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Biomedical subjects

G D Smith

Publications and source records attributed to G D Smith.

At least 55 records · Page 3Linked to original sources
PubMed2001

The metabolic, catecholamine and cardiovascular effects of exercise in human sympathetic denervation.

The cardiovascular and metabolic responses to supine leg exercise were measured in 9 healthy subjects (controls) and in 19 subjects with two primary forms of autonomic failure (11 with peripheral sympathetic denervation [pure autonomic failure; PAF], 8 with central sympathetic failure [multiple system atrophy; MSA]). With exercise, blood pressure increased in controls and fell markedly in subjects with PAF and MSA. Blood pressure returned to baseline in controls, but remained low in the PAF and MSA groups. With exercise, heart rate increased more in controls than the PAF and MSA groups. Resting plasma noradrenaline concentrations in controls and in subjects with MSA were similar, but were lower in subjects with PAF. With exercise, plasma noradrenaline concentrations increased in controls and were unchanged in subjects with PAF; there was no significant increase in the MSA group. Resting plasma lactate, pyruvate and lactate/pyruvate ratios were similar in all three groups. With exercise, lactate concentrations increased until 2 minutes post exercise in all groups. Pyruvate concentrations after 9 minutes' exercise were higher in controls than in the PAF group but were similar to the MSA group; thereafter, concentrations increased similarly in all groups. The lactate/pyruvate ratio increased until 2 minutes post exercise in all groups. Resting plasma free fatty acids, and beta-hydroxybutyrate were similar in all groups. Plasma glycerol concentrations in control and MSA subjects were similar; concentrations were lower in PAF subjects. With exercise, plasma free fatty acids and glycerol concentrations remained unchanged in all groups; beta-hydroxybutyrate concentrations decreased less in control subjects than in PAF and MSA subjects. In conclusion, there were similar concentrations of plasma free fatty acids, glycerol and beta-hydroxybutyrate in control, PAF and MSA subjects; this could indicate up-regulation of beta-receptors in AF, or that sympathetic activity plays a smaller role in lipolysis. Plasma lactate and pyruvate concentrations increased similarly in all groups, despite marked differences in BP; this suggested an impairment of production or clearance of lactate in AF. A role for lactate-induced vasodilatation, not compensated for by sympathetic vasoconstriction, remains speculative.

3-Hydroxybutyric Acid↗
PubMed2001

Characterisation of a human acid-sensing ion channel (hASIC1a) endogenously expressed in HEK293 cells.

Acid-sensing ion channels (ASICs) are a new and expanding family of proton-gated cation (Na+/Ca2+) channels that are widely expressed in sensory neurons and the central nervous system. Their distribution suggests that they may play a critical role in the sensation of the pain that accompanies tissue acidosis and may also be important in detecting the subtle pH variations that occur during neuronal signalling. Here, using whole-cell patch-clamp electrophysiology and reverse transcriptase-polymerase chain reaction (RT-PCR), we show that HEK293 cells, a commonly used cell line for the expression and characterisation of many ion channels, functionally express an endogenous proton-gated conductance attributable to the activity of human ASIC1a. These data therefore represent the first functional characterisation of hASIC1 and have many important implications for the use of HEK293 cells as a host cell system for the study of ASICs, vanilloid receptor-1 and any other proton-gated channel. With this latter point in mind we have devised a simple desensitisation strategy to selectively remove the contribution of hASIC1a from proton-gated currents recorded from HEK293 cells expressing vanilloid receptor-1.

Acid Sensing Ion Channels↗
PubMed2001

The socioeconomic position of employed women, risk factors and mortality.

Many studies have demonstrated the graded association between socioeconomic position and health. Few of these studies have examined the cumulative effect of socioeconomic position throughout the lifecourse, and even fewer have included women. Those that have explored gender differences affirm the importance of studying the factors that predict women and men's health separately. This study addresses the associations between cross-sectional and longitudinal socioeconomic position, risk factors for cardiovascular disease and mortality from various causes. Analyses are based on data from a cohort of working Scottish women recruited between 1970 and 1973. Five socioeconomic measures were explored in relation to diastolic blood pressure, plasma cholesterol concentration, body mass index, forced expiratory volume in 1 s (FEV1). amount of recreational exercise taken, cigarette smoking and alcohol consumption. In general, for each of the five measures of socioeconomic position, there were significant differences in at least one of the age-adjusted physiological risk factors for cardiovascular disease (diastolic blood pressure, plasma cholesterol concentration, body mass index, FEV1). There were also significant differences in the percentage of current cigarette smokers according to different measures of socioeconomic position, although this was not the case for the other behavioural risk factors for cardiovascular disease (amount of recreational exercise taken, and alcohol consumption). Measures of socioeconomic position were also examined in relation to cause of death for the women who died before 1 January 1999. After adjusting for age and risk factors, a composite measure of lifetime socioeconomic experience was a more potent predictor of all cause mortality and mortality from cardiovascular disease than other measures of socioeconomic position. It therefore seems that conventional measurcs of socioeconomic position, estimated at one point in time, do not adequately capture the effects of socioeconomic circumstances on the risk of mortality among employed women. Thus, a broader range of explanatory factors for mortality differentials than currently exists must be considered, and must include consideration of factors operating throughout the lifecourse.

