Association of hypertension and hypokalemia with Cushing's syndrome caused by ectopic ACTH secretion: a series of 58 cases.

Cushing's syndrome is associated with hypertension in approximately 80% of cases. Hypertension contributes to the marked increased mortality risk of past or current Cushing's syndrome, largely because of increased cardiovascular risk. Observation of the pathophysiological effect of chronically elevated ACTH and cortisol values in patients with ectopic ACTH secretion complements the available data from acute studies of the effects of ACTH and glucocorticoid infusions in normal volunteers. In a retrospective case review, we identified 58 patients with Cushing's syndrome caused by ectopic ACTH secretion, who were treated at the National Institutes of Health between 1983-1997. The diagnosis of an ectopic ACTH cause was confirmed by inferior petrosal sinus sampling and/or pathologic examination of tumor. The commonest causes were bronchial carcinoid (40%) and thymic carcinoid (10%), but 18 of 58 (31%) patients had an unknown source of ectopic ACTH. Hypertension (systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg in adults) was noted in 45 of 58 (78%) ectopic Cushing's patients, a prevalence similar to that noted in other endogenous Cushing's syndrome etiologies. Hypertension was severe, deemed to require 3 or more drugs by the treating physicians, in 26 of 58 (45%) patients. Hypokalemia was much more prevalent than in patients with other causes of Cushing's syndrome, affecting 33 of 58 (57%) patients. The range of plasma ACTH (17-1557 pg/mL, normal

Establishment of metanephros transplantation in mice highlights contributions by both nephrectomy and pregnancy to developmental progression

Background: It has been demonstrated that embryonic kidneys (metanephroi) xenotransplanted into the omentum of adult recipients continue to develop and display immune protection due to their more nave immune presentation. To date, this has been achieved using rat, pig and human metanephroi, with unilateral nephrectomy (UNX) of recipient rats a requisite of renal development. The aim of this study was to adapt this approach for use in mice and examine the parameters affecting successful onward development in this species. Methods: Metanephroi at embryonic age (E) 13.5 were transplanted either onto the body wall, abdominal fat pads or omentum of recipient isogenic C57/Bl6 mice using either sutures or polyglycolic acid mesh. Having established greatest success with polyglycolic acid mesh on the body wall, E12.5 and 15.5 days metanephroi from C57/Bl6 mice were then transplanted onto the body wall of control (non-pregnant non-UNX), UNX or 12.5 days post-coitum pregnant isogenic recipients. After 7 days, implanted tissue was harvested and examined using histology and immunohistochemistry for markers of renal maturation. The mean number of S-shaped bodies and glomeruli per section were recorded and statistically analysed for significant differences between all recipient groups and untransplanted metanephroi. The degree of development was scored qualitatively. Results: Transplanted E12.5 metanephroi developed S-shaped bodies and glomeruli in all recipient groups, although there were statistically higher numbers of S-shaped bodies in UNX (n = 2) and pregnant recipients (n = 9) than in control recipients (n = 4). Continued development, as indicated by mature vascularized glomeruli, was only observed in those E15.5 metanephroi transplanted into pregnant recipients (n = 11) with a 15.5-fold increase in S-shaped bodies and 4-fold increase in glomeruli compared with control transplants (n = 12). Conclusions: We have successfully established metanephros transplantation in mice and demonstrated enhancement of onward development of E12.5 metanephroi in response to both pregnancy and UNX. Using E15.5 metanephroi, continued development only occurred in pregnant recipients, implying pregnancy provides an environment conducive to continued organogenesis. This murine assay, when coupled with transgenically-tagged strains of mice, will allow the investigation of the relative contribution of donor and recipient cells to this process. Copyright (C) 2005 S. Karger AG, Basel.

Increasing the efficacy of Judas goats by sterilisation and pregnancy termination

The use of Judas goats to locate remnant animals is a potentially powerful tool for enhancing goat-eradication efforts, which are especially important to island conservation. However, current Judas goat methodology falls short of its potential efficacy. Female Judas goats are often pregnant at the time of deployment or become impregnated in the field; pregnant females leave associated goats to give birth, causing downtime of Judas goat operations. Further, male Judas goats may inseminate remnant females. Sterilising Judas goats prior to deployment removes these inefficiencies. Here, we describe two methods (epididymectomy for males and tubal occlusion for females) that sterilise Judas goats while still maintaining sexual motivation and other behaviours associated with intact animals. These surgeries are straightforward, time efficient, and may be conducted in the field by staff with minimal training. Given the widespread and deleterious impacts of non-native herbivores to ecosystems and the importance of Judas operations in detecting animals at low densities, sterilisation and termination of pregnancy should be applied routinely in Judas goat (and possibly other species) programs to increase the efficacy of low-density control operations and eradication campaigns.

