Epidemiological applications of long-term stress in daily life.
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Biomedical subjects
Publications and source records attributed to E Brunner.
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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.
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Partial molecular alignment leads to an incomplete averaging of anisotropic magnetic interactions such as magnetic dipole interaction or chemical shift anisotropy. In the present contribution we quantitatively describe and evaluate the effects induced by the addition of magnetically oriented lipid bicelles in homonuclear two-dimensional (2D) NMR correlation (COSY) spectra of proteins. It is shown that 2D COSY experiments allow the measurement of H(N)-H(alpha) residual dipole couplings of positive sign which can be used for structure refinement. In contrast to the double- and triple-resonance experiments previously proposed, these measurements can be carried out even on nonisotope-enriched samples.
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Type 2 diabetes is associated with an increased risk of cognitive dysfunction. These effects seem particularly true for memory functions. This article examines how diabetes and the biological changes that occur with diabetes such as hyperglycemia, changes in insulin concentration, hypertension, and changes in lipid levels might lead to these alterations in cognitive functioning, with an emphasis on the mechanisms leading to changes in memory.
BACKGROUND: The objective was to investigate whether socioeconomic differences in fat intake may explain socioeconomic differences in cardiovascular diseases. METHODS: The Malmö Diet and Cancer Study is a prospective cohort study. The baseline examinations used in the present cross-sectional study were undertaken in 1992-1994. Dietary habits were assessed using a modified diet history method consisting of a 7-day menu book and a 168-item questionnaire. A subpopulation of 11 837 individuals born 1926-1945 was investigated. This study examined high fat intake, defined as >35.9% among men and >34.8% among women (25% quartile limit) of the proportion of the non-alcohol energy intake contributed by fat. The subfractions saturated, mono-unsaturated and poly-unsaturated fatty acids and the P:S ratio (polyunsaturated/saturated fatty acids) were analysed in the same way. The uppermost quartile (75%) of total and subgroup fat intake was also studied. Socioeconomic differences before and after adjustment for low energy reporting (LER), defined as energy intake below 1.2 x Basal Metabolic Rate, were examined. RESULTS: No socioeconomic differences in fat intake were seen between the SES groups, except for self-employed men, and male and female pensioners. Approximately 20% in most SES groups were LER. The LER and body mass index were strongly related. The SES pattern of fat intake remained unchanged after adjustment for age, country of origin and LER in a logistic regression model. The results for the subfractions of fat and the P:S ratio did not principally differ from the total fat results. CONCLUSIONS: This study provides no evidence that fat intake contributes to the inverse socioeconomic differences in cardiovascular diseases.
Data from the Whitehall II Study and others have demonstrated a role for the metabolic syndrome and fibrinogen underlying the association between social position and coronary heart disease. In this study, we examined the role of an additional hemostatic factor and marker of endothelial dysfunction, von Willebrand factor (vWF). Four thousand five hundred and forty-eight men and 1837 women were examined in the third phase of the study, which took place between 1991 and 1993. Employment grade was used as a measure of socioeconomic position. An inverse relation between employment grade and vWF was evident (P<0.0003). This employment grade gradient was apparent overall, and the relation persisted even when nonsmokers and participants with poor health were removed from the analyses (P=0.02). The difference between the highest (unified grades 1 to 6) and lowest (clerical/support) employment grades in vWF concentrations was 8.9 IU/dL (95% CI 6.0, 11.8; P<0.001) for men and 6.9 IU/dL (95% CI 4.0, 9.7; P=0.06) for women. vWF was associated with a number of biological factors that themselves showed an employment grade gradient, including fibrinogen (P<0.001), fasting and postload glucose (P<0.05) levels, and fasting and postload insulin (P<0.01) levels. Associations with smoking and alcohol intake were apparent. Smoking showed a threshold effect, such that only men who smoked >21 cigarettes per day produced a significantly increased vWF level (P<0.05) compared with lighter smokers. The health-related behaviors explained 25% of the grade gradient in men and 28% in women, while the biological factors accounted for 32% in men and 22% in women. We conclude that there is a grade gradient in vWF that was not fully explained by health-related behaviors and risk factors for coronary heart disease. These data are consistent with the hypothesis that endothelial dysfunction is part of the explanation for social inequalities in cardiovascular disease.
