Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations

Background From the mid-1980s to mid-1990s, the WHO MONICA Project monitored coronary events and classic risk factors for coronary heart disease (CHD) in 38 populations from 21 countries. We assessed the extent to which changes in these risk factors explain the variation in the trends in coronary-event rates across the populations. Methods In men and women aged 35-64 years, non-fatal myocardial infarction and coronary deaths were registered continuously to assess trends in rates of coronary events. We carried out population surveys to estimate trends in risk factors. Trends in event rates were regressed on trends in risk score and in individual risk factors. Findings Smoking rates decreased in most male populations but trends were mixed in women; mean blood pressures and cholesterol concentrations decreased, body-mass index increased, and overall risk scores and coronary-event rates decreased. The model of trends in 10-year coronary-event rates against risk scores and single risk factors showed a poor fit, but this was improved with a 4-year time lag for coronary events. The explanatory power of the analyses was limited by imprecision of the estimates and homogeneity of trends in the study populations. Interpretation Changes in the classic risk factors seem to partly explain the variation in population trends in CHD. Residual variance is attributable to difficulties in measurement and analysis, including time lag, and to factors that were not included, such as medical interventions. The results support prevention policies based on the classic risk factors but suggest potential for prevention beyond these.

Social-cognitive and perceived environment influences associated with physical activity in older Australians

Background, Regular physical activity in older adults can facilitate healthy aging, improve functional capacity, and prevent disease. However, factors associated with physical inactivity in older populations are poorly understood. This study attempts to identify social-cognitive and perceived environmental influences associated with physical activity participation in older populations. Methods. In a randomly selected sample of 449 Australian adults age 60 and older, we assessed self-reported physical activity and a range of social-cognitive and perceived environmental factors. Respondents were classified as sufficiently active and inactive based on energy expenditure estimates (kcal/week) derived from self-reported physical activity. Two logistic regression models, with and without self-efficacy included, were conducted to identify modifiable independent predictors of physical activity. Results. Significantly more males than females were physically active. Physical activity participation was related to age with a greater proportion of those age 65-69 being active than those age 60-64 or 70 or older. High self-efficacy, regular participation of friends and family, finding footpaths safe for walking, and access to local facilities were significantly associated with being active. Conclusion. Identifying predictors of physical activity in older populations, particularly social support, facility access, and neighbourhood safety, can inform the development of policy and intervention strategies to promote the health of older people. (C) 2000 American Health Foundation and Academic Press.

Regarding "Edema and leg volume: Methods of assessment" (Letters to the Editor)

I noted with interest the article by Drs Perrin and Guex, entitled &dquo;Edema and leg volume: Methods of assessment,&dquo; published in Angiology 51:9-12, 2000. This was a timely and comprehensive review of the various methods in clinical use for the assessment of peripheral edema, notably in the leg. I would like to take this opportunity to alert readers to a further technique useful for this purpose, namely, bioelectrical impedance analysis. An early reportl described its use for the measurement of edema in the leg, but other than its successful use for the assessment of edema in the arm following masteCtoMy,2,1 the potential of the method remains to be fully realized. This is unfortunate since the method directly and quantifiably measures edema.

Expression of RANTES and CCR1 in oral lichen planus and association with mast cell migration

Background: T lymphocytes and mast cells infiltrate the lamina propria in oral lichen planus (OLP). Chemokines and their receptors are involved in T cell and mast cell migration and accumulation during the inflammatory process. Methods: In the present study, we investigated the role of RANTES and its receptors in OLP using immunohistochemistry, RT-PCR and an in vitro chemotaxis assay. Results: RANTES and CCR1 were expressed on T cells and mast cells in OLP, while OLP lesional T cell supernatants stimulated CCR1 mRNA expression in a human leukemia mast cell line (HMC-1). TNF-alpha stimulated CCR1, CCR4 and CCR5 mRNA expression in the same cell line. OLP lesional T cell supernatants stimulated HMC-1 migration, which was partly inhibited by anti-RANTES antibody. Conclusions: The present study shows, for the first time, the distribution of RANTES and CCR1 in OLR It is hypothesized that RANTES and CCR1 may play important roles in mast cell trafficking and related events in OLP.

Developing qualitative career assessment processes

Assessment has been integral to career counseling since the early 1900s. During that time, the greatest amount of attention was focused on quantitative assessment. Thus, there is still very little to guide the development and conduct of qualitative assessment in career counseling. The authors present an overview of qualitative career assessment and its theoretical underpinnings and propose suggestions that could guide the development of qualitative career assessment instruments.

