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D G Cook

Publications and source records attributed to D G Cook.

At least 73 records · Page 4Linked to original sources
PubMed1996

Expression and analysis of presenilin 1 in a human neuronal system: localization in cell bodies and dendrites.

Mutations in the recently identified presenilin 1 gene on chromosome 14 cause early onset familial Alzheimer disease (FAD). Herein we describe the expression and analysis of the protein coded by presenilin 1 (PS1) in NT2N neurons, a human neuronal model system. PS1 was expressed using recombinant Semliki Forest virions and detected by introduced antigenic tags or antisera to PS1-derived peptides. Immunoprecipitation revealed two major PS1 bands of approximately 43 and 50 kDa, neither of which were N-glycosylated or O-glycosylated. Immunoreactive PS1 was detected in cell bodies and dendrites of NT2N neurons but not in axons or on the cell surface. PS1 was also detected in BHK cells, where it was also intracellular and colocalized with calnexin, a marker for the rough endoplasmic reticulum. A mutant form of PS1 linked to FAD did not differ from the wild-type protein at the light microscopic level. The model system described here will enable studies of the function of PS1 in human neurons and the role of mutant PS1 in FAD.

Alzheimer Disease↗
PubMed1996

Home visiting by general practitioners in England and Wales.

OBJECTIVE: To use data from the fourth national survey of morbidity in general practice to investigate the association between home visiting rates and patients' characteristics. DESIGN: Survey of diagnostic data on all home visits by general practitioners. SETTING: 60 general practices in England and Wales. SUBJECTS: 502 493 patients visited at home between September 1991 and August 1992. MAIN OUTCOME MEASURES: Home visiting rates per 1000 patient years and home visiting ratios standardised for age and sex. RESULTS: 10.1% (139 801/1 378 510) of contacts with general practitioners took place in patients' homes. The average annual home visiting rate was 299/1000 patient years. Rates showed a J shaped relation with age and were lowest in people aged 16-24 years (103/1000) and highest in people aged > or = 85 years (3009/1000). 1.3% of patients were visited five or more times and received 39% of visits. Age and sex standardised home visiting ratios increased from 69 (95% confidence interval 68 to 70) in social class I to 129 (128 to 130) in social class V. The commonest diagnostic group was diseases of the respiratory system. In older age groups, diseases of the circulatory system was also a common diagnostic group. Standardised home visiting ratios for the 60 practices in the study varied nearly eightfold, from 28 to 218 (interquartile range 67 to 126). CONCLUSIONS: Home visits remain an important component of general practitioners' workload. As well as the strong associations between home visiting rates and patient characteristics, there were also large differences between practices in home visiting rates. A small number of patients received a disproportionately high number of home visits. Further investigation of patients with high home visiting rates may help to explain the large differences in workload between general practices and help in allocation of resources to practices.

Adolescent↗
PubMed1996

Cardiovascular risk factors in British children from towns with widely differing adult cardiovascular mortality.

OBJECTIVE: To examine whether cardiovascular risk factors differ in children from towns in England and Wales with widely differing adult cardiovascular death rates. DESIGN: School based survey conducted during 1994 in 10 towns, five with exceptionally high adult cardiovascular mortality (standardised mortality ratio 131-143) and five with exceptionally low adult cardiovascular mortality (64-75). Towns were surveyed in high-low pairs. SUBJECTS: 3415 white children aged 8-11 years with physical measurements (response rate 75%), including 1287 with blood samples (response rate 64%), of whom 515 had blood samples taken 30 minutes after a glucose load. RESULTS: Children in towns with high cardiovascular mortality were on average shorter than those in towns with low mortality (mean difference 1.2 cm; 95% confidence interval 0.3 to 2.1 cm; P = 0.02) and had a higher ponderal index (0.34 kg/m3; 0.16 to 0.52 kg/m3; P = 0.006). Mean systolic pressure was higher in high mortality towns, particularly after adjustment for height (2.0 mm Hg; 0.8 to 3.2 mm Hg; P = 0.009). Mean waist:hip ratio, total cholesterol concentration, and 30 minute post-load glucose measurements were similar in high and low mortality towns. The differences in height and blood pressure between high and low mortality towns were unaffected by standardisation for birth weight. CONCLUSIONS: The differences in height, ponderal index, and blood pressure between towns with high and low cardiovascular mortality, if persistent, may have important future public health implications. Their independence of birth weight suggests that the childhood environment rather than the intrauterine environment is involved in their development.