Maternal health during pregnancy and perinatal mortality in Bangladesh: evidence form a large-scale community-based clinical trial

Perinatal mortality is very high in Bangladesh. In this setting, few community-level studies have assessed the influence of underlying maternal health factors on perinatal outcomes. We used the data from a community-based clinical controlled trial conducted between 1994 and 1997 in the catchment areas of a large MCH/FP hospital located in Mirpur, a suburban area of Dhaka in Bangladesh, to investigate the levels of perinatal mortality and its associated maternal health factors during pregnancy. A total of 2007 women were followed after recruitment up to delivery, maternal death, or until they dropped out of the study. Of these, 1584 who gave birth formed our study subjects. The stillbirth rate was 39.1 per 1000 births [95% confidence interval (CI) 39.0, 39.3] and the perinatal mortality rate (up to 3 days) was 54.3 per 1000 births [95% CI 54.0, 54.6] among the study population. In the fully adjusted logistic regression model, the risk of perinatal mortality was as high as 2.7 times [95% CI 1.5, 4.9] more likely for women with hypertensive disorders, 5.0 times [95% CI 2.3, 10.8] as high for women who had antepartum haemorrhage and 2.6 times [95% CI 1.2, 5.8] as high for women who had higher haemoglobin levels in pregnancy when compared with their counterparts. The inclusion of potential confounding variables such as poor obstetric history, sociodemographic characteristics and preterm delivery influenced only marginally the net effect of important maternal health factors associated with perinatal mortality. Perinatal mortality in the study setting was significantly associated with poor maternal health conditions during pregnancy. The results of this study point towards the urgent need for monitoring complications in high-risk pregnancies, calling for the specific components of the safe motherhood programme interventions that are designed to manage these complications of pregnancy.

Hypertension, dyslipidemia, body mass index, Diabetes and smoking status in aboriginal australians in a remote community

Objectives: Study objectives were: 1) to describe the differences in the prevalence of CHID risk factors between Aboriginal people in a remote community and the general Australian population; and 2) to compare the predicted risks of CHD events between Aboriginal and non-Aboriginal Australians. Design: A cross-sectional study. Participants: 681 Aboriginal adults aged 25 to 74 years. Results: Aboriginal young adults had substantially higher prevalence of diabetes compared to non-Aboriginal Australians. The prevalence ratios for diabetes were 12.5, 5.6, 3.2, 1.3, and 0.73 for 25-, 35-, 45-, 55-, and 65- to 74-year-old females, respectively, The corresponding values for males were 12.1, 2.7, 2.9, 0.69, and 0.42. Young females had a higher prevalence of obesity, overweight, and abnormal waist circumference, while males and females 45 years and older tended to have a lower prevalence of overweight and ab. normal waist circumference. Compared to the general population, Aboriginal adults had a lower prevalence of abnormal total cholesterol but a higher prevalence of abnormal HDL, triglycerides, hypertension, and smoking. The risk ratios of abnormal total cholesterol for females ages 2534, 35-44, 45-54, 55-64, and 65-75 years were 0.38, 0.53, 0.48, 0.48, and 0.41, respectively. Conclusions: Aboriginal people in the remote community experienced different levels of CHD risk predictors from the general Australian population. They had a lower prevalence of abnormal total cholesterol and a higher prevalence of abnormal HDL, smoking, diabetes, and hypertension.

Nephron number, hypertension, renal disease, and renal failure

Essential hypertension is one of the most common diseases in the Western world, affecting about 26.4% of the adult population, and it is increasing (1). Its causes are heterogeneous and include genetic and environmental factors (2), but several observations point to an important role of the kidney in its genesis (3). In addition to variations in tubular transport mechanisms that could, for example, affect salt handling, structural characteristics of the kidney might also contribute to hypertension. The burden of chronic kidney disease is also increasing worldwide, due to population growth, increasing longevity, and changing risk factors. Although single-cause models of disease are still widely promoted, multideterminant or multihit models that can accommodate multiple risk factors in an individual or in a population are probably more applicable (4,5). In such a framework, nephron endowment is one potential determinant of disease susceptibility. Some time ago, Brenner and colleagues (6,7) proposed that lower nephron numbers predispose both to essential hypertension and to renal disease. They also proposed that hypertension and progressive renal insufficiency might be initiated and accelerated by glomerular hypertrophy and intraglomerular hypertension that develops as nephron number is reduced (8). In this review, we summarize data from recent studies that shed more light on these hypotheses. The data supply a new twist to possible mechanisms of the Barker hypothesis, which proposes that intrauterine growth retardation predisposes to chronic disease in later life (9). The review describes how nephron number is estimated and its range and some determinants and morphologic correlates. It then considers possible causes of low nephron numbers. Finally, associations of hypertension and renal disease with reduced nephron numbers are considered, and some potential clinical implications are discussed.

