Hopital de la Pitie Salpetriere

Paris, France

Hopital de la Pitie Salpetriere

Paris, France
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Sammler D.,University of Lille Nord de France | Sammler D.,Max Planck Institute for Human Cognitive and Brain Sciences | Baird A.,University of Lille Nord de France | Valabregue R.,University Pierre and Marie Curie | And 7 more authors.
Journal of Neuroscience | Year: 2010

The cognitive relationship between lyrics and tunes in song is currently under debate, with some researchers arguing that lyrics and tunes are represented as separate components, while others suggest that they are processed in integration. The present study addressed this issue by means of a functional magnetic resonance adaptation paradigm during passive listening to unfamiliar songs. The repetition and variation of lyrics and/or tunes in blocks of six songs was crossed in a 2 X 2 factorial design to induce selective adaptation for each component. Reductions of the hemodynamic response were observed along the superior temporal sulcus and gyrus (STS/STG) bilaterally. Within these regions, the left mid-STS showed an interaction of the adaptation effects for lyrics and tunes, suggesting an integrated processing of the two components at prelexical, phonemic processing levels. The degree of integration decayed toward more anterior regions of the left STS, where the lack of such an interaction and the stronger adaptation for lyrics than for tunes was suggestive of an independent processing of lyrics, perhaps resulting from the processing of meaning. Finally, evidence for an integrated representation of lyrics and tunes was found in the left dorsal precentral gyrus (PrCG), possibly relating to the build-up of a vocal code for singing in which musical and linguistic features of song are fused. Overall, these results demonstrate that lyrics and tunes are processed at varying degrees of integration (and separation) through the consecutive processing levels allocated along the posterior-anterior axis of the left STS and the left PrCG. Copyright © 2010 the authors.

Echaniz-Laguna A.,Hopitaux Universitaires | Dubourg O.,Institute Of Myologie | Carlier P.,Hopital de la Pitie Salpetriere | Carlier R.-Y.,APHP | And 7 more authors.
Neurology | Year: 2014

Objective: To clarify the phenotypic spectrum and incidence of TRPV4 mutations in patients with inherited axonal neuropathies. Methods: We screened for TRPV4 mutations in 169 French unrelated patients with inherited axonal peripheral neuropathy. Ninety-five patients had dominant Charcot-Marie-Tooth type 2 (CMT2) disease, and 74 patients, including 39 patients with distal hereditary motor neuropathy, 14 with congenital spinal muscular atrophy and arthrogryposis, 13 with CMT2, and 8 with scapuloperoneal spinal muscular atrophy, presented with additional vocal cord paralysis and/or skeletal dysplasia. Results: No deleterious TRPV4 mutation was identified in the 95 patients with "pure" CMT2 (0/95). In contrast, 12 of 74 patients (16%) with neuropathy and vocal cord paralysis and/or skeletal dysplasia presented pathogenic TRPV4 mutations, including 7 patients with distal hereditary motor neuropathy, 2 with scapuloperoneal spinal muscular atrophy, 2 with congenital spinal muscular atrophy and arthrogryposis, and one with CMT2. Investigation of affected relatives allowed us to study 17 patients. All patients had childhood-onset motor neuropathy and showed a variety of associated findings, including foot deformities (100% of cases), kyphoscoliosis (100%), elevated serum creatine kinase levels (100%), vocal cord paralysis (94%), scapular winging (53%), respiratory insufficiency (29%), hearing loss (24%), skeletal dysplasia (18%), and arthrogryposis (12%). Eight missense mutations were observed in these 12 families, including 2 previously unreported. Six mutations were de novo events, and 2 asymptomatic carriers were identified. Conclusion: With 16% of patients affected in our series, this study demonstrates that TRPV4 mutations are a major cause of inherited axonal neuropathy associated with a large spectrum of additional features. © 2014 American Academy of Neurology.

Genser B.,University of Heidelberg | Genser B.,Federal University of Bahia | Silbernagel G.,University of Tübingen | De Backer G.,Ghent University | And 10 more authors.
European Heart Journal | Year: 2012

