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Amri N.,University Pierre and Marie Curie | Djole S.X.,University Pierre and Marie Curie | Djole S.X.,Hospital la Pitie Salpetriere | Djole S.X.,Félix Houphouët-Boigny University | And 9 more authors.
American Journal of Pathology | Year: 2016

The muscle segment homeogenes Msx1 and Msx2 play a major role in tooth and bone formation. Periodontal osteoclast impairment also occurs in Msx2 null mutant mice, which is restored by overexpression of the receptor activator of NF-κB targeted in osteoclast lineage. Here, we investigated the role of Msx2 in dentinogenesis. Experiments were performed on Msx2−/− mice and the MDPC-23 odontoblastic cell line. After Msx2 gene silencing, real-time quantitative RT-PCR data showed significant overexpression of Runx2, Bglap, Dspp, and Alpl. Of three inhibitors of Wnt/β-catenin signaling (Dkk1, SostDc1, and Sost/Sclerostin), only Sost was expressed in postnatal teeth and overexpressed in Msx2−/− tooth samples. Initial crown dentin formation—primary dentinogenesis—occurred fairly normally in Msx2−/− teeth, albeit with distorted cusp patterns. Later stages of tooth development were characterized by a deviation from secondary toward tertiary dentinogenesis with osteodentin formation and impaired dentin deposition leading to limited root elongation. In Msx2−/−/receptor activator of NF-κB–transgenic double mutants, the dentin phenotype, notably in the roots, was rescued and sclerostin levels were normalized. These data suggest that Msx2 may act indirectly on dentinogenesis by controlling osteoclast activity and the signaling network related to eruption, supporting and further extending the concept that Msx2 controls formation of mineralized tissues by inhibition of the Wnt/β-catenin pathway; Sost in dentin and Dkk1 in bone, as previously demonstrated. © 2016 American Society for Investigative Pathology


Sirvent A.,Hospital Archet | Dhedin N.,Hospital La Pitie Salpetriere | Michallet M.,Hospital E Herriot | Mounier N.,Hospital Archet | And 22 more authors.
Biology of Blood and Marrow Transplantation | Year: 2010

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have a very poor prognosis. However, they may achieve long-term survival by undergoing allogeneic stem cell transplantation (SCT). The purpose of this study was to assess the outcome of all adult patients with DLBCL whose treatment included a reduced-intensity conditioning (RIC) regimen for allogeneic SCT and whose data were reported in the French Society of Marrow Transplantation and Cellular Therapy registry. Sixty-eight patients (median age: 48 years) were transplanted from October 1998 to January 2007. They had received a median of 2 regimens of therapy prior to allogeneic SCT, and 54 (79%) had already undergone SCT. Prior to transplantation, 32 patients (47%) were in complete remission (CR). For all patients but 1, conditioning regimens were based on fludarabine (Flu), which was combined with other chemotherapy drugs in 50 cases (74%) and with total body irradiation (TBI) in 17 (25%). For 56 patients (82%), the donor was an HLA-matched sibling, and peripheral blood was the most widely used source of stem cells (57 patients, 84%). With a median follow-up of 49 months, estimated 2-year overall survival (OS), progression-free survival (PFS), and the cumulative incidence of relapse were 49%, 44%, and 41%, respectively. The 1-year cumulative incidence of nonrelapse mortality (NRM) was 23%. According to multivariate analysis, the patients in CR before transplantation had a significantly longer PFS and a lower CI of relapse than patients transplanted during partial remission or stable or progressive disease. These results suggest that reduced-intensity allergenic transplantation is an attractive therapeutic option for patients with high-risk DLBCL. © 2010 American Society for Blood and Marrow Transplantation.


Dauvilliers Y.,Gui Of Chauliac Hospital | Dauvilliers Y.,Sleep Disorders Center | Arnulf I.,National Ref. Netwk. for Orphan Dis. Narcol. | Arnulf I.,Hospital la Pitie Salpetriere | And 21 more authors.
Brain | Year: 2013

