Obstetrics and Gynaecology - Research Publications
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ItemPublic and/or private health care: tuberculosis patients' perspectives in Myanmar.(Springer Science and Business Media LLC, 2009-07-28)BACKGROUND: Tuberculosis is a major public health problem in Myanmar as in other developing countries. About 73% of TB patients seek care at private general practitioners' clinics before presenting to the public TB centre, raising questions about how best to prevent transmission and maintain treatment regimens. METHOD: The study was conducted in two townships in Yangon Division in Myanmar in 2004, and examined treatment seeking behaviour of TB patients and their views towards public and private health care services. This was an exploratory descriptive study. Both quantitative and qualitative research methods were employed in data collection from TB patients, health care professionals, and members of various agencies involved in TB Control Programme. RESULTS: A considerable delay was found between the onset of symptoms of TB and seeking treatment (five days - two months). General practitioners were the first point of contact in all cases. Old TB patients influenced the treatment seeking behaviour and choice of treatment clinics of new TB patients. Most patients viewed the public health sector as a place to obtain free treatment and the private sector as a fee-paying, convenient and better place to seek treatment. CONCLUSION: The involvement of private general practitioners is crucial for effective TB control in Myanmar. The selection of GPs for partnership with the public sector is vital to the success of public-private partnership in controlling TB.
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ItemValidating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium(NATURE PUBLISHING GROUP, 2009-01-22)The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.
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ItemPriorities for Endometriosis Research: Recommendations From an International Consensus Workshop(SAGE PUBLICATIONS INC, 2009-04)Endometriosis is an estrogen-dependent disorder where endometrial tissue forms lesions outside the uterus. Endometriosis affects an estimated 10% of women in the reproductive-age group, rising to 30% to 50% in patients with infertility and/or pain, with significant impact on their physical, mental, and social well-being. There is no known cure, and most current medical treatments are not suitable long term due to their side-effect profiles. Endometriosis has an estimated annual cost in the United States of $18.8 to $22 billion (2002 figures). Although endometriosis was first described more than 100 years ago, current knowledge of its pathogenesis, spontaneous evolution, and the pathophysiology of the related infertility and pelvic pain, remain unclear. A consensus workshop was convened following the 10th World Congress on Endometriosis to establish recommendations for priorities in endometriosis research. One major issue identified as impacting on the capacity to undertake endometriosis research is the need for multidisciplinary expertise. A total of 25 recommendations for research have been developed, grouped under 5 subheadings: (1) diagnosis, (2) classification and prognosis, (3) treatment and outcome, (4) epidemiology, and (5) pathophysiology. Endometriosis research is underfunded relative to other diseases with high health care burdens. This may be due to the practical difficulties of developing competitive research proposals on a complex and poorly understood disease, which affects only women. By producing this consensus international research priorities statement it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis.
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ItemImproving the outcome of infants born at <30 weeks' gestation - a randomized controlled trial of preventative care at home(BMC, 2009-12-03)BACKGROUND: Early developmental interventions to prevent the high rate of neurodevelopmental problems in very preterm children, including cognitive, motor and behavioral impairments, are urgently needed. These interventions should be multi-faceted and include modules for caregivers given their high rates of mental health problems. METHODS/DESIGN: We have designed a randomized controlled trial to assess the effectiveness of a preventative care program delivered at home over the first 12 months of life for infants born very preterm (<30 weeks of gestational age) and their families, compared with standard medical follow-up. The aim of the program, delivered over nine sessions by a team comprising a physiotherapist and psychologist, is to improve infant development (cognitive, motor and language), behavioral regulation, caregiver-child interactions and caregiver mental health at 24 months' corrected age. The infants will be stratified by severity of brain white matter injury (assessed by magnetic resonance imaging) at term equivalent age, and then randomized. At 12 months' corrected age interim outcome measures will include motor development assessed using the Alberta Infant Motor Scale and the Neurological Sensory Motor Developmental Assessment. Caregivers will also complete a questionnaire at this time to obtain information on behavior, parenting, caregiver mental health, and social support. The primary outcomes are at 24 months' corrected age and include cognitive, motor and language development assessed with the Bayley Scales of Infant and Toddler Development (Bayley-III). Secondary outcomes at 24 months include caregiver-child interaction measured using an observational task, and infant behavior, parenting, caregiver mental health and social support measured via standardized parental questionnaires. DISCUSSION: This paper presents the background, study design and protocol for a randomized controlled trial in very preterm infants utilizing a preventative care program in the first year after discharge home designed to improve cognitive, motor and behavioral outcomes of very preterm children and caregiver mental health at two-years' corrected age. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12605000492651.
