Changes of overweight and obesity in the adult Swiss population according to educational level, from 1992 to 2007.

In many high income developed countries, obesity is inversely associated with educational level. In some countries, a widening gap of obesity between educational groups has been reported. The aim of this study was to assess trends in body mass index (BMI) and in prevalence of overweight and obesity and their association with educational level in the adult Swiss population. Four cross-sectional National health interview surveys conducted in 1992/93 (n = 14,521), 1997 (n = 12,474), 2002 (n = 18,908) and 2007 (n = 17,879) using representative samples of the Swiss population (age range 18-102 years). BMI was derived from self-reported data. Overweight was defined as BMI > or = 25 and <30 kg/m(2), and obesity as BMI > or = 30 kg/m(2). Mean (+/- standard deviation) BMI increased from 24.7 +/- 3.6 in 1992/3 to 25.4 +/- 3.6 kg/m2 in 2007 in men and 22.8 +/- 3.8 to 23.7 +/- 4.3 kg/m(2) in women. Between 1992/3 and 2007, the prevalence of overweight + obesity increased from 40.4% to 49.5% in men and from 22.3% to 31.3% in women, while the prevalence of obesity increased from 6.3% to 9.4% in men and from 4.9% to 8.5% in women. The rate of increase in the prevalence of obesity was greater between 1992/3 and 2002 (men: +0.26%/year; women: +0.31%/year) than between 2002 and 2007 (men: +0.10%/year; women: +0.10%/year). A sizable fraction (approximately 25%) of the increasing mean BMI was due to increasing age of the participants over time. The increase was larger in low than high education strata of the population. BMI was strongly associated with low educational level among women and this gradient remained fairly constant over time. A weaker similar gradient by educational level was apparent in men, but it tended to increase over time. In Switzerland, overweight and obesity increased between 1992 and 2007 and was associated with low education status in both men and women. A trend towards a stabilization of mean BMI levels was noted in most age categories since 2002. The increase in the prevalence of obesity was larger in low education strata of the population. These findings suggest that obesity preventive measures should be targeted according to educational level in Switzerland.

Metabolic and respiratory effects of infused sodium acetate in healthy human subjects.

The metabolic and respiratory effects of intravenous 0.5 M sodium acetate (at a rate of 2.5 mmol/min during 120 min) were studied in nine normal human subjects. O2 consumption (VO2) and CO2 production (VCO2) were measured continuously by open-circuit indirect calorimetry. VO2 increased from 251 +/- 9 to 281 +/- 9 ml/min (P < 0.001), energy expenditure increased from 4.95 +/- 0.17 kJ/min baseline to 5.58 +/- 0.16 kJ/min (P < 0.001), and VCO2 decreased nonsignificantly (211 +/- 7 ml/min vs. 202 +/- 7 ml/min, NS). The extrapulmonary CO2 loss (i.e., bicarbonate generation and excretion) was estimated at 48 +/- 5 ml/min. This observation is consistent with 1 mol of bicarbonate generated from 1 mol of acetate metabolized. Alveolar ventilation decreased from 3.5 +/- 0.2 l/min basal to 3.1 +/- 0.2 l/min (P < 0.001). The minute ventilation (VE) to VO2 ratio decreased from 22.9 +/- 1.3 to 17.6 +/- 0.9 l/l (P < 0.005), arterial PO2 decreased from 93.2 +/- 1.9 to 78.7 +/- 1.6 mmHg (P < 0.0001), arterial PCO2 increased from 39.2 +/- 0.7 to 42.1 +/- 1.1 mmHg (P < 0.0001), pH from 7.40 +/- 0.005 to 7.50 +/- 0.007 (P < 0.005), and arterial bicarbonate concentration from 24.2 +/- 0.7 to 32.9 +/- 1.1 (P < 0.0001). These observations indicate that sodium acetate infusion results in substantial extrapulmonary CO2 loss, which leads to a relative decrease of total and alveolar ventilation.

Quantification of clenbuterol at trace level in human urine by ultra-high pressure liquid chromatography-tandem mass spectrometry.

