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Biomedical subjects

D G Cook

Publications and source records attributed to D G Cook.

At least 19 recordsLinked to original sources

Ethnic differences in fibrinogen levels: the role of environmental factors and the beta-fibrinogen gene.

Fibrinogen is a cardiovascular risk factor, but little is known about levels in ethnic groups that differ in their cardiovascular risk. Fibrinogen was measured in 479 Black individuals, 459 South Asian Indians, and 453 Whites aged 40-59 years living in south London, England, from March 1994 to July 1996. Genotype was determined at two sites in the promoter of the beta-fibrinogen gene (G-455-->A and C-148-->T). Plasma fibrinogen levels were lower in Blacks than in Whites by 0.22 g/liter (95% confidence interval (CI): 0.08, 0.36) in men and 0.11 g/liter (95% CI: -0.01, 0.23) in women. These differences were not explained by measured environmental variables, including smoking, or by genotypes. The fibrinogen levels of South Asians were not consistently different from those of WHITES: The A-455 and T-148 alleles were less common in Blacks than in either Whites or South ASIANS: In Whites and South Asians, but not in Blacks, there was complete allelic association between the two variants. In Blacks, the T allele rather than the A allele was associated with higher fibrinogen levels. The average fibrinogen-raising effect of the T-148 allele across all ethnic groups was 0.14 g/liter (95% CI: 0.02, 0.26 g/liter) in women and 0.15 g/liter (95% CI: 0.03, 0.27 g/liter) in men. Low fibrinogen levels in Blacks may partly explain their lower risk of ischemic heart disease in the United KINGDOM:

Adult↗

Variable effects of the APOC3-482C > T variant on insulin, glucose and triglyceride concentrations in different ethnic groups.

AIMS/HYPOTHESIS: The apolipoprotein C3-482C> T variant modulates insulin and glucose concentrations after an oral glucose tolerance test (OGTT) in young healthy white men. We evaluated the effect of this variant in different ethnic groups with different rates of Type II (non-insulin-dependent) diabetes mellitus and coronary heart disease. METHODS: We investigated the -482C > T in a population-based cross-sectional study of white subjects (n = 462), South Asians (n = 442) and subjects of West African and Afro-Caribbean origin (n = 462), whose OGTT and fasting plasma triglyceride concentrations had been measured. RESULTS: The -482T allele frequency differed between the three groups: 0.25 (95 % CI 0.22-0.28) in white subjects, 0.44 (0.41-0.47) in South Asians and 0.71 (0.68-0.74) in black subjects (p < 0.0001). A positive association was found between body mass index and genotype in black women (p = 0.009) and in black men (p = 0.056) but not in white subjects or South Asians. Associations between -482C > T and fasting insulin were found in white subjects, where -482T allele carriers had higher concentrations (adjusted for age and sex, p = 0.007, also including smoking and body mass index, p = 0.038). Higher triglyceride concentrations (p = 0.004 and p = 0.007 in the two models) but not glucose concentrations were also associated with -482C > T. In black subjects, decreased fasting insulin (p = 0.04) and fasting glucose (p = 0.004) were associated with -482C > T. No relation was observed between genotype and any post-load measured. CONCLUSIONS/INTERPRETATION. Allele frequencies of the -482C > T and associations with insulin, glucose and triglyceride concentrations vary considerably among ethnic groups. Although the results are consistent among white subjects across different studies, the associations among black subjects and South Asians differ.

Adult↗

Performance of a new pubertal self-assessment questionnaire: a preliminary study.

