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Biomedical subjects

Richard Mitchell

Publications and source records attributed to Richard Mitchell.

18 recordsLinked to original sources
PubMed2006

Self-rated life expectancy and lifetime socio-economic position: cross-sectional analysis of the British household panel survey.

BACKGROUND: The association between mortality risk and socio-economic position (SEP) across the lifecourse is established. This study investigates whether people's own ratings of their life expectancy are also associated with lifetime SEP. Health behaviour messages, which often emphasize the long-term benefits of behavioural change, may be received differently depending on people's perceptions of their life chances. METHODS: Cross-sectional analysis of 4780 adults aged 25-64 interviewed in the British Household Panel Survey in 2001. RESULTS: Just under a quarter of respondents did not think it likely they would live to 75 or older. People in lower SEPs were more likely to be pessimistic about their life expectancy. This applied across a number of socio-economic measures (father's social class, educational achievement, own social class, and household income). Eight socio-economic lifecourse pathways were compared. In comparison to those following the most advantaged pathway, those experiencing sustained socio-economic disadvantage were most likely to be pessimistic about their longevity, but those experiencing sustained upward mobility did not differ. Comparisons with measures of self-rated general health and limiting illness suggest that self-rated life expectancy is at least partially independent of current health status. CONCLUSIONS: This study shows that people's own perceptions of their life expectancy are associated with lifetime SEP. Self-rated life expectancy, in part, appears to reflect something over and above current health status and smoking behaviour. Given its ease of collection, it would be informative to include self-rated life expectancy in future studies.

Adult↗
PubMed2006

Novel locus for an inherited cardiomyopathy maps to chromosome 7.

BACKGROUND: Genetic mutations are the most common cause of hypertrophic cardiomyopathy (HCM) and an increasingly recognized cause of dilated cardiomyopathy. Autosomal dominant HCM is caused by mutations in sarcomere proteins; such mutations are not universally present, however, and fail to account for &40% of cases of phenotypic HCM. To add further complexity, other genetic origins can mimic the gross clinical phenotype of HCM, and mutations in sarcomere genes have been demonstrated to cause dilated cardiomyopathy. METHODS AND RESULTS: To explore novel genetic causes of inherited cardiomyopathies, genome-wide linkage analysis was used to study one kindred (4 generations, 32 individuals) with predominant clinical features of left ventricular hypertrophy in addition to cardiac dilation, end-stage heart failure, and sudden death. Of note, histopathology from 2 family members did not demonstrate myocyte disarray and fibrosis, indicating that this phenotype is not typical sarcomere mutation HCM. Direct DNA sequencing was performed on sarcomere genes known to cause HCM and dilated cardiomyopathy, and no mutations were identified. Linkage was then established to a novel locus on chromosome 7 (7p12.1-7q21). A maximum 2-point logarithm of odds score of 4.11 was obtained. Recombination events refine the disease interval between D7S506 and D7S3314, corresponding to a distance of 27.2 megabases. CONCLUSIONS: The discovery of a novel genetic locus in this family provides more evidence that molecular pathways leading to inherited cardiac hypertrophy extend beyond the sarcomere. Identification of the causal gene mutation and additional genotype-phenotype correlation studies will provide fundamental insight into mechanisms of cardiac remodeling.

Alleles↗
PubMed2006

Adult blood pressure and climate conditions in infancy: a test of the hypothesis that dehydration in infancy is associated with higher adult blood pressure.

The authors hypothesized that individuals born in the early 20th century who experienced the hottest and driest summers during infancy would be more likely to have suffered severe infant diarrhea and dehydration, and consequently have had higher blood pressure in adulthood, than those who experienced cooler and wetter summers. In this context, these climate data act as an instrumental variable for the association of early-life dehydration with later blood pressure. For 3,964 randomly selected British women born between 1919 and 1940 and whose blood pressure was measured at age 60-79 years, a one standard deviation (1.3 degrees C) higher mean summer temperature in the first year of life was associated with a 1.12-mmHg (95% confidence interval: 0.33, 1.91) higher adult systolic blood pressure, and a one standard deviation higher mean summer rainfall (33.9 mm) was associated with lower systolic blood pressure (-1.65 mmHg, 95% confidence interval: -2.44, -0.85). Equivalent results for diastolic blood pressure were 0.11 (95% confidence interval: -0.65, 0.86) and -0.32 (95% confidence interval: -0.71, 0.05). The climate variables were not associated with potential confounding factors such as socioeconomic position or lifestyle risk factors. These findings provide some evidence in favor of the hypothesis that dehydration in infancy is associated with higher adult blood pressure.