Adult↗
PubMed1996

Age and sex differences in the management of ischaemic heart disease.

OBJECTIVE: To investigate age and sex differences in the utilisation of hospital services for ischaemic heart disease. DESIGN: Analysis of routine mortality data and hospital activity data. SETTING: South West Thames Regional Health Authority. SUBJECTS: Residents of the South West Thames Regional Health Authority who in 1991 either died from ischaemic heart disease or were admitted to an NHS hospital in England and Wales with a main diagnosis of ischaemic heart disease. MAIN OUTCOME MEASURES: Ratio of consultant episodes to deaths from ischaemic heart disease (as a proxy measure of the utilisation of hospital care), and the percentages of consultant episodes in which further investigation (angiography or catheterisation) or revascularisation treatment (coronary artery bypass grafting or angioplasty) were carried out. RESULTS: The ratio of episodes to deaths was similar in men and women (odds ratio for men vs. women 0.96, 95% confidence intervals 0.90 to 1.03). The percentage of episodes in which further investigation was carried out was higher in men than women (odds ratio for men vs. women 1.46, 95% confidence intervals 1.25 to 1.70) as was the percentage of episodes in which revascularisation treatment was carried out (odds ratio for men vs. women 1.46, 95% confidence intervals 1.20 to 1.77). The ratio of episodes to deaths, the percentage of episodes in which further investigation was carried out, and the percentage of episodes in which revascularisation treatment was carried out all declined with age (all p values < 0.001). CONCLUSIONS: Women with ischaemic heart disease are as likely as men to be admitted to hospital, but after admission are less likely to undergo further investigation and revascularisation treatment. Elderly patients with ischaemic heart disease are less likely than younger patients to be admitted to hospital; after admission, they are also less likely to undergo further investigation and revascularisation treatment. Further research is needed to determine whether these age and sex differences in the use of hospital services are clinically justified.

Adult↗
PubMed1996

Health and social precursors of unemployment in young men in Great Britain.

OBJECTIVE: To identify health and socioeconomic factors in childhood that are precursors of unemployment in early adult life and to examine the hypothesis that young men who become unemployed are more likely to have accumulated risks to health during childhood. DESIGN: Longitudinal birth cohort study. The amount of unemployment experienced in early adult life up to age 32 years was the outcome measure used. Exposure measures to indicate vulnerability to future ill health were: height at age 7 years and the Bristol social adjustment guide (BSAG) at age 11 years, a measure of behavioural maladjustment. Socioeconomic measures were: social class at birth, crowding at age 7, qualifications attained before labour market entry, and region of residence. SETTING: Great Britain. SUBJECTS: Altogether 2256 men with complete data from the national child development study (NCDS). The NCDS has collected data on all men and women born in one week in 1958 and has followed them up using interviews, self completion questionnaires, and medical examinations at birth and at ages 7, 11, 16, 23 and 33 years. RESULTS: A total of 269 men (11.9%) experienced more than one year of unemployment between ages 22 and 32 years. Poor socioeconomic conditions in childhood and a lack of qualifications were associated with an increased risk of unemployment. Geographical region was also significant in determining the risk of unemployment. Men with short stature and poor social adjustment in childhood were more likely to experience unemployment in adult life, even after controlling for socioeconomic background, education, and parental height. These differences remained when those with chronic childhood illnesses were excluded from the analysis. The adjusted relative odds for experiencing more than one year of unemployment between ages 22 and 32 years for men who were in the top fifth of the BSAG distribution (most maladjusted) compared with those in the bottom fifth were 2.36 (95% CI 1.49, 3.73). The adjusted relative odds for experiencing more than one year of unemployment between ages 22 and 32 years for men who were in the bottom fifth of the distribution of height at age 7 years (indicating slowest growth) compared with those in the top fifth, were 2.41 (95% CI 1.43, 4.04). Adult height was not significantly associated with unemployment. CONCLUSION: The relationship between unemployment and poor health arises, in part, because men who become unemployed are more likely to have accumulated risks to health during childhood, reflected by slower growth and a greater tendency to behavioural maladjustment. Short stature in childhood is a significant indicator of poor socioeconomic circumstances in childhood and reflects earlier poor development.

