Bourdeaut F.,Nantes University Hospital Center |
Bourdeaut F.,French Institute of Health and Medical Research |
Lequin D.,University Pierre and Marie Curie |
Brugieres L.,Institute Gustave Roussy |
And 28 more authors.
Clinical Cancer Research | Year: 2011
Purpose: Germline hSNF5/INI1 mutations are responsible for hereditary cases of rhabdoid tumors (RT) that constitute the rhabdoid predisposition syndrome (RPS). Our study provides the first precise overview of the prevalence of RPS within a large cohort of RT. Experimental Design: hSNF5/INI1 coding exons were investigated by sequencing and by multiplex ligation-dependent probe amplification. Results: Seventy-four constitutional DNAs from 115 apparently sporadic RT were analyzed from 1999 to 2009. Germline mutations were found in 26 patients (35%). Data from 9 individuals from 5 RPS families (siblings) were also studied. The median age at diagnosis was much lower (6 months) in patients with germline mutation (P < 0.01) than in patients without (18 months). Nevertheless, 7 of 35 patients with germline mutation (20%) developed the disease after 2 years of age. The mutation could be detected in only 1 parent whereas germline blood DNA was wild type in the 20 other parent pairs, therefore indicating the very high proportion of germ-cell mosaicism or of de novo mutations in RPS. The former hypothesis could be clearly documented in 1 case in which prenatal diagnosis was positive in a new pregnancy. Finally, the 2 years' overall survival was 7% in mutated and 29% in wild-type patients, mainly due to the worse outcome of RT in younger patients. Conclusions: Our results show a high proportion of germline mutations in patients with RT that can be found at any age and up to 60% in the youngest patients. Genetic counseling is recommended given the low but actual risk of familial recurrence. ©2011 AACR.
PubMed | CHR Metz Thionville, Besancon University Hospital Center, Southwestern Medical Center, CHU St Etienne and 9 more.
Type: Journal Article | Journal: Haematologica | Year: 2015
Blastic plasmacytoid dendritic cell neoplasm is an aggressive malignancy derived from plasmacytoid dendritic cells. There is currently no accepted standard of care for treating this neoplasm, and therapeutic strategies have never been prospectively evaluated. Since blastic plasmacytoid dendritic cell neoplasm cells express high levels of interleukin-3 receptor chain (IL3-R or CD123), antitumor effects of the interleukin-3 receptor-targeted drug SL-401 against blastic plasmacytoid dendritic cell neoplasm were evaluated in vitro and in vivo. The cytotoxicity of SL-401 was assessed in patient-derived blastic plasmacytoid dendritic cell neoplasm cell lines (CAL-1 and GEN2.2) and in primary blastic plasmacytoid dendritic cell neoplasm cells isolated from 12 patients using flow cytometry and an in vitro cytotoxicity assay. The cytotoxic effects of SL-401 were compared to those of several relevant cytotoxic agents. SL-401 exhibited a robust cytotoxicity against blastic plasmacytoid dendritic cell neoplasm cells in a dose-dependent manner. Additionally, the cytotoxic effects of SL-401 were observed at substantially lower concentrations than those achieved in clinical trials to date. Survival of mice inoculated with a blastic plasmacytoid dendritic cell neoplasm cell line and treated with a single cycle of SL-401 was significantly longer than that of untreated controls (median survival, 58 versus 17 days, P<0.001). These findings indicate that blastic plasmacytoid dendritic cell neoplasm cells are highly sensitive to SL-401, and support further evaluation of SL-401 in patients suffering from blastic plasmacytoid dendritic cell neoplasm.
Jalenques I.,CHU Clermont Ferrand |
Jalenques I.,Clermont University |
Rondepierre F.,CHU Clermont Ferrand |
Massoubre C.,CHU St Etienne |
And 10 more authors.
British Journal of Dermatology | Year: 2016
Background Psychiatric disorders have been extensively documented in patients with systemic lupus erythematosus (SLE). However, the prevalence of psychiatric disorders in patients with skin-restricted lupus (SRL) remains unknown, although SRL is more common than SLE. Objectives To assess current and lifetime prevalence of Axis I psychiatric disorders among outpatients with SRL and to examine the factors associated with psychiatric disorders among such patients. Methods A multicentre case-control study involving outpatients with SRL and controls matched for sex, age and education level. The Mini International Neuropsychiatric Interview was used for psychiatric evaluation. Results We evaluated 75 patients and 150 controls. Of these, 49% of patients vs. 13% of controls fulfilled the criteria for at least one current psychiatric disorder (P < 0·001). The following disorders were significantly more frequent among patients than controls: current and lifetime major depressive disorder (9% vs. 0%, P < 0·001 and 44% vs. 26%, P = 0·01), generalized anxiety disorder (23% vs. 3%, P < 0·001 and 35% vs. 19%, P = 0·03), panic disorder (7% vs. 0%, P = 0·004 and 21% vs. 3%, P < 0·001), current suicide risk (24% vs. 7%, P = 0·003), alcohol dependence (7% vs. 0%, P = 0·004) and lifetime agoraphobia (20% vs. 9%, P = 0·01). Lupus duration and lupus past treatment by thalidomide were significantly higher among patients with current psychiatric disorders. Conclusions This study demonstrates a high prevalence of several psychiatric disorders (anxiety, depression, suicide risk, alcohol dependence) in patients with SRL. © 2016 British Association of Dermatologists.
