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Biomedical subjects

G D Smith

Publications and source records attributed to G D Smith.

At least 145 records · Page 8Linked to original sources
PubMed1999

Alcohol consumption and mortality from all causes, coronary heart disease, and stroke: results from a prospective cohort study of scottish men with 21 years of follow up.

OBJECTIVES: To relate alcohol consumption to mortality. DESIGN: Prospective cohort study. SETTING: 27 workplaces in the west of Scotland. PARTICIPANTS: 5766 men aged 35-64 when screened in 1970-3 who answered questions on their usual weekly alcohol consumption. MAIN OUTCOME MEASURES: Mortality from all causes, coronary heart disease, stroke, and alcohol related causes over 21 years of follow up related to units of alcohol consumed per week. RESULTS: Risk for all cause mortality was similar for non-drinkers and men drinking up to 14 units a week. Mortality risk then showed a graded association with alcohol consumption (relative rate compared with non-drinkers 1. 34 (95% confidence interval 1.14 to 1.58) for 15-21 units a week, 1. 49 (1.27 to 1.75) for 22-34 units, 1.74 (1.47 to 2.06) for 35 or more units). Adjustment for risk factors attenuated the increased relative risks, but they remained significantly above 1 for men drinking 22 or more units a week. There was no strong relation between alcohol consumption and mortality from coronary heart disease after adjustment. A strong positive relation was seen between alcohol consumption and risk of mortality from stroke, with men drinking 35 or more units having double the risk of non-drinkers, even after adjustment. CONCLUSIONS: The overall association between alcohol consumption and mortality is unfavourable for men drinking over 22 units a week, and there is no clear evidence of any protective effect for men drinking less than this.

Adult↗
PubMed1999

Population requirement for primary hip-replacement surgery: a cross-sectional study.

BACKGROUND: There has been a long-standing failure in many countries to satisfy the demand for several elective surgical treatments, including total hip replacement. We set out to estimate the population requirement for primary total hip replacement in England. METHODS: We undertook a cross-sectional study of a stratified random sample of 28,080 individuals aged 35 and over from 40 general practices in inner-city, urban, and rural areas of Avon and Somerset, UK. Prevalent disease was identified through a two-stage process: a self-report screening questionnaire (22,978 of 26,046 responded) and subsequent clinical examination. Incident disease was estimated from the point prevalence by statistical modelling. The requirement for total hip replacement surgery was estimated on the basis of pain and loss of functional ability, with adjustment for evidence of comorbidity and patients' treatment preferences. FINDINGS: 3169 people reported hip pain on the screening questionnaire. 2018 were invited for clinical examination, and 1405 attended. The prevalence of self-reported hip pain was 107 per 1000 (95% CI 101-113) for men and 173 per 1000 (166-180) for women. The prevalence of hip disease severe enough to require surgery was 15.2 (12.7-17.8) per 1000 aged 35-85 years. The corresponding annual incidence of hip disease requiring surgery was estimated as 2.23 (1.56-2.90), which suggests an overall requirement in England of 46,600 operations per year for patients who expressed a preference for, and were suitable for, surgery; the recent actual provision in England was about 43,500. INTERPRETATION: This research suggests that the satisfaction of demand for total hip replacement, given agreed criteria for surgery, is a realistic objective.

Adult↗
PubMed1999

On 'globbicity' of low-resolution protein structures.

Using Harker's [Harker (1953). Acta Cryst. 6, 731-736] idea of spherically averaged polyatomic groups or 'globs' as the units of structure suitable for analyzing low-resolution diffraction data from protein crystals, 'globbic' scattering factors have been calculated for main-chain peptide units and amino-acid side-chain groups to 3 A resolution via Debye's [Debye (1915). Ann. Phys. (Leipzig), 46, 809-823] scattering formula. It is shown that the scattering factors are insensitive to intra-globbic conformational variation and can be approximated fairly well by a single-Gaussian formula, i.e. fg(s) = Zg exp(-1.7Zgs2), where s = (sin theta)/lambda and Zg is the total electron count for the atoms of the glob. Phase errors due to the globbic approximation and their effect on electron-density maps at 3.5 A resolution have been assessed via calculations for the crambin structure; this analysis indicates that the globbic scattering factors will be useful in efforts to develop procedures for direct-methods phasing of diffraction data to approximately 3.5 A resolution from protein crystals.

Crystallography, X-Ray↗
PubMed1999

Contribution of nitric oxide to exercise-induced hypotension in human sympathetic denervation.

