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Biomedical subjects

G D Smith

Publications and source records attributed to G D Smith.

At least 73 records · Page 4Linked to original sources
PubMed2001

Are women more sensitive to smoking than men? Findings from the Renfrew and Paisley study.

BACKGROUND: Prescott et al. found that the relative risks associated with smoking for respiratory and vascular deaths were higher for women who inhale than for inhaling men, and found no gender differences in relative risks of smoking-related cancers. The purpose of the present study was to assess whether these findings are reproducible, using data from the Renfrew and Paisley study. METHODS: Age-standardized mortality rate differences and age-adjusted mortality rate ratios (using Cox's proportional hazard model) were calculated for male and female smokers by amount smoked compared with never smokers. These analyses were repeated after excluding non-inhalers. RESULTS: The all-cause mortality rate ratio was higher for men than for women in all categories of amount smoked, although this difference was only statistically significant in the light smokers (1.83 [95% CI : 1.61-2.07] for men and 1.41 [95% CI : 1.28-1.56] for women, P = 0.001). The cause-specific mortality rate ratios tended to be higher for men than for women, and this difference was most substantial for neoplasms (2.57 [95% CI : 2.01-3.29] for male light smokers and 1.35 [95% CI : 1.14-1.61] for female light smokers, P < 0.001) and, in particular, for lung cancer (11.10 [95% CI : 5.89-20.92] for male light smokers and 4.73 [95% CI : 2.99-7.50] for female light smokers, P = 0.03). Furthermore, looking at the rate differences the effects of smoking were uniformly greater in men than in women. These results were virtually unchanged after excluding non-inhalers. CONCLUSION: We found similar results to Prescott et al. when all smokers were considered, but could not reproduce their findings when non-inhalers were excluded. Given the fact that we showed greater rate differences in men than in women, we think that it is too early to conclude that women may be more sensitive than men to some of the deleterious effects of smoking.

Cause of Death↗
PubMed2001

Phosphorylation of mitogen-activated protein kinase is regulated by protein kinase C, cyclic 3',5'-adenosine monophosphate, and protein phosphatase modulators during meiosis resumption in rat oocytes.

Mitogen-activated protein (MAP) kinase, protein kinase C (PKC), cAMP, and okadaic acid (OA)-sensitive protein phosphatases (PPs) have been suggested to be involved in oocyte meiotic resumption. However, whether these protein kinases and phosphatases act by independent pathways or interact with each other in regulating meiosis resumption is unknown. In the present study, we aimed to determine the regulation of meiosis resumption and MAP kinase phosphorylation by PKC, cAMP, and OA-sensitive PPs in rat oocytes using an in vitro oocyte maturation system and Western blot analysis. We found that ERK1 and ERK2 isoforms of MAP kinases existed in a dephosphorylated (inactive) form in germinal vesicle breakdown (GVBD)-incompetent and GVBD-competent germinal vesicle intact (GVI) oocytes as well as GVBD oocytes at equivalent levels. These results indicate that MAP kinases are not responsible for the initiation of normal meiotic resumption in rat oocytes. However, when GVBD-incompetent and GVBD-competent oocytes were incubated in vitro for 5 h, MAP kinases were phosphorylated (activated) in GVBD-competent oocytes, but not in meiotic-incompetent oocytes, suggesting that oocytes acquire the ability to phosphorylate MAP kinase during acquisition of meiotic competence. We also found that both meiosis resumption and MAP kinase phosphorylation were inhibited by PKC activation or cAMP elevation. Moreover, these inhibitory effects were overcome by OA, which inhibited PP1/PP2A activities. These results suggest that both cAMP elevation and PKC activation inhibit meiosis resumption and MAP kinase phosphorylation at a step prior to OA-sensitive protein phosphatases. In addition, inhibitory effects of cAMP elevation on meiotic resumption and MAP kinase phosphorylation were not reversed by calphostin C-induced PKC inactivation, indicating that cAMP inhibits both meiotic resumption and MAP kinase activation in a PKC-independent manner.

Animals↗
PubMed2001

Homocysteine and coronary heart disease in the Caerphilly cohort: a 10 year follow up.

