BSR guidelines on standards of care for persons with rheumatoid arthritis.
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Adolescent↗
Biomedical subjects
M Shipley
Publications and source records attributed to M Shipley.
Gender differences in the relationship of partner's social class to behavioural risk factors and social support in the Whitehall II study.
In most countries health inequality in women appears to be greater when their socio-economic position is measured according to the occupation of male partners or spouses than the women's own occupations. Very few studies show social gradients in men's health according to the occupation of their female partners. This paper aims to explore the reasons for the differences in social inequality in cardiovascular disease between men and women by analysing the associations between own or spouses (or partners) socio-economic position and a set of risk factors for prevalent chronic diseases. Study participants were married or cohabiting London based civil servants included in the Whitehall II study. Socio-economic position of study participants was measured according to civil service grade; socio-economic position of the spouses and partners according to the Registrar General's social class schema. Risk factors were smoking, diet, exercise, alcohol consumption, and measures of social support. In no case was risk factor exposure more affected by the socio-economic position of a female partner than that of a male study participant. Wives' social class membership made no difference at all to the likelihood that male Whitehall participants were smokers, or took little exercise. Female participants' exercise and particularly smoking habit was, in contrast, related to their spouse's social class independently of their own grade of employment. Diet quality was affected equally by the socio-economic position of both male and female partners. Unlike the behavioural risk factors, the degree of social support reported by women participants was in general not strongly negatively affected by their husband or partner being in a less advantaged social class. However, non-employment in the husband or partner was associated with relatively lower levels of positive, and higher negative social support, while men with non-working wives or partners were unaffected. Studying gender differences in health inequality highlights some of the problems in health inequality research more broadly. We are brought face to face with the fact that the development of conceptual models that can be applied consistently to aetiology in both men and women are still at an early stage of development. Closer attention is needed to the different processes behind material power and 'emotional power' within the household when investigating gender differences in health and risk factors.
Adult↗
Unique neuronal tracers show migration and differentiation of SVZ progenitors in organotypic slices.
Continual neurogenesis in the subventricular zone (SVZ) of postnatal and adult mammalian forebrain has been well documented, but the mechanisms underlying cell migration and differentiation in this region are poorly understood. We have developed novel in vivo and in vitro methods to investigate these processes. Using stereotaxic injections of a variety of tracers/tracker [Cholera Toxin beta subunit (CTb-), Fluorogold (FG), and Cell Tracker Green (CTG)], we could efficiently label SVZ cells. Over several days, labeled cells migrate along the rostral migratory stream (RMS) to their final differentiation site in the olfactory bulb (OB). The compatibility of these tracers/trackers with immunohistochemistry allows for cell labeling with multiple dyes (e.g., CTb and CTG) and/or specific cell antigens. To investigate the dynamics of migration we labeled SVZ progenitor cells with small injections of CTG and monitored the movements of individual cells in fresh parasagittal brain slices over several hours using time-lapse confocal microscopy. Our observations suggest that tangential cell migration along the RMS occurs more rapidly than radial cell migration into the OB granule cell layer. To investigate migration over longer time periods, we developed an in vitro organotypic slice in which labeled SVZ progenitors migrate along the RMS and differentiate within the OB. The phenotypic characteristics of these cells in vitro were equivalent to those observed in vivo. Taken together, these methods provide useful tools investigating cell migration and differentiation in a preparation that maintains the anatomical organization of the RMS.
Animals↗
Opinions and experiences in general practice on osteoporosis prevention, diagnosis and management.
We determined to survey the general practice population regarding their attitudes to and knowledge of osteoporosis as a baseline prior to publication of national guidelines for the management of osteoporosis. All 2515 general practitioners registered in the 10 Health Authorities of the North Thames region, London, UK were surveyed by a postal questionnaire. Responses relating to epidemiology, public health and education on osteoporosis were analyzed. The overall response was 1153 (46%). General practitioners who responded were younger, predominantly female and in group practice. There is considerable awareness of the importance of preventing osteoporosis. General practitioners are active in identifying groups at risk, particularly those who are aged 40 years and older. A prevention strategy for osteoporosis is viewed as effective. However, two thirds of general practitioners remain unconvinced about the efficacy of drug therapy. Education on osteoporosis is considered inadequate. General practitioners would welcome further information on management issues and access to osteoporosis services. In conclusion, educational initiatives will be important both at undergraduate and postgraduate levels to increase awareness and knowledge of osteoporosis. General practitioners are aware of the public health impact of this condition and express a preference for educational material of direct relevance to the care of their patients. Therefore better cooperation between primary and secondary care should lead to ways of breaking down barriers to change in clinical practice and promoting fully integrated care of patients with osteoporosis.
