymphatic targeted drug delivery system for tumor metastasis. Cancer Biology and Medicine 11, 247–54, 2014 l

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

CASE STUDY

Use of pimobendan for the treatment of hypertrophic cardiomyopathy in a cat ZL KAMSMA, BVSc5 student,

Massey University

Introduction

Hypertrophic Cardiomyopathy (HCM) is characterised by left and/or right ventricular hypertrophy (Ferasin 2009). The thickening of the ventricular musculature results in a narrowed lumen and compromised blood flow, causing backflow of blood from the ventricles to the atrium and thus diastolic dysfunction. This can occur secondary to hypertension or hormonal dysfunction (e.g. hyperthyroidism), or infiltrative disease of the myocardium (e.g. lymphoma). However, typical HCM is an idiopathic condition that occurs when myocardial hypertrophy occurs in the absence of hemodynamic load or metabolic cause (Abbott 2010). In Maine Coon and Ragdoll cats, mutations in the cardiac myosin binding C gene is responsible for hereditary (or familial) HCM, explaining the increased prevalence in these breeds (Mary et al. 2010). The mode of inheritance is thought to be autosomal dominant, with those homozygous for the defective gene developing severe disease at a much younger age than heterozygotes (i.e. incomplete dominance). Other breeds of cats, including Persians, Norwegian forest cats and Bengals have familial HCM, however, the genetic underpinnings are less well understood than that of the Maine Coon. Conventional treatment of hypertrophic cardiomyopathy consists of medical management to reduce myocardial oxygen demand and increase diastolic filling time and coronary perfusion. This is typically achieved by reducing heart rate and contractility with calcium channel blockers, such as diltiazem, or beta adrenergic blockers such as atenolol (Nelson and Couto 2009). Diuretics and ACE inhibitors are added as required to manage pulmonary oedema associated with congestive heart failure (White 2015).

However, based on survival data from recent studies on cats with HCM (Doreste et al. 2014), the recommended

treatment of this condition has changed and will be discussed in this case report.

Case history

A male entire domestic shorthair cat, acquired by the owner as an adult 5 years previously, was presented due to increased respiratory rate and effort of 2-days duration. He had previously been missing for 3 weeks, returning 1 week prior to presentation. Initially he was eating and drinking well, then became inappetant 3 days before presentation and the owner began syringe-feeding Royal Canin recovery diet and water (80 mL and 200 mL respectively, over 2 days). The cat had a history of an intermittent guttural cough for several years and recurrent bilateral conjunctivitis that had been intermittently treated with topical antibiotics as prescribed by their regular veterinarian.

Clinical findings

On physical exam the cat was dull and lethargic, with a respiratory rate of 80 breaths per minute with marked abdominal effort. On thoracic auscultation there was a diffuse increase in harsh lung sounds bilaterally with moist crackles heard cranioventrally. A grade 3/6 pan-systolic parasternal heart murmur was initially missed in the first clinical exam due to respiratory noise, then subsequently detected on auscultation over the cranial sternum. Oxygen saturation (SpO2), measured by pulse oximetry, was 93% at admission. A blood sample collected by jugular venipuncture was submitted for complete blood count (CBC) and serum biochemistry. The CBC results were suggestive of marked dehydration with a packed cell volume of 63% and a total protein of 65 g/L (reference range 54–74 g/L). Venous blood gas analysis showed elevated pCO2 at 49 mmHg (reference range 34.0–38.0 mmHg). Haematology and serum biochemistry were otherwise within the reference ranges. Differential diagnoses considered for respiratory distress included inflammatory

or bronchitis (inflammatory or infectious), infectious or aspiration pneumonia (infectious or due to aspiration given the history of syringe feeding and crackles ausculatated cranioventrally), pulmonary oedema (cardiogenic, noncardiogenic), pleural space disease and neoplasia. Differentials for the heart murmur included valvular insufficiency (congenital, infectious, degenerative) or cardiomyopathy (hypertrophic, dilated, intermediate or constricted). Thoracic radiographs (Figure 1a and 1b), showed mild cardiomegaly with distended pulmonary vessels accentuated in the caudal and accessory lung lobes and an interstitial to alveolar lung pattern. Together these observations are suggestive of decompensated cardiomyopathy with cardiogenic pulmonary oedema. There was also generalised bronchial lung pattern suggestive of chronic inflammatory bronchitis. A brief thoracic ultrasound examination conducted by an emergency clinician revealed subjectively marked thickening of the left ventricular musculature with marked reduction of the luminal cavity and moderate left atrial distension. No atrial ‘smoke’ or thrombus was visualised. A full echocardiogram was recommended but not possible due to financial constraints of the owner. Blood was taken for a feline total T4 assay to rule out hyperthyroidism, a common cause of HCM in cats. The T4 concentration was low at 16 nmol/L (reference range 20–40 nml/L), consistent with euthyroid sick syndrome. Blood pressure was normal with an average reading of 125/68 (MAP 89) mmHg. These results ruled out hyperthyroidism and hypertension as contributing factors to the cardiomyopathy. An electrocardiograph was performed and showed a normal heart rate and rhythm, with normal QRS morphology. This indicates that while there were structural and functional abnormalities of the heart, there were no electrical abnormalities detected within the window of examination.

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

a Figure 1. Right lateral (a) and ventrodorsal (b) thoracic radiographs of a male entire cat diagnosed with hypertrophic cardiomyopathy showing mild cardiomegaly with distended pulmonary vessels, an interstitial-to-alveolar lung pattern and a generalised bronchial lung pattern.

Bilateral conjunctivitis was also present with mucopurulent occular discharge, corneal oedema and neovascularisation and blepharospasm. There was no abnormal corneal staining seen with fluorescein, indicating there were no corneal lesions. A Schirmer tear test revealed marked reduction in tear production with moisture wetting the test strip for 5 mm in left eye and 3 mm in right eye. From this the cat was diagnosed with keratoconjunctivitis sicca.

Treatment

To prevent bacterial infection and maintain corneal hydration chloramphenicol eye ointment (Chlorsig; Sigma Pharmaceuticals Ltd, Clayton VIC, Australia) was prescribed for twice daily application and Poly Visc lubricating eye ointment (Alcon Laboratories, Australia) to be applied five times daily.

Intravenous fluids (lactated Ringer’s solution (LRS); Baxter Healthcare, Deerfield, IL, USA) were initially administered at a maintenance rate of 2.5 mL/kg/ hour overnight prior to the diagnosis of cardiomyopathy.

Discussion

Due to its respiratory distress, the cat was placed in an oxygen cage on admission. With the oxygen concentration set initially between 45–60%.

When pulmonary oedema was identified the fluids were disconnected and intravenous I/V furosemide was administered at an initial dose rate of 3 mg/kg 2-hourly. The cat responded well to the furosemide with a marked decrease in respiratory rate and effort. His SpO2 improved to 96% and he was gradually weaned off the oxygen cage. After initial stabilisation, the furosemide dose was reduced to 2 mg/kg QID afterwhich the patient was switched to oral furosemide (Lasix; Sanofi Aventis, France) at a dose of 1.5 mg/kg BID. To help manage the effects of HCM and congestive heart failure pimobendan 34

(Vetmedin; Boehringer Ingelheim Vetmedica Inc, St Joseph, MO, USA) was prescribed at a dose rate of 0.25 mg/kg PO SID or (one 1.25 mg tablet daily). This was well tolerated and the cat appears to be managing well.

The cat is currently doing well, with a stable resting respiratory rate of 20–30 breaths per minute. The owner has been advised to regularly record respiratory rate in order to recognise progression of the disease and to allow medication to be titrated to effect. Pimobendan is a phosphodiesterase -3 inhibitor that acts as a positive inotrope with vasodilatory and anti-platelet properties. It sensitises cardiomyocytes to calcium, thus enhancing cardiac contractility without increasing myocardial oxygen consumption (Plumb 2015). Studies in healthy cats (Hanzlicek et al. 2012; Miyagawa et al. 2016) have shown that it produces no adverse cardiac effects at clinical doses and it is well tolerated. While pimobendan has been used with success to treat feline dilated cardiomyopathy (Hambrook and Bennett 2012) it was thought to be contraindicated in feline HCM since increased contractility was thought not to be beneficial given

the already narrowed ventricular lumen and reduced cardiac blood flow and the potential for aggravation of left ventricular outflow obstruction. It is still noted as contraindicated for HCM in Plumb’s Veterinary Drug Handbook (Plumb 2015). However, a 2014 study by Doreste et al. found that pimobendan improves the median survival time of cats with HCM, from 103 days in the control group to 626 days for those cats receiving pimobendan. It has also been recommended for end stage HCM in order to increase systolic function (White 2015). This is because pimobendan causes reduced preload and increased diastolic relaxation (Smith et al. 2015). In in vitro studies, pimobendan has also been demonstrated to have antiplatelet aggregation effects (Hambrook and Bennett 2012), which may contribute to the prevention of thrombus formation. In the 2014 retrospective case-control study by Doreste et al., pimobendan was administered from the day that congestive heart failure was confirmed (either by diagnosis of pulmonary oedema or of pleural, pericardial or peritoneal effusion). Cats in the pimobendan group received 0.15–1.0 mg/kg/d of pimobendan (divided between 2 or 3 doses). The recommended dose for dogs with congestive heart failure is 0.5 mg/kg. Pimobendan has been shown to have a longer half-life and maximal concentration in cats as compared to dogs at a similar dose per weight basis, which may allow for lower effective doses (Hanzlicek et al. 2012). Further research is required to investigate this, as well as a prospective case-control study on the use of pimobendan in HCM.