Melphalan dosing regimens for management of recurrent melanoma by isolated limb perfusion: Application of a physiological pharmacokinetic model based on melphalan distribution in the isolated perfused rat hindlimb

The optimal dosing schedule for melphalan therapy of recurrent malignant melanoma in isolated limb perfusions has been examined using a physiological pharmacokinetic model with data from isolated rat hindlimb perfusions (IRHP), The study included a comparison of melphalan distribution in IRHP under hyperthermia and normothermia conditions. Rat hindlimbs were perfused with Krebs-Henseleit buffer containing 4.7% bovine serum albumin at 37 or 41.5 degrees C at a flow rate of 4 ml/min. Concentrations of melphalan in perfusate and tissues were determined by high performance liquid chromatography with fluorescence detection, The concentration of melphalan in perfusate and tissues was linearly related to the input concentration. The rate and amount of melphalan uptake into the different tissues was higher at 41.5 degrees C than at 37 degrees C. A physiological pharmacokinetic model was validated from the tissue and perfusate time course of melphalan after melphalan perfusion. Application of the model involved the amount of melphalan exposure in the muscle, skin and fat in a recirculation system was related to the method of melphalan administration: single bolus > divided bolus > infusion, The peak concentration of melphalan in the perfusate was also related to the method of administration in the same order, Infusing the total dose of melphalan over 20 min during a 60 min perfusion optimized the exposure of tissues to melphalan whilst minimizing the peak perfusate concentration of melphalan. It is suggested that this method of melphalan administration may be preferable to other methods in terms of optimizing the efficacy of melphalan whilst minimizing the limb toxicity associated with its use in isolated limb perfusion.

Caring for someone with dementia in a rural town .2. Services

Dementia care in rural areas is in need of attention from researchers, planners and policy makers. Family carers in these areas face some significant challenges, in terms of managing the care where support services are often unavailable or inaccessible. This paper reports on a qualitative study in which a group of rural based carers participated in a focus group and interviews. Through this process, the carers' perceptions of support services were explored. Content analysis of the data revealed that, despite a number of supportive aspects of rural life, these carers felt in need of more services, a finding supported by current literature.

Out of the shadows: The critical sociology of sport in Australia, 1986 to 1996

The sociology of sport in Australia has reached a key point in its development. A critical tradition in the subdiscipline has been established over the last decade, but its intellectual and institutional progress has been uneven. This article briefly traces the emergence of critical sports sociology in a country outside the major centers in the UK and U.S., its break with functionalist approaches, and its attempts to overcome the neglect of local mainstream sociology. The authors proceed to examine (self-reflexively) the changes of theoretical direction and the new lines of research that are being explored in the field. A recent ''skirmish'' with narrative history over the preferred theories and methods in sports analysis is discussed as illustrative of the difficulties encountered by an energetic but small, dispersed and underorganized scholarly movement in Australia.

Selective down-regulation of the astrocyte glutamate transporters GLT-1 and GLAST within the medial thalamus in experimental wernicke's encephalopathy

Although earlier studies on thiamine deficiency have reported increases in extracellular glutamate concentration in the thalamus, a vulnerable region of the brain in this disorder, the mechanism by which this occurs has remained unresolved. Treatment with pyrithiamine, a central thiamine antagonist, resulted in a 71 and 55% decrease in protein levels of the astrocyte glutamate transporters GLT-1 and GLAST, respectively, by immunoblotting in the medial thalamus of day 14 symptomatic rats at loss of righting reflexes. These changes occurred prior to the onset of convulsions and pannecrosis. Loss of both GLT-1 and GLAST transporter sites was also confirmed in this region of the thalamus at the symptomatic stage using immunohistochemical methods. In contrast, no change in either transporter protein was detected in the non-vulnerable frontal parietal cortex. These effects are selective; protein levels of the astrocyte GABA transporter GAT-3 were unaffected in the medial thalamus. In addition, astrocyte-specific glial fibrillary acidic protein (GFAP) content was unchanged in this brain region, suggesting that astrocytes are spared in this disorder. Loss of GLT-1 or GLAST protein was not observed on day 12 of treatment, indicating that down-regulation of these transporters occurs within 48 h prior to loss of righting reflexes. Finally, GLT-1 content was positively correlated with levels of the neurofilament protein alpha -internexin, suggesting that early neuronal drop-out may contribute to the down-regulation of this glutamate transporter and subsequent pannecrosis. A selective, focal loss of GLT-1 and GLAST transporter proteins provides a rational explanation for the increase in interstitial glutamate levels, and may play a major role in the selective vulnerability of thalamic structures to thiamine deficiency-induced cell death.

Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites - In vivo assessment using phospho-specific antibodies

Recent studies have provided evidence that breast cancer susceptibility gene products (Brca1 and Brca2) suppress cancer, at least in part, by participating in DNA damage signaling and DNA repair. Brca1 is hyperphosphorylated in response to DNA damage and co-localizes with Rad51, a protein involved in homologous-recombination, and Nbs1·Mre11·Rad50, a complex required for both homologous-recombination and nonhomologous end joining repair of damaged DNA. Here, we report that there is a qualitative difference in the phosphorylation states of Brca1 between ionizing radiation (IR) and UV radiation. Brca1 is phosphorylated at Ser-1423 and Ser-1524 after IR and UV; however, Ser-1387 is specifically phosphorylated after IR, and Ser-1457 is predominantly phosphorylated after UV. These results suggest that different types of DNA-damaging agents might signal to Brca1 in different ways. We also provide evidence that the rapid phosphorylation of Brca1 at Ser-1423 and Ser-1524 after IR (but not after UV) is largely ataxia telangiectasia mutated (ATM) kinase-dependent. The overexpression of catalytically inactive ATM and Rad3 related (ATR) kinase inhibited the UV-induced phosphorylation of Brca1 at these sites, indicating that ATR controls Brca1 phosphorylation in vivo after the exposure of cells to UV light. Moreover, ATR associates with Brca1; ATR and Brca1 foci co-localize both in cells synchronized in S phase and after exposure of cells to DNA-damaging agents. ATR can itself phosphorylate the region of Brca1 phosphorylated by ATM (Ser-Gln cluster in the C terminus of Brca1, amino acids 1241-1530). However, there are additional uncharacterized ATR phosphorylation site(s) between residues 521 and 757 of Brca1. Taken together, our results support a model in which ATM and ATR act in parallel but somewhat overlapping pathways of DNA damage signaling but respond primarily to different types of DNA lesion.

Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites - In vivo assessment using phospho-specific antibodies

Recent studies have provided evidence that breast cancer susceptibility gene products (Brca1 and Brca2) suppress cancer, at least in part, by participating in DNA damage signaling and DNA repair. Brca1 is hyperphosphorylated in response to DNA damage and co-localizes with Rad51, a protein involved in homologous-recombination, and Nbs1.Mre11.Rad50, a complex required for both homologous-recombination and nonhomologous end joining repair of damaged DNA. Here, we report that there is a qualitative difference in the phosphorylation states of Brca1 between ionizing radiation (IR) and UV radiation. Brca1 is phosphorylated at Ser-1423 and Ser-1524 after IR and W; however, Ser-1387 is specifically phosphorylated after IR, and Ser-1457 is predominantly phosphorylated after W. These results suggest that different types of DNA-damaging agents might signal to Brca1 in different ways. We also provide evidence that the rapid phosphorylation of Brca1 at Ser-1423 and Ser-1524 after IR (but not after W) is largely ataxia telangiectasia mutated (ATM) kinase-dependent. The overexpression of catalytically inactive ATM and Rad3 related (ATR) kinase inhibited the UV-induced phosphorylation of Brca1 at these sites, indicating that ATR controls Brca1 phosphorylation in vivo after the exposure of cells to UV light. Moreover, ATR associates with Brca1; ATR and Brca1 foci co-localize both in cells synchronized in S phase and after exposure of cells to DNA-damaging agents. ATR can itself phosphorylate the region of Brca1 phosphorylated by ATM (Ser-Gln cluster in the C terminus of Brca1, amino acids 1241-1530), However, there are additional uncharacterized ATR phosphorylation site(s) between residues 521 and 757 of Brca1, Taken together, our results support a model in which ATM and ATR act in parallel but somewhat overlapping pathways of DNA damage signaling but respond primarily to different types of DNA lesion.

A decision support process to compare Riparian revegetation options in Scheu Creek catchment in North Queensland

While riparian vegetation can play a major role in protecting land, water and natural habitat in catchments, there are high costs associated with tree planting and establishment and in diverting land from cropping. The distribution of costs and benefits of riparian revegetation creates conflicts in the objectives of various stakeholder groups. Multicriteria analysis provides an appropriate tool to evaluate alternative riparian revegetation options, and to accommodate the conflicting views of various stakeholder groups. This paper discusses an application of multicriteria analysis in an evaluation of riparian revegetation policy options for Scheu Creek, a small sub-catchment in the Johnstone River catchment in north Queensland, Australia. Clear differences are found in the rankings of revegetation options for different stakeholder groups with respect to environmental, social and economic impacts. Implementation of a revegetation option will involve considerable cost for landholders for the benefits of society. Queensland legislation does not provide a means to require farmers to implement riparian revegetation, hence the need for subsidies, tau incentives and moral suasion. (C) 2001 Academic Press.

