Constitutive expression of a chimeric receptor that delivers IL-2/IL-15 signals allows antigen-independent proliferation of CD8+CD44high but not other T cells.

We have prepared transgenic mice whose T cells constitutively express a chimeric receptor combining extracellular human IL-4R and intracellular IL-2Rbeta segments. This receptor can transmit IL-2/IL-15-like signals in response to human, but not mouse, IL-4. We used these animals to explore to what extent functional IL-2R/IL-15R expression controls the capacity of T cells to proliferate in response to IL-2/IL-15-like signals. After activation with Con A, naive transgenic CD8+ and CD4+ T cells respond to human IL-4 as well as to IL-2. Without prior activation, they failed to proliferate in response to human IL-4, although human IL-4 did prolong their survival. Thus, IL-2-induced proliferation of activated T cells requires at least one other Ag-induced change apart from the induction of a functional IL-2R. However, a fraction of CD8+CD44high T cells proliferate in human IL-4 without antigenic stimulation or syngeneic feeder cells. In contrast, CD4+CD44high T cells are not constitutively responsive to human IL-4. We conclude that although all transgenic T cells express a functional chimeric receptor, only some CD8+CD44high T cells contain all molecules required for entry into the cell cycle in response to human IL-4 or IL-15.

L'magerie forensique [Forensic imaging].

In recent years, modern techniques of medical imaging such as MDCT (multidetector-computed tomography) and MRI (magnetic resonance imaging) have pioneered post mortem (pm) investigations, especially in forensic medicine. Particularly pm angiography permits investigating the vascular system in a way which is not possible by performing only conventional autopsy. Beside these radiological methods, other modem visualizing techniques like the three dimensional (3D) surface scan have been implemented in order perform reconstructions of complex cases. By the use of pm imaging techniques, more objective and accurate documentations can be realized that permit an increase of quality in forensic investigations.

Quantitative ultrasound of the heel and fracture risk assessment: an updated meta-analysis.

Meta-analysis of prospective studies shows that quantitative ultrasound of the heel using validated devices predicts risk of different types of fracture with similar performance across different devices and in elderly men and women. These predictions are independent of the risk estimates from hip DXA measures.Introduction Clinical utilisation of heel quantitative ultrasound (QUS) depends on its power to predict clinical fractures. This is particularly important in settings that have no access to DXA-derived bone density measurements. We aimed to assess the predictive power of heel QUS for fractures using a meta-analysis approach.Methods We conducted an inverse variance random effects meta-analysis of prospective studies with heel QUS measures at baseline and fracture outcomes in their follow-up. Relative risks (RR) per standard deviation (SD) of different QUS parameters (broadband ultrasound attenuation [BUA], speed of sound [SOS], stiffness index [SI], and quantitative ultrasound index [QUI]) for various fracture outcomes (hip, vertebral, any clinical, any osteoporotic and major osteoporotic fractures) were reported based on study questions.Results Twenty-one studies including 55,164 women and 13,742 men were included in the meta-analysis with a total follow-up of 279,124 person-years. All four QUS parameters were associated with risk of different fracture. For instance, RR of hip fracture for 1 SD decrease of BUA was 1.69 (95% CI 1.43-2.00), SOS was 1.96 (95% CI 1.64-2.34), SI was 2.26 (95%CI 1.71-2.99) and QUI was 1.99 (95% CI 1.49-2.67). There was marked heterogeneity among studies on hip and any clinical fractures but no evidence of publication bias amongst them. Validated devices from different manufacturers predicted fracture risks with similar performance (meta-regression p values > 0.05 for difference of devices). QUS measures predicted fracture with a similar performance in men and women. Meta-analysis of studies with QUS measures adjusted for hip BMD showed a significant and independent association with fracture risk (RR/SD for BUA = 1.34 [95%CI 1.22-1.49]).Conclusions This study confirms that heel QUS, using validated devices, predicts risk of different fracture outcomes in elderly men and women. Further research is needed for more widespread utilisation of the heel QUS in clinical settings across the world.

Le rein de l'enfant face à la chimiothérapie [The kidney in children under chemotherapy].

Nowadays more and more children survive after an intensive anti-tumoral therapy. The price to pay consists of numerous and relatively frequent long-term sequelae (secondary tumors, neuropsychological deficits, endocrine or cardiac damage). After chemotherapy, we sometimes observe renal side-effects, either tubular (metabolic acidosis, hypokalemia, hypomagnesemia, proteinuria, Fanconi syndrome, rickets) or glomerular (acute or chronic decreased GFR). These renal toxic side-effects are encountered especially after cisplatinum and ifosfamide, less frequently after carboplatin and cyclophosphamide. The pediatrician has to be aware of these toxic nephrologic side-effects, to look out for them and monitor carefully the renal function of all paediatric patients receiving these potentially nephrotoxic chemotherapies.