The impact of increased serum concentrations of plant sterols on cardiovascular risk is unclear. We conducted a systematic review and meta-analysis aimed to investigate whether there is an association between serum concentrations of two common plant sterols (sitosterol, campesterol) and cardiovascular disease (CVD). We systematically searched the databases MEDLINE, EMBASE, and COCHRANE for studies published between January 1950 and April 2010 that reported either risk ratios (RR) of CVD in relation to serum sterol concentrations (either absolute or expressed as ratios relative to total cholesterol) or serum sterol concentrations in CVD cases and controls separately. We conducted two meta-analyses, one based on RR of CVD contrasting the upper vs. the lower third of the sterol distribution, and another based on standardized mean differences between CVD cases and controls. Summary estimates were derived by fixed and random effects meta-analysis techniques. We identified 17 studies using different designs (four casecontrol, five nested casecontrol, three cohort, five cross-sectional) involving 11 182 participants. Eight studies reported RR of CVD and 15 studies reported serum concentrations in CVD cases and controls. Funnel plots showed evidence for publication bias indicating small unpublished studies with non-significant findings. Neither of our meta-analyses suggested any relationship between serum concentrations of sitosterol and campesterol (both absolute concentrations and ratios to cholesterol) and risk of CVD. Our systematic review and meta-analysis did not reveal any evidence of an association between serum concentrations of plant sterols and risk of CVD. © 2011 The Author.

Ardehali A.,University of California at Los Angeles | Esmailian F.,Cedars Sinai Heart Institute | Deng M.,University of California at Los Angeles | Soltesz E.,Cleveland Clinic | And 8 more authors.
The Lancet | Year: 2015

Background The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation. Methods We did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712. Findings Between June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events. Interpretation Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study. Funding TransMedics. © 2015 Elsevier Ltd.

Catala M.,HOpital de La Pitie Salpetriere | Catala M.,University Pierre and Marie Curie | Kubis N.,University Paris Diderot
Handbook of Clinical Neurology | Year: 2013

The nervous system is divided into the central nervous system (CNS) composed of the brain, the brainstem, the cerebellum, and the spinal cord and the peripheral nervous system (PNS) made up of the different nerves arising from the CNS. The PNS is divided into the cranial nerves III to XII supplying the head and the spinal nerves that supply the upper and lower limbs. The general anatomy of the PNS is organized according to the arrangement of the fibers along the rostro-caudal axis. The control of the development of the PNS has been unravelled during the last 30 years. Motor nerves arise from the ventral neural tube. This ventralization is induced by morphogenetic molecules such as sonic hedgehog. In contrast, the sensory elements of the PNS arise from a specific population of cells originating from the roof of the neural tube, namely the neural crest. These cells give rise to the neurons of the dorsal root ganglia, the autonomic ganglia and the paraganglia including the adrenergic neurons of the adrenals. Furthermore, the supportive glial Schwann cells of the PNS originate from the neural crest cells. Growth factors as well as myelinating proteins are involved in the development of the PNS. © 2013 Elsevier B.V.

Moriarty P.M.,University of Kansas Medical Center | Jacobson T.A.,Emory University | Bruckert E.,Hopital de la Pitie Salpetriere | Thompson P.D.,Hartford Hospital | And 3 more authors.
Journal of Clinical Lipidology | Year: 2014

Background Statin intolerance has been a major limitation in the use of statins, especially at higher doses. New effective treatments are needed for lowering low-density lipoprotein cholesterol (LDL-C) in patients who cannot tolerate daily statin doses. Objective ODYSSEY ALTERNATIVE (NCT01709513) evaluates efficacy and safety of alirocumab, a fully human proprotein convertase subtilisin/kexin type 9 monoclonal antibody, in patients with well-documented statin intolerance and moderate to very high cardiovascular risk. Methods This is a phase 3, multicenter, randomized, double-blind, double-dummy study in statin-intolerant patients. Intolerance was defined as inability to take at least 2 different statins because of muscle-related adverse events (AEs), 1 at the lowest approved starting dose. Patients first received single-blind subcutaneous and oral placebo for 4 weeks, and were withdrawn if they developed muscle-related AEs after the placebo treatment. Continuing patients were randomized (2:2:1 ratio) to alirocumab 75 mg self-administered via single 1 mL prefilled pen every 2 weeks or ezetimibe 10 mg/day or atorvastatin 20 mg/day (statin rechallenge), for 24 weeks. Alirocumab dose was increased to 150 mg every 2 weeks (also 1 mL) at week 12 depending on week 8 LDL-C level. The primary endpoint is percent change in LDL-C from baseline to week 24 by intent-to-treat analysis. Muscle-related AEs were assessed by spontaneous patient reports and clinic queries. Results A total of 314 patients have been randomized. Conclusions This is the first and only study of a new class of LDL-C-lowering agents in patients selected with a rigorously documented intolerance to statins, using a placebo run-in and statin control arm. © 2014 National Lipid Association.