Clenbuterol is a ^6;2 agonist agent with anabolic properties given by the increase in the muscular mass in parallel to the decrease of the body fat. For this reason, the use of clenbuterol is forbidden by the World Anti-Doping Agency (WADA) in the practice of sport. This compound is of particular interest for anti-doping authorities and WADA-accredited laboratories due to the recent reporting of risk of unintentional doping following the eating of meat contaminated with traces of clenbuterol in some countries. In this work, the development and the validation of an ultra-high pressure liquid chromatography coupled to electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method for the quantification of clenbuterol in human urine is described. The analyte was extracted from urine samples by liquid-liquid extraction (LLE) in basic conditions using tert butyl-methyl ether (TBME) and analyzed by UHPLC-MS/MS with a linear gradient of acetonitrile in 9min only. The simple and rapid method presented here was validated in compliance with authority guidelines and showed a limit of quantification at 5pg/mL and a linearity range from 5pg/mL to 300pg/mL. Good trueness (85.8-105%), repeatability (5.7-10.6% RSD) and intermediate precision (5.9-14.9% RSD) results were obtained. The method was then applied to real samples from eighteen volunteers collecting urines after single oral doses administration (1, 5 and 10_6;g) of clenbuterol-enriched yogurts.

Molecular mechanisms for the regulation of skin homeostasis

L'ubiquitination est une modification des protéines conservée, consistant en l'addition de résidus « ubiquitine » et régulant le destin cellulaire des protéines. La protéine « TRAF-interacting protein » TRAIP (ou TRIP) est une ligase E3 qui catalyse l'étape finale de l'ubiquitination. TRAIP est conservé dans l'évolution et est nécessaire au développement des organismes puisque l'ablation de TRAIP conduit à la mort embryonnaire aussi bien de la drosophile que de la souris. De plus, la réduction de l'expression de TRAIP dans des kératinocytes épidermiques humains réprime la prolifération cellulaire et induit un arrêt du cycle cellulaire en phase Gl, soulignant le lien étroit entre TRAIP et la prolifération cellulaire. Comme les mécanismes de régulation de la prolifération jouent un rôle majeur dans l'homéostasie de la peau, il est important de caractériser la fonction de TRAIP dans ces mécanismes. En utilisant des approches in vitro, nous avons déterminé que la protéine TRAIP est instable, modifiée par l'addition d'ubiquitine et ayant une demi-vie d'environ 4 heures. Nos analyses ont également révélé que l'expression de TRAIP est dépendante du cycle cellulaire, atteignant un pic d'expression en phase G2/M et que l'induction de son expression s'effectue principalement au cours de la transition Gl/S. Nous avons identifié le facteur de transcription E2F1 comme en étant le responsable, en régulant directement le promoteur de TRAIP. Aussi, TRAIP endogène ou surexprimée est surtout localisée au niveau du nucléole, une organelle nucléaire qui est désassemblée pendant la division cellulaire. Pour examiner la localisation subcellulaire de TRAIP pendant la mitose, nous avons imagé la protéine TRAIP fusionnée à une protéine fluorescente, à l'intérieur de cellules vivantes nommées HeLa, à l'aide d'un microscope confocal. Dans ces conditions, TRAIP est majoritairement localisée autour des chromosomes en début de mitose, puis est arrangée au niveau de l'ADN chromosomique en fin de mitose. La détection de TRAIP endogène à l'aide d'un anticorps spécifique a confirmé cette localisation. Enfin, l'inactivation de TRAIP dans les cellules HeLa par interférence ARN a inhibé leur capacité à s'arrêter en milieu de mitose. Nos résultats suggèrent que le mécanisme sous-jacent peut être lié au point de contrôle de l'assemblage du fuseau mitotique. - Ubiquitination of proteins is a post-translational modification which decides the cellular fate of the protein. The TRAF-interacting protein (TRAIP, TRIP) functions as an E3 ubiquitin ligase mediating addition of ubiquitin moieties to proteins. TRAIP interacts with the deubiquitinase CYLD, a tumor suppressor whose functional inactivation leads to skin appendage tumors. TRAIP is required for early embryonic development since removal of TRAIP either in Drosophila or mice by mutations or knock¬out is lethal due to aberrant regulation of cell proliferation and apoptosis. Furthermore, shRNA- mediated knock-down of TRAIP in human epidermal keratinocytes (HEK) repressed cell proliferation and induced a Gl/S phase block in the cell cycle. Additionally, TRAIP expression is strongly down- regulated during keratinocyte differentiation supporting the notion of a tight link between TRAIP and cell proliferation. We thus examined the biological functions of TRAIP in epithelial cell proliferation. Using an in vitro approach, we could determine that the TRAIP protein is unstable, modified by addition of ubiquitin moieties after translation and exhibits a half-life of 3.7+/-1-6 hours. Our analysis revealed that the TRAIP expression is modulated in a cell-cycle dependent manner, reaching a maximum expression level in G2/M phases. In addition, the expression of TRAIP was particularly activated during Gl/S phase transition and we could identify the transcription factor E2F1 as an activator of the TRAIP gene promoter. Both endogenous and over-expressed TRAIP mainly localized to the nucleolus, a nuclear organelle which is disassembled during cell division. To examine the subcellular localization of TRAIP during M phase, we performed confocal live-cell imaging of a functional fluorescent protein TRAIP-GFP in HeLa cells. TRAIP was distributed in the cytoplasm and accumulated around mitotic chromosomes in pro- and meta-phasic cells. TRAIP was then confined to chromosomal DNA location in anaphase and later phases of mitosis. Immune-detection of endogenous TRAIP protein confirmed its particular localization in mitosis. Finally, inactivating TRAIP expression in HeLa cells using RNA interference abrogated the cells ability to stop or delay mitosis progression. Our results suggested that TRAIP may involve the spindle assembly checkpoint.