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

The cat in this case was given IV fluid therapy with LRS prior to thoracic radiographs being taken. Intravenous fluids should be administered with caution to any patient with possible indications of cardiac disease due to the potential to aggravate volume overload and venous congestion. As up to a third of cats with HCM have no audible murmur, lack of a murmur should not be used to rule-out cardiac disease as inappropriate treatment could severely worsen the condition. In congestive heart failure, volume overload occurs due to the activation of the renin-angiotensin-aldosterone system. Renin content of the kidney is elevated in cats with HCM (Taugner 2001). This is because renin is synthesised by the juxtaglomerular apparatus in response to decreased renal perfusion, which occurs in HCM due to the decreased contractile ability of the heart and the decreased luminal volume resulting in reducing stroke volume. The increased renin activates angiotensinogen to create angiotensin I, which is converted by angiotensin converting enzyme (ACE) to angiotensin II, thus stimulating the generation of aldosterone in the adrenal glands (Taugner 2001). Aldosterone acts on epithelial cells of the distal collecting ducts, where it increases absorption of sodium ions and excretion of potassium (Sisson 2004), thus resulting in fluid retention and increased vascular volume. While this would be beneficial in normal physiological state (e.g. acute haemorrhage), in cardiac disease the decreased renal perfusion is due to a reduced cardiac output rather than hypovolemia. As such increasing blood volume only results in hypervolemia and further compromise in cardiac function. Administration of further sodium, such as in the form of isotonic crystalloids, can result in increased fluid retention and thus contributes to pulmonary oedema. If fluid must be used to correct dehydration in a patient with compromised cardiac function, the fluid should have a lower sodium concentration compared to the patient’s plasma (DeFransesco 2008). A common choice is 0.45% NaCl + 5% dextrose, supplemented with potassium as required, as this results in a net decrease of sodium. Care however, must be taken when administering any hypotonic fluid as rapid administration can result in serious complications such cerebral oedema. Due to the turbulent blood flow in the left atrium, cats with HCM are also at risk of developing an atrial clot or thrombus. These can detach, forming thromboemboli which can become lodged in narrowing

sections of the vasculature, creating a thromboembolism. This most commonly occurs at the aortic trifurcation (commonly known as saddle thrombus). Clot inhibitors may be prescribed at diagnosis of cardiomyopathy or after a thromboembolic event to reduce the risk of this occurring. However, the frequency of cardiogenic embolism amongst cats with HCM is only 6% (Hogan and Brainard 2015) therefore it is uncommon to prescribe medication prior to an initial thromboembolic event unless there is evidence for increased risk on imaging (e.g. atrial smoke). Current research on the benefits of different types of clot inhibitors is currently underway and will likely provide further recommendation on preventative treatment. While we can manage the clinical signs in the short-to-medium term, HCM is an irreversible disease and will eventually progress to a point that cannot be medically managed. Survival times of up to 2 years are reported if there is good initial therapy and excellent home care. The history of a guttural cough and bronchial pattern in this case is suggestive of inflammatory bronchitis. Definitive diagnosis would require airway sampling which is contraindicated in this patient due to the underlying heart disease. Empirical treatment for bronchial disease was not started in this instance as the patient responded well to treatment with furosemide alone, but further follow-up for this condition may be required. Keratoconjunctivitis sicca is typically immune mediated and so is treated with immunomodulatory drugs such as topical cyclosporine or tacrolimus. However, due to the owner’s financial constraints and the shortened life span associated with HCM, the decision was made to treat this condition symptomatically by treating secondary infection and providing lubrication. In conclusion, pimobendan is a beneficial treatment for the management of feline HCM. Furthermore care must be taken in the selection and administration of IV fluid therapy for patients with cardiac disease, in order to prevent exacerbation of pulmonary oedema.

Acknowledgements

The author thanks the veterinarians, Dr Julia Giles and Dr Phillip Hyndman, and the veterinary nurses and students at Massey University Veterinary Teaching Hospital who were involved with the care of this cat.

References

Abbott JA. Feline hypertrophic cardiomyopathy: an update. The Veterinary Clinics of North America: Small Animal Practice 40, 658–700, 2010 DeFransesco TC. Maintaining fluid and electrolyte balance in heart failure. Veterinary Clinics of North America: Small Animal Practice 38, 727–45, 2008 Doreste YR, Stern JA, Keene BW, Tou SP, Atkins CE, DeFrancesco TC, Ames MK, Hodge TE, Meurs KM. Case-control study of the effects of pimobendan on survival time in cats with hypertrophic cardiomyopathy and congestive heart failure. Journal of the American Veterinary Medical Association 245, 534–9, 2014 Ferasin L. Feline myocardial disease 1: Classification, pathophysiology and clinical presentation. Journal of Feline Medicine and Surgery 11, 3–13, 2009 Hambrook LE, Bennett PF. Effect of pimobendan on the clinical outcome and survival of cats with non-taurine responsive dilated cardiomyopathy. Journal of Feline Medicine and Surgery 14, 233–9, 2012 Hanzlicek AS, Gehring R, KuKanich B, KuKanich KS, Borgarelli M, Smee N, Olson EE, Margiocco M. Pharmacokinetics of oral pimobendan in healthy cats. Journal of Veterinary Cardiology 14, 489–96, 2012 Hogan DF, Brainard BM. Cardiogenic embolism in the cat. Journal of Veterinary Cardiology 17, 202–14, 2015 Mary J, Chetboul V, Sampedrano CC, Abitbol M, Gouni V, Trehiou-Sechi E, Tissier R, Queney G, Pouchelon J, Thomas A. Prevalence of the MYBPC3A31P mutation in a large European feline population and association with hypertrophic cardiomyopathy in the Maine Coon breed. Journal of Veterinary Cardiology 12, 155–61, 2010 Miyagawa Y, Machida N, Toda N, Tominaga Y, Takemura N. Comparison of the effects of long-term pimobendan and benazepril administration in normal cats. The Journal of Veterinary Medical Science 78, 1099–106, 2016 Nelson RW, Couto CG. Small Animal Internal Medicine (4th ed). Pp 142–55. Mosby/Elsevier, St. Louis, Missouri, USA, 2009 Plumb DC. Plumb’s Veterinary Drug Handbook (8th ed). Pp 1168–72. PharmaVet Inc, Wisconsin, USA, 2015 Sisson DD. Neuroendocrine evaluation of cardiac disease. Veterinary Clinics of America: Small Animal Practice 34, 1105–26, 2004 Smith WK, Tilley LP, Oyama M, Sleeper MM. Manual of Canine and Feline Cardiology (5th ed). Pp 160–7. Elsevier, St. Louis, Missouri, USA. 2015 White AJM. End-stage hypertrophic cardiomyopathy in a cat. The Canadian Veterinary Journal 56, 509–11, 2015 Taugner FM. Stimulation of the renin– angiotensin system in cats with hypertrophic cardiomyopathy. Journal of Comparative Pathology 125, 122–9, 2001 l

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

CASE REPORT

Not your usual yellow dog: A case of leptospirosis in a South Island dog ANGELA WRIGHT BVSc, Veterinarian at Vetco Limited, Southland

Case presentation Case history

An eight-year-old male neutered colliecross working dog presented in February 2016 with a 3-day history of lethargy, vomiting and anorexia. He had vomited approximately two to three times per day for the last 3 days. The small amount of food being consumed was often immediately vomited up. There was no known access to any toxins, rubbish or animal carcasses that the owner was aware of. There had been no change in his diet or routine over the past few weeks. The dog had been born in Southland and had never left the Southland sheep and beef farm on which he lived. There was no contact with any animals (stock or companion) from further north than Dunedin.

Clinical presentation

The dog appeared quiet, alert and responsive. There was a small pile of jelly-like diarrhoea on the deck of the truck on which he had travelled to the clinic. On physical examination the heart rate and temperature were normal. His heart and lung sounds were also normal. All mucous membranes were severely icteric and capillary refill time could not be measured. There was no reaction to abdominal palpation and no abdominal abnormalities were palpated. The dog had a prolonged skin tent so was assumed to be moderately dehydrated. Contact: 03 206 6170

Differential diagnosis

The main differentials for the icterus which were considered at this stage were hepatic/cholestatic (toxin ingestion, infectious canine hepatitis, hepatic neoplasia, trauma, cholelithiasis) or haemolytic (immune-mediated haemolytic anaemia, toxin/drug, neoplasia, DIC).

Investigations

The dog was admitted to hospital. A blood sample was taken and intravenous fluid therapy with 0.9% sodium chloride at 4 ml/kg/hour as initiated. The blood sample was submitted to Gribbles Veterinary, Dunedin for serum biochemistry (Table 1) and a complete blood count (CBC, Table 2).

The major changes in the biochemistry were increases in all liver enzymes and severe azotemia. RBC levels were within normal limits thus a hemolytic cause of the icterus was ruled out. The elevated liver enzymes indicated that the hyperbilirubinemia was of hepatic/ cholestatic origin. The increased amylase was also consistent with liver damage although could also have indicated pancreatitis. Azotemia coupled with the increased phosphate and low chloride indicated that there was also renal failure occurring. The CBC showed a neutrophila with toxic changes indicating there was an inflammatory response somewhere.

