PubMed Health⌕ Search

Biomedical subjects

Phyllis C Leppert

Publications and source records attributed to Phyllis C Leppert.

15 recordsLinked to original sources
PubMed2006

Utility of screening for other causes of infertility in women with "known" polycystic ovary syndrome.

We investigated the prevalence of abnormal screening results (questionnaire and testing for other causes of oligo-ovulation, male or tubal factor infertility) in a group of 1,313 oligo-ovulatory women (included and excluded subjects) whose condition was screened for inclusion in the Pregnancy in Polycystic Ovary Syndrome trial, a multicenter clinical trial that was conducted at 13 sites in the United States. Other than failure to demonstrate laboratory evidence of hyperandrogenemia, the most common reasons for subject exclusion were persistent oligospermia and tubal factor infertility.

Causality↗
PubMed2006

The Pregnancy in Polycystic Ovary Syndrome study: baseline characteristics of the randomized cohort including racial effects.

OBJECTIVE: To report the baseline characteristics and racial differences in the polycystic ovary syndrome (PCOS) phenotype from a large multicenter clinical trial (PPCOS). DESIGN: Double-blind, randomized trial of three treatment regimens (with extended release metformin or clomiphene citrate). SETTING: Academic medical centers. PATIENT(S): Six hundred twenty-six infertile women with PCOS, aged 18-39 years, with elevated T levels and oligomenorrhea (exclusion of secondary causes), seeking pregnancy, with > or = 1 patent fallopian tube, normal uterine cavity, and a partner with sperm concentration > or = 20 x 10(6)/mL in > or = 1 ejaculate. INTERVENTION(S): Baseline characterization. MAIN OUTCOME MEASURE(S): Historical, biometric, and biochemical measures of PCOS. RESULT(S): There were no significant differences in baseline variables between treatment groups. The overall mean (+/-SD) age of the subjects was 28.1 +/- 4.0 years, and the mean body mass index was 35.2 kg/m2 (+/-8.7). Polycystic ovaries (PCOs) were present in 90.3% of the subjects, and the mean volume of each ovary was 10 cm3 or more. Of the subjects, 7% had ovaries that were discordant for PCO morphology. At baseline, 18.3% of the subjects had an abnormal fasting glucose level (> 100 mg/dL). Asians tended to have a milder phenotype, and whites and African Americans were similar in these measures. CONCLUSION(S): The treatment groups were well matched for baseline parameters, and we have added further information to the PCOS phenotype.

Adolescent↗
PubMed2006

The promise and perils of microarray analysis.

Microarray analysis has provided a novel means of identifying clues into the mechanisms of disease development. As a methodology, microarray analysis holds the promise for genome-wide screening in which 2 tissues (diseased and normal) are compared, and molecular pathways that defined the phenotype of the disease could be precisely defined. Alternatively, microarray experiments can be used to differentially compare pathologically similar diseased tissues to predict response to chemotherapy and risk of recurrence. However, the clinician should be aware that various sources of error can influence microarray analysis results. Sources of error can be minimized but not eliminated, explaining why meticulously conducted experiments in different laboratories or using different platforms result in different lists of genes. Confirmation and validation of genome-wide microarray results using ancillary methods remains a critical step. With proper confirmatory studies and cautious interpretation, microarray analysis represents a powerful tool for molecular discovery.

Female↗
PubMed2006

A new hypothesis about the origin of uterine fibroids based on gene expression profiling with microarrays.

This article will discuss some recent insights based on our microarray studies that have emphasized the role the extracellular matrix, transforming growth factor beta, and collagen structure in fibroid formation. These studies led to appreciation of molecular similarities between fibroids and keloids. Collectively, these observations suggest a model of fibroid development based on an abnormal response to tissue repair, resulting in disordered healing and formation of an altered extracellular matrix.

Extracellular Matrix↗
PubMed2004

Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids.

