Exercise and postprandial thermogenesis in obese women before and after weight loss.

The magnitude of thermogenesis induced by a test meal (17% protein, 54% CHO, and 29% fat) was assessed using indirect calorimetry in six obese women before and after weight loss (mean loss: 11.2 kg) and compared with six nonobese matched controls at rest for 5 h and during and following graded moderate exercise on a bicycle ergometer at three workloads. The test meal contained 60% of the energy expended in basal state over 24 h (736-1020 kcal/meal according to the group). In obese subjects the net absolute increase in energy expenditure (delta EE) in response to the meal was similar between exercising and resting conditions (delta EE = 0.27 vs 0.32 kcal/min, respectively) but tended to be lower in obese women after weight loss (delta EE = 0.19 kcal/min while exercising and 0.25 kcal/min while resting, p less than 0.05) and in control subjects (delta EE = 0.16 vs. 0.25 kcal/min, respectively: p less than 0.05). These results show that the thermogenic response to a meal is not potentiated by moderate exercise.

Whole-body protein turnover and resting energy expenditure in obese, prepubertal children.

BACKGROUND: Obesity is becoming more frequent in children; understanding the extent to which this condition affects not only carbohydrate and lipid metabolism but also protein metabolism is of paramount importance. OBJECTIVE: We evaluated the kinetics of protein metabolism in obese, prepubertal children in the static phase of obesity. DESIGN: In this cross-sectional study, 9 obese children (x +/- SE: 44+/-4 kg, 30.9+/-1.5% body fat) were compared with 8 lean (28+/-2 kg ,16.8+/-1.2% body fat), age-matched (8.5+/-0.2 y) control children. Whole-body nitrogen flux, protein synthesis, and protein breakdown were calculated postprandially over 9 h from 15N abundance in urinary ammonia by using a single oral dose of [15N]glycine; resting energy expenditure (REE) was assessed by indirect calorimetry (canopy) and body composition by multiple skinfold-thickness measurements. RESULTS: Absolute rates of protein synthesis and breakdown were significantly greater in obese children than in control children (x +/- SE: 208+/-24 compared with 137+/-14 g/d, P < 0.05, and 149+/-20 compared with 89+/-13 g/d, P < 0.05, respectively). When these variables were adjusted for fat-free mass by analysis of covariance, however, the differences between groups disappeared. There was a significant relation between protein synthesis and fat-free mass (r = 0.83, P < 0.001) as well as between protein synthesis and REE (r = 0.79, P < 0.005). CONCLUSIONS: Obesity in prepubertal children is associated with an absolute increase in whole-body protein turnover that is consistent with an absolute increase in fat-free mass, both of which contribute to explaining the greater absolute REE in obese children than in control children.

Diet-induced thermogenesis measured over a whole day in obese and nonobese women.

The overall thermogenic response to food intake measured over a whole day in 20 young nondiabetic obese women (body fat mean +/- SEM: 38.6 +/- 0.7%), was compared with that obtained in eight nonobese control women (body fat: 24.7 +/- 0.9%). The energy expenditure of the subjects was continuously measured over 24 h with a respiration chamber, and the spontaneous activity was assessed by a radar system. A new approach was used to obtain the integrated thermogenic response to the three meals ingested over the day (from 8:30 AM to 10:30 PM). This method allows to subtract the energy expended for physical activity from total energy expenditure and to calculate the integrated dietary-induced thermogenesis as the difference between the energy expended without physical activity and basal metabolic rate. The thermogenic response to the three meals (expressed in percentage of the total energy ingested) was found to be blunted in obese women (8.7 +/- 0.8%) as compared with that of controls (14.8 +/- 1.1%). There was an inverse correlation between the percentage body fat and the diet-induced thermogenesis (r = -0.61, p less than 0.001). In addition, the relative increase in diurnal urinary norepinephrine excretion was lower in obese than in the control subjects. It is concluded that a low overall thermogenic response to feeding may be a contributing factor for energy storage in some obese subjects; a blunted response of the sympathetic nervous system could explain this low thermogenic response.

Clinical features of myocardial infarction and myocarditis in young adults: a retrospective study.