Table 1. Serum biochemistry results for a dog diagnosed with leptospirosis due to Leptospira interrogans serovar Pomona

Analyte Na K Na:K ratio Cl Cre Urea PO4 Chol TP Alb Glo Agr Ca Bili ALP ALT AST CK AMY

Units Mmol/L Mmol/L Ratio Mmol/L Umol/L Mmol/L Mmol/L Mmol/L G/L G/L G/L Ratio Mmol/L Umol/L IU/L IU/L IU/L IU/L IU/L

Reference range 141–153 4–5.4 27–36 106–117 48–109 2.5–9 0.92–1.82 3.27–9.82 54–74 33–44 19–35 0.52–1.7 2.08–2.82 0–3 0–87 0–88 0–51 0–385 0–1074

Initial presentation 148 5.2 28.5 89 L 620 H 55.6 H 4.01 H 6.3 66 40 27 1.49 2.37 384.4 H 942 H 234 H 125 H 502 H 2479 H

First revisit

Second revisit

99 12.7 H

62 33 29 1.15

613 H 271 H

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

1 40 36

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

Table 2. CBC results for a dog diagnosed with leptospirosis due to Leptospira interrogans serovar Pomona

Analyte RBC Hb HCT MCV MCH MCHC Plat NRC WBC Neut Neutab Band Bandab Lymph Lymphab

Units

Reference range

Result

X 10 /L G/L L/L FL PG G/L X 109/L /100LEU X 109/L % X 109/L % X 109/L % X 109/L

5.5–8.2 120–180 0.37–0.55 65–78 20–25 310–360 200–500 0–0 6–15

7.32 183 H 0.54 73 25 341 333 4H 24.2 H 88 21.3 H 4 1.0 H 8 1.9

Based on hepatic and renal damage coupled with an inflammatory response the reporting pathologist suggested we considered leptospirosis as a differential in this dog. However cholestasis and pancreatitis were still being considered. To provide support for a diagnosis of leptospirosis, urine was collected by freecatch and submitted for testing with the PCR test that detects Leptospira spp DNA. This test is typically positive early in infection, often prior to seroconversion. The urine sample was weakly positive for Leptospira spp. DNA. Serological testing to confirm this diagnosis was offered however because the dog was responding well to treatment the owner declined due to the extra cost. Zoetis (manufacturer of leptospirosis vaccines) and Gribbles Veterinary offered to cover the cost of serological testing due to the rarity of the diagnosis in this geographic location. A blood sample was collected before the dog was discharged from

3.6–11.5 0–0.5 0.7–4.8

the hospital and subjected to Leptospira serological testing using MAT (Table 3).

Treatment

The results of the serology and PCR test along with the clinicopathologic abnormalities (leukocytosis, hyperbilirubinemia, azotemia, elevated AST, ALP, ALT and CK) and clinical signs were strongly suggestive of leptospirosis; however at this stage the serovar could not be determined. The recommended treatment for leptospirosis in dogs is a broad-spectrum penicillin-family antibiotic for 14 days (Schuller et. al. 2014). Treatment with 1000000IU penicillin (Benzylpenicillin Sodium, Novartis, Auckland, NZ) injected slowly I/V, twice daily was started. Gentamycin (Genta 50, Phoenix Pharm Distributors, Auckland, NZ) 5 mg/kg, SQ, was also given once daily to ensure broad-spectrum antibiotic cover as when treatment was started a diagnosis of leptospirosis

Table 3. Leptospira antibody titres detected by MAT for a dog diagnosed with leptospirosis due to Leptospira interrogans serovar Pomona

Leptospira serovar

Sample taken before dischargea

First revisit (titre after dilution)a

Ballum

>1/1600

1/1600 (1/1600)

Pomona

>1/1600

>1/1600 (1/25600)

Copenhageni

>1/1600

>1/1600 (1/1600)

Hardjo

1/1600

>1/1600 (1/1600)

The standard procedure at Gribbles Veterinary Pathology is to dilute samples up to 1/1600 so that

samples that give a reaction at this dilution are reported as >1/1600. If requested higher dilutions can be tested. The results of these higher dilutions are shown in brackets.

had not been established and secondary infection was also a concern. Intravenous fluid therapy with 0.9% NaCl at 4 ml/kg/hour (1.5x maintenance) was continued. As the dog was still not eating and had continued to vomit, he was given 0.2 mg/kg metoclopramide (Metoclopramide hydrochloride, Pfizer, Bently, West Australia) SQ and was syringe-fed Hills A/D diet (Hill’s Pet Nutrition, Topeka, KS, USA). This treatment was maintained for 3 days after which the vomiting decreased slightly in frequency but still occurred after feeding. On the third day of treatment, haematemesis began to occur immediately after the administration of each dose of penicillin. Sucralfate (Carafate, Aspen Pharmacare Australia, St. Leonards, NSW, Australia) at 25 mg/ kg, given orally for a single dose and 2 mg/kg Peptisoothe (ranitidine, AFT Pharmaceuticals, Auckland, NZ) S/C, once daily, were added to his treatment regime as gastroprotectants. In addition, the I/V penicillin was changed to a different formulation (Bovipen, Virbac, Hamilton, NZ) given S/C once daily at 30 mg/kg. To stimulate his appetite, a supplement containing multiple B-group vitamins (Multiject B, Bayer Animal Health, Auckland, NZ) was given at a rate of 5 ml once daily administered via IV fluids. Over the following 2–3 days the dog’s appetite improved slightly such that a small amount of Hill’s A/D as consumed from his bowl when offered. He also began to drink voluntarily so after 5 days of hospitalization, intravenous fluid therapy was discontinued. At this point the S/C penicillin treatment was replaced with amoxicillin-clavulanic acid tablets (Juroclav, 500 mg, Jurox Ltd, Rutherford, NSW, Australia) given orally at 12.5 mg/kg, twice daily. After 8 days in the clinic the vomiting ceased and he was discharged 24 hours later with a further 12 days of Juroclav tablets (for a total of 20 days treatment with penicillin or amoxicillin-clavulanic acid). The owner was also given 2 L of SteriGENE (halogenated tertiary amine and organic salts, Ethical agents, Manukau, NZ) with which to disinfect the dogs kennel and surrounding areas. Immediately before discharge a blood sample was taken for serological testing.

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

Follow-up care

At a revisit appointment 2 weeks after discharge, the dog was much brighter and less lethargic with a normal appetite. He had gained weight (2 kg) but his mucous membranes remained slightly icteric. The dog was vaccinated against leptospirosis using Leptoguard (Zoetis New Zealand Limited, Auckland, NZ). This vaccine contains inactivated Leptospira interrogans serovar Icterohaemorrhagiae and provides protection against the L. interrogans serovar Copenhageni which most commonly affects dogs in New Zealand. A blood sample was submitted for a serum biochemistry panel to monitor kidney and liver function (Table 1) and for Leptospira antibody titres using MAT (Table 3). He was again positive for Leptospira antibodies and the highest titre was for serovar Pomona which suggested this was the infecting serovar (with cross-reactivity occurring to the other serovars tested). Serum biochemistry revealed ALT, ALP and urea remained elevated above normal (Table 1). However ALP and urea were markedly lower than the previous measurement. Furthermore, creatinine was within the normal range. Thus kidney function appeared to be returning to normal but there was concern for ongoing hepatocellular injury. The dog had developed a rash on his abdomen which was treated with Cortavance spray (hydrocortisone aceponate, Virbac). The dog was examined again at a revisit 4 weeks later where the owner reported that his appetite and energy levels had returned to normal. Liver enzymes and function tests were all within normal limits (Table 1). The abdominal rash had resolved. However he now had a number of alopecic, pruritic areas scattered over his body. A trichogram was negative, however demodecosis was suspected possibly due to immunosuppression, so he was treated with Bravecto (1000 mg fluralaner, MSD Animal Health, Upper Hutt, NZ) and a second dose given 5 weeks later. At this visit the booster dose of Leptoguard was given. This vaccine protects against the Copenhageni

serovar which typically infects dogs in New Zealand (Cave et al. 2014) but not against Pomona, which was the likely cause of this dog’s infection. Because of the risk of continued exposure to serovars not present in the vaccines registered for dogs, it was decided to vaccinate this dog with Leptoshield (Zoetis New Zealand Limited) which is registered for use in cattle, deer, sheep and goats for protection against L. borgpetersenii serovar Hardjo and L. interrogans serovar Pomona. The dog was given an initial dose of this vaccine and a second dose 5 weeks later.

Discussion

Leptospirosis is an important disease worldwide. Most mammals, including humans, can be infected by the bacteria making it an important zoonosis. The bacteria itself is a spirochete which is highly mobile. Due to high mobility the organisms can cause multi-organ damage and lead to serious lifethreatening disease. There are two pathogenic species of Leptospira in New Zealand, L. interrogans and L. borgpertersenii. Leptospira occur as subtypes or serovars each adapted to a host species. Animals infected with their host-specific serovar may not show any signs of illness. However the bacteria migrate to the kidneys and are shed in the urine of infected host animals. Other non-host animals become infected when this urine comes into contact with mucous membranes (mouth, nose, ears, cuts etc.) If a non-host species is infected they will show clinical signs, which may be severe. In dogs, clinical signs include: fever, anorexia, depression, hepatitis, jaundice, renal failure and death. Historically, clinical disease in dogs in NZ has been believed to be a ‘Taupo and North’ issue. However, a serological survey undertaken at Massey University in 2013 (Harland, et al. 2013) of 655 dogs, showed no significant difference between the North and South Islands for the risk of exposure to L. interrogans Copenhageni (transmitted by the brown rat). Copenhageni was most prevalent serovar detected by serology with L. borgpetersenii Hardjo (commonly carried by cattle) found in working dogs. In recent years, there have been several reports in which dogs in NZ have been

diagnosed with clinical disease from not only Copenhageni, but to L. interrogans Pomona (maintained by cattle, pigs and sheep) (Harland 2015) and Hardjo (maintained by cattle, deer and sheep) (Sides 2012). Most cases of leptospirosis caused by Pomona seen in the North Island have been linked back to spread from cattle (Thompson and Taylor et. al. 2015). The property this dog came from is a store cattle property in which cattle are brought in, fattened up and then sold on. There was no known history of leptospirosis vaccination of cattle on the property. The cattle were all sourced from the local area with none being brought down from the North Island or upper South Island where cases of leptospirosis are commonly reported. The dog had also never left the property and there had only been one other dog on the property, which had lived in Dunedin its entire life. Given the above information, the assumption was made that the dog had contracted this infection from the cattle on the property although it is unlikely this will ever be confirmed. Testing and vaccination of the cattle on the property was discussed and is something this farmer will definitely consider in the future due to the zoonotic risk, it is also possible that he will ensure he buys only vaccinated stock in the future. Possum numbers on the property were reported to be low by the owner, however this should still be considered as a potential source of infection in this case since possums may be accidental hosts for L. pomona. If this dog did contract the infection from another animal on the farm it begs the question – why is leptospirosis not more commonly diagnosed in the lower South Island of New Zealand? Are dogs not getting clinical disease in this area, or are we not correctly diagnosing it? Are we missing some of these infections by not testing for leptospires, or perhaps testing at the wrong time? We may also be overlooking subclinical or mild disease. Studies have shown that there is no significant difference between the prevalence of positive titres to Leptospira throughout New Zealand. Although the disease is diagnosed more commonly in the Northern areas of New Zealand, it is currently unknown why this is (Harland et al. 2013).

