Effects of pathophysiological concentrations of albumin on NHE3 activity and cell proliferation in primary cultures of human proximal tubule cells

The progression of renal disease correlates strongly with hypertension and the degree of proteinuria, suggesting a link between excessive Na+ reabsorption and exposure of the proximal tubule to protein. The present study investigated the effects of albumin on cell growth and Na+ uptake in primary cultures of human proximal tubule cells (PTC). Albumin (1.0 mg/ml) increased cell proliferation to 134.1 +/- 11.8% (P < 0.001) of control levels with no change in levels of apoptosis. Exposure to 0.1 and 1.0 mg/ml albumin increased total Na-22(+) uptake to 119.1 &PLUSMN; 6.3% (P = 0.005) and 115.6 &PLUSMN; 5.3% (P < 0.006) of control levels, respectively, because of an increase in Na+/H+ exchanger isoform 3 (NHE3) activity. This was associated with an increase in NHE3 mRNA to 161.1 +/- 15.1% (P < 0.005) of control levels in response to 0.1 mg/ml albumin. Using confocal microscopy with a novel antibody raised against the predicted extracellular NH2 terminus of human NHE3, we observed in nonpermeabilized cells that exposure of PTC to albumin (0.1 and 1.0 mg/ml) increased NHE3 at the cell surface to 115.4 &PLUSMN; 2.7% (P < 0.0005) and 122.4 +/- 3.7% (P < 0.0001) of control levels, respectively. This effect was paralleled by significant increases in NHE3 in the subplasmalemmal region as measured in permeabilized cells. These albumin-induced increases in expression and activity of NHE3 in PTC suggest a possible mechanism for Na+ retention in response to proteinuria.

Topographic plasticity in primary visual cortex is mediated by local corticocortical connections

The placement of monocular laser lesions in the adult cat retina produces a lesion projection zone (LPZ) in primary visual cortex (V1) in which the majority of neurons have a normally located receptive field (RF) for stimulation of the intact eye and an ectopically located RF ( displaced to intact retina at the edge of the lesion) for stimulation of the lesioned eye. Animals that had such lesions for 14 - 85 d were studied under halothane and nitrous oxide anesthesia with conventional neurophysiological recording techniques and stimulation of moving light bars. Previous work suggested that a candidate source of input, which could account for the development of the ectopic RFs, was long-range horizontal connections within V1. The critical contribution of such input was examined by placing a pipette containing the neurotoxin kainic acid at a site in the normal V1 visual representation that overlapped with the ectopic RF recorded at a site within the LPZ. Continuation of well defined responses to stimulation of the intact eye served as a control against direct effects of the kainic acid at the LPZ recording site. In six of seven cases examined, kainic acid deactivation of neurons at the injection site blocked responsiveness to lesioned-eye stimulation at the ectopic RF for the LPZ recording site. We therefore conclude that long-range horizontal projections contribute to the dominant input underlying the capacity for retinal lesion-induced plasticity in V1.

The prevalence of childhood obesity in primary school children in urban Khon Kaen, Northeast Thailand

Childhood obesity is a serious public health problem because of its strong association with adulthood obesity and the related adverse health consequences. The published literature indicates a rising prevalence of childhood obesity in both developed and developing countries. However no data exists on the prevalence in Northeast Thailand, one of the poorest regions of the country and one that has experienced a recent economic transition. The objective of this study was to estimate the prevalence of obesity in seven to nine year old children in urban Khon Kaen, Northeast Thailand. A cross-sectional school based survey was conducted to determine the prevalence of obesity in children of urban Khon Kaen, Thailand. Multi-staged cluster sampling was used to select 12 school clusters of 72 children each between the ages of 7 and 9 years, in primary school grades 1, 2 and 3 from government, private and demonstration schools. A total of 864 seven to nine year old school children were studied. Anthropometric measurements of standing height and weight were taken for all subjects to the nearest tenth of a centimetre and tenth of a kilogram respectively. Childhood obesity was defined as a weight-for-height Z-score above 2.0 standard deviations of the National Center for Health Statistics/World Health Organisation reference population median. The prevalence of childhood obesity was 10.8% (95% CI: 7.6, 13.9). Obesity was significantly more prevalent in boys than girls. The biggest difference was observed between the three school types, with the highest prevalence of obesity found at teacher training demonstration schools and the lowest at the government schools. This study provides the first data on childhood obesity prevalence in Northeast Thailand. The prevalence of 10.8 per cent is lower than that found in two other urban areas of Thailand but slightly higher than expected for this relatively poor region. If this prevalence rate increases, as observed in other countries in economic transition, the incidence of non-communicable diseases associated with obesity is also likely to increase, thus raising cause for concern and reason for intervention to both control and prevent obesity during childhood.