OBJECTIVES: To evaluate the prevalence and clinical presentation of myocardial infarction (MI) and myocarditis in young adults presenting with chest pain (CP) and an elevated serum troponin I (TnI) to the emergency department (ED). DESIGN: Retrospective, observational, single-centre study. PARTICIPANTS: All consecutive patients 18-40 years old admitted to the ED for CP with an elevated TnI concentration. PRIMARY OUTCOME MEASURES: Prevalence of MI, myocarditis and the characterisation of clinical presentation. RESULTS: 1588 patients between 18 and 40 years old were admitted to the ED with CP during 30 consecutive months. 49 (3.1%) patients with an elevated TnI (>0.09 μg/l) were included. 32.7% (16/49) were diagnosed with MI (11 ST-elevation myocardial infarction (STEMI) and 5 non-ST-elevation myocardial infarction (NSTEMI)) and 59.2% (29/49) with myocarditis. Compared with patients with myocarditis, MI patients were older (34.1±3.8 vs 26.9±6.4, p=0.0002) with more cardiovascular risk factors (mean 2.06 vs 0.69). Diabetes (18.8% vs 0%, p=0.0039), dyslipidaemia (56.2% vs 3.4%, p<0.0001) and family history of coronary artery disease (CAD) (37.5% vs 10.3% p=0.050) were associated with MI. Fever or recent viral illness were present in 75.9% (22/29) of patients with myocarditis, and in 0% of MI patients (p<0.0001). During follow-up, two patients with myocarditis were re-admitted for CP. CONCLUSIONS: In this study, 32.7% of patients <40-year-old admitted to an ED with CP and elevated TnI had a diagnosis of MI. Key distinctive clinical factors include diabetes, dyslipidaemia, family history of CAD and fever or recent viral illness.

Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study.

The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.

Preoperative immunonutrition in patients at nutritional risk: results of a double-blinded randomized clinical trial.

Background/Objectives:To evaluate the impact of preoperative immunonutrition (IN) on postoperative morbidity in patients at risk of malnutrition undergoing major gastrointestinal (GI) surgery.Subjects/Methods:The combination of malnutrition and major GI surgery entails high morbidity. The Nutritional Risk Score (NRS) reliably identifies patients who need preoperative nutrition; the optimal nutritional formula for these patients still needs to be defined. In all, 152 patients with a NRS3 and undergoing elective major GI surgery were randomized between IN or isocaloric-isonitrogenous nutrition (ICN) given for 5 days preoperatively. Patients and caregivers were blinded for the allocated intervention. Thirty days complication rate was the primary endpoint. Infections, length of hospital stay and compliance were considered as secondary outcomes.Results:Overall, 145 patients were available for analysis; the 73 patients in the IN group matched well with the 72 ICN patients with regards to patient's and surgical characteristics. In all, 39 IN and 33 ICN patients experienced a total of 48 and 50 postoperative complications, respectively (P=0.723). Both groups did not differ significantly concerning infectious (13 vs 9) complications. Independent risk factors for overall complications were malignant disease (odds ratio (OR)=4.304; confidence interval (CI) 1.317-14.002) and operative time (OR=1.004; CI 1.000-1.008).Conclusion:In patients at nutritional risk, complications, infections and hospital stay after major GI surgery were comparable regardless of preoperative supplementation with IN or ICN.

Clinical outcome following combination of cutting balloon angioplasty and coronary β-radiation for in-stent restenosis : a report from the RENO registry

RESUME : Actuellement la brachythérapie endovasculaire reste le seul traitement efficace pour la resténose intrastent. Malgré ceci, la limitation majeure de cette technique est la resténose aux extrémités du stent (effet de bord) due à une couverture incomplète par la source radioactive (geographical miss). Le ballon coupant et qui ne glisse pas pourrait limiter le barotraumatisme engendré par la dilatation et qui avec la diminution de la radiation aux extrémités de la source radioactive, est à la base du geographical miss. Cette étude prospective a pour but d'examiner l'efficacité du traitement de la resténose intrastent par la combinaison d'angioplastie avec cutting ballon et β - irradiation. Le registre « Radiation in Europe NOvoste » (RENO) inclut tous les patients traités par β - irradiation coronaire avec le système Beta-CathTM System (Novoste Corporation, Brussels, Belgium) n'ayant pas été inclus dans une autre étude randomisée. Un premier sous-groupe de ces patients (groupe 1, n=166), représente les patients traités par cutting ballon et β - irradiation intra coronaire. Ce groupe a été défini d'une manière prospective et les résultats cliniques à 6 mois ont été comparés par rapport aux autres patients qui ont reçu un traitement par dilatation coronaire conventionnelle et β - irradiation (groupe 2, n=712). A 6 mois de suivi, on a retrouvé une différence significative entre les 2 groupes par rapport à la nécessité d'une nouvelle revascularisation du vaisseau préalablement traité (10,2% de récidive dans le groupe 1 contre 16,6 % dans le groupe 2 , p=0,04). Le nombre d'événements cardiaques majeurs (mortalité, infarctus du myocarde et revascularisation) a également été diminué de manière significative (10,8% contre 19,2% ; />=0,01). Cette observation a été confirmée par une analyse multivariée qui indique un risque diminué pour les événements cardiaques majeurs à 6 mois, (rapport de côtes : 0,49 ; intervalle de confiance 0,27-0,88 ; p=0,02). Comparé à l'angioplastie coronarienne avec ballon conventionnel, l'utilisation de cutting ballon avant la β - irradiation dans le traitement de la resténose intrastent démontre une meilleure évolution clinique à 6 mois. ABSTRACT: At present, vascular brachytherapy is the only efficient therapy for in-stent restenosis. Nevertheless edge restenosis often relat¬ed to geographical miss has been identified as a major limitation of the technique. The non-slippery cutting balloon has the potential to limit vascular barotraumas which, together with low-dose irradiation at both ends of the radioactive source, are the prerequisite for geographical miss. This prospective study aimed to examine the efficacy of combining cut¬ting balloon angioplasty and brachytherapy for in-stent restenosis. The Radiation in Europe NOvoste (RENO) registry prospectively tracked all patients who had been treated by coronary β-radiation with the Beta-CathTM System (Novoste Corporation. Brussels, Belgium) but were not included in a randomized radiation trial, A subgroup of patients with in-stent restenosis treated by cutting balloon angioplasty and coronary β-radiation (group 1, n = 166) was prospectively defined, and clinical outcomes of patients at 6 months were compared with those of patients treated by conventional angioplasty and coronary β -radiation (group 2, n = 712). At 6-month follow-up, there was a significant difference between groups 1 and 2 in- target vessel revascularization (10.2% versus 16.6% respectively; p = 0.04) and in the incidence of major adverse clinical events (MACE) including, death, myocardial infarction, and revascularization (10.8% versus 19.2%; p= 0.01). This observation was confirmed by a multivariate analysis indicating a. lower risk for MACE at 6 months (odds ratio: 0.49; confidence intervals: 0.27-0.88; p = 0.02). Compared to conventional angioplasty, cutting balloon angio¬plasty prior to coronary beta-radiation with the Beta-CathTM System seems to improve the 6-month clinical outcome in patients with in-stent restenosis.

