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Biomedical subjects

D Purdie

Publications and source records attributed to D Purdie.

At least 37 records · Page 2Linked to original sources

Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis.

Steatosis is a frequent histological finding in chronic hepatitis C infection; however, the pathophysiology of steatosis and its role in disease progression have not been established. We studied 148 consecutive patients with untreated chronic hepatitis C to assess the effect of body mass index, diabetes mellitus, alcohol consumption, hepatic iron content, and viral load on steatosis and hepatic fibrosis. Ninety-one patients (61%) had steatosis: grade 1 (<30% hepatocytes involved) in 61 (41%), grade 2 (30%-70% hepatocytes involved) in 17 (11%), and grade 3 (>70% hepatocytes involved) in 13 (9%). After adjusting for potential confounding variables, a highly significant relationship was found primarily between steatosis and body mass index (P <.0001). The mean (+/-SD) body mass index of patients with no steatosis was 23.9 +/- 4.3 kg/m2, whereas for grade 1 steatosis it was 26.5 +/- 5.1 kg/m2, and for grade 2 and 3 steatosis combined the body mass index was 28.4 +/- 4. 9 kg/m2. Hepatic fibrosis was significantly associated with age (P =. 002). After adjusting for potential confounding variables, including age, hepatic fibrosis was also significantly associated with steatosis (P <.03). There was no significant association between hepatic iron content, alcohol intake, gender, and viral load and steatosis or fibrosis. These findings suggest that increasing body mass index has a role in the pathogenesis of steatosis in chronic hepatitis C and that steatosis may contribute to fibrosis. The association between body mass index and steatosis and fibrosis has important prognostic and therapeutic implications in the management of patients with chronic hepatitis C virus.

Adult↗

Predictive factors of age at menopause in a large Australian twin study.

Various studies have investigated potential predictors of age at natural menopause but have produced inconsistent results. The relationship between age at natural menopause and socioeconomic, reproductive, and health behavioral factors was evaluated using longitudinal data from 5961 Australian female twins, aged 17 to 88 years at the time of study. The sample consisted of women voluntarily enrolled in the Australian Twin Registry. Failure-time analysis was the principal statistical method used to handle censored observations. Kaplan-Meier estimates showed the overall median age at natural menopause to be 51 years (95% confidence interval, 50-51). Median age at menopause was earlier for women with earlier birth year, women with late age of menarche, women who had no children, or women who were smokers. Differences in age at menopause between social, occupational, and educational groups were statistically significant (Mantel-Cox test, p < 0.001) for education, major occupational classification, combined income, and self-rated social class, with higher age at menopause for higher levels of each variable. A Cox proportional hazards model was used to estimate the odds ratio of the occurrence of natural menopause among different sub-groups, adjusted to reflect simultaneous effects of all other significant covariates. This large study provided clear trends of association in predictors relating to age at menopause. These trends may help to resolve uncertainties and conflicting results identified in studies of comparable white samples. The nature of the twin data also sets a solid background for future analyses of genetic and environmental variance components using statistical modeling or related methods.

Adolescent↗

Tubal sterilisation, hysterectomy and decreased risk of ovarian cancer. Survey of Women's Health Study Group.

We have examined the effect of tubal sterilisation and hysterectomy on risk of ovarian cancer in a large case-control study in eastern Australia involving 824 women aged 18-79 years, diagnosed with epithelial ovarian cancer between 1990 and 1993, and 855 controls randomly selected from the electoral roll. Relative risks for ovarian cancer were estimated using multiple categorical regression to adjust for age, parity, oral contraceptive use and other risk factors. Tubal sterilisation was associated with a 39% reduction in risk of ovarian cancer (RR 0.61, 95% CI 0.46-0.85) and hysterectomy with a 36% reduction (RR 0.64, 95% CI 0.48-0.85). Risk remained low 25 years after surgery and was reduced irrespective of sterilisation technique, and estimates were similar among various types of epithelial ovarian cancer. The greatest reduction (74%) was observed among women with primary peritoneal tumours. Pelvic infection and use of vaginal sprays or contraceptive foams were not related to ovarian cancer, while use of talc in the perineal region slightly but significantly increased risk among women with patent fallopian tubes. Reportedly heavy or painful menses, perhaps associated with retrograde flow, were associated with ovarian cancer, and reduction in risk of disease after hysterectomy was greatest among women who had heavy periods. Our findings support the theory that contaminants from the vagina, such as talc, and from the uterus, such as endometrium, gain access to the peritoneal cavity through patent fallopian tubes and may enhance the malignant transformation of ovarian surface epithelium. Surgical tubal occlusion may reduce the risk of ovarian cancer by preventing the access of such agents.

