Women's acceptability of misoprostol treatment for incomplete abortion by midwives and physicians : secondary outcome analysis from a randomized controlled equivalence trial at district level in Uganda

OBJECTIVE: This study aimed to assess women´s acceptability of diagnosis and treatment of incomplete abortion with misoprostol by midwives, compared with physicians. METHODS: This was an analysis of secondary outcomes from a multi-centre randomized controlled equivalence trial at district level in Uganda. Women with first trimester incomplete abortion were randomly allocated to clinical assessment and treatment with misoprostol by a physician or a midwife. The randomisation (1:1) was done in blocks of 12 and stratified for health care facility. Acceptability was measured in expectations and satisfaction at a follow up visit 14-28 days following treatment. Analysis of women's overall acceptability was done using a generalized linear mixed-effects model with an equivalence range of -4% to 4%. The study was not masked. The trial is registered at ClinicalTrials.org, NCT 01844024. RESULTS: From April 2013 to June 2014, 1108 women were assessed for eligibility of which 1010 were randomized (506 to midwife and 504 to physician). 953 women were successfully followed up and included in the acceptability analysis. 95% (904) of the participants found the treatment satisfactory and overall acceptability was found to be equivalent between the two study groups. Treatment failure, not feeling calm and safe following treatment, experiencing severe abdominal pain or heavy bleeding following treatment, were significantly associated with non-satisfaction. No serious adverse events were recorded. CONCLUSIONS: Treatment of incomplete abortion with misoprostol by midwives and physician was highly, and equally, acceptable to women. TRIAL REGISTRATION: ClinicalTrials.gov NCT01844024.

Diet and hypertension in the Asia-pacific region : a brief review

In this paper, the possible reasons for the prevalence of hypertension in the Asia–Pacific region are examined, along with its likely dietary, nutritional and sociocultural causes. This brief survey indicates the need for more comprehensive blood pressure monitoring and surveillance throughout the region. Findings from research conducted in the region and elsewhere suggest that a variety of aetiological factors predict the occurrence of hypertension, most of which are similar to those observed in western populations. However, several lines of research suggest that obesity, abdominal obesity and a number of dietary constituents, in addition to salt, may play relatively greater roles than in western populations. It is argued that hypertension may be prevented via a combination of individual, community and governmental approaches which promote social capital, environmentally sustainable food production and the public health.

Calpain 3 gene expression in skeletal muscle is associated with body fat content and measures of insulin resistance

OBJECTIVE: To investigate whether skeletal muscle gene expression of calpain 3 is related to obesity and insulin resistance.

DESIGN: Cross-sectional studies in 27 non-diabetic human subjects and in Psammomys obesus, a polygenic animal model of obesity and type 2 diabetes.

MEASUREMENTS: Expression of CAPN3 in skeletal muscle was measured using Taqman fluorogenic PCR. In the human subjects, body composition was assessed by DEXA and insulin sensitivity was measured by euglycemic-hyperinsulinemic clamp. In Psammomys obesus, body composition was determined by carcass analysis, and substrate oxidation rates, physical activity and energy expenditure were measured by whole-body indirect calorimetry.

RESULTS: In human subjects, calpain 3 gene expression was negatively correlated with total (P=0.022) and central abdominal fat mass (P=0.034), and with blood glucose concentration in non-obese subjects (P=0.017). In Psammomys obesus, calpain 3 gene expression was negatively correlated with circulating glucose (P=0.013) and insulin (P=0.034), and with body fat mass (P=0.049). Indirect calorimetry revealed associations between calpain 3 gene expression and carbohydrate oxidation (P=0.009) and energy expenditure (P=0.013).

CONCLUSION/INTERPRETATION: Lower levels of expression of calpain 3 in skeletal muscle were associated with reduced carbohydrate oxidation and elevated circulating glucose and insulin concentrations, and also with increased body fat and in particular abdominal fat. Therefore, reduced expression of calpain 3 in both humans and Psammomys obesus was associated with phenotypes related to obesity and insulin resistance.