Relationship between cigarette smoking and abdominal obesity

Background: Although smokers tend to have a lower body-mass index (BMI) than non-smokers, smoking may affect body fat (BF) distribution. Some studies have assessed the association between smoking, BMI and waist circumference (WC), but, to our knowledge, no population-based studies assessed the relation between smoking and BF composition. We assessed the association between amount of cigarette smoking, BMI, WC and BF composition. Method: Data was analysed from a cross-sectional population-based study including 6'187 Caucasians aged 32-76 and living in Switzerland. Height, weight and WC were measured. BF, expressed in percent of total body weight, was measured by electrical bioimpedance. Abdominal obesity was defined as a WC 0102 cm for men and 088 cm for women and normal WC as <94 cm for men and <80 cm for women. In men, excess BF was defined as %BF 028.1, 28.7, 30.6 and 32.6 for age groups 32-44, 45-54, 55-64 and 65-76, respectively; the corresponding values for women were 35.9, 36.5, 40.5 and 44.4. Cigarette smoking was assessed using a self-reported questionnaire. Results: 29.3% of men and 25.0% of women were smokers. Prevalence of obesity, abdominal obesity, and excess of BF was 16.9% and 26.6% and 14.2% in men and 15.0%, 33.0% and 27.5% in women, respectively. Smokers had lower age-adjusted mean WC and percent of BF compared to non-smokers. However, among smokers, mean age-adjusted WC and BF increased with the number of cigarettes smoked per day: among light (1-10 cig/day), moderate (11-20) and heavy smokers (>20), mean ± SE %BF was 22.4 ± 0.3, 23.1 ± 0.3 and 23.5 ± 0.4 for men, and 31.9 ± 0.3, 32.6 ± 0.3 and 32.9 ± 0.4 for women, respectively. Mean WC was 92.9 ± 0.6, 94.0 ± 0.5 and 96.0 ± 0.6 cm for men, and 80.2 ± 0.5, 81.3 ± 0.5 and 83.3 ± 0.7 for women, respectively. Compared with light smokers, the age-adjusted odds ratio (95% Confidence Interval) for excess of BF was 1.04 (0.58 to 1.85) for moderate smokers and 1.06 (0.57 to 1.99) for heavy smokers in men (p-trend = 0.9), and 1.35 (0.92 to 1.99) and 2.26 (1.38 to 3.72), respectively, in women (p-trend = 0.04). Odds ratio for abdominal obesity vs. normal WC was 1.32 (0.81 to 2.15) for moderate smokers and 1.95 (1.16 to 3.27) for heavy smokers in men (p-trend <0.01), and 1.15 (0.79 to 1.69) and 2.36 (1.41 to 3.93) in women (p-trend = 0.03). Conclusion: WC and BF were positively and dose-dependently associated with the number of cigarettes smoked per day in women, whereas only WC was dose dependently and significantly associated with the amount of cigarettes smoked per day in men. This suggests that heavy smokers, especially women, are more likely to have an excess of BF and to accumulate BF in the abdomen compared to lighter smokers.

