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Biomedical subjects

E Brunner

Publications and source records attributed to E Brunner.

At least 55 records · Page 3Linked to original sources
PubMed1999

A prospective, randomized, sequential, crossover trial of large-volume versus normal-volume leukapheresis procedures: effect on progenitor cells and engraftment.

BACKGROUND: The influence of leukapheresis size on the number of harvested peripheral blood progenitor cells is still unclear. A prospective randomized crossover trial was thus performed, to evaluate the effect of large-volume leukapheresis (LVL) versus normal-volume leukapheresis (NVL) on progenitor cells and engraftment in 26 patients with breast cancer and 15 patients with non-Hodgkin's lymphoma who were eligible for peripheral blood progenitor cell transplantation. STUDY DESIGN AND METHODS: Patients were randomly assigned to undergo either LVL on Day 1 and on Day 2 or vice versa. The number of progenitor cells was evaluated in the harvest and before and after leukapheresis in the peripheral blood. RESULTS: The number of harvested CD34+ cells (4.8 x 10(6) vs. 3.4 x 10(6)/kg body weight, p < 0.001) and colony-forming units-granulocyte-macrophage (3.1 x 10(5) vs. 2.4 x 10(5)/kg body weight, p = 0.0026) was significantly higher for LVL procedures than for NVL procedures. The median extraction efficacy, defined as the difference between the yield in the harvest and the decrease in the total number of CD34+ cells in peripheral blood during leukapheresis, was significantly (p < 0.0001) higher for LVL than for NVL (2.6 x 10(8) and 8 x 10(7), respectively). In patients with breast cancer, the median amount of CD34+ cells in the harvest and the median extraction efficacy were higher for LVL than for NVL (p < 0.0001). This was not found for patients with non-Hodgkin's lymphoma. CONCLUSION: LVL results in a higher yield of CD34+ cells and colony-forming units-granulocyte-macrophage than NVL, but only in patients with breast cancer and with high numbers of CD34+ cells in the peripheral blood before leukapheresis.

Adult↗
PubMed1999

Antidepressant action of sulpiride. Results of a placebo-controlled double-blind trial.

The purpose of this multicenter, randomized, double-blind, placebo-controlled parallel-group comparative study was to prove the efficacy and tolerance of sulpiride (150-300 mg) against placebo in mild to moderate depressive syndrome. The primary criterion of efficacy was the course of the HAMD total score from day 1 to day 42, compared between the two treatment groups. The duration of the treatment was six weeks, preceded by a one-week placebo run-in phase. The HAMD, CGI and KUSTA scores were determined, the tolerance assessed, and the laboratory parameters and serum prolactin levels determined before, during and at the end of the trial. 177 outpatients aged from 18 to 70 years with mild to moderate depressive syndrome (ICD-10: F32.0, F32.1, F33.0, F33.1) and a score of 18-27 points on the 21-item HAMD scale were randomized, 171 of whom (sulpiride: n=83; placebo: n=88) were included in the intention-to-treat analysis. All the baseline data recorded for the two groups displayed comparable values. The decrease of the HAMD score between day 1 and day 42 yielded a difference of 2.5 points in favour of the sulpiride group. This difference is statistically significant (p = 0.0007). The evaluations of the cases treated for at least 14 days or for 42 days (per protocol) showed consistent values. The analysis of the CGI values showed similarly distinct and clinically relevant differences for sulpiride in comparison with placebo. The evaluation of the KUSTA scores yielded mostly comparable values for the two groups. Adverse events occurred with about the same type and frequency in both groups, with severe adverse events occurring only in two placebo patients. The laboratory parameters revealed no significant differences between the treatment groups, with the exception of prolactin which moderately exceeded the range of normal in 50% of the patients treated with sulpiride. This trial proved that sulpiride is effective and well-tolerated when given in a mean dose of 181 mg per day for mild and moderate depression.

Adult↗
PubMed1999

When does cardiovascular risk start? Past and present socioeconomic circumstances and risk factors in adulthood.

