AAFP Conference poster session
A total of seven clinical/research abstracts were accepted for presentation at the inaugural poster session held during the 2016 AAFP Conference in Washington, DC, USA, 3–6 November.
Safety and Efficacy of Zydax, a Disease-Modifying Osteoarthritis Drug for Domestic Cats
Kevin R Scott, Jennifer A Kempker, Meaghan M Wachter, Tennery A Carttar, Brian L Hamm, Karen G Greenwood
Parnell, Overland Park, KS, USA
Email: karen.greenwood@parnell.com
Purpose: Three studies were performed to test laboratory safety and tolerability of Zydax (Parnell; 25 mg/ml), a disease-modifying osteoarthritis drug (DMOAD), in domestic cats. This is a novel treatment for osteoarthritis that is expected to be efficacious and safe for long-term use in cats.
Summary of background/objectives, methods, results and conclusions: Zydax contains a novel compound based upon improvements to pentosan polysulfate (PPS), with a higher sulfation rate and narrower range of molecular weights than other PPS products. Zydax has been shown to protect cartilage explants against IL-1β challenge in an ex vivo model of osteoarthritis and to inhibit ADAMTS4 (aggrecanase 1) when other PPS products had no inhibitory activity.
Zydax is a known treatment for osteoarthritis and is already approved for use in dogs and horses in Australia. Zydax is used extensively off-label in Australia for treatment of osteoarthritis in cats but no data have been presented from controlled laboratory or field studies using Zydax or any other PPS products in cats. Parnell has therefore designed four studies to assess efficacy, safety and tolerability in cats prior to pivotal studies.
The first was a 1 month toleration study in 12 laboratory cats dosed once weekly at a high dose of 25 mg/kg. The second and third were pharmacodynamic evaluations of coagulation parameters following a single dose of Zydax at 25 mg/kg to six cats and a crossover study of a single dose of Zydax at 0, 3, 9 and 15 mg/kg in eight cats. Endpoints were clinical pathology and assessments of the impact of treatment on coagulation parameters; for example, activated partial thromboplastin time (aPTT), fibrinogen, prothrombin time (PT) and buccal mucosal bleeding time scores as well as clinical observations and adverse events. The fourth study is ongoing and is a blinded, randomized, placebo-controlled pilot field efficacy study using subcutaneous injections of 3 mg/kg of Zydax dosed once weekly for 4 weeks. Efficacy endpoints include client-specific outcome measures (CSOMs) and activity monitoring data. The CSOMs are tailored for each cat and owner to identify tasks that are impeded due to osteoarthritis, and assessment is made of whether they improve during the course of the study. Activity monitoring will identify changes in mobility related to relief of osteoarthritic pain.
The safety studies identified no clinically or toxicologically significant effects of Zydax on clinical chemistry or hematology. However, a transient and proportional prolongation of aPTT and PT was noted after dosing; these parameters returned to normal by 18 h in all but the top dose group where two cats remained over reference interval for 48 h. Fibrinogen was within normal limits, except for one cat, which returned to normal by 24 h. A dose-proportional lymphocytosis was also noted and returned to normal by 24 h. A dose-proportional effect on pain was seen during injection, but resolved immediately. Mild erythema and bruising were noted in several cats, but neither adverse event was prolonged and both resolved without intervention.
Overall, Zydax is well tolerated and safe in cats. Pending the outcome of the efficacy trial this product will offer a novel treatment for osteoarthritis in cats.
Primary Adrenal Lymphoma Causing Hypoaldosteronism in a Cat
Jessica F Romine, Angela R Kozicki, Marc S Elie
BluePearl Veterinary Partners, Southfield, MI, USA
Email: jessica.romine@bluepearlvet.com
Purpose: The presentation, clinical findings and progression of disease in a case of primary adrenal lymphoma in a cat are described.