Guillaume B.,Hopital de la Pitie Salpetriere
Bulletin de l'Academie Nationale de Medecine | Year: 2011

The immune reconstitution inflammatory syndrome (IRIS), occurring in chronically HIVinfected patients, is a set of heterogeneous pathological manifestations attributed to an excessive and deregulated immune response to various pathogens and non infectious stimuli shortly after initiation of antiretroviral therapy. Mycobacteria and fungi are the main causes of IRIS, but many other pathogens and autoimmunelinflammatory disorders have also been incriminated. Diagnosis is difficult and the optimal therapeutic strategy remains to be determined. Steroids have been recommended for tuberculosis-associated IRIS. Outcome is generally favorable, with the exception of central nervous system involvement.

Roupret M.,Hopital de la Pitie Salpetriere
Nature Reviews Urology | Year: 2016

Outcome prediction in patients with bladder cancer has improved through the development of nomograms and predictive models. However, integration of further characteristics such as lymphovascular invasion (LVI) might increase the accuracy and clinical utility of these instruments. Assessment and reporting of LVI in specimens from transurethral resection of the bladder tumour (TURBT) or biopsy in patients with non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC) might enable improved staging, prognostication and clinical decision-making. In NMIBC, presence of LVI in TURBT and biopsy samples seems to be associated with understaging and increased risks of disease recurrence and progression. In MIBC, presence of LVI is associated with features of aggressive disease and predicts recurrence and survival. Integration of LVI status into predictive models might aid clinical decision-making regarding intravesical instillation schedules and regimens, early radical cystectomy in patients with high-grade T1 disease and perioperative chemotherapy. However, LVI assessment is hampered by insufficient reproducibility and reliability, lack of routine evaluation and limited concordance between findings in TURBT and radical cystectomy specimens. Standardization of the pathological criteria defining LVI is warranted to improve its reporting in routine clinical practice and its utility as a care-changing prognostic marker. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Seisen T.,Hopital de la Pitie Salpetriere | Colin P.,Hopital Prive de la Louviere | Roupret M.,Hopital de la Pitie Salpetriere
Nature Reviews Urology | Year: 2015

The conservative management of upper tract urothelial carcinoma (UTUC) was traditionally restricted to patients with imperative indications only. However, current recommendations suggest selected patients with normal, functioning contralateral kidneys should also be considered for such an approach. A risk-adapted strategy to accurately select patients who could benefit from kidney-sparing surgery without compromising their oncological safety has been advocated. A number of kidney-sparing surgical procedures are available. Despite the advent of ureteroscopic management, segmental ureterectomy and the percutaneous approach both have specific indications for use that predominantly depend on the tumour location and progression risk. These kidney-sparing procedures are cost-effective, and when used to treat patients with low-risk UTUC, are associated with oncological outcomes similar to radical nephroureterectomy. Systematic second-look endoscopy combined with upper tract instillations of topical chemotherapeutic agents after ureteroscopic or percutaneous surgery and a single early intravesical instillation of mitomycin C after any kidney-sparing procedure might decrease the risks of local recurrence and progression. Meticulous and stringent endoscopic monitoring of the upper and lower urinary tract is a key component of the conservative management of UTUC. Local recurrences are often suitable for repeat conservative therapy, whereas disease progression should be treated with delayed radical nephroureterectomy.

Allilaire J.-F.,Hopital de la Pitie Salpetriere
Bulletin de l'Academie Nationale de Medecine | Year: 2012

Borderline personality disorders are complex clinical states with highly polymorphic symptoms and signs, leading to delays in their diagnosis and treatment. All international classifications emphasize certain clinical criteria such as unstable identity and interpersonal relationships, feelings of emptiness or boredom, and pathological impulsiveness. The prevalence is about 2 %, with a female-male sex ratio of 2 or 3 to 1. Both adolescents and adults may be affected. There is a high risk of suicide, addictive behaviors, eating disorders, and criminality. These individuals frequently have a history of trauma in early childhood, such as separation, loss, physical or sexual abuse, or affective privation. Subjective signs and symptoms are particularly important in the diagnostic and therapeutic evaluation, and this requires an empathie and subtle approach. Standardized and semi-structured interviews may help to identify comorbidities such as thymic disorders, anxiety, addiction, eating disorders, and, in some cases, psychotic symptoms. The psychiatric bio-psycho-social model takes into account multiple pathogenic factors, such as trauma during early development, temperamental instability and other emotional disorders, as well as psychosocial, neurobio-logical (5HT, etc.) and genetic vulnerabilities. Treatment requires optimal integration of psychotherapeutic andpharmacotherapeutic approaches. Emergency intervention must be available in case of delirious or suicidal behavior. The clinical course is often lengthy and complex, but outcome may be favorable, provided the principal risk-suicide-is correctly managed.

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