Adult↗
PubMed2001

Measurements of field enhancement introduced by a local electrode.

Direct measurements of field enhancement introduced by a local electrode have been carried out on a scanning atom probe (SAP). The results show that an enhancement factor of more than 2 can be obtained simply by reducing the specimen-to-electrode distance from 1.5 mm to 10 microm. Further enhancement can be achieved if the electrode has a smaller aperture. This suggests that a specimen with tip radius of approximately 200 nm, which usually is too blunt to be analysed in a standard atom probe, could now be analysed by SAP. The capability of analysing blunt tips will expand the applicability of SAP to a much broader range of materials.

Journal Article↗
PubMed2001

Socio-economic position and cardiovascular risk factors in an Italian rural population.

Cardiovascular disease (CVD) is the leading industrial world cause of mortality. Lower social class groups have higher incidence of CVD and also display less favourable risk factor profiles. To investigate the association and gradient between major cardiovascular risk factors (smoking habit, serum lipid profile, blood pressure, relative body weight) and socio-economic position (proxy measures selected: education and occupation) data on 2592 men and 2866 women were analysed. The effect of potential confounding factors and effect modifiers was estimated. Linear and logistic regression modelling was performed for continuous and dichotomous outcomes respectively. The lower the grade of employment or the level of education, the higher was the prevalence of obesity in the study population. The association was stronger in women than in men. Higher education was associated with a lower prevalence of smoking among men and a higher prevalence among women. Systolic blood pressure was negatively related to socio-economic position in both men and women in the age-adjusted models. Attention should be concentrated on socio-economic differences in obesity and blood pressure in this population.

Adult↗
PubMed2001

Physical activity and cause-specific mortality in men: further evidence from the Whitehall study.

Reports of studies relating physical activity to stroke and cancer sub-types indicate inconsistent findings. Some are hampered by low statistical power, owing to a low number of events, and a failure to adjust for potential confounding variables. The purpose of this study was to relate physical activity to 12 mortality endpoints in a prospective cohort study of 11,663 men aged 40-64 years who responded to an enquiry about travel activity during a baseline medical examination conducted between 1967 and 1969. During 25 years of follow-up there were 4672 deaths. Travel activity was inversely related to mortality attributable to all-causes, coronary heart disease, respiratory disease and lung cancer, whereas the association with stroke was positive. There was evidence for attenuation of some of these associations on adjustment for potentially confounding variables. Our simplistic measure of physical activity may, in part, explain the weak associations seen.

Adult↗
PubMed2001

Job insecurity in white-collar workers: toward an explanation of associations with health.

This article describes 2 studies that examined changes in psychosocial work characteristics (job strain model) and health-related behaviors as potential explanations of the job insecurity-health relationship in a longitudinal cohort of white-collar British civil servants. Job insecurity arising from anticipation of change was associated with a modest increase in self-reported morbidity, whereas chronic job insecurity was associated with some adverse physiological changes. Anticipation of change and chronic job insecurity were associated with adverse changes in other psychosocial work characteristics, but few changes were significant and consistent across both exposure groups. Changes in health-related behaviors associated with either exposure were slight. Apart from a minor role for social support at work in both sexes and a modest role for job demands in women, adverse changes in these factors explain little of the job insecurity-health relationship.

Adult↗
PubMed2001

The incidence and aetiology of stroke in the Caerphilly and Speedwell Collaborative Studies I: methods and incidence of events.