Brunelin J.,University of Lyon |
Jalenques I.,CHU Clermont Ferrand |
Jalenques I.,Clermont University |
Trojak B.,CHU Dijon |
And 10 more authors.
Brain Stimulation | Year: 2014
Context The aim of this study was to assess whether the combination of low frequency repetitive transcranial magnetic stimulation (rTMS) and venlafaxine (150-225 mg/day) is effective and safe for treatment-resistant unipolar depression (TRD).Method In a multicenter (18 centers) randomized double blind controlled trial with three arms, 170 patients were allocated to receive active rTMS combined with active venlafaxine (n = 55), active rTMS combined with placebo venlafaxine (n = 60) or sham rTMS combined with active venlafaxine (n = 55). The patients received once daily sessions of active or sham 1 Hz rTMS applied over the right dorsolateral prefrontal cortex (360 pulses/day delivered at 120% of the resting motor threshold) for two to six weeks; rTMS was combined with active or sham venlafaxine (mean dose: 179.0 ± 36.6 mg/day). The primary outcome was the number of patients who achieved remission, which was defined as an HDRS17 score <8.Results We reported a similar significant antidepressant effect in the 3 groups (P < 10-6), with a comparable delay of action and a comparable number of remitters at the endpoint (28% in the combination group, 41% in the rTMS group and 43% in the venlafaxine group; P = 0.59).Conclusions Low frequency rTMS appears to be as effective as venlafaxine and as effective as the combination of both treatments for TRD. Because of its short session duration (the duration of one session was 8.5 min) and its safety, slow rTMS might be a useful alternative treatment for patients with TRD. © 2014 Elsevier Inc.
PubMed | CHU St Etienne, Assistance publique Hopitaux de Paris and Center ORTHEO
Type: | Journal: Annals of physical and rehabilitation medicine | Year: 2016
The Western Ontario Shoulder Instability Index (WOSI) is a specific self-questionnaire which measures the functional impact during patients everyday life activities in order to evaluate the therapeutic care face to a chronic scapula-humeral instability. In his original version in English, it is valid, reliable and sensible to change. The goal of this study is to translate and culturally adapt the original algo-functional score WOSI in French and to evaluate metrological quality of this version with patients suffering of chronic instability after scapula-humeral luxation.The WOSI has been translated and culturally adapted in French according to recommendations. Several groups were constituted (Non-operated group [NOG], Operated group [OG], TotG=NOG+OG, PPOG: chronic shoulder instability during pre- and postoperation, and TmG: control group) in order to analyze built versions validity by comparing WOSI French version to Rowe, WalchDuplay, QuickDASH scores, and Visual Analogical Scale (VAS) pain; and reliability by the reproducibility and the internal consistency.WOSI French version was done and accepted by an expert group (n=7). There was a significant correlation between the WOSI and the different algo-functional scores for GTot, for GO and for GNO (except for VAS pain and QuickDASH for the last group); correlation between the WOSI and the VAS pain was also significant (r=0.48 P<0.01). The reproducibility (n=27) was good: the Intra-Class Correlation (ICC) for the total score was 0.88 (IC 95%: 0.47-0.98), variating from 0.80 to 0.94 including the 4domains and from 0.70 to 0.94 for the different items separately. The Cronbach alpha was 0.953. As for TotG, the Standard Error Measure (SEM) and the Minimal Detectable Change (MDC) was respectively 12.2 (5.7%) and 333 (15.9%).WOSI French version is disponible, culturally adapted and translate, validate and reliable. We suggest to use it for the follow up of patient with chronic scapula-humeral instability.
PubMed | Besancon University Hospital Center, CHU St Etienne, Lyon University Hospital Center, University of Lyon and 5 more.
Type: Journal Article | Journal: Brain stimulation | Year: 2014
The aim of this study was to assess whether the combination of low frequency repetitive transcranial magnetic stimulation (rTMS) and venlafaxine (150-225 mg/day) is effective and safe for treatment-resistant unipolar depression (TRD).In a multicenter (18 centers) randomized double blind controlled trial with three arms, 170 patients were allocated to receive active rTMS combined with active venlafaxine (n = 55), active rTMS combined with placebo venlafaxine (n = 60) or sham rTMS combined with active venlafaxine (n = 55). The patients received once daily sessions of active or sham 1 Hz rTMS applied over the right dorsolateral prefrontal cortex (360 pulses/day delivered at 120% of the resting motor threshold) for two to six weeks; rTMS was combined with active or sham venlafaxine (mean dose: 179.0 36.6 mg/day). The primary outcome was the number of patients who achieved remission, which was defined as an HDRS17 score <8.We reported a similar significant antidepressant effect in the 3 groups (P < 10(-6)), with a comparable delay of action and a comparable number of remitters at the endpoint (28% in the combination group, 41% in the rTMS group and 43% in the venlafaxine group; P = 0.59).Low frequency rTMS appears to be as effective as venlafaxine and as effective as the combination of both treatments for TRD. Because of its short session duration (the duration of one session was 8.5 min) and its safety, slow rTMS might be a useful alternative treatment for patients with TRD.