Reduced nephron number and glomerulomegaly in Australian Aborigines: A group at high risk for renal disease and hypertension

Aborigines in remote areas of Australia have much higher rates of renal disease, as well as hypertension and cardiovascular disease, than non-Aboriginal Australians. We compared kidney findings in Aboriginal and non-Aboriginal people in one remote region. Glomerular number and mean glomerular volume were estimated with the disector/fractionator combination in the right kidney of 19 Aborigines and 24 non-Aboriginal people undergoing forensic autopsy for sudden or unexpected death in the Top End of the Northern Territory. Aborigines had 30% fewer glomeruli than non-Aborigines-202000 fewer glomeruli per kidney, or an estimated 404000 fewer per person (P=0.036). Their mean glomerular volume was 27% larger (P=0.016). Glomerular number was significantly correlated with adult height, inferring a relationship with birthweight, which, on average, is much lower in Aboriginal than non-Aboriginal people. Aboriginal people with a history of hypertension had 30% fewer glomeruli than those without-250000 fewer per kidney (P=0.03), or 500000 fewer per person, and their mean glomerular volume was about 25% larger. The lower nephron number in Aboriginal people is compatible with their susceptibility to renal failure. The additional nephron deficit associated with hypertension is compatible with other reports. Lower nephron numbers are probably due in part to reduced nephron endowment, which is related to a suboptimal intrauterine environment. Compensatory glomerular hypertrophy in people with fewer nephrons, while minimizing loss of total filtering surface area, might be exacerbating nephron loss. Optimization of fetal growth should ultimately reduce the florid epidemic of renal disease, hypertension, and cardiovascular disease.

Leaking urine in Australian women: Prevalence and associated conditions

The paper aims to (1) assess the prevalence of leaking urine and to (2) explore associations between leaking urine and a variety of other symptoms, conditions, surgical procedures and life events in three large cohorts of Australian women, who are participants in the Australian Longitudinal Study on Women's Health. Young women aged 18-23 (N = 14,000), mid-age women, 45-50 (N 13,738) and older women, 70-75 (N = 12,417), were recruited randomly from the national HIC/Medicare database. Leaking urine was reported by approximately one in eight young women [estimated prevalence 12.8% (95% CI: 12.2-13.3)] and one in three mid-age women [36.1% (CI: 35.2-37.0)] and older women [35.0% (CI: 34.1-35.9)]. Leaking urine was significantly associated with parity, conditions which increase the pressure on the pelvic floor such as constipation and obesity, past gynecological surgery and conditions which can impact on bladder control. The study showed that fewer than half the women had sought help for the problem and that younger women were less likely to be satisfied with the help available for this problem. Strategies for continence promotion, including opportunistic raising of the issue at the time of cervical screening and pregnancy care are suggested, so that the health and social outcomes of untreated chronic incontinence in women might be improved.

Association of a glucocorticoid receptor gene marker with human essential hypertension.

Recently, a bi-allelic polymorphism in the glucocorticoid receptor gene (GRL) has been shown to be associated with individuals at high risk of developing hypertension and accumulation of abdominal visceral fat, a known risk factor for cardiovascular disease. The evaluate the role of GRL in essential hypertension and obesity, case-control studies were conducted using 88 hypertensive, 123 normotensive, 150 lean and 94 obese subjects. Genotypes for a highly polymorphic microsatellite marker (D5S207) located within 200 kb of the glucocorticoid receptor gene, were determined by PCR. Allele frequencies between hypertensive and normotensive groups were significantly (P = 0.0005) different whereas no significant differences were observed between lean and obese populations. In conclusion, the results suggest that the glucocorticoid receptor gene or perhaps another gene located in close proximity and in linkage disequilibrium with D5S207, is involved in hypertension development

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.