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Baklouti F.,University Claude Bernard Lyon 1 | Moriniere M.,University Claude Bernard Lyon 1 | Haj-Khelil A.,University Claude Bernard Lyon 1 | Feneant-Thibault M.,Service de biochimie | And 5 more authors.
Blood Cells, Molecules, and Diseases | Year: 2011

Complete loss of protein 4.1R in red blood cell membrane is a very rare condition in humans. We here explore the third case. The morphological and biochemical observations suggested that the proband suffers from homozygous hereditary elliptocytosis. Both parents, who are consanguineous, have an elliptocytosis with no cell fragmentation, typical of a heterozygous 4.1R deficiency with a silent allele. A genomic deletion was found; it encompasses about 50. kb of genomic DNA, and suppresses the two key exons 2 and 4, which contain the two functional AUG translation initiation sites in erythroid and nonerythroid cells. The alternative first exons are intact, hence preserving the transcription potential of the altered gene. Extensive analysis of 4.1R transcripts revealed multiple splicing defects upstream of the deleted sequences. Importantly, we found that most of the transcripts generated from the altered gene are intercepted by the nonsense-mediated mRNA decay mechanism, suggesting that the massive degradation of the mRNA species jeopardizes the production of shortened but functional protein 4.1R from an alternative translation initiation site downstream of the deletion. © 2011 Elsevier Inc.


Vuillaumier-Barrot S.,Assistance Publique Hopitaux de Paris | Vuillaumier-Barrot S.,French Institute of Health and Medical Research | Bouchet-Seraphin C.,Assistance Publique Hopitaux de Paris | Chelbi M.,Assistance Publique Hopitaux de Paris | And 29 more authors.
American Journal of Human Genetics | Year: 2012

Cobblestone lissencephaly is a peculiar brain malformation with characteristic radiological anomalies. It is defined as cortical dysplasia that results when neuroglial overmigration into the arachnoid space forms an extracortical layer that produces agyria and/or a "cobblestone" brain surface and ventricular enlargement. Cobblestone lissencephaly is pathognomonic of a continuum of autosomal-recessive diseases characterized by cerebral, ocular, and muscular deficits. These include Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama muscular dystrophy. Mutations in POMT1, POMT2, POMGNT1, LARGE, FKTN, and FKRP identified these diseases as alpha-dystroglycanopathies. Our exhaustive screening of these six genes, in a cohort of 90 fetal cases, led to the identification of a mutation in only 53% of the families, suggesting that other genes might also be involved. We therefore decided to perform a genome-wide study in two multiplex families. This allowed us to identify two additional genes: TMEM5 and ISPD. Because TMEM has a glycosyltransferase domain and ISPD has an isoprenoid synthase domain characteristic of nucleotide diP-sugar transferases, these two proteins are thought to be involved in the glycosylation of dystroglycan. Further screening of 40 families with cobblestone lissencephaly identified nonsense and frameshift mutations in another four unrelated cases for each gene, increasing the mutational rate to 64% in our cohort. All these cases displayed a severe phenotype of cobblestone lissencephaly A. TMEM5 mutations were frequently associated with gonadal dysgenesis and neural tube defects, and ISPD mutations were frequently associated with brain vascular anomalies. © 2012 The American Society of Human Genetics.


Michallet M.,Center Hospitalier Lyon Sud | Luporsi E.,Center Alexis Vautrin | Soubeyran P.,Institute Bergonie | Amar N.A.,Center Hospitalier Of Troyes | And 11 more authors.
BMC Cancer | Year: 2014