Perfusion and diffusion MRI of glioblastoma progression in a four-year prospective temozolomide clinical trial.

PURPOSE: This study was performed to determine the impact of perfusion and diffusion magnetic resonance imaging (MRI) sequences on patients during treatment of newly diagnosed glioblastoma. Special emphasis has been given to these imaging technologies as tools to potentially anticipate disease progression, as progression-free survival is frequently used as a surrogate endpoint. METHODS AND MATERIALS: Forty-one patients from a phase II temolozomide clinical trial were included. During follow-up, images were integrated 21 to 28 days after radiochemotherapy and every 2 months thereafter. Assessment of scans included measurement of size of lesion on T1 contrast-enhanced, T2, diffusion, and perfusion images, as well as mass effect. Classical criteria on tumor size variation and clinical parameters were used to set disease progression date. RESULTS: A total of 311 MRI examinations were reviewed. At disease progression (32 patients), a multivariate Cox regression determined 2 significant survival parameters: T1 largest diameter (p < 0.02) and T2 size variation (p < 0.05), whereas perfusion and diffusion were not significant. CONCLUSION: Perfusion and diffusion techniques cannot be used to anticipate tumor progression. Decision making at disease progression is critical, and classical T1 and T2 imaging remain the gold standard. Specifically, a T1 contrast enhancement over 3 cm in largest diameter together with an increased T2 hypersignal is a marker of inferior prognosis.

Predictors and Moderators of Clinical Outcomes in Adolescents with Severe Mental Disorders After an Assertive Community Treatment.

Previous studies have shown that stressful life events (SLEs), gender, social functioning and pretreatment severity are some of the predictors and/or moderators of treatment outcome in psychiatric care. The current study explored the effect of these predictors and moderators on the treatment outcome related to assertive community treatment (ACT) proposed to young people with severe mental disorders. 98 patients were assessed for externalizing and emotional difficulties, at admission and then at discharge of an ACT. Analyses revealed significant improvements in terms of symptomatology. In particular, regression analyses showed that pretreatment severity is a significant predictor of the outcome on emotional symptoms and is moderated by SLE on the outcome on externalizing symptoms. Furthermore, higher social functioning proved to predict better outcome on externalizing symptoms. Our results further evidence that these factors can explain inter-individual differences in outcome related to ACT. The theoretical and clinical implications of these results are discussed.

Quetiapine and norquetiapine in plasma and cerebrospinal fluid of schizophrenic patients treated with quetiapine: correlations to clinical outcome and HVA, 5-HIAA, and MHPG in CSF.