Plasma Level of Mmp-9 as Predictive Factor for Response and Progression Free Survival in Patients Treated with Bevacizumab (Bev) and Pegylated Liposomal Doxorubicin (Pld): Sakk 24/06

Background: There is currently no identified marker predicting benefit from Bev in patients with breast cancer (pts). We monitored prospectively 6 angiogenesis-related factors in the blood of advanced stage pts treated with a combination of Bev and PLD in a phase II trial of the Swiss Group for Clinical Cancer Research, SAKK.Methods: Pts received PLD (20 mg/m2) and Bev (10 mg/kg) every 2 weeks for a maximum of 12 administrations, followed by Bev monotherapy until progression or severe toxicity. Blood samples were collected at baseline, during treatment and at treatment discontinuation. Enzyme-linked immunosorbent assays (Quantikine, R&DSystems and Reliatech) were used to measure vascular endothelial growth factor (VEGF), placental growth factor (PlGF), matrix metalloproteinase 9 (MMP-9) and soluble VEGF receptors -1, -2 and -3. The natural log-transformed (ln) data for each factor was analyzed by analysis of variance (ANOVA) model to investigate differences between the mean values of the subgroups of interest (where a = 0.05), based on the best tumor response by RECIST.Results: 132 samples were collected in 41 pts. The mean of baseline ln MMP-9 levels was significantly lower in pts with tumor progression than those with tumor response (p=0.0202, log fold change=0.8786) or disease control (p=0.0035, log fold change=0.8427). Higher MMP-9 level was a significant predictor of superior progression free survival (PFS): p=0.0417, hazard ratio=0.574, 95% CI=0.336-0.979. In a multivariate cox proportional hazards model, containing performance status, disease free interval, number of tumor sites, visceral involvement and prior adjuvant chemotherapy, using stepwise regression baseline MMP-9 was still a statistically 117P Table 1. SOLTI-0701* AC01B07* NU07B1* SOR+CAP N=20 PL+CAP N=33 SOR+ GEM/CAP N=23 PL+ GEM/CAP N=27 SOR+PAC N=48 PL+PAC N=46 Baseline characteristics Age, median (range), y 49 (32-72) 53 (30-78 54 (32-69) 57 (31-82) 50 (27-80) 52 (23-74) AJCC stage, n (%) IIIB/IIIC 3 (15) 6 (18) 0 (0) 3 (11) 8 (17) 9 (20) IV 17 (85) 27 (82) 23 (100) 24 (89) 40 (83) 37 (80) Metastatic site, n (%) Non-visceral 3 (15) 6 (18) 7 (30) 6 (22) 9 (19) 17 (37) Visceral 17 (85) 27 (82) 16 (70) 21 (78) 39 (81) 29 (63) Prior metastatic chemo, n (%) 8 (40) 15 (45) 21 (91) 25 (93) - - Efficacy PFS, median, mo 4.3 2.5 3.1 2.6 5.6 5.5 HR (95% CI)_ 0.60 (0.31, 1.14) 0.57 (0.30, 1.09) 0.86 (0.50, 1.45) 1-sided P value_ 0.055 0.044 0.281 Overall survival, median, mo 17.5 16.1 Pending 14.7 18.2 HR (95% CI)_ 0.98 (0.50, 1.89) 1.11 (0.64, 1.94) 1-sided P value_ 0.476 0.352 Safety N=20 N=33 N=22 N=27 N=46 N=46 Tx-emergent Grade 3/4, n (%) 15 (75) 16 (48) 20 (91) 17 (63) 36 (78) 16 (35) Grade 3§ hand-foot skin reaction/ syndrome 8 (40) 5 (15) 8 (36) 0 (0) 14 (30) 2 (4) *Efficacy results based on intent-to-treat population and safety results based on safety population (pts who received study drug[s]); _Cox regression within each subgroup; _log-rank test within each subgroup; §maximum toxicity grade for hand-foot skin reaction/syndrome; AJCC, American Joint Committee on Cancer mittedabstractsª The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com Downloaded from annonc.oxfordjournals.org at Bibliotheque Cantonale et Universitaire on June 6, 2011 significant factor (p=0.0266). The results of the other measured factors were presented elsewhere.Conclusions: Higher levels of MMP-9 could predict tumor response and superior PFSin pts treated with a combination of Bev and PLD. These exploratory results justify further investigations of MMP-9 in pts treated with Bev combinations in order to assess its role as a prognostic and predictive factor.Disclosure: K. Zaman: Participation in advisory board of Roche; partial sponsoring ofthe study by Roche (the main sponsor was the Swiss Federation against Cancer (Oncosuisse)). B. Thu¨rlimann: stock of Roche; Research grants from Roche. R. vonMoos: Participant of Advisory Board and Speaker honoraria

