Obstetrics and Gynaecology - Research Publications

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    Is optimal first-line chemotherapy deliverable in all newly diagnosed ovarian cancers? A population-based study.
    McNally, OM ; Delaney, E ; Petty, RD ; Cruickshank, ME ; Hutcheon, AW ; Parkin, DE (Springer Science and Business Media LLC, 2003-09-15)
    NICE guidance recommends the use of paclitaxel and a platinum therapy for all cases of ovarian cancer. We report our experience of treating 133 patients with ovarian cancer over a 3-year period. Where indicated, 91% received chemotherapy. A taxane/platinum combination was found to be appropriate in 63% of patients only.
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    IL-11 and IL-11Ralpha immunolocalisation at primate implantation sites supports a role for IL-11 in placentation and fetal development.
    Dimitriadis, E ; Robb, L ; Liu, Y-X ; Enders, AC ; Martin, H ; Stoikos, C ; Wallace, E ; Salamonsen, LA (Springer Science and Business Media LLC, 2003-04-11)
    Embryo implantation, endometrial stromal cell decidualization and formation of a functional placenta are critical processes in the establishment and maintenance of pregnancy. Interleukin (IL)-11 signalling is essential for adequate decidualization in the mouse uterus and IL-11 promotes decidualization in the human. IL-11 action is mediated via binding to the specific IL-11 receptor alpha (IL-11Ralpha). The present study examined immunoreactive IL-11 and IL-11Ralpha in cycling rhesus monkey endometrium, at implantation sites in cynomolgus and rhesus monkeys and in human first trimester decidua and defined distinct spatial and temporal patterns. In cycling rhesus monkey endometrium, IL-11 and IL-11Ralpha increased in both basalis and functionalis regions during the secretory compared with the proliferative phase, with changing cellular locations in luminal and glandular epithelium and stroma. The patterns were similar overall to those previously described in human endometrium. Differences were seen in immunostaining during implantation in cynomologus and rhesus monkey. In the cynomolgus, very little staining for IL-11 or IL-11Ralpha was seen in syncytio- and cyto-trophoblast cells in the villi between days 12 and 150 of pregnancy although there was moderate staining in cytotrophoblast in the shell between days 12 and 17 and in subpopulations of cytotrophoblast cells invading the arteries at day 17. By contrast in the rhesus monkey between days 24 and 35 of pregnancy and in human first trimester placenta, cyto- and syncytio-trophoblast in the villi but not cytotrophoblast in the shell were positively stained. The most intense staining for both IL-11 and IL-11Ralpha was present within the decidua in the maternal component of implantation sites in all three primates but moderate staining was also present in maternal vascular smooth muscle and glands perivascular cells and epithelial plaques. These results are consistent with a role for IL-11 both during decidualization and placentation in primates.
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    Patients' preferences for involvement in treatment decision making in Japan.
    Sekimoto, M ; Asai, A ; Ohnishi, M ; Nishigaki, E ; Fukui, T ; Shimbo, T ; Imanaka, Y (Springer Science and Business Media LLC, 2004-03-01)
    BACKGROUND: A number of previous studies have suggested that the Japanese have few opportunities to participate in medical decision-making, as a result both of entrenched physician paternalism and national characteristics of dependency and passivity. The hypothesis that Japanese patients would wish to participate in treatment decision-making if adequate information were provided, and the decision to be made was clearly identified, was tested by interview survey. METHODS: The subjects were diabetic patients at a single outpatient clinic in Kyoto. One of three case study vignettes (pneumonia, gangrene or cancer) was randomly assigned to each subject and, employing face-to-face interviews, the subjects were asked what their wishes would be as patients, for treatment information, participation in decision-making and family involvement. RESULTS: 134 patients participated in the study, representing a response rate of 90%. The overall proportions of respondents who preferred active, collaborative, and passive roles were 12%, 71%, and 17%, respectively. Respondents to the cancer vignette were less likely to prefer an active role and were more likely to prefer family involvement in decision-making compared to non-cancer vignette respondents. If a physician's recommendation conflicted with their own wishes, 60% of the respondents for each vignette answered that they would choose to respect the physician's opinion, while few respondents would give the family's preference primary importance. CONCLUSIONS: Our study suggested that a majority of Japanese patients have positive attitudes towards participation in medical decision making if they are fully informed. Physicians will give greater patient satisfaction if they respond to the desire of patients for participation in decision-making.