We describe the performance of a new, self-assessment questionnaire that aims to measure pubertal status by using gender-specific line drawings of the Tanner puberty stages. The study was carried out on 103 children aged 12-16 years attending a paediatric endocrinology outpatient clinic and used physical examination by clinic doctors as the 'gold standard'. Of 133 consecutive, eligible children, 108 (81%) agreed to participate in the study. Data were collected from 62 (60%) males and 41 (40%) females. Mean age was 14.78 years (SD = 1.26 years, range 12.08-16.98 years). For the pubic hair distribution Tanner stage, there was agreement to within one Tanner stage for 90 children (88%), weighted kappa statistic for inter-rater agreement = 0.68 [95% CI 0.49,0.87]. For the female breast/male genitalia Tanner stage, there was agreement to within one Tanner stage for 75 children (76%), kappa = 0.48 [95% CI 0.31,0.64]. The children tended to underestimate their stage of pubertal development. Overall, the kappa statistics implied good agreement for the pubic hair question and moderate agreement for the breast/genitalia stage question in both girls and boys. The questionnaire may prove useful in situations such as large-scale epidemiological studies, in which direct examination of children to determine pubertal status is not possible, and further validation in normal adolescents is warranted.

Adolescent↗

Differences in hormone replacement therapy use by social class, region and psychological symptoms.

OBJECTIVE: To describe the relationship between socio-demographic factors, heart disease risk factors, psychological symptoms and the use of hormone replacement therapy by English women. DESIGN: Cross-sectional analysis of a population-based survey. SETTING: England. POPULATION: 13,214 women aged 40-69 years who participated in the nurse-administered schedule of the Health Survey for England between 1993 and 1996. OUTCOME: Current hormone replacement therapy use. RESULTS: Women from social classes II and I and women who live in the south of England were more likely to use hormone replacement therapy independently of a range of socio-demographic factors including education. The adjusted odds ratio for social classes II and I compared with social classes IV and V was 1.51 (95% CI 1.20 to 1.91) and for women in the South of England was 1.38 (95% CI 1.18 to 1.62). Women with a history of heart disease and those with high cholesterol levels were less likely to use hormone replacement therapy. Women with psychological symptoms were more likely to be prescribed hormone replacement therapy, as were those who had recently seen a doctor. CONCLUSION: There is marked socio-demographic inequity in use of hormone replacement therapy. This may accentuate existing inequalities in health and reduce any potential benefits of Hormone Replacement Therapy for public health. The relationship between psychological symptoms, use of medical services and use of hormone replacement therapy suggests that hormone replacement therapy is prescribed for the management of psychological symptoms.

Adult↗

Do income questions and seeking consent to link medical records reduce survey response rates? A randomised controlled trial among older people.

Traditional measures of socioeconomic status may not be reliable for older people and income may be a useful measure for research into inequalities in health. At the same time, researchers increasingly wish to link survey findings to individual data taken from medical records. For this, consent must be sought. To examine whether questions on household income and seeking consent for medical record linkage affected response rates, a postal health survey of patients aged 65 to 74 was undertaken in an inner London practice. The overall response rate was 62.8%. In this study, the inclusion of an income question or seeking consent to access medical records did not reduce response rates to a health survey among older people.

Aged↗

Do children who become autistic consult more often after MMR vaccination?

A close temporal association has been reported between the measles, mumps, and rubella (MMR) vaccination and dramatic behavioural decline in children subsequently diagnosed as autistic. We hypothesised that such a decline would be reflected in increased consultations with the child's general practitioner. The Doctor's Independent Network database was used to examine whether children subsequently diagnosed as autistic consulted more frequently than controls after MMR vaccination. No difference in consulting behaviour was seen in the six months post MMR. Any dramatic effect of MMR on behaviour seems unlikely.

Autistic Disorder↗

Use of alternative medicines in a multi-ethnic population.