Attitude of Health Personnel↗
Relative contribution of early life and adult socioeconomic factors to adult morbidity in the Whitehall II study.
STUDY OBJECTIVE: To determine the relative contribution of adult compared with early life socioeconomic status as predictors of morbidity attributable to coronary heart disease (CHD), chronic bronchitis and depression in the Whitehall II study of British civil servants. DESIGN: Prospective observational study with mean 5.3 years (range 3.7-7.6) follow up. SETTING: 20 civil service departments originally located in London. PARTICIPANTS: 6895 male and 3413 female office-based civil servants aged 35-55 years at baseline. OUTCOME MEASURES: New cases at follow up of CHD, chronic bronchitis and depression defined using validated questionnaires. MAIN RESULTS: Employment grade was inversely associated with CHD, chronic bronchitis and depression in men (odds ratio per unit decrease in grade 1.30, 1.44 and 1.20 respectively). Employment grade was strongly related to father's social class. Chronic bronchitis, in women, and depression, in men, were more common among those with fathers of higher social class. When mutual adjustment was made for father's social class, grade at entry to the civil service and current grade, the strongest effects on adult morbidity were found for current grade. Among participants in whom neither parent had died < or =70 years of age the inverse association with adult SES was maintained. CONCLUSIONS: Adult socioeconomic status was a more important predictor of morbidity attributable to coronary disease, chronic bronchitis and depression than measures of social status earlier in life. In this population, the importance of social circumstances early in life may be in the way they influence employment and social position and thus exposures in adult life.
Adult↗
Psychosocial risk factors for coronary disease in White, South Asian and Afro-Caribbean civil servants: the Whitehall II study.
BACKGROUND: Psychosocial factors are associated with the etiology and prognosis of coronary heart disease (CHD) in White populations; however, previous studies have not examined the distribution of psychosocial factors in ethnic groups with coronary rates higher (South Asian) and lower (Afro-Caribbean) than those of Whites. STUDY OBJECTIVE: To determine whether ethnic differences in psychosocial risk factors parallel those in CHD mortality. DESIGN: Cross-sectional survey. SETTING: 20 civil service departments in London. PARTICIPANTS: 8973 White, 577 South Asian, and 360 Afro-Caribbean office-based civil servants, aged 35-55 years. OUTCOME MEASURES: Minor psychiatric morbidity (General Health Questionnaire), social supports (marital status, social networks, negative aspects of support, confiding/emotional support, social support at work), psychosocial work characteristics (job control, effort-reward imbalance), hostility levels and presence of Type A personality. RESULTS: South Asians, compared to Whites, had more depression, higher negative supports, less social support at work, less job control, more effort-reward imbalance and higher levels of hostility, when adjusting for age and sex. Afro-Caribbeans, compared to Whites, had lower minor psychiatric morbidity and lower Type A scores. The remaining psychosocial factors showed either no ethnic differences in distribution, or differences contrary to those predicted from coronary event rates. Adjustment for employment grade made little difference to these associations. CONCLUSION: Among South Asians, the majority of whom were Indian, the distribution of psychosocial factors was consistent with ethnic differences in coronary rates; the pattern for Afro-Caribbeans was less consistent. Further research is required to test the extent to which psychosocial factors predict coronary events within ethnic groups and to characterize better psychosocial measures.
Adult↗
Identification of Staphylococcus aureus enterotoxins A and B genes by PCR-ELISA.