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    The PAV trial: does lactobacillus prevent post-antibiotic vulvovaginal candidiasis? Protocol of a randomised controlled trial [ISRCTN24141277].
    Pirotta, M ; Gunn, J ; Chondros, P ; Grover, S ; Hurley, S ; Garland, S (Springer Science and Business Media LLC, 2004-03-28)
    BACKGROUND: Complementary and alternative medicines are used by many consumers, and increasingly are being incorporated into the general practitioner's armamentarium. Despite widespread usage, the evidence base for most complementary therapies is weak or non-existent. Post-antibiotic vulvovaginitis is a common problem in general practice, for which complementary therapies are often used. A recent study in Melbourne, Australia, found that 40% of women with a past history of vulvovaginitis had used probiotic Lactobacillus species to prevent or treat post-antibiotic vulvovaginitis. There is no evidence that this therapy is effective. This study aims to test whether oral or vaginal lactobacillus is effective in the prevention of post-antibiotic vulvovaginitis. METHODS/DESIGN: A randomised placebo-controlled blinded 2 x 2 factorial design is being used. General practitioners or pharmacists approach non-pregnant women, aged 18-50 years, who present with a non-genital infection requiring a short course of oral antibiotics, to participate in the study. Participants are randomised in a four group factorial design either to oral lactobacillus powder or placebo and either vaginal lactobacillus pessaries or placebo. These interventions are taken while on antibiotics and for four days afterwards or until symptoms of vaginitis develop. Women self collect a vaginal swab for culture of Candida species and complete a survey at baseline and again four days after completing their study medications. The sample size (a total of 496--124 in each factorial group) is calculated to identify a reduction of half in post-antibiotic vulvovaginitis from 23%, while allowing for a 25% drop-out. An independent Data Monitoring Committee is supervising the trial. Analysis will be intention-to-treat, with two pre-specified main comparisons: (i) oral lactobacillus versus placebo and (ii) vaginal lactobacillus versus placebo.
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    Proteomic-based identification of haptoglobin-1 precursor as a novel circulating biomarker of ovarian cancer
    Ahmed, N ; Barker, G ; Oliva, KT ; Hoffmann, P ; Riley, C ; Reeve, S ; Smith, AL ; Kemp, BE ; Quinn, MA ; Rice, GE (NATURE PUBLISHING GROUP, 2004-07-05)
    Screening for specific biomarkers of early-stage detection of ovarian cancer is a major health priority due to the asymptomatic nature and poor survival characteristic of the disease. We utilised two-dimensional gel electrophoresis (2DE) to identify differentially expressed proteins in the serum of ovarian cancer patients that may be useful as biomarkers of this disease. In this study, 38 ovarian cancer patients at different pathological grades (grade 1 (n=6), grade 2 (n=8) and grade 3 (n=24)) were compared to a control group of eight healthy women. Serum samples were treated with a mixture of Affigel-Blue and protein A (5 : 1) for 1 h to remove high abundance protein (e.g. immunoglobulin and albumin) and were displayed using 11 cm, pH 4-7 isoelectric focusing strips for the first dimension and 10% acrylamide gel electrophoresis for the second dimension. Protein spots were visualised by SYPRO-Ruby staining, imaged by FX-imager and compared and analysed by PDQuest software. A total of 24 serum proteins were differentially expressed in grade 1 (P<0.05), 31 in grade 2 (P<0.05) and 25 in grade 3 (P<0.05) ovarian cancer patients. Six of the protein spots that were significantly upregulated in all groups of ovarian cancer patients were identified by nano-electrospray quadrupole quadrupole time-of-flight mass spectrometry (n-ESIQ(q)TOFMS) and matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOFMS) as isoforms of haptoglobin-1 precursor (HAP1), a liver glycoprotein present in human serum. Further identification of the spots at different pathological grades was confirmed by Western blotting using monoclonal antibody against a haptoglobin epitope contained within HAP1. Immunohistochemical localisation of HAP1-like activity was present in malignant ovarian epithelium and stroma but strong immunostaining was present in blood vessels, areas with myxomatous stroma and vascular spaces. No tissue localisation of HAP1-like immunoreactivity was observed in normal ovarian surface epithelium. These data highlight the need to assess circulating concentration of HAP1 in the serum of ovarian cancer patients and evaluate its potential as a biomarker in the early diagnosis of ovarian cancer.
