Luc Mouthon

Université Paris-Sorbonne - Paris IV, Lutetia Parisorum, Île-de-France, France

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Publications (560)1546.85 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to describe the presentation and outcomes of patients with granulomatosis with polyangiitis (GPA) presenting with CNS involvement.
    Rheumatology (Oxford, England) 09/2014; · 4.24 Impact Factor
  • Paul Legendre, Luc Mouthon
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    ABSTRACT: Pulmonary arterial hypertension (PAH) is a classical complication of connective tissue diseases (CTD), particularly in systemic sclerosis (SSc), systemic lupus erythematous (SLE) or mixed connective tissue diseases (MCTD). The prevalence of PAH in SSc, as measured by right heart catheterization (RHC), is estimated between 7.85 to 13%. The detection of PAH in SSc is based on trans-thoracic echocardiography. Early detection in pulmonary hypertension is the best way to improve the survival in these diseases. In the DETECT study, 19% of high-risk PAH patients with SSc (SSc diagnosed less than 3 years before and DLco<60% predicted) have PAH as measured by RHC. Specific treatments for PAH are less efficient in PAH related to SSc than in idiopathic PAH. The main characteristic of PAH related to CTD other than SSc is a good response to immunosuppressive treatment, with an improvement in 50% of cases in SLE or MCTD. The prognosis of PAH associated with CTD seem to improve with the diversification of treatments available, but remains reserved. Therapeutic combinations and new molecules should allow to improve the prognosis.
    Presse medicale (Paris, France : 1983). 08/2014;
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    ABSTRACT: Intravenous immunoglobulin (IVIg) is used in the therapy of various autoimmune and inflammatory diseases. Recent studies in experimental models propose that anti-inflammatory effects of IVIg are mainly mediated by α2,6-sialylated Fc fragments. These reports further suggest that α2,6-sialylated Fc fragments interact with DC-SIGN(+) cells to release IL-33 that subsequently expands IL-4-producing basophils. However, translational insights on these observations are lacking. Here we show that IVIg therapy in rheumatic patients leads to significant raise in plasma IL-33. However, IL-33 was not contributed by human DC-SIGN(+) dendritic cells and splenocytes. As IL-33 has been shown to expand basophils, we analyzed the proportion of circulating basophils in these patients following IVIg therapy. In contrast to mice data, IVIg therapy led to basophil expansion only in two patients who also showed increased plasma levels of IL-33. Importantly, the fold-changes in IL-33 and basophils were not correlated and we could hardly detect IL-4 in the plasma following IVIg therapy. Thus, our results indicate that IVIg-induced IL-33 is insufficient to mediate basophil expansion in autoimmune patients. Hence, IL-33 and basophil-mediated anti-inflammatory mechanism proposed for IVIg might not be pertinent in humans.
    Scientific Reports 07/2014; 4:5672. · 5.08 Impact Factor
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    ABSTRACT: Ischemic digital ulcers (DU) are frequent and severe complications of systemic sclerosis (SSc). The purpose of our study was to assess the effect of DU on hand disability and pain in patients with SSc.
    The Journal of rheumatology. 06/2014;
  • Journal of the European Academy of Dermatology and Venereology 06/2014; · 2.69 Impact Factor
  • La Revue de Médecine Interne 06/2014; 35:A33–A34. · 0.90 Impact Factor
  • La Revue de Médecine Interne 06/2014; 35:A35–A36. · 0.90 Impact Factor
  • La Revue de Médecine Interne 06/2014; 35:A32. · 0.90 Impact Factor
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    ABSTRACT: La polychondrite chronique atrophiante (PCA) est une affection rare caractérisée par une inflammation récidivante parfois suivie de dégénérescence des cartilages de l’oreille, du nez, du larynx et de l’arbre trachéobronchique. Les manifestations révélatrices sont le plus souvent articulaires et les chondrites sont absentes initialement dans la moitié des cas. Leur survenue secondairement permet alors de rectifier le diagnostic d’une polyarthrite, d’une inflammation oculaire, ou d’une atteinte cutanée ou audiovestibulaire non étiquetée. Une pathologie auto-immune associée est présente chez un tiers des patients. La PCA résulte d’une réaction auto-immune contre certains antigènes du cartilage encore inconnus, suivie d’une protéolyse enzymatique de la matrice cartilagineuse. Le diagnostic est clinique. Il peut être aidé par les critères de Michet. Les anticorps anti-collagène de type II et anti-matriline-1 ne sont ni sensibles ni spécifiques et ne peuvent pas être utilisés à visée diagnostique. L’évaluation clinique et biologique est complétée par les données comparatives du scanner thoracique dynamique expiratoire, de l’IRM, de l’échographie Doppler cardiaque, des épreuves fonctionnelles respiratoires et pour certains de l’endoscopie bronchique mais qui comporte le risque d’aggraver l’état respiratoire. Le traitement de la PCA n’est pas codifié. Il est adapté, en fonction de l’activité et de la sévérité de la maladie, de façon individuelle. La corticothérapie reste la base du traitement que la plupart des patients prennent au long cours. Les immunosuppresseurs sont utilisés dans les formes respiratoires ou vasculaires sévères ou en cas de corticorésistance ou corticodépendance. Le méthotrexate est souvent efficace. Le cyclophosphamide est utilisé dans les formes sévères.