We developed PCR-enzyme linked immunosorbent (ELISA) assays to detect Staphylococcus aureus enterotoxins A and B genes. The assays use internal biotin-labelled oligonucleotides as capture probes for immobilizing and subsequently detecting target sequences on microtiter plates. The detection limits of the PCR-ELISAs were approximately 250 gene copies, versus 2500 gene copies by agarose gel analysis. The sensitivity of the assays, as determined from a reference panel of 46 coded samples that included DNA purified from 31 different bacterial species and strains, SEA and SEB plasmid controls, and no-template controls was 100%. No cross-reactivity was observed with DNA from non-staphylococcal species. Using 27 clinical isolates of S. aureus, the SEA PCR-ELISA identified the enterotoxin A (sea) gene in 26 samples, and the SEB PCR-ELISA identified the enterotoxin B (seb) gene in all 27 samples. Compared with conventional antigen capture ELISAs for SEA and SEB toxins, the PCR-ELISAs showed overall superior detection limits. The sensitivity and specificity levels of the SEA PCR-ELISA and the SEA toxin ELISA were comparable within their respective detection thresholds, but the sensitivity and specificity of the SEB PCR-ELISA was much greater than that of SEB toxin ELISA.
Bacteria↗
Impact of socioeconomic status on coronary mortality in people with symptoms, electrocardiographic abnormalities, both or neither: the original Whitehall study 25 year follow up.
OBJECTIVES: To determine the impact of socioeconomic status (SES) on coronary heart disease (CHD) mortality in people with and without prevalent CHD at baseline. DESIGN: Cohort study with 25 year follow up; prevalent CHD was defined by Q, ST or T wave electrocardiographic (ECG) abnormalities or symptoms (defined by the Rose chest pain questionnaire and self reported doctor diagnosis) or both. SES was defined by four civil service employment grades. SETTING: London. PARTICIPANTS: 17 907 male civil servants aged 40-69 years. MAIN OUTCOME MEASURES: CHD mortality (n=2695 deaths). RESULTS: The lowest versus highest employment grade was associated with increased CHD mortality (age adjusted hazard ratio 1.56 (95% CI 1.2, 2.1)), prevalence of symptoms and, among symptomatic participants only, the prevalence of Q, ST or T abnormalities. Thirty one per cent of CHD deaths occurred in participants with prevalent CHD at baseline. Among participants without Q, ST or T abnormality employment grade was associated with CHD mortality; the hazard ratios (lowest v highest grade) adjusted for age, systolic and diastolic blood pressure were 1.72 (95% CI 1.4, 2.1) for asymptomatic and 1.52 (95% CI 1.1, 2.1) for symptomatic participants; among participants with Q, ST or T abnormality the corresponding hazard ratios were 1.46 (95% CI 0.7, 2.9) and 1.14 (95% CI 0.6, 2.0) respectively. CONCLUSIONS: SES was inversely associated with CHD mortality in civil servants with and without prevalent CHD at baseline. Further distinguishing the relative contribution of SES to the initiation and progression of CHD requires repeated measures studies of pre-clinical and clinical measures of CHD.
Adult↗
Re-survey of the Whitehall study of London civil servants: changes in risk factors for cardiovascular disease during 29 years of follow-up.
BACKGROUND: Substantial uncertainty persists about the relevance of blood pressure and cholesterol to the risk of cardiovascular disease in the elderly. OBJECTIVE: To investigate the determinants of cardiovascular risk in old age, and the relevance of such risk factors when recorded in middle and old age. METHODS: A re-survey in 1997 of 8537 survivors of a cohort of men who were originally examined in 1967-1970 when aged 40-69 years. RESULTS: Completed questionnaires were received from 7050 (82%) of the survivors, and blood pressure and blood samples from 5427 (64%). The response rate declined with increasing age, was inversely related to markers of socioeconomic status in 1967-70 and in 1997, and was lower in those who had been current smokers or had a higher blood pressure level in 1967-70. After excluding those with reported cardiovascular disease (25% of respondents), the mean levels of total cholesterol and apolipoprotein B were lower in older age groups, whereas apolipoprotein A1 levels did not vary much with age. Among those with risk factors recorded both in 1967-70 and 1997, the prevalence of smoking had declined by two-thirds (32% in 1970 and 12% in 1997), the prevalence of diabetes had increased (0.3% versus 4.5%), and the mean systolic blood pressure had increased by 16 mmHg (130 versus 146 mmHg), but the diastolic blood pressure had not changed materially (80 versus 81 mmHg), and the measured levels of total cholesterol had increased by 0.5 mmol/l (although that change may be artefactual). CONCLUSION: Follow-up of vital status in this cohort should permit an assessment of the relevance of risk factors recorded in middle and old age to cardiovascular disease in old age.
