Decreased alcohol self-administration and increased alcohol sensitivity and withdrawal in CB1 receptor knockout mice

Recent advances in the understanding of the neurobiological basis of alcohol dependence suggest that the endocannabinoid system may play a key role in the reinforcing effects of ethanol. In the present study, disruption of CB1 receptors in mice generated on a CD1 background decreased both ethanol consumption and preference. This decreased ethanol self-administration was associated with increased sensitivity to the acute intoxicating effects of ethanol. Mutant mice were more sensitive to the hypothermic and sedative/hypnotic effects of acute ethanol administration (1.5-4.0 g/kg), although plasma ethanol concentrations did not differ from those of controls. Moreover, wild-type mice exhibited normal locomotor activation caused by 1.0-2.5 g/kg injection of ethanol, whereas mutant mice displayed sedation in response to the injection of the same ethanol doses. The severity of alcohol withdrawal-induced convulsions was also increased in CB1(-/-) mice. Our results suggest that CB1 receptors participate in the regulation of ethanol drinking and demonstrate that their disruption lead to increased ethanol sensitivity and withdrawal severity.     

Degree of concurrency among experts in data collection and diagnostic hypothesis generation during clinical encounters

BACKGROUND: Given that there are variations in clinicians' reasoning, methods to elaborate scoring checklists for standardised patient-based assessment need to be valid. The use of data elicited by experts solving problems independently has been advocated as a method of setting performance standards. AIMS: To determine the degree of concurrence and common characteristics among items independently elicited by doctors during patient encounters and to assess the number of experts needed to derive reliable performance standards. METHODS: Six experienced internists worked-up the same 7 chief complaints with standardised patients (SPs). A stimulated recall of the recorded encounter was then performed. The degree of concurrence of the collected history and physical examination information and the generated diagnostic hypotheses was computed. Reliability was derived from generalisability analyses. RESULTS: By case, experts elicited a mean of 114 information items (SD = 15) and generated 30 diagnostic hypotheses (SD = 6). A high concurrence (80-100%) was observed for a mean of 22 information items (20%; SD = 6) and 7 diagnostic hypotheses (24%; SD = 2). More than a third of the 153 highly concurrent information items were clarification questions. At least 3 doctors were needed to obtain a reliability of 0.80 or higher when deriving the scoring checklists. CONCLUSION: The limited concurrency in data elicited by clinicians during a patient encounter supports the use of high-fidelity methods to develop performance checklists used in SP-based assessment. It also suggests that relying only on information collected to assess clinical competence may not be sufficient. Additional criteria, such as structure and style of work-up, should be further explored.     

The effects of decanted sediments on embryogenesis in oysters (Crassostrea gigas)

Sediments act as sinks for contaminants of natural and anthropogenic origin, constituting a risk to the living organisms. In this study, sediments were collected from three sites on the coast of southwest France. The objective of this research was to determine the effects of sediments on embryonic development of bivalves and to identify precisely when the contaminants affect the embryos and induce them to develop in an abnormal way. The toxicity of decanted sediments and overlying waters were assessed using the oyster embryo bioassay. The physical characteristics and contaminant levels in the sediments were measured, including polycyclic aromatic hydrocarbon (PAH) and metal concentrations. Despite contaminant concentrations for PAH and metals only exceeding the effects range-low levels, all decanted sediments tested induced deleterious effects on the embryonic development of oysters, while no significant abnormalities were observed for overlying waters. The study results suggest that abnormal larvae mainly are caused by direct contact with contaminated sediments.     

Cutaneous malignant melanoma and neurofibromatosis type 1

Neurofibromatosis 1 (NF1) is a genetically transmitted disease occurring approximately once in 3000 live births and resulting from mutations of the NF1 gene that encodes a protein named neurofibromin, a negative regulator of the ras-dependent pathway. An excess of neoplasia especially tumours of neuroectodermal origin is classically observed. The occurrence of malignant melanoma in patients with NF1 has already been described in scattered clinical reports but little is known as to the characteristics of melanoma arising in NF1 patients. A multicentric retrospective study was conducted on a panel of French referring centres for a period of 13 years to identify patients with both melanoma and NF1. Patients with mucosal or ocular melanoma were excluded. The diagnosis of malignant melanoma was based on specific histology whereas NF1 was identified according to the criteria proposed by the NIH Consensus Conference. All patient fulfilling criteria for both melanoma and NF1 were investigated using a common procedure recording clinical and histological data along with prognostic factors for the two diseases. Eleven patients were identified with both diseases. The clinical pattern of NF1 was quite similar to the classical form of the disease, but some unusual features were present as regards to the melanoma: a sex-ratio of 10 women for one man and an average age lower than expected (median age=33 years) for melanoma occurrence. Among prognostic factors, median thickness was high compared to large series of melanoma in the literature (3.20 versus 1.5 mm). Another neoplasia occurred in three patients. An increase in melanoma incidence in patients with NF1 remains hypothetical but our small series of malignant melanoma arising in NF1 patients displays a large female preponderance, a higher thickness than expected and a frequent association with a second neoplasia. The peculiar female proneness for cancer whatever its localization and the risk of multiple neoplasias have already been reported in NF1 patients and could be true for malignant melanoma as well.     