Adolescent↗

Analysis of loss of heterozygosity and KRAS2 mutations in ovarian neoplasms: clinicopathological correlations.

The molecular events that give rise to ovarian epithelial neoplasms are not well understood. In particular, it is not known whether adenocarcinomas arise from benign or low malignant potential (LMP) precursors. We have examined a large series of benign (25) and LMP (31) ovarian tumors for loss of heterozygosity (LOH) at multiple loci on 17 chromosomes. LOH was observed in benign tumors on chromosomes 6 (14%) and 9 (5%) and on the X chromosome (33%) only. LOH on these chromosomes was also detected in a small number of LMP neoplasms, suggesting that these may derive sometimes from benign precursors. In addition, we examined LOH in 93 adenocarcinomas. Analysis of associations between LOH events showed that LOH on chromosomes 5 and 17 (P = 0.0002) and on chromosomes 17 and 18 (P = 0.00007) were associated significantly with each other, which suggests that these may represent cooperative, progressive events. No novel significant associations were identified between LOH events and stage, grade, or histology, which would indicate the existence of genetic heterogeneity in ovarian neoplasms. KRAS2 mutations were detected more often in LMP neoplasms than in malignant tumors (P = 0.004) and were detected more often in Stage I/II malignant tumors than in Stage III/IV malignant tumors (P = 0.033), suggesting that LMP tumors with KRAS2 mutations are unlikely to progress to frank malignancy. Univariate (but not multivariate) survival analysis showed that LOH of chromosomes 11 (P = 0.039) and 17 (P = 0.04) was associated with a significantly worse prognosis. Replication of these novel findings is necessary, and the identification, isolation, and characterization of the critical genes affected by LOH will determine their importance in the pathogenesis of ovarian malignancies.

Chromosome Deletion↗

Breastfeeding, menopause, and epithelial ovarian cancer.

No previous study has examined the modifying effect of menopausal status on the association between lactation and ovarian cancer risk. We recruited 824 epithelial ovarian cancer cases and 855 community controls in three Australian states, collecting reproductive and lactation histories by means of a contraceptive calendar and pregnancy and breastfeeding record. We report results in women with at least one liveborn infant for unsupplemented breastfeeding, in line with a biological model linking suppression of ovulation to reduction in ovarian cancer risk. We derived odds ratios from multiple logistic regression models including number of liveborn children, age, age at first or last birth, and other potential confounders, overall and by menopausal status. Estimates of relative risk of ovarian cancer per month of full lactation were 0.99 [95% confidence interval (CI) = 0.97-1.00] overall and 1.00 (95% CI = 0.99-1.01) and 0.98 (95% CI = 0.95-1.01) among post- and premenopausal women, respectively. We tailored a lactation variable to the incessant ovulation hypothesis by progressively discounting breastfeeding the longer after birth it occurred, finding odds ratios similar to those for the unmodified duration variable. We found no association of note among postmenopausal women. Breastfeeding seems to be somewhat protective against ovarian cancer, but only before menopause.

Adult↗

Validity of self-reported hysterectomy and tubal sterilisation. The Survey of Women's Health Study Group.

Both hysterectomy and tubal sterilisation offer significant protection from ovarian cancer, and the risk of cardiovascular disease in women is lowered after hysterectomy. Since little is known about the accuracy of women's self-reports of these procedures, we assessed their reliability and validity using data obtained in a case-control study of ovarian cancer. There was 100 per cent repeatability for both positive and negative histories of hysterectomy and tubal sterilisation among a small sample of women on reinterview. Verification of surgery was sought against surgeons' or medical records, or if these were unavailable, from randomly selected current general practitioners for 51 cases and 155 controls reporting a hysterectomy and 73 cases and 137 controls reporting a tubal sterilisation. Validation rate for self-reported hysterectomy against medical reports (32 cases, 96 controls) was 96 per cent (95 per cent confidence interval (CI) 91 to 99) and for tubal sterilisation (32 cases, 77 controls) it was 88 per cent (CI 81 to 93), which is likely to be an underestimate. Although findings are based on small numbers of women for whom medical reports could be ascertained, they are consistent with other findings that suggest women have good recall of past histories of hysterectomy and tubal sterilisation; this allows long-term effects of these procedures to be studied with reasonable accuracy from self-reports.

