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rue Saint Pierre, France

Rondelet B.,Free University of Colombia | Dewachter C.,Free University of Colombia | Kerbaul F.,Free University of Colombia | Kerbaul F.,La Timone University Hospital | And 6 more authors.
European Heart Journal | Year: 2012

Aims Three-month chronic systemic-to-pulmonary shunting in growing piglets has been reported as an early pulmonary arterial hypertension (PAH) model with preserved right ventricular (RV) function. We sought to determine whether prolonged shunting might be associated with more severe PAH and RV failure.Methods and resultsFourteen growing piglets were randomized to a sham operation or the anastomosis of the left innominate artery to the pulmonary arterial trunk. Six months later, the shunt was closed and the animals underwent haemodynamic evaluation followed by tissue sampling for pathobiological assessment. Prolonged shunting had resulted in increased mean pulmonary artery pressure (22 ± 2 versus 17 ± 1 mmHg) and pulmonary arteriolar medial thickness, while cardiac output was decreased. However, RV-arterial coupling was markedly deteriorated, with a ∼50 decrease in the ratio of end-systolic to pulmonary arterial elastances (Ees/Ea). Lung tissue expressions of endothelin-1, angiopoietin-1, and bone morphogenetic protein receptor-2 were similarly altered compared with previously observed after 3-month shunting. At the RV tissue level, pro-apoptotic ratio of Bax-to-Bcl-2 expressions and caspase-3 activation were increased, along with an increase in cardiomyocyte size, while expressions in voltage-gated potassium channels (Kv1.5 and Kv2.1) and angiogenic factors (angiopoietin-2 and vascular endothelial growth factor) were decreased. Right ventricular expressions of pro-inflammatory cytokines [interleukin (IL)-1α, IL-1β, tumour necrosis factor-α (TNF-α)] and natriuretic peptide precursors (NPPA and NPPB) were increased. There was an inverse correlation between RV Ees/Ea and pro-apoptotic Bax/Bcl-2 ratios. Conclusions Prolonged left-to-right shunting in piglets does not further aggravate pulmonary vasculopathy, but is a cause of RV failure, which appears related to an activation of apoptosis and inflammation. © 2011 The Author. Source


Tabareau-Delalande F.,University of Tours | Collin C.,University of Tours | Gomez-Brouchet A.,Toulouse University Hospital Center | Bouvier C.,La Timone University Hospital | And 5 more authors.
Modern Pathology | Year: 2015

To evaluate the diagnostic value of MDM2 status in craniofacial fibro-osseous lesions, we investigated MDM2 expression by immunohistochemistry and analyzed MDM2 amplification by qPCR in 30 cases of ossifying fibroma (including 13 cases of the juvenile variant) and 17 cases of fibrous dysplasia. Two cases of uncommon extragnathic psammomatoid fibrous dysplasia and a mixed control group of 15 cases of low-grade osteosarcoma and 15 cases of well-differentiated/dedifferentiated liposarcoma were included. MDM2 amplification was found in 33% of ossifying fibromas (peak of 69% for the juvenile variant) and in 12% of fibrous dysplasia, in none of which was MDM2 overexpressed. All control cases exhibited MDM2 amplification and overexpression. To investigate possible polysomy of chromosome 12, we studied RASAL1 amplification, a gene telomeric to MDM2 on the long arm of chromosome 12. RASAL1 amplification was reported in all benign fibro-osseous lesions exhibiting MDM2 amplification but not in controls. Simultaneous amplification of these two genes was significantly higher in juvenile ossifying fibromas compared with fibrous dysplasia (P=0.004), non-juvenile ossifying fibromas (P=0.001), and all other benign craniofacial fibro-osseous lesions combined (P=0.0001). Of the nine cases of juvenile ossifying fibroma exhibiting amplification, three were locally invasive and four were recurrent, suggesting aggressive disease. The two cases of extragnathic psammomatoid fibrous dysplasia also showed MDM2 and RASAL1 amplification with no MDM2 overexpression. This large chromosome 12 rearrangement, spanning MDM2 and RASAL1, is the first recurrent molecular abnormality to be reported in juvenile ossifying fibroma. It may represent both a molecular diagnostic marker and a characteristic of more aggressive forms with a higher risk of recurrence. Finally, the presence of this rearrangement in extragnathic psammomatoid fibro-osseous lesions mimicking ossifying fibromas might reflect a common molecular pathway in their pathogenesis and calls into question the classification of such lesions within fibrous dysplasia. © 2015 USCAP, Inc. Source


