Obstetrics and Gynaecology - Research Publications
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ItemIs optimal first-line chemotherapy deliverable in all newly diagnosed ovarian cancers? A population-based study.(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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ItemLaparoscopic surgical techniques for endometriosis and adenomyosis.(Hindawi Limited, 2000)The details of surgical techniques for laparoscopic removal of endometriosis and adenomyosis are described briefly in textbooks and gynaecological journal articles. We have described a wide variety of techniques for the various procedures required in the treatment of endometriosis and adenomyosis, excluding hysterectomy. The principles are based upon those used in removal of primary cancer lesions. The limitations of thermal ablation are discussed, and evidence of improved results after excision of lesions have been submitted for publication.
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ItemNo Preview AvailableIL-11 and IL-11Ralpha immunolocalisation at primate implantation sites supports a role for IL-11 in placentation and fetal development.(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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ItemProgressive genetic aberrations detected by comparative genomic hybridization in squamous cell cervical cancer.(Springer Science and Business Media LLC, 2000-12)Genetic changes orchestrated by human papillomaviruses are the most important known factors in carcinogenesis of the uterine cervix. However, it is clear that additional genetic events are necessary for tumour progression. We have used comparative genomic hybridization to document non-random chromosomal gains and losses within a subset of 37 cervical carcinomas matched for clinical stage Ib, but with different lymph node status. There were significantly more chromosomal changes in the primary tumours when the lymph nodes were positive for metastases. The most frequent copy number alterations were loss of 3p, 11q, 6q and 10q and gain of 3q. The smallest areas of loss and gain on chromosome 3 were 3p14-22 and 3q24-26. The study identifies progressive DNA copy number changes associated with early-stage invasive cervical cancers with and without lymph node metastases, a factor of potential prognostic and therapeutic value.
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ItemNo Preview AvailablePatients' preferences for involvement in treatment decision making in Japan.(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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ItemNo Preview AvailableIs antenatal group B streptococcal carriage a predictor of adverse obstetric outcome?(Hindawi Limited, 2000)OBJECTIVES: While early-onset neonatal GBS sepsis is positively associated with premature birth and prolonged rupture of membranes, there is debate in the literature as to whether maternal GBS colonization is a predictor of adverse obstetric outcome. This is a critical issue to resolve for appropriate management (expectant vs. interventional management) of the patient presenting with premature rupture of membranes, who has no overt signs of sepsis, but who is colonized with GBS. METHODS: Since 1981 it has been hospital policy to screen all public patients antenatally for genital carriage of GBS by collection of a low vaginal swab at 28-32 weeks. All patients colonized with GBS antenatally are given penicillin as intrapartum chemoprophylaxis. Review of all GBS-colonized antenatal patients for a 12-month period (580 of 4,495 patients) and a randomized (every fourth consecutive antenatal patient) number of noncolonized patients (958) was made. Lower vaginal GBS colonization and other risk factors for preterm delivery were assessed using univariate and multivariate generalized linear modeling. RESULTS: In the study group, the maternal GBS colonization rate was 12.9%. When cofounding variables were controlled in a multivariate analysis, the association between antepartum GBS colonization and preterm labor and preterm rupture of membranes was not significant. CONCLUSION: Maternal antenatal carriage of GBS does not predict preterm labor. Therefore it is appropriate that expectant management occur for a GBS-colonized woman who ruptures her membranes, is not in labor, and has no evidence of sepsis.
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ItemNo Preview AvailableThe PAV trial: does lactobacillus prevent post-antibiotic vulvovaginal candidiasis? Protocol of a randomised controlled trial [ISRCTN24141277].(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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ItemProteomic-based identification of haptoglobin-1 precursor as a novel circulating biomarker of ovarian cancer(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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ItemDownregulation of urokinase plasminogen activator receptor expression inhibits Erk signalling with concomitant suppression of invasiveness due to loss of uPAR-β1 integrin complex in colon cancer cells(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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ItemGenetic aberrations detected by comparative genomic hybridisation in vulvar cancers(SPRINGERNATURE, 2002-03-18)Squamous cell carcinoma of the vulva is a disease of significant clinical importance, which arises in the presence or absence of human papillomavirus. We used comparative genomic hybridisation to document non-random chromosomal gains and losses within human papillomavirus positive and negative vulvar cancers. Gain of 3q was significantly more common in human papillomavirus-positive cancers compared to human papillomavirus-negative cancers. The smallest area of gain was 3q22-25, a chromosome region which is frequently gained in other human papillomavirus-related cancers. Chromosome 8q was more commonly gained in human papillomavirus-negative compared to human papillomavirus-positive cancers. 8q21 was the smallest region of gain, which has been identified in other, non-human papillomavirus-related cancers. Chromosome arms 3p and 11q were lost in both categories of vulvar cancer. This study has demonstrated chromosome locations important in the development of vulvar squamous cell carcinoma. Additionally, taken together with previous studies of human papillomavirus-positive cancers of other anogenital sites, the data indicate that one or more oncogenes important in the development and progression of human papillomavirus-induced carcinomas are located on 3q. The different genetic changes seen in human papillomavirus-positive and negative vulvar squamous cell carcinomas support the clinicopathological data indicating that these are different cancer types.