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in Journal of the American Veterinary Medical Association

Abstract

Objective—To compare the in vitro imMunosuppressive effects of cyclosporine and 4 novel immunosuppressive drugs on lymphocytes in whole blood collected from healthy cats.

Sample Population—Whole blood samples collected from 10 healthy adult domestic shorthair cats.

Procedure—Mitogen-stimulated lymphocyte proliferation in whole blood incubated with and without various concentrations of cyclosporine, tacrolimus, sirolimus, mycophenolic acid (MPA), or A771726 was measured by use of [3H]thymidine incorporation. Drug concentrations that resulted in a 50% inhibition of mitogen-induced proliferation (IC50) were calculated. Lymphocyte viability was determined by use of the trypan blue dye exclusion method.

Results—An obvious dose-response relationship for the antiproliferative effects of each drug was detected. Mean IC50 determined with concanavalin A was 46 nMfor cyclosporine, 9 nMfor tacrolimus, 12 nM for sirolimus, 16 nM for MPA, and 30 mM for A771726, whereas with pokeweed mitogen, mean IC50 was 33 nM for cyclosporine, 5 nMfor tacrolimus, 15 nM for sirolimus, 14 nM for mycophenolic acid, and 25 mM for A771726. Mitogen-stimulated and nonstimulated lymphocytes remained viable, regardless of drug evaluated.

Conclusions and Clinical Relevance—Tacrolimus, sirolimus, MPA, and A771726 inhibited in vitro mitogen- stimulated proliferation of feline lymphocytes in a dose-dependent manner. These novel immunosuppressive drugs may be useful for management of immune-mediated inflamMatory diseases and prevention and treatment of rejection in cats that undergo organ transplantation. (Am J Vet Res 2000;61: 906–909)

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in American Journal of Veterinary Research

Abstract

Objective—To use in vitro assays to evaluate the effects of a novel immunosuppressive agent, FTY720, on biological functions (migration, phagocytosis, and production of reactive-oxygen species [ROS]) of feline peripheral neutrophils and determine the cytotoxic effects of FTY720 on feline peripheral neutrophils.

Sample Population—Peripheral neutrophils obtained from 8 healthy cats.

Procedure—Peripheral neutrophils were isolated from blood samples obtained from the 8 cats and exposed to the phosphorylated form of FTY720 (FTY720-P). A fluorescence-based in vitro evaluation of migration was performed. Phagocytosis of microbes and production of ROS were evaluated by use of a 2-color flow cytometry system. Samples of whole blood obtained from the cats were incubated with various concentrations of FTY720-P, fluorescein-labeled Staphylococcus aureus, and dihydroethidium. Cytotoxic effects were evaluated by use of propidium iodide staining.

Results—Addition of FTY720-P caused a slight non-significant decrease in phagocytosis and production of ROS by feline peripheral neutrophils. Migration activity of feline peripheral neutrophils was significantly increased by the addition of FTY720-P. Addition of FTY720-P at concentrations considered for clinical use did not increase the death rate of feline peripheral neutrophils.

Conclusions and Clinical Relevance—FTY720 does not inhibit critical functions of feline peripheral neutrophils in vitro.

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in American Journal of Veterinary Research

Abstract

Objective—To determine long-term outcome of cats treated conservatively or surgically for peritoneopericardial diaphragmatic hernia (PPDH).

Design—Retrospective study.

Animals—67 cats with PPDH.

Procedure—Medical records of cats with a diagnosis of PPDH made from 1987 through 2002 were reviewed. Information regarding long-term outcome was obtained from owners.

Results—Prevalences of PPDH in domestic longhair and Himalayan cats were significantly greater and prevalence of PPDH in domestic shorthair cats was significantly lower than prevalence of PPDH in the hospital cat population over the 15-year study period. Historical problems most commonly related to the respiratory and gastrointestinal tracts. Peritoneopericardial diaphragmatic hernia was the primary diagnosis in 40 cats and an incidental finding in 27 cats. One cat died prior to arrival at the Veterinary Medical Teaching Hospital. Thirty-seven of 66 cats were treated surgically, and 29 were treated conservatively. The postoperative mortality rate was 14%. Postoperative complications developed in 29 of 37 cats, the most common of which was hyperthermia. Two of 22 conservatively treated cats had progression of clinical signs necessitating surgical intervention or resulting in death. Owner satisfaction with treatment choice and long-term outcome was rated as very satisfied by 88% of owners of surgically treated cats and 68% of owners of conservatively treated cats.

Conclusions and Clinical Relevance—Cats with overt clinical signs attributable to PPDH are good candidates for surgical herniorrhaphy. Postoperative complications may develop but are generally minor and self-limiting. Long-term outcome of cats treated conservatively or surgically was rated as very good by most owners. (J Am Vet Med Assoc 2004;224:728–732)

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To document the signalment; history; clinical signs; clinicopathologic, diagnostic imaging, and surgical findings; perioperative complications; and long-term clinical results of ameroid ring constrictor (ARC) placement on single extrahepatic portosystemic shunts (PSS) in cats.

Design—Retrospective study.

Animals—23 cats treated with an ARC on a single extrahepatic PSS.

Procedure—An ARC was placed surgically around the PSS. Portal pressure was measured prior to ARC placement, with complete temporary PSS occlusion, and after ARC placement. Cats were scheduled for recheck transcolonic portal scintigraphy 8 to 10 weeks after surgery. Follow-up information was obtained by telephone interview with the owners.