Meeting in the middle: Improving communication in primary health care consultations with people with an intellectual disability

The increased presence and participation in Australian society of people with an intellectual disability provides challenges for the provision of primary health care. General practitioners (GPs) identify themselves as ill equipped to provide for this heterogeneous population. A major obstacle to the provision of appropriate health care is seen as inadequate communication between the GP and the person with an intellectual disability, who may or may not be accompanied by a carer or advocate. This qualitative study in which five GPs, three people with intellectual disability, seven carers and two advocates (parent and friend) were interviewed was conducted in Brisbane, Australia. The aim was to better understand the factors that have an impact upon the success of communication in a medical consultation. Findings suggested that GPs were concerned with the aspects of communication difficulties which influenced their ability to adequately diagnose, manage and inform patients. Implications for practice management were also identified. People with intellectual disability reported frustration when they felt that they could not communicate adequately with the GP and annoyance when they were not included in the communication exchange. Carers were strong advocates for the person with intellectual disability, but indicated insufficient skill and knowledge to provide the level of assistance required in the consultation. The outcome was a model of cooperation that outlined the responsibilities of all players in the medical encounter, prior to, during and after the event.

Physical activity promotion in primary care: Bridging the gap between research and practice

Background: Aflifle a growing literature supports the effectiveness of physical activity interventions delivered in the primary care setting, few studies have evaluated efforts to increase physician counseling on physical activity during routine practice (i.e., outside the context of controlled research). This paper reports the results of a dissemination trial of a primary care-based physical activity counseling intervention conducted within the context of a larger, multi-strategy, Australian community-based, physical activity intervention, the 10,000 Steps Rockhampton Project. Methods: All 23 general practices and 66 general practitioners (GPs, the Australian equivalent of family physicians) were invited to participate. Practice visits were made to consenting practices during which instruction in brief physical activity counseling was offered, along with physical activity promotion resources (print materials and pedometers). The evaluation, guided by the RE-AIM framework, included collection of process data, as well as pre-and post-inteivention data from a mailed GP survey, and data from the larger project's random-digit-dialed, community-based, cross-sectional telephone survey that was conducted in Rockhampton and a comparison community, Results: Ninety-one percent of practices were visited by 10,000 Steps staff and agreed to participate, with 58% of GPs present during the visits. General practitioner survey response rates were 67% (n =44/66 at baseline) and 71% (n =37/52, at 14-month follow-up). At follow-up, 62% had displayed the poster, 81% were using the brochures, and 70% had loaned pedometers to patients, although the number loaned was relatively small. No change was seen in GP self-report of the percentage of patients counseled on physical activity. However, data from the telephone surveys showed a 31% increase in the likelihood of recalling GP advice on physical activity in Rockhampton (95% confidence interval [CI]=1.11-1.54) compared to a 16% decrease (95% CI=0.68-1.04) in the comparison community. Conclusions: This dissemination study achieved high rates of GP uptake, reasonable levels of implementation, and a significant increase in the number of community residents counseled on physical activity. These results suggest that evidence-based primary care physical activity counseling protocols can be translated into routine practice, although the initial and ongoing investment of time to develop partnerships with relevant healthcare organizations, and the interest generated by the overall 10,000 Steps program should not be underestimated. ((C) 2004 American journal of Preventive Medicine.