Aged↗
PubMed2006

Evaluating health effects of transport interventions methodologic case study.

BACKGROUND: There is little evidence about the effects of environmental interventions on population levels of physical activity. Major transport projects may promote or discourage physical activity in the form of walking and cycling, but researching the health effects of such "natural experiments" in transport policy or infrastructure is challenging. METHODS: Case study of attempts in 2004-2005 to evaluate the effects of two major transport projects in Scotland: an urban congestion charging scheme in Edinburgh, and a new urban motorway (freeway) in Glasgow. RESULTS: These interventions are typical of many major transport projects. They are unique to their context. They cannot easily be separated from the other components of the wider policies within which they occur. When, where, and how they are implemented are political decisions over which researchers have no control. Baseline data collection required for longitudinal studies may need to be planned before the intervention is certain to take place. There is no simple way of defining a population or area exposed to the intervention or of defining control groups. Changes in quantitative measures of health-related behavior may be difficult to detect. CONCLUSIONS: Major transport projects have clear potential to influence population health, but it is difficult to define the interventions, categorize exposure, or measure outcomes in ways that are likely to be seen as credible in the field of public health intervention research. A final study design is proposed in which multiple methods and spatial levels of analysis are combined in a longitudinal quasi-experimental study.

City Planning↗
PubMed2006

Leisure time exercise and personal circumstances in the working age population: longitudinal analysis of the British household panel survey.

OBJECTIVES: Investigate the impact of social, economic, and family circumstances on participation in weekly leisure time exercise. DESIGN: Longitudinal regression analysis of the British household panel survey. PARTICIPANTS: 9473 people (4521 men and 4952 women) giving 27,881 person years of responses across eight years and four survey waves. MAIN RESULTS: There was considerable variation among people in regular exercise participation over time. Having children was associated with a reduced likelihood of exercise for both men and women, although there were sex differences in this association according to the age of the youngest child. For both men and women working long hours was associated with a reduced likelihood of exercise, as was having a lower grade job. Retired men and women were more likely to exercise, as were those who attended a fee paying school. There was no strong independent association between household income and exercise. CONCLUSIONS: For most people, participation in leisure time exercise "comes and goes" rather than being something they always or never do. Those with time pressures from work or domestic life are less likely to participate in leisure time physical activity. There are important sex differences in the impact of having children, with women experiencing longer term detrimental effects. Working long hours reduces leisure time exercise participation. Opportunities for physical activity as part of our daily working routines should be increased.

Adolescent↗
PubMed2005

Does usage of domestic heating influence internal environmental conditions and health?

BACKGROUND: Housing conditions are recognised as an important determinant of health. In the UK, interventions to improve domestic heating are in place with the expectation that they will improve health. As a component of evaluating such policies, this study assesses whether specific health outcomes are significantly associated with the extent and duration of domestic heating use, either directly or via a possible mediating effect of internal environmental conditions. METHODS: Baseline data from a prospective controlled study evaluating the health effects of a publicly-funded programme of heating improvements in Scotland were used to assess associations among heating use, internal conditions, and three specific health outcomes. RESULTS: There were significant associations (P < 0.01) between measures of heating use and the presence of environmental problems in the home, such as mould and condensation. The presence of such problems was, in turn, found to be significantly predictive of two health outcomes derived from the SF-36 (P < 0.01) and of adult wheezing (P < 0.05). The direction of significant associations was highly consistent: greater levels of heating were associated with reduced likelihood of environmental problems, and the presence of environmental problems was linked to poorer health status. Heating use was not directly associated with the health outcomes considered. CONCLUSIONS: The study findings are consistent with a conceptual model in which health may be influenced by usage patterns of domestic heating, via the mediating effect of poor internal environmental conditions. Since these findings are based on cross-sectional data, interpretation must be carried out cautiously. However, if confirmed by planned future work they have important implications for policy initiatives relating to domestic heating and fuel poverty.

Adult↗
PubMed2005

High rates of ischaemic heart disease in Scotland are not explained by conventional risk factors.