STUDY OBJECTIVES: To compare associations of childhood and adult socioeconomic position with cardiovascular risk factors measured in adulthood. To estimate the effects of adult socioeconomic position after adjustment for childhood circumstances. DESIGN: Cross sectional survey, using the relative index of inequality method to compare socioeconomic differences at different life stages. SETTING: The Whitehall II longitudinal study of men and women employed in London offices of the Civil Service at study baseline in 1985-88. PARTICIPANTS: 4774 men and 2206 women born in the period 1930-53 who were administered questions on early socioeconomic circumstances. MAIN RESULTS: Adult occupational position (employment grade) was inversely associated (high status-low risk) with current smoking and leisure time physical inactivity, with waist/height, and with metabolic risk factors HDL cholesterol, triglycerides, post-load glucose and fibrinogen. Associations of these variables with childhood socioeconomic position (father's Registrar General Social Class) were weaker or absent, with the exception of smoking in women. Childhood social position was associated with adult weight in both sexes and with current smoking, waist/height, HDL cholesterol and fibrinogen in women. Height, a measure of health capital or constitution, was weakly linked with father's social class and more strongly linked with own employment grade. The combination of childhood disadvantage (low father's class) together with a low status clerical occupation in men was particularly associated with higher body mass index as an adult (interaction test p < 0.001). Adjustment for earlier socioeconomic position--using father's class and own education level simultaneously--did not weaken the effects of adult socioeconomic position, except in the case of smoking in women, when the grade effect was reduced by 59 per cent. CONCLUSIONS: Cardiovascular risk factors in adulthood were in general more strongly related to adult than to childhood socioeconomic position. Among women but not men there was a strong but unexplained link between father's class and adult smoking habit. In both sexes degree of obesity was associated with both childhood and adulthood social position. These findings suggest that the socially patterned accumulation of health capital and cardiovascular risk begins in childhood and continues, according to socioeconomic position, during adulthood.

Adult↗
PubMed1999

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↗
PubMed1999

[Antioxidants and cardiovascular diseases in the Czech population].

The authors studied the possible association between plasma antioxidants and the high rates of cardiovascular diseases in the Czech Republic. The report has three parts. First, plasma antioxidants levels were compared in a random sample of population of two Czech districts (70 men and 66 women) and in British civil servants (246 men and I 12 women). Second, plasma antioxidants were compared in random samples of men aged 45-64 in Pardubice (Czech Republic, n = 185) and Augsburg (Bavaria, n = 142). Both Breat Britain and Bavaria have substantially lower mortality from cardiovascular disease than the Czech Republic. Third, a case control study examined the relation between low levels of plasma antioxidants and the risk of non-fatal myocardial infarction (52 cases and 144 controls, all males). Blood samples were taken, stored and analysed under strictly standardised conditions. Geometric means of beta-carotene, alpha-tocopherol and the alpha-tocopherol/total cholesterol ratio were substantially lower in Czechs than in Brits (all p-values less than 0.001). For example, the mean concentration of beta carotene in plasma of Czech men was only a half of that in British men (0.39 vs. 0.77 mumol/l). Similarly, mean alpha- and beta-carotene and lycopene among Czech men were substantially lower than in Bavarian men. Mean homocysteine was higher in Czechs (10.5 mumol/l) and in Bavarians (8.9 mumol/l, p < 0.001). Means of vitamin E were similar. In the case-control study, the risk of myocardial infarction was elevated among men with below median plasma levels of beta carotene (age adjusted odds ratio 3.33, 95% confidence interval 1.43-8.33) and alfa-tocopherol (odds ratio 1.89, 95% confidence interval 0.94-3.85). The low levels of carotenoids and high levels of homocysteine in plasma of Czechs may reflect low dietary intakes of fresh fruits and vegetables. Antioxidants or factors related to their dietary intakes may be one of the causes of the high cardiovascular mortality in the Czech Republic.

Adult↗
PubMed1998

The use of the Panic and Agoraphobia Scale in a clinical trial.