OBJECTIVE: Prospective assessment of the risk of coronary heart disease associated with total serum homocyst(e)ine (homocysteine) concentration. DESIGN: Nested case-control study. SETTING: Caerphilly and surrounding villages in south Wales, UK. PARTICIPANTS: 2290 men who participated in phase II of the study in 1984. After a mean follow up of 10 years, 312 men developed coronary heart disease and were compared with 1248 randomly selected, age frequency matched controls. MAIN OUTCOME MEASURE: Acute myocardial infarction or death from coronary heart disease. RESULTS: The geometric mean serum homocysteine concentration was higher in cases (12.2 micromol/l, 95% confidence interval (CI) 11.8 to 12.6 micromol/l) than in controls (11.8 micromol/l, 95% CI 11.3 to 12.5 micromol/l) (p = 0.09). There was a graded increase in the odds ratio of coronary heart disease across quintiles of the homocysteine concentration distribution compared with the first (p = 0.04), which was attenuated when adjusted for confounding variables (p = 0.4). There was a small but non-significant increase in the adjusted odds ratio of coronary heart disease per standard deviation change in the log distribution of homocysteine concentration (OR = 1.07 (95% CI.93 to 1.24), p = 0.34). Comparing the top quintile of the homocysteine concentration with the remaining 80%, the adjusted odds ratio of coronary heart disease was 1.03 (95% CI 0.73 to 1.45) (p = 0.8) and comparing the top 5% with the remaining 95% it was 1.05 (95% CI 0.56 to 1.95) (p = 0.9). CONCLUSIONS: These findings do not support the hypothesis that a raised homocysteine concentration is a strong independent risk factor for coronary heart disease. Randomised controlled trials of homocysteine lowering treatment such as folic acid are needed before generalizing the early positive results of observational studies.

Biomarkers↗
PubMed2001

Leg length, insulin resistance, and coronary heart disease risk: the Caerphilly Study.

BACKGROUND: Adult height has been inversely associated with coronary heart disease risk in several studies. The mechanism for this association is not well understood, however, and this was investigated by examining components of stature, cardiovascular disease risk factors and subsequent coronary heart disease in a prospective study. METHODS: All men aged 45-59 years living in the town of Caerphilly, South Wales were approached, and 2512 (89%) responded and underwent a detailed examination, which included measurement of height and sitting height (from which an estimate of leg length was derived). Participants were followed up through repeat examinations and the cumulative incidence of coronary heart disease-both fatal and non-fatal-over a 15 year follow up period is the end point in this report. RESULTS: Cross sectional associations between cardiovascular risk factors and components of stature (total height, leg length and trunk length) demonstrated that factors related to the insulin resistance syndrome-the homeostasis model assessment of insulin resistance, fasting triglyceride levels and total to HDL cholesterol ratio-were less favourable in men with shorter legs, while showing reverse or no associations with trunk length. Fibrinogen levels were inversely associated with leg length and showed a weaker association with trunk length. Forced expiratory volume in one second was unrelated to leg length but strongly positively associated to trunk length. Other risk factors showed little association with components of stature. The risk of coronary heart disease was inversely related to leg length but showed little association with trunk length. CONCLUSION: Leg length is the component of stature related to insulin resistance and coronary heart disease risk. As leg length is unrelated to lung function measures it is unlikely that these can explain the association in this cohort. Factors that influence leg length in adulthood-including nutrition, other influences on growth in early life, genetic and epigenetic influences-merit further investigation in this regard. The reported associations suggest that pre-adult influences are important in the aetiology of coronary heart disease and insulin resistance.

Anthropometry↗
PubMed2001

Are the effects of psychosocial exposures attributable to confounding? Evidence from a prospective observational study on psychological stress and mortality.

STUDY OBJECTIVES: To examine the association between perceived psychological stress and cause specific mortality in a population where perceived stress was not associated with material disadvantage. DESIGN: Prospective observational study with follow up of 21 years and repeat screening of half the cohort five years from baseline. Measures included perceived psychological stress, coronary risk factors, and indices of lifecourse socioeconomic position. SETTING: 27 workplaces in Scotland. PARTICIPANTS: 5388 men (mean age 48 years) at first screening and 2595 men at second screening who had complete data on all measures. MAIN OUTCOME MEASURES: Hazard ratios for all cause mortality and mortality from cardiovascular disease (ICD9 390-459), coronary heart disease (ICD9 410-414), smoking related cancers (ICD9 140, 141, 143-9, 150, 157, 160-163, 188 and 189), other cancers (ICD9 140-208 other than smoking related), stroke (ICD9 430-438), respiratory diseases (ICD9 460-519) and alcohol related causes (ICD9 141, 143-6, 148-9, 150, 155, 161, 291, 303, 571 and 800-998). RESULTS: At first screening behavioural risk (higher smoking and alcohol consumption, lower exercise) was positively associated with stress. This relation was less apparent at second screening. Higher stress at first screening showed an apparent protective relation with all cause mortality and with most categories of cause specific mortality. In general, these estimates were attenuated on adjustment for social position. This pattern was also seen in relation to cumulative stress at first and second screening and with stress that increased between first and second screening. The pattern was most striking with regard to smoking related cancers: relative risk high compared with low stress at first screening, age adjusted 0.64 (95% CI 0.42, 0.96), p for trend 0.016, fully adjusted 0.69 (95% CI 0.45, 1.06), p for trend 0.10; high compared with low cumulative stress, age adjusted 0.69 (95% CI 0.44, 1.09), p for trend 0.12, fully adjusted 0.76 (95% CI 0.48, 1.21), p for trend 0.25; increased compared with decreased stress, age adjusted 0.65 (95% CI 0.40, 1.06), p for trend 0.09, fully adjusted 0.65 (95% CI 0.40, 1.06), p for trend 0.08. CONCLUSIONS: This implausible protective relation between higher levels of stress, which were associated with increased smoking, and mortality from smoking related cancers, was probably a product of confounding. Plausible reported associations between psychosocial exposures and disease, in populations where such exposures are associated with material disadvantage, may be similarly produced by confounding, and of no causal significance.