BACKGROUND: The prevalence and cost of regular use of non-prescribed alternative medicines are rising around the world, yet, little evidence is available that demonstrates the safety, efficacy, or effectiveness of specific alternative medicine interventions. It is of interest to understand how and why these practices have become so popular in different societies with different health care organizations and provisions, and which factors predict the regular use of alternative medicines. METHODS: We assessed the prevalence and the predictors of regular use of non-prescribed vitamin supplements, cod liver oil, primrose oil, and garlic in a cross-sectional population-based study in South London of 1,577 men and women, aged 40-59 years (883 women, 523 White, 549 of African origin and 505 of South Asian origin), when allowing for potential confounders. RESULTS: The prevalence of regular users of alternative medicines was 10.4% (164/1,577); 7.4% (116) made regular use of non-prescribed vitamin supplements, whereas 5.3% (84) used either cod liver oil, primrose oil, or garlic preparations. When adjusted for age, ethnicity and social class, women were more likely than men to use at least one alternative medicine (OR 2.09 [95% CI 1.45-3.00]). This was true both for vitamin supplements (1.98 [1.29-3.03]) and for oil or garlic supplements (1.91 [1.17-3.14]). The use of oil or garlic (P<.005) but not vitamin supplements (P=.32) varied by ethnic group. In particular, Black people of African origin were more likely to use alternative medicines than either Whites (1.78 [1.07-2.94]) or South Asians (1.66 [1.07-2.59]), the least common users. People in social classes IV and V were less likely to use alternative medicines (0.53 [0.31-0.90]) than those in social classes I and II, though this was due more to lesser use of non-prescribed vitamin supplements than of cod liver oil, primrose oil or garlic. These associations were not attenuated by further adjustment for body mass index, smoking, marital status and age at leaving full-time education. CONCLUSIONS: The regular users of alternative medicines in London are more likely to be women, of African origin, and of higher socioeconomic status. Given the lack of evidence of efficacy and safety of these alternative medicines, it is important to understand the cultural differences in values and beliefs about traditional medicine that may underlie these findings.

Adult↗

Children's exposure to passive smoking in England since the 1980s: cotinine evidence from population surveys.

OBJECTIVE: To determine whether children's exposure to passive smoking has changed since the late 1980s. DESIGN: Cross sectional surveys of nationally representative samples of secondary school children carried out between 1988 and 1998 by Office for National Statistics. SETTING: England. SUBJECTS: Secondary school children aged 11-15. MAIN OUTCOME MEASURES: Salivary cotinine concentrations in non-smoking children. RESULTS: Cotinine concentrations in all non-smoking children almost halved between 1988 and 1998, from a geometric mean of 0.96 (95% confidence interval 0.83 to 1.11) ng/ml in 1988 to 0.52 (0.43 to 0.62) ng/ml in 1998. This reduction was largely due to reductions in exposure in children from non-smoking households and to decreases in the percentage of parents who smoked. Children living with mothers or fathers who smoked experienced little reduction in exposure. CONCLUSIONS: Exposure to passive smoking among children in England has approximately halved since the late 1980s. This reduction is partly explained by the fall in the percentage of both mothers and fathers who smoke and is also likely to reflect reductions of smoking in public places. However, there is only limited evidence that children from smoking households have experienced a reduction in exposure through parents' avoidance of smoking in their presence.

Adolescent↗

Cholesterol and arterial distensibility in the first decade of life: a population-based study.

BACKGROUND: Blood cholesterol levels are a key determinant of coronary heart disease risk in adults, but the importance of lipid levels in the general population during childhood is less clear. We related arterial distensibility, a marker of vascular function known to be altered early in atherosclerosis, to the lipid profile of a population-based sample of children aged 9 to 11 years. METHODS AND RESULTS: A noninvasive ultrasound technique was used to measure arterial distension during the cardiac cycle in the brachial arteries of 361 children from 4 towns in the United Kingdom. This measure was related to their pulse pressure to assess arterial distensibility. All the children had previously had a comprehensive assessment of cardiovascular risk including a full lipid profile, cotinine-assessed smoke exposure, serum glucose, and questionnaire data on socioeconomic and dietary factors. Mean total cholesterol in the population was 4.72 [SD 0.75] mmol/L. There was a significant, inverse relation between cholesterol and distension of the artery across this range (linear regression coefficient -11.8 microm. mmol(-1). L(-1), P=0.003). Similar relationships were demonstrated with LDL and apolipoprotein B (-12.9 microm. mmol(-1). L(-1), P=0. 005 and -36.9 microm/mmol/L, P=0.01). HDL and triglyceride levels showed no consistent association with distensibility. CONCLUSIONS: LDL cholesterol levels had an impact on arterial distensibility in the first decade of life. Furthermore, the functional differences in the arterial wall were demonstrated within the lipid range found in normal children, a finding that raises the possibility that cholesterol levels in the general population during childhood may already be relevant to the development of vascular disease.