A new scale for assessing severity in PDA (Panic Disorder with/without Agoraphobia) has recently been developed: the Panic and Agoraphobia Scale [P & A (Bandelow, 1995)]. The objective of this study was to test whether the scale is sensitive to changes during a treatment trial. Thirty-seven patients (mean age, 32.7; S.D., 6.3) with PDA were treated with imipramine (75-150 mg/day) for 8 weeks in an open prospective trial. Patients with concurrent agoraphobia were instructed in practising self-exposure to agoraphobic situations. The total scores on the P & A, the Hamilton Anxiety Scale (HAMA) and the Clinical Global Impression Scale (CGI) were used as the main efficacy criteria. Treatment results were excellent, as could be shown by a decrease in the average severity scores of the P & A observer-rated version from 28.9 (S.D., 8.1) to 13.3 (S.D., 11.8; rank statistic T(N) = 6.7; P < 0.0001). The largest effect size r(w) of all clinician-rated scales was seen with the observer-rated version of the P & A, although closely followed by the CGI and the HAMA. Among the self-rated scales, the P & A (self-rated version) also showed the largest effect size. All five subscores of the P & A showed significant improvements. The highest treatment effect sizes could be seen in the 'panic attacks' subscore, followed by the 'anticipatory anxiety' subscore. The new Panic and Agoraphobia Scale (P & A) is a useful tool for measuring treatment efficacy in panic disorder trials.

Adult↗
PubMed1998

Surface NMR Using Laser-Polarized 129Xe under Magic Angle Spinning Conditions

NMR signals of surface nuclei of solids may be enhanced by the transfer of spin polarization from laser-polarized noble gases. Until now such experiments have not been feasible under conditions of magic angle spinning. In the present contribution it is shown that laser-polarized 129Xe can be inserted into a spinning rotor under continuous-flow conditions using helium as a carrier gas. Effective adsorption of xenon on the sample occurs at temperatures of about 163-173 K making possible the observation of a spin polarization induced nuclear Overhauser effect (SPINOE) from the laser-polarized 129Xe to surface 1H nuclei of SiO2 (AEROSIL300). This technique opens the way to selectively enhanced high-resolution multinuclear surface NMR experiments. Copyright 1998 Academic Press. Copyright 1998 Academic Press

Journal Article↗
PubMed1998

Could antioxidants play a role in high rates of coronary heart disease in the Czech Republic?

OBJECTIVES: To compare plasma levels of antioxidant vitamins in the Czech population with those in a western European population, and to investigate whether plasma levels of antioxidant vitamins in Czech population are related to risk of MI. DESIGN: The study has two parts: a cross-sectional survey and a population based case-control study. SETTING: Adult population in two districts of the Czech Republic, and London based civil servants group as the comparison. SUBJECTS: A random sample of men and women aged 25-64y resident in two districts were selected for the cross- sectional survey. Subjects in the age group 40-49 y were compared to a sample of British civil servants of the same age enrolled in the Whitehall II Study. Men in the Czech sample served as controls to 52 male cases of first non-fatal myocardial infarction (MI) which occurred in the same population. Plasma samples were obtained from venepuncture during an interview in hospital in the population sample and immediately after hospitalization in the MI cases. MAIN OUTCOME MEASURES: Plasma levels of beta-carotene and alpha-tocopherol, and the event of MI. Identical protocol and one laboratory was used for all analyses. RESULTS: The mean plasma levels of beta-carotene and alpha-tocopherol in healthy Czech men and women were substantially lower than in a subsample of British civil servants examined in the same laboratory. Smoking was strongly related to beta-carotene in both populations but differences between Czechs and Brits were present in both smokers and non-smokers. In the case-control study among Czech men, low levels of the vitamins were strongly related to an increases risk of MI. Age-adjusted odds ratios for concentrations below the median were 3.33 (95% confidence interval 1.43-8.33) for beta-carotene and 1.89 (0.94-3.45) for alpha-tocopherol; further adjustment for a range of variables reduced these estimates only slightly. CONCLUSIONS: Plasma concentrations of antioxidants in the Czech population appeared to be very low, and men with low levels of these substances are at increased risk of MI. This indicates that sub-optimal intake of antioxidants or related dietary factors may have played a role in the high rates of coronary heart disease in this population.

Adult↗
PubMed1998

Behavioural and biological correlates of physical functioning in middle aged office workers: the UK whitehall II study.

