Dysmegakaryopoiesis, a clue for an early diagnosis of familial platelet disorder with propensity to acute myeloid leukemia in case of unexplained inherited thrombocytopenia associated with normal-sized platelets
Latger-Cannard V.,Nancy University Hospital Center |
Philippe C.,University of Lorraine |
Jonveaux P.,University of Lorraine |
Lecompte T.,Nancy University Hospital Center |
And 2 more authors.
Journal of Pediatric Hematology/Oncology | Year: 2011
We report dysmegakaryopoiesis in a case of familial platelet disorder with predisposition to acute myeloid leukemia (familial platelet disorder/acute myeloid leukemia phenotype Mendelian Inheritance in Man number 601 399). Slight reduction of the number of megakaryocytes with high nucleocytoplasmic ratio, strongly basophilic cytoplasm and poorly lobulated nuclei are suggestive of megakaryocytic dysplasia. © 2011 Lippincott Williams & Wilkins, Inc.
Kepler C.K.,Thomas Jefferson University |
Millhouse P.,Thomas Jefferson University |
Lonjon G.,Publique Hopitaux de Paris |
Koerner J.D.,Thomas Jefferson University |
And 3 more authors.
Journal of Spinal Disorders and Techniques | Year: 2015
Study Design: Multinational survey of spine trauma surgeons. Objectives: To survey spine trauma surgeons, examine the variety of management practices for thoracolumbar fractures, and investigate the need for future areas of study. Background: Attempts to develop a universal thoracolumbar classification system represent the first step in standardizing treatment of thoracolumbar injuries, but there is little consensus regarding diagnosis and management of these injuries. Methods: A survey questionnaire regarding a fictional neurologically intact patient with a burst fracture was administered to 46 spine surgeons. The questionnaire consisted of 2 domains: management of thoracolumbar fractures and management of postoperative infection. Survey results were compiled and evaluated and consensus arbitrarily assumed when the majority of surgeons agreed on a single question answer. Results: Although majority consensus was reached on most questions, the interobserver reliability was poor. Consensus was achieved that magnetic resonance imaging should be performed during initial imaging. The majority would also operate regardless of magnetic resonance imaging findings, and would not operate at night. The favored technique was a posterior approach with decompression. Percutaneous fusion was considered a viable option by the majority of surgeons. No consensus was reached regarding instrumentation levels or construct length. The majority would use posterolateral bone grafting, and would not remove instrumentation nor perform an anterior reconstruction. Consensus was reached that postoperative bracing is unnecessary. Regarding management of infection, consensus was reached to use intraoperative vancomycin powder but not culture the nares before surgery. The majority used a set time period for antibiotic treatment when a drain was required, and would not apply supplementary bone graft at the time of final debridement and closure. Conclusions: There is lack of consensus regarding the appropriate management of thoracolumbar fractures. In the future, multicenter prospective studies are necessary to establish guidelines for the management of thoracolumbar fractures. Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Chaudeurge A.,French Institute of Health and Medical Research |
Wilhelm C.,CNRS Complex Systems and Materials Laboratory |
Wilhelm C.,University Paris Diderot |
Chen-Toumoux A.,French Institute of Health and Medical Research |
And 16 more authors.
Cell Transplantation | Year: 2012
Therapeutic intracavitary stem cell infusion currently suffers from poor myocardial homing. We examined whether cardiac cell retention could be enhanced by magnetic targeting of endothelial progenitor cells (EPCs) loaded with iron oxide nanoparticles. EPCs were magnetically labeled with citrate-coated iron oxide nanoparticles. Cell proliferation, migration, and CXCR4 chemokine receptor expression were assessed in different labeling conditions and no adverse effects of the magnetic label were observed. The magnetophoretic mobility of labeled EPCs was determined in vitro, with the same magnet as that subsequently used in vivo. Coronary artery occlusion was induced for 30 min in 36 rats (31 survivors), followed by 20 min of reperfusion. The rats were randomized to receive, during brief aortic cross-clamping, direct intraventricular injection of culture medium (n = 7) or magnetically labeled EPCs (n = 24), with (n = 14) or without (n = 10) subcutaneous insertion of a magnet over the chest cavity (n = 14). The hearts were explanted 24 h later and engrafted cells were visualized by magnetic resonance imaging (MRI) of the heart at 1.5 T. Their abundance in the myocardium was also analyzed semiquantitatively by immunofluorescence, and quantitatively by real-time polymerase chain reaction (RT-PCR).Although differences in cell retention between groups failed to be statistically significant using RT-PCR quantification, due to the variability of the animal model, immuno-staining showed that the average number of engrafted EPCs was significantly ten times higher with than without magnetic targeting. There was thus a consistent trend favoring the magnet-treated hearts, thereby suggesting magnetic targeting as a potentially new mean of enhancing myocardial homing of intravascularly delivered stem cells. Magnetic targeting has the potential to enhance myocardial retention of intravascularly delivered endothelial progenitor cells. © 2012 Cognizant Comm. Corp.