MRI following severe perinatal asphyxia: preliminary experience.

In 30 children suffering from severe perinatal asphyxia an attempt was made to determine the early prognostic signs of severe hypoxic-ischemic brain injury with magnetic resonance imaging (MRI). Ten early (1-4 days of age), 16 intermediate (2-4 weeks of age), and 38 late MRI (older than 1 month of age) procedures were performed on a 2.35 T MR-system. Severe cerebral necrosis was suspected by T2 hyperintensity of the white matter, with blurred limits to the cortex in early MRI, and was confirmed by T1 hyperintensity of the cortex in intermediate MRI. Severe cerebral necrosis was established at 3 months of age. Of the 11 children with this pattern (group A), 8 had severe and 3 had moderate cerebral palsy on subsequent examination. Thirteen children (group B) had normal late MRI scans; none developed severe cerebral palsy or marked mental retardation. Two children (group C) had focal ischemic lesions. Four children had intracranial hemorrhage (group D). Groups A and B did not differ in the severity of their perinatal histories and findings, suggesting that MRI during the first 3 months is of significant prognostic value.

Fouilles suisses à Derecik, Büyükorhan, province de Bursa (Turquie). Rapport préliminaire 2007-2008

La découverte en 2001 d'une église et de son pavement sur le site de Derecik près de la ville de Büyükorhan en Turquie a suscité de premières fouilles par les archéologues du Musée archéologique de Bursa, capitale de province, la même année. La présentation des mosaïques en 2006 aux participants d'un colloque organisé par l'Université Uludag de Bursa a permis l'intervention d'une équipe suisse sur les lieux dès 2007. Deux années de fouille et d'observations ont conduit à distinguer plusieurs phases de construction de l'église elle-même et de l'emplacement sur lequel elle est implantée. Un temple de construction légère l'a précédée, vraisemblablement dédié à Zeus, et au moins trois phases de construction la caractérisent, complétées par des aménagements postérieurs. L'occupation des lieux est attestée depuis le IIe siècle ap. J.-C., sinon avant, jusqu'aux invasions arabes du VIIIe siècle ap. J.-C.

Les proches des personnes souffrant d'une démence [Caring for the caregiver]

Les syndromes démentiels évoluent sur plusieurs années et touchent la personne dans sa globalité, altérant ses fonctions cognitives, son comportement et ses capacités relationnelles. Le patient perd peu à peu son indépendance. Les proches vont alors jouer un rôle essentiel auprès de lui et devront s'adapter à l'évolution de ses besoins, assumant progressivement surveillance, guidance et aide concrète. L'inestimable contribution des familles et les difficultés liées à l'exercice de ce rôle sont encore trop peu reconnues. De nombreuses études décrivent les conséquences négatives de l'aide naturelle. Toutefois les données sont moins riches quant aux déterminants de ces conséquences. Les proches ont souvent besoin d'information, de conseil et de soutien psychologique. Les programmes psychoéducatifs sont une des possibilités d'aide auprès de l'entourage de patients déments. Dementing disorders usually evolve over several years and alter cognitive performances, behavior and social abilities. Progressively, the patients lose their independence. Families will play a key role for the demented patient and have to adapt to the evolution of his or her needs. They will have to watch over, guide and help the demented proxy. The families' invaluable contribution and the numerous difficulties they encounter while they care for their demented proxy are insufficiently recognized. The deleterious consequences on the carers are currently better known than the determinants of these consequences. Families often need information, counselling and psychological support. Psycho-educational programs represent one of the possible strategies to help families and carers of patients with dementia

Epidemiology of small intestinal atresia in Europe: a register-based study.