An increased incidence of narcolepsy in children was detected in Scandinavian countries where pandemic H1N1 influenza ASO3-adjuvanted vaccine was used. A campaign of vaccination against pandemic H1N1 influenza was implemented in France using both ASO3-adjuvanted and non-adjuvanted vaccines. As part of a study considering all-type narcolepsy, we investigated the association between H1N1 vaccination and narcolepsy with cataplexy in children and adults compared with matched controls; and compared the phenotype of narcolepsy with cataplexy according to exposure to the H1N1 vaccination. Patients with narcolepsy-cataplexy were included from 14 expert centres in France. Date of diagnosis constituted the index date. Validation of cases was performed by independent experts using the Brighton collaboration criteria. Up to four controls were individually matched to cases according to age, gender and geographic location. A structured telephone interview was performed to collect information on medical history, past infections and vaccinations. Eighty-five cases with narcolepsy-cataplexy were included; 23 being further excluded regarding eligibility criteria. Of the 62 eligible cases, 59 (64% males, 57.6% children) could be matched with 135 control subjects. H1N1 vaccination was associated with narcolepsy-cataplexy with an odds ratio of 6.5 (2.1-19.9) in subjects aged <18 years, and 4.7 (1.6-13.9) in those aged 18 and over. Sensitivity analyses considering date of referral for diagnosis or the date of onset of symptoms as the index date gave similar results, as did analyses focusing only on exposure to ASO3-adjuvanted vaccine. Slight differences were found when comparing cases with narcolepsy-cataplexy exposed to H1N1 vaccination (n = 32; mostly AS03-adjuvanted vaccine, n = 28) to non-exposed cases (n = 30), including shorter delay of diagnosis and a higher number of sleep onset rapid eye movement periods for exposed cases. No difference was found regarding history of infections. In this sub-analysis, H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France. Even if, as in every observational study, the possibility that some biases participated in the association cannot be completely ruled out, the associations appeared robust to sensitivity analyses, and a specific analysis focusing on ASO3-adjuvanted vaccine found similar increase. © The Author (2013).


Romain B.,École Centrale Paris | Letort V.,École Centrale Paris | Lucidarme O.,Hospital La Pitie Salpetriere | Rouet L.,Philips | Dalche-Buc F.,French Institute for Research in Computer Science and Automation
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention | Year: 2013

Today's follow-up of patients presenting abdominal tumors is generally performed through acquisition of dynamic sequences of contrast-enhanced CT. Estimating parameters of appropriate models of contrast intake diffusion through tissues should help characterizing the tumor physiology, but is impeded by the high level of noise inherent to the acquisition conditions. To improve the quality of estimation, we consider parameter estimation in voxels as a multi-task learning problem (one task per voxel) that takes advantage from the similarity between two tasks. We introduce a temporal similarity between tasks based on a robust distance between observed contrast-intake profiles of intensity. Using synthetic images, we compare multi-task learning using this temporal similarity, a spatial similarity and a single-task learning. The similarities based on temporal profiles are shown to bring significant improvements compared to the spatial one. Results on real CT sequences also confirm the relevance of the approach.


Romain B.,École Centrale Paris | Romain B.,Philips | Romain B.,University of Évry Val d'Essonne | Letort V.,École Centrale Paris | And 4 more authors.
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2012

CT perfusion imaging is used for the follow-up of abdominal tumors. A specificity of our work is that patients are breathing freely during image acquisition (5 minutes). We propose an automatic 3D image registration to compensate for respiratory motion. The registration is computed in two main steps: global translation in the z-direction and 3D multiresolution blockmatching. Within this algorithm, the choice of similarity measure largely determines the algorithm robustness in presence of intensity shifts due to contrast diffusion. We exploit a modified entropy-based similarity measure to improve the quality of registration. We also propose two relevant criteria allowing to quantify the registration quality: one based on the gradients of difference images and one based on the smoothness of enhanced-intensity curves. © 2012 Springer-Verlag.


Romain B.,Philips | Romain B.,École Centrale Paris | Romain B.,DeVry University | Letort V.,École Centrale Paris | And 4 more authors.
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2012

Objective. CT abdominal perfusion is frequently used to evaluate tumor evolution when patients are undergoing an-tiangiogenic therapy. Parameters depending on longer-term dynamics of the diffusion of the contrast medium (e. g. permeability) could help assessing the treatment efficacy. To this end, dynamic image sequences are obtained while patients breath freely. Prior to any analysis, one needs to compensate the respiratory motion. The goal of our study is to optimize the CT reconstruction parameters (filter of reconstruction, thickness of image volumes) for our registration method. We also aim at proposing relevant criteria allowing to quantify the registration quality. Methods. Registration is computed in 4 steps: z-global rigid registration, local refinements with multiresolution blockmatching, regularization and warping. Two new criteria are defined to evaluate the quality of registration: one for spatial evaluation and the other for temporal evaluation. Results. The two measures decrease after registration (58% and 10% average decrease for the best reconstruction parameters for the spatial and temporal criteria respectively) which is consistent with visual inspection of the images. They are therefore used to determine the best combination of reconstruction parameters. © 2012 SPIE.