Stroke mortality and morbidity remain high despite downward trends in incidence and case fatality. Population-based longitudinal studies which include collection of risk factor data are required for a better understanding of stroke aetiology. From a representative cohort of men from South Wales and South-west England, followed up for a median of 17 y, details of possible cerebrovascular events were collected from questionnaires, hospital admission data, general practitioner records, death certificates, radiology records and post-mortem reports. Radiology records, and strokes and transient ischaemic attacks were independently validated. There were 433 strokes and 163 transient ischaemic attacks identified during follow-up. Of these, 333 were the first ever in a lifetime strokes of which 139 were definite ischaemic, 20 were haemorrhagic and 168 were probable ischaemic strokes. The crude incidence rate for stroke was 445 (95% confidence interval 398-493) per 100 000 person years. The age-standardised rates for 10 y age-bands were: 45-54 y 91 (10-172); 55-64 y 351 (269-432) and 65-74 y 855 (669-1040). The 30 d case-fatality rate was 21.0% (70/333) for all strokes and 19.2% (60/312) for ischaemic strokes. For transient ischaemic attacks the age-standardised incidence rates for the same 10 y age bands were 92 (4-179), 111 (64-157), and 273 (167-80), respectively. These rates for stroke transient ischaemic attack are likely to be accurate given the high ascertainment of events in this representative population of middle-aged men. Such studies, reporting reliable measures of cerebrovascular events, are important for measuring burden of disease, and for analysis of risk factor associations to help improve understanding of stroke aetiology and inform preventive efforts.

Cohort Studies↗
PubMed2001

The incidence and aetiology of stroke in the Caerphilly and Speedwell Collaborative Studies II: risk factors for ischaemic stroke.

Reduction of stroke burden requires preventive interventions targeted at important risk factors. This report presents the analysis of risk factors for ischaemic stroke from a representative cohort of middle aged men from South Wales and south-west England. Data on risk factors were collected through validated questionnaires and physical and clinical measurements. Details of possible cerebrovascular events were retrieved, classified into ischaemic, haemorrhagic and uncertain subtypes, and validated. The ratio of definite ischaemic to definite haemorrhagic strokes was calculated. This showed that the vast majority of strokes of unknown subtype were likely to ischaemic. After exclusion of known haemorrhagic strokes and subarrachnoid haemorrhages the remaining strokes were labelled ischaemic. Hazard ratios for possible risk factors were calculated for all ischaemic, and for fatal and non-fatal strokes. There were 293 ischaemic strokes. Statistically significant age-adjusted hazard ratios were: 1.50 (95% confidence interval 1.16-1.95) for being in a manual social class, 1.82 (1.24-2.67) if smoking >15 cigarettes/d at enrollment, 1.19 (1.13-1.24) and 1.23 (1.14-1.34) per 10 mmHg increase in systolic and diastolic blood pressure, respectively, 0.67 (0.46-0.96) for the top quintile high density lipoprotein-cholesterol:cholesterol ratio compared to the bottom quintile, 2.04 (1.40-2.99) for presence of angina, 3.90 (2.01-7.58) for presence of atrial fibrillation, and 3.35 (1.90-5.80) for presence of diabetes. Risk factors were more strongly associated with fatal than non-fatal strokes. Multivariate analyses revealed that, while there was some attenuation of the effect of social class, angina and elevated BP, the risks from atrial fibrillation and diabetes were increased.

Brain Ischemia↗
PubMed2001

The vanilloid receptor (VR1)-mediated effects of anandamide are potently enhanced by the cAMP-dependent protein kinase.

The endogenous cannabinoid receptor ligand, anandamide (AEA), is a full agonist of the vanilloid receptor type 1 (VR1) for capsaicin. Here, we demonstrate that the potency and efficacy of AEA at VR1 receptors can be significantly increased by the concomitant activation of protein kinase A (PKA). In human embryonic kidney (HEK) cells over-expressing human VR1, AEA induces a rise in cytosolic Ca(2+) concentration that is mediated by this receptor. The EC(50) for this effect was decreased five-fold in the presence of forskolin (FRSK, 1-5 microM) or the cAMP analogue, 8-Br-cAMP (10-100 microM). The effects of 8-Br-cAMP and FRSK were blocked by a selective PKA inhibitor. The FRSK (10 nM) also potently enhanced the sensory neurone- and VR1-mediated constriction by AEA of isolated guinea-pig bronchi, and this effect was abolished by a PKA inhibitor. In rat dorsal root ganglia slices, AEA-induced release of substance P, an effect mediated by VR1 activation, was enhanced three-fold by FRSK (10 nM). Thus, the ability of AEA to stimulate sensory VR1, with subsequent neuropeptide release, appears to be regulated by the state of activation of PKA. This observation supports the hypothesis that endogenous AEA might stimulate VR1 under certain pathophysiological conditions.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

A randomized trial of thermal ablative therapy versus expandable metal stents in the palliative treatment of patients with esophageal carcinoma.

