Obstetrics and Gynaecology - Research Publications

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    New strategies for treating myomas.
    Wood, C ; Maher, P (Hindawi Limited, 1996)
    Laparoscopic minilaparotomy in 6 patients using the Maher abdominal elevator facilitated both quicker enucleation and morcellation of the myoma and suture of the myoma cavity. Myoma reduction in 12 patients by electrosurgery resulted in a 60% reduction in myoma diameter with failure in 2 patients. This technique may avoid myomectomy and be particularly useful in patients with infertility or near menopause.
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    LIMITATIONS OF THE CLONAL AGAR ASSAY FOR THE ASSESSMENT OF PRIMARY HUMAN OVARIAN TUMOR-BIOPSIES
    BERTONCELLO, I ; BRADLEY, TR ; CAMPBELL, JJ ; DAY, AJ ; MCDONALD, IA ; MCLEISH, GR ; QUINN, MA ; ROME, R ; HODGSON, GS (CHURCHILL LIVINGSTONE, 1982-01-01)
    114 biopsy specimens from 70 patients with ovarian carcinoma at all stages of disease were submitted for assessment of clonogenic capacity in agar. A highly significant correlation was found between agar clonogenicity and patient survival after biopsy. However, problems related to inherent tumour heterogeneity, quality of sample and tissue disaggregation indicate that this technique may have limited applicability in the routine assessment of patients. Only 41 biopsy specimens (36%) from 31 patients (44.3%) complied with the prerequisite criteria for agar clonogenic assessment, namely: (a) the confirmed presence of malignant cells in the biopsy, (b) the ability to prepare a single-cell suspension, and (c) adequate viable cell numbers for assay. Furthermore, although the dominant patterns of agar clonogenic growth could be identified and correlated with stage of disease, the heterogeneity in both initial clonogenic capacity and "self-renewal" capacity assessed by the ability of primary clones to propagate in liquid culture and reclone in agar was too inconsistent for the assay to be used as a prognostic index for the individual patient.
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    Role of genital mycoplasmas in bacteremia: should we be routinely culturing for these organisms?
    Garland, SM ; Kelly, VN (Hindawi Limited, 1996)
    OBJECTIVE: The purpose of this study was to examine the role of the genital mycoplasmas Mycoplasma hominis and Ureaplasma urealyticum as causes of bacteremia in a tertiary referral obstetrical, gynecological, and neonatal intensive care facility, over a period of 12 years from 1983 to 1994 inclusively. METHODS: All clinically significant blood cultures were reviewed and the percentage of septicemic episodes for genital mycoplasmas was compared to the total isolation rate, including conventional bacteria. RESULTS: The overall positivity rate for all pathogenic organisms isolated from the blood cultures of infants ranged from 4.5% to 7.7% per annum. U. urealyticum represented 0.8% of these positive isolates and M. hominis 0.4%. For adults, the overall positivity rate from blood cultures ranged from 6.5% to 13.5%, with U. urealyticum representing 9.6% of these positive isolates and M. hominis 9.9%. CONCLUSIONS: With M. hominis having an established role in such clinical entities as postabortal and postpartum fever and U. urealyticum strongly implicated with chronic lung disease in low birth weight infants, it is appropriate to examine blood cultures for genital mycoplasmas in an obstetric institution.
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    Do antepartum herpes simplex virus cultures predict intrapartum shedding for pregnant women with recurrent disease?
    Garland, SM ; Lee, TN ; Sacks, S (Wiley, 1999)
    OBJECTIVE: To examine antenatal screening as a predictor of intrapartum shedding of herpes simplex virus (HSV) and to determine its usefulness in guiding the appropriate route of delivery for patients with recurrent HSV in pregnancy. METHODS: A population of 198 pregnant women with a history of recurrent genital HSV were cultured in the last weeks of their pregnancy by specially-trained personnel and intrapartum by their delivering attendants. RESULTS: Of cultures from a total of 906 antenatal visits, 17% were culture positive, with an asymptomatic shedding rate of 3.4%. Asymptomatic shedding occurred in 12.6% of women. Over the 8-week antepartum period, viral culture-positivity rates for each visit ranged from 11% to 19.5%. This provided an expected delivery culture-positivity rate of 15.3%. However, actual intrapartum viral culture positivity occurred in only three of 191 women (1.5%; P < 0.001). Because previous studies have suggested antepartum culture positivity fails to predict intrapartum viral shedding, evaluations, including cultures, as well as predictive values for subsequent culture positivities, were determined under the supervision of an infectious disease specialist. Under these conditions, positive predictive values were 59% when the interval between visits was 2 days, but only 19% when days between visits were >2 (P < 0.0001). No cases of neonatal herpes were seen in this population, although cesarean deliveries were performed in 31% of the patient population, with genital herpes as the indication for 56% of those. CONCLUSIONS: Antepartum serial screening by viral culture is not predictive of an infant's risk of intrapartum viral exposure when conducted at weekly intervals. However, more frequent assessments of patients can be predictive of an infant's exposure risk to HSV; for patients with frequent recurrent disease near term or primary infection in pregnancy, frequent late antepartum screening may be appropriate.
