Obstetrics and Gynaecology - Research Publications
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ItemShift work, hCLOCK T3111C polymorphism, and endometriosis risk(LIPPINCOTT WILLIAMS & WILKINS, 2008-05)BACKGROUND: Endometriosis, a dysplastic disease affecting approximately 5%-10% of US reproductive-age women, has been linked to exposures indicating high circulating estrogen levels. One such exposure may be night shift work, which has been associated with menstrual disruption and increased risk of 2 other estrogen-influenced diseases, breast cancer and adverse coronary events. METHODS: In this population-based case-control study, cases were 235 women aged 18 to 49 years who were enrolled in a large health-maintenance organization in the state of Washington, and who were first diagnosed with surgically-confirmed endometriotic disease between April 1, 1996 and March 31, 2001. Controls were 545 randomly selected women enrolled in the same program who did not have a history of endometriosis. Study participants were asked about night shift work in all paid full-time or part-time jobs they had worked from age 18 to the reference date. Genotypes for T3111C hCLOCK were determined for a subset of 218 cases and 456 controls. RESULTS: Any night shift work was associated with a 50% increase in risk of endometriosis (odds ratio = 1.48 [95% confidence interval = 0.96-2.29]), and working more than half of shifts on a job at night was associated with a nearly doubled disease risk (1.98 [1.01-3.85]). Changing sleep patterns on days off was associated with further increases in disease risk. T3111C hCLOCK polymorphism was unrelated to endometriosis status and did not modify the effect of shift work on endometriosis. CONCLUSIONS: These findings suggest that some aspects of night shift work may influence the development of endometriosis.
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ItemNo Preview AvailableMelatonin receptor potentiation of cyclic AMP and the cystic fibrosis transmembrane conductance regulator ion channel(MUNKSGAARD INT PUBL LTD, 1999-03)We have used the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel as a model system to study the cAMP signal transduction pathways coupled to the Xenopus melatonin receptor. During forskolin (Fsk) stimulation, melatonin reduced the amplitude of the CFTR currents in oocytes injected with in vitro transcribed cRNAs for the Xenopus melatonin receptor and CFTR. Pertussis toxin (Ptx) treatment eliminated melatonin inhibition of Fsk stimulated CFTR currents. In oocytes injected with cRNA for melatonin receptors, serotonin receptors (5-HT7), and CFTR Cl- channels, application of melatonin together with serotonin (5-HT) activated an additional inward current showing potentiation of adenylyl cyclases by melatonin receptors. Subthreshold activation of 5-HT7 receptors was sufficient and necessary to permit activation of CFTR channels by melatonin. Preexposure to melatonin desensitized the melatonin receptor mediated response. Therefore, based on this model system, the effects of melatonin in vivo could be either positive or negative modulation of other neuronal inputs, depending on the mode of adenylyl cyclase stimulation.
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ItemNo Preview AvailableCloning and characterization of Kir3.1 (GIRK1) C-terminal alternative splice variants(ELSEVIER SCIENCE BV, 1997-06)Southern blot analysis of RT-PCR products from brain and heart revealed multiple products for a C-terminal region of Kir3.1. Sequencing yielded clones for wild-type Kir3.1 and three Kir3.1 C-terminal alternative splice variants, including a unique alternative exon. Two of these variants encoded truncated Kir3.1 molecules. Tissue distribution and electrophysiological characterization of a single truncated variant, Kir3.1(00) were then examined. Kir3.1 channels are gated by G-protein beta gamma-subunits binding to the C-terminal domain, thus, the truncation of Kir3.1(00) removes a major functional domain. When incorporated into heteromeric channels with other family members (Kir3.1, 3.2 or 3.4) several functional changes were observed: (1) Kir3.1(00) changes G-protein activation of Kir3 channels; (2) Kir3.1(00) is restricted in its ability to assemble with other channel subunits as heteromers; and (3) incorporation of Kir3.1(00) into heteromeric channel complexes alters the kinetics of channel re-activation.
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ItemNo Preview AvailableThe sensitivity of N-methyl-D-aspartate receptors to lead inhibition is dependent on the receptor subunit composition(WILLIAMS & WILKINS, 1996-07)Pb+2 is a potent inhibitor of N-methyl-D-aspartate (NMDA) receptors and its action is dependent on neuronal maturation. Developmentally regulated expression of NMDA receptor subunits may underlie the changing sensitivity to Pb+2. In oocytes expressing in vitro transcribed cRNAs for zeta 1 epsilon 1 or zeta 1 epsilon 2 NMDA receptor subunits, Pb+2 inhibited glutamate-activated currents with IC50 values of 0.87 +/- 0.25 and 1.21 +/- 0.22 microM, respectively, and NMDA-activated currents with IC50 values of 1.37 +/- 0.47 and 1.11 +/- 0.33 microM, respectively. In oocytes expressing zeta 1 epsilon 1 epsilon 2 subunits, the IC50 values for Pb+2 blockade of NMDA- or glutamate-activated currents were significantly larger when compared to zeta 1 epsilon 1 or zeta 1 epsilon 2 combinations. Pb+2 concentrations greater than 1 microM inhibited glutamate-activated currents with an IC50 of 6.1 +/- 1.22 microM and NMDA-activated currents with an IC50 of 6.64 +/- 3.34 microM. Pb+2 reduced the maximal current amplitude consistent with a noncompetitive block. zeta 1 epsilon 1 epsilon 2 NMDA receptors were potentiated by low concentrations of Pb+2 ( < 1.0 microM). These data suggest that brain regions with zeta 1 epsilon 1 or zeta 1 epsilon 2 NMDA receptors subunits would be more vulnerable to Pb+2 toxicity than those with zeta 1 epsilon 1 epsilon 2 NMDA-receptors, which are expressed later in development. These data provide a mechanism for the reported changes in the efficacy of block of NMDA receptors by Pb+2 during development.