Uterine leiomyomas are prevalent estrogen-responsive clonal tumors, but the specific genetic alterations that contribute to their development have not been elucidated. To identify genes involved in the formation of leiomyomas, we used global expression profiling to compare clonal tumors with normal myometrium. Contrary to expectation, genes involved in estrogen action were not differentially expressed between leiomyoma and normal myometrium. Genes encoding extracellular-matrix proteins were prominently featured, suggesting their involvement in formation of a myofibroblast phenotype. Analysis of the extracellular matrix in the leiomyomas revealed a disordered collagen fibril orientation. Expression of the collagen-binding protein dermatopontin was found to be consistently decreased in leiomyoma by both reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR (mean underexpression = 9.41-fold) regardless of leiomyoma size, leiomyoma location, patient race, and patient age. This expression pattern was observed in 11 subjects and a total of 23 leiomyoma:myometrium pairs. Decreased expression of dermatopontin was also associated with keloid formation, a fibrotic disease that shares epidemiologic similarities with leiomyoma. Immunohistochemical studies of leiomyomas and keloids demonstrated reduced levels of dermatopontin in both tissues. In addition, ultrastructural analysis revealed that the orientation of the collagen fibrils in the keloid tissues strongly resembled that in the leiomyomas. Reduction in dermatopontin was associated with an increase in transforming growth factor-beta3 (TGFB3) mRNA levels in leiomyomas, whereas other genes involved in dermatopontin signaling were not differentially expressed. These findings suggest that leiomyoma development involves a myofibroblast cell phenotype characterized by dysregulation of genes encoding extracellular-matrix proteins. In particular, decreased expression of dermatopontin represents a molecular link between the leiomyoma and keloid phenotypes.

Adult↗
PubMed2004

The changing face of peer review at the National Institutes of Health.

OBJECTIVE: To discuss the new peer review system at the National Institutes of Health (NIH) and to present the process undertaken to accomplish these changes, with an emphasis on the reproductive sciences. DESIGN: A discussion of the many NIH committees and their composition and reports leading to the changes in peer review affecting the reproductive sciences. RESULT(S) AND CONCLUSION(S): The Center for Scientific Review (CSR), which reviews grants for all NIH Institutes, will initiate the Cellular, Molecular, and Integrative Reproduction, the Integrative and Clinical Endocrinology and Reproduction, and the Pregnancy and Neonatology study sections in February 2004. The National Institute of Child Health and Human Development (NICHD)'s Division of Scientific Review has the following subcommittees, which started review in July 2003: Pediatrics; Developmental Biology; Biobehavior and Behavior Sciences; Population Science; Obstetrics and Maternal-Fetal Biology; Reproduction, Andrology, and Gynecology; and Function, Integration, and Rehabilitation Science.

National Institutes of Health (U.S.)↗
PubMed2004

Histological dating of timed endometrial biopsy tissue is not related to fertility status.

OBJECTIVE: To assess the ability of histological dating to discriminate between women of fertile and infertile couples. The utility of histological dating of endometrium in the evaluation of infertile couples is uncertain. DESIGN: Prospective multicenter study, with subjects randomly assigned to biopsy timing. Criterion standard for infertility was 12 months of unprotected, regular intercourse without conception and for fertility at least one live birth within 2 years. SETTING: University-based infertility practices. PATIENT(S): Volunteer subjects (847) recruited at 12 clinical sites participating in the National Institutes of Health-funded Reproductive Medicine Network. Inclusion criteria included ages 20-39 years, regular menstrual cycles, and no hormonal treatment or contraceptive use for 1 month before the study. Fertile controls were excluded if they had a history of infertility, recurrent pregnancy loss, or recent breastfeeding. INTERVENTION(S): Subjects underwent daily urinary LH testing. After detection of the LH surge, subjects were randomized to biopsy in the mid (days 21-22) or the late (days 26-27) luteal phase. Pathologists at each site estimated the cycle day based on standard criteria. For the primary analysis, an out-of-phase biopsy was defined as a greater than 2-day delay in the histological maturation of the endometrium. MAIN OUTCOME MEASURE(S): The proportion of out-of-phase biopsies in fertile and infertile women was compared using logistic regression models with age at randomization as a covariate. Comparisons were also made between fertile vs. infertile at the midluteal or late luteal phase time points. RESULT(S): Biopsies were evaluated (301 mid and 318 late; N = 619). Out-of-phase biopsy results poorly discriminated between women from fertile and infertile couples in either the midluteal (fertile: 49.4%, infertile: 43.2%) or late luteal phase (fertile: 35.3%, infertile 23.0%). Results did not substantially differ using alternative definitions of "out-of-phase" or standardized cycle day. CONCLUSION(S): Histological dating of the endometrium does not discriminate between women of fertile and infertile couples and should not be used in the routine evaluation of infertility.

