Anti-Müllerian hormone and inhibin B variability during normal menstrual cycles.

Objective: To describe anti-Müllerian hormone (AMH) variation across normal menstrual cycles.

Design: Cohort study.

Setting: Academic environment.

The influence of reproductive hormones on brain function in the menopausal transition.

Reproductive hormones have long been thought to have a significant impact on brain function in humans. Estrogens, progestins and androgens have all been shown to have effects on nerve growth and function in vitro. The neurofunctional domains of cognition, mood and sleep are now receiving increased study to determine both the relationship of endogenous sex steroids through the menopausal transition and the effect of menopausal hormone therapy on these complex functions.

Pandemic influenza planning: addressing the needs of children.

Children represent one quarter of the US population. Because of its enormous size and special needs, it is critically important to address this population group in pandemic influenza planning. Here we describe the ways in which children are vulnerable in a pandemic, provide an overview of existing plans, summarize the resources available, and, given our experience with influenza A(H1N1), outline the evolving lessons we have learned with respect to planning for a severe influenza pandemic.

Synthesis and evaluation of inhibitors of cytochrome P450 3A (CYP3A) for pharmacokinetic enhancement of drugs.

The HIV protease inhibitor ritonavir (RTV) is also a potent inhibitor of the metabolizing enzyme cytochrome P450 3A (CYP3A) and is clinically useful in HIV therapy in its ability to enhance human plasma levels of other HIV protease inhibitors (PIs). A novel series of CYP3A inhibitors was designed around the structural elements of RTV believed to be important to CYP3A inhibition, with general design features being the attachment of groups that mimic the P2-P3 segment of RTV to a soluble core. Several analogs were found to strongly enhance plasma levels of lopinavir (LPV), including 8, which compares favorably with RTV in the same model.

Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome.

This study was undertaken to determine whether grape seed extracts (GSE) that contain powerful vasodilator phenolic compounds lower blood pressure in subjects with the metabolic syndrome. The subjects were randomized into 3 groups-(a) placebo, (b) 150 mg GSE per day, and (c) 300 mg GSE per day-and treated for 4 weeks. Serum lipids and blood glucose were measured at the beginning of the study and at the end.

Testosterone, sex hormone-binding globulin and free androgen index among adult women: chronological and ovarian aging.

Background: In this study, levels and rates of change in total testosterone (T), sex hormone-binding globulin (SHBG) and free androgen index (FAI) were related to chronological age and to the final menstrual period (FMP) as an indicator of ovarian aging.

Methods: Data were annually acquired over a 15-year period in 629 women of the Michigan Bone Health and Metabolism Study cohort. Data were censored for hormone therapy use.

Circulating dehydroepiandrosterone sulfate concentrations during the menopausal transition.

Context: A previous report from the Study of Women Across the Nation indicated a rise in dehydroepiandrosterone sulfate (DHEAS) during the menopausal transition using data from three annual visits.

Objective: Our objective was to examine changes in DHEAS with chronological and ovarian aging, expanding the original analyses to include 10 yr of annual data.

Design: A longitudinal observational study and cross-sectional analyses of baseline data were conducted.

Racial differences in women who have a hysterectomy for benign conditions.

Objective: To evaluate if there are racial differences between African-American and Caucasian women who have hysterectomy for benign conditions in terms of (1) presenting symptoms (prolapse, vaginal bleeding, pain, and known history of leiomyomas), (2) serum estradiol and testosterone levels at the visit before hysterectomy, and (3) uterine weight.

Methods: A multi-ethnic, multisite, community-based longitudinal cohort study of 3,302 women ages 42-52 at enrollment was conducted. During 9 years of follow-up, 203 African-American and Caucasian women reported a hysterectomy, 90 with evidence of uterine leiomyomas.

Synthesis and biological characterization of B-ring amino analogues of potent benzothiadiazine hepatitis C virus polymerase inhibitors.

Benzothiadiazine inhibitors of the HCV NS5B RNA-dependent RNA polymerase are an important class of non-nucleoside inhibitors that have received considerable attention in the search for novel HCV therapeutics. Research in our laboratories has identified a novel series of tetracyclic benzothiadiazine inhibitors of HCV polymerase bearing a benzylamino substituent on the B-ring. Compounds in this series exhibit low-nanomolar activities in both genotypes 1a and 1b polymerase inhibition assays and subgenomic replicon assays.