STUDY OBJECTIVES: (1) To identify behavioural and biological correlates of poor physical functioning and (2) to determine whether such associations are independent of disease. DESIGN: Potential correlates were obtained from questionnaires and screening visits at baseline and five year follow up. Physical functioning was measured at follow up using the 10 item scale from the short-form 36 health survey. SETTING: London offices at baseline. PARTICIPANTS: 10,308 civil servants (6895 men and 3413 women), with a median age (range) of 49 years (39-63) at follow up. MAIN RESULTS: Multiple logistic regression showed that cigarette smoking, physical activity, body mass index (BMI), triglycerides, fibrinogen, and insulin were independently associated with poor physical functioning for men. For women, physical activity, eating habits, body mass index, fibrinogen, and insulin were independently associated with poor physical functioning. For example, among men, current smokers who had smoked more than 20 pack years were 1.89 (95% CI 1.35 to 2.67) times as likely to have poor physical functioning as never smokers. Men with BMI of 30 kg/m2 or more were 1.71 (95% CI 1.13 to 2.59) times as likely to have poor physical functioning as those with BMI < 20 kg/m2. The corresponding odds ratio for women was 2.66 (95% CI 1.80 to 3.93). With the exceptions of fibrinogen and insulin, associations remained on exclusion of subjects with physical disease. CONCLUSIONS: Risk factors established for physical diseases are associated with poor physical functioning in a population of working age. These associations may be independent of current disease.

Adult↗
PubMed1997

Contribution of job control and other risk factors to social variations in coronary heart disease incidence.

BACKGROUND: The first Whitehall Study showed an inverse social gradient in mortality from coronary heart disease (CHD) among British civil servants--namely, that there were higher rates in men of lower employment grade. About a quarter of this gradient could be attributed to coronary risk factors. We analysed 5-year CHD incidence rates from the Whitehall II study to assess the contribution to the social gradient of psychosocial work environment, social support, coronary risk factors, and physical height. METHODS: Data were collected in the first three phases of examination of men and women in the Whitehall II study. 7372 people were contacted on all three occasions. Mean length of follow-up was 5.3 years. Characteristics from the baseline, phase 1, questionnaire, and examination were related to newly reported CHD in people without CHD at baseline. Three self-reported CHD outcomes were examined: angina and chest pain from the Rose questionnaire, and doctor-diagnosed ischaemia. The contribution of different factors to the socioeconomic differences in incident CHD was assessed by adjustment of odds ratios. FINDINGS: Compared with men in the highest grade (administrators), men in the lowest grade (clerical and office-support staff) had an age-adjusted odds ratio of developing any new CHD of 1.50. The largest difference was for doctor-diagnosed ischaemia (odds ratio for the lowest compared with the highest grade 2.27). For women, the odds ratio in the lowest grade was 1.47 for any CHD. Of factors examined, the largest contribution to the socioeconomic gradient in CHD frequency was from low control at work. Height and standard coronary risk factors made smaller contributions. Adjustment for all these factors reduced the odds ratios for newly reported CHD in the lowest grade from 1.5 to 0.95 in men, and from 1.47 to 1.07 in women. INTERPRETATION: Much of the inverse social gradient in CHD incidence can be attributed to differences in psychosocial work environment. Additional contributions were made by coronary risk factors--mainly smoking--and from factors that act early in life, as represented by physical height.

Adult↗
PubMed1997

Stress and the biology of inequality.

It is well established that health depends on socioeconomic circumstances, but the biology of this relation is not well described. Psychosocial factors operating throughout the life course, beginning in early life, influence a variety of biological variables. Research with non-human primates shows the effects of dominance hierarchy on biology, and similar metabolic differentials are evident in a hierarchy of white collar civil servants. The neuroendocrine "fight or flight" response produces physiological and metabolic alterations which parallel those observed with lower socioeconomic status. The biological effects of the psychosocial environment could explain health inequalities between relatively affluent groups.

Adaptation, Psychological↗
PubMed1997

pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila.

