Search

Background: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and features in common with the metabolic syndrome (MetS)--factors shown to predict cardiovascular risk and type 2 diabetes. We investigated the prevalence and characteristics of the MetS in PCOS by three definitions-World Health Organization (WHO), National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP-III) and International Diabetes Federation (IDF)--and compared that with the background population., Methods: Cross-sectional study of 168 women with PCOS and 883 age-matched controls from the Australian Diabetes, Obesity and Lifestyle (AusDiab) study., Results: Prevalence of the MetS in PCOS subjects was 33% by WHO, 37% by NCEP-ATP-III and 40% by IDF criteria, compared with 10% by NCEP-ATP-III and 13% by IDF in controls (P < 0.001). MetS by WHO criteria was not calculated in the AusDiab population. Age was an independent predictor of MetS in PCOS and controls. The prevalence of MetS was significantly higher among those with PCOS (P = 0.027) in obese women (BMI > 30 kg/m(2)), and higher but not significantly so in overweight (BMI 25-30 kg/m(2)) women (P = 0.052). Dehydroepiandrosterone sulphate was associated with a lower risk of the MetS--Odds ratio 0.86 (95% confidence interval, 0.77-0.97, P = 0.011)., Conclusions: An approximate 4-fold increase in the prevalence of the MetS in women with PCOS compared with the general population, consistent with the proposed major role of insulin and obesity in the syndrome, implies greater risk of cardiometabolic disease in women with PCOS. However, this estimate is likely to vary according to PCOS definition, ethnicity and different aetiological pathways to PCOS.

We aimed to examine moderators and mediators of behaviour change in a cognitive lifestyle program for drug-treated overweight hypertensives in Perth, Australia. We collected data at baseline, 4 months (post-intervention) and 1-year follow-up in a randomized controlled trial of a program that focused on weight loss, diet, and exercise. Mediation analysis used regression models that estimate indirect effects with bootstrapped confidence limits. Outcomes examined were saturated fat intake (% energy) and physical activity (hours per week). In total, 90/118 individuals randomized to usual care and 102/123 to the program-completed follow-up. Sex was a moderator of response post-intervention for diet and physical activity, with a greater response among women with usual care and among men with the program. Change in self-efficacy was a mediator of dietary change post-intervention [effect size (ES) -0.055, 95% confidence interval (CI) -0.125, -0.005] and at follow-up (ES 0.054, 95% CI -0.127, -0.005), and in physical activity post-intervention (ES 0.059, 95% CI 0.003, 0.147). These findings highlight different responses of men and women to the program, and the importance of self-efficacy as a mediator. Mediators for physical activity in the longer term should be investigated in other models, with appropriate cognitive measurements, in future trials.

Cognitive changes are reported infrequently in programs targeting cardiovascular risk. We examined self-efficacy, behavioral barriers and health beliefs in a lifestyle program for drug-treated hypertensives that aimed to reduce blood pressure, antihypertensive drug needs and cardiovascular risk. In a randomized controlled trial, we compared usual care (controls) and a 4-month program focusing on weight loss, diet and exercise. Outcomes were assessed at baseline, 4 months and 1-year follow-up. Of 241 individuals randomized, 102/123 in the program and 90/118 of controls completed follow-up. In the program group, dietary barriers fell by 14% at 4 months (controls 2%, P = 0.025) and by 8% at follow-up (controls 3%, P = 0.010). Exercise barriers fell by 11% at 4 months (controls 3%, P = 0.020) and 17% (controls 4%, P = 0.002) at follow-up. Dietary self-efficacy improved by 3% at 4 months (controls -1%, P = 0.003) and by 2% at follow-up (controls -1%, P = 0.051). Exercise self-efficacy increased by 8% at 4 months (controls 3%, P < 0.001) and by 5% at follow-up (controls 3%, P = 0.130). Changes in cognitive variables predicted changes in health-related behaviors at 4 months and follow-up. A cognitively based lifestyle program in treated hypertensives is associated with improvements in cognitive measures in the shorter and longer term.