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

Initially the dog was vaccinated with the vaccine registered for use in dogs (Leptoguard) in the hope that when the causative serovar was identified it would be covered by this vaccination. Unfortunately this was not the case. After collegial discussion the decision was made to vaccinate the dog off-label, with the tri-valent vaccine registered for use in large animals (Leptoshield). The off-label vaccination has been used in the North Island without any reports of vaccination site reactions (Cave et. al. 2014). A preliminary study of 20 dogs showed that use of this vaccine in dogs is effective in raising antibodies to serovars Pomona, Hardjo and Copenhageni although the authors note that the titres do not guarantee protection (Cave et al. 2014). Furthermore no adverse events were noted. This provides sufficient justification for off-label use where significant risk for exposure to serovars not contained in the on-label vaccine has been identified, until such time as a fully tested and licensed canine vaccine for these serovars becomes available in New Zealand. Since this dog had become naturally infected with the bacteria it was debatable as to whether vaccination was required at all. However the duration of immunity after natural infection with Leptospira in dogs is not known (Schuller et al. 2015). There are

no reports of dogs that have recovered from leptospirosis becoming re-infected. However given the risk of ongoing exposure to potentially a variety of serovars, vaccination as soon as possible after clinical recovery is recommended (Schuller et al. 2015). The vaccination was given a month after the dog was discharged to ensure his immune system was recovered from the initial infection and thus able to mount a full response. As leptospirosis is a zoonotic disease extra care had to be taken when dealing with this dog’s urine while he was in the hospital. His cage was cleaned twice daily with Trigene, which is labeled to kill leptospirochetes and barrier nursing was put in place. Locations where the dog urinated while being walked outside was marked and washed down with Trigene also. Due to the rarity of this diagnosis in this region of New Zealand, it was decided to write this as a case study for others to read. Increased awareness that this disease has been diagnosed in an area not previously known to be a problem, in a dog with no known exposure to animals from further North, may prompt veterinarians to consider leptospirosis in their list of differentials for animals with consistent clinical signs even in the absence of a suspicious history.

Acknowledgements

Thanks to Zoetis for paying for serological testing and Gribbles Veterinary, especially John Gill, for the help and for paying for the first serology test. Thanks also to Alison Harland for comments on this article.

References

Cave N, Allot S, Harland A. The serological response of working farm dogs to a vaccine containing Leptospira interrogans serovars Copenhageni and Pomona, and L. borgpetersenii serovar Hardjo. New Zealand Veterinary Journal 67, 87–90, 2014 Harland AL. Epidemiology of canine leptospirosis in New Zealand: a thesis presented in fulfilment of the requirements for the degree of Master of Veterinary Science at Massey University, Palmerston North, New Zealand. 2015 Harland AL, Cave NJ, Jones BR, Benschop J, Donald JJ, Midwinter AC, Squires RA, Collins-Emerson JM. A serological survey of leptospiral antibodies in dogs in New Zealand. New Zealand Veterinary Journal 61, 98–106, 2013 Schuller S, Francey T, Hartmann K, Hugonnard M,Kohn B, Nally JE and Sykes J. European consensus statement on leptospirosis in dogs and cats. Journal of Small Animal Practice 56, 159–79, 2015 Sides R. Crook bulls to canine urine: the permutations of a leptospirosis outbreak. Proceedings of the society of sheep and beef cattle veterinarians of the NZVA, 2012 Thompson J, Taylor D. Diagnosis of leptospirosis in dogs. Vetscript 28(3) 18–20, 2015 l

Erratum

Companion Quarterly would like to apologise for the omission of information from the article entitled Angiostrongylosis by B Jones and WE Pomroy on page 14 of the September 2016 issue. The omitted information is shown below:

Current MPI policy re: angiostrongylosis

The biosecurity risks associated with imported dogs were assessed by MPI in the 2009 import risk analysis for cats, dogs, and canine semen (http://www.mpi.govt.nz/document-vault/2796). Since the natural hosts of Angiostrongylus cantonensis are rats and dogs, and cats are aberrant hosts in which the larvae are unable to complete their life cycle, this parasite was not identified as a hazard in imported dogs. Angiostrongylus vasorum was assessed to be a risk in imported dogs, which are required to be treated twice with a product (or combination of products) registered for the control of nematodes and cestodes at the manufacturer’s recommended dose. The first treatment must be given in the 30 days prior to the date of shipment and at least two weeks before the second treatment, and the second treatment must be given in the four days prior to the date of shipment.

Human infection with A cantonensis

Infection is most often in young children after they have eaten molluscs. Infection in adults can be accidental but one celebrated case was the ‘Aussie bloke’ who ate slugs as a dare during a stag night! (with a XXXX maybe…?) He developed severe neurological signs. Angiostrongylus infection has been diagnosed in NZ in a traveller returning to the country. Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

RESEARCH NEWS

Honest placebos

Source: pixabay.com

This article is based on an article published in a Pain supplement in Nature by Jo Marchant (Marchant 2016). She is a freelance science journalist based in London. My comments are in italics. Although the modern idea of the placebo effect was first established in 1955 the neuroscientist Jon Levine was first to describe "the biology of the placebo". He administered I/V saline to post-operative patients telling them it might be morphine. Some of them (about 1/3) reported a significant reduction of pain. He reversed this by secretly adding naloxone to the drip thus blocking opioid receptors. The patients' pain returned (A different sort of ethics approval in 1978!). This demonstrated that the placebo response could be blocked biochemically. Levine argued that the patientâ&#x20AC;&#x2122;s analgesic response to the placebo was mediated by endogenous endorphins. This conclusion has since been backed by brain imaging studies. Placebos (for pain) can also raise levels of endocannabinoids or dopamine or depress prostaglandin levels. The

thinking is that placebos affect the expectations of how severe the pain is going to be.

with chronic lower back pain achieved modest to dramatic changes in disability and pain over 3 weeks.

New evidence suggests that, in some cases, placebo responses may be learned in the manner of a Pavlovian response. This can be achieved in some cases by substituting the placebo after pain has been relieved regularly with conventional drugs. This learned response is sometimes so strong that it works even when the patient is aware that a placebo is being employed.

It might be too much to ask dogs and cats to swallow this, yet there may be opportunities to employ the learned response. Patients that could be candidates might be those with arthritic pain where response to drugs is marginal, or even better, where response to drugs is good but is accompanied by side effects. I look forward to a published study!

Marchant refers to recent work by Kaptchuk. Chronic pain is often poorly controlled by drugs whose side effects are often problematic. He suggests giving placebos openly. In a 2010 study he treated irritable bowel syndrome patients with sugar pills telling them that was what they were getting and that placebos may well work for them. In 59% of patients it worked adequately compared with 35% in the nontreatment group. This was a better result than for most drug treatments. A similar study by Carvalho with 97 patients

Relevant reading

Marchant J. Honest Fakery. 2016. Nature 535; S14â&#x20AC;&#x201C;15 (Full text available at: http://www.nature.com/nature/journal/ v535/n7611_supp/full/535S14a.html) Marchant J. Cure: A Journey into the science of Mind over Body. Canongate, Edinburgh, UK, 2016 Kaptchuk TJ, Friedlander E, Kelley JM, Sanchez MN, Kokkotou E, Singer JP, Kowalczykowski M, Miller FG, Kirsch I, Lembo AJ. Placebos without deception: a randomized controlled trial in irritable bowel syndrome PLoS One 22, e15591, 2010 l

Allan Bell

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

CONFERENCE REPORT

Highlights from the Australian and New Zealand College of Veterinary Scientists Science Week conference Gold Coast, Australia, July 2016 This article was written as part of the requirements for receiving the Hill’s Pet Nutrition/CAV Educating the Educators Grant

DR PRU GALLOWAY, BVSc

MANZCVS FANZCVS, registered Specialist in Feline Medicine. Catmed Ltd, Hill's Pet Nutrition Adjunct Senior Lecturer in Feline Medicine, Massey University. I was fortunate enough to be awarded a Hill’s Pet Nutrition/CAV Educating the Educators Scholarship to assist in attending the Australian and New Zealand College of Veterinary Scientists (ANZCVS) ‘Science Week’ in July 2016.

The ANZCVS website states “The College Science Week conference encourages excellence in veterinary science. College Members, Fellows and invited guests who are at the forefront in their fields will present the latest scientific information across a number of disciplines”. Praise doesn’t come much higher than the words of a Kiwi 2016 Specialist attendee “This is the best conference I have been to”. In 2016 for the first time there was a feline masterclass pre-day with three reknown Specialists from the UK. The day was so popular it will likely be run biennially. Here's a selection of topics relevant to Kiwi small animal vets, some in short

Photo courtesy of ANZCVS

note format in the interests of being concise.

Transmission:

Feline haemoplasmas

• All three are in found saliva but experimentally have been unable to establish infection with saliva.

Severine Tasker, Bristol University. Three species infect cats: • Mycoplasma haemofelis; acute infection often causes severe haemolytic anaemia. • 'Candidatus Mycoplasma haemominutum' and 'Candidatus Mycoplasma turicensis'; acute infection can drop the PCV but doesn't usually cause anaemia unless there is concurrent disease or immunocompromise.

• Probably not transmitted by fleas.

• Can induce infection by SC injection of blood, but not blood PO. Diagnosis: Blood smear of non-EDTA blood: • Low sensitivity (need 107 to 108 organisms to see on cytology!) • Marked fluctuation in numbers until start of antibiotics • Dry slide quickly or cells can crenate and can misidentify as haemoplasma.

