Cardiac involvement in hypertension

Despite improved patient detection and pharmacologic therapy, the effect of treatment of hypertension on mortality from coronary artery-related events remains unresolved. Left ventricular (LV) hypertrophy, a known consequence of hypertension, is associated with an excess mortality independent of other known cardiovascular risk factors. Recently, LV hypertrophy accompanying hypertension has been associated with ominous ventricular arrhythmias. However, it does not necessarily follow that regression of LV hypertrophy will reduce this increased mortality. Diastolic dysfunction, manifested by reduced ventricular distensibility of the hypertrophying left ventricle, appears to be an early characteristic of the hypertensive heart since echocardiographic techniques have demonstrated diastolic filling abnormalities in untreated essential hypertensives even before significant LV hypertrophy appears. Not all antihypertensive agents diminish LV mass and improve diastolic dysfunction. Certain sympatholytic agents, calcium antagonists, β-adrenergic blockers, and the angiotensin-converting enzyme inhibitors appear to diminish LV hypertrophy. However, future studies are needed to determine if these agents that appear to reverse findings of LV hypertrophy and improve diastolic dysfunction will also reduce risk of coronary artery disease and related events.     

Evidence for hair cell degeneration as the primary lesion in hearing loss of the elderly

All patients in a geriatric unit showed a hearing loss with a mean value of approximately 60 dB HL. Auditory brain stem evoked responses had normal amplitudes but, in most cases, waves I and II were absent. Extratympanic electrocochleograms produced well-marked action potentials with evidence of a type of recruitment. These results suggest a primary disturbance of cochlear function peripheral to the cochlear nerve. Examination of stained surface preparations of the organ of Corti showed complete atrophy of all hair cells at the end of the basal coil and severe outer hair cell loss in all three coils. This was accompanied by a severe alteration - giant stereociliary degeneration - in some surviving cells in all cases, but no other consistent alterations in the cochlea. These findings point towards degenerative change in the hair cells as the basis for hearing loss in the elderly.     

Assessing population health care need using a claims-based ACG morbidity measure: a validation analysis in the Province of Manitoba

OBJECTIVES: To assess the ability of an Adjusted Clinical Group (ACG)-based morbidity measure to assess the overall health service needs of populations. Data Sources/Study Setting. Three population-based secondary data sources: registration and health service utilization data from fiscal year 1995-1996; mortality data from vital statistics reports from 1996-1999; and Canadian census data. The study included all continuously enrolled residents in the universal health care plan in Manitoba. STUDY DESIGN: Using 60 small geographic areas as the units of analysis, we compared a population-based "ACG morbidity index," derived from individual ACG assignments in fiscal year 1995-1996, with the standardized mortality ratio (ages < 75 years) for 1996-1999. Key variables included a population-based socioeconomic status measure and age- and sex-standardized physician utilization ratios. DATA EXTRACTION METHODS: The ACGs were assigned based on the complement of diagnoses assigned to persons on physician claims and hospital separation abstracts. The ACG index was created by weighting the ACGs using average health care expenditures. PRINCIPAL FINDINGS: The ACG morbidity index had a strong positive linear relationship with the subsequent rate of premature death in the small areas of Manitoba. The ACG index was able to explain the majority of the relationships between mortality and both socioeconomic status and physician utilization. CONCLUSIONS: In Manitoba, ACGs are closely related to premature mortality, commonly accepted as the best single indicator for health service need in populations. Issues in applying ACGs in settings where needs adjustment is a primary objective are discussed.     

A theoretical and empirical analysis of context: neighbourhoods,smoking and youth

Numerous studies are currently addressing the issue of contextual effects on health and disease outcomes. The majority of these studies fall short of providing a theoretical basis with which to explain what context is and how it affects individual disease outcomes. We propose a theoretical model, entitled collective lifestyles, which brings together three concepts from practice theory: social structure, social practices and agency. We do so in an attempt to move away from both behavioural and structural-functionalist explanations of the differential distribution of disease outcomes among areas by including a contextualisation of health behaviours that considers their meaning. We test the framework using the empirical example of smoking and pre-adolescents in 32 communities across Québec, Canada. Social structure is operationalised as characteristics and resources; characteristics are the socio-economic aggregate characteristics of individuals culled from the 1996 Canadian Census, and resources are what regulates and transforms smoking practices. Information about social practices was collected in focus groups with pre-adolescents from four of the participating communities. Using zero-order and partial correlations we find that a portrait of communities emerges. Where there is a high proportion of more socio-economically advantaged people, resources tend to be more smoking discouraging, with the opposite being true for disadvantaged communities. Upon analysis of the focus group material, however, we find that the social practices in communities do not necessarily reflect the "objectified" measures of social structure. We suggest that a different conceptualisation of accessibility and lifestyle in contextual studies may enable us to improve our grasp on how differential rates of disease come about in local areas.     

Bax gene expression alters Ca(2+) signal transduction without affecting apoptosis in an epithelial cell line

Bax is an oncogene that has proapoptotic properties but not all cells that express Bax undergo apoptosis. Bax may have a function unrelated to apoptosis. To elucidate the role of Bax in cell signaling, an epithelial cell line called SMG-C6 was transfected with the human bax gene. Stable transfectants were studied for their response to carbachol, a muscarinic receptor agonist, by measuring the increase in intracellular free Ca(2+) and Ca(2+) influx. Carbachol-mediated release of Ca(2+) from intracellular stores was significantly higher in Bax transfectants compared to control transfectants (empty vector). Ca(2+) influx was also increased in Bax transfectants. Bax had no affect on the storage operated channels. However, the concentration of Ca(2+) in the intracellular stores (i.e., mitochondria and granules) was 40-50% lower in the Bax transfectants. There was no significant difference in thapsigargin-mediated apoptosis in Bax transfectants compared to wild-type and control transfectants. Measurement of glutathione was reduced in the Bax transfectant. Restoration of glutathione levels with glutathione monoethyl ester partially normalized Ca(2+) mobilization and storage capacity in the mitochondria to control levels. This study shows that sub-apoptotic levels of Bax can reduce Ca(2+) content in intracellular stores and Ca(2+) homeostasis. Bax may mediate these effects by reducing the levels of antioxidants resulting in mild oxidative stress.