Gamma Knife radiosurgery after previous microvascular decompression decreases the chances of pain free in classical trigeminal neuralgia

Purpose: To evaluate the safety-efficacy of Gamma Knife surgery (GKS) as a second treatment for classical trigeminal neuralgia (CTN), and the influence of prior microvascular decompression (MVD). Methods: Between July 1992 and November 2010, 737 patients have been operated with GKRS for ITN and prospectively evaluated in Timone University Hospital in Marseille, France. Among these, 54 patients had a previous history of MVD. Radiosurgery using a Gamma Knife (model B or C or Perfexion) was performed on the basis of on both MR and CT targeting. A single 4 mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 3.9-11.9) anteriorly to the emergence of the nerve (retrogasserian target). A median maximum dose of 85 Gy (range 70-90) was delivered. Here, the 45 patients with previous MVD and a follow-up longer than one year are evaluated (the patients with megadolichobasilar artery compression and multiple sclerosis were excluded). Results: The median age in this series was 56.75 years (range 28.09-82.39). The median follow-up period was 39.48 months (range 14.10-144.65). All the patients had a past history of surgery, with at least one previous failed MVD, but also radiofrequency lesion (RFL) in 16 patients (35.6%), balloon microcompression in 7 (15.6%) and glycerol rhizotomy in 1 (2.2%). Thirty-five patients (77.8%) were initially pain free after GKS within a median time of 14 days (range 0, 180). Patients from this group had less probability of being pain free compared to our global population of essential trigeminal neuralgia without previous MVD history (p=0.010, hazard ratio of 0.64). Their probability of remaining pain free at 3, 5, 7 and 10 years was 66.5%, 59.1%, 59.1% and 44.3%, respectively. Twelve patients (34.3%) initially pain free experienced a recurrence with a median delay of 31.21 months (range 3.40-89.93). The hypoesthesia actuarial rate at 1 year was 9.1% and remained stable till 12 years with a median delay of onset of 8 months (range 8-8). Conclusions: Retrogasserian GKS proofed to be safe and effective on the long-term basis even after failed previous MVD. Even if the initial result of pain free was only 77.8%, the toxicity was low with only 9.1% hypoesthesia. No patient reported a bothersome hypoesthesia. The probability of maintaining pain relief in the long-term was of 44.3% at 10 years.

Nicotine-induced release of vasopressin in the conscious rat: role of opioid peptides and hemodynamic effects.

Nicotine has been shown to stimulate the release of vasopressin and to cause significant hemodynamic changes. The mechanisms leading to enhanced vasopressin secretion and the vascular consequences of the high plasma vasopressin levels during nicotine infusion have not yet been determined. Therefore, the purposes of the present study were 1) to examine in normal conscious rats the role of opioid peptides in the nicotine-induced increase in plasma vasopressin levels and 2) to assess the role of vasopressin in the hemodynamic effects of nicotine (20 micrograms/min for 15 min) using a specific V1 antagonist of the vascular actions of vasopressin. Plasma vasopressin levels were significantly increased in the nicotine-treated animals (39.5 +/- 10 vs. 3.7 +/- 0.6 pg/ml in the controls, P less than .01). Pretreatment with naloxone, an antagonist of opioids at their receptors, did not reduce the vasopressin levels (47.7 +/- 9 pg/ml). Nicotine also increased mean blood pressure (122.5 +/- 2.5 to 145.2 +/- 3.3 mm Hg, P less than .01) and decreased heart rate (461 +/- 6 to 386 +/- 14.5 beats/min, P less than .05). Administration of the vasopressin V1 antagonist before the nicotine infusion did not affect the systemic hemodynamics or the regional blood flow distribution, as assessed by radiolabeled microspheres. Thus, these results suggest that the nicotine-induced secretion of vasopressin is not mediated by opioid receptors and that the high plasma vasopressin levels do not exert any significant hemodynamic effect on cardiac output or blood flow distribution.

