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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)

Full access
in American Journal of Veterinary Research

Abstract

Objective

To evaluate the disposition of fentanyl after IV and transdermal administrations. The hypothesis was that transdermal administration of fentanyl would result in a measurable plasma opioid concentration.

Design

Each dog received 2 treatments in a randomized, crossover design.

Animals

6 clinically normal Beagles.

Procedure

2 treatments consisting of IV fentanyl (50 μg/kg of body weight) and transdermal fentanyl (50 μg/h) administrations. Plasma fentanyl concentrations were measured at fixed times, and pharmacokinetic values were calculated.

Results

Intravenous pharmacokinetics of fentanyl was similar to those previously described in dogs and provided the distribution and clearance data necessary to calculate the rate of absorption of the transdermally administered opioid. The transdermal fentanyl patch produced average steady-state concentrations of 1.6 ng/ml. The actual rate of delivery of transdermal fentanyl was 35.7 (range, 13.7 to 49.8) μg/h, which represented 71.48% (range, 27.45 to 99.56%) of the theoretical rate of delivery. The mean elimination half-life of fentanyl after patch removal was 1.39 hours.

Conclusions

Transdermally administered fentanyl resulted in fairly constant plasma concentrations, in the range generally considered to be analgesic, from 24 to 72 hours after application of the patch. The rate of drug delivery was less than expected, and there was substantial individual variation.

Clinical Relevance

Transdermally administered fentanyl has the potential to be a clinically useful analgesic regimen in dogs, and further evaluation of its analgesic actions and potential side effects is warranted. (Am J Vet Res 1996; 57:715–719)

Free access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

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)

Full access
in Journal of the American Veterinary Medical Association

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.

Full access
in American Journal of Veterinary Research

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)

Full access
in Journal of the American Veterinary Medical Association

Objective—

To evaluate vestibulovaginal stenosis in dogs.

Design—

Retrospective study.

Animals—

18 dogs with vestibulovaginal stenosis diagnosed between January 1987 and June 1995.

Procedure—

Signalment, results of physical examination, and diagnostic testing, treatment, and outcome were analyzed.

Results—

Mean age at initial examination was 4.6 years. Problems reported by the owners included signs of chronic urinary tract infection (6 dogs), urinary incontinence (4), failure to mate (4), signs of chronic vaginitis (2), and inappropriate urination (1). One dog did not have evidence of a clinical problem. Vestibulovaginal stenosis was detected by means of digital vaginal examination (18/18 dogs), vaginoscopy (17/17 dogs), and positive-contrast vaginography (9/10 dogs). Bacteria were isolated from the urine of 11 of 15 dogs. Twelve of 18 dogs were treated. Manual dilation (4 dogs) and T-shaped vaginoplasty (4) were less successful than vaginectomy (2) or resection of the stenotic area (3). Four of 6 dogs with signs of recurrent urinary tract infection underwent surgical correction, and none of these dogs subsequently had urinary tract infection. Three of 4 dogs with urinary incontinence responded to medical or surgical treatment for sphincter incompetence or for ectopic ureters.

Clinical Implications—

Surgical correction of vestibulovaginal stenosis is indicated in dogs that have mating difficulties or signs of recurrent urinary tract infection or chronic vaginitis, but stenosis is probably an incidental finding in most dogs with urinary incontinence. Vaginectomy and vaginal resection and anastomosis are the preferred surgical options. (J Am Vet Med Assoc 1996;209:1889–1893)

Free access
in Journal of the American Veterinary Medical Association
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.

Full access
in Journal of the American Veterinary Medical Association