Prognostic significance of angiogenesis evaluated by CD105 expression compared to CD31 in 905 breast carcinomas: correlation with long-term patient outcome

Our purpose was to determine the respective prognostic significance of CD105 and CD31 immunoexpression in node negative patients with breast carcinoma, since angiogenesis induces blood borne metastases and death in carcinomas. CD105 (endoglin) has been reported as expressed by activated endothelial cells and consequently should better reflect neoangiogenesis in malignant tumors. Comparison of CD31 and CD105 immunocytochemical expression was undertaken in a series of 905 breast carcinomas. Results were compared to patients' long-term (median = 11.3 years) outcome. Univariate (Kaplan-Meier) analysis showed that the number of CD105+ microvessels (cut-off 15 vessels) correlated significantly with poor overall survival (p=0.001). This correlation was less significant in node negative patients (p=0.035). The number of CD31+ microvessels (cut-off 25 vessels) similarly correlated with poor survival (p=0.032) but not in the subgroup of node negative patients. Marked CD105 expression also correlated with a high risk for metastasis in all patients (p=0.0002) and in the subset of node negative patients (p=0.001). Similarly metastasis risk in node negative patients correlated with marked CD31 immunocytochemical expression (p=0.02). Multivariate analysis (Cox model) identified CD105, but not CD31 immunoexpression, as an independent prognostic indicator. Our results suggest that: i) in breast carcinomas, immunoselection of microvessels containing activated CD105 labelled endothelial cells is endowed with a stronger prognostic significance, as compared to CD31 vessels labelling; ii) the CD105 immunoexpression may be considered as a potential tool for selecting node negative patients with a poorer outcome and higher metastasis risk; iii) in these patients specific antiangiogenic therapy targeted by anti-CD105 conjugates can be further developed.     

Intestinal transplantation

Advances in immunosuppressive treatment as well as better monitoring and control of acute rejection have brought intestinal transplantation (ITx) into the realm of standard treatment for permanent intestinal failure. The results from the intestinal Transplant International Registry (www.intestinaltransplant.org) indicate that ITx is currently an acceptable clinical modality for selected patients with permanent intestinal failure¹. The goal of this short review is to deal with indications, clinical results and complications of ITx. Although it has been used in humans for the past two decades, very few data are available regarding graft function and its monitoring.     

Left ventricular outflow obstruction in rhabdomyoma of infancy: meta-analysis of the literature

Primary heart tumors are exceptional in infants and children. Most common is the rhabdomyoma, often associated with tuberous sclerosis (Bourneville's disease). This tumor is generally believed to have no hemodynamic effects in the majority of cases. Recently, severe obstruction of the left ventricular outflow tract by a solitary tumor was diagnosed during pregnancy and emergency surgery was needed soon after birth.     

Nondigestible carbohydrates in the diets of infants and young children: a commentary by the ESPGHAN Committee on Nutrition

The consumption of nondigestible carbohydrates is perceived as beneficial by health professionals and the general public, but the translation of this information into dietary practice, public health recommendations, and regulatory policy has proved difficult. Nondigestible carbohydrates are a heterogeneous entity, and their definition is problematic. Without a means to characterize the dietary components associated with particular health benefits, specific attributions of these cannot be made. Food labeling for "fiber" constituents can be given only in a general context, and the development of health policy, dietary advice, and education, and informed public understanding of nondigestible carbohydrates are limited. There have, however, been several important developments in our thinking about nondigestible carbohydrates during the past few years. The concept of fiber has expanded to include a range of nondigestible carbohydrates. Their fermentation, fate, and effects in the colon have become a defining characteristic; human milk, hitherto regarded as devoid of nondigestible carbohydrates, is now recognized as a source for infants, and the inclusion of nondigestible carbohydrates in the diet has been promoted for their "prebiotic" effects. Therefore, a review of the importance of nondigestible carbohydrates in the diets of infants and young children is timely. The aims of this commentary are to clarify the current definitions of nondigestible carbohydrates, to review published evidence for their biochemical, physiologic, nutritional, and clinical effects, and to discuss issues involved in defining dietary guidelines for infants and young children.     

Sleep microstructure around sleep onset differentiates major depressive insomnia from primary insomnia

In the present study we investigate whether alterations of sleep propensity or of wake propensity are implicated in sleep initiation disturbances encountered in major depressive insomnia and in primary insomnia. For this purpose, the time course of electroencephalogram (EEG) power density during the period preceding sleep onset and during the first non-rapid eye movement (REM) period was examined in three age and gender matched groups of 10 women and 11 men (healthy controls, primary insomniacs and depressive insomniacs). In contrast to healthy controls and depressive insomniacs, patients with primary insomnia did not experience a gradual decrease of their alpha and beta1 power during the sleep onset period and had a lower delta activity in the 5 min preceding sleep onset. Compared with the two other groups, depressive patients exhibit less dynamic changes in slow wave activity during the first non-REM period. The present results suggest that hyperarousal (high 'Process W') may mainly be implicated in the sleep initiation difficulties of primary insomniacs whereas the homeostatic sleep regulation process seems to be partially maintained. In our major depressed patients, the sleep initiation disturbances appeared to relate to a lower sleep pressure (low 'Process S') rather than to hyperarousal. This study supports the idea that different mechanisms are implicated in sleep disturbances experienced by primary insomniacs and major depressive insomniacs.