Case description: A 10-year-old, 5.1 kg (11.2 lb), male castrated cat was presented for signs of lethargy and decreased appetite at home after being previously healthy. Serum biochemical analysis identified normal potassium (5.1 mEq/l, reference interval [RI] 3.4–5.6 mEq/l) and severe hyponatremia (123 mEq/l, RI 145–158 mEq/l) with an Na/K ratio of 24 (RI 32–41). Baseline serum cortisol was normal at 2.1 µg/dl, but serum aldosterone was markedly decreased with a pre-adrenocorticotropic hormone stimulation level of 13 pmol/l (RI 194–388 pmol/l) and post-adrenocorticotropic hormone stimulation level of 21 pmol/l (RI 277–721 pmol/l). Hematologic and biochemical analyses were otherwise unremarkable. Abdominal ultrasound revealed bilaterally enlarged adrenal glands with no other abnormalities noted; thoracic radiographs also did not identify any signs of metastasis. Fine-needle aspiration identified lymphoma of the adrenal glands, and PCR for antigen receptor rearrangement was positive for B-cell clonal expansion.
The cat was treated with fludrocortisone and combination cyclophosphamide-vincristine-doxorubicin-prednisolone (CHOP) chemotherapy. Stable disease was achieved for a short period of time following vincristine and cyclophosphamide, but was followed by progressive adrenal enlargement and electrolyte derangements that responded to neither doxorubicin nor adjustments in fludrocortisone dosage. Ultrasonographic metastasis was not identified at any time, and other organ derangements were not noted on hematologic or biochemical analyses. The cat was euthanized 55 days after initial presentation.
To the authors’ knowledge, this is the first report of primary adrenal lymphoma in a cat, with presenting signs initially compatible with hypoadrenocorticism. The patient did not show significant response to chemotherapy, which may indicate a poor prognosis for lymphoma at this site. This is consistent with reports of primary adrenal lymphoma in humans, where it is a rare but well-described disease. Lymphoma should be a differential for cats presenting with adrenal enlargement or clinical signs and biochemical changes consistent with hypoadrenocorticism, and future cases should be reported for comparison to establish trends in presentation and response to therapy.
Accuracy of a Point-of-Care Luteinizing Hormone Test for the Determination of Reproductive Status in Domestic Cats
Matthew R Krecic1, Brian A DiGangi2
1Zoetis US, Florham Park, NJ, USA
2Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA
Email: matthew.krecic@zoetis.com
Purpose: The aim of the study was to determine the performance of a commercially available luteinizing hormone (LH) test for confirming the reproductive status of domestic cats.
Summary of background/objectives, methods, results and conclusions: In the absence of a medical history or physical evidence of surgical sterilization (eg, tattoo or surgical removal of ear tip), definitively determining the reproductive status of adult cats (ie, sexually intact or neutered) may be difficult for veterinarians. Such determination is necessary for the proper diagnosis and treatment of medical conditions, as well as to decide whether or not a cat is a candidate for surgical sterilization. A commercially available, point-of-care test for LH – Witness LH (Zoetis) – has been developed for reproductive management in bitches and queens, yet may also be used to aid in the determination of reproductive status of both.
To determine the performance of a commercially available LH test for confirming the reproductive status of domestic cats, convenience serum samples were collected from sexually intact cats undergoing elective sterilization surgery as well as known previously neutered cats, and analyzed for LH. Test results were compared with the known reproductive status of the cats. Serum samples from 67 sexually intact cats and from 54 previously neutered cats were analyzed.
Overall test sensitivity was 83.6% (95% CI: 72.5–91.5%) and test specificity was 90.7% (95% CI: 79.7–96.9%). Overall test accuracy was 86.8%. Analyzing the results of only female cats (n = 68; 35 sexually intact and 33 neutered) yielded test sensitivity of 81.8% (95% CI: 64.5–93.0%), test specificity of 88.6% (95% CI: 73.3–96.8%) and test accuracy of 85.2%. The sera of four queens unexpectedly yielded positive LH results. Two of the four queens displayed signs of estrus and therefore an LH surge may have yielded the single positive test result for each. Analyzing the results of only male cats (n = 53; 19 sexually intact and 34 neutered) yielded a test sensitivity of 85.3% (95% CI: 68.9–95.1%), a test specificity of 94.7% (95% CI: 74.0–99.9%) and a test accuracy of 88.7%.