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ItemNo Preview AvailableMelatonin receptors activate heteromeric G-protein coupled Kir3 channels(RAPID SCIENCE PUBLISHERS, 1996-02-29)The effects of melatonin on circadian pacemaker activity in the central nervous system may be the result of melatonin receptor activation of G-protein coupled potassium channels which inhibit the action potential firing of neurons. Xenopus laevis and human1a melatonin receptors stimulated heteromeric G-protein activated inwardly rectifying potassium channels (Kir3.1/Kir3.2) when expressed in vitro in oocytes. Pertussis toxin reduced iodo-melatonin (87.1% reduction) and melatonin (90.3% reduction) stimulated currents in a time-dependent manner for cells expressing X. laevis receptors. A similar pertussis toxin inhibition was observed for human melatonin receptors (melatonin, 78.9% reduction). This suggests a potential role for heteromeric Kir3 channels in the receptor-mediated actions of melatonin in vivo.
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ItemNo Preview AvailableUterine leiomyoma and menstrual cycle characteristics in a population-based cohort study(OXFORD UNIV PRESS, 2004-10)BACKGROUND: We examined the association of uterine leiomyoma with menstrual cycle characteristics in a population of non-care-seeking women. METHODS: This cross-sectional study uses data from the Seveso Women's Health Study (SWHS), a population-based cohort in Italy. Participants included 341 premenopausal women, 30-60 years old, who had an intact uterus and were not pregnant, lactating, or using oral contraception or intra-uterine devices. We examined the presence of any ultrasound-detected uterine leiomyoma in relation to self-reported menstrual cycle length, flow length and heaviness of flow. The association of leiomyoma number, volume, tissue layer location and axial position with menstrual cycle characteristics was also examined. RESULTS: Uterine leiomyomata were detected in 73 women (21.4%). After adjustment for covariates, the presence of a leiomyoma was not significantly related to menstrual cycle length, flow length or heaviness of flow [odds ratio (OR) for scanty flow =1.9, 95% confidence interval (CI) 0.8-4.3; OR for heavy flow =1.3, 95% CI 0.7-2.5; relative to moderate flow]. Number, volume, tissue layer location (subserosal or intramural) and axial position (anterior or posterior) of the leiomyoma were also not related to menstrual cycle characteristics. CONCLUSION: In this Italian population of women not seeking gynaecological care, menstrual characteristics are not related to leiomyoma.
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ItemNo Preview AvailableBurden of community-onset Escherichia coli bacteremia in seniors(UNIV CHICAGO PRESS, 2005-05-01)BACKGROUND: Although Escherichia coli is a well-recognized cause of urinary tract infection in seniors, little is known about the burden of invasive E. coli infection in this population. METHODS: We conducted a population-based cohort study of 46,238 noninstitutionalized Group Health Cooperative members>or=65 years of age to ascertain incidences of community-onset E. coli bacteremia and, for comparison, pneumococcal bacteremia, and we then performed a case-control study to identify risk factors for community-onset E. coli bacteremia. RESULTS: The overall rate of community-onset E. coli bacteremia in the study cohort was 150 cases/100,000 person-years, which was approximately 3 times higher than the rate of pneumococcal bacteremia. In the case-control study, urinary catheterization and urinary incontinence were the only factors associated with an increased risk of E. coli bacteremia in men (62 cases), whereas cancer, renal failure, congestive heart failure, coronary artery disease, and urinary incontinence were associated with an increased risk of E. coli bacteremia in women (119 cases). CONCLUSIONS: E. coli appears to be the leading cause of community-onset bacteremia in seniors, and, on the basis of these rates, we estimate that 53,476 cases occur in noninstitutionalized seniors each year in the United States. Community-onset E. coli bacteremia in seniors is, therefore, an infection of public health importance.
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ItemLifetime occupational history and risk of endometriosis(SCANDINAVIAN JOURNAL WORK ENVIRONMENT & HEALTH, 2009-05)OBJECTIVES: Endometriosis is the presence of functioning endometrial glands and stroma outside the uterine cavity, most often in the pelvic peritoneal cavity. Women with endometriosis commonly have dysmenorrhea, dyspareunia, pain, menorrhagia, and/or metrorrhagia. Disease complications can include adhesions, chronic pain, and infertility. In this exploratory case-control study, we investigated the relationship between lifetime occupational history and surgically confirmed endometriosis in a population-based sample. METHODS: We conducted interviews with participants, all reproductive-aged female members of a large health-maintenance organization who were first diagnosed with surgically confirmed endometriosis between April 1, 1996 and March 31, 2001. Interviews were also conducted with randomly selected controls, reproductive-aged female enrollees of the same organization from the same time period. Each reported job was coded using US Census Occupations and Industries codes, and classified into categories. We used unconditional logistic regression to compare having worked in a given job class with never having done so. RESULTS: Our study found that an increased risk of endometriosis was associated with having worked as a flight attendant, service station attendant, or health worker, particularly as a nurse or health aide (flight attendant: odds ratio (OR) 9.80, 95% CI 1.08-89.02; service station attendant: OR 5.77, 95% CI 1.03-32.43; health worker: OR 1.49, 95% CI 1.03-2.15). Income and education did not make a difference in the OR estimates for the occupations examined. CONCLUSIONS: This exploratory study suggested that there might be an associated risk of endometriosis for those women who have worked as a flight attendant, service station attendant, or health worker, particularly a nurse.
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ItemNo Preview AvailableMenopause.(Random House Australia, 2006-08)This book is designed to help you participate as an equal partner in your health care.