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    Downregulation of urokinase plasminogen activator receptor expression inhibits Erk signalling with concomitant suppression of invasiveness due to loss of uPAR-beta 1 integrin complex in colon cancer cells
    Ahmed, N ; Oliva, K ; Wang, Y ; Quinn, M ; Rice, G (NATURE PUBLISHING GROUP, 2003-07-21)
    Cancer invasion is regulated by cell surface proteinases and adhesion molecules. Interaction between specific cell surface molecules such as urokinase plasminogen activator receptor (uPAR) and integrins is crucial for tumour invasion and metastasis. In this study, we examined whether uPAR and beta1 integrin form a functional complex to mediate signalling required for tumour invasion. We assessed the expression of uPAR/beta1 integrin complex, Erk signalling pathway, adhesion, uPA and matrix metalloproteinase (MMP) expression, migration/invasion and matrix degradation in a colon cancer cell line in which uPAR expression was modified. Antisense inhibition of the cell surface expression of uPAR by 50% in human colon carcinoma HCT116 cells (A/S) suppressed Erk-MAP kinase activity by two-fold. Urokinase plasminogen activator receptor antisense treatment of HCT116 cells was associated with a 1.3-fold inhibition of adhesion, approximately four-fold suppression of HMW-uPA secretion and inhibition of pro-MMP-9 secretion. At a functional level, uPAR antisense resulted in a four-fold decline in migration/invasion and abatement of plasmin-mediated matrix degradation. In empty vector-transfected cells (mock), uPA strongly elevated basal Erk activation. In contrast, in A/S cells, uPA induction of Erk activation was not observed. Urokinase plasminogen activator receptor associated with beta1 integrin in mock-transfected cells. Disruption of uPAR-beta1 integrin complex in mock-transfected cells with a specific peptide (P25) inhibited uPA-mediated Erk-MAP kinase pathway and inhibited migration/invasion and plasmin-dependent matrix degradation through suppression of pro-MMP-9/MMP-2 expression. This novel paradigm of uPAR-integrin signalling may afford opportunities for alternative therapeutic strategies for the treatment of cancer.
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    Apaf-1 and caspase-9 do not act as tumor suppressors in myc-induced lymphomagenesis or mouse embryo fibroblast transformation
    Scott, CL ; Schuler, M ; Marsden, VS ; Egle, A ; Pellegrini, M ; Nesic, D ; Gerondakis, S ; Nutt, SL ; Green, DR ; Strasser, A (ROCKEFELLER UNIV PRESS, 2004-01-05)
    Based on experiments with cultured fibroblasts, the apoptosis regulators caspase-9 and Apaf-1 are hypothesized to function as tumor suppressors. To investigate their in vivo role in lymphomagenesis, an IgH enhancer-driven c-myc transgene was crossed onto Apaf-1(-/-) and caspase-9(-/-) mice. Due to perinatal lethality, Emu-myc transgenic Apaf-1(-/-) or caspase-9(-/-) fetal liver cells were used to reconstitute lethally irradiated recipient mice. Surprisingly, no differences were seen in rate, incidence, or severity of lymphoma with loss of Apaf-1 or caspase-9, and Apaf-1 was not a critical determinant of anticancer drug sensitivity of c-myc-induced lymphomas. Moreover, loss of Apaf-1 did not promote oncogene-induced transformation of mouse embryo fibroblasts. Thus, Apaf-1 and caspase-9 do not suppress c-myc-induced lymphomagenesis and embryo fibroblast transformation.
