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Biomedical subjects

S Bingham

Publications and source records attributed to S Bingham.

At least 37 records · Page 2Linked to original sources

Effects of dietary nutrients and food groups on bone loss from the proximal femur in men and women in the 7th and 8th decades of age.

We measured the impact of diet, anthropometry, physical activity and lifestyle variables on rates of hip bone mineral density (BMD) loss in 470 white men and 474 white women aged 67-79 years at recruitment dwelling in the community. The subjects were recruited from a prospective population-based diet and cancer study (EPIC-Norfolk) in Eastern England. Dietary intake was measured at baseline using 7-day food diaries and used to calculate intakes of some 31 nutrients and 22 food groups. Standardised questionnaires were used to collect data on anthropometry, physical activity and lifestyle variables. BMD loss (percent per annum; % p.a.) was measured using dual-energy X-ray absorptiometry performed on two occasions an average of 3 years apart (range 2-5 years). The mean rate of BMD change at the total hip region was -0.17% p.a. (SD 1.3% p.a.) in men and -0.41% p.a. (SD 1.2% p.a.) in women. In both men and women, weight gain protected against (and weight loss promoted) BMD loss ( P<0.0001). Markers of current physical activity were protective. In men, an increase of 1 l/s in FEV(1) was associated with an increase in BMD at an average rate of 0.25% p.a. ( P=0.013). In women, for every ten trips made per day climbing a flight of stairs, BMD increased at a rate of 0.22% p.a. ( P=0.005) and additionally a 10% increase in activities of daily living score was associated with BMD increasing at a rate of 0.12% p.a. ( P=0.011) in women. Nutritional variation appeared to have less impact on BMD loss. In men there was no evidence of an effect of any of the nutrients evaluated. However, in women, low intake of vitamin C was associated with faster rate of BMD loss. Women in the lowest tertile (7-57 mg/day) of vitamin C intake lost BMD at an average rate of -0.65% p.a., which was significantly faster compared to loss rates in the middle (58-98 mg/day) and upper (99-363 mg/day) tertiles of intake, which were -0.31% p.a. and -0.30% p.a., respectively ( P=0.016). There was no effect of fruits and vegetables, combined or separately, on rate of BMD loss. The results confirm that weight maintenance (or gain) and commonly practiced forms of physical activity appear to protect against BMD loss in this age group. Measures such as ensuring good general nutrition to guard against weight loss in the non-overweight elderly and maintenance of physical fitness could be valuable in protecting against BMD loss. The protective effect of vitamin C in women needs to be further investigated in other prospective cohort or intervention studies.

Aged↗

Modest evidence for linkage and possible confirmation of association between NOTCH4 and schizophrenia in a large Veterans Affairs Cooperative Study sample.

Wei and Hemmings [2000: Nat Genet 25:376-377], using 80 British parent-offspring trios, identified a number of NOTCH4 variants and haplotypes that showed statistically significant evidence of association to schizophrenia. Specifically, the 10 repeat allele of a (CTG)(n) marker and the 8 repeat allele of a (TAA)(n) marker demonstrated excess transmission to affected individuals; SNP21 and haplotypes SNP2-(CTG)(n) and SNP12-SNP2-(CTG)(n) also showed significant associations. In an attempt to replicate these findings, we tested for linkage and association between the same five markers used by Wei and Hemmings in 166 families collected from a multi-center study conducted by the Department of Veterans Affairs (DVA) Cooperative Study Program (CSP). The families include 392 affected subjects (schizophrenia or schizoaffective disorder, depressed) and 216 affected sibling pairs. The families represent a mix of European Americans (n = 62, 37%), African Americans (n = 60, 36%), and racially mixed or other races (n = 44, 27%). We identified moderate evidence for linkage in the pooled race sample (LOD = 1.25) and found excess transmission of the 8 (P = 0.06) and 13 (P = 0.04) repeat alleles of the (TAA)(n) marker to African American schizophrenic subjects. The 8 and 13 repeat alleles were previously identified to be positively associated with schizophrenia by Wei and Hemmings [2000: Nat Genet 25:376-377] and Sklar et al. [2001: Nat Genet 28:126-128], respectively.

Alleles↗

Television viewing and low participation in vigorous recreation are independently associated with obesity and markers of cardiovascular disease risk: EPIC-Norfolk population-based study.