Nitric oxide control of large veins in the toad Bufo marinus

This study examined the nitric oxide (NO) control of the vascular smooth muscle of the ventral abdominal vein and vena cava of the toad, Bufo marinus, by using anatomical and physiological approaches. Nicotinamide adenine di-nucleotide phosphate-diaphorase histochemistry and immunohistochemistry using endothelial nitric oxide synthase (NOS) and neural NOS antibodies produced no evidence for endothelial NOS in the veins, but, neural NOS-immunoreactive perivascular nerves were present. Acetylcholine (10^–5 M) caused a vasodilation in both veins that was endothelium-independent, and which was blocked by the soluble guanylyl cyclase inhibitor, ODQ (10^–5 M). The NOS inhibitors, L-NNA (10^–4 M) and L-NAME (10^–4 M), did not significantly reduce the vasodilatory effect of acetylcholine in the veins; this suggested that the vasodilation was not due to NO. However, in the presence of phenoxybenzamine (10^–7–10^–8 M), L-NNA significantly reduced the vasodilatory effect of acetylcholine in the veins. This unusual response is due to phenoxybenzamine partially inactivating the muscarinic receptor pool in the veins. In addition, the neural NOS inhibitor, vinyl-L-NIO (10^–5 M), significantly reduced the acetylcholine-mediated vasodilation in the presence of phenoxybenzamine. The results show that in toad veins, nitrergic nerves rather than an endothelial NO system are involved in NO-mediated vasodilation.

α2β1 integrin affects metastatic potential of ovarian carcinoma spheroids by supporting disaggregation and proteolysis

Background: Ovarian cancer is characterized by a wide-spread intra-abdominal metastases which represents a major clinical hurdle in the prognosis and management of the disease. A significant proportion of ovarian cancer cells in peritoneal ascites exist as multicellular aggregates or spheroids. We hypothesize that these cellular aggregates or spheroids are invasive with the capacity to survive and implant on the peritoneal surface. This study was designed to elucidate early inherent mechanism(s) of spheroid survival, growth and disaggregation required for peritoneal metastases.

Methods: In this study, we determined the growth pattern and adhesive capacity of ovarian cancer cell lines (HEY and OVHS1) grown as spheroids, using the well established liquid overlay technique, and compared them to a normal ovarian cell line (IOSE29) and cancer cells grown as a monolayer. The proteolytic capacity of these spheroids was compared with cells grown as a monolayer using a gelatin zymography assay to analyze secreted MMP-2/9 in conditioned serum-free medium. The disaggregation of cancer cell line spheroids was determined on extracellular matrices (ECM) such as laminin (LM), fibronectin (FN) and collagen (CI) and the expression of α2, α3, αv, α6 and β1 interin was determined by flow cytometric analysis. Neutralizing antibodies against α2, β1 subunits and α2β1 integrin was used to inhibit disaggregation as well as activation of MMPs in spheroids.

Results: We demonstrate that ovarian cancer cell lines grown as spheroids can sustain growth for 10 days while the normal ovarian cell line failed to grow beyond 2 days. Compared to cells grown as a monolayer, cancer cells grown as spheroids demonstrated no change in adhesion for up to 4 days, while IOSE29 cells had a 2–4-fold loss of adhesion within 2 days. Cancer cell spheroids disaggregated on extracellular matrices (ECM) and demonstrated enhanced expression of secreted pro-MMP2 as well as activated MMP2/MMP9 with no such activation of MMP's observed in monolayer cells. Flow cytometric analysis demonstrated enhanced expression of α2 and diminution of α6 integrin subunits in spheroids
versus monolayer cells. No change in the expression of α3, αv and β1 subunits was evident. Conversely, except for αv integrin, a 1.5–7.5-fold decrease in α2, α3, α6 and β1 integrin subunit expression was observed in IOSE29 cells within 2 days. Neutralizing antibodies against α2, β1 subunits and α2β1 integrin inhibited disaggregation as well as activation of
MMPs in spheroids.

Conclusion: Our results suggest that enhanced expression of α2β1 integrin may influence spheroid disaggregation and
proteolysis responsible for the peritoneal dissemination of ovarian carcinoma. This may indicate a new therapeutic target
for the suppression of the peritoneal metastasis associated with advanced ovarian carcinomas.

The problem of obesity : is there a role for antagonists of the renin-angiotensin system?