Aims: To examine risk for coronary heart disease (CHD) and cardiovascular disease (CVD) in relation to alcohol in a cohort of Australian Aborigines., Methods: In 1988-1989, alcohol intake, drinking pattern, and beverage preference were elicited by interviewer-administered questionnaire in Western Australian Aborigines (258 men, 256 women) and cardiovascular outcomes ascertained through linkage to mortality and hospital admission records to 2002., Results: In proportional hazards models, risk for CHD, relative to lifetime abstainers, was significantly increased in ex-drinkers [Hazard ratio (HR) 2.29, 95% CL 1.23, 4.27], those drinking 41-60 g/day in men or 21-40 g/day in women (HR 2.80, 95% CL 1.04, 7.53), and those drinking >150 g/day for men or >100 g/day for women (HR 2.25, 95% CL 1.03, 4.90) with a J-shaped relationship. Low-to-moderate drinkers had lower waist girth, exercised more, and had a lower prevalence of overweight and smoking than at-risk drinkers. A preference for wine was associated with lower HR (0.28, 95% CL 0.10, 0.95). With CVD, only ex-drinkers showed significantly increased risk (HR 1.87, 95% CL 1.20, 2.91)., Conclusions: More favourable health-related behaviours in low-to-moderate drinkers suggest that lower risk could be mediated by lifestyle, as proposed in other populations.

Context: In patients with primary hypothyroidism, anecdotal evidence suggests that well-being is optimized by fine adjustment of T(4) dosage, aiming for a serum TSH concentration in the lower reference range. This has not been tested in a clinical trial., Objective: Our objective was to test whether adjustment of T(4) dosage aiming for a serum TSH concentration less than 2 mU/liter improves well-being compared with a serum TSH concentration in the upper reference range., Design: We conducted a double-blind, randomized clinical trial with a crossover design., Participants: Fifty-six subjects (52 females) with primary hypothyroidism taking T(4) (>/=100 microg/d) with baseline serum TSH 0.1-4.8 mU/liter participated., Interventions: Each subject received three T(4) doses (low, middle, and high in 25-microg increments) in random order., Outcome Measures: Outcome measures included visual analog scales assessing well-being (the primary endpoint) and hypothyroid symptoms, quality of life instruments (General Health Questionnaire 28, Short Form 36, and Thyroid Symptom Questionnaire), cognitive function tests, and treatment preference., Results: Mean (+/- sem) serum TSH concentrations were 2.8 +/- 0.4, 1.0 +/- 0.2, and 0.3 +/- 0.1 mU/liter for the three treatments. There were no significant treatment effects on any of the instruments assessing well-being, symptoms, quality of life, or cognitive function and no significant treatment preference., Conclusions: Small changes in T(4) dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life, despite the expected changes in serum TSH and markers of thyroid hormone action. These data do not support the suggestion that the target TSH range for the treatment of primary hypothyroidism should differ from the general laboratory range.

OxyContin, a controlled-release formulation of oxycodone, is increasingly abused. Monitoring patient compliance by urine drug testing may deter illegal diversion of OxyContin. Two urine immunoassays were evaluated with a 100 ng/mL cutoff for oxycodone. The Microgenics Corporation Oxycodone DRI on the Bayer ADVIA 1650 and a point-of-care (POC) immunoassay, Monitect Oxycodone POC from Branan Medical Corporation, were compared to gas chromatography-mass spectrometry (GC-MS) with a detection limit of 50 ng/mL free oxycodone. Between-day precision for DRI yielded coefficients of variation from 3.9% to 7.0% at 75 and 125 ng/mL. Fifty-two positive and 52 negative urines were tested. The DRI had a 100% agreement with GC-MS. Two positive specimens had free oxycodone < 50 ng/mL, but oxycodone metabolites, oxymorphone and oxycodone glucuronide > 100 ng/mL, were identified by GC-MS analysis. The POC assay had two false positives and 15 indeterminate (+/-) results. Codeine or hydrocodone was present in all but one of these samples. There was no interference with DRI from morphine, codeine, hydrocodone, hydromorphone, dihydrocodeine, or 6-monoacetyl morphine. Four-hundred and ninety urine samples were subsequently tested with DRI to estimate the oxycodone-positive rate at our hospital, and 47 (9.4%) were positive. The confirmation rate with GC-MS for free oxycodone, not including metabolites, was 93%. The Microgenics DRI offers good performance for oxycodone urine testing and is a better choice for the clinical laboratory than the POC assay. Confirmation of screened positive samples requires a method that can detect total oxycodone and oxymorphone.