Results—An ARC was successfully placed in 22 of 23 cats. Intraoperative complications, consisting of PSS hemorrhage, occurred in 2 cats. Mean (± SD) portal pressure (n = 15) was 6.7 ± 2.9 mm Hg before PSS manipulation, 18.6 ± 7.7 mm Hg with complete temporary PSS occlusion, and 6.9 ± 2.7 mm Hg after ARC placement. Postoperative complications developed in 77% (17 of 22) of cats after ARC placement, and included central blindness, hyperthermia, frantic behavior, and generalized motor seizures. Perioperative mortality rate was 4.3% (1 of 23). Persistent shunting was identified in 8 of 14 cats. Overall, 75% (15 of 20) of cats had an excellent longterm outcome.

Conclusions and Clinical Relevance—Placement of an ARC on single extrahepatic PSS in cats resulted in low surgical complication and perioperative mortality rates, but most cats did have substantial postoperative complications. Persistent shunting was common, although many cats with persistent shunting were clinically normal. (J Am Vet Med Assoc 2002;220: 1341–1347)

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine outcome of renal transplantation in cats with renal failure associated with calcium oxalate urolithiasis.

Design—Retrospective case series.

Animals—19 cats.

Procedure—Medical records were reviewed for evaluation of signalment, preoperative clinical signs, physical examination results, dietary history, clinicopathologic data, abdominal imaging, postoperative diet, complications, and long-term outcome.

Results—The domestic shorthair was the most common breed represented. There were 13 spayed females and 7 castrated males. Mean age was 6.8 years. Clinical signs included weight loss, lethargy, vomiting, anorexia, polyuria, and polydipsia. Before surgery, cats received commercially available canned or dry food (n = 10), a prescription renal failure diet (5), a commercial diet to manage struvite crystalluria (1), or an unknown diet (3). Seventeen cats were anemic. All cats were azotemic. Hypercalcemia was detected in 7 cats. Abdominal imaging revealed nephrolithiasis, ureterolithiasis, or both in all cats. Median duration of survival of all cats was 605 days. Eight cats were alive 282 to 2,005 days (median, 1,305 days) after surgery. Eleven cats died 2 to 1,197 days (median, 300 days) after surgery. Five cats formed calculi in their allograft (120 to 665 days). Two of the 5 cats that formed calculi were hypercalcemic. Four of the 5 cats died following complications associated with formation of calculi.

Conclusions and Clinical Relevance—Renal transplantation appears to be a viable option for cats in renal failure secondary to calcium oxalate urolithiasis. In addition to reported complications in renal transplant recipients, formation of calculi within the allograft may also occur.

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate long-term clinical outcome in dogs with upper airway obstruction treated with laryngeal web resection and mucosal apposition.

Design—Retrospective case series.

Animals—15 client-owned dogs with laryngeal web formation.

Procedures—Medical records of dogs with laryngeal webs treated with a single procedure of web resection with mucosal apposition by use of a ventral laryngotomy were reviewed. Signalment, history, clinical signs, intraoperative complications, postoperative complications, and hospitalization time were recorded. Owners were interviewed 6 months to 6 years after surgery.

Results—Most dogs had a history of oral ventriculocordectomy. Duration of clinical signs ranged from 3 months to 3 years. The most common clinical sign reported was exercise intolerance. Postoperative complications were observed in 4 dogs. Follow-up information was available in 10 dogs, and clinical outcome was classified as excellent in 7 and good in 3.

Conclusions and Clinical Relevance—A single surgical procedure of web resection with mucosal apposition for the treatment of laryngeal web formation in dogs resulted in low morbidity and was associated with a good to excellent outcome.

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To describe pharmacokinetics of multidose oral administration of tacrolimus in healthy cats and evaluate the efficacy of tacrolimus in the prevention of allograft rejection in cats with renal transplants.

Animals—6 healthy research cats.

Procedure—Cats received tacrolimus (0.375 mg/kg, PO, q 12 h) for 14 days. Blood tacrolimus concentrations were measured by a high performance liquid chromatography-mass spectrometry assay. Each cat received an immunogenically mismatched renal allograft and native kidney nephrectomy. Tacrolimus dosage was modified to maintain a target blood concentration of 5 to 10 ng/mL. Cats were euthanatized if plasma creatinine concentration exceeded 7 mg/dL, body weight loss exceeded 20%, or on day 50 after surgery. Kaplan-Meier survival curves were plotted for 6 cats treated with tacrolimus and for 8 cats with renal transplants that did not receive immunosuppressive treatment.

Results—Mean (± SD) values of elimination half-life, time to maximum concentration, maximum blood concentration, and area under the concentration versus time curve from the last dose of tacrolimus to 12 hours later were 20.5 ± 9.8 hours, 0.77 ± 0.37 hours, 27.5 ± 31.8 ng/mL, and 161 ± 168 hours × ng/mL, respectively. Tacrolimus treated cats survived longer (median, 44 days; range, 24 to 52 days) than untreated cats (median, 23 days; range, 8 to 34 days). On histologic evaluation, 3 cats had evidence of acute-active rejection, 1 cat had necrotizing vasculitis, and 2 cats euthanatized at study termination had normal appearing allografts.

Conclusions and Clinical Relevance—Tacrolimus may be an effective immunosuppressive agent for renal transplantation in cats. (Am J Vet Res 2003;64:926–934)

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in American Journal of Veterinary Research