Biomedical subjects
Publications and source records attributed to W Donovan.
Skin flaps were raised in 83 rats. In 58 of them the skin cycle was determined before the flap was raised, and in 25 of them the flap was raised without regard to cycle. There was no significant difference in the surviving length of flaps raised in early anagen, midanagen, telogen, or in randomly selected animals.
The blood supply of random skin flaps in the pig is mainly in a microvascular plexus in the deeper layer of the dermis. However, there is vasculature in both the dermis and the subcutaneous fat, with good collaterals between the two systems.
Tissue gas levels were measured in experimental skin flaps in rabbits, rats, and pigs. Devascularization of the flaps led to a fall in PO2 and a rise in PCO2 levels. Application of DMSO to ischemic rabbit flaps led to a fall in PCO2, DMSO and H2O2 led to a rise in PO2, an effect that lasted up to 90 min. Neither drug had an effect on the gas levels of flaps in either rats or pigs.
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Ketoconazole was given to 18 patients with coccidioidomycosis. Fourteen had received prior antifungal chemotherapy with amphotericin B, miconazole, or both. Ten patients had pulmonary disease, two had meningitis, and six had extrameningeal disseminated disease. The initial dose of ketoconazole was 200 mg per day; it was later increased to 400 mg per day for some patients. All strains of Coccididioides immitis tested were sensitive to ketoconazole. Approximately 2-4 hr after an oral dose of 200 mg of ketoconazole, levels of the drug in blood peaked at approximately 2 micrograms/ml. Higher concentrations in blood were achieved with a 400-mg dose. Improvement was measured by physical examination, conversion of cultures previously positive for C. immitis to negative, decrease in erythrocyte sedimentation rate by 50%, and decrease in titer of complement fixation antibody by two or more dilutions. One patient died after one week of treatment with ketoconazole and could not be evaluated; two other patients with coccidioidal meningitis could not be evaluated. Six of nine patients with pulmonary disease showed radiographic improvement, and their sputum cultures, which had been positive, became negative. Four of the six patients with disseminated disease improved. There were few adverse reactions to ketoconazole, which can be safely administered for prolonged periods to patients with coccidioidomycosis. These findings suggest that ketoconazole may be effective for treatment of this disease and indicate that trials comparing the efficacy of ketoconazole with that of amphotericin B are warranted.
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