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ItemImpact of ritual pollution on lactation and breastfeeding practices in rural West Bengal, India(BIOMED CENTRAL LTD, 2009)BACKGROUND: Breastfeeding in India is universal and prolonged. Several cultural practices are associated with lactation and breastfeeding in India, mainly revolving around the concept of ritual purity and 'hot and cold' foods, food avoidance, restricted diet after childbirth, and remaining in seclusion for a certain time period because of the polluting effects of childbirth. This study on breastfeeding practices explored how the concept of ritual pollution influenced practices after delivery, including during lactation and breastfeeding. METHODS: The study was conducted in four villages of West Bengal State in India, representing different levels of socioeconomic development, religion, and caste/tribe from September 1993 to April 1994. One hundred households with one woman respondent from each household were selected from each village. Both qualitative and quantitative methods were employed for data collection. A survey questionnaire was administered to 402 respondents and in-depth interviews were conducted with 30 women in the reproductive age group (13-49 years), and 12 case studies were documented with women belonging to different caste, religious, and tribal groups. RESULTS: Belief in 'impurity and polluting effects of childbirth' necessitated seclusion and confinement of mothers after childbirth in the study villages. Breastfeeding was universal and prolonged, and food proscriptions were followed by mothers after childbirth to protect the health of their newborn. Initiation of breastfeeding was delayed after birth because of the belief that mother's milk is 'not ready' until two-to-three days postpartum. Generally, colostrum was discarded before putting the infant to the breast in the study villages. Breastfeeding lasted up to five years, and the majority of women in the sample introduced supplementary food before six months. Most infants in the study villages were given a prelacteal feed immediately after birth, only a small number of women (35) exclusively breastfed - after giving a prelacteal feed - until six months in the study villages. CONCLUSION: Cultural and traditional practices have considerable implications on lactation and breastfeeding, and in the overall well-being and health of mothers and infants. Breastfeeding programs should take into account traditional beliefs and concepts when communicating with families about practices such as food restriction and food avoidance.
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ItemVaginal repair with mesh versus colporrhaphy for prolapse: a randomised controlled trial(WILEY-BLACKWELL PUBLISHING, INC, 2009-09)OBJECTIVE: To compare vaginal repair augmented by mesh with traditional colporrhaphy for the treatment of pelvic organ prolapse. DESIGN: Prospective randomised controlled trial. SETTING: Tertiary teaching hospital. POPULATION: One hundred and thirty-nine women with stage >or=2 prolapse according to the pelvic organ prolapse quantification (POP-Q) system requiring both anterior and posterior compartment repair. METHODS: Subjects were randomised to anterior and posterior vaginal repair with mesh augmentation (mesh group, n = 69) or traditional anterior and posterior colporrhaphy (no mesh group, n = 70). MAIN OUTCOME MEASURES: The primary outcome was the absence of POP-Q stage >or=2 prolapse at 12 months. Secondary outcomes were symptoms, quality-of-life outcomes and satisfaction with surgery. Complications were also reported. RESULTS: For subjects attending the 12-month review, success in the mesh group was 81.0% (51 of 63 subjects) compared with 65.6% (40/61) in the no mesh group and was not significantly different (P-value = 0.07). A high level of satisfaction with surgery and improvements in symptoms and quality-of-life data were observed at 12 months compared to baseline in both groups, but there was no significant difference in these outcomes between the two groups. Vaginal mesh exposure occurred in four women in the mesh group (5.6%). De novo dyspareunia was reported by five of 30 (16.7%) sexually active women in the mesh group and five of 33 (15.2%) in the no mesh group at 12 months. CONCLUSION: In this study, vaginal surgery augmented by mesh did not result in significantly less recurrent prolapse than traditional colporrhaphy 12 months following surgery.
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ItemAssessing knowledge of human papillomavirus and collecting data on sexual behavior: computer assisted telephone versus face to face interviews(BMC, 2009-11-23)BACKGROUND: Education campaigns seeking to raise awareness of human papillomavirus (HPV) and promoting HPV vaccination depend on accurate surveys of public awareness and knowledge of HPV and related sexual behavior. However, the most recent population-based studies have relied largely on computer-assisted telephone interviews (CATI) as opposed to face to face interviews (FTFI). It is currently unknown how these survey modes differ, and in particular whether they attract similar demographics and therefore lead to similar overall findings. METHODS: A comprehensive survey of HPV awareness and knowledge, including sexual behavior, was conducted among 3,045 Singaporean men and women, half of whom participated via CATI, the other half via FTFI. RESULTS: Overall levels of awareness and knowledge of HPV differed between CATI and FTFI, attributable in part to demographic variations between these survey modes. Although disclosure of sexual behavior was greater when using CATI, few differences between survey modes were found in the actual information disclosed. CONCLUSION: Although CATI is a cheaper, faster alternative to FTFI and people appear more willing to provide information about sexual behavior when surveyed using CATI, thorough assessments of HPV awareness and knowledge depend on multiple survey modes.