Aims: We examined the thermoregulatory response to heat exposure in patients with chronic heart failure., Methods and Results: Skin blood flow (SkBF) was measured in HF subjects and matched controls. Cutaneous vascular conductance (CVC) was calculated from laser-Doppler SkBF and blood pressure. To assess the nitric oxide contribution to thermoregulatory responses, subcutaneous microdialysis membranes were placed beneath the laser-Doppler probes to infuse N(G)-nitro-l-arginine methyl ester (l-NAME), or Ringer's solution. Core (T(C)) and skin temperatures (five sites, T(Sk)) were continuously recorded. Subjects were studied during normothermia then at 38 degrees C, 50%RH within a climate chamber. T(C) and T(Sk) did not differ between HF and controls during normothermia and heating induced similar increases in both groups. During heating, CVC rose in both groups, but significantly less so in HF (HF 43.9+/-7.8 vs. controls 58.0+/-7.5% CVC(max), P<0.05). l-NAME attenuated SkBF responses in the control (58.0+/-7.5 vs. 34.6+/-5.1% CVC(max), P<0.001) and HF subjects (43.9+/-7.8 vs. 27.0+/-2.2% CVC(max), P<0.005), with a larger effect evident in the controls (P<0.05)., Conclusion: HF patients exhibit impaired thermoregulatory responses to heat exposure. Lower SkBF in HF, which defends blood pressure during heat exposure, also predisposes these subjects to heat intolerance.

Background: Previous studies concerning Alu I/D polymorphism in the ACE gene and ADPKD severity have used the Alu genotypes as a representative of the true biological variable, namely ACE activity. However, wide individual and ethnic differences in the proportion of variance in ACE activity explained by the I/D genotype may have confounded these studies. This investigation examines the association between ADPKD severity and ACE in terms of plasma enzyme activity and I/D genotypes in individuals from three different countries., Methods: Blood samples were collected from 307 ADPKD patients (116 Australian, 124 Bulgarian and 67 Polish) for determination of ACE activity levels and I/D genotypes. Chronic renal failure (CRF) was present in 117 patients and end-stage renal failure (ESRF) in 68 patients., Results: ACE activity was related to the I/D genotype, showing a dosage effect of the D allele (P=0.006). The proportion of variance due to the Alu polymorphism was 14%. No difference in ACE activity and I/D genotype distribution was found between patients with CRF versus normal renal function (P=0.494; P=0.576) or between those with ESRF versus those without ESRF (P=0.872; P=0.825). No effect of the I/D genotype on age at development and progression to renal failure (CRF; ESRF) was detected in the overall group, and in subgroups based on ethnic origin, linkage status and sex., Conclusion: ACE is not likely to play a role as a determinant of ADPKD phenotype severity.

Lifestyle factors are critical determinants of blood pressure levels operating against a background of genetic susceptibility. Excess body fat is a predominant cause of hypertension with additive effects of dietary salt, alcohol, and physical inactivity. Controlled trials in hypertensives show blood pressure lowering effects of supplemental potassium, fibre, n-3 fatty acids, and diets rich in fruit and vegetables and low in saturated fats. Some population studies show an inverse relationship between dietary protein and blood pressure levels. Regular coffee drinking raises blood pressure in hypertensives. The role of "stress" remains enigmatic, with "job strain" being a possible independent risk factor for hypertension.

In a pilot health promotion program for couples, we aimed to build on re-evaluation of attitudes to health occurring early in marriage, and social support provided by partners, to address the weight gain and physical inactivity which may follow marriage. A randomized controlled trial lasting 16 weeks used six modules focusing on nutrition and physical activity but including information about alcohol and smoking. Thirty-four of 39 couples enrolled completed the study. Self-efficacy for diet and physical activity increased significantly in the program group while ranking of barriers to healthy behaviours decreased and ranking of beliefs about the benefits of health behaviours increased relative to controls. Intake of fat, take-away foods and alcohol decreased, and consumption of fruit, vegetables and reduced-fat foods increased significantly in the program group. Physical activity in the program group increased by the equivalent of 50 min of brisk walking weekly but did not differ significantly from controls. Cholesterol fell significantly by 6% more in the program group than controls. In focus groups, participants unanimously found the program valuable. Health promotion programs designed for couples can achieve short-term changes in behaviour and risk factors. Larger trials with longer-term monitoring, incorporating feedback from focus groups and cost-benefit analysis, are in progress.