Adult↗
PubMed2004

Absence of secretory endometrium after false-positive home urine luteinizing hormone testing.

OBJECTIVE: To examine the proportion of cases with proliferative endometrium on biopsies performed after positive home urine LH testing. DESIGN: Multicenter clinical trial of the usefulness of endometrial biopsy in the evaluation of infertility, with women from fertile and infertile couples randomly assigned to midluteal vs. late luteal phase endometrial sampling. SETTING: Twelve clinical sites of the National Institutes of Health/National Institute of Child Health and Human Development-sponsored Reproductive Medicine Network. PATIENT(S): All women in the study had regular menstrual cycles. Fertile volunteers who had delivered a live born infant within the past 2 years without medical intervention were recruited through advertisements at participating sites. Infertile women with regular cycles were recruited from the clinical practices of the sites' physicians. INTERVENTION(S): Interview, informed consent, subject-interpreted home urine LH testing, and endometrial biopsy in either the midluteal or late luteal phase. MAIN OUTCOME MEASURE(S): Proportion of cases with proliferative endometrium on biopsy. RESULT(S): In both fertile and infertile women, more than 7% of endometrial biopsies performed 7-13 days after a positive home urine LH test revealed proliferative endometrium. CONCLUSION(S): Patient interpretation of home urine LH test kits not uncommonly results in false-positive tests. Women planning menstrual cycle testing or procedures related to ovulation may benefit from additional confirmatory testing.

Adult↗
PubMed2004

Comparative ultrastructure of collagen fibrils in uterine leiomyomas and normal myometrium.

OBJECTIVE: To examine the ultrastructural characteristics of extracellular matrix and mature collagen fibrils in uterine leiomyomas and compare them with those in adjacent normal myometrium. DESIGN: Analysis of paired leiomyoma-myometrium in surgical specimens. SETTING: Research center and tertiary care center. SUBJECT(S): Women undergoing medically indicated hysterectomy for symptomatic uterine leiomyomas. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Appearance and spatial orientation of the collagen fibrils in leiomyomas compared with myometrium. RESULT(S): Observation of specimens at x 12,500 magnification indicated that collagen fibrils were more abundant, loosely packed, and arrayed in a nonparallel manner in leiomyomas compared with myometrium. Random areas were examined at x 6,500 to x 64,000 magnification and revealed collagen fibrils of equal diameter in both leiomyomas and myometrium. However, an ordered and regular barbed appearance was present in collagen fibrils from myometrium but was lacking in leiomyomas. CONCLUSION(S): Leiomyomas contain an abnormal collagen fibril structure and orientation, which suggests that the well-regulated fibril formation in myometrium is altered in leiomyomas. Alterations in collagen genes may play a role in the pathogenesis of leiomyomas.

Adult↗
PubMed2003

Strategy for elucidating differentially expressed genes in leiomyomata identified by microarray technology.

OBJECTIVE: cDNA microarray technology identifies genes that are differentially expressed between tissues. Our previous study identified several genes that might contribute to the fibroid phenotype. We therefore sought to confirm genes involved in three distinct signal transduction pathways. DESIGN: Evaluation of differential mRNA and protein expression of Dlk, Frizzled-2, and CD-24 in fibroids compared with adjacent myometrium. University hospital. PATIENT(S): Five women undergoing medically indicated hysterectomy for symptomatic fibroids. INTERVENTION(S): Microarray analysis of up to 33000 genes, reverse transcriptase-polymerase chain reaction (RT-PCR), real-time RT-PCR, Western blot, and immunohistochemistry. MAIN OUTCOME MEASURE(S): Expression of mRNA transcripts and protein in fibroid compared with myometrium.A more extensive microarray confirmed differential expression of Frizzled-2 and CD-24 but did not confirm Dlk overexpression. RT-PCR and real-time PCR demonstrated equivalent Dlk mRNA expression between fibroid and myometrium (ratio, 1.02), a slight Frizzled-2 overexpression (ratio, 2.09), and robust CD-24 overexpression in fibroids (ratio, 12.35). Western blot and immunohistochemistry confirmed Frizzled-2 overexpression, but did not confirm Dlk overexpression. CONCLUSION(S): Microarray technology is the first phase of tissue evaluation, but changes in gene expression must be confirmed. Confirmed genes can then be used to generate hypotheses testing their involvement in fibroid development.

