Pathologic studies of acute rejection of mismatched feline musculocutaneous flaps. Effect of cyclosporine and prednisolone.

The gracilis musculocutaneous flap was developed as an allograft model to study acute rejection and immunosuppression in the cat. Twelve adult cats received a MLC incompatible flap. Six of the cats received cyclosporine oral solution and prednisolone (0.5 mg/kg/24 hr) for 100 days and six cats were not treated. Trough whole-blood levels of cyclosporine in the treatment group were maintained at approximately 750 ng/ml for 70 days, then 500 ng/ml for the remaining 30 days. Three flaps failed due to technical problems; 5 flaps were studied in the treatment group and 4 in the untreated group. All 5 flaps in the treatment group survived the 100 day treatment period and were rejected 30 +/- 26 days following cessation of treatment. Prior to discontinuation of treatment, with the exception of one cat, inflammatory changes associated with rejection were not observed in biopsy specimen. The flaps in the untreated group survived 13 +/- 1.5 days. Histopathologic examination of the flaps revealed little difference in the appearance of acute rejection and rejection after cessation of therapy. The most prominent lesion was a vasculitis with extensive perivascular lymphohistocytic inflammation. The lymphoid infiltrates consisted predominantly of T cells of both major classes (CD4 and CD8). Full-thickness epidermal necrosis and subsequent bacterial invasion followed vascular compromise.

Mizoribine serum levels associated with enterotoxicity in the dog.

To prevent or minimize mizoribine enterotoxicity in organ transplant recipients and to differentiate mizoribine enterotoxicity from other causes of enteritis, serum levels of mizoribine that produced subclinical and clinical signs of enterotoxicity were determined in the dog. When mizoribine was administered orally at 12-hr intervals, half the dogs studied showed clinical evidence of gastrointestinal disturbances (vomiting, diarrhea, and anorexia) without histopathologic signs of enterotoxicity. Using a 24-hr oral-dose schedule, clinical signs of gastrointestinal disturbances and histopathologic evidence (mucosal degeneration, crypt degeneration, and necrosis) of enterotoxicity were encountered when the mean 12-hr mizoribine serum level was 0.97 +/- 0.4 microgram/ml or greater. Histopathologic signs of enterotoxicity with repeated positive fecal occult blood assays and without clinical signs of gastrointestinal disturbances occurred when the mean 12-hr serum level was 0.53 +/- 0.17 microgram/ml or greater. Oral administration of cyclosporine did not exacerbate mizoribine enterotoxicity in the dog when administered with mizoribine at a dose that produced histopathologic signs of enterotoxicity.