Cervical epithelial abnormalities are significantly associated with non-HPV lower genital tract infection in female contacts of warts*

Objectives

• 1 To assess the prevalence of cervical epithelial abnormalities in female sexual partners of men with anogenital warts.
• 2 To examine the possible association between non-HPV lower genital tract infection, and cervical epithelial abnormalities.

Design Retrospective review of the medical records of all female sexual partners of men with anogenital warts attending the GUM clinic in 1990. Setting and patients The department of Genito-Urinary Medicine (GUM), Royal Victoria Hospital, Belfast. Sixty-two female sexual partners of men with anogenital warts. Methods Cervical cytology and colposcopy was performed on all patients. Biopsies were taken of colposcopically identified cervical epithelial abnormalities, Non-HPV lower genital tract infection was detected by routine genito-urinary screening. Demographic data and sexual history were obtained by questionnaire. Outcome measured Overall prevalence of cervical epithelial abnormalities and correlation to the presence of non-HPV lower genital tract infection in the female. Results The overall prevalence of cervical epithelial abnormalities detected with colposcopy and biopsy was 46.8%. The prevalence of koilocytosis and cervical intraepithelial neoplasia (CIN) was 69.6% when non-HPV lower genital tract infection was detected by routine genito-urinary screening. When no infection was detected the prevalence was 33.3% (P < 0.05).     

Diagnostic irradiation of women during the reproductive period.

The date of onset of the last menstrual period should be given on radiographic requisitions for all women of reproductive age. Every effort should be made to avoid unnecessary irradiation of any woman who might be pregnant. Radiation damage in the first 2 weeks of pregnancy, however, should be "all or none", resulting in either a miscarriage or a normal child. Diagnostic radiology procedures are not indications for therapeutic abortion. Ultrasound has now replaced ionizing radiation in most examinations of the fetus and placenta. Pelvimetry should be done only when the decision to do a cesarean section hinges on precise knowledge of measurements of the bony pelvis. On the rare occasion when a radiograph of the fetus is necessary the woman should be prone for the examination. All such examinations are best ordered after consultation with a radiologist. Radiography of distant areas with the beam directed away from the woman's abdomen can be done without concern at any stage of pregnancy.     

Isoform selectivity and kinetics of morphine 3- and 6-glucuronidation by human udp-glucuronosyltransferases: evidence for atypical glucuronidation kinetics by UGT2B7.

Morphine elimination involves UDP-glucuronosyltransferase (UGT) catalyzed conjugation with glucuronic acid to form morphine 3- and 6-glucuronides (M3G and M6G, respectively). It has been proposed that UGT2B7 is the major enzyme involved in these reactions, but there is evidence to suggest that other isoforms also catalyze morphine glucuronidation in man. Thus, we have characterized the selectivity and kinetics of M3G and M6G formation by recombinant human UGTs. UGT 1A1, 1A3, 1A6, 1A8, 1A9, 1A10, and 2B7 all catalyzed M3G formation, but only UGT2B7 formed M6G. The kinetics of M3G formation by the UGT1A family isoforms was consistent with a single enzyme Michaelis-Menten model, with apparent Km values ranging from 2.6 to 37.4 mM. In contrast, M3G and M6G formation by UGT2B7 exhibited atypical kinetics. The atypical kinetics may be described by a model with high- and low-affinity Km values (0.42 and 8.3 mM for M3G, and 0.97 and 7.4 mM for M6G) from fitting to a biphasic Michaelis-Menten model. However, a multisite model with an interaction between two identical binding sites in a negative cooperative manner provides a more realistic approach to modeling these data. According to this model, the respective binding affinities (Ks) for M3G and M6G were 1.76 and 1.41 mM, respectively. These data suggest that M6G formation may be used as a selective probe for UGT2B7 activity, and morphine glucuronidation by UGT2B7 appears to involve the simultaneous binding of two substrate molecules, highlighting the need for careful analysis of morphine glucuronidation kinetics in vitro.     

Comparison of fresh and cryopreserved rat hepatocyte suspensions for the prediction of in vitro intrinsic clearance.

Freshly isolated hepatocytes are currently regarded as the most superior in vitro model for use in prediction studies, in particular to provide estimates of in vivo intrinsic clearance (CL(int)). However, due to their loss of viability within 4 h and a decrease in cytochrome P450-dependent metabolism upon culture, newer cellular models are being developed. Cryopreserved hepatocytes have several potential advantages, but to date evaluation of the utility of this model for estimating in vitro CL(int) has been limited to the substrate depletion approach. We have incubated eight compounds with suspensions of freshly isolated and cryopreserved rat hepatocytes and obtained in vitro CL(int) via metabolite formation kinetics (for 14 pathways). A substantial range of in vitro CL(int) values (0.1-98 microl/min/10(6)cells) was obtained in both models, and the freshly isolated suspension data were in good agreement with the literature. Cryopreserved suspensions were able to give a comparable estimation (within 2-fold) of in vitro CL(int) to fresh cells for six pathways, namely tolbutamide, three diazepam metabolites, propranolol, and 7-hydroxylation of warfarin. A higher estimation of in vitro CL(int) was obtained for the three other metabolites of warfarin due to a decrease in the K(M) values. Lower estimations of in vitro CL(int) were observed for four compounds (six pathways), and this was particularly pronounced (4-16%) for pathways showing atypical Michaelis-Menten kinetic profiles (dextromethorphan, nordiazepam) but less so (25-45%) for pathways showing biphasic Michaelis-Menten kinetics (7-ethoxycoumarin and phenytoin).     

美国教学医院教师专业发展的全国性调查

在当前医学教育持续变革的背景中,医学教师的专业发展成为广泛关注的焦点.为了解目前美国以提高教师的教学技能为目标的教师专业发展(faculty development,FD)活动的参与率、课程设计、教学方法和评估策略等情况,美国约翰·霍普金斯大学预防、流行病学和临床研究中心采取邮件调查的方式,对美国277家教学医院进行了调查.