Evaluation of platelet function screening tests to detect platelet procoagulant deficiency in dogs with Scott syndrome.

Background: Clinical diagnosis of platelet dysfunction is complex and technically challenging. The wide repertoire of platelet responses requires a test panel to assess different parameters of platelet reactivity. While "global" hemostasis analyzers and whole blood assays have potential for testing platelet function, their ability to evaluate platelet procoagulant activity is ill-defined.

2-Pyridyl P1'-substituted symmetry-based human immunodeficiency virus protease inhibitors (A-792611 and A-790742) with potential for convenient dosing and reduced side effects.

A series of symmetry-based HIV protease inhibitors was designed and synthesized. Modification of the core regiochemistry and stereochemistry significantly affected the potency, metabolic stability, and oral bioavailability of the inhibitors, as did the variation of a pendent arylmethyl P3 group. Optimization led to the selection of two compounds, 10c (A-790742) and 9d (A-792611), for advancement to preclinical studies.

Delayed symptoms of cerebrospinal fluid leak following lumbar decompression.

Numerous reports in the literature describe cerebrospinal fluid (CSF) leaks resulting from dural tears; however, most of these reports document symptoms of incidental durotomy occurring ,48 hours postoperatively. This case report describes patients with symptoms of CSF leak occurring a few days to a few weeks after lumbar spine surgery who required additional surgery to repair the dura and alleviate their symptoms. Records for patients who had lumbar spine surgery performed by 2 spine surgeons at a single institution between 1990 and 2005 were reviewed.

Longitudinal changes in sexual functioning as women transition through menopause: results from the Study of Women's Health Across the Nation.

Objective: Sexual functioning is an important component of women's lives. The extent to which the menopausal transition is associated with decreased sexual functioning remains inconclusive. This study seeks to determine if advancing through the menopausal transition is associated with changes in sexual functioning.

The use of structural analysis to develop antecedent-based interventions for students with autism.

Evidence continues to maintain that the use of antecedent variables (i.e., instructional practices, and environmental characteristics) increase prosocial and adaptive behaviors of students with disabilities (e.

Levels of sex steroid and cardiovascular disease measures in premenopausal and hormone-treated women at midlife: implications for the "timing hypothesis".

Background: The "timing hypothesis," in addressing findings from the Women's Health Initiative trial, suggests that hormone therapy (HT) should be initiated within 6 years of the menopause transition to extend a favorable estrogenic environment after menopause.

Methods: We compared sex steroid and cardiovascular profiles at the 5-year follow-up visit in a community-based, longitudinal study of the menopause transition (Study of Women's Health Across the Nation). Women aged 47 to 57 years were in 1 of 4 groups: premenopausal, women using conjugated equine estrogen with or without progestin, or postmenopausal (<5 years) without HT use.

Diagnostic and assessment findings: a bridge to academic planning for children with autism spectrum disorders.

Increasing numbers of children diagnosed and treated for autism spectrum disorders (ASDs) has impacted both neuropsychologists and educators. Though both play key evaluative and treatment roles, there is no available method or process in place enabling the translation of the neuropsychological report recommendations into a format educational teams can easily use, leading to a gap between neuropsychological recommendations and educational planning. In the following, we review the areas evaluated by a neuropsychologist when assessing a child with an ASD, discuss the domains targeted by educational teams when designing an educational plan, and then present a process that has met with some success creating a "bridge" between the diagnostic/assessment process and the subsequent academic planning.

Pyrrolo-C as a molecular probe for monitoring conformations of the tRNA 3' end.

All mature tRNA molecules have the conserved CCA sequence at the 3' end with a range of dynamic conformations that are important for tRNA functions. We present here the details of a general approach to fluorescent labeling of the CCA sequence with the fluorescent base analog pyrrolo-C (PyC) at position 75 as a molecular probe for monitoring the dynamics of the tRNA 3' end. Using Escherichia coli tRNA(Cys) as an example, we achieve such labeling by first synthesizing the tRNA as a transcript up to C74 and then employing the tRNA CCA-adding enzyme to incorporate PyC75 and A76, using pyrrolo-CTP (PyCTP) and ATP as the respective substrates.