The commercially available point-of-care LH test is a useful adjunct to historical and physical examination findings for determination of reproductive status in domestic cats. Test results, especially those that are negative, should be interpreted cautiously in conjunction with clinical and historical findings. Consideration should be given to repeat testing 24 h later for those queens with signs of estrus.
Pharmacokinetics of Intravenous and Subcutaneous Dolasetron and Pharmacodynamics of Subcutaneous Dolasetron in Healthy Cats
Andrea Herndon, Liberty Sieberg, Leigh Davis, Amber Caress, Ryan J Hansen, Luke Wittenburg, Dan L Gustafson, Jessica M Quimby
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA
Email: aherndon@rams.colostate.edu
Purpose: Dolasetron is a 5-HT3 receptor antagonist antiemetic. Pharmacokinetic and pharmacodynamic studies in cats have not been previously performed. The purpose of this study was to evaluate these parameters in healthy research cats.
Summary of background/objectives, methods, results and conclusions: Five healthy research cats with unremarkable complete blood count, serum biochemistry and urinalyses were utilized. Jugular catheters were placed under ketamine/butorphanol sedation. Each cat received 0.8 mg/kg subcutaneous or intravenous dolasetron in a crossover manner. Serum samples were obtained at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36 and 48 h after administration of dolasetron. Serum was separated and frozen prior to analysis. Dolasetron and hydrodolasetron concentrations were measured using liquid chromatography/tandem mass spectrometry. Non-compartmental pharmacokinetic modeling was performed. Pharmacokinetic parameters are summarized in the table below.
Pharmacokinetic parameters for 0.8 mg/kg dolasetron
| Parameter | Intravenous | Subcutaneous |
|---|---|---|
| Cmax (ng/ml) | 140.58 ± 105.97 | 78.3 ± 26.07 |
| Tmax (h) | 0.4 ± 0.14 | 0.63 ± 0.25 |
| T1/2 λ (h) | 4.23 ± 1.78 | 0.63 ± 0.25 |
| AUC INF_obs (h*ng/ml) | 351.06 ± 136.4 | 454.02 ± 173.68 |
Cmax = maximum serum concentration; Tmax = time to maximum serum concentration; T1/2 λ = elimination half-life; AUC INF_obs = area under the curve
No significant differences were found between intravenous and subcutaneous routes of administration. The two routes have equivalent metabolite exposure but with the subcutaneous route there is substantially lower parent drug exposure. Serum levels were not detectable beyond 12 h. These five healthy research cats were administered subcutaneous dolasetron at 0.8 mg/kg or 1.0 mg/kg prior to administration of xylazine. This did not significantly reduce the mean number of emetic events, number of lip licks, time to onset of vomiting or nausea score when compared with untreated cats. No significant differences were found using one-way ANOVA or t-tests. The above pharmacodynamic study suggests dolasetron is not an adequate antiemetic drug for use in feline patients.
Development and Validation of a Scale to Measure Cat Care and Understanding of Cats’ Behavioral Needs: The Cat Care and Needs Scale (CCANS)
Mikel M Delgado1, Gretchen M Reevy2
1University of California at Berkeley, Berkeley, CA, USA
2California State University, East Bay, Hayward, CA, USA
Email: mikeldelgado@berkeley.edu
Purpose: The objective of this study was to develop a scale to measure how well cat guardians meet the welfare needs of their pet cats.
Summary of background/objectives, methods, results and conclusions: Cats are one of the most frequently kept pets. Despite their popularity, many cats suffer from poor welfare and behavioral problems, which impact their quality of life and may affect their retention in an adoptive home. Although many studies have examined the level of attachment people have to their pets, and people report high levels of affection for their pets, we do not know how attachment translates into caretaking and understanding of cats’ needs. In other words, are highly attached cat guardians more likely to take good care of their cats?