Adult↗
PubMed1995

Using data from the 1991 census.

The 1991 census for England and Wales provides a substantial amount of data on demography, ethnicity, housing tenure, employment status, and other social factors for geographical areas ranging in size from enumeration districts upwards. Many in the health service and in the academic community are making use of the data in the 1991 census. However, users of census data need to be aware of the problems and limitations of these data, which include the format of the data, data modification and suppression, sampling error, and underenumeration. An important innovation of the 1991 census was that the census form included a question on the postcode of respondents; this allowed the Office of Population Censuses and Surveys to produce a postcode-enumeration district look up table which overcomes many of the problems previously encountered in trying to assign postcodes to enumeration districts. The new look up table also includes the grid reference of postcodes, and this will improve the geographical referencing of census data.

Data Collection↗
PubMed1995

Do general practitioners influence the uptake of breast cancer screening?

OBJECTIVES: To investigate the relative importance of patient and general practice characteristics in explaining variations between practices in the uptake of breast cancer screening. DESIGN: Ecological study examining variations in breast cancer screening rates among 131 general practices using routine data. SETTING: Merton, Sutton, and Wandsworth Family Health Services Authority, which covers parts of inner and outer London. MAIN OUTCOME MEASURE: Percentage of eligible women aged 50-64 who attended for mammography during the first round of screening for breast cancer (1991-1994). RESULTS: Of the 43,063 women eligible for breast cancer screening, 25,826 (60%) attended for a mammogram. Breast cancer screening rates in individual practices varied from 12.5% to 84.5%. The estimated percentage list inflation for the practices was the variable most highly correlated with screening rates (r = -0.69). There were also strong negative correlations between screening rates and variables associated with social deprivation, such as the estimated percentage of the practice population living in households without a car (r = -0.61), and with variables that measured the ethnic make-up of practice populations, such as the estimated percentage of people in non-white ethnic groups (r = -0.60). Screening rates were significantly higher in practices with a computer than in those without (59.5% v 53.9%, difference 5.6%, 95% confidence interval 1.1 to 10.2%). There was no significant difference in screening rates between practices with and without a female partner; with and without a practice nurse; and with and without a practice manager. In a forward stepwise multiple regression model that explained 58% of the variation in breast cancer screening rates, four factors were significant independent predictors (at P = 0.05) of screening rates: list inflation and people living in households without a car were both negative predictors of screening rates, and chronic illness and the number of partners in a practice were both positive predictors of screening rates. The practice with the highest screening rate (84.5%) contacted all women invited for screening to encourage them to attend for their mammogram and achieved a rate 38% higher than predicted from the regression model. Breast cancer screening rates were on average lower than cervical cancer screening rates (mean difference 14.5%, standard deviation 12.0%) and were less strongly associated with practice characteristics. CONCLUSIONS: The strong negative correlation between breast cancer screening rates and list inflation shows the importance of accurate age-sex registers in achieving high breast cancer screening rates. Breast cancer screening units, family health services authorities, and general practitioners need to collaborate to improve the accuracy of the age-sex registers used to generate invitations for breast cancer screening. The success of the practice with the highest screening rate suggests that practices can influence the uptake of breast cancer screening among their patients. Giving general practitioners a greater role in breast cancer screening, either by offering them financial incentives or by giving them clerical support to check prior notification lists and contact nonattenders, may also help to increase breast cancer screening rates.

Breast Neoplasms↗
PubMed1995

Annual night visiting rates in 129 general practices in one family health services authority: association with patient and general practice characteristics.