Prognostic importance of anaemia in patients with acute pulmonary embolism.

Although associated with adverse outcomes in other cardiopulmonary diseases, limited evidence exists on the prognostic value of anaemia in patients with acute pulmonary embolism (PE). We sought to examine the associations between anaemia and mortality and length of hospital stay in patients with PE. We evaluated 14,276 patients with a primary diagnosis of PE from 186 hospitals in Pennsylvania, USA. We used random-intercept logistic regression to assess the association between anaemia at the time of presentation and 30-day mortality and discrete-time logistic hazard models to assess the association between anaemia and time to hospital discharge, adjusting for patient (age, gender, race, insurance type, clinical and laboratory variables) and hospital (region, size, teaching status) factors. Anaemia was present in 38.7% of patients at admission. Patients with anaemia had a higher 30-day mortality (13.7% vs. 6.3%; p <0.001) and a longer length of stay (geometric mean, 6.9 vs. 6.6 days; p <0.001) compared to patients without anaemia. In multivariable analyses, anaemia remained associated with an increased odds of death (OR 1.82, 95% CI: 1.60-2.06) and a decreased odds of discharge (OR 0.85, 95% CI: 0.82-0.89). Anaemia is very common in patients presenting with PE and is independently associated with an increased short-term mortality and length of stay.

Outcomes and reoperations after total correction of complete atrio-ventricular septal defect

BACKGROUND: Surgical correction of complete atrio-ventricular septal defect (AVSD) achieves satisfactory results with low morbidity and mortality, but may require reoperation. Our recent operative results at mid-term were followed-up. METHODS: From June 2000 to December 2007, 81 patients (Down syndrome; n=60), median age 4.0 months (range 0.7-118.6) and weight 4.7kg (range 2.2-33), underwent complete AVSD correction. Patch closure for the ventricular septal defect (VSD; n=69) and atrial septal defect (ASD; n=42) was performed with left atrio-ventricular valve (LAVV) cleft closure (n=76) and right atrio-ventricular valve (RAVV) repair (n=57). Mortality, morbidity, and indications for reoperation were retrospectively studied; the end point 'time to reoperation' was analyzed using Kaplan-Meier curves. Follow-up was complete except in two patients and spanned a median of 28 months (range 0.4-6.1 years). RESULTS: In-hospital mortality was 3.7% (n=3) and one late death occurred. Reoperation was required in 7/79 patients (8.9%) for LAVV insufficiency (n=4), for a residual ASD (n=1), for right atrio-ventricular valve insufficiency (n=1), and for subaortic stenosis (n=1). At last follow-up, no or only mild LAVV and RAVV insufficiency was present in 81.3% and 92.1% of patients, respectively, and 2/3 of patients were medication-free. Risk factors for reoperation were younger age (<3 months; p=0.001) and lower weight (<4kg; p=0.003), and a trend towards less and later reoperations in Down syndrome (p<0.2). CONCLUSIONS: Surgical correction of AVSD can be achieved with low mortality and need for reoperation, regardless of Down syndrome or not. Immediate postoperative moderate or more residual atrio-ventricular valve insufficiency will eventually require a reoperation, and could be anticipated in patients younger than 3 months and weighing <4kg.

Les activations autonomiques nocturnes sont associées au diabète et à l'hypertension dans la population générale