Contact: 70 Pharazyn St, Lower Hutt 04 569 8830

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

• Doesn't differentiate M.haemofelis from M. haemominutum • Doesn't detect M.turicensis

Pica:

PCR:

• Not associated with severity of anaemia.

• Ideally real-time quantitative PCR (qPCR). ELISA serology: • Development has been limited by inability to culture haemoplasmas (a ready source of antigen is needed for protein-based serological assays). • Titres maximal in early infection, so may identify acute infection. • A positive titre doesn't identify type of haemoplasma. • Can be more sensitive than PCR (antibody-positive/PCR-negative infections have occurred) Future: Combined qPCR and serology most sensitive for diagnosis.

• More common with bone marrow or immune-mediated disease. Often multiple mechanisms to anaemia – so features of both regenerative and non-regenerative anaemia may be present. Regenerative anaemia: • Slide agglutination: 1 drop of EDTA blood and 4 drops of saline. • Look for aggregate reticulocytes. However if anaemia is mild may not see increase in reticulocytes (but serial increasing PCVs can confirm anaemia is regenerative).

Treatment:

• Usually increased MCV and decreased MCHC (can be normal MCV and decreased MCHC).

• Can't eliminate infection 100%; can demonstrate negative sequential qPCR but can't PCR-test the whole cat!

Feline inflammatory bowel disease (IBD) – what’s new?

• Doxycycline, 10 mg/kg PO daily for 3+ weeks, or pradofloxacin, 5–10 mg/ kg/d. Marbofloxacin, 2 mg/kg/d not effective.

IBD is the most common cause of chronic GI signs in cats

• Avoid routine use of corticosteroids; even cats with positive Coombs tests usually respond to antibiotics and supportive care alone (e.g. fluids and if severe anaemia, a blood transfusion). Prevention: • PCR-test blood donors. • ? house cats indoors (outdoor status has been identified as a risk factor)? • ? vector control for fleas/ticks? • vaccination in future as protective immunity develops after M.haemofelis infection, but there is no crossprotection between haemoplasma species.

Feline anaemia tips

Severine Tasker, Bristol University. Features of feline RBCs: • RBC mass 20–30% less than dogs. • Feline haemoglobin (Hb); - has inherent low 02 affinity – so cats tolerate anaemia better as Hb releases O2 readily. 46

- increased sulphydryl groups so prone to oxidation (Heinz bodies).

Kit Sturgess, UK.

• Vomiting is more common than diarrhoea in cats and ~ 10% present with weight loss only. • ‘New’ name for IBD is chronic inflammatory enteropathy. • Defined as a chronic, self-perpetuating, non-resolving, immune dysregulation. • Complex interplay between environmental factors (such as the intestinal microbiota and diet) and dysregulated host responses in a genetically susceptible individual. • Diagnosis requires gut biopsy and exclusion of all known triggers e.g. GI infections/parasites, food sensitivity, hyperthyroidism, pancreatitis. • May be triggered by previous infection e.g. some cats with successfully treated Giardia develop chronic gut inflammation. • Leads to increased numbers of immune cells in the lamina propria with secondary changes such as villous blunting and fibrosis. However as immune cells are normal residents of the lamina propria, is it

really inflammatory, or is it failure of apoptosis (programmed cell death). And is it the lympholytic rather than the anti-inflammatory effect of corticosteroids that are beneficial in managing IBD? • Clonality testing = significantly better predictor of survival than cytology/ histology/immunohistochemistry, so suggests should do routinely on gut biopsies Management – more studies needed to ascertain ‘best’ approach, individualise for each patient but Kit’s approach for ‘known’ or strongly suspected cases of IBD is: 1 Diet for 2–3 weeks e.g. hypoallergenic, limited antigen. May be benefit to diets with increased omega-3 fatty acids for their anti-inflammatory effect. 2 If no or partial response add metronidazole or tetracycline for 2–3 weeks. 3 If no or partial response add immunosuppressive drugs. • Prednisolone is initial drug of choice. • Budesonide: a corticosteroid with strong first pass metabolism so has few effects outside the gut – useful for cats where systemic corticosteroids are best avoided such as diabetes mellitus or cardiac disease. Expensive. Dose is ~ 1.5 mg per cat/d tapering to every 2–3 days as maintenance dose. • Chlorambucil: 2 mg q48 hours for cats over 4k g and q72 hours if under 4 kg. Monitor CBC and liver enzymes. Handling precautions needed as is a chemotherapy drug. • Ciclosporin: monitor serum levels, caution risk of fatal toxoplasmosis if serum levels too high especially, but not exclusively, if exposed to Toxoplasma for the first time during treatment. • Mycophenolate mofetil: new immunosuppressive drug, blocks proliferation of T and B cells. Little data on use in cats, so not a first line treatment. Use suspension 10 mg/kg PO BID. Side effects: bone marrow suppression, nausea, vomiting, diarrhoea, infection. 4 If concurrent hypocobalaminaemia, daily oral supplementation with

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

cyanocobalamin (250 μg/day) is an alternative to injectable vitamin B12.

Other GI tips:

• Mast cells may be important in the inflammatory environment of IBD: ? future role for tyrosine kinase receptor inhibitors? • ‘High through put’ 16S RNA gene sequencing can identify bacterial communities; in future may help with monitoring of IBD. • Babies given antibiotics; gut microbiota takes 2 years to recover!

Gastrointestinal histopathology for medics: what I’d like to have known as a medicine resident that I didn’t know Arnon Gal, Massey University.

Arnon has dual specialisation in small animal internal medicine and pathology. He is a great speaker; make sure you attend if he comes your way. • Due to the nature of tissue processing and slide preparation, the pathologist only examines a tiny part of the submitted specimen. So lesions can be missed – if the results are not what you expect, ask for more sections to be cut from the paraffin block.

more information the pathologists have the better. Limitations of small endoscopic biopsy samples include:

Negative prognostic factors

• Harder to orientate so that villi are in the correct longitudinal section.

• Hypocobalaminaemia.

• Misses the gut wall layers beyond the submucosa. For example lymphoma in the deeper wall layers may be misdiagnosed as IBD if there is overlying inflammation in the mucosa and submucosa. • Misses the metres of small bowel beyond the proximal duodenum and distal ileum and extra-intestinal structures such as mesenteric lymph nodes. Interpreting gut biopsies: • The gut is the largest immune organ with 90% of all lymphocytes in the body, so it's normal to see lymphocytes in gut biopsies. Must see concurrent structural change to identify pathologic lesions. Always ask “do the changes seen fit with the animal’s clinical presentation?” • Acute inflammation; neutrophils/ necrosis. • Chronic changes; lymphocytes, plasma cells, architectural changes, fibrosis, granulation tissue.

• Size matters; bigger is better. Full thickness gut biopsies (obtained at ex lap or laparoscopically) provide more information and where possible are preferable to endoscopic samples for diagnosing IBD and lymphoma.

• Intra-epithelial nests of lymphocytes – inflammatory change but not necessarily pathological (can see in sled dogs that race long distances).

• Many chronic enteridities are patchy/ multi-focal rather than diffuse; at ex lap the surgeon can palpate the gut and biopsy abnormal areas.

• Transmural invasion.

• Don’t use a punch biopsy for full thickness gut biopsy, as often leaves mucosa behind. • Mesenteric lymph nodes drain the gut; so many pathologies affecting the gut are detected in these nodes. Always biopsy these nodes if you are taking gut biopsies and always biopsy liver and spleen. • Biopsy of mesenteric lymph nodes: get a wedge (or deep punch) – need capsule, cortex and medulla. • Provide a good history and take a photo of lesions during surgery. The

• Limited published information on survival and optimal treatment.

Criteria for malignancy: • Metastasis (e.g. to mesenteric lymph node). • Heterogeneity and nuclear changes.

Protein losing enteropathy (PLE) in the dog Julian Dandrieux, Melbourne University.

• PLE is associated with lymphangectasia, chronic enteropathy (otherwise known as IBD), crypt lesions and intestinal mucosal ulcerative damage. • Median survival typically 6 months to one year but some Yorkies, and sporadically other breeds, are long term responders.

• Hypoalbuminaemia. • Crypt abscesses. • Low 25-OH-vitamin D (in dogs with chronic IBD and especially with PLE). Diagnosis: • Often via endoscopy due to risk of full thickness biopsy if hypoalbuminaemic. • Most dogs with PLE have a reactive hepatopathy. • Some have concurrent small cell lymphoma. • Diagnosing small cell lymphoma can be challenging; use clonality testing with PCR for antigen receptor rearrangements (PARR). Positive test = increased risk of neoplasia. Therapy: Aggressive therapy with diet and immunosuppressive drugs needed in most cases. 1 Diet options: hypoallergenic, low fat or home-cooked. • Some respond to diet alone but as PLE can progress rapidly and is potentially fatal, only try this in dogs that are clinically well with a good appetite. • OK to continue with diet alone if clinical signs improve and serum albumin increases by day 7. • If histopathology confirms primary lymphangectasia, good success with ultra low fat diet, however corticosteroids are often used concurrently initially as lymphatic leakage can trigger inflammation. 2 Antibiotics: role in management of PLE is poorly understood. • Metronidazole is most commonly used, but there are concerns it may contribute to intestinal dysbiosis. • Indicated if invasive bacteria in gut wall. • Fluorescent in situ hybridisation (FISH) studies on formalin-fixed tissue very sensitive for bacteria. • More studies needed.

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

3 Immunosuppressive drugs: • Prednisolone usually first line; often combined with other drugs for steroid sparing effect. • Retrospective study suggests prednisolone and chlorambucil better than prednisolone and azathioprine, but prospective studies needed. • If concurrent small cell lymphoma use chlorambucil and prednisolone. • Cyclosporine for refractory cases. Prognosis: • Guarded, but assess by response to treatment. • Significantly worse if concurrent small cell lymphoma (vs. chronic enteropathy or idiopathic lymphangectasia).