    Revue du Rhumatisme 05/2014;
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    ABSTRACT: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are a heterogeneous group of diseases corresponding to necrotising inflammation of small vessels with a wide range of clinical presentations. At least two of the diseases are believed to exhibit a common ground of pathophysiological mechanisms. These are granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis) and microscopic polyangiitis (MPA). ANCA directed against proteinase 3 (PR3) are preferentially associated with GPA, and anti-myeloperoxidase (MPO) ANCA are associated mainly with MPA and eosinophilic GPA (formerly known as Churg-Strauss syndrome). Anti-MPO and anti-PR3 antibodies can activate neutrophils in vitro. In vivo data are available for humans and mice on the pathogenicity of anti-MPO but it is more controversial for PR3-ANCA. A recent genome-wide association study of patients with ANCA-associated vasculitides confirmed the genetic contribution to the pathogenesis of these conditions, with significant association of PR3-ANCA and human leukocyte antigen-DP and the genes encoding α1-antitrypsin and PR3. MPO-ANCA were significantly associated with human leukocyte antigen-DQ. Thus, recent results from epidemiological studies, genome-wide association study and therapeutic trials have suggested that these entities are, in fact, distinct. We have summarised these results and discuss the idea that these two entities should be studied separately as the nature of the two auto-antigens suggests at a molecular level despite shared ANCA involvement.
    Postgraduate medical journal 05/2014; 90(1063):290-6. · 1.38 Impact Factor
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    ABSTRACT: Objectives: Ischaemic digital ulcers (DUs) are a common complication of systemic sclerosis (SSc). This study aimed to characterize patients with SSc and ongoing DUs treated with the endothelin receptor antagonist bosentan in clinical practice in France. Method: An observational, retrospective, longitudinal study was conducted in 10 French expert centres. Medical records from randomly selected adult SSc patients who received treatment with bosentan for DU prevention from March 2007 to December 2010 were analysed. The primary objective was to determine the profile of patients at treatment initiation. Secondary objectives were to monitor bosentan dosing, treatment schedule, and reasons for treatment termination. Results: The study included 89 patients (mean age 52 years, 69% female, 44% diffuse cutaneous SSc). At bosentan treatment initiation, the mean duration of Raynaud's phenomenon was 15 ± 12 years, and the mean time since first episode with DU was 6.5 ± 7 years. Most patients had a history of at least two episodes with DUs, separated by < 12 months (61%), and had received intravenous iloprost (63%). Previous DU complications included auto-amputation (8%), surgical amputation (6%), osteitis (6%), and gangrene (4.5%). Active smokers (25%) had a history of significantly more surgical amputation (p = 0.004) and osteitis (p = 0.004) than non-smokers. At least one active DU at bosentan initiation was detected in 82% of patients. Bosentan was used according to prescription guidelines and was well tolerated; six patients (7%) withdrew from treatment because of raised liver enzymes. Conclusions: Patients treated with bosentan for DU prevention in France have severe, refractory, ongoing ulcerative disease. Active smoking was correlated to a history of DU complications. Tolerance of bosentan was comparable to previous studies.
    Scandinavian journal of rheumatology 04/2014; · 2.51 Impact Factor
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    ABSTRACT: We report a case of severe mitral stenosis caused by Libman-Sacks endocarditis, as an initial manifestation of systemic lupus erythematosus (SLE) in a 20-year-old woman. Cardiac magnetic resonance imaging (MRI) demonstrated a thickening of the mitral valve with basal endocardial thickening exhibiting defect on first-pass perfusion short-axis acquisition and delayed enhancement in keeping with extensive fibrous endocarditis. The patient underwent successful mechanical mitral valve replacement. This case illustrates that MRI is useful in diagnosing this recognised but uncommon cardiac complication of SLE and excluding differential diagnosis such as valve tumour and infective endocarditis with perivalvular abscesses.