OBJECTIVE: This study describes the associations between sedentary behaviour (television viewing) and participation in vigorous recreational activity with obesity and with biomarkers of cardiovascular disease (CVD) risk profile. DESIGN: Cross-sectional analysis of the EPIC-Norfolk cohort study. SETTING: The study is a population-based study of participants living in Norfolk, UK. SUBJECTS: A total of 15 515 men and women aged between 45 and 74 y, recruited through General Practice lists, who completed the detailed physical activity questionnaire. RESULTS: Following exclusion of those with self-reported myocardial infarction, stroke and diabetes, 14 189 participants remained for the analysis. Self-reported television viewing was positively and participation in vigorous activity negatively associated with markers of obesity, blood pressure and plasma lipids. In multiple regression analysis, adjusting for age, alcohol, smoking, treatment for hypertension, vigorous and total physical activity, these associations remained significant. For women who participated in more than 1 h/week of vigorous activity and who watched fewer than 2 h of television each day, the adjusted mean body mass index was 1.92 kg/m(2) less than for women who reported participating in no vigorous activity and who watched more than 4 h of television each day (P<0.001). The equivalent figure for men was 1.44 kg/m(2) (P<0.001). In a similar analysis, with blood pressure as the outcome, mean diastolic blood pressure difference between the extreme groups of vigorous activity and television viewing was 3.6 mmHg in men (P<0.001) and 2.7 mmHg (P=0.001) in women. CONCLUSIONS: These data suggest that time spent participating in vigorous recreational physical activity and television viewing, an indicator of a sedentary lifestyle, are associated with obesity and markers of CVD disease risk independent of total reported physical activity. Whether these observations represent the true underlying aetiological relations or are a manifestation of the different precision with which the subdimensions of activity are measured remains uncertain.

Aged↗

Residential area deprivation predicts smoking habit independently of individual educational level and occupational social class. A cross sectional study in the Norfolk cohort of the European Investigation into Cancer (EPIC-Norfolk).

OBJECTIVES: To investigate the independent association between individual and area based measures of socioeconomic status and cigarette smoking habit. DESIGN AND SETTING: Cross sectional, population based study. PARTICIPANTS AND METHODS: 12 579 men and 15 132 women aged 39-79 years living in the general community participating in the EPIC-Norfolk Study in 1993-1997. The association between social class, educational status, Townsend residential deprivation level, and cigarette smoking status was examined. MAIN OUTCOME MEASURES: Cigarette smoking status at baseline survey. RESULTS: Social class, educational level, and residential deprivation level independently related to cigarette smoking habit in both men and women. Multivariate age adjusted odds ratios for current smoking in men were 1.62 (95% CI 1.45 to 1.81) for manual compared with non-manual social class, 1.32 (95% CI 1.17 to 1.48) for those with educational level less than O level compared with those with O level qualifications or higher and 1.84 (95% CI 1.62 to 2.08) for high versus low area deprivation level. For women, the odds ratios for current smoking for manual social class were 1.14 (95% CI 1.03 to 1.27); 1.31 (95% CI 1.18 to 1.46) for low educational level and 1.68 (95% CI 1.49 to 1.90) for high residential deprivation respectively. CONCLUSIONS: Residential deprivation level using the Townsend score, individual social class, and educational level all independently predict smoking habit in both men and women. Efforts to reduce cigarette smoking need to tackle not just individual but also area based factors. Understanding the specific factors in deprived areas that influence smoking habit may help inform preventive efforts.

Adult↗

Cross-sectional association between total level and type of alcohol consumption and glycosylated haemoglobin level: the EPIC-Norfolk Study.

OBJECTIVE: To investigate the association between total level and type of alcohol consumed and glycaemia. DESIGN: Cross-sectional study. SETTING: The EPIC-Norfolk Study, a population-based cohort study of diet and chronic disease. SUBJECTS AND METHODS: Non-diabetic men (n=2842) and women (n=3572), aged 40-78 y. Alcohol intake was assessed by self-reported questionnaire, and glycaemia measured by glycosylated haemoglobin (HbA(1c)). RESULTS: Ten percent of men and 18% of women reported drinking no alcohol. Among drinkers, median alcohol intake was 8 units/week for men and 3 units/week for women. In analyses stratified by sex and adjusted for age, total energy intake, education, fruit and vegetable intake, smoking, family history of diabetes, physical activity, body mass index and waist:hip ratio, alcohol intake was inversely associated with HbA(1c) in men and women, although the association was stronger in women. A 1 unit/week increase in alcohol intake was associated with 0.0049% (s.e.=0.00223; P-value=0.028) and 0.017% (s.e.=0.00343; P-value <0.001) reduction in HbA(1c) in men and women respectively. In similar multivariate analyses, wine intake was inversely associated with HbA(1c) in men, and wine, spirits and beer intake were inversely associated with HbA(1c) in women. When also adjusted for total alcohol intake, only the association between wine intake and HbA(1c) in men remained significant. CONCLUSION: Alcohol intake was associated with lower HbA(1c) level, an association not explained by confounding. The distinction between type of alcohol consumed was particularly important in men.