Vegetarian diets lower blood pressure (BP), but attempts to identify dietary components responsible have been unsuccessful. Isoflavonoids are commonly consumed as part of vegetarian diets. The objective of this study was to assess the effect of isoflavonoid supplementation on BP. Fifty-nine subjects with high-normal range systolic BP completed a randomized, double blind, placebo-controlled trial of two-way parallel design and 8 weeks duration. One tablet containing 55 mg of isoflavonoids, including 30 mg of genistein, 16 mg of biochanin A (a genistein precursor), 1 mg of daidzein, and 8 mg of formononetin (a daidzein precursor), or one placebo tablet, was taken daily with the evening meal. Significant increases in urinary excretion of genistein (5.22 mg/day, 95% CI: 3.72, 6.72) and daidzein (2.53 mg/day, 95% CI: 1.66, 3.40) were observed in the group taking the isoflavonoid supplement. There were no significant changes in isoflavonoid excretion in the placebo group. Clinic BP was measured at two visits, and ambulatory BP monitoring was performed over one 24-h period, at baseline and postintervention. There was no significant difference between groups, after adjustment for baseline values, in postintervention clinic supine BP (systolic 1.2 mm Hg, 95% CI: -2.3, 4.7; diastolic 0.6 mm Hg, 95% CI: -1.9, 2.5), clinic erect BP (systolic 1.7 mm Hg, 95% CI: -4.0, 8.4; diastolic 0.4 mm Hg, 95% CI: -2.4, 3.2), or 24-h ambulatory BP (systolic -1.4 mm Hg, 95% CI: -4.4, 1.6; diastolic -0.8 mm Hg, 95% CI: -2.3, 0.7). Adjustment for age, gender, and weight change did not alter the result. Therefore, these results do not support the hypothesis that isoflavonoids, and genistein in particular, are major contributors to the BP lowering effect of vegetarian diets.

Escherichia coli from 138 fecal samples from aboriginal children, in whom no other enteric pathogen was isolated (including enterovirulent E. coli), were examined for HEp-2 cell adhesion. Twenty-five (36.8%) of 68 children with diarrhea and 32 (45.7%) of 70 without diarrhea had diffusely adherent isolates, which were thus not associated with diarrhea (P > .25). However, after age stratification, children > or = 18 months showed a significant association of diffusely adherent E. coli with diarrhea (P < or = .05). Enteroaggregative E. coli were isolated from 12 children with diarrhea (17.6%) and 15 without diarrhea (21.4%); thus, there was no association with diarrhea (P > or = .5). Sixteen children with diarrhea (23.5%) and 6 without diarrhea (8.6%) carried isolates that caused detachment of the HEp-2 cell monolayer from the glass coverslip when examined in the adhesion assay and were significantly associated with diarrhea (P < or = .05). These isolates, termed cell-detaching E. coli, were different from all recognized classes of enterovirulent E. coli.

In a group of 343 working men, only 34 of whom regularly drank more than 60 ml of ethanol per day, logistic regression was used to determine the combination of biomarkers which best discriminated between those who regularly drank less than 30 ml or 30 ml or more of ethanol daily. The index consisted of apolipoprotein A-II, uric acid, gamma-glutamyl transpeptidase and mean corpuscular volume. Even with the relatively low level of alcohol intake reported in these subjects (assessed using a 7-day retrospective alcohol diary), the groups with higher or lower intake of alcohol were separated with a sensitivity of 68%, a specificity of 74% and a positive predictive value of 71%. Systolic blood pressure, adjusted for age and body mass index, was also linearly related to alcohol intake, and when included in the biomarker index improved the proportion correctly classified from 71% to 75%. Using the biomarkers only, 94% of subjects regularly drinking at least 80 ml of ethanol equivalent per day and 100% of the non-drinkers were correctly classified.

Aborigines were admitted to hospital in Western Australia 2.8 times as frequently as other persons in 1977-1988. Their highest relative admission rates were in the 0-5 years age group, mostly for respiratory and gastrointestinal infections. Relative admission rates (all ages) for some categories were: infectious and parasitic, 4 to 10-fold; respiratory, 5-fold; nervous system, 4-fold; injury and poisoning, 3 to 5-fold; mental disorders, double the non-Aboriginal rate. Admissions for respiratory illnesses were consistently much higher in Aborigines of all ages. There were some significant declines in relative hospital admission rates for Aborigines over the study period.

