Prise en charge psychoéducative pour sevrage de benzodiazépines en cure thermale (et enquête auprès de médecins généralistes)

International audienceThe prevalence of benzodiapezine (BZD) consumption is assessed as 18.6% over 12 months and 11.3% over 30 days [1]. Within the framework of a transversal study with general practitioners (GP), 2000 GP representatives were picked by drawing lots. 300 provided information on 997 BZD-treated patients (15.6% patients/GP). 4.2% of the patients revealed the association of a length of treatment greater than recommended, with a notification to reduce or stop treatment by BZD, and others had expressed their wish to stop the treatment altogether. The weekly number of patients can be estimated at 47,189 for whom BZD withdrawal has been indicated. At the close of this work, a group of experts offered to draw up a procedure on in-care for BZD withdrawal in spa therapy for groups of 6 to 12 patients, stable regular BZD over-consumers for at least 3 months. This protocol associates daily crenotherapy treatment, personalized psychotherapeutic follow-up, consistent medical care and psycho-educative workshops. It is completed by a post-cure 6-month follow-up. There is an experimental phase under way in 2010 and 2011

Pre and Post Synaptic NMDA Effects Targeting Purkinje Cells in the Mouse Cerebellar Cortex

N-methyl-D-aspartate (NMDA) receptors are associated with many forms of synaptic plasticity. Their expression level and subunit composition undergo developmental changes in several brain regions. In the mouse cerebellum, beside a developmental switch between NR2B and NR2A/C subunits in granule cells, functional postsynaptic NMDA receptors are seen in Purkinje cells of neonate and adult but not juvenile rat and mice. A presynaptic effect of NMDA on GABA release by cerebellar interneurons was identified recently. Nevertheless whereas NMDA receptor subunits are detected on parallel fiber terminals, a presynaptic effect of NMDA on spontaneous release of glutamate has not been demonstrated. Using mouse cerebellar cultures and patch-clamp recordings we show that NMDA facilitates glutamate release onto Purkinje cells in young cultures via a presynaptic mechanism, whereas NMDA activates extrasynaptic receptors in Purkinje cells recorded in old cultures. The presynaptic effect of NMDA on glutamate release is also observed in Purkinje cells recorded in acute slices prepared from juvenile but not from adult mice and requires a specific protocol of NMDA application

Morphological docking of secretory vesicles

Calcium-dependent secretion of neurotransmitters and hormones is essential for brain function and neuroendocrine-signaling. Prior to exocytosis, neurotransmitter-containing vesicles dock to the target membrane. In electron micrographs of neurons and neuroendocrine cells, like chromaffin cells many synaptic vesicles (SVs) and large dense-core vesicles (LDCVs) are docked. For many years the molecular identity of the morphologically docked state was unknown. Recently, we resolved the minimal docking machinery in adrenal medullary chromaffin cells using embryonic mouse model systems together with electron-microscopic analyses and also found that docking is controlled by the sub-membrane filamentous (F-)actin. Currently it is unclear if the same docking machinery operates in synapses. Here, I will review our docking assay that led to the identification of the LDCV docking machinery in chromaffin cells and also discuss whether identical docking proteins are required for SV docking in synapses

Early phase clinical trials of anticancer agents in children and adolescents — an ITCC perspective

In the past decade, the landscape of drug development in oncology has evolved dramatically; however, this paradigm shift remains to be adopted in early phase clinical trial designs for studies of molecularly targeted agents and immunotherapeutic agents in paediatric malignancies. In drug development, prioritization of drugs on the basis of knowledge of tumour biology, molecular 'drivers' of disease and a drug's mechanism of action, and therapeutic unmet needs are key elements; these aspects are relevant to early phase paediatric trials, in which molecular profiling is strongly encouraged. Herein, we describe the strategy of the Innovative Therapies for Children with Cancer (ITCC) Consortium, which advocates for the adoption of trial designs that enable uninterrupted patient recruitment, the extrapolation from studies in adults when possible, and the inclusion of expansion cohorts. If a drug has neither serious dose-related toxicities nor a narrow therapeutic index, then studies should generally be started at the adult recommended phase II dose corrected for body surface area, and act as dose-confirmation studies. The use of adaptive trial designs will enable drugs with promising activity to progress rapidly to randomized studies and, therefore, will substantially accelerate drug development for children and adolescents with cancer

The Association of Interpleural Ropivacaine and Epidural Following Major Thoracic Surgery: A Randomised Clinical Trial Investigating Pharmocokinetics and Benefits

Interpleural blockades (IPB) can be effective in reducing this pain, but results after thoracotomy are controversial. The current study investigates the effects of the association of ropivacaine-based IPB and morphine epidurals after posterolateral thoracic surgery. Method: In this prospective, randomised, triple blind, placebo-controlled trial, patients received either intermittent ropivacaine IPB (R-group), (30 mg every 6 hours over 48 hours) or a placebo containing saline serum (P-group). The two groups had a morphine lumbar epidural. Pain was evaluated via patients’ reports and total morphine requirements. Results: 90 patients participated. There were no significant differences between levels of pain reported on mobilisation or morphine consumption between the two groups. For the principal criterion of VAS-A≥70 over the first 48 hours, this corresponds to a RR of 1.3(95%= 0.4-3.8). Patients in the R-group reported higher levels of pain at rest on day 2. The mean peak plasma concentrations of ropivacaine remained inferior to toxic plasma concentration levels. Conclusion: Postoperative interpleural infusions of 30 mg of ropivacaine every 6 hours in association with morphine epidurals are safe and feasible but do not improve postoperative experience of pain

Genetic abnormalities detected by comparative genomic hybridization in a human endometriosis-derived cell line

Comparative genomic hybridization (CGH) was used in parallel with fluorescence in-situ hybridization (FISH) and conventional karyotyping to perform a genome-wide survey of DNA gains and losses in the endometriosis-derived permanent cell line, FbEM-1. The cytogenetic analysis showed a complex karyotype with numerical changes and multiple chromosome aberrations, including the der(1) complement marker exhibiting a large homogenous staining region (HSR). The chromosomal rearrangement interpreted as der(5) t(5;6)(q34;p11) was found in the majority of the metaphases indicating a clonal abnormality. Repeated CGH experiments demonstrated over-representation of chromosomes 1, 2, 3, 5, 6p, 7, 16, 17q, 20, 21q and 22q, while chromosomes 6q, 9, 11p, 12, 13q, 18 and X were under-represented. Using DNA from the original endometriotic tissues, including a peritoneal implant and ovarian endometrioma, CGH analysis revealed loss of DNA copy number on 1p, 22q and chromosome X, while gain was found on chromosomal arms 6p and 17q. FISH analysis confirmed that the gain at 17q includes amplification of the proto-oncogene HER-2/neu in 16% of the FbEM-1 nuclei and in 12% of cells from the primary ovarian endometrioma tissue. These findings demonstrate that FbEM-1 cells share certain molecular cytogenetic features with the original tissue and suggest that chromosomal instability is important in the development of endometriosis