Gene analysis in patients with premature ovarian failure or gonadal dysgenesis: a preliminary study

OBJECTIVE: The aim of this study was to evaluate the presence of mutations in the coding region of the QM gene and fragile X in patients with premature ovarian failure and gonadal dysgenesis. METHODS: After approval by the local Ethics Committee, blood samples, in EDTA, of 100 normally ovulating women, 23 with premature ovarian failure (POF) and 14 with gonadal dysgenesis 46XX, aged less than 40 years, were screened for mutation in the QM gene coding region. All patients with POF have 46, XX karyotype and serum levels of follicle-stimulating hormone (FSH) over 30 mIU/mL. In addition, all samples from patients with premature ovarian failure underwent analysis for fragile X. RESULTS: The QM gene located at a hotspot region (Xq28) showed five points of mutations in a patient with premature ovarian failure. Four of them were able to change the amino acid sequence of the protein. None of our patients were diagnosed as having pre or mutant X fragile syndrome. CONCLUSION: Our study suggests that Xq28 (QM gene) may be involved in ovary failure. However, further studies are needed to confirm this hypothesis.     

Racial Differences in Pregnancy Intention,Reproductive Coercion,and Partner Violence among Family Planning Clients: A Qualitative Exploration

Background

Unintended pregnancy (UIP) is a persistent public health concern in the United States disproportionately experienced by racial/ethnic minorities and women of low socioeconomic status. UIP often occurs with experiences of reproductive coercion (RC) and intimate partner violence (IPV). The purpose of the study was to qualitatively describe and compare contexts for UIP risk between low-income Black and White women with histories of IPV/RC.

The Association Between Park Facilities and Duration of Physical Activity During Active Park Visits

Public parks provide places for urban residents to obtain physical activity (PA), which is associated with numerous health benefits. Adding facilities to existing parks could be a cost-effective approach to increase the duration of PA that occurs during park visits. Using objectively measured PA and comprehensively measured park visit data among an urban community-dwelling sample of adults, we tested the association between the variety of park facilities that directly support PA and the duration of PA during park visits where any PA occurred. Cross-classified multilevel models were used to account for the clustering of park visits (n?=?1553) within individuals (n?=?372) and parks (n?=?233). Each additional different PA facility at a park was independently associated with a 6.8% longer duration of PA bouts that included light-intensity activity, and an 8.7% longer duration of moderate to vigorous PA time. Findings from this study are consistent with the hypothesis that more PA facilities increase the amount of PA that visitors obtain while already active at a park.     

Intracellular pharmacokinetics of once versus twice daily zidovudine and lamivudine in adolescents

Zidovudine (ZDV) and lamivudine (3TC) metabolism to triphosphates (TP) is necessary for antiviral activity. The aims of this study were to compare ZDV-TP and 3TC-TP concentrations in adolescents receiving twice daily (BID) and once daily (QD) regimens and to determine the metabolite concentrations of ZDV and 3TC during chronic therapy on a QD regimen. Human immunodeficiency virus-infected patients (12 to 24 years) taking ZDV (600 mg/day) and 3TC (300 mg/day) as part of a highly active antiretroviral therapy regimen received QD and BID regimens of ZDV and 3TC for 7 to 14 days in a crossover design. Serial blood samples were obtained over 24 h on the QD regimen. Intracellular mono-, di-, and triphosphates for ZDV and 3TC were measured. The median ratio of BID/QD for ZDV-TP predose concentrations was 1.28 (95% confidence interval [CI] = 1.00 to 2.45) and for 3TC-TP was 1.12 (95% CI = 0.81 to 1.96). The typical population estimated half-lives (+/- the standard error of the mean) were 9.1 +/- 0.859 h for ZDV-TP and 17.7 +/- 2.8 h for 3TC-TP. Most patients had detectable levels of the TP of ZDV (24 of 27) and 3TC (24 of 25) 24 h after dosing, and half-lives on a QD regimen were similar to previously reported values when the drugs were given BID. Lower, but not significantly different, concentrations of ZDV-TP were demonstrated in the QD regimen compared to the BID regimen (P = 0.056). Although findings were similar between the BID and QD groups, the lower concentrations of ZDV and the number of patients below the level of detection after 24 h suggests that ZDV should continue to be administered BID.     

A review and critique of U.S. EPA's risk assessments for asbestos

U.S. Environmental Protection Agency (EPA) recently conducted a risk assessment for exposure to Libby amphibole asbestos that is precedent-setting for two reasons. First, the Agency has not previously conducted a risk assessment for a specific type of asbestos fiber. Second, the risk assessment includes not only an inhalation unit risk (IUR) for the cancer endpoints, but also a reference concentration (RfC) for nonmalignant disease. In this paper, we review the procedures used by the Agency for both cancer and nonmalignant disease and discuss the strengths and limitations of these procedures. The estimate of the RfC uses the benchmark dose method applied to pleural plaques in a small subcohort of vermiculite workers in Marysville, Ohio. We show that these data are too sparse to inform the exposure–response relationship in the low-exposure region critical for estimation of an RfC, and that different models with very different exposure–response shapes fit the data equally well. Furthermore, pleural plaques do not represent a disease condition and do not appear to meet the EPA's definition of an adverse condition. The estimation of the IUR for cancer is based on a subcohort of Libby miners, discarding the vast majority of lung cancers and mesotheliomas in the entire cohort and ignoring important time-related factors in exposure and risk, including effect modification by age. We propose that an IUR based on an endpoint that combines lung cancer, mesothelioma, and nonmalignant respiratory disease (NMRD) in this cohort would protect against both malignant and nonmalignant disease. However, the IUR should be based on the entire cohort of Libby miners, and the analysis should properly account for temporal factors. We illustrate our discussion with our own independent analyses of the data used by the Agency.     

Hemodynamic comparison of intravenous amrinone and dobutamine in patients with chronic congestive heart failure

Amrinone, a new inotropic agent, has been shown to be beneficial in patients with congestive heart failure. However, its hemodynamic effects have not been compared with those of currently useful catecholamines. In this study, the effects of intravenously administered dobutamine and amrinone were compared in eight patients with severe chronic congestive heart failure. Dobutamine was infused until a maximal increase in cardiac index was reached or undesirable effects were produced. This dose was then continued for 8 hours. After a return of hemodynamic values to baseline level, amrinone was infused at a rate of 40 μg/kg per min for 1 hour and then 10 μg/kg per min for 24 hours. Both drugs significantly improved cardiac index while simultaneously decreasing systemic vascular resistance and right atrial and pulmonary wedge pressures (p <0.05). Initially no differences could be found between the drugs. However, with prolonged infusion amrinone produced a sustained improvement whereas dobutamine had a decreased effectiveness. Thus, amrinone is comparable in effect with the optimal dose of dobutamine and would appear to be an extremely promising drug in the acute treatment of severe congestive heart failure.