There are no data in the literature about the effects of glucocorticoid deprivation on GH-releasing peptide-6 (GHRP-6)-induced GH release. The aims of this study were to evaluate GH responsiveness to GHRP-6 1) after metyrapone administration in normal men, and 2) in patients with chronic hypocortisolism after glucocorticoid withdrawal for 72 h. In normal subjects, metyrapone ingestion did not alter significantly GH responsiveness to GHRP-6 [n = 8; peak, 39.3 +/-7.1 microg/L; area under the curve (AUC), 1958.8 +/- 445.7 microg/min x L; mean +/- SE] compared to placebo (n = 8; peak, 21.9 +/- 4.5; AUC, 1131.0 +/- 229.6). In patients with chronic hypocortisolism (n = 8), GH responses to GHRP-6 were similar both during replacement therapy (peak, 11.8 +/- 3.9; AUC, 563.2 +/- 208.7) and after withdrawal of prednisone (peak, 14.4 +/- 4.5; AUC, 695.6 +/- 272.9) and did not differ from those in controls. Interestingly, after glucocorticoid withdrawal, GH responsiveness to GHRP-6 in patients with chronic hypocortisolism was significantly lower than that in normal subjects pretreated with metyrapone. Our data suggest that short term glucocorticoid deprivation does not have a major impact on GHRP-6-dependent GH-releasing mechanisms. However, in long standing hypocortisolism, subtle changes in GHRP-6 secretory pathways may be present.
OBJECTIVE: To determine patient satisfaction with the postoperative recovery period and surgical outcome after facial laser resurfacing. DESIGN: Survey. PATIENTS: Patients who underwent facial laser resurfacing by two of the authors (PAA or DAFE) between 1995 and 1996. Questionnaires were completed by 47 of 100 patients. INTERVENTIONS: Facial laser resurfacing with the Sharplan CO2 laser and SilkTouch Scanner. MAIN OUTCOME MEASURES: Questionnaire. Statistical analysis was generated from a 5-point analogue scale. RESULTS: The overall side effects were moderate in severity, were well tolerated, and met the expectations of our patients. Redness was the most frequent side effect with an average duration of 3 months. Most patients returned to occupational and social activities at 2.5 weeks. Moderate lifestyle disruption was more frequent after full-face laser resurfacing than partial-face laser resurfacing. Excellent improvement was achieved for removal of fine wrinkles, improvement of skin quality, and sun-damaged skin. Good improvement was obtained for acne scarring and deep rhytids. Overall goals were attained in 89% of patients. CONCLUSIONS: Laser resurfacing produced excellent results for fine rhytids, skin quality, and sun-damaged skin. Return to social and occupational activities may occur early in recovery with the use of camouflage make-up. Patient education and close follow-up are necessary in the postoperative period.
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Dominant mutations have served as invaluable tools for Drosophila geneticists. Here we analyze the dominant eye mutation Glazed (Gla) that was described by T. H. Morgan more than 50 years ago. We show that Gla causes the loss of photoreceptor cells during pupal stages, in a process reminiscent of apoptosis, with a concomitant overproduction of eye pigment. This phenotype is very similar to that caused by the loss of D-APC, a negative regulator of Wingless (Wg) signal transduction. Genetic analyses reveal however that the Gla gain-of-function phenotype can be reverted to wild-type. By generating a P-element-induced revertant of Gla we demonstrate that Gla is allelic to wg. The molecular lesion in Gla indicates that the insertion of a roo retrotransposon leads to ectopic expression of wg during pupal stages. We show that the Gla phenotype is similar to that caused by ectopic expression of Wg driven by the sevenless (sev) enhancer. In both cases Wg exerts its effect, at least in part, by negatively regulating the expression of the Pax2 homolog sparkling (spa). Gla represents not only the first dominant allele of wg, but it may also be the first allele ever described for wg.