STUDY OBJECTIVES: To (1) compare prevalence of socioeconomic, behavioural, and physiological ischaemic heart disease (IHD) risk factors in Scotland with a comparable nation (England) and (2) find out if their distribution explains Scotland's comparatively higher IHD rate (1.62 (1.30, 2.02)). DESIGN, SETTING, AND PARTICIPANTS: Cross sectional, individual level observational study with data on socioeconomic, behavioural, and physiological characteristics, 6064 respondents from Scotland and England, (2362 and 3702 respectively), aged 45-74 and with data on all required items. MAIN RESULTS: There were significant and meaningful differences between the Scottish and English in the prevalence of several IHD risk factors. However, a substantially and significantly higher risk of IHD persisted among the Scottish respondents (1.50 (1.17, 1.91)) despite control for a wide range of risk factors. CONCLUSIONS: Interpretation must be cautious because these are cross sectional data, however higher levels of conventional IHD risk factors contribute to but do not explain the comparatively high rates of IHD in Scotland. Alternative explanations for, and policy interventions to tackle, Scottish rates of IHD must be considered.

Aged↗
PubMed2004

Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels.

A radioligand binding assay for the HERG (human ether-a-go-go-related gene) K(+) channel was developed to identify compounds which may have inhibitory activity and potential cardiotoxicity. Pharmacological characterization of the [(3)H]astemizole binding assay for HERG K(+) channels was performed using HERG-expressing HEK293 cells. The assay conditions employed yielded 90% specific binding using 10 microg/well of membrane protein with 1.5 nM of [(3)H]astemizole at 25 degrees C. The K(d) and B(max) values were 5.91 +/- 0.81 nM and 6.36 +/- 0.26 pmol/mg, respectively. The intraassay and interassay variations were 11.4% and 14.9%, respectively. Binding affinities for 32 reference compounds (including dofetilide, cisapride, and terfenadine) with diverse structures demonstrated a similar potency rank order for HERG inhibition to that reported in the literature. Moreover, the [(3)H]astemizole binding data demonstrated a rank order of affinity that was highly correlated to that of inhibitory potency in the electrophysiological studies for HERG in HEK293 (r(SP) = 0.91, P<0.05). In conclusion, the [(3)H]astemizole binding assay is rapid and capable of detecting HERG inhibitors.

Astemizole↗
PubMed2003

Ultrasound imaging of the intervertebral disc.

STUDY DESIGN: In vitro ultrasound imaging of dog intervertebral discs was performed. OBJECTIVE: To determine the reliability of ultrasound imaging in the detection of structural changes associated with disc pathology. SUMMARY OF BACKGROUND DATA: Little work has been done to evaluate the potential applications of ultrasound in the imaging of intervertebral discs. Initial in vitro studies, however, have indicated that ultrasound imaging is capable of producing images of the disc that contain a high degree of structural information. METHODS: Explanted lumbosacral discs from 13 nonchondrodystrophic dogs, mean age 5 years and 8 months, were stripped of all surrounding tissues and scanned using ultrasound before being sectioned and photographed. The ultrasound images were graded according to criteria chosen to reflect progressive stages of disc degeneration, allowing correlation with the grading scale used to assess the photographic images of the discs. Grades assigned to each disc were compared using Cronbach's alpha to determine the reliability of the images obtained using ultrasound. RESULTS: The results for the anterior anulus fibrosus produced an alpha value of 0.924; those for the nucleus pulposus produced a value of 0.821; whereas those for the posterior anulus fibrosus produced a value of 0.882. Where the grade given to the ultrasound image did not match those given in visual assessment, the disparity was never greater than one grade. Ultrasound images of several discs demonstrated echo patterns that matched, in both location and appearance, real structural defects identifiable on the sectioned discs. CONCLUSIONS: Ultrasound images of intervertebral discs relate well to their pathologic condition. In addition, ultrasound is able to locate specific pathologic defects.

Animals↗
PubMed2003

Global analysis of cellular transcription following infection with an HIV-based vector.

We have examined the changes in cellular transcription resulting from infection with HIV-based vectors. Previous work suggested that the incoming viral genome may under some circumstances be detected as DNA damage, so to explore this possibility, we compared the transcriptional response to infection with an HIV-based vector to the response to treatment with the DNA-damaging agent etoposide. Expression levels of about 12,000 cellular RNA transcripts were determined in a human B-cell line at different times after either treatment. Statistical analysis revealed that the infection with the lentivirus vector resulted in quite modest changes in gene expression. Treatment with etoposide, in contrast, caused drastic changes in expression of genes known or inferred to be involved in apoptosis. Statistically significant though subtle parallels in the cellular transcriptional responses to etoposide treatment and HIV-vector infection could be detected. Several further data sets analyzing infections with HIV-based vectors or wild-type HIV-1 showed similar modest effects on cellular transcription and very modest parallels among different data sets. These findings establish that HIV-vector or HIV-1 infection has remarkably little effect on cellular transcription. The statistical methods described here may be of wide use in mining microarray data sets. Our observations support the idea that gene therapy with HIV-based vectors should not be particularly toxic to cells due to disruption of cellular transcription.