Obesity is a major health problem worldwide; it is associated with more than 30 medical conditions and is a leading cause of unnecessary deaths. Adipose tissue not only acts as an energy store, but also behaves like an endocrine organ, synthesising and secreting numerous hormones and cytokines. Angiotensin II (ANG II) is the biologically active component of the renin-angiotensin system (RAS). The RAS is present in adipose tissue and evidence suggests that ANG II is intimately linked to obesity. Indeed, ANG II increases fat cell growth and differentiation, increases synthesis, uptake and storage of fatty acids and triglycerides and possibly inhibits lipolysis. Evidence obtained using genetically modified animals has shown that the amount of body fat is directly related to the amount of ANG II, i.e., animals with low levels of ANG II have reduced fat stores while animals with excessive ANG II have increased fat stores. In humans, epidemiological evidence has shown that body fat is correlated with angiotensinogen, a precursor of ANG II, or other components of the RAS. Furthermore, blocking the production and/or actions of ANG II with drugs or natural substances decreases body fat. The decrease in body fat caused by such treatments predominantly occurs in abdominal fat depots and appears to be independent of energy intake and digestibility. Clearly, ANG II has an important role in the accumulation of body fat and the possibility exists that treatment of obesity will be enhanced by the use of natural or synthetic substances that interfere with ANG II.

Overweight, obesity and metabolic syndrome in rural southeastern Australia

OBJECTIVE: To measure the prevalence of overweight, obesity and the metabolic syndrome (MetS) in rural Australia.

DESIGN, SETTING AND PARTICIPANTS: Cross-sectional surveys were conducted in two rural areas in Victoria and South Australia in 2004-2005. A stratified random sample of men and women aged 25-74 years was selected from the electoral roll. Data were collected by a self-administered questionnaire, physical measurements and laboratory tests.

MAIN OUTCOME MEASURES: Prevalence of overweight and obesity, as defined by body mass index (BMI) and waist circumference; prevalence of MetS and its components.

RESULTS: Data on 806 participants (383 men and 423 women) were analysed. Based on BMI, the prevalence of overweight and obesity combined was 74.1% (95% CI, 69.7%-78.5%) in men and 64.1% (95% CI, 59.5%-68.7%) in women. Based on waist circumference, the prevalence of overweight and obesity was higher in women (72.4%; 95% CI, 68.1%-76.7%) than men (61.9%; 95% CI, 57.0%-66.8%). The overall prevalence of obesity was 30.0% (95% CI, 26.8%-33.2%) based on BMI (> or = 30.0 kg/m(2)) and 44.7% (95% CI, 41.2%-48.1%) based on waist circumference (> or = 102 cm [men] and > or= 88 cm [women]). The prevalence of MetS as defined by the US National Cholesterol Education Program Adult Treatment Panel III 2005 criteria was 27.1% (95% CI, 22.7%-31.6%) in men and 28.3% (95% CI, 24.0%-32.6%) in women; based on International Diabetes Federation criteria, prevalences for men and women were 33.7% (95% CI, 29.0%-38.5%) and 30.1% (95% CI, 25.7%-34.5%), respectively. Prevalences of MetS, central (abdominal) obesity, hyperglycaemia, hypertension and hypertriglyceridaemia increased with age.

CONCLUSIONS: In rural Australia, prevalences of MetS, overweight and obesity are very high. Urgent population-wide action is required to tackle the problem.

Benefits of a year-long workplace weight loss program on cardiovascular risk factors

Objective: To assess the effectiveness of a year-long workplace weight loss program in reducing risk factors of coronary heart disease.

Design: A randomised, controlled study of low fat (25% of dietary energy) diet- and/or moderate exercise-induced weight loss interventions in free-living, middle-aged men. Compliance was monitored from food and activity diaries at monthly blood pressure measurement sessions. Blood was sampled and body composition determined from dual energy X-ray absorptiometry before and after 12 months.

Subjects and setting: Fifty-eight overweight men (mean [+ or -] SD age: 43.4 [+ or -] 5.7 years; BMI 29.0 [+ or -] 2.6 kg/[m.sup.2]), recruited from a national corporation, were instructed into diet (n = 18) exercise (a 21) or control (n = 19) groups over 12 months; 16 control subjects combined diet and exercise (n = 16) for the subsequent 12 months.

Main outcome measures: At 12 months, weight, total and regional fat and lean mass, dietary energy and percentage dietary fat intake, physical activity indices, systolic and diastolic blood pressure, serum insulin, blood lipids and lipoproteins.

Statistical analyses: Differences between groups were tested using analysis of variance with Scheffe post hoc test. Differences between pre- and post-intervention variables were tested using Students' paired t-tests. Pearson's correlation coefficient and univariate linear regression identified association between dependent variables, multiple stepwise regression identified specific predictors.

