Cryptosporidium infection after renal transplantation in an endemic area.

BACKGROUND: Cryptosporidium is one of the common causes of infective diarrhea in post-transplant patients in endemic areas. However, data are limited on Cryptosporidium infection in recipients of solid organ transplantation. The aim of this study was to determine the incidence, disease manifestation, management, and outcome of Cryptosporidium infection in living-donor renal transplant recipients (RTR). METHODS: We performed a detailed retrospective review of the data on all RTR who had diarrheal illness requiring evaluation and hospitalization, and Cryptosporidium infection. RESULTS: During the study period, 119/1235 (8.98%) RTR developed diarrhea, and Cryptosporidium was found in 34/119 (28.5%). Nine of 680 (1.3%) patients were on a cyclosporine (CSA)-based regimen, and 25/643 (3.8%) patients were on a tacrolimus (Tac)-based regimen. The relative risk of developing Cryptosporidium infection was lower on the CSA-based regimen, compared with the Tac-based regimen (odds ratio [OR]: 0.35, 95% confidence interval [CI]: 0.17-0.72, P = 0.003). Twelve of the 34 patients had acute graft dysfunction, mainly caused by combined Tac toxicity and dehydration. Mean serum creatinine and trough Tac level were 2.04 ± 0.65 mg/dL and 8.24 ± 1.19 ng/dL, respectively. Nitazoxanide alone was used in 13 patients, and nitazoxanide in combination with fluoroquinolone in 21 patients, with duration of treatment ranging from 16 to 60 days. Tac was changed to CSA in 8/11 patients. The clearance of cysts and response to nitazoxanide alone were significantly lower, compared with combination therapy (61.53% vs. 95.23%, P = 0.01, 38.46 vs. 85.71%, P = 0.004, respectively). The OR for cyst clearance and response was also significantly lower with nitazoxanide alone, in comparison with combination therapy (OR: 0.65, 95% CI: 0.34-0.92, P = 0.01, OR: 0.45, 95% CI: 0.21-0.81, respectively). Four (16%) of 24 patients with response had relapse. CONCLUSION: Patients with Tac and mycophenolate mofetil combination therapy had a significantly high risk of Cryptosporidium infection. Cryptosporidial infection may require prolonged nitazoxanide therapy, either alone or in combination, with or without reduction in immunosuppression.

In vitro inhibition of estrogen sulfoconjugation by some 2- and 4-substituted estra-1,3,5(10)-trien-17 beta-ols1a.

Hormone-responsive rat and human mammary tumor, unlike normal epithelium, actively sulfoconjugates estrogens. The title compounds (9-11) were synthesized in search of specific inhibitors of estrogen sulfotransferase as a possible means of developing effective chemotherapeutic agents for treatment of hormone-dependent human mammary cancer. 4-Nitroestrone 3-triflate (7a) was converted to the corresponding estradiol derivative (8a) in 93% yield by reduction with NaBH4 under phase-transfer conditions. Catalytic reduction (10% Pd/C) of the latter gave 4-aminoestra-1,3,5(10)-trien-17 beta-ol (9a) in 77% yield. These same reactions were applied consecutively to 4-nitroestrone 3-nonaflate (7b) to give 9a in 56% overall yield. The amino steroid (9a) was converted to 4-fluoroestra-1,3,5(10)-trien-17 beta-ol (10a) via a Balz-Schiemann reaction, in 17% overall yield. Successive NaBH4 and (10% Pd/C) catalytic reductions of 4-fluoroestrone 3-O-(1-phenyl-1H-tetrazol-5-yl) ether (2b) provided a less satisfactory route to 10a. MCPBA oxidation of 9a gave 4-nitroestra-1,3,5(10)-trien-17 beta-ol (11a) in 56% yield. The same series of reactions were applied to 2-nitroestrone 3-triflate (7c) to give 2-amino- (9b), 2-fluoro- (10b), and 2-nitro- (11b) estra-1,3,5(10)-trien-17-ols in comparable yields. Substitution in the A ring results in improved inhibition of porcine endometrial sulfotransferase sulfoconjugation of estradiol relative to estra-1,3,5(10)-trien-17 beta-ol (4a). Moreover, electronegative substitution at C-4 of 4a is more effective than at C-2. In particular, the Ki (2.43 +/- 0.16 microM) of 11a is sixfold smaller than that of the unsubstituted steroid (4a).

Some pharmacological actions of the essential oil of Blumea membranacea.

The essential oil obtained from the plant Blumea membranacea produced a marked and long lasting fall in blood pressure in anaesthetized dogs. The oil exerted a direct depressant action on frog heart and spasmolytic effect on rabbit ileum. It also depressed the conditioned avoidance response, adversely affected rotarod performance and potentiated the pentobarbitone induced hypnosis in rats.

Pyrazinamide induced thrombocytopenia.

A case of thrombocytopenia caused by pyrazinamide is reported in a patient receiving chemotherapy for pulmonary tuberculosis.