Buffet A.,Publique Hopitaux de Paris |
Smati S.,Nantes University Hospital Center |
Mansuy L.,Nantes University Hospital Center |
Mnara M.,CEA DAM Ile-de-France |
And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014
Context: HIF2A germline mutations were known to cause congenital polycythemia. Recently, HIF2A somatic mutations were found in several patients with polycythemia and paraganglioma, pheochromocytoma, or somatostatinoma, suggesting the occurrence of a de novo postzygotic HIF2A mutation that has not been demonstrated clearly. Patients: Patient 1 is a woman suffering from polycythemia diagnosed at the age of 16 years. She was operated on for a pheochromocytoma at 45 years and for two abdominal paragangliomas at 59 years. Shewasalso diagnosed with somatostatinoma. Patient 2 is ayoungboywhosufferedfrom polycythemia since infancy. He underwent surgery for a nonfunctional adrenal paraganglioma at the age of 9 years. Methods: We sequenced by Sanger and next-generation sequencing the HIF2A gene in DNA extracted from tumors, leukocytes, and buccal cells. Results: In patient 1, we identified a somatic HIF2A mutation (c.1586T>C; p.Leu529Pro) in DNA extracted from both paragangliomas. The mutation was detected as a somatic mosaic in DNA extracted from somatostatinoma and was absent from germline DNA. In patient 2,wefound an HIF2A heterozygous mutation (c.1625T>C; p.Leu542Pro) in the paraganglioma, but the mutation was also present as a mosaic in leukocyteDNAand inDNAextracted from buccal cells (3.3 and 8.96% of sequencing reads, respectively). Both mutations disrupt the hydroxylation domain of the HIF2&alfa; protein. Conclusions: Our study shows that HIF2A-related tumors are caused by postzygotic mutations occurring in early developmental stages. Potential germline mosaicism should be considered during the familial genetic counseling when an individual has been diagnosed with HIF2A-related polycythemia-paraganglioma syndrome. Copyright © 2014 by the Endocrine Society.
Mahut B.,Cabinet la Berma |
Trinquart L.,University of Paris Descartes |
Trinquart L.,French Institute of Health and Medical Research |
Le Bourgeois M.,Publique Hopitaux de Paris |
And 11 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2010
Background: Exhaled NO can be partitioned in its bronchial and alveolar sources, and the latter may increase in the presence of recent asthmatic symptoms and in refractory asthma. The aim of this multicentre prospective study was to assess whether alveolar NO fraction and FENO could be associated with the level of asthma control and severity both at the time of measurement and in the subsequent 3 months. Methods: Asthma patients older than 10 years, nonsmokers, without recent exacerbation and under regular treatment, underwent exhaled NO measurement at multiple constant flows allowing its partition in alveolar (with correction for back-diffusion) and bronchial origins based on a two-compartment model of NO exchange; exhaled NO fraction at 50 ml/s (FENO,0.05) was also recorded. On inclusion, severity was assessed using the four Global initiative for asthma (GINA) classes and control using Asthma Control Questionnaire (ACQ). Participants were followed-up for 12 weeks, control being assessed by short-ACQ on 1st, 4th, 8th and 12th week. Results: Two-hundred patients [107 children and 93 adults, median age (25th; 75th percentile) 16 years (12; 38)], 165 receiving inhaled corticosteroid, were included in five centres. The two-compartment model was valid in 175/200 patients (87.5%). Alveolar NO and FENO,0.05 did not correlate to control on inclusion or follow-up (either with ACQ /short-ACQ values or their changes), nor was influenced by severity classes. Alveolar NO negatively correlated to MEF25-75% (rho = -0.22, P < 0.01). Conclusion: Alveolar and exhaled NO fractions are not indexes of control or severity in asthmatic children and adults under treatment. © 2009 John Wiley & Sons A/S.