BACKGROUND: Rates of night visiting by general practitioners have increased steadily over the last 30 years and vary widely between general practices. AIM: An ecological study was carried out to examine night visiting rates by general practices in one family health services authority, and to determine the extent to which differences in night visiting rates between practices could be explained by patient and practice characteristics. METHOD: The study examined the variation in annual night visiting rates, based on night visit fees claimed between April 1993 and March 1994, among 129 general practices in Merton, Sutton and Wandsworth Family Health Services Authority, London. RESULTS: Practices' annual night visiting rates varied from three per 1000 to 75 per 1000 patients. The percentages of the practice population aged under five years and aged five to 14 years were both positively correlated with night visiting rates (r = 0.38 and r = 0.35, respectively), as were variables associated with social deprivation such as the estimated percentage of the practice population living in one-parent households (r = 0.24) and in households where the head of household was classified as unskilled (r = 0.20). The percentage of the practice population reporting chronic illness was also positively associated with night visiting rates (r = 0.26). The percentages of the practice population aged 35 to 44 years and 45 to 54 years were both negatively associated with night visiting rates (r = -0.34 and r = -0.31, respectively) as was the estimated list inflation for a practice (r = -0.31). There was no significant correlation between night visiting rates and the distance of the main practice surgery from the nearest hospital accident and emergency department. There was also no association between night visiting rates and permission to use a deputizing service. In a stepwise multiple regression model, the multiple correlation coefficient was 0.56 with four factors (percentage of the practice population aged under five years, percentage aged 35-44 years, percentage who were chronically ill and estimated list inflation) explaining 32% of the variation in night visiting rates. CONCLUSION: Only about one third of the variation in night visiting rates between practices could be explained by patient and practice variables derived from routine data. Population-based research using data collected on individual patients and practices is required to improve current understanding of the patient and practice characteristics that influence the demand for night visits and of why night visiting rates vary so widely between practices.

Adolescent↗
PubMed1994

Using patient and general practice characteristics to explain variations in cervical smear uptake rates.

OBJECTIVES: To produce practice and patient variables for general practices from census and family health services authority data, and to determine the importance of these variables in explaining variation in cervical smear uptake rates between practices. DESIGN: Population based study examining variations in cervical smear uptake rates among 126 general practices using routine data. SETTING: Merton, Sutton, and Wandsworth Family Health Services Authority, which covers parts of inner and outer London. MAIN OUTCOME MEASURE: Percentage of women aged 25-64 years registered with a general practitioner who had undergone a cervical smear test during the five and a half years preceding 31 March 1992. RESULTS: Cervical smear uptake rates varied from 16.5% to 94.1%. The estimated percentage of practice population from ethnic minority groups correlated negatively with uptake rates (r = -0.42), as did variables associated with social deprivation such as overcrowding (r = -0.42), not owning a car (r = -0.41), and unemployment (r = -0.40). Percentage of practice population under 5 years of age correlated positively with uptake rate (r = 0.42). Rates were higher in practices with a female partner than in those without (66.6% v 49.1%; difference 17.5% (95% confidence interval 10.5% to 24.5%)), and in computerised than in non-computerised practices (64.5% v 50.5%; 14.0% (6.4% to 21.6%)). Rates were higher in larger practices. In a stepwise multiple regression model that explained 52% of variation, five factors were significant predictors of uptake rates: presence of a female partner; children under 5; overcrowding; number of women aged 35-44 as percentage of all women aged 25-64; change of address in past year. CONCLUSIONS: Over half of variation in cervical smear uptake rates can be explained by patient and practice variables derived from census and family health services authority data; these variables may have a role in explaining variations in performance of general practices and in producing adjusted measures of practice performance. Practices with a female partner had substantially higher uptake rates.

Adult↗
PubMed1994

Loss of employment and mortality.

