Efficacy of vinblastine in central nervous system Langerhans cell histiocytosis: a nationwide retrospective study

<p>Abstract</p> <p>Background</p> <p>Vinblastine (VBL) is the standard treatment for systemic Langerhans cell histiocytosis (LCH), but little is known about its efficacy in central nervous system (CNS) mass lesions.</p> <p>Methods</p> <p>A retrospective chart review was conducted. Twenty patients from the French LCH Study Group register met the inclusion criteria. In brief, they had CNS mass lesions, had been treated with VBL, and were evaluable for radiologic response.</p> <p>Results</p> <p>The median age at diagnosis of LCH was 11.5 years (range: 1-50). Intravenous VBL 6 mg/m²was given in a 6-week induction treatment, followed by a maintenance treatment. The median total duration was 12 months (range: 3-30). Eleven patients received steroids concomitantly. Fifteen patients achieved an objective response; five had a complete response (CR: 25%), ten had a partial response (PR: 50%), four had stable disease (SD: 20%) and one patient progressed (PD: 5%). Of interest, four out of the six patients who received VBL without concomitant steroids achieved an objective response. With a median follow-up of 6.8 years, the 5-year event-free and overall survival was 61% and 84%, respectively. VBL was well-tolerated and there were no patient withdrawals due to adverse events.</p> <p>Conclusion</p> <p>VBL, with or without steroids, could potentially be a useful therapeutic option in LCH with CNS mass lesions, especially for those with inoperable lesions or multiple lesions. Prospective clinical trials are warranted for the evaluation of VBL in this indication.</p

Multifocal Ectopic Purkinje-Related Premature Contractions: A New SCN5A-Related Cardiac Channelopathy.: MEPPC: a new SCN5A-related cardiac channelopathy

International audienceOBJECTIVES: The aim of this study was to describe a new familial cardiac phenotype and to elucidate the electrophysiological mechanism responsible for the disease. BACKGROUND: Mutations in several genes encoding ion channels, especially SCN5A, have emerged as the basis for a variety of inherited cardiac arrhythmias. METHODS: Three unrelated families comprising 21 individuals affected by multifocal ectopic Purkinje-related premature contractions (MEPPC) characterized by narrow junctional and rare sinus beats competing with numerous premature ventricular contractions with right and/or left bundle branch block patterns were identified. RESULTS: Dilated cardiomyopathy was identified in 6 patients, atrial arrhythmias were detected in 9 patients, and sudden death was reported in 5 individuals. Invasive electrophysiological studies demonstrated that premature ventricular complexes originated from the Purkinje tissue. Hydroquinidine treatment dramatically decreased the number of premature ventricular complexes. It normalized the contractile function in 2 patients. All the affected subjects carried the c.665G>A transition in the SCN5A gene. Patch-clamp studies of resulting p.Arg222Gln (R222Q) Nav1.5 revealed a net gain of function of the sodium channel, leading, in silico, to incomplete repolarization in Purkinje cells responsible for premature ventricular action potentials. In vitro and in silico studies recapitulated the normalization of the ventricular action potentials in the presence of quinidine. CONCLUSIONS: A new SCN5A-related cardiac syndrome, MEPPC, was identified. The SCN5A mutation leads to a gain of function of the sodium channel responsible for hyperexcitability of the fascicular-Purkinje system. The MEPPC syndrome is responsive to hydroquinidine

Evaluation de la prévalence de l'insuffisance cardiaque deux ans après la survenue d'un infarctus du myocarde sans élévation du segment ST (étude rétrospective sur 105 patients hospitalisés au CHU de Dijon)

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Rôle du médecin généraliste dans le dépistage et la prise en charge des troubles de l'acquisition du langage oral chez l'enfant (réalisation d'une enquête de faisabilité auprès des médecins généralistes d'un test de dépistage le ERTL 4)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Functional analysis reveals splicing mutations of the CASQ2 gene in patients with CPVT: implication for genetic counselling and clinical management.

International audienceCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and severe arrhythmogenic disorder. Although usually transmitted in a recessive form, few cases of dominant mutations have been reported. Thirteen mutations in the CASQ2 gene have been reported so far in association with CPVT. We performed molecular analysis of the CASQ2 gene in 43 probands with CPVT and identified eight mutations in five patients. Six mutations were novel: one was a single nucleotide deletion, three affected consensus splice sites, and two had unknown consequences: the c.939 + 5G>C and the synonymous c.381C>T variations. We demonstrated that these two variations affected CASQ2 splicing using a splicing minigene assay. These data increased significantly the number of CASQ2 mutations described in association with CPVT, revealed the high prevalence of splicing and truncating mutations in this gene and brought new insight regarding the dominant inheritance of the disease. Moreover, our report of the first splicing abnormalities in CASQ2 caused by intronic mutation or synonymous change underlines the absolute necessity to perform extensive molecular analysis for genetic diagnosis and counseling of CPVT.Hum Mutat 32:1-5, 2011. © 2011 Wiley-Liss, Inc

En Languedoc au XIIIe siècle

Le sac de Béziers : il est peu d’événements du Moyen Age qui aient eu un tel retentissement auprès de ses contemporains et peu qui aient ensuite, au fil des siècles, acquis un telle portée symbolique. Peu de villes aussi qui aient connu, au cours de leur histoire, pareilles alternances d’opulence et de malheurs. En 1209, la Croisade des Albigeois s’ouvre par la prise de Béziers. Riche et forte parmi les autres villes languedociennes, qui aurait pu alors penser qu’elle serait prise et pillée par une armée que son immensité même fragilisait ? « Tuez-les tous, Dieu reconnaîtra les siens » ! stupeur ! Ensanglantée, Béziers ne s’est plus guère rebellée. Qu’aurait été le XIIIe siècle languedocien si Narbonne et Béziers avaient réalisé l’impossible cause commune ? Mais le Languedoc est multiple, une mosaïque d’intérêts divergents. Ces divergences font sa faiblesse et sa force. Car un demi-siècle plus tard, malgré sa haute noblesse terrassée, le Languedoc, et Béziers au premier plan, font preuve d’une étonnante capacité de rebond et de renouvellement. À l’occasion du huitième centenaire de cet épisode tragique de la Croisade, un groupe de médiévistes, spécialistes des pays d’oc, l’a reconsidéré en le mettant au centre d’une histoire aussi large que nécessaire, politique, sociale, économique, culturelle, à partir de documents peu ou mal connus. De part et d’autre de cette horrible année 1209, son passé de vicomté languedocienne et son avenir intégré au royaume de France apparaissent sous des traits nouveaux