Reaching for a diagnosis of feline infectious peritonitis Severine Tasker, University of Bristol.

A single minimally invasive diagnostic test does not exist. • Definite diagnosis is via histopathology with immunologic staining to identify feline Corona virus (FCoV) antigen in lesions. Identification of FCoV antigen in body cavity effusions strongly supports a diagnosis. • Signalment; most cats are <3 years old, often recent stressor (e.g. rehoming, desexing), breed predisposition (e.g. in Australia Burmese, Australian Mist, British short hair and Cornish Rex]). • Wet form: ‘typical’ body cavity or pericardial effusions. Fever common, progresses quickly. • Dry form: neurological signs (ataxia, seizures, nystagmus), uveitis, skin papules, fever less common, progresses more slowly. • FCoV serology of little value, can have high titres in healthy cats and ~ 10% of cats with confirmed FIP have negative titres.

• PCR targeting the S–protein mutation is not specific for FIP. Treatment of FIP: a recent paper shows promise for a coronavirus protease inhibitor in cats experimentally infected with FIP (Kim Y, Liu H, Galasiti Kankanamalage AC, et al. Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor. PLoS Pathogens 12: e1005531, 2016). Research abstract:

Diagnosis of feline leukaemia virus (FeLV) infection in client-owned domestic cats in Australia: watch out, false positives about! Mark Westman et al., Sydney University.

• Compared the accuracy of three point-of-care FeLV antigen kits (IDEXX SNAP-FIV/FeLV Combo, Witness FeLV/FIV and Anigen Rapid-FIV/FeLV) using blood and saliva. • 563 blood samples and 419 saliva samples. • Collected from 491 FeLV uninfected cats and 72 infected cats (45 progressive infections and 27 regressive). • Diagnostic gold standard qPCR for FeLV provirus. Test kit IDEXX SNAP(using blood) FIV/FeLV

Witness FeLV/FIV

Anigen Rapid-FIV/ FeLV

sensitivity

63%

57%

specificity

94% (p=0.004) 98%

98%

For saliva sensitivity and specificity were 52% and 100% respectively for all three tests. Conclusions: • All test kits gave false positives; but IDEXX SNAP FIV/FELV gave significantly more.

Supportive findings;

• No combination of tests eliminated false positives.

• Fluctuating non-responsive pyrexia.

• Need PCR to assess FeLV status with confidence.

• Neutrophilia, lymphopenia and mild to moderate nonregenerative anaemia.

• Confirm all positive tests with FeLV provirus PCR (this includes sick cats).

• Increased serum globulins: 90% in a 2016 study of 231 cats (but only 15% had increased TP).

• Any cats with exposure to FeLV that test negative with pointof-care tests also confirm with PCR.

• Increased serum globulins with albumin:globulin ratio <0.4.

• If PCR is unavailable or rapid confirmation of FeLV status is needed, repeat p27 antigen test with a different kit (this reduces but doesn’t eliminate false positives).

• Jaundice – especially in the wet form. • Body cavity effusions very helpful in diagnosis; serial ultrasound may be needed to detect. Viscous, straw coloured, protein rich (>35 g/L) with low cellularity (<5 x109/L) non-degenerate neutrophils and macrophages. If available, FCoV RT-PCR on effusions and immunostaining for FCoV antigen in effusions are strongly supportive, but not all cases are positive and false positives can occur.

• RT-PCR on tissue or CSF – high viral loads with qPCR is supportive and quicker than histopathology.

• Some false positives may be due to cats having anti-mouse antibodies in blood (kits use mouse antigen). • Whole blood had more false positives than serum/plasma (though this may be less of an issue with newer test kits). • Saliva is unsuitable as a screening test for large populations of cats.

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

Determining the FIV status of FIVvaccinated cats using point-of-care antibody kits Mark Westman et al., Sydney University. Journal of Comparative Immunology, Microbiology and Infectious Diseases. 42, 43–52, 2015

Some point-of-care FIV test kits do not detect vaccinal FIV antibody.

• There was no significant reduction in risk of vaccinated cats becoming infected with FIV compared to unvaccinated controls (p=0.14). But there was a trend for some protection and the study was underpowered. Conclusions: • Is a protective rate of 56% high enough to recommend vaccination of at-risk cats?

• 119 vaccinated cats and 239 unvaccinated Australian cats.

• Use additional measures to minimise risk of infection e.g. modular pet parks, cat curfews or confining indoors.

• FIV status confirmed with FIV RealPCR™ (sensitivity 92%, specificity 99%).

• Annual FIV test recommended in vaccinated cats to ensure they aren't getting infected.

• Witness FeLV/FIV and Anigen Rapid FeLV/FIV kits could discern true FIV infection status of cats irrespective of vaccinal history (respective sensitivity was 100% and 100%, and specificity was 98% and 100%).

Longevity and mortality of cats attending primary care veterinary practices in England

• IDEXX SNAP FeLV/FIV combo could not determine if antibodies were due to natural FIV infection or vaccination. • Ability of a test to discriminate antibodies from vaccine vs. natural infection is not dependent on which antibodies the test detects e.g. p15 vs. p24 vs. gp40, so all kits need to be evaluated individually. • Value: in areas where FIV vaccines are used, can identify if FIV-infected or not with a quick in-house test, avoiding the expense/delay of FIV PCR.

The protective rate of the feline immunodeficiency virus vaccine; an Australian field study Mark Westman et al., Sydney University. Aim: • To determine the protective rate (effectiveness) of Fel-O-Vax FIV vaccine in client-owned cats in Australia. Retrospective case control study: • 89 vaccinated cats and 212 unvaccinated controls matched for age, sex and post-code.

O’Neill DG et al. Journal of Feline Medicine and Surgery 17, 125–133, 2015

Large epidemiologic study of 118,016 cats attending 90 veterinary practices in England, of which 4009 cats with confirmed deaths were randomly selected for detailed study. I was impressed by the large number of cats in this study. Median lifespan was 14 years: • bi-phasic incidence of death with peaks at 1–2 years and 16–17 years. • crossbred 14 years vs. purebred 12.5 years (p<0.0001). Cause of death: • Trauma 12.2%. • Renal disease 12.1%. • Non-specific illness 11.2%. • Neoplasia 10.8%. • cats >5 years old: kidney disease = biggest killer (13.6%).

Endocrine response to critical illness Joehan Schoman, University of Pretoria.

Relative adrenal insufficiency doesn’t exist.

Inclusion criteria:

• It arose through misinterpretation of human data.

• FIV antibody testing before vaccination (unless <6 months old at first vaccination), annual on-time vaccination for at least 3 consecutive years.

• Etomidate is used as a sedative in ICU and suppresses synthesis of glucocorticoids. Takes 3 days for ACTH to return to normal after a single dose of etomidate.

• FIV status confirmed with point-of-care antibody testing and PCR plus virus isolation if results were discordant or in any suspected vaccine breakthroughs (i.e.FIV- vaccinated, FIVinfected cats).

• When the paper on relative adrenal insufficiency in humans was published they didn’t know etomidate was the reason why cortisol levels were low!

Results:

• Diagnose with cortisol:ACTH ratio <0.01.

• 5 cats had vaccine breakthroughs (5/89, 6%) and 25 control cats were FIV-infected (25/212, 12%).

• Cortisol can vary 20% between different analysers so use your lab’s reference range.

• All vaccine breakthroughs were FIV type A (the vaccine contains subtypes A and D).

No benefit to thyroxine supplementation in severe illness.

• Vaccine 'protective rate' (effectiveness) was 56%. Note this is not the same as 'preventable fraction' used in lab studies as in the latter infection is ensured, whereas in field studies viral exposure cannot be guaranteed.

Hypoadrenocorticism.

Sepsis: fluid overload increases death risk, so don’t give large fluid boluses. l

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

CONFERENCE REPORT

Veterinary Dental Forum Monterey, California, USA, October 2015 This article was written as part of the requirements for receiving the Hill’s Pet Nutrition/CAV Educating the Educators Grant

ANGUS FECHNEY BVSc, Companion Animal Dental Service A review of this conference by Geraldine Gorman has previously appeared in the CAS Newsletter (Volume 27, Issue 1, page 39). Below are further excerpts from a very worthwhile and enjoyable 2015 American Veterinary Dental Forum

Feline oral inflammation

(Cindy Bell, ACVP and Jason Soukup, DAVDC, Centre for Comparative Oral and Maxillofacial Pathology and Brook Niemiec, DAVDC) Patient evaluation: age, anatomical distribution of lesions, occlusion (pyogenic granulomas may be caused by malocclusion) breed Clinical tests recommended: full-mouth radiographs, testing for Bartonella henselae, calicivirus, FeLV, FIV (BUT interestingly Dr Soukup does not test for these as it does not alter the treatment options for the different conditions). Refer to a dermatologist if eosinophilic granuloma is present. Biopsy: ensure samples are large enough, multiple, towards the centre of the lesion and deep without compromising any further surgery that might be required for full excision, particularly if neoplasia is suspected.