We developed the Cat Care and Needs Scale (CCANS) by surveying 505 cat guardians with 59 items examining their caretaking habits and interactions in regards to a pet cat. Items included ‘I or other members of my family play with interactive toys (eg, feather wands, cat dancers, string toys) with my cat at least once per day,’ and ‘My cat is rarely home alone without human company for more than 10 h at a time.’ Items were scored on a 7-point Likert scale. We assessed the psychometric properties of the proposed scale items using item response theory and evaluated the dimensionality of the scale through exploratory factor analysis. From these 59 items, 31 items were retained.
We validated the 31-item CCANS by surveying 1553 cat guardians. From an exploratory factor analysis conducted on this larger data set, four factors related to cat care emerged. The first factor had eight items related to exercise and mental stimulation (Cronbach’s alpha [α] = 0.808). The second factor had nine items related to social interactions, quality time spent with the cat and the guardian’s satisfaction with their cat’s behavior (α = 0.704). The third factor had six items related to daily care, grooming and cleaning up after the cat (α = 0.712). The fourth factor had eight items related to veterinary and professional care, and the guardian’s financial ability to care for the cat (α = 0.666). The overall reliability for the CCANS was α = 0.882.
Of the 1553 cat guardians completing the CCANS, 1377 also completed the Pet Attachment Questionnaire (PAQ), which has two scales measuring anxious and avoidant attachment to a pet. The CCANS was negatively correlated with avoidant attachment (r = 0.44, P <0.001), suggesting that guardians with low scores on avoidant attachment, and thus having a secure relationship with their cat, also had higher scores on the CCANS. There was no relationship between anxious attachment and the CCANS.
We propose the CCANS can be used to assess people’s understanding of behavioral and other care needs of cats and that meeting these needs is related to having a secure relationship with a pet cat. These results are informing our ongoing research examining cat care, pet attachment and human personality factors.
Virilizing Adrenal Tumors: A Rare Cause of Excessive Sex Hormone Production in Cats
Julia P Sumner1, Robert M Dudley2, Sean E Hulsebosch3
1Cornell University, College of Veterinary Medicine, Ithaca, NY, USA
2Medvet Columbus Medical and Cancer Centers for Pets, Worthington, OH, USA
3University of California-Davis, School of Veterinary Medicine, Davis, CA, USA
Email: jsumner@cornell.edu
Purpose: The clinical findings, treatment and outcome of three cats with virilizing adrenocortical tumors are described. There is a paucity of knowledge regarding these tumors in cats, in particular the prognosis for resolution of behavioral signs. The purpose of this study was to report on this condition, and to raise awareness of this important differential for neutered cats displaying overt sexual behavior.
Summary of background/objectives, methods, results and conclusions: Adrenocortical tumors are seldom reported in cats. The most common clinical signs are associated with subsequent hyperaldosteronism or hyperadrenocorticism. Rarely cats with adrenocortical tumors present with behavioral changes secondary to excessive sex hormone production without concurrent hypercortisolemia or hyperaldosteronemia. Differential diagnoses in these cases include retained gonadal tissue (ovarian remnant or retained testicle) or administration of exogenous sex hormones.
A call for cases was placed to the Veterinary Society of Surgical Oncologists, the American College of Veterinary Internal Medicine and the Society of Veterinary Soft Tissue Surgery. Cats were included if they were neutered, showing signs of overt sexual behavior and diagnosed with an adrenocortical tumor. Cats were excluded if they had concurrent signs of hyperadrenocorticism or hyperaldosteronism. Data were retrieved on clinical presentation, diagnostics, treatment and outcome.
Three domestic shorthair cats matched the inclusion criteria: a 4-year-old neutered female (case 1), an 11-year-old neutered male (case 2) and a 6-year-old neutered male (case 3). All cats were neutered at a young age. Presenting complaints included urine spraying, aggression and sexualized behavior (mounting, howling and lordosis). The female cat had estradiol levels of an intact female: 33.02 pg/ml (reference interval <25 pg/ml neutered female). The male cats had penile spines (Figure 1) and testosterone levels of intact males: 0.15 ng/ml (case 2) and 4.0 ng/ml (case 3) (reference interval <0.01 ng/ml castrated male).