Adult↗
PubMed2001

Homocysteine and ischaemic stroke in men: the Caerphilly study.

OBJECTIVE: To assess the risk of ischaemic stroke associated with total serum homocyst(e)ine (tHcy) concentration. DESIGN: Cohort study. SETTING: Caerphilly, South Wales PARTICIPANTS: 2254 men age 50 to 64 years recruited between 1984 and 1988. RESULTS: 107 men developed ischaemic stroke and mean follow up time was 10.2 years. There was no significant difference in mean serum total homocyst(e)ine levels between stroke cases (12.2 micromol 95% CI 11.6 to 13.1) and non-cases (11.7 micromol 95% CI 11.5 to 11.9) (p=0.14). There was no significant risk for a standard deviation increase in homocyst(e)ine (adjusted hazard ratio = 1.1, 95% CI 0.9 to 1.4). An interaction was observed between homocyst(e)ine and age at entry (p=0.003). The adjusted odds ratio comparing the top quintile of homocyst(e)ine with the rest was 2.5 (95% CI 1.0 to 6.2) for strokes occurring under 65 years and 0.5 (95% CI 0.2 to 1.3) at 65 years or older (p value for interaction =0.02). Risk also differed by blood pressure status. The adjusted hazard ratio for a standard deviation increase in homocyst(e)ine was 0.8, (95% CI 0.6 to 1.2) for normotensive men and 1.3 (95% CI 1.1 to 1.7) for hypertensive men (p value for interaction =0.01). CONCLUSIONS: Overall, there is no significant relation between homocyst(e)ine and ischaemic stroke in this cohort. However, its aetiological importance may be greater for premature ischaemic strokes (<65 years) and in hypertensive men.

Aged↗
PubMed2001

Milk, coronary heart disease and mortality.

STUDY OBJECTIVE: To study the association between reported milk consumption and cardiovascular and all cause mortality. DESIGN: A prospective study of 5765 men aged 35-64 at the time of examination. SETTING: Workplaces in the west of Scotland between 1970 and 1973. PARTICIPANTS: Men who completed a health and lifestyle questionnaire, which asked about daily milk consumption, and who attended for a medical examination. MAIN RESULTS: 150 (2.6%) men reported drinking more than one and a third pints a day, Some 2977 (51.6%) reported drinking between a third and one and a third pints a day and 2638 (45.8%) reported drinking less than a third of a pint a day. There were a total of 2350 deaths over the 25 year follow up period, of which 892 deaths were attributed to coronary heart disease. The relative risk, adjusted for socioeconomic position, health behaviours and health status for deaths from all causes for men who drank one third to one and a third pints a day versus those who drank less than a third of a pint was 0.90 (95% CI 0.83, 0.97). The adjusted relative risk for deaths attributed to coronary heart disease for men who drank one third to one and a third pints a day versus those who drank less than one third of a pint was 0.92 (95% CI 0.81, 1.06). CONCLUSIONS: No evidence was found that men who consumed milk each day, at a time when most milk consumed was full fat milk, were at increased risk of death from all causes or death from coronary heart disease.

Adult↗
PubMed2001

The relation between questions indicating transient ischaemic attack and stroke in 20 years of follow up in men and women in the Renfrew/Paisley Study.

STUDY OBJECTIVE: Transient ischaemic attack (TIA) is often a precursor to stroke, so identification of people experiencing TIA could assist in stroke prevention by indicating those at high risk of stroke who would benefit most from intervention for other stroke risk factors. The objective of this study was to investigate whether answers to a simple questionnaire for TIA could predict the occurrence of stroke in the following 20 years. DESIGN: Prospective cohort study, conducted between 1972 and 1976, with 20 years of follow up. SETTING: Renfrew and Paisley, Scotland. PARTICIPANTS: 7052 men and 8354 women aged 45-64 years at the time of screening completed a questionnaire and attended a physical examination. The questionnaire asked participants if they had ever, without warning, suddenly lost the power of an arm, suddenly lost the power of a leg, suddenly been unable to speak properly or suddenly lost consciousness. These four questions were taken as indicators of TIA and were related to subsequent stroke mortality or hospital admission. MAIN RESULTS: For women, each question was significantly related to stroke risk, whereas for men only the question on loss of power of arm was significantly related to stroke risk. Men and women answering two or more questions positively had double the relative rate of stroke compared with men and women answering none of the questions positively, even after adjusting for other risk factors for stroke. CONCLUSIONS: A simple questionnaire for TIA could help predict stroke over 20 years of follow up. Targeting men and women who report TIA with early treatment could help to prevent strokes from occurring.

Adult↗