    The international journal of cardiovascular imaging 04/2014; · 2.15 Impact Factor
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    ABSTRACT: Anti-endothelial cell antibodies (AECAs) have been reported to cause endothelial cell dysfunction, but their specific targets have never been identified in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs). Proteins from human umbilical vein endothelial cells (HUVECs) were separated by 2-dimensional electrophoresis (2-DE). 2-D immunoblots were used to compare serum IgG reactivities from 30 patients with AAV and 12 healthy controls (HCs). Proteins identified as target antigens by MALDI- TOF-TOF mass spectrometry included lamin A/C, vimentin, α-enolase, far upstream binding protein 2 (FUBP2) and protein disulfide-isomerase A3 precursor (PDIA3). Antibodies targeting lamin A, vimentin, α-enolase, FUBP2 and PDIA3 were identified in 57.1%, 64.3%, 35.7%, 50% and 0% of patients with microscopic polyangiitis and 8%, 3.3%, 7.2%, 0% and 6.7% of HCs respectively. IgG from patients with microscopic polyangiitis had stronger reactivity against HUVEC than other groups and HCs and induced stronger Erk phosphorylation in HUVECs than IgG from HCs.
    Clinical Immunology 04/2014; · 3.77 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the efficacy and safety of rituximab (RTX) associated with glucocorticoid treatment based on disease severity, as a remission induction treatment for granulomatosis with polyangiitis (GPA) (Wegener's) and to analyze the results of long-term maintenance therapy with low doses of RTX in a routine time-based protocol. This single-center retrospective study used standardized data collection from all GPA patients receiving RTX between 2002 and 2013. The remission induction regimen consisted of RTX and glucocorticoids, adapted according to disease severity. Once remission was achieved, patients received RTX maintenance treatment (500 mg every 6 months) for 18 months. Sixty-six GPA patients received RTX for remission induction. After six months, a response had been achieved in 78.8% of these patients, with a moderate oral prednisone regimen (mean dose at baseline, 32.8 ± 23.4 mg/day). Subglottic stenosis increased the risk of treatment failure (OR = 31.2, P = 0.0104). RTX maintenance treatment was continued for 18 months in 92% of the GPA patients, who were followed for 34.2 ± 26.2 months (mean total cumulative RTX dose of 4.6 ± 1.7 g). The relapse rate was 11.2/100 patient-years. The relapses occur a mean of 13.5 ± 14.7 months after the last RTX infusion. Twenty-one severe adverse events were recorded; 13.6% patients had severe infections. We conclude that in this single-center cohort, RTX associated with glucocorticoid treatment adapted for disease severity appeared to induce remission effectively in GPA patients. Maintenance treatment with low doses of RTX in a routine time-based protocol was safe and associated with low rates of relapse on treatment.
    Journal of Autoimmunity 04/2014; · 8.15 Impact Factor
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    ABSTRACT: Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria.We recruited 40 patients (24 female) of mean age 44.2 ± 12.2 (19-70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-γ release by natural killer (NK) cell were performed. Mean follow-up was 6.9 ± 6.7 (0.14-24.3) years. Infectious, autoimmune, and neoplastic events were recorded, as were outcomes of interleukin 2 therapy.In all, 25 patients had opportunistic infections (12 with human papillomavirus infection), 14 had autoimmune symptoms, 5 had malignancies, and 8 had mild or no symptoms. At the time of diagnosis, the mean cell counts were as follows: mean CD4 cell count: 127/mm (range, 4-294); mean CD8: 236/mm (range, 1-1293); mean CD19: 113/mm (range, 3-547); and mean NK cell count: 122/mm (range, 5-416). Most patients had deficiency in CD8, CD19, and/or NK cells. Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01). Patients with autoimmune manifestations had increased CD8 T-cell count. Proliferation of thymic precursors, as assessed by T-cell rearrangement excision circles, was increased. Six patients died (15%). CD4 T-cell count <150/mm and NK cell count <100/mm were predictors of death.In conclusion, ICL is a heterogeneous disorder often associated with deficiencies in CD8, CD19, and/or NK cells. Long-term prognosis may be related to initial CD4 and NK cell deficiency.