In a study of 843 independent-living men and women aged between 60 and 87 in Perth, Western Australia, stepwise multiple regression, after correction for initial levels of systolic blood pressure, showed that postural fall in systolic blood pressure was positively related to alcohol intake of more than 20 ml/day, the use of sleeping tablets and higher levels of anxiety on the Spielberger state-trait scale, and negatively related to body mass index. Postural fall in blood pressure was not significantly related to treatment for hypertension, age, sex, patterns of usual physical activity, tea or coffee drinking, or the diagnosis of diabetes mellitus. This analysis is the first to examine the relationship between lifestyle factors and the magnitude of the fall in systolic blood pressure on standing after adjustment for the association between the change in a variable and its initial level. Our analysis suggests the need for further study of the possible role of lifestyle factors such as the use of sleeping tablets and alcohol in postural hypotension in the elderly.

A total of 112 EPEC strains isolated from children with diarrhoea in New Zealand were examined for mannose-resistant HEp-2 cell adherence and production of exotoxins. Enterotoxin production was not detected in any of the strains examined. Verotoxin production was detected in 13 (11.6%) strains and of these 4 were also found to adhere to HEp-2 cells. HEp-2 cell adherence was displayed by a total of 29 (25.8%) strains of which 22 were diffusely adherent. Only 3 (2.7%) strains were shown to belong to the new virulence phenotype, entero-aggregative adherence, when examined in the adherence assay. We identified one strain with the novel characteristic of causing detachment of HEp-2 cells from glass coverslips and are further investigating this possible virulence mechanism. These results suggest that if EPEC strains are to be considered as a cause of diarrhoea, the search for new virulence factors must be extended.

A prospective, 12-month study of 975 non-Aboriginal children with diarrhea and age- and sex-matched children without diarrhea, in Perth, Western Australia, was designed to investigate the significance of enterotoxigenic Aeromonas species as a cause of diarrhea. Enterotoxigenic Aeromonas species were found in the fecal specimens of 10.8% of the patients with diarrhea but in only 0.7% of those without diarrhea. Most Aeromonas species were isolated during the summer. Other important bacterial pathogens included Campylobacter, Salmonella, Shigella, and enterotoxigenic Escherichia coli; rotavirus infections appeared to be much less important in the Western Australian environment. Most of the patients were younger than two years of age and about one-quarter had mixed bacterial and/or viral intestinal infections. Enterotoxigenic Aeromonas species can be identified with 97% accuracy using a simple hemolysin assay which should be considered for use by routine diagnostic laboratories, particularly in children's hospitals.

Pre-incubation with anticholera toxin (ACT) significantly reduced intestinal secretion induced by cell-free broth preparations of heat-labile toxins (LT) of Escherichia coli and Aeromonas hydrophila in jejunal perfusion experiments in rats in vivo. Pre-incubation with ACT also prevented cytotoxicity by E. coli LT in the Y1 cell culture system. Pre-incubation had no effect on cytotoxicity in Y1 and L132 cell lines or on haemolytic activity with cell-free preparations of A. hydrophila. In another series of experiments rats were immunized with cholera toxin given as an intraperitoneal priming dose followed 12 days later by intraduodenal boosting. Immunization significantly protected against net intestinal fluid secretion induced by enterotoxigenic E. coli and A. hydrophila and by cholera toxin.

Soft-drink powdered mixtures have been developed which are bactericidal against a range of enteric bacteria and Staphylococcus aureus and which kill some enteric viruses in vitro. These mixtures could be used to help reduce risks of water-borne diarrhoeal illnesses, and as the basis for oral rehydration solutions, which would resist bacterial contamination after their preparation, to treat patients with diarrhoeal dehydration.

The reproducibility of the infant mouse assay for Escherichia coli ST and heat-labile enterotoxins of Aeromonas spp. is improved if both intestinal weight to remaining body weight ratio (IW/RBW) and the amount of diarrhoea produced are considered as criteria for classifying enterotoxigenic strains. Animals with profuse diarrhoea may have IW/RBW ratios below the widely accepted critical value for a positive test. Using pools of supernatants from broth cultures of three different strains of E. coli, 15% of ST producers would have been regarded as negative using IW/RBW ratio as the only criterion of a positive test. In testing single supernatants, 25% of ST producing E. coli would not have been correctly classified using IW/RBW alone. A scoring system which incorporates IW/RBW ratios and the amount of diarrhoea produced improves the usefulness of the test by allowing clear separation of positive and negative strains. The scoring system is also applicable to older mice for assay of E. coli ST so that a wider age range of mice can be used allowing increased use of animal facilities.