Obstetrics and Gynaecology - Research Publications

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    Progressive genetic aberrations detected by comparative genomic hybridization in squamous cell cervical cancer.
    Allen, DG ; White, DJ ; Hutchins, AM ; Scurry, JP ; Tabrizi, SN ; Garland, SM ; Armes, JE (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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    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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    Is antenatal group B streptococcal carriage a predictor of adverse obstetric outcome?
    Garland, SM ; Kelly, N ; Ugoni, AM (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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    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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    Genetic aberrations detected by comparative genomic hybridisation in vulvar cancers
    Allen, D ; Hutchins, AM ; Hammet, F ; White, DJ ; Scurry, J ; Tabrizi, S ; Garland, SM ; Armes, JE (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.
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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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    Prevalence of sexually transmitted infections (Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and human papillomavirus) in female attendees of a sexually transmitted diseases clinic in Ulaanbaatar, Mongolia.
    Garland, SM ; Tabrizi, SN ; Chen, S ; Byambaa, C ; Davaajav, K (Hindawi Limited, 2001)
    BACKGROUND: Epidemiological data suggest that the prevalence of syphilis, gonorrhea and trichomoniasis has increased in both urban and rural areas of Mongolia. These data are primarily substantiated by notifications of cases of clinically apparent disease in both rural and urban areas, plus laboratory diagnoses from the AIDS/STD Reference Center, Ulaanbaatar. In the past 5 years, however, there has been a marked decline in the total number of patients being screened for sexually transmitted infections (STIs). An assessment of true prevalence of STIs in a female population attending an urban sexually transmitted diseases (STD) clinic was therefore commenced. METHODS: Consecutive women attending an STD clinic in Ulaanbaatar had genital samples collected by the insertion and immediate removal of a tampon, which was then tested for the presence of Neisseria gonorrhoeae, Chlamydia trachomatis, human papillomavirus (HPV) and Trichomonas vaginalis, using polymerase chain reaction (PCR) amplification. RESULTS: A total of 110 women were studied (mean age 26.7 years). Overall, 58 (53%) patients had one or more pathogens identified; 43 (39%) had a single pathogen, while 15 (14%) had mixed pathogens. C. trachomatis was found in 15 (14%), N. gonorrhoeae in 12 (11%), T. vaginalis in nine (8%) and HPV in 39 (36%). Among the 39 HPV-positive patients, oncogenicgenotypes (16, 18, 31, 33, 35, 39, 45, 51, 52) were found in 17(44%) patients. CONCLUSIONS: Sexually transmitted infections as defined by PCR were common, and found in 53% of female attendees of an urban STD clinic in Mongolia. As infections with conventional STIs increase the risk of human immunodeficiency virus (HIV) transmission, it is imperative that strategies be introduced to reduce the prevalence of STIs. Furthermore, detection of oncogenic HPV was common, indicating that it is vital that a strategy to reduce cervical cancer such as a pre-cancer cervical cytology screening program also be introduced.
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    Effect of lactobacillus in preventing post-antibiotic vulvovaginal candidiasis: a randomised controlled trial
    Pirotta, M ; Gunn, J ; Chondros, P ; Grover, S ; O'Malley, P ; Hurley, S ; Garland, S (B M J PUBLISHING GROUP, 2004-09-04)
    OBJECTIVE: To test whether oral or vaginal lactobacillus can prevent vulvovaginitis after antibiotic treatment. DESIGN: Randomised, placebo controlled, double blind, factorial 2x2 trial. SETTING: Fifty general practices and 16 pharmacies in Melbourne, Australia. PARTICIPANTS: Non-pregnant women aged 18-50 years who required a short course of oral antibiotics for a non-gynaecological infection: 278 were enrolled in the study, and results were available for 235. INTERVENTIONS: Lactobacillus preparations taken orally or vaginally, or both, from enrollment until four days after completion of their antibiotic course. MAIN OUTCOME MEASURES: Participants' reports of symptoms of post-antibiotic vulvovaginitis, with microbiological evidence of candidiasis provided by a self obtained vaginal swab. RESULTS: Overall, 55/235 (23% (95% confidence interval 18% to 29%)) women developed post-antibiotic vulvovaginitis. Compared with placebo, the odds ratio for developing post-antibiotic vulvovaginitis with oral lactobacillus was 1.06 (95% confidence interval 0.58 to 1.94) and with vaginal lactobacillus 1.38 (0.75 to 2.54). Compliance with antibiotics and interventions was high. The trial was terminated after the second interim analysis because of lack of effect of the interventions. Given the data at this time, the chances of detecting a significant reduction in vulvovaginitis with oral or vaginal lactobacillus treatment were less than 0.032 and 0.0006 respectively if the trial proceeded to full enrollment. CONCLUSIONS: The use of oral or vaginal forms of lactobacillus to prevent post-antibiotic vulvovaginitis is not supported by these results. Further research on this subject is unlikely to be fruitful, unless new understandings about the pathogenesis of post-antibiotic vulvovaginitis indicate a possible role for lactobacillus.