OBJECTIVE: To assess effect of unemployment and early retirement on mortality in a group of middle aged British men. DESIGN: Prospective cohort study (British Regional Heart Study). Five years after initial screening, information on employment experience was obtained with a postal questionnaire. SETTING: One general practice in each of 24 towns in Britain. SUBJECTS: 6191 men aged 40-59 who had been continuously employed for at least five years before initial screening in 1978-80: 1779 experienced some unemployment or retired during the five years after screening, and 4412 remained continuously employed. MAIN OUTCOME MEASURE: Mortality during 5.5 years after postal questionnaire. RESULTS: Men who experienced unemployment in the five years after initial screening were twice as likely to die during the following 5.5 years as men who remained continuously employed (relative risk 2.13 (95% confidence interval 1.71 to 2.65). After adjustment for socioeconomic variables (town and social class), health related behaviour (smoking, alcohol consumption, and body weight), and health indicators (recall of doctor diagnoses) that had been assessed at initial screening the relative risk was slightly reduced, to 1.95 (1.57 to 2.43). Even men who retired early for reasons other than illness and who appeared to be relatively advantaged and healthy had a significantly increased risk of mortality compared with men who remained continuously employed (relative risk 1.87 (1.35 to 2.60)). The increased risk of mortality from cancer was similar to that of mortality from cardiovascular disease (adjusted relative risk 2.07 and 2.13 respectively). CONCLUSIONS: In this group of stably employed middle aged men loss of employment was associated with an increased risk of mortality even after adjustment for background variables, suggesting a causal effect. The effect was non-specific, however, with the increased mortality involving both cancer and cardiovascular disease.

Adult↗
PubMed1994

Passive exposure to tobacco smoke in children aged 5-7 years: individual, family, and community factors.

OBJECTIVE: To examine the importance of parental smoking on passive exposure to tobacco smoke in children and the social and geographical patterns of exposure. DESIGN: Cross sectional study. SETTING: Schools in 10 towns in England and Wales; five towns with high adult cardiovascular mortality and five with low rates. SUBJECTS: 4043 children aged 5-7 years of European origin. MAIN OUTCOME MEASURES: Salivary cotinine concentration and parents self reported smoking habits. RESULTS: 1061 (53.0%) children were exposed to cigarette smoke at home or by an outside carer. Geometric mean cotinine rose from 0.29 (95% confidence interval 0.28 to 0.31) ng/ml in children with no identified exposure to 4.05 (3.71 to 4.42) ng/ml in households where both parents smoked and 9.03 (6.73 to 12.10) ng/ml if both parents smoked more than 20 cigarettes a day. The effect of mothers' smoking was greater than that of fathers', especially at high levels of consumption. After adjustment for known exposures geometric mean cotinine concentrations rose from 0.52 ng/ml in social class I to 1.36 ng/ml in social class V (P < 0.0001); and were doubled in high mortality towns compared with the low mortality towns (P = 0.002). In children with no identified exposure similar trends by social class and town were observed and the cotinine concentrations correlated with the prevalence of parental smoking, both between towns (r = 0.69, P = 0.02) and between schools within towns (r = 0.50, P < 0.001). CONCLUSIONS: Mothers' smoking is more important that fathers' despite the lower levels of smoking by mothers. Children not exposed at home had low cotinine concentration, the level depending on the prevalence of smoking in the community.

Age Factors↗
PubMed1994

Binding of human immunodeficiency virus type I (HIV-1) gp120 to galactosylceramide (GalCer): relationship to the V3 loop.

The primary receptor for the human immunodeficiency virus (HIV) is the CD4 molecule. However, a large body of evidence has demonstrated that some cells that do not express the CD4 receptor can be infected by HIV-1 and HIV-2, indicating that an alternative mechanism of infection must exist for some cell types. Recently it was reported that antibodies against the glycosphingolipid, galactosylceramide (Gal beta 1-1'Cer;GalCer), blocked infection of several CD4 negative cell lines derived from the brain and colon. The hypothesis that GalCer might be involved in the process of HIV entry into these cells was further supported by the finding that recombinant gp120 bound GalCer with high affinity in a high performance thin layer chromatography (HPTLC) binding assay. We have examined the interactions between GalCer and gp120, and found that the oligosaccharides that constitute a large proportion of the molecular mass of this glycoprotein are not involved in binding to this glycolipid. Furthermore, using a panel of monoclonal and monospecific antibodies we have determined that gp120 binds GalCer, and the related molecule 3' sulfo galactosylceramide (sulfatide), at a site that is conformationally close to the its principal neutralizing domain (V3 loop) or at the V3 loop itself.