Antigens, CD↗
PubMed2002

Ascorbic acid status in postmenopausal women with hormone replacement therapy.

OBJECTIVES: Hormone oral contraceptives affected ascorbic acid status adversely in young women. In vitro, estrogens and progesterone inhibited ascorbic acid accumulation in intestinal cells. This is a pilot study to examine the relation between hormone replacement therapy (HRT) and plasma ascorbic acid levels among a group of healthy non-smoking postmenopausal women. METHODS: Healthy non-smoking postmenopausal women aged 48-72 years, 34 with HRT and 21 without HRT, were recruited in summer, 1997. Their fasting plasma ascorbic acid levels were measured and information on ascorbic acid intakes (diet and supplements) was collected through questionnaires. RESULTS: Women taking HRT in this study did not have significantly lower plasma ascorbic acid levels compared with non-HRT users. When subjects were further divided into groups based on ascorbic acid supplementation, HRT users without supplement had a lower mean plasma ascorbic acid level (54+/-16 microM, n=10) compared with non-HRT users (66+/-14 microM, n=12) (P=0.08 for the effect of therapy). HRT users and non-users taking ascorbic acid supplement had similar plasma levels (66+/-10 microM, n=24; 66+/-12 microM, n=9, respectively). CONCLUSION: HRT does not affect ascorbic acid status of healthy well-nourished non-smoking postmenopausal women that are using ascorbic acid supplement. Future larger case-control or supplement intervention study is needed.

Aged↗
PubMed2002

Providing research and research training infrastructures for clinical research in the reproductive sciences.

The Reproductive Sciences Branch of the National Institutes of Child Health and Human Development has created pioneering new research and research training programs that address the impending shortage of physician-scientists in obstetrics, gynecology, and women's health and the need to bolster translational and clinical research. This article provides a brief overview of the Specialized Cooperative Centers Program in Reproduction Research, the National Cooperative Program for Infertility Research, the Reproductive Medicine Network, the Reproductive Scientist Development Program, the Women's Reproductive Health Research Career Development Program, and the Contraception and Infertility Research Loan Repayment Program and describes how these programs collectively create an infrastructure to promote the next generation of physician-scientists and to provide an information exchange between basic and clinical investigators. A key component in increasing the number of clinical investigators is the Contraception and Infertility Research Loan Repayment Program. This program has enabled clinicians to be involved in research without having to be concerned about educational loan debt. Other component programs provide basic/translational, clinical hypothesis-oriented research and clinical trials research infrastructure. The programs created are individually strong and collectively poised to support translational and clinical research efforts and to build a well-trained cadre of physician-scientists. The collective use of these types of programs is proposed as a model for the National Institutes of Health.

Contraception↗
PubMedDate not supplied

A survey of past obstetrics and gynecology research fellows.

OBJECTIVE: To survey obstetrician-gynecologist-scientists to determine factors that enhanced or hindered research careers. METHODS: A pretested mail survey was sent to 107 obstetrician-gynecologists who had received research fellowship awards from professional organizations during the years 1971-1999. Demographic information along with face-value, forced-choice and yes-no questions as well as those asking for a single response using a Likert-type scale were requested. Two open-ended questions were also asked. The questionnaire was designed to obtain at least a 60% return. RESULTS: A 62.2% return demonstrated that 92% of this group of former fellows holds academic positions. Twenty-four percent of respondents had no research mentors in the first 5 years after fellowship, and 58% had or have National Institutes of Health grant awards, with an average of two grants. The majority believed they did not have adequate time to conduct research, stating that 80% or more time was necessary for a successful research career. CONCLUSION: Career success of the respondents is variable and is related to mentors, time allocated to research, and funding. The obstetrics and gynecology specialty must find ways to provide increased mentoring and time allocation to encourage funding opportunities.

Career Choice↗