Adult↗
Detection of Francisella tularensis in infected mammals and vectors using a probe-based polymerase chain reaction.
We investigated the use of a TaqMan 5' nuclease assay (5NA) directed against the Francisella tularensis outer membrane protein (Fop) gene and a polymerase chain reaction-enzyme immunoassay (PCR-EIA) directed against the tul 4 gene for detection of this organism in experimentally infected mice and in field-collected tick vectors. We also evaluated the use of specially formulated filter paper (FTA) for rapid sample preparation. The 5NA had a detection limit of 1 pg of genomic DNA (<100 colony-forming units) and could be completed within several hours. The PCR-EIA could detect 1 pg of genomic DNA and 10 attograms (ag) (22 copies) of cloned insert, but takes longer to perform. Both assays were genus-specific, and successfully detected F. tularensis in mouse tissues (5NA) and in tick extracts (PCR-EIA). The FTA paper provided inexpensive, rapid, template preparation for the tick extracts, mouse tissues, and DNA obtained from clinical specimens. These probe-based assays have the potential to provide rapid, real-time/high-throughput molecular diagnostics in field situations.
Animals↗
Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies.
In prospective studies, disease rates during follow-up are typically analyzed with respect to the values of factors measured during an initial baseline survey. However, because of "regression dilution," this generally tends to underestimate the real associations of disease rates with the "usual" levels of such risk factors during some particular exposure period. The "regression dilution ratio" describes the ratio of the steepness of the uncorrected association to that of the real association. To assess the relevance of the usual value of a risk factor during particular exposure periods (e.g., first, second, and third decades) to disease risks, regression dilution ratios can be derived by relating baseline measurements of the risk factor to replicate measurements from a reasonably representative sample of study participants after an interval equivalent to about the midpoint of each exposure period (e.g., at 5, 15, and 25 years, respectively). This report illustrates the impact of this time interval on the magnitude of the regression dilution ratios for blood pressure and blood cholesterol. The analyses were based on biennial remeasurements over 30 years for participants in the Framingham Study (Framingham, Massachusetts) and a 26-year resurvey for a sample of men in the Whitehall Study (London, England). They show that uncorrected associations of disease risk with baseline measurements underestimate the strength of the real associations with usual levels of these risk factors during the first decade of exposure by about one-third, the second decade by about one-half, and the third decade by about two-thirds. Hence, to correct appropriately for regression dilution, replicate measurements of such risk factors may be required at varying intervals after baseline for at least a sample of participants.
Adult↗
Myocyte loss in chronic heart failure.
This study examined whether or not there is progressive loss of individual myocytes in established heart failure, accounting for the progressive left ventricular dysfunction; whether such loss is by necrosis or apoptosis; and whether such loss is more pronounced in ischaemic heart disease or idiopathic dilated cardiomyopathy. Tissue for patients undergoing cardiac transplantation for clinical end-stage heart disease was used. The clinical diagnosis was not known to the observer at the time of analysis. Indices of potential myocyte loss were: detection of apoptotic nuclei in situ, using the TUNEL method, immunohistochemistry for CD120a, CD120b, CD95, perforin and granzyme B; binding of C9 complex; and lipofuscin deposition within macrophages. Interstitial macrophages and T cells and their relationship to myocyte loss were also examined. There is indeed low grade myocyte loss in chronic heart failure, but there was no difference between the disease groups; rather, there was marked patient-to-patient variation within each category. Thus in chronic heart failure myocyte loss does occur, and both necrosis and apoptosis contribute to this loss, irrespective of the underlying nature of the disease. Any mechanism which accounts for myocyte loss must be common to both conditions, rather than specific for a pre-operative diagnosis.
Adult↗
Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure.