Figure 1.
Penile spines were present in this cat despite early neutering
All cats underwent surgical adrenalectomy. Adrenal tumors (two right, one left) ranged in size from 0.8 cm (case 1) to 3.3 cm (case 2). The contralateral adrenal gland in all cases had normal dimensions. Histopathology was consistent with an adrenocortical carcinoma in cases 2 and 3, and an adenoma in case 1. Behavioral signs resolved following adrenalectomy in all cases, within 3–5 days (case 3) to 3 months (case 2). Case 2 was hypocortisolemic following surgery and required 3 months of tapering glucocorticoid supplementation. Case 1 had recurrence of elevated hormone levels and possible regrowth of the tumor (as seen on abdominal ultrasound) at 16 months postoperatively. Case 2 was alive and doing well at the time of reporting (11 months postoperatively). Case 3 was euthanized at 15 months postoperatively for a presumptive gastric mass.
One of the cats had significant postoperative cortisol suppression, likely due to the suppressive effects of high androgen levels on the contralateral adrenal gland. Glucocorticoid supplementation in the perioperative period and close monitoring of cortisol suppression should be considered in these cats.
It appears that with removal of the tumor, the prognosis is good for resolution of behavioral signs. More cases are required to fully understand survival statistics in these cats.
Evaluation of the Efficacy of a New Pheromone Product vs Placebo in the Management of Feline Aggression in Multi-Cat Households
Theresa L DePorter1, Aurélie Lopez2, Elodie Ollivier2
1Oakland Veterinary Referral Services, Behavioral Medicine, Bloomfield Hills, MI, USA
2Ceva Santé Animale, Libourne, France
Email: theresadax@aol.com
Purpose: Aggression and social tension among housemate cats is common and puts cats at risk of injury or relinquishment.
Summary of background/objectives, methods, results and conclusions: In this pilot study, a new pheromone product by Ceva Santé Animale was evaluated for efficacy to reduce aggression between housemate cats by randomized double-blind placebo-controlled trial in 45 multi-cat households (pheromone [n = 20], placebo [n = 25]) that reported aggression for at least 2 weeks (range 17–3931 days, average = 822 days). Each household included two to five cats. Volunteers attended a group meeting on day -7 (D-7) and the veterinary behaviorist described behaviors to be monitored for 7 weeks using the Oakland Feline Social Interaction Scale (OFSIS), which assessed the frequency and intensity of 12 aggressive interactions (eg, bite, swat, stare, block, hiss or scream). Participants were provided directions for safely handling aggressive events. Punishment techniques were discouraged. Plug-in diffusers with the new pheromone product or placebo were utilized from D0 to D28. Participants completed a daily diary of aggressive events and a weekly OFSIS.
The OFSIS scores (possible 0 to 360) were similar at baseline (mean ± SE pheromone, 105.1 ± 11.1 vs placebo, 109.6 ± 8.5 at D-7, and 83.4 ± 10.4 vs 83.5 ± 8.3 at D0). The pheromone group showed a lower mean OFSIS score than placebo at D7 (47.8 ± 6.3 vs 61.8 ± 7.7), D14 (30.8 ± 4.9 vs 48.0 ± 8.3), D21 (21.8 ± 3.9 vs 40.7 ± 7.4) and D28 (33.2 ± 9.7 vs 47.0 ± 9.7), which continued post-treatment at D35 (32.5 ± 8.0 vs 55.0 ± 10.5) and D42 (31.2 ± 8.1 vs 59.0 ± 9.0). (Repeated measures ANOVA F[1, 43] = 4.34, P = 0.0431.)
This study suggests that this new pheromone is a promising treatment for the management of aggression between housemate cats.