Moreau C.,University of Paris Descartes |
Moreau C.,French Institute of Health and Medical Research |
Pautas E.,University of Paris Descartes |
Pautas E.,French Institute of Health and Medical Research |
And 10 more authors.
Journal of Thrombosis and Haemostasis | Year: 2011
Background:Initiating warfarin is challenging in frail elderly patients because of low-dose requirements and interindividual variability. Objectives:We investigated whether incorporating VKORC1 and CYP2C9 genotype information in different models helped to predict the warfarin maintenance dose when added to clinical data and INR values at baseline (Day0), and during warfarin induction. Patients:We prospectively enrolled 187 elderly inpatients (mean age, 85.6years), all starting on warfarin using the same 'geriatric dosing-algorithm' based on the INR value measured on the day after three 4-mg warfarin doses (INR3) and on INR6±1. Results:On Day0, the clinical model failed to accurately predict the maintenance dose (R2<0.10). Adding the VKORC1 and CYP2C9 genotypes to the model increased R2 to 0.31. On Day3, the INR3 value was the strongest predictor, completely embedding the VKORC1 genotype, whereas the CYP2C9 genotype remained a significant predictor (model- R2 0.55). On Day6±1, none of the genotypes predicted the maintenance dose. Finally, the simple 'geriatric dosing-algorithm' was the most accurate algorithm on Day3 (R2 0.77) and Day6 (R2 0.81), under-estimating (≥1mg) and over-estimating the dose (≥1mg) in fewer than 10% and 2% of patients, respectively. Clinical models and the 'geriatric dosing-algorithm' were validated on an independent sample. Conclusions:Before starting warfarin therapy, the VKORC1 genotype is the best predictor of the maintenance dose. Once treatment is started using induction doses tailored for elderly patients, the contribution of VKORC1 and CYP2C9 genotypes in dose refinement is negligible compared with two INR values measured during the first week of treatment. © 2011 International Society on Thrombosis and Haemostasis.
Husson B.,Publique Hopitaux de Paris
Journal of Neuroimaging | Year: 2012
Background and Purpose: Neuroborreliosis is a rare cause of stroke in children. We aim here to demonstrate the diagnostic value of gadolinium-enhanced magnetic resonance imaging (MRI) for demonstrating vessel wall abnormality in a child with brainstem stroke. Results: We report here the case of an 8-year-old boy with cerebral vasculitis and stroke due to Lyme neuroborreliosis. Imaging studies revealed the presence of ischemic lesions in the pons and cerebellum, with focal stenosis of the basilar artery on magnetic resonance angiography and focal gadolinium enhancement of the basilar artery wall. Nine months after treatment, clinical outcome was favorable, with no enhancement of the basilar artery. Conclusions: Gadolinium-enhanced MRI provided additional information facilitating the diagnosis of vasculitis in a child with Lyme neuroborreliosis and stroke. The location of vessel wall enhancement was correlated with the topography of the acute infarct, and the lack of vessel lumen obstruction supported the diagnosis of vasculitis rather than any other cause. © 2010 by the American Society of Neuroimaging.
Guet-Revil let H.,University of Paris Descartes |
Guet-Revil let H.,Institute National Of La Sante Et Of La Recherche U1151 Eq11 |
Coignard-Biehler H.,Publique Hopitaux de Paris |
Jais J.-P.,University of Paris Descartes |
And 16 more authors.
Emerging Infectious Diseases | Year: 2014
Hidradenitis suppurativa (HS) is a frequent skin disease characterized by recurrent nodules or abscesses and chronic suppurating lesions. In the absence of clear pathophysiology, HS is considered to be an inflammatory disease and has no satisfactory medical treatment. Recently, prolonged antimicrobial treatments were shown to improve or resolve HS lesions. We prospectively studied the microbiology of 102 HS lesions sampled from 82 patients by using prolonged bacterial cultures and bacterial metagenomics on 6 samples. Staphylococcus lugdunensis was cultured as a unique or predominant isolate from 58% of HS nodules and abscesses, and a polymicrobial anaerobic microflora comprising strict anaerobes, milleri group streptococci, and actinomycetes was found in 24% of abscesses or nodules and in 87% of chronic suppurating lesions. These data show that bacteria known to cause soft tissue and skin infections are associated with HS lesions. Whether these pathogens are the cause of the lesions or are secondary infectious agents, these findings support targeted antimicrobial treatment of HS. © 2014, Centers for Disease Control and Prevention (CDC). All rights reserved.