Adult↗

Examination of genetic linkage of chromosome 15 to schizophrenia in a large Veterans Affairs Cooperative Study sample.

Previous studies have reported genetic linkage evidence for a schizophrenia gene on chromosome 15q. Here, chromosome 15 was examined by genetic linkage analysis using 166 schizophrenia families, each with two or more affected subjects. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Study Program, consisted of 392 sampled affected subjects and 216 affected sibling pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizo-affective disorder, depressed. Participating families had diverse ethnic backgrounds. The largest single group were northern European American families (n = 62, 37%), but a substantial proportion was African American kindreds (n = 60, 36%). The chromosome 15 markers tested were spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the region surrounding the alpha-7 nicotinic cholinergic receptor subunit gene (CHRNA7). These markers were genotyped and the data analyzed using semiparametric affecteds-only linkage analysis. In the European American families, there was a maximum Z-score of 1.65 between markers D15S165 and D15S1010. These markers are within 1 cM from CHRNA-7, the site previously implicated in schizophrenia. However, there was no evidence for linkage to this region in the African America kindreds.

Adult↗

Frequency of eating and concentrations of serum cholesterol in the Norfolk population of the European prospective investigation into cancer (EPIC-Norfolk): cross sectional study.

OBJECTIVES: To examine the relation between self reported eating frequency and serum lipid concentrations in a free living population. DESIGN: Cross sectional population based study. SETTING: Norfolk, England. PARTICIPANTS: 14 666 men and women aged 45-75 years from the Norfolk cohort of the European prospective investigation into cancer (EPIC-Norfolk). MAIN OUTCOME MEASURES: Concentrations of blood lipids. RESULTS: Mean concentrations of total cholesterol and low density lipoprotein cholesterol decreased in a continuous relation with increasing daily frequency of eating in men and women. No consistent relation was observed for high density lipoprotein cholesterol, body mass index, waist to hip ratio, or blood pressure. Mean cholesterol concentrations differed by about 0.25 mmol/l between people eating more than six times a day and those eating once or twice daily; this difference was reduced to 0.15 mmol/l after adjustment for possible confounding variables, including age, obesity, cigarette smoking, physical activity, and intake of energy and nutrients (alcohol, fat, fatty acids, protein, and carbohydrate). CONCLUSIONS: Concentrations of total cholesterol and low density lipoprotein cholesterol are negatively and consistently associated with frequency of eating in a general population. The effects of eating frequency on lipid concentrations induced in short term trials in animals and human volunteers under controlled laboratory conditions can be observed in a free living general population. We need to consider not just what we eat but how often we eat.

Aged↗

Dorsal root ganglion neurons show increased expression of the calcium channel alpha2delta-1 subunit following partial sciatic nerve injury.

Neuropathic pain is associated with changes in the electrophysiological and neurochemical properties of injured primary afferent neurons. A mRNA differential display study in rat L(4/5) dorsal root ganglia (DRGs) revealed upregulation of the calcium channel alpha2delta-1 subunit 2 weeks after partial sciatic nerve ligation (Seltzer model of neuropathic pain). The upregulated transcript appeared to represent previously unidentified sequence from the 3'-untranslated region of rat alpha2delta-1 mRNA. In situ hybridization using L(5) DRGs from sham operated rats showed that 73, 40 and 19% of small (<700 microm(2)), medium (700-1100 microm(2)) and large (>1100 microm(2)) neuronal profiles, respectively, expressed alpha2delta-1 mRNA. Two weeks following nerve injury there was a significant ipsilateral increase, both in the percentage of DRG neurons expressing alpha2delta-1 mRNA and in the intensity of the hybridization signal. Comparison of this ipsilateral expression with that in sham animals, revealed that for small, medium and large neurons, respectively, the proportion of neurons labelled increased by 1.2-, 1.8- and 2.7-fold, while the hybridization signal in alpha2delta-1-labelled neurons increased by 2.8-, 2.5- and 3.7-fold. The most intensely labelled neuronal profiles in ipsilateral, sham and contralateral DRGs, were generally those with small cross-sectional areas. The alpha2delta-1 auxiliary subunit is known to modulate calcium channel function in heterologous expression systems via its association with the pore-forming alpha1 calcium channel subunit. Therefore the increased levels of this subunit in the populations of primary afferents described may, via modulation of calcium-dependent processes such as neurotransmitter release and neuronal excitability, influence the processing of sensory information.