Contact: A. Fechney@massey.ac.nz, (027) 587 0005

Source: pixabay.com

Feline Chronic gingivostomatitis (FCGS) Features • No sex or breed predisposition • Generally a disease of middle-age • If young, then consider may have aggressive periodontitis rather than FCGS • Also consider differential of SCC • Not always bilateral Sometimes there is concurrent pyogenic granuloma (more nodular). Obviously must deal with concurrent tooth resorption and periodontitis. Most lesions are NOT ulcerated but there is erosion (the surface layers of epithelium are gone). Histologically mostly plasma cells with some “constipated” plasma cells (full of Ig)

Treatment options: Full mouth dental radiographs are strongly advised to identify subgingival disease and retained root tips. Extraction of grossly diseased teeth (those periodontally affected or fractured), scale and polish of the remaining teeth with thorough oral flush, is the minimal required intervention. Medical intervention then revolves around corticosteroids but these generally become less effective over time. Metronidazole and clindamycin may reduce severity. Cyclosporin (5–10 mg/kg) or gamma interferon may be effective in some cases. Full mouth extraction, or at least caudal extraction, is still considered the most effective long-term solution. Important to note (and discuss with clients) that despite this assertion, a retrospective study of 96 cats

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

with FCGS by researchers from the University of Pennsylvania found 30% cats had little to no improvement with caudal or full mouth extraction, 40% had moderate improvement, the remaining 30% had complete resolution. Of these latter 70%, two thirds of the group required further finite medical management to achieve positive outcomes. Recent work at UC Davis has shown cure rates for refractory cases in excess of 70% using mesenchymal stem cell therapy isolated from adipose tissue. However amplification methods for stem cells are significantly different from current commercial “table top” methods employed in general practice.

Gingivitis and periodontitis

Bimodal age distribution which drops off in later life probably since less teeth tend to be present in the mouth. Features of aggressive periodontitis (juvenile): • young, primary gingiva, Maine coons • alveolar bone expansion – often outward around maxillary canines “buttress bone”. Fibrosis as well as expansion of bone and osteoproliferaton, chronic and active,. • osteomyelitis (often quite profound looking and cancerous) • tooth resorption • periapical periodontitis Treatment options: Extraction of any significantly diseased teeth is warranted to decrease the degree of inflammation. Dental prophylaxis every 6–9 months (even if only minimal plaque is present), along with strict homecare, is critical. Where brushing is not possible, homecare alternatives include chlorhexidine rinses as well as plaque control diets and treats. In cases where gingival hyperplasia is present, early gingivectomy is recommended to remove psuedopockets, decrease inflammation, and facilitate plaque control.

Eosiniphilic granuloma

• Mostly on tongue, caudal soft palate, sometimes lip • May be very far back on base of tongue • Raised white plaque-like lesion, ulcerated, with minimal surface debris • Differentials include SCC • Eosinophililic aggregations (flame cells) form white/yellow area and once degranulated, form a foreign body type reaction – these often need surgical removal

Source: pixabay.com

• There should not be any radiographic bone change around pyogenic granuloma but may be periodontitis • Ulcerative, exuberant granulation tissue Treatment options: Surgical excision is often required as opposed to extraction of opposing maxillary PM4. Eliminate concurrent sources of inflammation.

Canine chronic ulcerative stomatitis (Jamie Anderson, DAVDC)

Treatment options: Ideally confirm the diagnosis with histopathology and perform allergy evaluation. Initially treat mild cases with antibiotics alone and more severe cases with a combination of antibiotics and corticosteroids (beware longer term side effects). For nonresponsive or refractory cases, can include cyclosporin in place of corticosteroids.

The oral mucosa has its own immune system which:

Pyogenic granuloma

• 70% of cases were castrated males and 70% were >9 years old • Terriers predisposed but not small dog problem only • Often chronic dermatitis present as well • 42% and 47% respectively, had abnormal CBC or serum biochemistry but most elevations were mild

• Mostly associated with buccal mucosa caudally but also sometimes around mandibular molars • Almost always from masticatory trauma • Often occurs after extraction of mandibular molar. Critical issue – do not bring too much tissue over ridge either lingually or bucally of removed molar

• prevents pathogen entry • has limited response to commensal organisms • T cells important • is a cytokine-rich environment Case series study of canine chronic ulcerative stomatitis (n=20)

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

• Although mucosal ulcers were very commonly over dentate areas, 38% had ulceration over edentulous areas • Most lesions were symmetrical and 30% had grade III periodontitis (25–50% bone loss) and 30% had grade IV (>50% bone loss) • Most if not all teeth associated with ulcers had radiographic evidence of bone loss • All had lymphocytic-plasmacytic gingivostomatitis to varying degrees.

Oronasal fistula

(Sharon Startup, DAVDC) Oronasal fistulae are most frequently caused by advanced periodontal disease and therefore are more likely (over time) to be bilateral. However other causes include orthodontic trauma from a maloccluded mandibular canine tooth impinging on the hard palate leading to an eventual communication. Clinical signs associated with oronasal fistulae include sneezing with or without mucopurulent or hemorrhagic nasal discharge. Small dolichocephalic breeds like miniature dachshunds and toy poodles appear predisposed to palatal bone loss of the maxillary canines Oronasal fistulae should be addressed as soon as possible after diagnosis. Single flap repair is usually sufficient for closure of oronasal fistulae. For large or recurring fistulae, a double flap repair or use of an auricular cartilage graft may be required. Options for single flap closure (pedicle flap): 1 Use vertical releasing incisions rostrally and caudally. Then must separate periosteum from more dorsal mucosa with releasing incision to allow greater mobility of the mucogingival flap. 2 Use vertical release rostrally and then horizontal release distally to P1/P2 and create an advancement flap. With careful elevation and surgery this method is more likely to preserve the blood supply and therefore the integrity of the flap. Points to note: • Make sure all granulation tissue is cleared and debrided. • Need to suture non-inflamed tissue. • No tension on created flap • Monocryl (monofilament) in preference to multifilament Vicryl • Always use simple interrupted over area of “air” and then can use continuous over vertical releasing incision. Reduce suture placement to about 1–1.5mm over air gap. • Uses burr to debride friable bone around edge of hard palate. Cover fistula so water is not sprayed into nasal cavity. Auricular grafts can also be used for larger defects as the membrane allows epithelialisation. This is an autograft and needs to be tacked down between bone and oral mucosa with a 2 mm overlap.

Monitoring deciduous teeth (Debra Nossman, DAVDC)

kittens with discrepancies noted e.g. shorter mandible relative to maxilla, impingement of teeth on soft tissue or other teeth, so that recommendations and if required, selective extraction or necessary orthodontics can be recommended early. Remember the rule of dental succession: “No two teeth should occupy the same space at the same time”. Age ranges for tooth eruption in the dog and cat are shown in Table 1. Table 1. Age ranges (months of age) for eruption of permanent dentition (From Wiggs, RB. Veterinary Dentistry: Principals and Practice, Wiley-Blackwell, 1997)

DOG 3–5 4–6 4–6 5–7

Incisors Canines Premolars Molars

CAT 3–4 4–5 4–6 4–5

Local anaesthetic agents (Mike Bartella, DACVAA)

See Table 2 for a list of local anaesthetics frequently used for analgesia during dental surgery. Table 2. Local anaesthetics frequently used during dental surgery.

Agent Bupivacaine Lidocaine Mepivacaine Ropivacaine

Onset Slow Fast Fast Slow

Duration (minutes) 180–240 60–120 90–180 300–480

Max dosea (mg/kg) 2 6 6 2

a The maximum dose provides the total volume for all blocks employed in a particular patient

Note:

- Take extra care not to inject intravascularly - Maximum dose for lidocaine in cats is 2 mg/kg so if needing 3–4 blocks are required in one patient, then it may be advisable to dilute lidocaine with saline. - Ropivicaine provides more vasoconstriction so is good for nasal biopsy Toxicity manifests as neurological signs first followed by cardiovascular effects (apart from bupivacaine which is more cardiotoxic) but these signs are often masked by general anaesthesia. If neurological signs are apparent on recovery then treatment for seizures, oxygen administration, re-intubation and controlled ventilation may be necessary. Depending on any cardiovascular effects, IV fluids, vasopressors, ionotropes, anticholinergics and CPR should be considered. If available, 20% lipid emulsion (4 ml/kg bolus, followed by 0.5 ml/ kg/min for 10 minutes is also recommended. Once again, I am extremely appreciative of the financial assistance that CAV, Hill’s Pet Nutrition, IVABS and Vetlearn have provided in order to facilitate my attendance at this international conference. l

It is important to monitor the exfoliation of deciduous teeth. Early detection of the problems caused by malocclusion is best. This involves a thorough oral examination of puppies and

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

Companion Animal Health Foundation Update CAHF is continuing to support NZ companion animal research through 2016 with the completion of several projects and the funding of one new project by Allan Bell to investigate the role of delta toxin from Staphylococcus pseudintermedius in canine dermatitis.

CATH WATSON, Chair

Companion Animal Health Foundation

Some of the projects currently underway have been making progress as follows: 1 Dr Fiona Hollinshead’s project on AMH as a potential predictive marker for fertility in bitches has been completed as was presented in Paris at the International Symposium for Canine and Feline Reproduction (ISCFR) in June. This should be published by the end of the year. 2 Dr Arnon Gal’s project to compare the diagnostic quality of bone marrow biopsy samples taken from different sites is well underway, with samples collected and the histopathology underway now. 3 A project involving genetic evaluation in four large dog breeds that have been selected for better elbow conformation using the NZVA Elbow Dysplasia (ED) scheme by Dr Andrew Worth is nearing completion and is in the process of being written up. 4 Alison Stickney’s project on comparing the prevalence of FIV in vaccinated vs unvaccinated cats in NZ is also well underway; the required samples have been collected and the results are being processed with some further PCR testing required to confirm the results. 5 Ben Leitch’s project on external fixators has been written up and is to be submitted to NZVJ.

6 The Kate Hill/Adam O’Connell investigation into clinical and biochemistry profiles of NZ working farm dogs has been completed and is being written up for publication. 7 Kate Hill’s investigation into the strains multidrug resistant Enterobacteriaceae and Staphylococcus aureus that are causing clinical infections in companion animals in NZ has been completed and is being written up for publication. As you can see, there is a range of veterinarians benefiting from grants provided by the CAHF; from academics to general practitioners. For example, those who are studying towards Massey University’s MVM qualification would be potential recipients of grants to go towards funding and completing their dissertation projects, with the assistance of an experienced researcher. So, if you feel that you can take advantage of the funds available, and what you have in mind ticks all the qualifying criteria set up by the fund (see www.healthypets.org.nz), then please do not hesitate in contacting us to discuss how we can help. Currently, CAHF funds are sitting fairly stable with payments for completed projects being similar to donations. Regular donations from the Vet Centre Marlborough’s memorial scheme and Waikiwi Vets have continued which are greatly appreciated. Pet Doctors has also made a significant donation recently which has helped boost the CAHF funds available for funding projects.