Follicle stimulating hormone and its rate of change in defining menopause transition stages.

Context/objective: The objective of the study was to identify menopause transition stages using acceleration or deceleration patterns of FSH rates of change from the late reproductive years to postmenopause.

Setting/participants: Participants were the Michigan Bone Health and Metabolism Study cohort of 629 women, aged 24-44 yr (in 1992/3), with 5757 annual FSH data points over a 14-yr period. DESIGN/MAIN OUTCOME MEASURES: The study was designed to relate acceleration/deceleration patterns in FSH rate of change to time to final menstrual period (FMP) and chronological age using nonparametric and piecewise regression modeling.

Estradiol rates of change in relation to the final menstrual period in a population-based cohort of women.

Context/objective: The aim was to characterize rates of change in serum estradiol (E2) levels across the menopausal transition and into early postmenopause.

Setting/participants: We studied the Michigan Bone Health and Metabolism Study cohort of 629 women with median age of 38 yr (interquartile range, 7) at the 1992-1993 baseline with annual assessment of E2 levels over the subsequent 15-yr period. DESIGN/MAIN OUTCOME MEASURES: The purpose was to describe patterns of acceleration/deceleration in (log)E2 rates of change before and after the final menstrual period (FMP) using nonparametric and piecewise regression modeling.

The endocrinology of the reproductive years.

Introduction: The relationship between reproductive physiology and reproductive behavior, a central theme in Professor Lorraine Dennerstein's career, is complex but presumably serves to optimize human reproduction.

Aim: To review the endocrinology of the reproductive years and significant work by Professor Dennerstein relating that endocrinology with reproductive behavior. METHODS/MAIN OUTCOME MEASURES: Published works of reproductive endocrinology by Professor Dennerstein.

Anti-mullerian hormone and inhibin B in the definition of ovarian aging and the menopause transition.

Context/objective: The objective of the study was to determine whether anti-Mullerian hormone (AMH) and inhibin B are viable endocrine biomarkers for framing the menopause transition from initiation to the final menstrual period (FMP).

Design: We assayed AMH, inhibin B, and FSH in 300 archival follicular phase specimens from 50 women with six consecutive annual visits commencing in 1993 when all women were in the pre- and perimenopausal menopause stages. Subsequently each woman had a documented FMP.

The relationship of bleeding patterns to daily reproductive hormones in women approaching menopause.

Objective: To discover early hormonal predictors of menopause and the stages of the menopausal transition and to understand the hormonal basis behind the bleeding abnormalities common in the menopausal transition.

Methods: A cohort of 804 women aged 42-52 collected first void urine samples daily for one complete menstrual cycle or 50 days (whichever came first) once a year for 3 years. Urine was assayed for excreted levels of follicle-stimulating hormone, luteinizing hormone, estrogen metabolites, and progesterone metabolites, which were normalized for creatinine concentration.

Changes in gallbladder volume in healthy dogs after food was withheld for 12 hours followed by ingestion of a meal or a meal containing erythromycin.

Objective: To assess the influence of meal ingestion and orally administered erythromycin on gallbladder volume in dogs.

Animals: 22 healthy dogs.

Procedures: Ultrasonographically determined gallbladder dimensions in unsedated dogs were used to calculate volume.

Clinical and clinicopathologic features of dogs that consumed foodborne hepatotoxic aflatoxins: 72 cases (2005-2006).

Objective: To characterize clinical signs, clinicopathologic features, treatments, and survival in dogs with naturally acquired foodborne aflatoxicosis.

Design: Retrospective case series.

Animals: 72 dogs that consumed aflatoxin-contaminated commercial dog food.

Synthesis, antiviral activity, and conformational studies of a P3 aza-peptide analog of a potent macrocyclic tripeptide HCV protease inhibitor.

BILN 2061 is a macrocyclic tripeptide inhibitor of hepatitis C virus NS3-4A protease that has shown efficacy in the clinic for treating patients infected with HCV. We have synthesized a P3 aza-peptide analog of a potent macrocyclic tripeptide inhibitor closely related to BILN 2061. This aza-derivative was found to be >2 orders of magnitude less active than the parent macrocycle in both isolated enzyme (HCV NS3-4A) and HCV subgenomic replicon assays.