Objectif : Les variations de l'amplitude de l'onde de pouls (AOP) dérivées du signal de l'oxymètre de pouls digital reflètent les variations du tonus sympathique durant le sommeil. Le but de cette étude était de démontrer la relation entre les chutes de l'AOP nocturnes et l'hypertension artérielle (HTA) ainsi que le diabète de type 2. Méthode: 1740 sujets (50.5 % de femmes, de 56.2 ± 10.5 ans, BMI 25.4 ± 4.4 kg/m2) participant à une étude de cohorte sur le sommeil (HypnoLaus) ont bénéficié d'un enregistrement polysomnographique complet (PSG) à domicile. L'index de chutes de l'AOP (AOPi) et la durée des chutes de l'AOP (AOPd) ont été mesurés pour chaque patient. Le diabète de type 2 a été défini par une glycémie à jeun de ≥ 7 mmol/L ou la prise d'un traitement antidiabétique. Une HTA a été définie par une TA systolique ≥ 130 mmHg, ou une TA diastolique ≥ 90 mmHg, ou la prise d'un traitement antihypertenseur. Les sujets ont été considérés comme n'ayant pas de troubles du sommeil s'ils avaient < 5 apnéeshypopnées/ heure (IAH), <15 mouvements périodiques des jambes/heure (IMPJ) et un score de somnolence d'Epworth <11/24. Résultats : L'AOPi moyen dans la population sans trouble du sommeil était de 40.2 ± 15.8 chutes/h. L'AOPd moyenne était de 13.7 ± 2.6 s. L'AOPd était significativement corrélée à la TA systolique (P=0.0038) et à la TA diastolique (P<0.0001). La prévalence d'HTA augmentait significativement avec l'AOPd (OR 1.66 (1.15 - 2.4) ; P <0.01). La prévalence de diabète de type 2 augmentait également significativement avec l'AOPd (OR 2.27 (1.46 - 5.75) ; P<0.01). Ces résultats restent significatifs indépendamment du sexe, de l'âge, du tour de cou ou de la taille, de la consommation d'alcool ou de tabac. Comparé avec d'autres marqueurs de fractionnement du sommeil, l'AOPd était le marqueur le plus significativement associé à l'HTA et au diabète de type 2. L'AOPi n'était pas associé à une augmentation du diabète ou de l'HTA. Il était par contre corrélé avec l'index apnées hypopnées (p < 0.0001) et de microréveils (p<0.0001). Conclusion : La durée des variations de l'amplitude de l'onde pouls pendant le sommeil (AOPd), et non sa fréquence (AOPi), est associée avec une augmentation de prévalence de diabète de type 2 et d'hypertension.

Expression of human estrogen receptor mutants in Xenopus oocytes: correlation between transcriptional activity and ability to form protein-DNA complexes.

The human estrogen receptor (hER) is a trans-acting regulatory protein composed of a series of discrete functional domains. We have microinjected an hER expression vector (HEO) into Xenopus oocyte nuclei and demonstrate, using Western blot assay, that the hER is synthesized. When nuclear extracts from oocytes were prepared and incubated in the presence of a 2.7 kb DNA fragment comprising the 5' end of the vitellogenin gene B2, formation of estrogen-dependent complexes could be visualized by electron microscopy over the estrogen responsive element (ERE). Of crucial importance is the observation that the complex formation is inhibited by the estrogen antagonist tamoxifen, is restored by the addition of the hormone and does not take place with extracts from control oocytes injected with the expression vector lacking the sequences encoding the receptor. The presence of the biologically active hER is confirmed in co-injection experiments, in which HEO is co-introduced with a CAT reporter gene under the control of a vitellogenin promoter containing or lacking the ERE. CAT assays and primer extensions analyses reveal that both the receptor and the ERE are essential for estrogen induced stimulation of transcription. The same approach was used to analyze selective hER mutants. We find that the DNA binding domain (region C) is essential for protein--DNA complex formation at the ERE but is not sufficient by itself to activate transcription from the reporter gene. In addition to region C, both the hormone binding (region E) and amino terminal (region A/B) domains are needed for an efficient transcription activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Quality of life depends on the drinking pattern in alcohol-dependent patients.

