Background: The circadian variation of clinical pharmacokinetics of tacrolimus in kidney transplant recipients receiving continuous intravenous administration has not been clarified. The aim of this study was to evaluate the circadian variation of this drug in continuous intravenous administration, with regard to the dosing scheme for conversion from intravenous to oral therapy. Methods:The blood concentration-time curve was studied in 10 living-related kidney transplant recipients, aged 18-51 years (mean, 36.5 years), 1 day before operation for preoperative oral administration, the third postoperative day for continuous intravenous administration and the sixth postoperative day at the conversion from intravenous to oral therapy. Results: Although the total body clearance of daytime was slightly higher than that of night-time, the intravenous tacrolimus infusion maintained an adequate therapeutic blood concentration for 24 h. There were significant differences between the preoperative and the postoperative state in the area under the curve, total body clearance and bioavailability for the oral administration. The mean absolute bioavailability was 17.7% in preoperative and 11.1% in postoperative state, respectively and a large interindividual variation was confirmed in this parameter, which was 7.0-27.2% for preoperative and 6.4-22.0% for postoperative area under the curve, respectively. Conclusion: This study proposes that intravenous administration is a safe and appropriate method to achieve the required blood concentration in patients with various tacrolimus metabolism in the early post-transplant period. As the oral tacrolimus absorption was found to be variable between preoperative and postoperative states in identical patients, the conversion dosage cannot be calculated from preoperative oral or postoperative intravenous pharmacokinetics. Frequent blood concentration monitoring is needed to ensure safe treatment.

A 62-year-old male with slight fever, anorexia and easy fatigability was found to have a tumor in the left adrenal gland by computed tomogram of abdomen. Further study of angiogram suggesting neoplasm of the left adrenal gland, eventually he was underwent surgical extirpation. Histological study, combined with immunohistochemical staining, revealed that the tumor measuring 8 x 4 x 6 cm was an angiosarcoma. The patient died of pulmonary dysfunction 42 days after the operation. Autopsy was not done. In the literature, 7 cases of adrenal angiosarcoma have been reported; ours is the 8th case.

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There is epidemiological evidence that vitamin D may be an important determinant of prostate cancer risk. Several studies have shown recently that inherited polymorphisms in the 3 0 -untranslated region (3 0 UTR) of the vitamin D receptor gene may be linked with prostate cancer risk and aggressive prostate cancer. This study analysed the vitamin D receptor gene polymorphisms in the 3 0 UTR, characterized by restriction enzymes BsmI, ApaI and TaqI, in Japanese prostate cancer patients to test whether the three polymorphisms are associated with risk of prostate cancer in the Japanese population, where the frequency of prostate cancer is much lower than in Western countries. MethodWe studied 222 prostate cancer patients and 209 benign prostatic hyperplasia patients, 128 male controls aged over 60 y who did not show evidence of prostate cancer or benign prostatic hyperplasia and 198 female controls. A polymerase chain reaction (PCR)-restriction fragment length polymorphism method was used to determine the three Bsml, ApaI and TaqIVDR gene polymorphisms. ResultsAs for the BsmI polymorphism, heterozygosity or homozygosity for the absence of the BsmI restriction site in the 3 0 UTR was associated with one-third of the risk of prostate cancer (P`0.0001; OR 3.44; 95% CI 2.76±4.29) and half the risk of benign prostatic hyperplasia (P`0.0005; OR 2.27; 95% CI 1.80±2.86), compared with the male controls. Furthermore, signi®cant differences in BsmI allelic frequency and genotype were found between the female and the male controls. The TaqI and ApaI polymorphisms did not show any signi®cant association with either prostate cancer or benign prostatic hyperplasia. ConclusionThe BsmI polymorphism in the vitamin D receptor gene may play a signi®cant role in protecting against prostate cancer and benign hyperplasia. The presence of at lest one allele that is absent from the BsmI restriction site may be signi®cantly associated with protection against prostate cancer and benign prostatic hyperplasia. Because of the racial difference in the strength of the linkage disequilibrium between the three polymorphisms, further studies may be required to apply the present results to other races.

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