Parents' life events and substance use among German adolescent girls: testing a family mediation model

In this cross-sectional study, data from 202 German adolescent girls (ages 13-17 years) and their parents were utilized to test whether the relationship between parents' stressful life events and their daughter's substance use was mediated by higher levels of parents' depressive symptoms, lower quality of the relationship between the parents, and poor parenting behaviour. Structural equation modelling revealed that these family characteristics did not account for the link between parents' stressful life events and adolescent girl's substance use. Further research is needed to better understand the mechanisms that account for such linkages.     

Hypothermia and brain-derived neurotrophic factor reduce glutamate synergistically in acute stroke

Moderate hypothermia and application of brain-derived neurotrophic factor (BDNF) have separately been identified as neuroprotective strategies in experimental cerebral ischemia. To assess their separate and combined effects on striatal glutamate release in the hyperacute phase of stroke, we inserted microdialysis probes into the striatum of rats 2 h before permanent middle cerebral artery occlusion (MCAO). The animals (N = 28) were randomly assigned to one of four treatment strategies commencing 30 min after MCAO: (1) hypothermia at 33 degrees C (n = 7); (2) intravenous BDNF infusion [300 microg/(kg/h) for 2 h, n = 7]; (3) combination of hypothermia and BDNF (n = 7); (4) control group (saline, n = 7). Infarct size at 5 h after MCAO was assessed with the silver-staining method. Total infarct volume was significantly reduced in the hypothermia (202.7 +/- 3.5 mm(3), P = 0.0002) and BDNF group (206.5 +/- 6.9 mm(3), P = 0.0006) as compared to control group (254.4 +/- 9.3 mm(3)). In the combination group, infarct size was further reduced with overall significance in post hoc tests (157.3 +/- 6.2 mm(3), P < 0.0001). Postischemic glutamate concentrations in the control group constantly remained significantly higher than in all other treatment groups. At 255 and 270 min after MCAO, striatal glutamate in the combination group decreased significantly more than in animals treated with hypothermia or BDNF alone.Combining hypothermia and BDNF therapy in the acute stage of ischemia has a synergistic effect in attenuating striatal glutamate release and reducing early infarct size.     

Oral contraception does not alter single dose saquinavir pharmacokinetics in women

AIMS: Women experience more adverse drug reactions (ADR) to antiretroviral therapy than men. This may be attributed to higher plasma concentrations of protease inhibitors due to pharmacokinetic interactions with hormonal preparations. Thus, in the present study we aimed to investigate the influence of oral contraceptives (OC) on the pharmacokinetics of the protease inhibitor saquinavir. METHODS: Saquinavir was administered in a hard gelatin capsule formulation (Invirase) to rule out confounding by pharmaceutical aids of the more frequently used soft gelatin capsule. After an overnight fast, eight healthy female participants ingested a single oral dose of 600 mg saquinavir immediately before and after the 19th dose of a combined, low dose OC (0.03 mg ethinylestradiol, 0.075 mg gestodene) in a prospective, fixed sequence study design. The first saquinavir application was scheduled on day 1, 2, or 3 of the individual menstrual cycle. Plasma concentrations of saquinavir and relative concentrations of its M2&M3-hydroxy metabolites were determined by LC/MS/MS for 48 h. RESULTS: Intake of OC resulted in a significant decrease in morning serum concentrations (before intake of OC, compared to day 19 of OC therapy) of 17beta-estradiol by -23.4 pg ml-1 (57%, 95%CI: -76% to -37.4%); progesterone by -0.25 ng ml-1 (33%, 95%CI: -45.3% to -21.5%); follicle-stimulating hormone by -4.06 U l-1 (82%, 95%CI: -96.5% to -67.7%); and luteinizing hormone by -3.49 U l-1 (74%, 95%CI: -93 to -54.6%). Conversely, sexual hormone binding globulin serum concentrations increased by 83.6 nmol l-1 (205%, 95%CI: 32.2% to 377%). Pharmacokinetic parameters of saquinavir (AUC, Cmax, tmax, t1/2, CLR) were not affected by OC, nor was the relative metabolic ratio of saquinavir/M2&M3-hydroxy saquinavir. Furthermore, there was no association of serum hormone concentrations or MDR1-polymorphisms (C3435T and G2677T) with pharmacokinetic parameters of saquinavir. CONCLUSIONS: There was no effect of OC on saquinavir pharmacokinetics. Thus, pharmacokinetic interactions of synthetic sexual steroids with saquinavir are not likely to account for the increased ADR to antiretroviral therapy seen in women.     

Cd Accumulation and Cd–Metallothionein as a Biomarker in <Emphasis Type="Italic">Cepaea hortensis</Emphasis> (Helicidae,Pulmonata) from Laboratory Exposure and Metal-polluted Habitats

