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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

Abstract

Objective—To determine whether histopathologic changes are detectable in grossly normal medial menisci from dogs with rupture of the cranial cruciate ligament (CCL).

Design—Case series.

Sample Population—40 medial menisci from dogs with rupture of the CCL and 20 medial menisci from control dogs without stifle joint disease.

Procedure—Data evaluated included age, duration of clinical signs, and whether rupture of the CCL was complete or incomplete. Three groups (n = 20/group) were also compared on the basis of 5 histologic criteria; group-1 menisci appeared grossly normal and were obtained from dogs with naturally occurring rupture of the CCL, group-2 menisci were grossly abnormal and were also obtained from dogs with naturally occurring CCL ruptures, and group-3 menisci were collected at postmortem from dogs without stifle joint disease that were of similar age and weight as dogs in groups 1 and 2.

Results—Group-2 menisci were significantly different from group-1 and -3 menisci in all histologic criteria. Group-1 menisci were significantly different from control menisci in only 1 of the 5 histologic criteria (cartilage differentiation). Dogs that were ≥ 3 years old had significantly more surface cellularity than did dogs that were < 3 years old. A significant difference was not detected between groups 1 and 2 with regard to completeness of rupture.

Conclusions and Clinical Relevance—Histologic changes in meniscal cartilage correlate with gross appearance of the cartilage at time of surgery for rupture of the CCL. On the basis of minimal histologic changes, routine removal of grossly normal menisci does not appear to be warranted. (J Am Vet Med Assoc 2001;218:1281–1284)

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in Journal of the American Veterinary Medical Association