The cardiovascular, catecholamine, and nitrate/nitrite (NO) responses to bicycle exercise were measured in 14 normal subjects (controls) and two groups with sympathetic denervation; 14 with peripheral autonomic failure (pure autonomic failure [PAF]); and 13 with central autonomic failure (multiple system atrophy [MSA]). With exercise, blood pressure increased in control subjects by 40 +/- 7/24 +/- 5 mm Hg (p < 0.001) and fell in PAF by 24 +/- 8/24 +/- 5 mm Hg (p < 0.02 and p < 0.007) and MSA by 31 +/- 7/11 +/- 3 mm Hg (p < 0.005 and p < 0.04). With exercise, the increase in heart rate was greater in control subjects (60 +/- 3 to 111 +/- 4/min; p < 0.0001) than in PAF (69 +/- 3 to 86 +/- 4/min; p < 0.0001) and MSA (70 +/- 4 to 90 +/- 4; p < 0.001). Resting plasma noradrenaline levels were similar in controls (291 +/- 51 pg ml(-1)) and MSA (257 +/- 49 pg ml(-1)), but lower in PAF (82 +/- 14 pg ml(-1)). With exercise, plasma noradrenaline increased in controls but was unchanged in PAF and MSA. Resting NOx was similar in controls (50 +/- 5 nmol/L; range, 23.3-87.6 nmol/L) and PAF patients (59+/-8 nmol/l; range, 19.3-116.4 nmol/L), but was higher in MSA patients (87 +/-14 nmol/L; p <0.025, range 15.4-157.2 nmol/L). With exercise, NOx was unchanged in control subjects and increased by 10% and 17% in PAF and MSA, respectively; these changes were not statistically significant. This study suggests that circulating changes in NOx levels do not exert a major role in exercise-induced hypotension in subjects with sympathetic denervation.

Autonomic Nervous System Diseases↗
PubMed1999

Modeling study of the effects of overlapping Ca2+ microdomains on neurotransmitter release.

Although single-channel Ca2+ microdomains are capable of gating neurotransmitter release in some instances, it is likely that in many cases the microdomains from several open channels overlap to activate vesicle fusion. We describe a mathematical model in which transmitter release is gated by single or overlapping Ca2+ microdomains produced by the opening of nearby Ca2+ channels. This model accounts for the presence of a mobile Ca2+ buffer, provided either that the buffer is unsaturable or that it is saturated near an open channel with Ca2+ binding kinetics that are rapid relative to Ca2+ diffusion. We show that the release time course is unaffected by the location of the channels (at least for distances up to 50 nm), but paired-pulse facilitation is greater when the channels are farther from the release sites. We then develop formulas relating the fractional release following selective or random channel blockage to the cooperative relationship between release and the presynaptic Ca2+ current. These formulas are used with the transmitter release model to study the dependence of this form of cooperativity, which we call Ca2+ current cooperativity, on mobile buffers and on the local geometry of Ca2+ channels. We find that Ca2+ current cooperativity increases with the number of channels per release site, but is considerably less than the number of channels, the theoretical upper bound. In the presence of a saturating mobile buffer the Ca2+ current cooperativity is greater, and it increases more rapidly with the number of channels. Finally, Ca2+ current cooperativity is an increasing function of channel distance, particularly in the presence of saturating mobile buffer.

Calcium↗
PubMed1999

Identification of seminiferous tubule aberrations and a low incidence of testicular microliths associated with the development of azoospermia.

OBJECTIVE: To evaluate the use of percutaneous testicular sperm aspiration in the assessment of azoospermia and its association with seminiferous tubule microliths. DESIGN: Case report. SETTING: Tertiary care fertility center in a university hospital. PATIENT(S): Male undergoing infertility evaluation. INTERVENTION(S): Testicular biopsy and percutaneous testicular aspiration. MAIN OUTCOME MEASURE(S): Serum hormone analysis, sperm concentration in semen, spermatogenesis in samples from testicular biopsies and aspirations, and microlith composition. RESULT(S): A patient presented for infertility evaluation with a history of severe oligospermia that progressed to azoospermia. The serum testosterone concentration (357 ng/dL) and LH concentration (9.2 mIU/mL) were normal and the serum FSH concentration (18.3 mIU/mL) was elevated. Testicular biopsy results indicated spermatogenic hypoplasia with limited spermatozoa. Seminiferous tubules obtained by percutaneous testicular aspiration were structurally aberrant, with multiple diverticula. Microliths averaging 120 microm in diameter were observed within and blocking the seminiferous tubules. The microliths were composed of calcium phosphate (hydroxyapatite) in both the core and peripheral regions. Electron microscopy revealed a high degree of collagen-like material within the peripheral zone. CONCLUSION(S): The presence of seminiferous tubule microliths is associated with the development of azoospermia. In patients with a low incidence of seminiferous tubule microliths and aberrant seminiferous tubule architecture, percutaneous testicular aspiration may provide a diagnostic advantage over testicular biopsy.

Adult↗
PubMed1999

Triglyceride as a risk factor for ischaemic heart disease in British men: effect of adjusting for measurement error.