These donations make it possible to continue funding veterinary-related companion animal research in NZ, but there is so much more that could be done. The CAHF trustees would like to encourage you all to consider ways in which you, your classmates, or your business can contribute to the fund. Some ideas for you to consider: 1 Memorial scheme – The Vet Centre Marlborough have a wonderful idea for those special pets or clients in their clinic where a donation is made by the clinic on their behalf, and they will receive a personal thank you from CAHF 2 Business donation from the sales of certain products or services e.g. Waikiwi Vets makes 6-monthly donations based on the number of euthanasias performed, with a set amount from each euthanasia going towards CAHF 3 Annual donation from you and your fellow Massey classmates 4 Organise a fundraising event through your workplace or classmates 5 A personal donation 6 Client donations – CAHF can provide brochures for clients about CAHF with donation details We greatly appreciate our donors, and would welcome new benefactors to apply these funds to furthering the interests of companion animals in New Zealand. l

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

What is your diagnosis? THE ANSWERS… 1 Radiographic findings

There is soft tissue swelling associated with the distal antebrachium and antebrachiocarpal joint. There is a permeative osteolytic lesion within the medial aspect of the distal radius. The lesion has a moderately wide transition zone and there appears to be significant destruction of the cranial and medial cortex of the distal radius. There is evidence of periosteal new bone production at the dorsal aspect of the metacarpal bones and the cranial aspect of the distal radius. These features indicate a highly destructive, predominantly osteolytic aggressive bone lesion.

2 Differential diagnoses

The top differential diagnosis for the radiographic findings given the signalment, history and physical examination is primary bone neoplasia. Primary bone tumours may be of mesenchymal, vascular or hematopoetic origin, and include: osteosarcoma, chondrosarcoma, fibrosarcoma, hemangiosarcoma, lymphoma and plasma cell tumours. Osteosarcoma is the most common primary bone tumour in dogs and accounts for up to 85% of skeletal tumours (Liptak et al. 2004; Dernell et al. 2007). The average age of onset is 7 years, however a bimodal distribution of incidence has been noted, with an earlier small peak at 18–24 months and a larger one at 10 years. The majority of osteosarcomas are appendicular, with the most common sites being the distal radius and proximal humerus. Osteosarcoma is a locally aggressive tumour and which tends to rapidly metastasize to the lungs, with 90% of affected dogs having undetectable (microscopic) metastatic disease at admission (Liptak et al. 2004; Dernell et al. 2007). Other differentials include secondary bone neoplasia (metastatic disease), bone cyst and bacterial or fungal osteomyelitis (the latter does not occur in New Zealand). 54

3 Further diagnostic tests

To obtain a definitive diagnosis of the bone lesion either cytological analysis of a fine needle aspirate (FNA) or histopathological analysis of a tissue biopsy could be used. In this case FNA and cytology was selected to reduce the risk of pathological bone fracture, which is a known complication of biopsy. Under sedation FNAs were taken under ultrasound guidance of the distal radial bone mass and also of the right prescapular and superficial cervical lymph nodes to assess for metastasis. Cytology of the bone aspirates revealed a population of pleomorphic spindle cells consistent with a diagnosis of sarcoma. Further differentiation of the sarcoma type could not be determined as the cells did not display obvious features suggestive of osteoblastic origin. Cytology of the lymph node aspirates demonstrated reactive nodes without evidence of metastatic disease Given the propensity of osteosarcoma to rapidly metastasise to the lungs a radiographic assessment of the lungs is recommended. Three-view thoracic radiographs were performed in this case; they did not reveal any metastatic disease.

4 Treatment options available

Five primary treatment options exist for primary bone tumours in this location. These options and their associated survival times were discussed with the owners. a. Palliative care with pain medications only. Concerns with this option include unmanageable pain or pathological fracture. Death due to metastatic disease is expected in weeks to months. b. Thoracic limb amputation with scapulectomy. This option removes the source of pain, achieves local tumour control, and typically has rapid

recovery. The median survival time is 4–6 months, much of this with good quality of life. c. Thoracic limb amputation with chemotherapy; extends the median survival time to 1 year. Amputation is successful even in large breed dogs and dogs typically adapt rapidly to limb loss (Boston 2012; Renwick and Scurrell 2013) d. Limb-sparing surgery with chemotherapy. This becomes an option when the tumour is in the distal radius and has the same survival time as amputation with chemotherapy. e. Radiotherapy (no surgery); median survival time of 4–8 months with death as a result of local or metastatic disease. The owners in this case elected limbsparing surgery with chemotherapy. The primary goals of surgical treatment are to remove the source of pain, achieve local control and prevent further metastasis (Morello et al. 2003). Limbsparing surgery involves the removal of the neoplastic bone segment (most commonly the distal radius) with margins, and replacement of the bony deficit with an autograft, allograft or prosthesis, which is stabilised with a bone plate (Renwick and Scurrell 2013). Limb-sparing surgery has a higher rate of complications relative to amputation. These include such as infection, implant failure, prolonged recovery time and greater chance for local tumour recurrence due to narrower margins attained form the surgery. However, if it is anticipated the dog will not ambulate well after amputation (e.g. concurrent orthopaedic concerns) or the owner refuses amputation, then limb-sparing surgery is recommended. For surgical planning and further evaluation of metastasis, a CT scan of the right antebrachium and thorax was performed (Figure 2). The distal radial lesion exhibited cortical destruction

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

with fragmentation and comminution of the distal articular surface and medial styloid process of the radius. Importantly, for surgical planning the lesion did not involve the distal ulna or cross the antebrachiocarpal joint, but instead a long, poorly defined transition zone between normal and abnormal bone was present in the radius. This zone was longer than what was estimated on the radiographs. There was no evidence of thoracic metastasis on CT, which is able to detect lesion of 1â&#x20AC;&#x201C;2 mm in lungs (compared to >5 mm on plain radiographs (Picci etâ&#x20AC;&#x201A;al. 2001). Due to the large size of this dog there were significant concerns about potential implant failure. Due to the long transition zone identified on the CT scan, a large portion of the distal radius was resected to achieve suitable margins. A hybrid, 3.5 mm, 26-hole locking limb-sparing carpal arthrodesis bone plate was placed on the dorsal aspect of the antebrachium with a 120 mm stainless steel endoprosthesis in the bony deficit. A 20hole, broad DCP plate was placed on the medial aspect of the defect in an orthogonal position (Figures 3 and 4). Histopathology of the excised section of distal radius was consistent with a grade I osteosarcoma. No neoplastic cells were visible at the proximal surgical margin. On re-examination 3 months after surgery, the dog was ambulating with a mild, consistent weight-bearing lameness. No pain was elicited on palpation of the surgical site. The dog received his third dose of chemotherapy (doxorubicin at 30 mg/m2 I/V) and repeat thoracic radiographs revealed no evidence of metastasis. Figure 2. Medio-lateral CT image of the right antebrachium.

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

Figure 3. Intra-operative image of limb-sparing surgery of the distal aspect of the radius using a 120 mm endoprosthesis, 3.5 mm locking limb-sparing carpal arthrodesis bone plate and a 20-hole, 3.5 mm broad dynamic compression plate.

Figure 4. Immediate post-operative (A) cranio-caudal, and (B) medio-lateral radiographic views of the right antebrachium. Appropriate implant size, number, position and accurate limb alignment are present.

References

1 Dernell WS, Ehrhart NP, Straw RC, Vail DM. Tumors of the skeletal system. In: Withrow SJ, Vail DM, (eds). Withrow & MacEwen’s Small Animal Clinical Oncology, 4th Edtn. Pp 540-82. Saunders Elsevier, St Louis, MO, USA, 2007 2 Liptak J, Dernell W, Ehrhart N, Withrow S, Seguin B, Walsh P, Kuntz C. Management options for Canine appendicular osteosarcoma: curative intent treatment. Compendium of Continuing Education for the Practicing Veterinarian 26, 186–97, 2004 3 Boston S. Musculoskeletal neoplasia and limb-sparing surgery. In: Tobias & Johnston’s Veterinary Surgery Small Animal, Volume 1. Pp 1159–77. Saunders Elsevier, St Louis, MO, USA, 2012 56

4 Morello E, Vasconi E, Martano M, Peirone B, Buracco P. Pasteurised tumoral autograft and adjuvant chemotherapy for the treatment of canine distal radial osteosarcoma: 13 Cases. Veterinary Surgery 32, 539–44, 2003 5 Renwick A, Scurrell E. Orthogonal bone plate stabilization for limb-sparing surgery. Veterinary and Comparative Orthopaedics and Traumatology 26, 505–9, 2013 6 Picci P, Vanel D, Briccoli A, Talle K, Haakenaasen U, Malaguti C, Monti C, Ferrari C, Bacci G, Saeter G, Alvegard T. Computed tomography of pulmonary metastases from osteosarcoma: the less poor technique. A study of 51 patients with histological correlation. Annals of Oncology 12, 1601–4, 2001

Companion Quarterly: Official Newletter of the Companion Animal Veterinarians Branch of the NZVA | Volume 27 No 4 | December 2016

NZVA COMPANION ANIMAL SOCIETY NEWSLETTER

New Zealand Veterinary Association

Companion Animal Society Volume 27 No 1 March 2016

In This Issue ...

• Management of diabetes mellitus in cats • Diskospondylitis – a casebased review • Parasites in NZ cats and dogs - a survey • Conference report: American Veterinary Dental Forum 2015 • Specialist Profile: Robyn Gear • NZVJ Companion Animal Digest • What is your diagnosis?

VOLUME 27 NO 1 MARCH 2016