Sequence-specific 1H, 13C, and 15N assignments of the MAR-binding domain of chicken MeCP2/ARBP.
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Animals↗
Biomedical subjects
E Brunner
Publications and source records attributed to E Brunner.
Minireview: mechanisms by which the metabolic syndrome and diabetes impair memory.
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.
Dementia↗
Socioeconomic differences in fat intake in a middle-aged population: report from the Malmö Diet and Cancer Study.
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.
Body Mass Index↗
Social determinants of von willebrand factor: the Whitehall II study.
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.
Adult↗
Effects of short-term glucocorticoid deprivation on growth hormone (GH) response to GH-releasing peptide-6: studies in normal men and in patients with adrenal insufficiency.
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.
Addison Disease↗
Laser facial resurfacing: patient survey of recovery and results.
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.
Adult↗
Beyond 'substantial equivalence'.
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Animals↗
Health risks of genetically modified foods.
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Agriculture↗
The dominant mutation Glazed is a gain-of-function allele of wingless that, similar to loss of APC, interferes with normal eye development.
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.
Alleles↗
Gas flow MRI using circulating laser-polarized 129Xe.
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.
Equipment Design↗
Application of a new statistical approach to evaluate a clinical trial with panic disorder patients.
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.
Adult↗
Rose questionnaire angina in younger men and women: gender differences in the relationship to cardiovascular risk factors and other reported symptoms.
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.
Adult↗
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↗
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↗
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↗
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↗
[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↗