This study investigated concentrations of quetiapine and norquetiapine in plasma and cerebrospinal fluid (CSF) in 22 schizophrenic patients after 4-week treatment with quetiapine (600 mg/d), which was preceded by a 3-week washout period. Blood and CSF samples were obtained on days 1 and 28, and CSF levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were measured at baseline and after 4 weeks of quetiapine, allowing calculations of differences in HVA (ΔHVA), 5-HIAA (Δ5-HIAA), and MHPG (ΔMHPG) concentrations. Patients were assessed clinically, using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression Scale at baseline and then at weekly intervals. Plasma levels of quetiapine and norquetiapine were 1110 ± 608 and 444 ± 226 ng/mL, and the corresponding CSF levels were 29 ± 18 and 5 ± 2 ng/mL, respectively. After the treatment, the levels of HVA, 5-HIAA, and MHPG were increased by 33%, 35%, and 33%, respectively (P < 0.001). A negative correlation was found between the decrease in PANSS positive subscale scores and CSF ΔHVA (r(rho) = -0.690, P < 0.01), and the decrease in PANSS negative subscale scores both with CSF Δ5-HIAA (r(rho) = -0.619, P = 0.02) and ΔMHPG (r(rho) = -0.484, P = 0.038). Because, unfortunately, schizophrenic patients experience relapses even with the best available treatments, monitoring of CSF drug and metabolite levels might prove to be useful in tailoring individually adjusted treatments.

Energetic and metabolic cost of growth in Gambian infants.

The aim of the study was to measure the energy used for growth of healthy fullterm and breast-fed Gambian infants. The weight gain (WG) of 14 infants (mean age +/- SEM 17 +/- 1 d, weight 3.581 +/- 0.105 kg) was measured over a 2-week period; the energy intake (EI) from breast milk was assessed for 24 h in the middle of the study period by weighing the infant before and after each breast-feed. On the same day, sleeping energy expenditure (SEE) and respiratory quotient (RQ) were measured for 30 min on five occasions through the 24-h period. EI averaged 502 +/- 25 kJ/kg.d, and SEE 230 +/- 6 kJ/kg.d; thus, an average of 272 kJ/kg.d were available for physical activity and the energy stored for growth. The total energy spent by infants while sleeping and for periods of physical activity was calculated to be 1.7 x SEE. The mean RQ measured on five occasions averaged 0.879 +/- 0.009. SEE was correlated with WG (r = 0.747, P less than 0.005), with a slope of the regression line of 5.5 kJ/g; this value can be considered as an estimate of the energy spent for new tissue synthesis in the resting infant. The efficiency of weight gain was lower in this study (67%) than in studies conducted on fast-growing preterm infants or children recovering from malnutrition.

Postprandial thermogenesis in obese children before and after weight reduction.

The thermic effect of a meal (TEM) was measured in a group of 10 prepubertal obese children before (OB) and after (OA) weight reduction, and in a group of 10 age-matched control children (C) of normal body weight. Following a hypocaloric balanced diet for 6 +/- 1 months, the obese children lost 5.2 +/- 1.3 kg i.e. 11% of their initial body weight. The thermic response to the mixed liquid meal - fed at an energy level corresponding to 30% of the 24 h premeal resting metabolic rate - was found to be significantly lower in OB than in C children (61 +/- 25 kJ.3h-1 vs 79 +/- 21 kJ.3h-1, P less than 0.05), despite their higher test meal energy. After slimming, the TEM of obese children increased towards the controls' values (73 +/- 30 kJ.3h-1). These results support the hypothesis of the existence of a moderate thermogenic defect in some obese children which represents a consequence rather than an aetiological factor of obesity.

Toll-Interacting Protein Modulates Gut Flora Composition, Epithelial Barrier Integrity and Susceptibility to Colitis

Toll-like receptor ( TLR) s ignals are key to maintaining hostmicrobial i nteractions. T he T oll-interacting-protein (Tollip) is a ubiquitously-expressed inhibitor of inflammasome a nd TLR signaling. W e hypothesized that T ollip might control g ut homeostasis. G enetic ablation of T ollip d id not lead to spontaneous colitis b ut h ad d ramatic c onsequences on t he intestinal expression of the α-defensin cryptidin 4 and the C-type lectin R EGIIIβ. These c hanges were associated with intestinal dysbiosis a nd e nhanced colonization b y segmented filamentous bacteria - a k ey p ro-inflammatory component of the microbiota. Tollip deficiency increased susceptibility to dextran sulfate sodium (DSS) colitis and aggravated chronic Th17-driven colitis in IL-10-/- mice. Flora d epletion w ith a ntibiotics in T ollip-/- mice w as not sufficient to restore DSS colitis susceptibility and deletion of Tollip in n on-hematopoietic c ells using bone-marrow chimeras w as sufficient to increase s usceptibility t o DSS colitis. After D SS administration, we o bserved several e pithelial defects i n Tollip-/- mice including early tight junctions disruption, increased epithelial apoptosis, and increased intestinal permeability. Overall, our data show that T ollip significantly impacts intestinal h omeostasis by controlling b acterial ecology and intestinal r esponse to chemical and immunological stresses.