Staphylococcus aureus bacteremia, Australia

Staphylococcus aureus bacteremia (SAB) is common and increasing worldwide. A retrospective review was undertaken to quantify the number of cases, their place of acquisition, and the proportions caused by methicillin-resistant.S. aureus (MRSA) in 17 hospitals in Australia. Of 3,192 episodes, 1,571 (49%) were community onset. MRSA caused 40% of hospital-onset episodes and 12% of community-onset episodes. The median rate of SAB was 1.48/1,000 admissions (range 0.61-3.24; median rate for hospital-onset SAB was 0.7/1,000 and for community onset 0.8/1,000 admissions). Using these rates, we estimate that approximate to 6,900 episodes of SAB occur annually in Australia (35/100,000 population). SAB is common, and a substantial proportion of cases may be preventable. The epidemiology is evolving, with > 10% of community-onset SAB now caused by MRSA. This is an emerging infectious disease concern and is likely to impact on empiric antimicrobial drug prescribing in suspected cases of SAB.

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.

Kidney and related chronic disease profiles and risk factors in three remote Australian Aboriginal communities

Morbidities and deaths from noncommunicable chronic diseases are greatly increased in remote Australian Aboriginal communities, but little is known of the underlying community-based health profiles. We describe chronic-disease profiles and their risk factors in 3 remote communities in the Northern Territory. Consenting adults (18+ years of age) in 3 communities participated in a brief history and examination between 2000 and mid-2003 as part of a systematic program to improve chronic-disease awareness and management. Participation was 67%,128%, and 62% in communities A, B, and C, respectively with a total of 1070 people examined. Current smokers included 41% of females and 72% of males. Most men were current drinkers, but most women were not. Parameters of body weight differed markedly by community, with mean body mass index (BMC) varying from 21.4 to 27.9 kg/m(2). Rates of chronic diseases were excessive but differed markedly; an almost threefold difference in the likelihood of any morbidity existed between communities A and C. Rates increased with age, but the greatest numbers of people with morbidities were in the middle-aged group. Most people had multiple morbidities with tremendous overlap. Hypertension and kidney disease appear to be early manifestations of the integrated chronic-disease syndrome, while diabetes is a late manifestation or complication. Substantial numbers of new cases of disease were identified by testing, and blood pressure improved in treated people with hypertension. Wide variations occur in body habitus, risk factors, and chronic-disease rates among communities, but an overwhelming need for effective smoking interventions exists in all. Systematic screening is useful in identifying high-risk individuals, most at early treatable stages there. Findings are very important for estimating current treatment needs, future burdens of disease, and for needs-based health services planning. Resources required will vary according to the burden of disease. (C) 2005 by the National Kidney Foundation, Inc.

Baseline serum lipids and renal function in chronic kidney disease patients entering the LORD trial

Objective: Previous studies investigating associations between serum lipids and renal disease have generally not taken into account dietary intake or physical activity - both known to influence circulating lipids. Furthermore, inclusion of patients on HMG-CoA reductase inhibitors may also have influenced findings due to the pleiotropic effect of this medication. Therefore, the aim of this study is to determine the relationships between serum lipids and renal function in a group of patients not taking lipid-lowering medication and taking into account dietary intake and physical activity. Methods: Data from 100 patients enrolled in the Lipid Lowering and Onset of Renal Disease (LORD) trial were used in this study. Patients were included with serum creatinine > 120 mu mol/l, and excluded if they were taking lipid-lowering medication. Unadjusted and adjusted relationships were determined between fasting serum lipid concentrations (total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol/HDL ratio) and measures of renal function (estimated glomerular filtration rate (eGFR), creatinine clearance and serum creatinine) and urinary protein excretion. Results: Significant (p < 0.05) negative unadjusted relationships were found between lipids (total cholesterol, LDL and HDL cholesterol) and serum creatinine. In support of these findings, logarithmically-transformed lipids (total cholesterol, LDL and HDL cholesterol) were significantly associated with eGFR and creatinine clearance although the effects were of a smaller magnitude. Adjustment for dietary saturated fat intake and physical activity did not substantially change these effects. Conclusion: These data do not support the premise that lipids are associated with renal dysfunction in patients with normocholesterolemia.