Animals↗

Determination of changes in mRNA expression in a rat model of neuropathic pain by Taqman quantitative RT-PCR.

The aim of this study was to develop a rapid and accurate high throughput method of screening multiple genes across a single sample set to detect changes in gene expression in the dorsal root ganglion (DRG) following partial sciatic nerve ligation in the rat. Using Taqman quantitative RT-PCR, we show that expression of a number of genes, including galanin, vasointestinal peptide and neuropeptide Y are rapidly increased 24 h post-operation in the DRGs on the ligated side only. Other genes tested, including vanilloid receptor-1, substance P, galanin receptor-2 and housekeeping genes did not alter. Analysis of the expression of ASIC4 showed a small difference in expression at 7 days post ligation. By applying a statistical method for analysis of multiple variables, partial least squares, we show that the expression change of ASIC4 was significantly altered on the ligated side even though the change was small. This method will allow us to rapidly identify changes in expression of candidate genes that may be involved in adaptive responses in the DRG due to nerve injury.

Acid Sensing Ion Channels↗

Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Ascorbic acid (vitamin C) might be protective for several chronic diseases. However, findings from prospective studies that relate ascorbic acid to cardiovascular disease or cancer are not consistent. We aimed to assess the relation between plasma ascorbic acid and subsequent mortality due to all causes, cardiovascular disease, ischaemic heart disease, and cancer. METHODS: We prospectively examined for 4 years the relation between plasma ascorbic acid concentrations and mortality due to all causes, and to cardiovascular disease, ischaemic heart disease, and cancer in 19 496 men and women aged 45-79 years. We recruited individuals by post using age-sex registers of general practices. Participants completed a health and lifestyle questionnaire and were examined at a clinic visit. They were followed-up for causes of death for about 4 years. Individuals were divided into sex-specific quintiles of plasma ascorbic acid. We used the Cox proportional hazard model to determine the effect of ascorbic acid and other risk factors on mortality. FINDINGS: Plasma ascorbic acid concentration was inversely related to mortality from all-causes, and from cardiovascular disease, and ischaemic heart disease in men and women. Risk of mortality in the top ascorbic acid quintile was about half the risk in the lowest quintile (p<0.0001). The relation with mortality was continuous through the whole distribution of ascorbic acid concentrations. 20 micromol/L rise in plasma ascorbic acid concentration, equivalent to about 50 g per day increase in fruit and vegetable intake, was associated with about a 20% reduction in risk of all-cause mortality (p<0.0001), independent of age, systolic blood pressure, blood cholesterol, cigarette smoking habit, diabetes, and supplement use. Ascorbic acid was inversely related to cancer mortality in men but not women. INTERPRETATION: Small increases in fruit and vegetable intake of about one serving daily has encouraging prospects for possible prevention of disease.

Age Distribution↗

Empirical evidence of correlated biases in dietary assessment instruments and its implications.

Multiple-day food records or 24-hour recalls are currently used as "reference" instruments to calibrate food frequency questionnaires (FFQs) and to adjust findings from nutritional epidemiologic studies for measurement error. The common adjustment is based on the critical requirements that errors in the reference instrument be independent of those in the FFQ and of true intake. When data on urinary nitrogen level, a valid reference biomarker for nitrogen intake, are used, evidence suggests that a dietary report reference instrument does not meet these requirements. In this paper, the authors introduce a new model that includes, for both the FFQ and the dietary report reference instrument, group-specific biases related to true intake and correlated person-specific biases. Data were obtained from a dietary assessment validation study carried out among 160 women at the Dunn Clinical Nutrition Center, Cambridge, United Kingdom, in 1988-1990. Using the biomarker measurements and dietary report measurements from this study, the authors compare the new model with alternative measurement error models proposed in the literature and demonstrate that it provides the best fit to the data. The new model suggests that, for these data, measurement error in the FFQ could lead to a 51% greater attenuation of true nutrient effect and the need for a 2.3 times larger study than would be estimated by the standard approach. The implications of the results for the ability of FFQ-based epidemiologic studies to detect important diet-disease associations are discussed.