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ItemCRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool?(BMC, 2009-11-30)The search for a suitable biomarker which indicates immune system responses in cancer patients has been long and arduous, but a widely known biomarker has emerged as a potential candidate for this purpose. C-Reactive Protein (CRP) is an acute-phase plasma protein that can be used as a marker for activation of the immune system. The short plasma half-life and relatively robust and reliable response to inflammation, make CRP an ideal candidate marker for inflammation. The high- sensitivity test for CRP, termed Low-Reactive Protein (LRP, L-CRP or hs-CRP), measures very low levels of CRP more accurately, and is even more reliable than standard CRP for this purpose. Usually, static sampling of CRP has been used for clinical studies and these can predict disease presence or recurrence, notably for a number of cancers. We have used frequent serial L-CRP measurements across three clinical laboratories in two countries and for different advanced cancers, and have demonstrated similar, repeatable observations of a cyclical variation in CRP levels in these patients. We hypothesise that these L-CRP oscillations are part of a homeostatic immune response to advanced malignancy and have some preliminary data linking the timing of therapy to treatment success. This article reviews CRP, shows some of our data and advances the reasoning for the hypothesis that explains the CRP cycles in terms of homeostatic immune regulatory cycles. This knowledge might also open the way for improved timing of treatment(s) for improved clinical efficacy.
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ItemEarly biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs(BMC, 2009-03-10)BACKGROUND: Bronchopulmonary dysplasia (BPD) is closely associated with ventilator-induced lung injury (VILI) in very preterm infants. The greatest risk of VILI may be in the immediate period after birth, when the lungs are surfactant deficient, still partially filled with liquid and not uniformly aerated. However, there have been very few studies that have examined this immediate post-birth period and identified the initial injury-related pathways that are activated. We aimed to determine if the early response genes; connective tissue growth factor (CTGF), cysteine rich-61 (CYR61) and early growth response 1 (EGR1), were rapidly induced by VILI in preterm lambs and whether ventilation with different tidal volumes caused different inflammatory cytokine and early response gene expression. METHODS: To identify early markers of VILI, preterm lambs (132 d gestational age; GA, term approximately 147 d) were resuscitated with an injurious ventilation strategy (V(T) 20 mL/kg for 15 min) then gently ventilated (5 mL/kg) for 15, 30, 60 or 120 min (n = 4 in each). To determine if early response genes and inflammatory cytokines were differentially regulated by different ventilation strategies, separate groups of preterm lambs (125 d GA; n = 5 in each) were ventilated from birth with a V(T) of 5 (VG5) or 10 mL/kg (VG10) for 135 minutes. Lung gene expression levels were compared to levels prior to ventilation in age-matched control fetuses. RESULTS: CTGF, CYR61 and EGR1 lung mRNA levels were increased approximately 25, 50 and 120-fold respectively (p < 0.05), within 30 minutes of injurious ventilation. VG5 and VG10 caused significant increases in CTGF, CYR61, EGR1, IL1- , IL-6 and IL-8 mRNA levels compared to control levels. CTGF, CYR61, IL-6 and IL-8 expression levels were higher in VG10 than VG5 lambs; although only the IL-6 and CYR61 mRNA levels reached significance. CONCLUSION: CTGF, CYR61 and EGR1 may be novel early markers of lung injury and mechanical ventilation from birth using relatively low tidal volumes may be less injurious than using higher tidal volumes.
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ItemPlacenta-specific Methylation of the Vitamin D 24-Hydroxylase Gene IMPLICATIONS FOR FEEDBACK AUTOREGULATION OF ACTIVE VITAMIN D LEVELS AT THE FETOMATERNAL INTERFACE(ELSEVIER, 2009-05-29)Plasma concentrations of biologically active vitamin D (1,25-(OH)(2)D) are tightly controlled via feedback regulation of renal 1alpha-hydroxylase (CYP27B1; positive) and 24-hydroxylase (CYP24A1; catabolic) enzymes. In pregnancy, this regulation is uncoupled, and 1,25-(OH)(2)D levels are significantly elevated, suggesting a role in pregnancy progression. Epigenetic regulation of CYP27B1 and CYP24A1 has previously been described in cell and animal models, and despite emerging evidence for a critical role of epigenetics in placentation generally, little is known about the regulation of enzymes modulating vitamin D homeostasis at the fetomaternal interface. In this study, we investigated the methylation status of genes regulating vitamin D bioavailability and activity in the placenta. No methylation of the VDR (vitamin D receptor) and CYP27B1 genes was found in any placental tissues. In contrast, the CYP24A1 gene is methylated in human placenta, purified cytotrophoblasts, and primary and cultured chorionic villus sampling tissue. No methylation was detected in any somatic human tissue tested. Methylation was also evident in marmoset and mouse placental tissue. All three genes were hypermethylated in choriocarcinoma cell lines, highlighting the role of vitamin D deregulation in this cancer. Gene expression analysis confirmed a reduced capacity for CYP24A1 induction with promoter methylation in primary cells and in vitro reporter analysis demonstrated that promoter methylation directly down-regulates basal promoter activity and abolishes vitamin D-mediated feedback activation. This study strongly suggests that epigenetic decoupling of vitamin D feedback catabolism plays an important role in maximizing active vitamin D bioavailability at the fetomaternal interface.