Adult↗

Frequency and allelic association of common variants in the lipoprotein lipase gene in different ethnic groups: the Wandsworth Heart and Stroke Study.

The lower serum triglyceride (Tg), higher high density cholesterol (HDL-C) levels and low coronary heart disease (CHD) mortality in black populations, contrast with that in whites. By comparison, South Asian populations display a higher mortality from CHD associated with increased Tg and low HDL-C levels. Lipoprotein lipase (LPL) plays a major role in Tg metabolism. To determine if variation in the LPL gene contributes to the differences in lipid levels, we studied the frequencies and allelic associations of five common variants in the lipoprotein lipase (LPL) gene (-93T/G, D9N, N291S, S447X, and the HinddIII RFLP in intron 8) with serum Tg and HDL-cholesterol concentrations in population samples of middle-aged men and women of whites, South Asians, and blacks of African origin co-resident in South London. Significantly higher frequencies of the H(-) (P < 0.00001), N9 (P < 0.001), and -93G (P < 10(-10)) alleles were seen in blacks compared to the other two groups. Allelic association between -93G and N9, and H(+) and X447 was strong in all three groups. However, no association was observed between serum Tg and HDL-cholesterol concentrations and these variants in the three ethnic groups. A single common polymorphism in the LPL gene is unlikely to account for the differences in fasting serum Tg in populations of different ethnic background. The importance of the differences in frequencies and the mechanism(s) whereby these may contribute towards a beneficial LPL genotype in black populations remain to be determined.

Adult↗

C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors.

Whether or not C-reactive protein (CRP) predicts heart disease in adults because it is a marker of damage or atherosclerosis is difficult to assess. In children, there is no confounding with coronary disease or active smoking. We measured CRP in 699 children aged 10-11 years. CRP levels were 47% higher in girls than boys, and rose with age by 15%/year. CRP levels were 270% (95% CI, 155-439%) higher in the top fifth than the bottom fifth of Ponderal index (weight/height(3)). After adjustment, CRP levels remained 104% (95% CI, 23-236%) higher in the 56 children of South Asian origin. CRP was unrelated to: birth weight, height, social class, Helicobacter pylori infection or passive smoke exposure. CRP was correlated with several cardiovascular risk factors, but only fibrinogen (r = 0.33, P = 0.0001), HDL-cholesterol (r = -0.13, P = 0.0006), heart rate (r = 0.12, P = 0.002) and systolic blood pressure (r = 0.08, P = 0.02) remained statistically significant after adjustment. We conclude that adiposity is the major determinant of CRP levels in children while physical fitness has a small independent effect. The strong relationships with fibrinogen and HDL-cholesterol suggest a role for inflammation throughout life in the development of atherosclerosis and cardiovascular disease. Longitudinal studies are needed to determine whether these associations reflect long term elevations of these risk factors in some individuals, or short term fluctuations in different individuals.

Age Distribution↗

Western blotting is useful in the salivary diagnosis of Helicobacter pylori infection.