Khirani S.,Publique Hopitaux de Paris |
Ramirez A.,Publique Hopitaux de Paris |
Delord V.,D'Entraide des Polios et Handicapes Assistance |
Leroux K.,Publique Hopitaux de Paris |
And 6 more authors.
Respiratory Care | Year: 2014
Daytime mouthpiece ventilation is a useful adjunct to nocturnal noninvasive ventilation (NIV) in patients with neuromuscular disease. The aims of the study were to analyze the practice of mouthpiece ventilation and to evaluate the performance of ventilators for mouthpiece ventilation. METHODS: Practice of mouthpiece ventilation was assessed by a questionnaire, and the performance of 6 home ventilators with mouthpiece ventilation was assessed in a bench test using 24 different conditions per ventilator: 3 mouthpieces, a child and an adult patient profile, and 4 ventilatory modes. RESULTS: Questionnaires were obtained from 30 subjects (mean age 33 ± 11 y) using NIV for 12 ± 7 y. Fifteen subjects used NIV for > 20 h/day, and 11 were totally ventilatordependent. The subject-reported benefits of mouthpiece ventilation were a reduction in dyspnea (73%) and fatigue (93%) and an improvement in speech (43%) and eating (27%). The bench study showed that none of the ventilators, even those with mouthpiece ventilation software, were able to deliver mouthpiece ventilation without alarms and/or autotriggering in each condition. Alarms and/or ineffective triggering or autotriggering were observed in 135 of the 198 conditions. The occurrence of alarms was more common with a large mouthpiece without a filter compared to a small mouthpiece with a filter (P < .001), but it was not related to the patient profile, the ventilatory mode, or the type of ventilator. CONCLUSIONS: Subjects are satisfied with mouthpiece ventilation. Alarms are common with home ventilators, although less common in those with mouthpiece ventilation software. Improvements in home ventilators are needed to facilitate the expansion of mouthpiece ventilation. © 2014 by Daedalus Enterprises.
Bollee G.,Publique Hopitaux de Paris |
Bollee G.,University of Paris Descartes |
Dahan K.,Catholic University of Leuven |
Flamant M.,Publique Hopitaux de Paris |
And 10 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2011
Background UMOD mutations cause familial juvenile hyperuricemic nephropathy (FJHN) and medullary cystic kidney disease (MCKD), although these phenotypes are nonspecific. Design, setting, participants, & measurements: We reviewed cases of UMOD mutations diagnosed in the genetic laboratories of Necker Hospital (Paris, France) and of Université Catholique de Louvain (Brussels, Belgium). We also analyzed patients with MCKD/FJHN but no UMOD mutation. To determine thresholds for hyperuricemia and uric-acid excretion fraction (UAEF) according to GFR, these parameters were analyzed in 1097 patients with various renal diseases and renal function levels. Results: Thirty-seven distinct UMOD mutations were found in 109 patients from 45 families, all in exon 4 or 5 except for three novel mutations in exon 8. Median renal survival was 54 years. The type of mutation had a modest effect on renal survival, and intrafamilial variability was high. Detailed data available in 70 patients showed renal cysts in 24 (34.3%) of nonspecific localization in most patients. Uricemia was >75th percentile in 31 (71.4%) of 42 patients not under dialysis or allopurinol therapy. UAEF (n = 27) was <75th percentile in 70.4%. Among 136 probands with MCKD/FJHN phenotype, UMOD mutation was found in 24 (17.8%). Phenotype was not accurately predictive of UMOD mutation. Six probands had HNF1B mutations. Conclusions: Hyperuricemia disproportionate to renal function represents the hallmark of renal disease caused by UMOD mutation. Renal survival is highly variable in patients with UMOD mutation. Our data also add novel insights into the interpretation of uricemia and UAEF in patients with chronic kidney diseases. © 2011 by the American Society of Nephrology.