Trial of low-cost teledermatology in primary care

We examined the feasibility of a low-cost, store-and-forward teledermatology service for general practitioners (GPs) in regional Queensland. Digital pictures and a brief case history were transmitted by email. A service coordinator carried out quality control checks and then forwarded these email messages to a consultant dermatologist. On receiving a clinical response from the dermatologist, the service coordinator returned the message to the referring GP. The aim was to provide advice to rural Gps within one working day. Over six months, 63 referrals were processed by the teledermatology service, covering a wide range of dermatological conditions. In the majority of cases the referring doctors were able to treat the condition after receipt of email advice from the dermatologist; however, in 10 cases (16%) additional images or biopsy results were requested because image quality was inadequate. The average time between a referral being received and clinical advice being provided to the referring GPs was 46 hours. The number of referrals in the present study, 1.05 per month per site, was similar to that reported in other primary care studies. While the use of low-cost digital cameras and public email is feasible, there may be other issues, for example remuneration, which will militate against the widespread introduction of primary care teledermatology in Australia.

LPS regulates a set of genes in primary murine macrophages by antagonising CSF-1 action

We previously reported that bacterial products such as LPS and CpG DNA down-modulated cell surface levels of the Colony Stimulating Factor (CSF)-1 receptor (CSF-1R) on primary murine macrophages in an all-or-nothing manner. Here we show that the ability of bacterial products to down-modulate the CSF-IR rendered bone marrow-derived macrophages (BMM) unresponsive to CSF-1 as assessed by Akt and ERK 1/2 phosphorylation. Using toll-like receptor (th-)9 as a model CSF-1-repressed gene, we show that LPS induced tlr9 expression in BMM only when CSF-1 was present, suggesting that LPS relieves CSF-1-mediated inhibition to induce gene expression. Using cDNA microarrays, we identified a cluster of similarly CSF-1 repressed genes in BMM. By real time PCR we confirmed that the expression of a selection of these genes, including integral membrane protein 2B (itm2b), receptor activity-modifying protein 2 (ramp2) and macrophage-specific gene 1 (mpg-1), were repressed by CSF-1 and were induced by LPS only in the presence of CSF-1. This pattern of gene regulation was also apparent in thioglycollate-elicited peritoneal macrophages (TEPM). LPS also counteracted CSF-1 action to induce mRNA expression of a number of transcription factors including interferon consensus sequence binding protein 1 (Icsbp1), suggesting that this mechanism leads to transcriptional reprogramming in macrophages. Since the majority of in vitro studies on macrophage biology do not include CSF-1, these genes represent a set of previously uncharacterised LPS-inducible genes. This study identifies a new mechanism of macrophage activation, in which LPS (and other toll-like receptor agonists) regulate gene expression by switching off the CSF-1R signal. This finding also provides a biological relevance to the well-documented ability of macrophage activators to down-modulate surface expression of the CSF-1R. (C) 2005 Elsevier GmbH. All rights reserved.

Quantifying the association between physical activity and injury in primary school-aged children

BACKGROUND. Regular physical activity is strongly advocated in children, with recommendations suggesting up to several hours of daily participation. However, an unintended consequence of physical activity is exposure to the risk of injury. To date, these risks have not been quantified in primary school-aged children despite injury being a leading cause for hospitalization and death in this population. OBJECT. Our goal was to quantify the risk of injury associated with childhood physical activity both in and out of the school setting and calculate injury rates per exposure time for organized and non-organized activity outside of school. METHODS. The Childhood Injury Prevention Study prospectively followed a cohort of randomly selected Australian primary school- and preschool-aged children (4 to 12 years). Over 12 months, each injury that required first aid attention was registered with the study. Exposure to physical activity outside school hours was measured by using a parent-completed 7-day diary. The age and gender distribution of injury rates per 10 000 hours of exposure were calculated for all activity and for organized and non-organized activity occurring outside school hours. In addition, child-based injury rates were calculated for physical activity-related injuries both in and out of the school setting. RESULTS. Complete diary and injury data were available for 744 children. There were 504 injuries recorded over the study period, 396 (88.6%) of which were directly related to physical activity. Thirty-four percent of physical activity-related injuries required professional medical treatment. Analysis of injuries occurring outside of school revealed an overall injury rate of 5.7 injuries per 10 000 hours of exposure to physical activity and a medically treated injury rate of 1.7 per 10 000 hours. CONCLUSION. Injury rates per hours of exposure to physical activity were low in this cohort of primary school-aged children, with < 2 injuries requiring medical treatment occurring for every 10 000 hours of activity participation outside of school.