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    Screening protocols for group B streptococcus: are transport media appropriate?
    Teese, N ; Henessey, D ; Pearce, C ; Kelly, N ; Garland, S (Hindawi Limited, 2003)
    OBJECTIVE: To evaluate group B streptococcus (GBS) detection in an in vitro setting, using a low and controlled inoculum from swabs directly inoculated into a selective medium, as compared to delayed inoculation following a period in a commercial Amies transport medium with charcoal (Venturi Transystem Copan, Italy). STUDY DESIGN: Clinical isolates of GBS (n = 103), were inoculated into the Amies transport medium with charcoal in a concentration of 100 colony-forming units (cfu)/ml (10 cfu/swab). Swabs were then transferred to an enrichment broth (NPC) at time intervals of 0, 2, 4, 6 and 24 hours. Broths were then incubated for 18-24 hours at 35 degrees C in air, before being transferred to New Granada Medium Modified (NGM) for GBS detection and incubated for a further 18-24 hours at 35 degrees C in air. If the characteristic orange pigmented colonies were observed after this period, the specimen was recorded as + (1-10 colonies) or + + (more than 10 colonies). RESULTS: Overall 92.2% (95/103) of isolates were detected in all tubes and at all times. An additional two isolates were non-hemolytic, non-pigment forming GBS. Of note, 3.9% (4/103) were negative until 2 hours delayed inoculation and 1.9% (2/103) gave inconsistent results, likely due to the low inoculum used. CONCLUSION: Delayed inoculation into selective enrichment broth following a period in transport medium, even with a low inoculum, gave a similar and acceptable GBS detection rate to direct inoculation. Hence, Amies transport medium with charcoal is an appropriate transport medium to use, where it is not practical for clinical specimens to be directly inoculated into selective enrichment broth and as endorsed in the Centers for Diseases Control (CDC) Guidelines, 2002.
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    A failed RCT to determine if antibiotics prevent mastitis: Cracked nipples colonized with Staphylococcus aureus: A randomized treatment trial [ISRCTN65289389].
    Amir, LH ; Lumley, J ; Garland, SM (Springer Science and Business Media LLC, 2004-09-16)
    BACKGROUND: A small, non-blinded, RCT (randomised controlled trial) had reported that oral antibiotics reduced the incidence of mastitis in lactating women with Staphylococcus aureus (S. aureus)- colonized cracked nipples. We aimed to replicate the study with a more rigorous design and adequate sample size. METHODS: Our intention was to conduct a double-blind placebo-controlled trial to determine if an antibiotic (flucloxacillin) could prevent mastitis in lactating women with S. aureus-colonized cracked nipples. We planned to recruit two groups of 133 women with S. aureus-colonized cracked nipples. RESULTS: We spent over twelve months submitting applications to five hospital ethics committees and seven funding bodies, before commencing the trial. Recruitment to the trial was very slow and only ten women were randomized to the trial after twelve months, and therefore the trial was stopped early. CONCLUSIONS: In retrospect we should have conducted a feasibility study, which would have revealed the low number of women in these Melbourne hospitals (maternity wards and breastfeeding clinics) with damaged nipples. The appropriate use of antibiotics for breastfeeding women with cracked nipples still needs to be tested.
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    Uterine leiomyoma and menstrual cycle characteristics in a population-based cohort study
    Marino, JL ; Eskenazi, B ; Warner, M ; Samuels, S ; Vercellini, P ; Gavoni, N ; Olive, D (OXFORD UNIV PRESS, 2004-10-01)
    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.