BACKGROUND: Expandable metal stent insertion and thermal tumor ablation (TTA) both improve dysphagia in patients with advanced esophageal cancer, but no direct comparison study of their efficacy on health-related quality of life has been published. The aim of this study was to compare survival, relief of dysphagia, quality of life, and cost in patients treated by thermal ablation or stent insertion. METHODS: Sixty-five patients with histologically proven, inoperable esophageal and esophagogastric cancer were initially assessed by endoscopy, barium contrast radiography, and CT of the thorax and abdomen. Dysphagia and quality of life were serially assessed at monthly intervals. Patients were randomized to either repeated TTA or insertion of an expandable metal stent. RESULTS: Median survival was significantly longer for patients who underwent TTA; 125 days (17-546) versus 68 days (8-602) for those in whom a stent was inserted (p < 0.05), although relief of dysphagia was disappointing in both groups. Several patients in both groups had serious treatment-related complications and required further therapy. Median length of hospital stay and cost were greater for patients treated by TTA. Health-related quality of life was globally impaired in both groups at randomization and deteriorated significantly in the stent group. Pain was reported more commonly by patients with stents. CONCLUSIONS: The palliation of patients with advanced esophageal and esophagogastric cancer remains unsatisfactory. Health-related quality of life deteriorated in the stent group but not in the TTA group. Patients treated by TTA live longer than patients treated by stent insertion, but the cost of TTA is higher.

Aged↗
PubMed2001

Socio-economic position and coronary heart disease risk factors in youth. Findings from the Young Hearts Project in Northern Ireland.

BACKGROUND: This study investigates the existence of socioeconomic differentials in behavioural and biological risk factors for coronary heart disease in young people from Northern Ireland, taking into account differences in biological maturation. METHODS: A school-based prospective study, with measurements in 1989/1990 and 1992/1993. Socio-economic position was based on occupational level of the main family breadwinner. Behavioural risk factors included were physical inactivity, the intake of total energy, dietary fat and a number of micronutrients. Biological risk factors included were blood pressure, body fatness, lipoproteins and cardio-pulmonary fitness. Biological maturation was based on Tanner's stages. PARTICIPANTS: 251 boys and 258 girls who were measured at the age of 12 years and re-examined at the age of 15 years. RESULTS: Cross-sectional analyses showed that socio-economic differences in cholesterol intake (in boys) and physical inactivity and total energy intake (in girls) were present at 12 and 15 years of age, while differences in fat and fruit intake and smoking behaviour (in boys and girls) became established at the age of 15 years, with unfavourable levels in subjects in the manual group. Longitudinal analyses confirmed that differences in behavioural risk factors exist or develop during adolescence. No clear pattern of differences in biological risk factors was found by socio-economic position. Adjustment for biological maturation did not materially alter the results. CONCLUSION: Differences in lifestyle by socio-economic position seem to become established in adolescence. These differences however, are not (yet) reflected in differences in biological risk factors by socio-economic position.

Adolescent↗
PubMed2001

Social class differences in lung cancer mortality: risk factor explanations using two Scottish cohort studies.

BACKGROUND: The study investigated differences in lung cancer mortality risk between social classes. METHODS: Twenty years of mortality follow-up were analysed in 7052 men and 8354 women from the Renfrew/Paisley general population study and 4021 working men from the Collaborative study. RESULTS: More manual than non-manual men and women smoked, reported morning phlegm, had worse lung function and lived in more deprived areas. Lung cancer mortality rates were higher in manual than non-manual men and women. Significantly higher lung cancer mortality risks were seen for manual compared to non-manual workers when adjusting for age only and adjustment for smoking reduced these risks to 1.41 (95% CI : 1.12-1.77) for men in the Renfrew/Paisley study, 1.28 (95% CI : 0.94-1.75) for women in the Renfrew/Paisley study and 1.43 (95% CI : 1.02-2.01) for men in the Collaborative study. Adjustment for lung function, phlegm and deprivation category attenuated the risks which were of borderline significance for men in the Renfrew/Paisley study and non significant for women in the Renfrew/Paisley study and men in the Collaborative study. Adding extra socioeconomic variables, available in the Collaborative study only, reduced the difference between the manual and non-manual social classes completely. CONCLUSIONS: There is a difference in lung cancer risk between social classes, in addition to the effect of smoking. This can be explained by poor lung health, deprivation and poor socioeconomic conditions throughout life. As well as anti-smoking measures, reducing socioeconomic inequalities and targeting individuals with poor lung function for help with smoking cessation could help reduce future lung cancer incidence and mortality.

Chi-Square Distribution↗