Results: Weight loss with either diet or exercise resulted in a reduction in systolic blood pressure (-3.3 [+ or -] 1.7%), diastolic blood pressure (-4.8 [+ or -] 1.3%) and LDL cholesterol (-3.9 [+ or -] 2.8%), a rise in HDL cholesterol (+10.0 [+ or -] 3.8%) and a change in the LDL/HDL ratio (-8.9 [+ or -] 3.5%). Abdominal fat loss (-26.8 [+ or -] 3.6% after diet; -16.6 [+ or -] 4.5% after exercise; -21.0 [+ or -] 4.7% after diet and exercise) was the strongest predictor of change in blood pressure: twenty percent abdominal fat loss predicted a percentage fall of 2.4 [+ or -] 0.05% in systolic blood pressure and 5.4 [+ or -] 0.07% in diastolic blood pressure. Greater abdominal fat loss was associated with the greatest decrease in serum insulin (P < 0.05).

Conclusion: Modest changes in diet and exercise effected by a low cost workplace-based education program achieved weight loss, loss of abdominal fat, reduced blood pressure and serum insulin and improved blood lipid concentrations. (Nutr Diet 2002;59:87-96)

Body size, body composition, and fat distribution: a comparison of young New Zealand men of European, Pacific Island, and Asian Indian ethnicities

Aims To investigate body size and body fat relationships and fat distribution in young healthy men drawn from New Zealand European, Pacific Island, and Asian Indian populations.
Method A total of 114 healthy men (64 European, 31 Pacific Island, 19 Asian Indian) aged 17–30 years underwent measurements of height, weight, and body composition by total body dual-energy X-ray absorptiometry (DXA). Body mass index (BMI) was then calculated. Percent body fat (%BF), fat-free mass, bone mineral content, bone mineral density, abdominal fat, thigh fat, and appendicular skeletal muscle mass (ASMM) were obtained from the DXA scans.
Results For the same BMI, %BF for Pacific Island men was 4% points lower and for Asian Indian men was 7–8% points higher compared to Europeans. Compared to European men for the same %BF, BMI was 2–3 units higher for Pacific Island, and 3–6 units lower for Asian Indian. The ratio of abdominal fat to thigh fat, adjusted for height, weight, and %BF, was significantly higher for Asian Indian men than European (p=0.022) and Pacific Island (p=0.002) men. ASMM, adjusted for height and weight, was highest in Pacific Island and lowest in Asian Indian men.
Conclusions The relationship between %BF and BMI is different for European, Pacific Island, and Asian Indian men which may, at least in part, be due to differences in muscularity. Asian Indians have more abdominal fat deposition than their European and Pacific Island counterparts. Use of universal BMI cut-off points are not appropriate for comparison of obesity prevalence between these ethnic groups.

Change in women's body mass index and waist circumference, 1997 to 2002: the Nepean study

Objective: To investigate character istics associated with body mass index (BMI) and waist circumference stability over a five-year period in women with school-age children.

Methods: Women with 7–8 year-old children from western Sydney, Australia, had anthropometric measures taken in 1996/97 (n====436) and five years later (n=327). Socio-demographic characteristics examined at baseline included age, socioeconomic status, smoking, and number of children.

Results: Over five years, less than half of the women maintained a stable BMI (38.8%) or waist circumference (31.5%), with the majority gaining in both indicators of adiposity. BMI and socio-demographic characteristics were not predictive of BMI or waist circumference stability or decrease.

Conclusions and Implications: Total and abdominal adiposity increased in these Australian women who have children. The results support the need to develop effective weight gain prevention initiatives.

Surgical accountability in the 1880s: the death of Susan Nixon

Susan Nixon died in 1881 following a surgical error. Her surgeon, Dr W. E. Warren, excised a normal 7-month gravid uterus under the misapprehension that he was removing a tubular pregnancy. It is believed that Mrs Nixon was the first woman in Australia to have an abdominal hysterectomy and the second to have a live Caesarean section. The surgical misadventure that resulted in Mrs Nixon's death became a public scandal, which gained currency through both parliamentary debate and the popular press.

The purpose of referring to this case is to explore the mechanisms of accountability that surgeons faced in the 1880s − a decade of rapid change in the practice of surgery. The response of late nineteenth century society to surgical error and the resultant reaction of the medical profession have resonances that are relevant to surgeons practising today.