Bias↗

Patterns of physical activity and ultrasound attenuation by heel bone among Norfolk cohort of European Prospective Investigation of Cancer (EPIC Norfolk): population based study.

OBJECTIVES: To study associations between patterns of physical activity and ultrasound attenuation by the heel bone in men and women. DESIGN: Cross sectional, population based study. SETTING: Norfolk. PARTICIPANTS: 2296 men and 2914 women aged 45-74 registered with general practices participating in European Prospective Investigation into Cancer (EPIC Norfolk). RESULTS: Self reported time spent in high impact physical activity was strongly and positively associated with ultrasound attenuation by the heel bone, independently of age, weight, and other confounding factors. Men who reported participating in >/=2 hours/week of high impact activity had 8.44 dB/MHz (95% confidence interval 4.49 to 12.40) or 9.5%, higher ultrasound attenuation than men who reported no activity of this type. In women, the difference in ultrasound attenuation between those reporting any high impact activity and those reporting none was 2.41 dB/MHz (0.45 to 4.37) or 3.4% higher. In women this effect was similar in size to that of an age difference of four years. Moderate impact activity had no effect. However, climbing stairs was strongly independently associated with ultrasound attenuation in women (0.64 dB/MHz (0.19 to 1.09) for each additional five flights of stairs). There was a significant negative association in women between time spent watching television or video and heel bone ultrasound attenuation, which decreased by 0.08 dB/MHz (0.02 to 0.14) for each additional hour of viewing a week. CONCLUSIONS: High impact physical activity is independently associated with ultrasound attenuation by the heel bone in men and women. As low ultrasound attenuation has been shown to predict increased risk of hip fracture, interventions to promote participation in high impact activities may help preserve bone density and reduce the risk of fracture. However, in older people such interventions may be inappropriate as they could increase the likelihood of falls.

Age Factors↗

Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospective investigation of cancer and nutrition (EPIC-Norfolk).

OBJECTIVE: To examine the value of glycated haemoglobin (HbA(1c)) concentration, a marker of blood glucose concentration, as a predictor of death from cardiovascular and all causes in men. DESIGN: Prospective population study. SETTING: Norfolk cohort of European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). SUBJECTS: 4662 men aged 45-79 years who had had glycated haemoglobin measured at the baseline survey in 1995-7 who were followed up to December 1999. MAIN OUTCOME MEASURES: Mortality from all causes, cardiovascular disease, ischaemic heart disease, and other causes. RESULTS: Men with known diabetes had increased mortality from all causes, cardiovascular disease, and ischaemic disease (relative risks 2.2, 3.3, and 4.2, respectively, P <0.001 independent of age and other risk factors) compared with men without known diabetes. The increased risk of death among men with diabetes was largely explained by HbA(1c) concentration. HbA(1c) was continuously related to subsequent all cause, cardiovascular, and ischaemic heart disease mortality through the whole population distribution, with lowest rates in those with HbA(1c) concentrations below 5%. An increase of 1% in HbA(1c) was associated with a 28% (P<0.002) increase in risk of death independent of age, blood pressure, serum cholesterol, body mass index, and cigarette smoking habit; this effect remained (relative risk 1.46, P=0.05 adjusted for age and risk factors) after men with known diabetes, a HbA(1c) concentration >/=7%, or history of myocardial infarction or stroke were excluded. 18% of the population excess mortality risk associated with a HbA(1c) concentration >/=5% occurred in men with diabetes, but 82% occurred in men with concentrations of 5%-6.9% (the majority of the population). CONCLUSIONS: Glycated haemoglobin concentration seems to explain most of the excess mortality risk of diabetes in men and to be a continuous risk factor through the whole population distribution. Preventive efforts need to consider not just those with established diabetes but whether it is possible to reduce the population distribution of HbA(1c) through behavioural means.

Aged↗