Background: The approval of epoetin biosimilars in the European Union requires extensive scientific evaluation and stringent regulatory procedures, including post-marketing studies. The ORHEO (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) study was an observational, longitudinal, multicentre study performed in France to evaluate the efficacy and safety of biosimilar epoetins for the treatment of chemotherapy-induced anaemia (CIA) in the clinical setting.Methods: Patients >18 years with CIA (haemoglobin [Hb] <11 g/dL) in association with solid tumours, lymphoma or myeloma and eligible for treatment with an epoetin biosimilar were included in this study. Patient characteristics were recorded at baseline along with anaemia-related information, such as observed and target Hb (as chosen by the treating clinician), brand and dose of epoetin biosimilar prescribed, and details of any other treatments. Patients were then followed-up at 3 and 6 months. The primary endpoint was Hb response (defined as Hb reaching ≥10 g/dL, an increase of Hb ≥1 g/dL since inclusion visit or reaching physician-defined target Hb, with no blood transfusions in the 3 weeks prior to measurement). Other endpoints included adverse events, achievement of target Hb and associated treatments.Results: Overall, 2333 patients >18 years (mean age 66.5 years) with CIA (haemoglobin [Hb] <11 g/dL) in association with solid tumours, lymphoma or myeloma and eligible for biosimilar epoetin treatment were included. 99.9% of patients received epoetin zeta (median dose 30,000 IU/week). Mean baseline Hb was 9.61 g/dL, with 35.6% of patients having moderate anaemia (Hb 8-9.5 g/dL). Hb response was achieved in 81.6% and 86.5% of patients at 3 and 6 months, respectively. Overall mean change in Hb level was 1.52 ± 1.61 and 1.72 ± 1.61 g/dL at 3 and 6 months, respectively. Transfusion and thromboembolic event rates were 9.4% and 2.4% at 3 months, and 5.8% and 1.5% at 6 months, respectively.Conclusions: Epoetin zeta was effective and well tolerated in the management of CIA in patients with solid tumours, lymphoma and myeloma.Trial registration: Trial registration number: NCT02140736 (date of registration: 14 May 2014). © 2014 Michallet et al.; licensee BioMed Central Ltd.


Montagnac R.,Center Hospitalier Of Troyes | Schendel A.,Center Hospitalier Of Troyes | Vuiblet V.,Reims University Hospital Center | Peilleron B.,Center Aubois dUrologie | Piot O.,Reims University Hospital Center
Nephrologie et Therapeutique | Year: 2011

Bariatric surgery is now recognized as a sure and effective way for weight reduction in morbid obesity. However some procedures induce intestinal malabsorption leading to enteric hyperoxaluria. So bariatric surgery could place these patients not only at risk for nephrolithiasis but also for oxalate induced nephropathy and chronic renal failure. Because of the growing incidence of obesity worldwide, physicians and patients should be aware of such potential complications. There is no mean to discuss this treatment because of its spectacular efficiency on obesity and its comorbidities. But it is necessary to choose the surgical technique according to the risk factors of the patients. Following surgery, preventive treatment strategies are indicated, such as modified dietary lifestyle and specific drugs as we suggested to limit or even avoid these complications. However observance could fail in the long term. In case of oxalate nephropathy, surgery may be proposed to restore the intestinal tract but with the risk of overweight relapse. To illustrate this matter, we report here significant observations of three patients, which, having successfully benefited from the same bariatric surgery, have presented lithiasic complications for two of them and oxalate nephropathy leading to chronic renal failure and hemodialysis for the third. © 2010 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.


Afilal M.,University of Technology of Troyes | Yalaoui F.,University of Technology of Troyes | Dugardin F.,University of Technology of Troyes | Amodeo L.,University of Technology of Troyes | And 2 more authors.
Journal of Medical Systems | Year: 2016

Emergency department (ED) have become the patient’s main point of entrance in modern hospitals causing it frequent overcrowding, thus hospital managers are increasingly paying attention to the ED in order to provide better quality service for patients. One of the key elements for a good management strategy is demand forecasting. In this case, forecasting patients flow, which will help decision makers to optimize human (doctors, nurses…) and material(beds, boxs…) resources allocation. The main interest of this research is forecasting daily attendance at an emergency department. The study was conducted on the Emergency Department of Troyes city hospital center, France, in which we propose a new practical ED patients classification that consolidate the CCMU and GEMSA categories into one category and innovative time-series based models to forecast long and short term daily attendance. The models we developed for this case study shows very good performances (up to 91,24 % for the annual Total flow forecast) and robustness to epidemic periods. © 2016, Springer Science+Business Media New York.

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