Tassy S.,Aix - Marseille University | Tassy S.,Sainte Marguerite University Hospital | Deruelle C.,Aix - Marseille University | Mancini J.,Aix - Marseille University | And 3 more authors.
Frontiers in Human Neuroscience | Year: 2013

Psychopathy is a personality disorder frequently associated with immoral behaviors. Previous behavioral studies on the influence of psychopathy on moral decision have yielded contradictory results, possibly because they focused either on judgment (abstract evaluation) or on choice of hypothetical action, two processes that may rely on different mechanisms. In this study, we explored the influence of the level of psychopathic traits on judgment and choice of hypothetical action during moral dilemma evaluation. A population of 102 students completed a questionnaire with ten moral dilemmas and nine non-moral dilemmas. The task included questions targeting both judgment (Is it acceptable to... in order to...) and choice of hypothetical action (Would you...in order to...?). The level of psychopathic traits of each participant was evaluated with the Levenson Self-Report Psychopathy (LSRP) scale. Logistic regression fitted with the generalized estimating equations method analyses were conducted using responses to the judgment and choice tasks as the dependent variables and psychopathy scores as predictor. Results show that a high level of psychopathic traits, and more specifically those related to affective deficit, predicted a greater proportion of utilitarian responses for the choice but not for the judgment question. There was no first-order interaction between the level of psychopathic traits and other potential predictors. The relation between a high level of psychopathic traits and increased utilitarianism in choice of action but not in moral judgment may explain the contradictory results of previous studies where these two processes were not contrasted. It also gives further support to the hypothesis that choice of action endorsement and abstract judgment during moral dilemma evaluation are partially distinct neural and psychological processes. We propose that this distinction should be better taken into account in the evaluation of psychopathic behaviors. © 2013 Tassy, Deruelle, Mancini,Leistedt and Wicker. Source


Amant F.,Catholic University of Leuven | Lorusso D.,Italian National Cancer Institute | Mustea A.,University of Greifswald | Duffaud F.,La Timone University Hospital | Pautier P.,Institute Gustave Roussy
Sarcoma | Year: 2015

The treatment of advanced uterine leiomyosarcomas (U-LMS) represents a considerable challenge. Radiological diagnosis prior to hysterectomy is difficult, with the diagnosis frequently made postoperatively. Whilst a total abdominal hysterectomy is the cornerstone of management of early disease, the role of routine adjuvant pelvic radiotherapy and adjuvant chemotherapy is less clear, since they may improve local tumor control in high risk patients but are not associated with an overall survival benefit. For recurrent or disseminated U-LMS, cytotoxic chemotherapy remains the mainstay of treatment. There have been few active chemotherapy drugs approved for advanced disease, although newer drugs such as trabectedin with its pleiotropic mechanism of actions represent an important addition to the standard front-line systemic therapy with doxorubicin and ifosfamide. In this review, we outline the therapeutic potential and in particular the emerging evidence-based strategy of therapy with trabectedin in patients with advanced U-LMS. © 2015 Frédéric Amant et al. Source


Richieri R.,Sainte Marguerite University Hospital | Boyer L.,La Timone University Hospital | Reine G.,Toulon La Seyne Hospital | Loundou A.,University Hospital | And 4 more authors.
Schizophrenia Research | Year: 2011

Objective: This study aims to validate a self-administered, multidimensional QoL instrument based on the point of view of caregivers of individuals with schizophrenia. Methods: Data were collected through the departments of six psychiatric hospitals in France (n = 246). The item reduction and validation processes were based on both item response theory and classical test theory. Results: The S-CGQoL contains 25 items describing seven dimensions (Psychological and Physical Well-Being; Psychological Burden and Daily Life; Relationships with Spouse; Relationships with Psychiatric Team; Relationships with Family; Relationships with Friends; and Material Burden). The seven-factor structure accounted for 74.4% of the total variance. Internal consistency was satisfactory; Cronbach's alpha coefficients ranged from 0.79 to 0.92 in the whole sample. The scalability was satisfactory, with INFIT statistics falling within an acceptable range. In addition, the results confirmed the absence of DIF and supported the invariance of the item calibrations. Conclusion: The S-CGQoL is a self-administered QoL instrument that presents satisfactory psychometric properties and can be completed in 5. min, thereby fulfilling the goal of brevity sought in research and clinical practice. © 2010 Elsevier B.V. Source

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