Evolution of glucose induced thermogenesis in obese subjects with and without diabetes: a six-year follow-up study.

The thermogenic response to a 100 g oral glucose load was measured prospectively (by indirect calorimetry) in three groups of obese subjects: (1) normal glucose tolerance (n = 12, initial weight 86.4 +/- 3.9 kg, BMI 30.4 +/- 1.1 kg/m2; (2) impaired glucose tolerance (n = 8, initial weight 105.3 +/- 7.6 kg, body mass index (BMI) 37.6 +/- 2.9 kg/m2; (3) diabetes (n = 12), initial weight 102.1 +/- 5.3 kg, BMI 36.2 +/- 2.0 kg/m2). The thermogenic response to glucose averaged 6.8 +/- 1.1 and 7.0 +/- 1.0 per cent, in the two non-diabetic obese groups respectively, and was significantly lower in the obese diabetic group (3.1 +/- 0.8 per cent). With the evolution of obesity (i.e. 6 years later), the glucose-induced thermogenesis (GIT) was significantly reduced in the non-diabetic groups (P less than 0.05) to 4.1 +/- 0.8 and 3.0 +/- 1.1 per cent respectively, and was still blunted in the diabetic group (2.1 +/- 0.7 per cent). The decrease in GIT was accompanied by a reduction in glucose tolerance and insulin response with no change in fasting plasma insulin. These effects were observed despite the fact that the body weight of the subject did not change significantly over the 6-year period. It is concluded that the decrease in GIT which accompanies the worsening of glucose tolerance and the occurrence of diabetes is a mechanism which may contribute to maintain the obesity state by a reduction of energy expenditure.

Identifying the best body mass index metric to assess adiposity change in children.

OBJECTIVE: Although dual-energy X-ray absorptiometry (DEXA) is the preferred method to estimate adiposity, body mass index (BMI) is often used as a proxy. However, the ability of BMI to measure adiposity change among youth is poorly evidenced. This study explored which metrics of BMI change have the highest correlations with different metrics of DEXA change. METHODS: Data were from the Quebec Adipose and Lifestyle Investigation in Youth cohort, a prospective cohort of children (8-10 years at recruitment) from Québec, Canada (n=557). Height and weight were measured by trained nurses at baseline (2008) and follow-up (2010). Metrics of BMI change were raw (ΔBMIkg/m(2) ), adjusted for median BMI (ΔBMIpercentage) and age-sex-adjusted with the Centers for Disease Control and Prevention growth curves expressed as centiles (ΔBMIcentile) or z-scores (ΔBMIz-score). Metrics of DEXA change were raw (total fat mass; ΔFMkg), per cent (ΔFMpercentage), height-adjusted (fat mass index; ΔFMI) and age-sex-adjusted z-scores (ΔFMz-score). Spearman's rank correlations were derived. RESULTS: Correlations ranged from modest (0.60) to strong (0.86). ΔFMkg correlated most highly with ΔBMIkg/m(2) (r = 0.86), ΔFMI with ΔBMIkg/m(2) and ΔBMIpercentage (r = 0.83-0.84), ΔFMz-score with ΔBMIz-score (r = 0.78), and ΔFMpercentage with ΔBMIpercentage (r = 0.68). Correlations with ΔBMIcentile were consistently among the lowest. CONCLUSIONS: In 8-10-year-old children, absolute or per cent change in BMI is a good proxy for change in fat mass or FMI, and BMI z-score change is a good proxy for FM z-score change. However change in BMI centile and change in per cent fat mass perform less well and are not recommended.

Acute alcohol consumption and injury: risk associations and attributable fractions for different injury mechanisms.

OBJECTIVE: Most studies on alcohol as a risk factor for injuries have been mechanism specific, and few have considered several mechanisms simultaneously or reported alcohol-attributable fractions (AAFs)-which was the aim of the current study. METHOD: Data from 3,592 injured and 3,489 noninjured patients collected between January 2003 and June 2004 in the surgical ward of the emergency department of the Lausanne University Hospital (Switzerland) were analyzed. Four injury mechanisms derived from the International Classification of Diseases, 10th Revision, were considered: transportation-related injuries, falls, exposure to forces and other events, and interpersonal violence. Multinomial logistic regression models were calculated to estimate the risk relationships of different levels of alcohol consumption, using noninjured patients as quasi-controls. The AAFs were then calculated. RESULTS: Risk relationships between injury and acute consumption were found across all mechanisms, commonly resulting in dose-response relationships. Marked differences between mechanisms were observed for relative risks and AAFs, which varied between 15.2% and 33.1% and between 10.1% and 35.9%, depending on the time window of consumption (either 6 hours or 24 hours before injury, respectively). Low and medium levels of alcohol consumption generally were associated with the most AAFs. CONCLUSIONS: This study underscores the implications of even low levels of alcohol consumption on the risk of sustaining injuries through any of the mechanisms considered. Substantial AAFs are reported for each mechanism, particularly for injuries resulting from interpersonal violence. Observation of a so-called preventive paradox phenomenon is discussed, and prevention or intervention measures are described.