Ross River virus disease clusters and spatial relationship with mosquito biting exposure in Redland Shire, southern Queensland, Australia

The spatial heterogeneity in the risk of Ross River virus (family Togaviridae, genus Alphavirus, RRV) disease, the most common mosquito-borne disease in Australia, was examined in Redland Shire in southern Queensland, Australia. Disease cases, complaints from residents of intense mosquito biting exposure, and human population data were mapped using a geographic information system. Surface maps of RRV disease age-sex standardized morbidity ratios and mosquito biting complaint morbidity ratios were created. To determine whether there was significant spatial variation in disease and complaint patterns, a spatial scan analysis method was used to test whether the number of cases and complaints was distributed according to underlying population at risk. Several noncontiguous areas in proximity to productive saline water habitats of Aedes vigilax (Skuse), a recognized vector of RRV, had higher than expected numbers of RRV disease cases and complaints. Disease rates in human populations in areas which had high numbers of adult Ae. vigilax in carbon dioxide- and octenol-baited light traps were up to 2.9 times those in areas that rarely had high numbers of mosquitoes. It was estimated that targeted control of adult Ae. vigilax in these high-risk areas could potentially reduce the RRV disease incidence by an average of 13.6%. Spatial correlation was found between RRV disease risk and complaints from residents of mosquito biting. Based on historical patterns of RRV transmission throughout Redland Shire and estimated future human population growth in areas with higher than average RRV disease incidence, it was estimated that RRV incidence rates will increase by 8% between 2001 and 2021. The use of arbitrary administrative areas that ranged in size from 4.6 to 318.3 km2, has the potential to mask any small scale heterogeneity in disease patterns. With the availability of georeferenced data sets and high-resolution imagery, it is becoming more feasible to undertake spatial analyses at relatively small scales.

Synthesis of a highly pure lipid core peptide based self-adjuvanting triepitopic group A Streptococcal vaccine, and subsequent immunological evaluation

We have developed a highly pure, self-adjuvanting, triepitopic Group A Streptococcal vaccine based on the lipid core peptide system, a vaccine delivery system incorporating lipidic adjuvant, carrier, and peptide epitopes into a single molecular entity. Vaccine synthesis was performed using native chemical ligation. Due to the attachment of a highly lipophilic adjuvant, addition of 1% (w/v) sodium dodecyl sulfate was necessary to enhance peptide solubility in order to enable ligation. The vaccine was synthesized in three steps to yield a highly pure product (97.7% purity) with an excellent overall yield. Subcutaneous immunization of B10. BR (H-2(k)) mice with the synthesized vaccine, with or without the addition of complete Freund's adjuvant, elicited high serum IgG antibody titers against each of the incorporated peptide epitopes.

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.

Energy and calcium stores are preserved in girls and young women with CF, independent of disease severity: An explanation for the 'gender gap'?

Bioenergetics differ between males and females of many species. Human females apportion a substantial proportion of energy resources towards gynoid fat storage, to support the energetic burden of reproduction. Similarly, axial calcium accrual is favoured in females compared with males. Nutritional status is a prognostic indicator in cystic fibrosis (CF), but girls and young women are at greater risk of death despite equivalent nutritional status to males. The aim of this study was to compare fat (energy) and calcium stores (bone density) in males and females with CF over a spectrum of disease severity. Methods: Fat as % body weight (fat%) and lumbar spine (LS) and total body (TB) bone mineral density (BMD) were measured using dual absorption X-ray photometry in 127(59M) control and 101(54M) CF subjects, aged 9–25 years. An equation for predicted age at death had been determined using survival data and history of pulmonary function for the whole clinic, based on a trivariate normal model using maximum likelihood methods (1). For the CF group, a disease severity index (predicted age at death) was calculated from the derived equations according to each subjects history of pulmonary function, current age, and gender. Disease severity was classified according to percentile of predicted age at death (‘mild’ ≥75th, ‘moderate’ 25th–75th, ‘severe’ ≤25th percentile). Wt for age z-score was calculated. Serum testosterone and oestrogen were measured in males and females respectively. Fat% and LSBMD were compared between the groups using ANOVA. Results: There was an interaction between disease severity and gender: increasing disease severity was associated with greater deficits in TB (p=0.01), LSBMD (p