Animals↗
PubMed1994

Expression of foreign proteins in a human neuronal system.

The NT2N cell system offers an attractive way to overcome some of the technical limitations inherent in working with primary neuronal cultures. In particular, it is possible to obtain large quantities of neurons with which to perform biochemical experiments, and the growth of neurites can be synchronized and controlled by varying the substrate on which the cells grow. In addition, because the differentiated NT2N neurons are derived from a mitotically active precursor cell line in vitro, it is possible to employ a variety of techniques, that are not otherwise available when working directly with postmitotic neurons, to obtain expression of foreign proteins. Because they are fully polarized, NT2N cells offer a way to study protein sorting to axons and dendrites at both the biochemical and the morphological level. Further characterization of NT2N cells is underway, and more efficient ways to obtain expression of foreign proteins will no doubt be found.

Base Sequence↗
PubMed1994

A comparison of bone mineral density between Caucasian, Asian and Afro-Caribbean women.

1. We analysed the lumbar spine (L2-L4) and femoral neck bone mineral density results of Caucasian (n = 2232), Asian (Indian sub-continent) (n = 153) and Afro-Caribbean (n = 102) women referred for bone densitometry over a 30 month period. To assess the risk of osteoporosis, the results of Caucasian and Asian women were compared with those of a reference Caucasian population supplied by Lunar. 2. Subject characteristics were similar in all three groups, other than expected ethnic differences in stature and weight. We found that lumbar spine and femoral neck bone mineral density in Caucasians was lower than in Afro-Caribbeans, but higher than in Asians. Consistent with this, bone mineral density was also lower in Asians as compared with the reference Caucasian population, both at the lumbar spine and femoral neck. As a consequence, a higher proportion of Asian women were classified as being at increased risk of osteoporosis than Caucasian women. 3. Since ethnic differences in skeletal size might influence bone mineral density, we also obtained values for bone mineral content in Caucasian and Asian women that were corrected for projected skeletal area, and weight and years since menopause, using regression equations derived from the Caucasian study population. After this analysis, the difference in bone mineral content between Caucasians and Asians at the lumbar spine disappeared, while that at the femoral neck persisted. 4. We conclude that the assessment of risk of osteoporosis in Asian women by comparing bone mineral density with a reference Caucasian population may have limited validity because of the influence of skeletal size on such measurements.

Absorptiometry, Photon↗
PubMed1994

Chest illness in infancy and chronic respiratory disease in later life: an analysis by month of birth.

BACKGROUND: Cohorts born at different times of year differ in their risk of exposure to seasonal respiratory infections in early life, but are likely to have similar socioeconomic status and lifestyle thereafter. METHODS: We investigated the long-term consequences of acute chest illness in infancy for later development of chronic respiratory disease by analysing variations by month of birth in hospital admissions for respiratory illness (total n = 49,866), chronic respiratory symptoms and ventilatory function among British school children (n = 11,482) and middle-aged adults (total n = 55,829). RESULTS: Admission for bronchiolitis in the first year of life was three times more common for infants born September to November (autumn) than those born March to May, yet people born in the autumn experienced fewer respiratory symptoms and had better ventilatory function. In two surveys of middle-aged men, forced expiratory volume in one second/forced ventilatory capacity (FEV1/FVC) was significantly (P = 0.025) higher among autumn births. Hospital admissions for chronic bronchitis/emphysema and pneumonia varied little with season of birth. Admissions for asthma were significantly (P < 0.05) more common among children and young adults born in the autumn. CONCLUSIONS: These findings do not support the hypothesis of a causal link between chest illness in infancy and the later development of chronic bronchitis and emphysema. The variation in asthma admissions with month of birth deserves further investigation.

Adult↗