Sanchez O.,University of Paris Descartes |
Trinquart L.,University of Paris Descartes |
Planquette B.,University of Paris Descartes |
Couturaud F.,European University of Brittany |
And 11 more authors.
European Respiratory Journal | Year: 2013
We analysed a cohort of patients with normotensive pulmonary embolism (PE) in order to assess whether combining echocardiography and biomarkers with the pulmonary embolism severity index (PESI) improves the risk stratification in comparison to the PESI alone. The PESI was calculated in normotensive patients with PE who also underwent echocardiography and assays of cardiac troponin I and brain natriuretic peptide. 30-day adverse outcome was defined as death, recurrent PE or shock. 529 patients were included, 25 (4.7%, 95% CI 3.2-6.9%) had at least one outcome event. The proportion of patients with adverse events increased from 2.1% in PESI class I-II to 8.4% in PESI class III-IV, and to 14.3% in PESI class V (p<0.001). In PESI class I-II, the rate of outcome events was significantly higher in patients with abnormal values of biomarkers or right ventricular dilatation. In multivariate analysis, the PESI (class III-IV versus I-II, OR 3.1, 95% CI 1.2-8.3; class V versus I-II, OR 5.5, 95% CI 1.5-25.5 and echocardiography (right ventricular/left ventricular ratio, OR (for an increase of 0.1) 1.3, 95% CI 1.1-1.5) were independent predictors of an adverse outcome. In patients with normotensive PE, biomarkers and echocardiography provided additional prognostic information to the PESI. Copyright ©ERS 2013.
Capri Y.,French Institute of Health and Medical Research |
Capri Y.,Robert Debre University Hospital |
Capri Y.,University Paris Diderot |
Friesema E.C.H.,Erasmus Medical Center |
And 15 more authors.
Human Mutation | Year: 2013
SLC 16A2, the gene for the second member of the solute carrier family 16 (monocarboxylic acid transporter), located on chromosome Xq13.2, encodes a very efficient thyroid hormone transporter: monocarboxylate transporter 8, MCT8. Its loss of function is responsible in males for a continuum of psychomotor retardation ranging from severe (no motor acquisition, no speech) to mild (ability to walk with help and a few words of speech). Triiodothyronine uptake measurement in transfected cells and, more recently, patient fibroblasts, has been described to study the functional consequences of MCT8 mutations. Here, we describe three novel MCT8 mutations, including one missense variation not clearly predicted to be damaging but found in a severely affected patient. Functional studies in fibroblasts and JEG3 cells demonstrate the usefulness of both cellular models in validating the deleterious effects of a new MCT8 mutation if there is still a doubt as to its pathogenicity. Moreover, the screening of fibroblasts from a large number of patient fibroblasts and of transfected mutations has allowed us to demonstrate that JEG3 transfected cells are more relevant than fibroblasts in revealing a genotype-phenotype correlation. Demonstrating the deleterious effect of new sequence variants is critical for genetic diagnosis. In this paper, we demonstrate that functional studies measuring T3 transport in either patient fibroblasts or in JEG3 transfected cells are very easy and efficient tests in validating deleterious effects of new MCT8 mutations especially if there is still a doubt as to their pathogenicity. Moreover, our work establishes that JEG3 transfected cells are more relevant than fibroblasts in revealing a genotype-phenotype correlation for MCT8 diseases. © 2013 WILEY PERIODICALS, INC.
Forges F.,CHU St Etienne |
Simoens X.,Institute Of Cancerologie Of La Loire |
Chauvin F.,Institute Of Cancerologie Of La Loire
Journal of Oncology Pharmacy Practice | Year: 2011
The environmental contamination of the antineoplastic drugs circuit, due to the centralization of preparation and the increased number of the patients treated, brought about a new occupational hazard: the chronic exposure to low doses of antineoplastic drugs. The rationalization of the hospital budgets imposes a meticulous assessment of the devices available for the preparation, in order to justify their interest, even their cost. A prospective comparative study with parallel arms was led inside the Pharmacy of the Institut de Cancerologie de la Loire in order to evaluate the Spike Swan®, a transfer device. The aim was to assess the Spike Swan® effectiveness. The antineoplastic drugs environmental contamination within the isolators is considered as a potential starting point for a larger dissemination of cytotoxic products. Therefore, the primary endpoint was the surface contamination level with 5-fluorouracil and the comparator was the standard preparation technique using needles and aeration needles. This study did not show significant effectiveness for the Spike Swan® in reducing surface contamination. Nevertheless, this device could be used to prepare large volumes and to secure occasional handlers, because it is easy to handle. © The Author(s) 2010.