Members of the Wnt/Wingless (Wg) family of signalling proteins organize many aspects of animal development by regulating the expression of particular target genes in responding cells. Recent biochemical studies indicate that the vertebrate HMG-domain proteins Lef-1 and XTcf-3 can physically interact with beta-catenin, a homologue of Drosophila Armadillo (Arm), the most downstream component known in the Wnt signal transduction pathway. However, these studies do not address whether the endogenous Lef/Tcf family members are required in vivo to transduce Wnt signals. Using genetic methods in Drosophila, we define a new segment polarity gene, pangolin (pan), and show that its product is required in vivo for Wg signal transduction in embryos and in developing adult tissues. In addition, we show that pan encodes a Lef/Tcf homologue and provide evidence that its protein product binds to the beta-catenin homologue Armadillo in vivo. Finally, we demonstrate that Pan functions downstream of Arm to transduce the Wg signal. Thus, our results indicate that Pan is an essential component of the Wg transduction pathway and suggest that it acts directly to regulate gene transcription in response to Wg signalling.

Amino Acid Sequence↗
PubMed1997

Low job control and risk of coronary heart disease in Whitehall II (prospective cohort) study.

OBJECTIVE: To determine the association between adverse psychosocial characteristics at work and risk of coronary heart disease among male and female civil servants. DESIGN: Prospective cohort study (Whitehall II study). At the baseline examination (1985-8) and twice during follow up a self report questionnaire provided information on psychosocial factors of the work environment and coronary heart disease. Independent assessments of the work environment were obtained from personnel managers at baseline. Mean length of follow up was 5.3 years. SETTING: London based office staff in 20 civil service departments. SUBJECTS: 10,308 civil servants aged 35-55 were examined-6895 men (67%) and 3413 women (33%). MAIN OUTCOME MEASURES: New cases of angina (Rose questionnaire), severe pain across the chest, diagnosed ischaemic heart disease, and any coronary event. RESULTS: Men and women with low job control, either self reported or independently assessed, had a higher risk of newly reported coronary heart disease during follow up. Job control assessed on two occasions three years apart, although intercorrelated, had cumulative effects on newly reported disease. Subjects with low job control on both occasions had an odds ratio for any subsequent coronary event of 1.93 (95% confidence interval 1.34 to 2.77) compared with subjects with high job control at both occasions. This association could not be explained by employment grade, negative affectivity, or classic coronary risk factors. Job demands and social support at work were not related to the risk of coronary heart disease. CONCLUSIONS: Low control in the work environment is associated with an increased risk of future coronary heart disease among men and women employed in government offices. The cumulative effect of low job control assessed on two occasions indicates that giving employees more variety in tasks and a stronger say in decisions about work may decrease the risk of coronary heart disease.

Adult↗
PubMed1997

Can dietary interventions change diet and cardiovascular risk factors? A meta-analysis of randomized controlled trials.

OBJECTIVES: This study evaluated the effectiveness of dietary advice in primary prevention of chronic disease. METHODS: A meta-analysis was conducted of 17 randomized controlled trials of dietary behavior interventions of at least 3 months' duration. Results were analyzed as changes in reported dietary fat intakes and biomedical measures (serum cholesterol, urinary sodium, systolic and diastolic blood pressure) in the intervention group minus changes in the control group at 3 to 6 months and 9 to 18 months of follow-up. RESULTS: After 3 to 6 months, mean net changes in each of the five outcomes favored intervention. For dietary fat as a percentage of food energy, the change was -2.5% (95% confidence interval [CI] = -3.9%, -1.1%). Mean net changes over 9 to 18 months were as follows: serum cholesterol, -0.22 (95% CI = -0.39, -0.05) mmol/L; urinary sodium, -45.0 (95% CI = -57.1, -32.8) mmol/24 hours; systolic blood pressure, -1.9 (95% CI = -3.0, 0.8) mm Hg; and diastolic blood pressure, -1.2 (95% CI = -2.6, 0.2) mm Hg. CONCLUSIONS: Individual dietary interventions in primary prevention can achieve modest improvements in diet and cardiovascular disease risk status that are maintained for 9 to 18 months.

Cardiovascular Diseases↗