BACKGROUND: The salivary diagnosis of Helicobacter pylori infection offers attractive possibilities for the epidemiological study of infection in children. Salivary enzyme linked immunosorbent assay (ELISA) is less reliable then serum ELISA, owing to variable transudation of immunoglobulin. In addition, children are more difficult to study because of lower specific serum antibody concentrations to H pylori. The performance of salivary western blotting in comparison with serum western blotting and serum ELISA was investigated in school children. SUBJECTS AND METHODS: Paired serum and saliva specimens were obtained from 669 [corrected] school children aged 9-11 in 10 British towns. All saliva and serum specimens were first analysed by ELISA; subsequently, western blotting of both specimens was performed on 31 and 34 specimens, respectively, to establish the criteria for positivity for western blotting. The remaining 121 specimens were then tested blindly and saliva was compared with the serum. RESULTS: The sensitivity and specificity of salivary ELISA in the 669 [corrected] specimens was 32 of 50 (64%) and 530 of 619 (86%) [corrected], respectively, when compared with serum ELISA. The western blotting validation was performed on 28 subjects with positive serum and positive salivary ELISA, 28 saliva positives with negative serum, 16 saliva negatives with positive serum, and 50 doubly negative subjects. Compared with serum western blots, the sensitivity and specificity of salivary western blots was 38 of 47 (81%) and 68 of 75 (91%), respectively. Using serum ELISA as the gold standard, the sensitivity and specificity were 32 of 44 (73%) and 72 of 78 (92%), respectively, the specificity being significantly higher than salivary ELISA (p < 0.001). CONCLUSION: Salivary western blotting for IgG is useful in the diagnosis of H pylori infection and is superior to ELISA. It also permits the identification of pathogenic strains.

Blotting, Western↗

Impact of the new American Diabetes Association and World Health Organisation diagnostic criteria for diabetes on subjects from three ethnic groups living in the UK.

BACKGROUND AND AIM: The American Diabetes Association (ADA) recommends basing diabetes diagnosis on a fasting plasma glucose (FPG) of > or = 7.0 mmol/L and impaired fasting glucose (IFG) on 6.1 < or = FPG < 7.0 mmol/L. The new World Health Organisation (WHO) recommendations also adopt this FPG cut-off, but retain the oral glucose tolerance test (OGTT) where possible and the intermediate group of impaired glucose tolerance (IGT) in addition to IFG. We compare the effect of the new ADA and WHO diagnostic criteria in three ethnic groups. METHODS AND RESULTS: Three hundred and eighty whites, 340 South Asians and 347 subjects of African descent, aged 40-59 years and not known to have diabetes, were identified through South London general practices. Inevitably, the prevalence of new diabetes was lower under ADA than under WHO criteria (including post-load levels) for all three groups, falling from 5.7% overall to 3.3% (fall 2.4% 95% CI 1.6% to 3.6%). The largest fall was for South Asians from 9.1% to 5.0% (fall 4.1% 95% CI 2.2% to 6.8%). The prevalence of impaired glucose homeostasis under ADA criteria (IFG) was substantially less than under WHO criteria (IFG + IGT). Under WHO criteria, including a glucose tolerance test, there was marked variation by ethnic group in diabetes prevalence (p < 0.001) and IGT (p < 0.0001), both were most prevalent amongst South Asians. Under ADA criteria, (or new WHO criteria without OGTT) diabetes prevalence still differed significantly between groups (p < 0.01), but there was no difference in IFG prevalence (p = 0.43). CONCLUSIONS: Subjects with IGT but normal FPG are at greater risk of coronary heart disease. The new ADA definition fails to identify substantial numbers of such subjects, particularly among South Asians. Our study supports the retention of the OGTT in the new WHO criteria, particularly for South Asians.

Adult↗

Fibrinogen and factor VII levels are related to adiposity but not to fetal growth or social class in children aged 10-11 years.