OBJECTIVE: To assess the influence of differential precision in the measurement of the correlated variables total cholesterol and high density lipoprotein (HDL) cholesterol on the estimates of the risk of ischaemic heart disease (IHD) associated with plasma triglyceride levels. DESIGN, SETTING AND PARTICIPANTS: The Caerphilly Heart Disease Study (CHDS), a prospective cohort study of 2512 middle-aged men living in the town of Caerphilly, south Wales, UK. The results from two sub-studies were used to estimate the degree of measurement imprecision (laboratory error and within-person variation) in triglycerides, total cholesterol and HDL cholesterol. MAIN OUTCOME MEASURES: Multivariable risk estimates for major IHD calculated from logistic regression analysis, adjusted and not adjusted for measurement imprecision. Major IHD events were defined as death from IHD, clinical non-fatal myocardial infarction or electrocardiographic myocardial infarction. RESULTS: There were 261 men with major IHD events during follow-up. In age-adjusted analyses, taking measurement imprecision into account strengthened associations with IHD for all lipid factors. The odds ratio (OR) for one S.D. increase in triglycerides, ignoring measurement imprecision, was 1.36 (95% confidence interval [95% CI] 1.20-1.55) but 1.57 (95% CI 1.30-1.89) when taking imprecision into account. The standardised odds ratio for triglycerides adjusted for measurement imprecision and the two other lipid factors was 1.35 (95% CI 1.09-1.69). In this model, the triglyceride level showed a stronger association than total cholesterol (OR 1.28; 95% CI 1.05-1.56) and HDL cholesterol (OR for one S.D. decrease 1.20; 95% CI 0.97-1.49). When adding fasting blood glucose and diastolic blood pressure, however, the effect of triglycerides was reduced and ceased to be statistically significant (OR 1.19; 95% CI 0.95-1.49). This was further attenuated upon inclusion of body mass index, smoking status and history of pre-existing IHD. Total cholesterol remained a statistically significant (P < 0.05) risk factor in all models. CONCLUSIONS: In contrast to other cohort studies, triglyceride concentration in the CHDS shows an association with the risk of IHD which is independent of total and HDL cholesterol. This effect was pronounced after adjustment for measurement imprecision. It was reduced, however, when adjusted for other factors. While hypertriglyceridaemia may exert an influence independent of other lipid factors, insulin resistance is probably the underlying metabolic disturbance.

Adult↗
PubMed1999

Reconstructing the life course: health during early old age in a follow-up study based on the Boyd Orr cohort.

A method is described for investigating life course influences on health in early old age. The lives of some 300 individuals at present aged 65-75 y have been reconstructed from the archived records of a pre-WWII survey, in which they took part as children, and from lifegrid interviews with the same individuals 60 y later. Despite loss to study at several points those interviewed are shown to be representative of the British population socio-demographically, in comparison with the 1931 and 1991 decennial censuses, and physically, in comparison with the Health Survey for England. Bias is conservative because the most disadvantaged were disproportionately affected by loss to follow-up through death and because non-responders to interview were more disadvantaged as children than the interviewees. Representativeness and conservative bias, it is argued, justify the use of these data for investigating life course influences on health in early old age.

Aged↗
PubMed1999

Life course exposure and later disease: a follow-up study based on medical examinations carried out in Glasgow University (1948-68).

Evidence for the relationship between exposures in fetal life, infancy, childhood and early adulthood, and risk of chronic disease in later middle-age continues to accumulate. Further understanding of the associations between exposures acting over the life course and current morbidity and mortality in middle-age and later must depend upon the follow-up of previously established cohorts. This paper describes the design of, and background to, a follow-up of individuals who participated in a survey of student health in the University of Glasgow between 1948 and 1968. 15 332 students, almost a quarter of whom were female, had detailed medical information collected from a doctor-administered questionnaire and physical examination. Participation was voluntary; approximately 50% of the student population took part and these students were rep-resentative of the entire student population. Data collected include: socio-demographic, behavioural, developmental, anthropometric, and clinical details, as well as details of medical history and family health and structure. Data are over 95% complete for most variables. Over 40% of students were examined on two or more occasions with 1026 students (6.8%) having four or more examinations. Over 90% of students were from social classes I-III. Eighty-two per cent (12 533/15 322) of the students have been traced and flagged through the National Health Service Central Register and attempts are on-going to increase this figure. Those study members who have been traced are representative of the original cohort. To date 1111 (7.2%) of those traced have died. These data constitute a unique record of the health and physical development of a large cohort of students from Glasgow. Follow-up to investigate the relationship between indices of health and development, (height, weight, blood pressure), health behaviours and social circumstances in childhood and young adulthood, and mortality and morbidity in later adulthood is under way.

Anthropometry↗
PubMed1999

Blood pressure and birthweight in first year university students aged 18-25.

There have been many papers examining the relationship between blood pressure and birthweight but although the association is clearly established in adults and children findings in adolescence and young adults have been inconsistent. The objective of this study was to examine the relationship between blood pressure and birthweight in young adults. The blood pressure of 1358 university students aged 18-25 was recorded at a screening medical examination and their birthweight from parental report. Using linear regression analysis, systolic blood pressure, after adjustment for age, weight and height, decreased by 2.00 mmHg (-3.8, -0.2) for every kg increase in birthweight in females. The relationship was negative but non-significant in males. Substituting body mass index (BMI) for weight in the regression analysis produced similar results. There was a smaller and non-significant relationship between diastolic blood pressure and birthweight which is consistent with other studies. This study confirms the inverse relationship between systolic blood pressure and birthweight in young adults and provides some support for the hypothesis that undernutrition in utero contributes to the development of cardiovascular disease in adults.

Adolescent↗