    Medicine 03/2014; 93(2):61-72. · 4.35 Impact Factor
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    ABSTRACT: Systemic necrotizing vasculitides (SNV) are associated with more frequent subclinical atherosclerosis, suggesting that SNV might be associated with a higher risk of major cardiovascular events (MCVE). We aimed to identify factors predictive of MCVE in patients with SNV. Patients in remission from SNV were assessed for CV risk factors and subclinical atherosclerosis. MCVE was defined as myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, and/or death from CV causes. MCVE-free survival curves were compared using the log-rank test. Forty-two patients were followed for 7.1 ± 2.6 years. Eight patients (18.9%) had MCVE. The respective 5- and 10-year MCVE rates were 9.5% and 26.8%. National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III)-defined high-risk status [hazard ratio (HR) 5.02 (95% CI: 1.17-27.4), p = 0.03], BMI > 30 kg/m(2) [HR 4.84 (95% CI: 1.46-116), p = 0.02], and plaque detection in the abdominal aorta (p = 0.01) were significantly associated with MCVE. SNV characteristics, corticosteroid maintenance therapy, and C-reactive protein > 5 mg/l were not associated with MCVE. Plaque in the aorta was significantly associated with high-risk status (p < 0.001), while BMI and high-risk status were independent variables. Thus, a BMI > 30 kg/m(2) and/or a high-risk status were strongly associated with MCVE (p = 0.004). Carotid intima-media thickness (IMT) identified patients with early MCVE and was correlated with the time to MCVE (r(2) = 0.68, p = 0.01). These results suggest that factors associated with a higher MCVE risk in patients with SNV are NCEP/ATP III-defined high-risk status and BMI > 30 kg/m(2). Carotid IMT could help identify patients with SNV at risk of early MCVE.
    The Journal of Rheumatology 03/2014; · 3.26 Impact Factor
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    ABSTRACT: Objectives: To identify clinical, functional and health-related quality of life (HRQoL) correlates of clinically significant symptoms of anxiety and depression in patients with systemic sclerosis (SSc). Methods: Three-hundred-and-eighty-one patients fulfilling the American College of Rheumatology and/or the Leroy and Medsger criteria for SSc were assessed for visceral involvement, disability and HRQoL (assessed by SF-36). Clinically significant symptoms of anxiety and depression were evaluated with the Hospital Anxiety Depression Scale (HAD) (defined cut-off$8). Results: 9.2% the patients had limited SSc, 50.5% limited cutaneous SSc (lcSSc), and 40.3% diffuse cutaneous SSc (dcSSc). Overall, 40.4% and 58.8% of the patients had clinically significant symptoms of depression and anxiety, respectively. Compared to patients without clinically significant symptoms of depression, patients with clinically significant symptoms of depression had poorer health status, HRQoL mental and physical component, and greater global disability, hand disability and aesthetic impairment. Compared to patients without clinically significant symptoms of anxiety, patients with clinically significant symptoms of anxiety had poorer SF-36 mental and physical component scores. On multivariable analysis, excluding mental component score of SF-36, variables independently associated with clinically significant symptoms of depression and anxiety were global disability and physical component of SF-36, plus female gender for clinically significant symptoms of anxiety only. Remarkably, patients with and without clinically significant psychiatric symptoms were comparable for all disease-related clinical features assessed. Conclusion: High levels of clinically significant symptoms of anxiety and depression are observed among SSc patients. Clinically significant psychiatric symptoms are rather associated with increased disability and altered HRQoL, than with disease-specific organ manifestations. Copyright: ß 2014 Nguyen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The authors have no support or funding to report. Competing Interests: The authors have declared that no competing interests exist.
    PLoS ONE 02/2014; 9(2):e90484. · 3.53 Impact Factor
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    ABSTRACT: Systemic sclerosis per se should not be considered as an a priori contraindication for a pre-transplantation assessment in patients with advanced interstitial lung disease and/or pulmonary hypertension. For lung or heart-lung transplantation, a multidisciplinary approach, adapting the pre-transplant assessment to systemic sclerosis and optimizing systemic sclerosis patient management before, during and after surgery should improved the short- and long-term prognosis. Indications and contraindications for transplantation have to be adapted to the specificities of systemic sclerosis. A special focus on the digestive tract involvement and its thorough evaluation are mandatory before transplantation in systemic sclerosis. As the esophagus is almost always involved, isolated gastro-oesophageal reflux disease, pH metry and/or manometry abnormalities should not be a systematic per se contraindication for pre-transplantation assessment. Corticosteroids may be harmful in systemic sclerosis as they are associated with acute renal crisis. A low dose corticosteroids protocol for immunosuppression is therefore advisable in systemic sclerosis.