B-Lymphocytes↗
PubMed2003

What evidence implicates airway smooth muscle in the cause of BHR?

Bronchial hyperresponsiveness (BHR), the occurrence of excessive bronchoconstriction in response to relatively small constrictor stimuli, is a cardinal feature of asthma. Here, we consider the role that airway smooth muscle might play in the generation of BHR. The weight of evidence suggests that smooth muscle isolated from asthmatic tissues exhibits normal sensitivity to constrictor agonists when studied during isometric contraction, but the increased muscle mass within asthmatic airways might generate more total force than the lesser amount of muscle found in normal bronchi. Another salient difference between asthmatic and normal individuals lies in the effect of deep inhalation (DI) on bronchoconstriction. DI often substantially reverses induced bronchoconstriction in normals, while it often has much less effect on spontaneous or induced bronchoconstriction in asthmatics. It has been proposed that abnormal dynamic aspects of airway smooth muscle contraction velocity of contraction or plasticity- elasticity balance might underlie the abnormal DI response in asthma. We suggest a speculative model in which abnormally long actin filaments might account for abnormally increased elasticity of contracted airway smooth muscle.

Actins↗
PubMed2002

Population production and modelling mortality--an application of geographic information systems in health inequalities research.

Much research into spatial inequalities in health has sought the balance between compositional and contextual influences on observed patterns. Research published recently by the authors sought to determine whether composition of areas alone might account for the changing geography of mortality in Britain, between 1983 and 1993. The research required data describing Britain in terms of the numbers and location of people with every possible combination of age group, sex, social class and employment status. This paper describes the approach and the custom written geographic information system which estimated these data, and their subsequent application.

Female↗
PubMed2002

Life and death of the people of London: a historical GIS of Charles Booth's inquiry.

Social reformer Charles Booth undertook a massive survey into the social and economic conditions of the people of London at the end of the 19th century. An important innovation of his Inquiry was the construction of large, detailed maps displaying social class of inner London on a street-by-street basis. These provide a detailed and vivid picture of the geography of poverty and affluence at this time. These maps have been digitised, georeferenced and linked to contemporary ward boundaries allowing Booth's measurement of social class to be matched to the measurement of social class in the 1991 census of population and standardised mortality ratios derived for all causes of death in the survey area between 1991 and 1995. The social class data were used to derive an index of relative poverty for both time periods and a comparison of the geographies of relative poverty and their relationship with contemporary mortality was made. Although the overall standard of living had increased, the geography of poverty at the end of the 19th century was very similar to that at the end of the 20th century. Moreover, the geography of all causes of death for people over the age of 65 was more strongly related to the geography of poverty in the late 19th century than contemporary patterns of poverty. This relationship was also true for mortality for specific diseases that are related to deprivation in early life. The paper concludes that the spatial patterns of poverty in inner London are extremely robust and a century of change has failed to disrupt it.

Cause of Death↗
PubMed2002

Elevated risk of high blood pressure: climate and the inverse housing law.

BACKGROUND: In previous work the authors identified an 'inverse housing law' in Britain such that housing quality tends to be worse in areas of harsh climate than in areas where the climate is more benign. This study investigates whether an individual's risk of hypertension is associated with such a 'mismatch' between the quality of their housing and the climate to which they have been exposed. METHODS: Cross-sectional observational study based on Britain. Data came from the 5663 Health and Lifestyle Survey (HALS) participants for whom all relevant items were available. A two-stage study design was employed. First, the relationship between exposure to colder climate and housing quality was established. Second, the impact on risk of hypertension was determined for level of exposure to colder climate and housing quality. RESULTS: Analysis confirmed that amongst survey respondents, those with greater exposure to colder climate are more likely (1.32, 95% CI: 1.18-1.42) to live in poor quality housing than those with lower exposure to colder climate. This combination of higher exposure to colder climate plus residence in worse quality housing raises significantly the risk of diastolic hypertension (1.45, 95% CI: 1.18-1.77) and, more weakly, systolic hypertension (1.25, 95% CI: 1.01-1.53). CONCLUSIONS: There appears to be an 'inverse housing law' in Britain, whereby longer term residents of relatively cold areas are also more likely to live in worse quality housing and this combination of circumstances is associated with significantly higher risk of diastolic hypertension. The findings provide an example of how long term exposure to an adverse environment, which may stem from material disadvantage, can damage health.

Adult↗