Pattern and clinical significance of cancer-testis gene expression in head and neck squamous cell carcinoma

Les cancer-testis antigènes appartiennent à la famille des antigènes tumoraux spécifiques. Ils ont montré un pouvoir immunogène chez les patients porteurs de différents cancers. En effet, ils stimulent sélectivement les lymphocytes cytotoxiques, et leur expression spécifique dans les tissus tumoraux en fait une cible idéale pour une vaccination antitumorale. Le but de cette étude est d'identifier l'expression de certains de ces antigènes, d'analyser leur valeur pronostique et de déterminer la meilleure cible antigénique pour permettre une immunothérapie spécifique dans les carcinomes épidermoïdes des voies aérodigestives supérieures. Le profil et le taux d'expression de 12 cancer-testis antigènes (MAGE-A1, MAGE-A3, MAGE-A4, MAGEA10, MAGE-C2, NY-ESO-1, LAGE-1, SSX-2, SSX-4, BAGE, GAGE-1/2, GAGE-3/4) et de 3 autres antigènes tumoraux spécifiques (PRAME, HERV-K-MEL, NA-17A) ont été évalués par RT-PCR sur 57 échantillons de cancers ORL primaires. Les paramètres tumoraux et cliniques ont été prospectivement collectés afin de corréler ces données avec le résultat de nos investigations immunobiologiques. Quatre-vingt-huit pour cent des tumeurs expriment au moins 1 antigène. Une co-expression de 3 gènes ou plus est détectée chez 59% des patients. MAGE-A4 (60%), MAGE-A3 (51%), PRAME (49%) et HERV-K-MEL (42%) sont les gènes le plus fréquemment exprimés. Ils sont totalement absents des muqueuses saines avoisinantes. La présence de MAGE-A et NY-ESO-1 à la surface des cellules a été vérifiée par immunohistochimie. Nos analyses statistiques ont permis d'identifier une diminution de la survie liée au cancer chez les patients porteurs d'une tumeur exprimant de multiples cancer-testis antigènes et notamment MAGE-A4 dont l'expression indépendante d'autres éléments cliniques s'associe statistiquement à un taux de survie diminué. Nos résultats ont permis d'identifier un rôle pronostique de l'expression des gènes associés aux tumeurs dont l'expression est apparemment liée à un phénotype de malignité plus élevé. Cette constatation, corroborée par l'identification parallèle d'un infiltrat lymphocytaire spécifique confirme l'utilité potentielle de certains cancer-testis antigènes comme cible pour une immunothérapie ciblée dans les carcinomes des voies aérodigestives supérieures

Vesicular transport of d-serine in astrocytes

The concept of tripartite synapse suggests that astrocytes make up a functional synapse with pre- and postsynaptic neuronal elements to modulate synaptic transmission through the regulated release of neuromodulators called gliotransmitters. Release of gliotransmitters such as glutamate or D-serine has been shown to depend on Ca21-dependent exocytosis. However, the origin (cytosolic versus vesicular) of the released gliotransmitter is still a matter of debate. The existence of Ca21-regulated exocytosis in astrocytes has been questioned mostly because the nature of secretory organelles which are loaded with gliotransmitters is unknown. Here we show the existence of a population of vesicles that uptakes and stores glutamate and D-serine in astrocytes which are present in situ. Immunoisolated glial organelles expressing synaptobrevin 2 (Sb2) display morphological and biochemical features very similar to synaptic vesicles. We demonstrate that these organelles not only contain and uptake glutamate but also display a glia-specific transport activity for D-serine. Furthermore, we report that the uptake of D-serine is energized by a H1-ATPase present on the immunoisolated vesicles and that cytosolic chloride ions modulate the uptake of D-serine. Finally, we show that serine racemase (SR), the synthesizing enzyme for D-serine, is anchored to the membrane of glial organelles allowing a local and efficient concentration of the gliotransmitter to be transported. We conclude that vesicles in astrocytes do exist with the goal to store and release D-serine, glutamate and most likely other neuromodulators.