Cepaea hortensis is a widespread terrestrial pulmonate, contributing significantly to element fluxes in soil ecosystems. Due to its capacity of accumulating certain trace elements in its tissues, Cepaea hortensis can serve as a biological indicator of metal accumulation in contaminated areas. In response to Cd exposure this species and related helicid pulmonates are also able to synthesize an inducible, Cd-binding metallothionein (MT) isoform specifically serving in binding and detoxification of this metal. As shown by field-collected garden-snails from a metal-contaminated site near a zinc smelting works in Avonmouth (UK) and an unpolluted reference site in Reutte (Tyrol, Austria), Cd and Cd–MT concentrations in midgut gland of C. hortensisfrom these sites increased with rising Cd concentrations in the soil substrate from the same contaminated sites. By combining the results of these field data with laboratory experiments it appears that midgut gland Cd–MT of Cepaea hortensis seems to fulfil the criteria of a successful biomarker in many respects. First, the synthesis of the protein can rapidly be induced by Cd exposure. Second, the level of Cd–MT induction in C. hortensis directly reflects the intensity of metal exposure. Third, the induced signal of increased Cd–MT concentration in C. hortensis is persistent over extended periods of time. Fourth, the Cd–MT signal in C. hortensis seems to be very specific for Cd exposure. Regression analyses demonstrate that tissue levels of Cd and Cd–MT in C. hortensis depend on Cd concentrations in the substrate which is represented by either soil or plant material on which snails normally feed. In both cases the best fit for this dependence is exhibited by a semi-logarithmic relationship, with substrate (soil or plant feed) concentrations expressed on a logarithmic scale. It is concluded that C. hortensis and other related pulmonates can successfully be used either as biological indicators of Cd accumulation, or as key species in biomonitoring studies focusing on Cd–MT induction as a biomarker for Cd exposure.     

Bronchiolar columnar cell dysplasia—genetic analysis of a novel preneoplastic lesion of peripheral lung

Atypical adenomatous hyperplasia is the only known precursor lesion of lung adenocarcinomas (ACs) so far. Here, we describe a new dysplastic lesion in the bronchioles of peripheral lung for which we propose the name bronchiolar columnar cell dysplasia (BCCD). Eight of fourteen BCCDs were successfully analyzed by means of comparative genomic hybridization (CGH). The average number of chromosomal aberrations was 2.6 in BCCD and 14.7 in concomitant AC. Among the aberrations were losses of 3p, 9, 13, 14 and gains of 1q, 17, 19q and 20q. Summarizing our data from morphological and genetic analysis, we conclude that BCCD is a preneoplasia of the bronchiolar epithelium and most probably represents an additional precursor lesion of lung adenocarcinomas.     

Imaging techniques for evaluation of the uterine cavity and endometrium in premenopausal patients before minimally invasive surgery

A literature review compared the diagnostic effectiveness and accuracy of transvaginal sonography (TVS) hysterosonographic examination (HSE), hysteroscopy (HY), and magnetic resonance imaging (MRI) in abnormalities of the uterine cavity and endometrium in premenopausal patients referred to surgery and women with abnormal uterine bleeding. The studies varied much in terms of patient selection, number of observers, blinding and experience of observers, and definition of abnormality criteria. The diagnostic effectiveness of the techniques reviewed varied: TVS only reached intermediate quality levels as a diagnostic tool for exclusion of uterine cavity abnormalities and no data support that MRI, TVS, HY, or HSE may exclude hyperplasia without concomitant endometrial sampling. HY and HSE were equally effective and apparently outperformed TVS, especially for identification of polyps. However, all techniques carried a significant number of false positive results. MRI does not satisfy current diagnostic demands for detection of endometrial abnormalities, but it is sufficiently accurate for submucous myoma (SM) evaluation. TVS, HSE, and HY carry much observer variation as opposed to MRI. In experienced hands TVS should be a first choice modality, but its precision and consistency fall short of current needs and it should therefore be supplemented by other techniques. HSE or HY performed by experienced clinicians should be used as supplements to TVS for exclusion of polyps. MRI can be recommended as the first choice modality for exact evaluation of SM uterine in-growth before advanced minimal invasive treatment of myomas. Clinicians should be aware that modern imaging techniques may yield highly idiosyncratic results when used by inexperienced staff, and efforts should be made to reduce such observer variation. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the diagnostic strengths and weaknesses of the various diagnostic tests in the evaluation of abnormal uterine bleeding and to compare the accuracy of each test to the others.     

Prevalence and determinants of hormone replacement therapy in German women 1984-1995

OBJECTIVES: To describe trends in prevalence and determinants of hormone replacement therapy (HRT) in German women. METHODS: Three representative samples of women in Augsburg, Germany were examined in the MONICA surveys in 1984/85 (45-64 years; N=1013), 1989/90 and 1994/95 (both 45-74 years; N=1496 and 1475) by interview and anthropometry, and all drugs taken during the previous week were documented. The prevalence of HRT use was calculated by survey, age group and HRT type, and various characteristics were evaluated as determinants for any systemic HRT use by logistic regression. RESULTS: The prevalence of HRT use in women aged 45-64 years in 1984/85, 1989/90 and 1994/95 was 3, 9% (age 45-74, 6%) and 23% (17%), respectively. In 1994/1995, positive determinants of HRT use were daily consumption of salad and vegetables, having quit smoking (vs. current smoking), regular exercise, ever having taken oral contraceptives, body mass index <25 kg/m(2) and age, and negative determinants were not drinking alcohol and education for <9 years (all P-value <0.10 in multivariate model). After multiple adjustment, HRT users were five times more likely to have participated in cancer screening and to have visited a gynaecologist >or=5 times during the previous year, and were less likely not to have seen a general practitioner or gynaecologist (all P-values <0.001). CONCLUSION: HRT use increased substantially in Germany between 1984 and 1995. Women with characteristics associated with lower morbidity and mortality were more likely to use HRT, which agrees with the healthy-user phenomenon described in other countries.