Cardiac rupture is a fatal complication of acute myocardial infarction lacking treatment. Here, acute myocardial infarction resulted in rupture in wild-type mice and in mice lacking tissue-type plasminogen activator, urokinase receptor, matrix metalloproteinase stromelysin-1 or metalloelastase. Instead, deficiency of urokinase-type plasminogen activator (u-PA-/-) completely protected against rupture, whereas lack of gelatinase-B partially protected against rupture. However, u-PA-/- mice showed impaired scar formation and infarct revascularization, even after treatment with vascular endothelial growth factor, and died of cardiac failure due to depressed contractility, arrhythmias and ischemia. Temporary administration of PA inhibitor-1 or the matrix metalloproteinase-inhibitor TIMP-1 completely protected wild-type mice against rupture but did not abort infarct healing, thus constituting a new approach to prevent cardiac rupture after acute myocardial infarction.
Animals↗
Are risk factors for atherothrombotic disease associated with back pain sickness absence? The Whitehall II Study.
STUDY OBJECTIVE: To explore the previously stated hypothesis that risk factors for atherothrombotic disease are associated with back pain. DESIGN: Prospective (mean of four years of follow up) and retrospective analyses using two main outcome measures: (a) short (< or = 7 days) and long (> 7 days) spells of sickness absence because of back pain reported separately in men and women; (b) consistency of effect across the resulting four duration of spell and sex cells. SETTING: 14 civil service departments in London. PARTICIPANTS: 3506 male and 1380 female white office-based civil servants, aged 35-55 years at baseline. MAIN RESULTS: In age adjusted models, low apo AI was associated with back pain across all four duration-sex cells and smoking was associated across three cells. Six factors were associated with back pain in two cells: low exercise and high BMI, waist-hip ratio, triglycerides, insulin and Lp(a). On full adjustment (for age, BMI, employment grade and back pain at baseline), each of these factors retained a statistically significant effect in at least one duration-sex cell. Triglycerides were associated with short and long spells of sickness absence because of back pain in men in fully adjusted models with rate ratios (95% confidence intervals) of 1.53 (1.1, 2.1) and 1.75 (1.0, 3.2) respectively. There was little or no evidence of association in age adjusted models with: fibrinogen, glucose tolerance, total cholesterol, apoB, hypertension, factor VII, von Willebrand factor, electrocardiographic evidence of coronary heart disease and reported angina. CONCLUSIONS: In this population of office workers, only modest support was found for an atherothrombotic component to back pain sickness absence. However, the young age of participants at baseline and the lack of distinction between different types of back pain are likely to bias the findings toward null. Further research is required to ascertain whether a population sub-group of atherothrombotic back pain can be identified.
Absenteeism↗
Managing the painful shoulder.
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Diagnosis, Differential↗
Height and mortality from cancer among men: prospective observational study.
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Adult↗
Is cardiothoracic ratio in healthy middle aged men an independent predictor of coronary heart disease mortality? Whitehall study 25 year follow up.
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Administrative Personnel↗
Cardiothoracic ratio and relative heart volume as predictors of coronary heart disease mortality. The Whitehall study 25 year follow-up.
AIM: To examine the association of radiographic measures of heart size with mortality from coronary heart disease. METHODS AND RESULTS: One thousand, one hundred and ninety-one male civil servants aged 40-69 years were followed-up for mortality over 25 years in relation to cardiothoracic ratio and relative heart volume. A high cardiothoracic ratio and relative heart volume predicted coronary (n = 196 deaths) and all-cause mortality, but not respiratory or malignant mortality. After adjustment for age, systolic and diastolic blood pressure, the highest (> or = 0.47) compared to the lowest quintile of the cardiothoracic ratio (< 0.40) was associated with a rate ratio of 1.84 (95% CI 1.14-2.97) for the effect on coronary heart disease mortality. Further adjustment for heart rate, smoking, cholesterol, angina and ECG ischaemia had little effect, reducing the rate ratio to 1.65 (95% CI 1.01-2.70). Similar rate ratios were observed for relative heart volume. CONCLUSIONS: Cardiothoracic ratio within the range considered 'normal' in clinical practice predicted coronary heart disease mortality independent of established coronary heart disease risk factors. The relative heart volume, which uses measurements from the lateral as well as the posteroanterior chest X-ray, did not predict coronary heart disease any better than the cardiothoracic ratio. The extent to which left ventricular mass and systolic dysfunction-- pathophysiological correlates of the cardiothoracic ratio and relative heart volume--are independent risk factors for coronary heart disease should be further investigated.
Adult↗