Counselling overweight and obese patients in primary care: a prospective cohort study.

BACKGROUND: Primary care physicians are well positioned to provide counselling for overweight and obese patients, but no prospective study has assessed the effectiveness of this counselling in primary care. We aimed to evaluate weight reduction counselling by primary care physicians, and its relationship with weight change and patients' behaviour to control weight. DESIGN: A prospective cohort study. METHODS: We enrolled 523 consecutive overweight and obese patients from two Swiss academic primary care clinics. Physicians and patients were blinded to the study aims. We assessed the use of 10 predefined counselling strategies for weight reduction, and weight change and behaviour to control weight after 1 year. RESULTS: Sixty-five per cent of patients received some form of weight reduction counselling whereas 35% received no counselling. A total of 407 patients completed the 1-year follow-up. Those who received counselling lost on average (SD) 1.0 (5.0) kg after 1 year, whereas those who were not advised gained 0.3 (5.0) kg (P = 0.02). In multivariate analysis, each additional counselling strategy was associated with a mean weight loss of 0.2 kg (95% confidence interval 0.03-0.4, P = 0.02). Patients counselled by their physician had more favourable behaviour to control weight than those not counselled, such as setting a target weight (56 versus 36%) or visiting a dietician (23 versus 10%, both P < 0.001). CONCLUSIONS: Weight reduction counselling by primary care physicians is associated with a modest weight loss and favourable behaviour to control weight. However, many obese and overweight patients receive no advice on weight loss during primary care visits.

Endocavitary contact radiation therapy for ultrasonographically staged T1 N0 and T2 N0 rectal cancer.

BACKGROUND: The purpose of this study was to determine the long-term outcomes of patients undergoing endocavitary contact radiation therapy (ECR) for stage I rectal cancer. METHODS: A database of patients treated with ECR for biopsy-proven rectal adenocarcinoma from July 1986 to June 2006 was reviewed retrospectively. Only patients with primary, non-metastatic, ultrasonographically staged T1 N0 and T2 N0 cancer who had no adjuvant treatment were included. Patients received a median of 90 (range 60-190) Gy contact radiation, delivered transanally by a 50-kV X-ray tube in two to five fractions. RESULTS: Of 149 patients, 77 (40 T1, 37 T2) met the inclusion criteria. Median age was 74 (range 38-104) years, and median follow-up 69 (range 10-219) months. ECR failed in 21 patients (27 per cent) (persistent disease, four; recurrence, 17), of whom ten remained disease free after salvage therapy. The estimated 5-year disease-free survival rate was 74 (95 per cent confidence interval 63 to 83) per cent after ECR alone, and 87 (76 to 93) per cent when survival after salvage therapy for recurrence was included. CONCLUSION: ECR is a minimally invasive treatment option for early-stage rectal cancer. However, similar to other local therapies, ECR has a worse oncological outcome than radical surgery.

Bacterial biofilms and capsular contracture in patients with breast implants.

BACKGROUND: It has been hypothesized that bacterial biofilms on breast implants may cause chronic inflammation leading to capsular contracture. The association between bacterial biofilms of removed implants and capsular contracture was investigated. METHODS: Breast implants explanted between 2006 and 2010 at five participating centres for plastic and reconstructive surgery were investigated by sonication. Bacterial cultures derived from sonication were correlated with patient, surgical and implant characteristics, and the degree of capsular contracture. RESULTS: The study included 121 breast implants from 84 patients, of which 119 originated from women and two from men undergoing gender reassignment. Some 50 breast prostheses were implanted for reconstruction, 48 for aesthetic reasons and 23 implants were used as temporary expander devices. The median indwelling time was 4·0 (range 0·1-32) years for permanent implants and 3 (range 1-6) months for temporary devices. Excluding nine implants with clinical signs of infection, sonication cultures were positive in 40 (45 per cent) of 89 permanent implants and in 12 (52 per cent) of 23 temporary devices. Analysis of permanent implants showed that a positive bacterial culture after sonication correlated with the degree of capsular contracture: Baker I, two of 11 implants; Baker II, two of ten; Baker III, nine of 23; and Baker IV, 27 of 45 (P < 0·001). The most frequent organisms were Propionibacterium acnes (25 implants) and coagulase-negative staphylococci (21). CONCLUSION: Sonication cultures correlated with the degree of capsular contracture, indicating the potential causative role of bacterial biofilms in the pathogenesis of capsular contracture. Registration number: NCT01138891 (http://www.clinicaltrials.gov).