Rapid diagnosis in pediatric infectious diseases: The past, the present and the future

The focus of rapid diagnosis of infectious diseases of children in the last decade has shifted from variations of the conventional laboratory techniques of antigen detection, microscopy and culture to that of molecular diagnosis of infectious agents. Pediatricians will need to be able to interpret the use, limitations and results of molecular diagnostic techniques as they are increasingly integrated into routine clinical microbiology laboratory protocols. PCR is the best known and most successfully implemented diagnostic molecular technology to date. It can detect specific infectious agents and determine their virulence and antimicrobial genotypes with greater speed, sensitivity and specificity than conventional microbiology methods. Inherent technical limitations of PCR are present, although they are reduced in laboratories that follow suitable validation and quality control procedures. Variations of PCR together with advances in nucleic acid amplification technology have broadened its diagnostic capabilities in clinical infectious disease to now rival and even surpass traditional methods in some situations. Automation of all components of PCR is now possible. The completion of the genome sequencing projects for significant microbial pathogens, in combination with PCR and DNA chip technology, will revolutionize the diagnosis and management of infectious diseases.

Repeated blood pressure measurements in a sample of Swedish twins: heritabilities and associations with polymorphisms in the renin-angiotensin-aldosterone system Iliadou, Anastasia, Lichtenstein, Paul, Morgenstern, Ralf, Forsberg, Lena, Svensson, Richard, de Faire, Ulf, Martin, Nicholas, Pedersen, Nancy

Background Twin and family studies have shown that genetic effects explain a relatively high amount of the phenotypic variation in blood pressure. However, many studies have not been able to replicate findings of association between specific polymorphisms and diastolic and systolic blood pressure. Methods In a structural equation-modelling framework the authors investigated longitudinal changes in repeated measures of blood pressures in a sample of 298 like-sexed twin pairs from the population-based Swedish Twin Registry. Also examined was the association between blood pressure and polymorphisms in the angiotensin-I converting enzyme and the angiotensin 11 receptor type 1 with the 'Fulker' test Both linkage and association were tested simultaneously revealing whether the polymorphism is a Quantitative Trait Locus (QTL) or in linkage disequilibrium with the QTL. Results Genetic influences explained up to 46% of the phenotypic variance in diastolic and 63% of the phenotypic variance in systolic blood pressure. Genetic influences were stable over time and contributed up to 78% of the phenotypic correlation in both diastolic and systolic blood pressure. Non-shared environmental effects were characterised by time specific influences and little transmission from one time point to the next. There was no significant linkage and association between the polymorphisms and blood pressure. Conclusions There is a considerable genetic stability in both diastolic and systolic blood pressure for a 6-year period of time in adult life. Non-shared environmental influences have a small long-term effect Although associations with the polymorphisms could not be replicated, results should be interpreted with caution due to power considerations. (C) 2002 Lippincott Williams Wilkins.

Age and gender differences in objectively measured physical activity in youth

TROST. S. G., R. R. PATE, J. F. SALLIS, P. S. FREEDSON, W. C. TAYLOR, M. DOWDA, and J. SIRARD. Age and gender differences in objectively measured physical activity in youth. Med. Sci. Sports Ererc., Vol. 34, No. 2, pp. 350-355, 2002. Purpose: The purpose of this study was to evaluate age and gender differences in objectively measured physical activity (PA) in a population-based sample of students in grades 1-12. Methods: Participants (185 male, 190 female) wore a CSA 7164 accelerometer for 7 consecutive days. To examine age-related trends. students were grouped as follows: grades 1-3 (N = 90), grades 4-6 (N = 91), grades 7-9 (N = 96). and grades 10-12 (N = 92). Bouts of PA and minutes spent in moderate-to-vigorous PA (MVPA) and vigorous PA (VPA) were examined. Results: Daily MVPA and VPA exhibited a significant inverse relationship with grade level, with the largest differences occurring between grades 1d-3 and 4-6. Boys were more active than girls; however, for overall PA, the magnitudes of the gender differences were modest. Participation in continuous 20-min bouts of PA was low to nonexistent. Conclusion: Our results support the notion that PA declines rapidly during childhood and adolescence and that accelerometers are feasible alternatives to self-report methods in moderately sized population-level surveillance studies.