BACKGROUND: The epidemiology of congenital small intestinal atresia (SIA) has not been well studied. This study describes the presence of additional anomalies, pregnancy outcomes, total prevalence and association with maternal age in SIA cases in Europe. METHODS: Cases of SIA delivered during January 1990 to December 2006 notified to 20 EUROCAT registers formed the population-based case series. Prevalence over time was estimated using multilevel Poisson regression, and heterogeneity between registers was evaluated from the random component of the intercept. RESULTS: In total 1133 SIA cases were reported among 5126, 164 registered births. Of 1044 singleton cases, 215 (20.6%) cases were associated with a chromosomal anomaly. Of 829 singleton SIA cases with normal karyotype, 221 (26.7%) were associated with other structural anomalies. Considering cases with normal karyotype, the total prevalence per 10 000 births was 1.6 (95% CI 1.5 to 1.7) for SIA, 0.9 (95% CI 0.8 to 1.0) for duodenal atresia and 0.7 (95% CI 0.7 to 0.8) for jejunoileal atresia (JIA). There was no significant trend in SIA, duodenal atresia or JIA prevalence over time (RR=1.0, 95% credible interval (CrI): 1.0 to 1.0 for each), but SIA and duodenal atresia prevalence varied by geographical location (p=0.03 and p=0.04, respectively). There was weak evidence of an increased risk of SIA in mothers aged less than 20 years compared with mothers aged 20 to 29 years (RR=1.3, 95% CrI: 1.0 to 1.8). CONCLUSION: This study found no evidence of a temporal trend in the prevalence of SIA, duodenal atresia or JIA, although SIA and duodenal atresia prevalence varied significantly between registers.

Role of glutathione in macrophage activation: effect of cellular glutathione depletion on nitrite production and leishmanicidal activity.

We have examined the effects of two agents depleting the intracellular pool of glutathione (GSH) on macrophage activation induced by IFN-gamma + LPS, as measured by nitrite production and leishmanicidal activity. Diethylmaleate (DEM), which depletes intracellular GSH by conjugation via a reaction catalyzed by the GSH-S-transferase, strongly inhibited nitrite secretion and leishmanicidal activity when added before or at the time of addition of IFN-gamma + LPS; this inhibition was progressively lost when addition of DEM was delayed up to 10 hr. A close correlation was observed between levels of intracellular soluble GSH during activation and nitrite secretion. Inhibition was partially reversed by the addition of glutathione ethyl ester (GSH-Et). Buthionine sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthetase, also inhibited macrophage activation, although to a lesser extent than DEM despite a more pronounced soluble GSH depletion. This inhibition was completely reversed by the addition of GSH-Et. DEM and BSO did not alter cell viability or PMA-triggered O2- production by activated macrophages, suggesting that the inhibitory effects observed on nitrite secretion and leishmanicidal activity were not related to a general impairment of macrophage function. DEM and BSO treatment reduced iNOS specific activity and iNOS protein in cytosolic extracts. DEM also decreased iNOS mRNA expression while BSO had no effect. Although commonly used as a GSH-depleting agent, DEM may have additional effects because it can also act as a sulhydryl reagent; BSO, on the other hand, which depletes GSH by enzymatic inhibition, has no effect on protein-bound GSH. Our results suggest that both soluble and protein-bound GSH may be important for the induction of NO synthase in IFN-gamma + LPS-activated macrophages.

Could moderate alcohol consumption help prevent the metabolic syndrome and diabetes mellitus ?

Aim and purpose: Moderate alcohol consumption has been associated with lower risk of diabetes mellitus, but few data exist on the metabolic syndrome and on the metabolic impact of heavy drinking. The aim of our study was to investigate the complex relationship between alcohol and the metabolic syndrome and diabetes mellitus in a population-based study in Switzerland with high mean alcohol consumption. Design and methods: In 6188 adults aged 35 to 75, alcohol consumption was categorized as 0, 1-6, 7-13, 14-20, 21-27, 28-34 and >= 35 drinks/week or as nondrinkers, moderate (1-13 drinks), high (14-34 drinks) and very high (>= 35 drinks) alcohol consumption. The metabolic syndrome was defined according to the ATP-III criteria and diabetes mellitus as fasting glycemia >= 7 mmol/l or self-reported medication.We used multivariate analysis adjusted for age, gender, smoking status, physical activity and education level to determine the prevalence of the conditions according to drinking categories. Results: 73% (n = 4502) of the participants consumed alcohol, 16% (n = 993) were high drinkers and 2% (n = 126) very high drinkers. In multivariate analysis, alcohol consumption had a U-shaped relationship with the metabolic syndrome and diabetes mellitus. The prevalence of the metabolic syndrome significantly differed between nondrinkers (24%), moderate (19%), high (20%) and very high drinkers (29%) (P<= 0.005). The prevalence of diabetes mellitus also significantly differed between nondrinkers (6.0%), moderate (3.6%), high (3.8%) and very high drinkers (6.7%) (P<= 0.05). These relationships did not differ according to beverage types. Conclusions: The prevalence of the metabolic syndrome and diabetes mellitus decrease with moderate alcohol consumption and increase with heavy drinking, without differences according to beverage types. Recommending to limit alcohol consumption to 1-2 drinks/day might help prevent these conditions in primary care Metabolic Syndrome and Diabetes Mellitus.