We describe an experimental approach that combines multidimensional NMR experiments with a steadily renewed source of laser-polarized 129Xe. Using a continuous flow system to circulate the gas mixture, gas phase NMR signals of laser-polarized 129Xe can be observed with an enhancement of three to four orders of magnitude compared to the equilibrium 129Xe NMR signal. Due to the fact that the gas flow recovers the nonequilibrium 129Xe nuclear spin polarization in 0.2 to 4 s, signal accumulation on the time scale of seconds is feasible, allowing previously inaccessible phase cycling and signal manipulation. Several possible applications of MRI of laser-polarized 129Xe under continuous flow conditions are presented here. The spin density images of capillary tubes demonstrate the feasibility of imaging under continuous flow. Dynamic displacement profiles, measured by a pulsed gradient spin echo experiment, show entry flow properties of the gas passing through a constriction under laminar flow conditions. Further, dynamic displacement profiles of 129Xe, flowing through polyurethane foams with different densities and pore sizes, are presented.
In clinical trials in psychiatry, changes in severity are usually measured with ordinal level scales which are applied repeatedly during the trial, showing a constant decline in psychopathology scores as treatment leads to improvement. Previous non-parametric tests for repeated measures in factorial designs did not test the hypothesis that scale scores decrease constantly during the trial. A recently developed "rank test for ordered alternatives in a mixed model" was developed and applied to the data of a clinical trial in panic disorder. Thirty-seven outpatients with panic disorder and agoraphobia (PDA) were treated with imipramine (75-150 mg/day) in an 8-week open, prospective trial. Patients with intercurrent agoraphobia were instructed in practising self-exposure in their agoraphobic situations. The total score on the Panic and Agoraphobia Scale, the Hamilton Anxiety Scale (HAMA) and the Clinical Global Impression Scale (CGI) were used as the main efficacy measures. The new rank test showed significant treatment results in all scales applied. Treatment results were excellent, as was shown by a decrease in the average Panic and Agoraphobia Scale severity scores from 28.9 (range 14-45) to 13.3 (range 0-37; rank statistic Tn = 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 Panic and Agoraphobia Scale, although closely followed by the CGI and the HAMA. Among the self-rated scales, the Panic and Agoraphobia Scale also showed the largest effect size. All five subscores of the Panic and Agoraphobia Scale showed significant improvements. The highest treatment effect sizes were seen in the "panic attacks" subscore, followed by the "anticipatory anxiety" subscore. The new statistical test applied in this study, which has some advantages in comparison with previously applied tests, is suitable for psychiatric treatment evaluations since it can also be applied in the case of discrete repeated measurements.
Cross-sectional data from the Whitehall II study baseline were used to identify factors that may lead to the high levels of Rose angina reporting in women. 134 (4.0%) of 3350 women and 164 (2.4%) of 6830 men reported angina (P<0.001). Women with Rose angina had a poorer cardiovascular risk profile (degree of obesity, serum cholesterol and apolipoprotein B, blood pressure) and more electrocardiogram abnormalities (ST and T changes) than women without angina, but the associations were generally weaker than in men. Women who reported many other physical symptoms had a high prevalence of Rose angina (9.7%). Adjustment for symptom reporting reduced the age-adjusted gender difference to odds ratio (OR) = 0.93 (95% confidence interval [CI]: 0.56-1.56) for subjects with no symptoms, and to OR = 1.42 (95% CI = 1.05-1.90) for subjects at the upper quartile of symptom score. Among women a high level of general symptom reporting was associated with General Health Questionnaire (GHQ) minor psychiatric morbidity (51.9% prevalence), but GHQ caseness does not appear to be a predictor of Rose angina (OR 1.22 [0.67-2.21]) in this group. Coronary artery disease risk is raised in women with Rose angina, and this remains true in groups with high levels of general symptom reporting.
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.
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.