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    AUTOIMMUNITY CAUSED BY IGNORANT CD8(+) T-CELLS IS TRANSIENT AND DEPENDS ON AVIDITY
    HEATH, WR ; KARAMALIS, F ; DONOGHUE, J ; MILLER, J (AMER ASSOC IMMUNOLOGISTS, 1995-09-01)
    RIP-Kb mice, which express H-2Kb (Kb) molecules on their pancreatic beta cells, were used to examine the requirements for induction of autoimmune diabetes caused by CD8+ T cells. Previous studies showed that when these mice were crossed to mice expressing a Kb-specific TCR transgene, those CD8+ cells expressing the highest density of the transgenic TCR (presumably the highest avidity cells) were deleted intrathymically due to aberrant expression of Kb at this site. The remaining low avidity cells ignored Kb-bearing beta cells, even after priming, but were able to cause autoimmune diabetes when supplied with Il-2. To examine the properties of high avidity autoreactive CD8+ T cells, the thymic compartment of RIP-Kb mice was replaced with normal tissue to enable the maturation of CD8+ cells expressing the highest density of the transgenic TCR. These high avidity cells generally ignored Kb-expressing beta cells, but became autoaggressive after priming. Importantly, analysis of islet infiltration by CD8+ T cells revealed the presence of infiltrating cells in all mice examined within 3 wk of priming, but such infiltration was not usually apparent at later time points. In some cases, multiple primings were necessary for full development of autoimmunity. This implied that beta cells could act as transient targets for CD8+ T cell attack but could not sustain the stimulation of primed CD8+ cells. These studies indicate that the duration of priming stimulus and the avidity of the autoreactive CD8+ cells profoundly influence the severity of autoimmune disease.
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    Melatonin receptor potentiation of cyclic AMP and the cystic fibrosis transmembrane conductance regulator ion channel
    Nelson, CS ; Marino, JL ; Allen, CN (MUNKSGAARD INT PUBL LTD, 1999-03-01)
    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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    Cloning and characterization of Kir3.1 (GIRK1) C-terminal alternative splice variants
    Nelson, CS ; Marino, JL ; Allen, CN (ELSEVIER SCIENCE BV, 1997-06-01)
    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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    The sensitivity of N-methyl-D-aspartate receptors to lead inhibition is dependent on the receptor subunit composition
    Omelchenko, IA ; Nelson, CS ; Marino, JL ; Allen, CN (WILLIAMS & WILKINS, 1996-07-01)
    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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    Melatonin receptors activate heteromeric G-protein coupled Kir3 channels
    Nelson, CS ; Marino, JL ; Allen, CN (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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    Increased microvessel density in mucinous compared with malignant serous and benign tumours of the ovary
    Orre, M ; Lotfi-Miri, M ; Mamers, P ; Rogers, PAW (CHURCHILL LIVINGSTONE, 1998-06-01)
    Microvessel density of benign, borderline and malignant ovarian tumours was studied immunohistochemically using antibodies to the endothelial cell markers CD31, CD34 and factor VIII-related antigen. Microvessel density was compared in tumours of different histological subtype, stage and patient outcome. CD31-immunostained sections were examined and regions of high and average microvessel density were selected. Identical regions were located on CD34- and factor VIII-related antigen-immunostained serial sections and microvessel counts obtained and converted to vessels mm(-2). CD31 and CD34 immunostaining revealed increased microvessel density in both the high and average vessel density regions of mucinous (222.4 +/- 24.8; 79.9 +/- 8.5) compared with serous (105.4 +/- 20.7; 33.3 +/- 6.8) and benign (84.4 +/- 19.4; 20.4 +/- 4.4) tumours (P < 0.001). CD31 and CD34 immunostaining also revealed increased microvessel density in early-stage mucinous tumours (234.6 +/- 28.2; 87.8 +/- 9.2) compared with that observed in both early- (72.8 +/- 15; 12.9 +/- 2.4) and late- (115.6 +/- 26.5; 29.8 +/- 8.5) stage serous tumours (P < 0.001). No differences in microvessel density in samples from patients with differing outcomes were observed (P > 0.05). Reduced factor VIII-related antigen compared with CD31 and CD34 immunostaining was observed in both borderline and malignant mucinous and serous tumours (P < 0.02) but not in benign tumours (P > 0.05). Our results contradict the putative association between increased microvessel density and poor prognosis and suggest that the level and control of angiogenesis may differ between ovarian tumour types.