    La Presse Médicale. 01/2014;
  • Alexis Regent, Luc Mouthon
    Clinical Immunology. 01/2014;
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    ABSTRACT: Relapsing polychondritis (RP) is a rare disease in which recurrent bouts of inflammation, in some cases followed by destruction, affect the cartilage of the ears, nose, larynx, and tracheobronchial tree. At presentation, however, arthritis is the most common manifestation and more than half the patients have no evidence of chondritis. The subsequent development of chondritis provides the correct diagnosis in patients who present with polyarthritis, ocular inflammation, or skin or audiovestibular manifestations of unknown origin. A concomitant autoimmune disease is present in one-third of patients with RP. The pathogenesis of RP involves an autoimmune response to as yet unidentified cartilage antigens followed by cartilage matrix destruction by proteolytic enzymes. The diagnosis rests on clinical grounds and can benefit from use of Michet's criteria. Anti-collagen type II and anti-matrilin-1 antibodies are neither sensitive nor specific and consequently cannot be used for diagnostic purposes. In addition to the physical evaluation and laboratory tests, useful investigations include dynamic expiratory computed tomography, magnetic resonance imaging, Doppler echocardiography, and lung function tests. Bronchoscopy has been suggested as a helpful investigation but can worsen the respiratory dysfunction. The treatment of RP is not standardized. The drug regimen should be tailored to each individual patient based on disease activity and severity. Glucocorticoid therapy is the cornerstone of the treatment of RP and is used chronically in most patients. Immunosuppressive agents are given to patients with severe respiratory or vascular involvement and to those with steroid-resistant or steroid-dependent disease. Methotrexate is often effective. Cyclophosphamide is used in severe forms.
    Joint, bone, spine: revue du rhumatisme 01/2014; · 2.25 Impact Factor

Publication Stats

6k Citations
1,546.85 Total Impact Points


  • 2014
    • Université Paris-Sorbonne - Paris IV
      Lutetia Parisorum, Île-de-France, France
  • 2011–2014
    • Institut Cochin
      Lutetia Parisorum, Île-de-France, France
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
    • Université de Picardie Jules Verne
      Amiens, Picardie, France
  • 2005–2014
    • Université René Descartes - Paris 5
      • • Faculté de Médecine
      • • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
    • Université Paris Descartes
      • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
  • 2001–2014
    • Assistance Publique – Hôpitaux de Paris
      • Département de Médecine Interne
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • Institute Mutualiste Montsouris
      Lutetia Parisorum, Île-de-France, France
  • 2005–2013
    • Hôpital Cochin (Hôpitaux Universitaires Paris Centre)
      • • Service de Médecine Interne
      • • Service de Rhumatologie A
      Paris, Ile-de-France, France
  • 2012
    • Hedi Chaker Hospital
      Şafāqis, Şafāqis, Tunisia
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 2011–2012
    • Assistance Publique Hôpitaux de Marseille
      • Service de rhumatologie 2
      Marseille, Provence-Alpes-Cote d'Azur, France
    • Université de Rouen
      Mont-Saint-Aignan, Upper Normandy, France
  • 2010–2011
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      Lutetia Parisorum, Île-de-France, France
  • 2006–2011
    • Centre Hospitalier Régional Universitaire de Lille
      • Division of Internal Medicine
      Lille, Nord-Pas-de-Calais, France
  • 2006–2010
    • Université du Droit et de la Santé Lille 2
      Lille, Nord-Pas-de-Calais, France
  • 2009
    • Johns Hopkins University
      • Department of Medicine
      Baltimore, MD, United States
    • Lille Catholic University
      Lille, Nord-Pas-de-Calais, France
    • Centre Hospitalier Universitaire Rouen
      • Service d'Urologie
      Rouen, Upper Normandy, France
    • CHRU de Strasbourg
      Strasburg, Alsace, France
  • 1996–2009
    • Pierre and Marie Curie University - Paris 6
      • Centre de recherche des Cordeliers - UMR_S 872
      Paris, Ile-de-France, France
  • 1995–2009
    • French Institute of Health and Medical Research
      • Centre de Recherche des Cordeliers U872
      Lutetia Parisorum, Île-de-France, France
  • 2008
    • Hôpital Tenon (Hôpitaux Universitaires Est Parisien)
      • Service de Dermatologie - Allergologie
      Paris, Ile-de-France, France
  • 2007
    • Jawaharlal Institute of Postgraduate Medical Education & Research
      • Department of Medicine
      Pondicherry, Union Territory of Puducherry, India
  • 1999–2004
    • Université Paris 13 Nord
      Île-de-France, France
  • 1997
    • Hôpital Paris Saint Joseph
      Lutetia Parisorum, Île-de-France, France