Adolescent↗

Reproductive and other factors and risk of epithelial ovarian cancer: an Australian case-control study. Survey of Women's Health Study Group.

Of the few factors known to be associated with epithelial ovarian cancer, the most consistently observed relate to women's reproductive function, although even here uncertainties remain. We have undertaken a case-control study involving personal interviews with over 1,600 women, the largest of its kind to date, to investigate further the associations between women's reproductive histories and other factors and the development of ovarian cancer. Cases were drawn from women diagnosed with epithelial ovarian cancer in 3 Australian states, Queensland, New South Wales and Victoria, between August 1990 and December 1993, and controls were drawn at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed information about women's reproductive and contraceptive histories and other factors of interest, such as smoking and family history of ovarian or other cancer. Findings were based on data from 824 cases and 860 controls and confirmed the reduced risk of ovarian cancer associated with increasing parity and duration of use of the oral contraceptive pill (OCP), hysterectomy and tubal ligation. The strongest association of all was seen with use of the OCP for 10 years or more. An inverse association between ovarian cancer and age at first birth was observed, but this was not statistically significant. There were no associations between development of ovarian cancer and number of incomplete pregnancies, use of hormone replacement therapy or menstrual history. Among other factors considered, education after leaving school was negatively associated and high body mass index, family history of ovarian cancer, use of talc in the abdominal or perineal region and smoking were positively associated with occurrence of ovarian cancer.

Adolescent↗

General practitioner and patient response during a public education program to encourage skin examinations.

OBJECTIVE: To describe the response of general practitioners (GPs) and patients during the 1991 National Skin Cancer Awareness Week media campaign. DESIGN: Skin examinations in general practices in three representative regional towns in Queensland were monitored for five weeks around the time of the campaign and participating GPs were personally interviewed. OUTCOME MEASURES: Number and type of consultations in which the skin was examined for cancer before, during and after the campaign, and GPs' attitudes and beliefs about skin checks. RESULTS: The 46 GPs (47%) who participated, representing 60% of the practices, conducted 1805 consultations in which the skin was examined for cancer. The number of consultations in which skin examinations were conducted by each GP increased by 56% during the campaign. Skin checks were nearly always initiated by the patient (90%), and in only half of all cases was the examination given as the primary reason for the consultation. Sixty-two per cent of lesions were considered to be clinically benign. CONCLUSION: Public education programs may have an impact on the level of skin examinations requested in general practice consultations. Currently, patients are the principal initiators of such examinations during consultations--there is potential to increase the active role played by GPs in support of patient requests for the early detection of skin cancer.

Attitude to Health↗

Comparative effects of oestrogen and a progestogen on bone loss in postmenopausal women.

1. The value of progestogen therapy in the prevention of postmenopausal bone loss was assessed in 30 women, by a preliminary randomized controlled trial of gestronol or mestranol, in comparison with a placebo. 2. When the skeletal response was measured by photon absorptiometry, bone mineral loss was prevented by both the oestrogen and the progestogen. 3. We confirm that mestranol significantly reduced the urinary output of hydroxyproline-containing peptide, but this did not occur during gestronol therapy, suggesting that progestogen has a different action on bone, perhaps stimulating bone formation.

Adult↗

The effect of ovarian sex steroids on bone mineral status in the oöphorectomized rat and in the human.

The effect of oöphorectomy and hormone replacement therapy after oöphorectomy on bone mineral in the femur and vertebra of the rat has been studied. Oöphorectomy resulted in osteoporosis of the femur but not of the seventh caudal vertebra. The administration of a progestogen (ethynodiol diacetate 9 microgram/day) apparently prevented loss of bone mineral content of the femur. This was due to increased periosteal bone formation and widening of the femur. An oestrogen (mestranol 0.9 microgram/day) had no significant effect on the femoral osteoporosis but increased bone mineral content of the vertebra. Combined therapy with oestrogen and progestogen had no effect on any parameter of bone mineral content. The preliminary human study indicated that a progestogen may also be as effective as an oestrogen in prevention of post-menopausal bone loss. There was no evidence of reduction of bone resorption (as indicated by urinary hydroxyproline output) by the progestogen and therefore it is postulated that a progestogen might retard bone loss in the post-menopausal era by stimulating bone formation.

Animals↗