Case review: septic shock in the pregnant patient

This case study involves a 36-year-old female at 15 weeks gestation who presented with severe lower abdominal pain post amniocentesis and subsequently deteriorated into a state of septic shock whilst in the ED. The circumstances surrounding this patient's presentation and subsequent clinical course are presented. The assessment and management of septic shock is also described with specific consideration to this patient's pregnant state.

Overweight, obesity and metabolic syndrome in rural south-eastern Australia

Aims & rationale/Objectives : To measure the prevalence of overweight, obesity and the metabolic syndrome in rural Australia.</p>

Methods :Two cross-sectional population surveys of chronic disease risk factors were carried out in rural Victoria (Corangamite Shire) and South Australia (Limestone Coast) in 2004-05. For both surveys, a stratified random sample of the population aged 25 to 74 years was drawn from the electoral roll. The surveys comprised a self-administered questionnaire, physical measurements and laboratory tests.</p>

Principal findings : A total of 841 individuals had complete questionnaire, health check and measured MetS data. The prevalence of overweight and obesity was 75% in males and 64.7% in females defined by BMI. Using waist circumference, the prevalence of overweight and obesity was higher in females (72.9%) than in males (63.2%). The overall prevalence of obesity of was 30.1% when defined by BMI, but 44.8% when defined by waist circumference. The prevalence of metabolic syndrome according to NCEP ATP III 2005 criteria was 29.0% in males and 28.5% in females. According to IDF criteria, the prevalence for males and females were 30.5% and 36.3%, respectively. The prevalence of metabolic syndrome and central (abdominal) obesity, hyperglycaemia, hypertension, and hypertriglyceridaemia increased with age.

Discussion : The prevalence of overweight and obesity, in particular central obesity, in rural Australia is very high as is the prevalence of metabolic syndrome.

Implications : Urgent population wide action is required to turn this trend around and regular monitoring of the trends in response to such action is essential.

Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance

In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE^-/-) and compared with wild-type littermates. Compared with wild-type littermates, ACE^-/- mice had lower body weight and a lower proportion of body fat, especially in the abdomen. ACE^-/- mice had greater fed-state total energy expenditure (TEE) and resting energy expenditure (REE) than wild-type littermates. There were pronounced increases in gene expression of enzymes related to lipolysis and fatty acid oxidation (lipoprotein lipase, carnitine palmitoyl transferase, long-chain acetyl CoA dehydrogenase) in the liver of ACE^-/- mice and also lower plasma leptin. In contrast, no differences were detected in daily food intake, activity, fed-state plasma lipids, or proportion of fat excrete in fecal matter. In conclusion, the reduction in ACE activity is associated with a decreased accumulation of body fat, especially in abdominal fat depots. The decreased body fat in ACE^-/- mice is independent of food intake and appears to be due to a high energy expenditure related to increased metabolism of fatty acids in the liver, with the additional effect of increased glucose tolerance.

Dietary quality is associated with diabetes and cardio-metabolic risk factors1–3

In this study, our aim was to investigate the associations between diet quality and newly diagnosed diabetes, prediabetes, and cardio-metabolic risk factors. The analysis was based on 7441 participants of the Australian Diabetes, Obesity and Lifestyle study, a cross-sectional study of adults aged 25 y involving a 75-g oral glucose tolerance test. Diet quality was assessed via a dietary guideline index and FFQ data. Associations between diet quality and diabetes, prediabetes (impaired fasting glycemia, impaired glucose tolerance), and cardiovascular risk factors were investigated using linear and logistic regression adjusted for age, education, smoking, physical activity, sedentary behavior, and BMI. Higher diet quality was significantly associated with lower systolic and diastolic blood pressure among men, lower fasting plasma glucose among men and women, and lower systolic blood pressure, fasting plasma insulin, and 2-h plasma glucose and greater insulin sensitivity among women. Diet quality was inversely associated with abdominal obesity [odds ratio (OR) for top quartile: 0.68, 0.48–0.96], hypertension (OR: 0.50, 0.31–0.81), and type 2 diabetes (OR: 0.38, 0.18–0.80) among men. Lack of compliance with established dietary guidelines was associated with type 2 diabetes and cardio-metabolic risk factors. Further work is required to determine whether this dietary index has predictive validity for health in longitudinal studies.