AIMS: In patients with alcohol dependence, health-related quality of life (QOL) is reduced compared with that of a normal healthy population. The objective of the current analysis was to describe the evolution of health-related QOL in adults with alcohol dependence during a 24-month period after initial assessment for alcohol-related treatment in a routine practice setting, and its relation to drinking pattern which was evaluated across clusters based on the predominant pattern of alcohol use, set against the influence of baseline variables METHODS: The Medical Outcomes Study 36-Item Short-Form Survey (MOS-SF-36) was used to measure QOL at baseline and quarterly for 2 years among participants in CONTROL, a prospective observational study of patients initiating treatment for alcohol dependence. The sample consisted of 160 adults with alcohol dependence (65.6% males) with a mean (SD) age of 45.6 (12.0) years. Alcohol use data were collected using TimeLine Follow-Back. Based on the participant's reported alcohol use, three clusters were identified: 52 (32.5%) mostly abstainers, 64 (40.0%) mostly moderate drinkers and 44 (27.5%) mostly heavy drinkers. Mixed-effect linear regression analysis was used to identify factors that were potentially associated with the mental and physical summary MOS-SF-36 scores at each time point. RESULTS: The mean (SD) MOS-SF-36 mental component summary score (range 0-100, norm 50) was 35.7 (13.6) at baseline [mostly abstainers: 40.4 (14.6); mostly moderate drinkers 35.6 (12.4); mostly heavy drinkers 30.1 (12.1)]. The score improved to 43.1 (13.4) at 3 months [mostly abstainers: 47.4 (12.3); mostly moderate drinkers 44.2 (12.7); mostly heavy drinkers 35.1 (12.9)], to 47.3 (11.4) at 12 months [mostly abstainers: 51.7 (9.7); mostly moderate drinkers 44.8 (11.9); mostly heavy drinkers 44.1 (11.3)], and to 46.6 (11.1) at 24 months [mostly abstainers: 49.2 (11.6); mostly moderate drinkers 45.7 (11.9); mostly heavy drinkers 43.7 (8.8)]. Mixed-effect linear regression multivariate analyses indicated that there was a significant association between a lower 2-year follow-up MOS-SF-36 mental score and being a mostly heavy drinker (-6.97, P < 0.001) or mostly moderate drinker (-3.34 points, P = 0.018) [compared to mostly abstainers], being female (-3.73, P = 0.004), and having a Beck Inventory scale score ≥8 (-6.54, P < 0.001), at baseline. The mean (SD) MOS-SF-36 physical component summary score was 48.8 (10.6) at baseline, remained stable over the follow-up and did not differ across the three clusters. Mixed-effect linear regression univariate analyses found that the average 2-year follow-up MOS-SF-36 physical score was increased (compared with mostly abstainers) in mostly heavy drinkers (+4.44, P = 0.007); no other variables tested influenced the MOS-SF-36 physical score. CONCLUSION: Among individuals with alcohol dependence, a rapid improvement was seen in the mental dimension of QOL following treatment initiation, which was maintained during 24 months. Improvement was associated with the pattern of alcohol use, becoming close to the general population norm in patients classified as mostly abstainers, improving substantially in mostly moderate drinkers and improving only slightly in mostly heavy drinkers. The physical dimension of QOL was generally in the normal range but was not associated with drinking patterns.

Infections and functional impairment in nursing home residents: a reciprocal relationship.

OBJECTIVES: To determine the relationship between infections and functional impairment in nursing home residents. DESIGN: Prospective cohort study (follow-up period, 6 months). SETTING: Thirty-nine nursing homes in western Switzerland. PARTICIPANTS: A total of 1,324 residents aged 65 and older (mean age 85.7; 76.6% female) who agreed to participate, or their proxies, by oral informed consent. MEASUREMENTS: Functional status measured every 3 months. Two different outcomes were used: (a) functional decline defined as death or decreased function at follow-up and (b) functional status score using a standardized measure. RESULTS: At the end of follow-up, mortality was 14.6%, not different for those with and without infection (16.2% vs 13.1%, P=.11). During both 3-month periods, subjects with infection had higher odds of functional decline, even after adjustment for baseline characteristics and occurrence of a new illness (adjusted odds ratio (AOR)=1.6, 95% confidence interval (CI)=1.2-2.2, P=.002, and AOR=1.5, 95% CI=1.1-2.0, P=.008, respectively). The odds of decline increased in a stepwise fashion in patients with zero, one, and two or more infections. The analyses predicting functional status score (restricted to subjects who survived) gave similar results. A survival analysis predicting time to first infection confirmed a stepwise greater likelihood of infection in subjects with moderate and severe impairment at baseline than in subjects with no or mild functional impairment at baseline. CONCLUSION: Infections appear to be both a cause and a consequence of functional impairment in nursing home residents. Further studies should be undertaken to investigate whether effective infection control programs can also contribute to preventing functional decline, an important component of these residents' quality of life.