Early ultrastructural effects of gentamicin cochleotoxicity

Ultrastructural changes in the cochlear hair cells during the early stages of gentamicin intoxication were investigated after tri-aldehyde primary fixation and OSO4/K4Ru(CN)6 post-fixation. In cochleas treated for 5, 10 and 15 days with gentamicin the individual outer hair cells (OHC1, OHC2 and OHC3) were randomly affected. Degeneration of the inner hair cells was not observed at this stage. Ultrastructurally, the earliest identifiable changes were an increase in lysosomes, proliferation of the endoplasmic reticulum, and formation of Hensen's bodies. This was followed by dilatation of the endoplasmic reticulum and the nuclear envelope, giving rise to extensive cytoplasmic vacuolation. These results demonstrate that gentamicin-induced changes primarily involve the cell's synthetic apparatus. All further intracellular changes occur at a much later stage and are therefore to be considered secondary events.     

A 3 year retrospective review of intrauterine insemination, using cryopreserved donor spermatozoa and cycle monitoring by urinary or serum luteinizing hormone measurements

Insemination with donor spermatozoa is an integral part of infertility treatment. For the last 3 years in our unit, intrauterine insemination with donor spermatozoa (IUID) has been used in preference to vaginal insemination. In this retrospective study, patients were offered an initial course of five single intrauterine inseminations with cryopreserved donor spermatozoa and treatment was then reviewed. A total of 389 patients received 1465 inseminations. In all, 1119 cycles were monitored using luteinizing hormone serum analyses and 346 cycles using the urine home test kits. The clinical pregnancy rate per insemination for the cycles monitored by the serum assay was 18.0% (202/1119) compared with the urine cycles (13.7%, 46/346) (P <05). The pregnancy loss rate was not significantly different (14.4%, 29/202 and 21.7%, 10/46) (serum and urine cycles respectively). The viable clinical pregnancy rate was significantly higher (P <03) for the serum cycles than for the cycles using the urinary monitoring (15.5%, 173/1119 and 10.4%, 36/346 respectively). The cycles monitored by serum assay had a significantly higher cumulative viable clinical pregnancy rate (P <0001) of 70.2% after nine inseminations compared with the urine monitored cycles of 54.8%. The majority of patients opted for the serum cycles, with a minority self-selecting the urine cycles mainly for travelling convenience. The explanation for the significant differences between the viable clinical pregnancy rates per insemination and the cumulative viable clinical pregnancy rates may be due to the sensitivity of the urine home test kit or the patients' interpretation of the result.      

Hermansky-Pudlak syndrome type 4 in a patient from Sri Lanka with pulmonary fibrosis

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a platelet storage pool deficiency. Some patients also develop fatal pulmonary fibrosis and some have granulomatous colitis. Six human genes HPS1, ADB3A, HPS3, HPS4, HPS5, and HPS6 have been identified as cause of the six known subtypes of HPS. While there exist nearly 500 Puerto Rican and non-Puerto Rican HPS-1 patients, very few HPS-4 patients have been reported, and most of these have not been described in detail. We now delineate the clinical characteristics of an HPS-4 patient homozygous for a novel HPS-4 mutation, P685delC. The patient, the first individual with HPS reported from Sri Lanka, had severe pulmonary fibrosis, typical of HPS-1 disease, without granulomatous colitis. We conclude that pulmonary fibrosis occurs as part of HPS-4 and that HPS should be considered in all ethnic groups.     

脾内血管的应用解剖学研究盐酸喹那普利治疗原发性高血压的临床应用观察

目的　探讨盐酸喹那普利 (QuinaprilHydrochloride)治疗轻、中度原发性高血压的有效性和安全性。方法　全国 6家医院参加的一项多中心、随机、双盲、平行组间对照研究。结果　 113例原发性高血压病人治疗 8周后 ,总有效率达 85 84% ,统计学有显著性差异。盐酸喹那普利副反应较轻 ,对肾脏、肝脏、造血系统和心脏未见有害作用。结论　盐酸喹那普利是一种安全、疗效好、副反应小的治疗轻、中度原发性高血压的有效药物。     

Isolation,purification, and biological activity of mono- and dihydroxylated paclitaxel metabolites from human feces

Three metabolites of the cytotoxic drug paclitaxel (Taxol) were isolated and purified from the feces of cancer patients receiving the agent as an intravenous infusion. The procedures involved sample homogenization in water followed by liquid-liquid extraction with diethyl ether and high-performance liquid chromatography (HPLC). Approximately 1–3.5 mg of each metabolite was obtained from 100 g of feces. As judged from the chromatographic traces of analytical HPLC with ultraviolet (UV) detection at 227 nm, the purity of each compound was >97%. On-line photodiode-array detection demonstrated that the UV spectrum of the isolated compounds closely resembles that of the parent drug. Mass spectrometry provided evidence that these metabolites are mono- and dihydroxy-substituted derivatives, namely, 6-hydroxypaclitaxel, 3-p-hydroxypaclitaxel, and 6,3-p-dihydroxypaclitaxel. The two 6-hydroxy-substituted metabolites were shown to have lost their cytotoxicity in in vitro clonogenic assays using the A2780 human ovarian carcinoma and the CC531 rat colon-carcinoma tumor cell lines. In addition, the metabolites showed reduced myelotoxic effects as compared with paclitaxel in an in vitro hemopoietic progenitor toxicity assay. Our procedure for the isolation and purification of paclitaxel metabolites in milligram quantities should be useful for testing the biological activities of these compounds and for the preparation of calibration standards essential for pharmockinetics studies.