PubMed | Philips, Hospital La Pitie Salpetriere, École Centrale Paris and French Institute for Research in Computer Science and Automation
Type: Journal Article | Journal: Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention | Year: 2014

Todays follow-up of patients presenting abdominal tumors is generally performed through acquisition of dynamic sequences of contrast-enhanced CT. Estimating parameters of appropriate models of contrast intake diffusion through tissues should help characterizing the tumor physiology, but is impeded by the high level of noise inherent to the acquisition conditions. To improve the quality of estimation, we consider parameter estimation in voxels as a multi-task learning problem (one task per voxel) that takes advantage from the similarity between two tasks. We introduce a temporal similarity between tasks based on a robust distance between observed contrast-intake profiles of intensity. Using synthetic images, we compare multi-task learning using this temporal similarity, a spatial similarity and a single-task learning. The similarities based on temporal profiles are shown to bring significant improvements compared to the spatial one. Results on real CT sequences also confirm the relevance of the approach.


Gottschalk B.,Queen's University | Gysel M.,Queen's University | Barbosa-Barros R.,Hospital Of Messejana Dr Carlos Alberto Studart Gomes Ceara | De Sousa Rocha R.P.,Hospital Of Messejana Dr Carlos Alberto Studart Gomes Ceara | And 4 more authors.
Annals of Noninvasive Electrocardiology | Year: 2014

We report a case of a 68-year-old man admitted to the emergency department with syncope preceded by rapid palpitations. His admission ECG demonstrated a sustained ventricular tachycardia (VT) originating from the right ventricular outflow tract (RVOT). This report highlights the importance of distinguishing ventricular tachycardia caused by arrhythmogenic right ventricular dysplasia (ARVD) from the more benign idiopathic RVOT-VT. Furthermore, we demonstrate the utility of the Fontaine leads placement in increasing the sensitivity for uncovering epsilon waves, a highly specific electrocardiographic feature that increases diagnostic accuracy in patients with ARVD. ©2014 Wiley Periodicals, Inc.


Ismail D.,University College London | Smith V.V.,University College London | De Lonlay P.,University of Paris Descartes | Ribeiro M.-J.,University of Paris Descartes | And 9 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Background: Congenital hyperinsulinism (CHI) is a cause of persistent hypoglycemia. Histologically, there are two subgroups, diffuse and focal. Focal CHI is a consequence of two independent events, inheritance of a paternal mutation in ABCC8/KCNJ11 and paternal uniparental isodisomy of chromosome 11p15 within the embryonic pancreas, leading to an imbalance in the expression of imprinted genes. The probability of both events occurring within siblings is rare. Aim: We describe the first familial form of focal CHI in two siblings. Patients and Methods: The proband presented with medically unresponsive CHI. He underwent pancreatic venous sampling and Fluorine-18-L-dihydroxyphenylalanine positron emission tomography scan, which localized a 5-mm focal lesion in the isthmus of the pancreas. The sibling presented 8 yr later also with medically unresponsive CHI. An Fluorine-18-L-dihydroxyphenylalanine positron emission-computerised tomography scan showed a 7-mm focal lesion in the posterior section of theheadof the pancreas. Both siblingswerefoundtobeheterozygous fortwopaternally inherited ABCC8 mutations, A355T and R1494W. Surgical removal of the focal lesions in both siblings cured the Hyperinsulinaemic hypoglycaemia. Conclusion: This is the first report of focal CHI occurring in siblings. Genetic counseling for families of patients with focal CHI should be recommended, despite the rare risk of recurrence of this disease. Copyright © 2011 by The Endocrine Society.


PubMed | Philips, Hospital La Pitie Salpetriere, Laboratory of Mathematics in Interaction with Computer Science and French Institute for Research in Computer Science and Automation
Type: | Journal: Medical image analysis | Year: 2016

Patients follow-up in oncology is generally performed through the acquisition of dynamic sequences of contrast-enhanced images. Estimating parameters of appropriate models of contrast intake diffusion through tissues should help characterizing the tumour physiology. However, several models have been developed and no consensus exists on their clinical use. In this paper, we propose a unified framework to analyse models of perfusion and estimate their parameters in order to obtain reliable and relevant parametric images. After defining the biological context and the general form of perfusion models, we propose a methodological framework for model assessment in the context of parameter estimation from dynamic imaging data: global sensitivity analysis, structural and practical identifiability analysis, parameter estimation and model comparison. Then, we apply our methodology to five of the most widely used compartment models (Tofts model, extended Tofts model, two-compartment model, tissue-homogeneity model and distributed-parameters model) and illustrate the results by analysing the behaviour of these models when applied to data acquired on five patients with abdominal tumours.

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