Factors operating in fetal life or during childhood may be important in determining fibrinogen and factor VII concentrations in adult life, and particularly in explaining social gradients in cardiovascular disease risk. In 1994, the authors measured fibrinogen and factor VIIc levels in 641 children aged 10-11 years (61% response rate) from schools in five towns in England and Wales. Birth weight was obtained by maternal recall, and other data on measures of fetal growth were obtained from birth records. Fibrinogen levels were higher in girls (258.8 mg/dl) than in boys (245.4 mg/dl) (95% confidence interval (CI) for difference: 5.5, 21.5). Fibrinogen and factor VIIc levels were linearly related to adiposity, rising by 37.1 mg/dl (95% CI: 24.7, 49.5) and 13.0% of standard (95% CI: 6.3, 19.7), respectively, between the bottom and top quintiles of ponderal index (weight (kg)/height (m)3). Fibrinogen was independently related to heart rate (p < 0.001) and was negatively but nonsignificantly related to measures of physical activity. Factor VIIc was positively correlated with total cholesterol (p < 0.001). No relations were found with measures of fetal growth or social class. These data do not support the concept that fibrinogen or factor VII levels are determined in utero or by social factors in childhood. Adiposity and physical training appear to be the important determinants of fibrinogen and factor VII levels in childhood.

Adipose Tissue↗

Explaining variation in hospital admission rates between general practices: cross sectional study.

OBJECTIVES: To quantify the extent of the variation in hospital admission rates between general practices, and to investigate whether this variation can be explained by factors relating to the patient, the hospital, and the general practice. DESIGN: Cross sectional analysis of routine data. SETTING: Merton, Sutton, and Wandsworth Health Authority, which includes areas of inner and outer London. SUBJECTS: 209 136 hospital admissions in 1995-6 in patients registered with 120 general practices in the study area. MAIN OUTCOME MEASURES: Hospital admission rates for general practices for overall, emergency, and elective admissions. RESULTS: Crude admission rates for general practices displayed a twofold difference between the 10th and the 90th centile for all, emergency, and elective admissions. This difference was only minimally reduced by standardising for age and sex. Sociodemographic patient factors derived from census data accounted for 42% of the variation in overall admission rates; 45% in emergency admission rates; and 25% in elective admission rates. There was a strong positive correlation between factors related to deprivation and emergency, but not elective, admission rates, raising questions about equity of provision of health care. The percentage of each practice's admissions to different local hospitals added significantly to the explanation of variation, while the general practice characteristics considered added very little. CONCLUSIONS: Hospital admission rates varied greatly between general practices; this was largely explained by differences in patient populations. The lack of significant factors related to general practice is of little help for the direct management of admission rates, although the effect of sociological rather than organisational practice variables should be explored further. Admission rates should routinely be standardised for differences in patient populations and hospitals used.

Cross-Sectional Studies↗

The effects of adiposity and weight change on forced expiratory volume decline in a longitudinal study of adults.

OBJECTIVE: To investigate whether changes in anthropometric measures are related to lung function decline. DESIGN: A national 7-y follow up study in Great Britain. SUBJECTS: 3391 adults aged 18-73 y at baseline. MEASUREMENTS: The primary outcome measure was change in forced expiratory volume in one second (Delta FEV1), adjusted for age, height and sex. This was related to changes in weight, body mass index, waist circumference, hips circumference and waist to hip ratio. RESULTS: Changes in weight, body mass and waist circumference, adjusted for confounders including mean level, were all associated with changes in FEV1 (P<0.001), with all effects stronger in men than women (P<0.05). Change in waist to hip ratio was related in men (P=0.01), but not in women (P=0.34). A 10 kg weight increase induced an additional fall in FEV1 of 96 ml (95% confidence interval (95% CI 65-127 ml) in men, and 51 ml (95% CI. 27-75 ml) in women. In men, the effect increased with average weight and obesity and was more pronounced in middle age. This phenomenon was not present in women, possibly due to gender differences in weight distribution in later adult life. Smoking did not appear to influence the magnitude of effect in either sex. The detrimental effect of weight gain on FEV1 in subjects that stopped smoking between studies appeared small in comparison to the benefit of smoking cessation. CONCLUSION: Increases in adult body mass are predictors of FEV1 decline, especially among older and heavier men, where weight reduction may significantly slow lung function decline.

Adolescent↗