Center hospitalier University dAmiens
Center hospitalier University dAmiens
Ramello C.,Compiègne University of Technology |
Paullier P.,Compiègne University of Technology |
Ould-Dris A.,CNRS Integrated Transformations of Renewable Matter |
Monge M.,Leiden University |
And 3 more authors.
Toxicology in Vitro | Year: 2011
In this study we present a method for investigating the effect of acrolein, a nephrotoxic and urotoxic metabolite of the anticancerous prodrugs ifosfamide and cyclophosphamide, in a blood-renal barrier biochip. The real time monitoring of mass transfers of caffeine, vitamin B12 and albumin in the biochip was performed thanks to an in vitro dialysis method. The diffusion coefficients of the solutes and their dialysance from the apical to the basolateral compartments were found to be molecular weight and cell-membrane dependent, thus demonstrating the cell-barrier functionality. The toxicity induced by the acrolein led to modifications to mass transfer properties which appeared to be acrolein dose, time and solute molecular weight dependent. Solute mass transfer across the cell layer increased with acrolein concentrations. The sensitivity of this analysis method contributes to identify the mass transfer properties and to monitor the modification to the renal parameter when submitted to toxic cell compounds. The results provide the foundation for exploring kidney behavior in response to drugs thanks to a blood-tissue barrier model using a technique based on in vitro dialysis and real time analysis. © 2011 Elsevier Ltd.
Mismetti P.,Jean Monnet University |
Laporte S.,Jean Monnet University |
Pellerin O.,University of Paris Descartes |
Ennezat P.-V.,Joseph Fourier University |
And 20 more authors.
JAMA - Journal of the American Medical Association | Year: 2015
IMPORTANCE: Although retrievable inferior vena cava filters are frequently used in addition to anticoagulation in patients with acute venous thromboembolism, their benefit-risk ratio is unclear. OBJECTIVE: To evaluate the efficacy and safety of retrievable vena cava filters plus anticoagulation vs anticoagulation alone for preventing pulmonary embolism recurrence in patients presenting with acute pulmonary embolism and a high risk of recurrence. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label, blinded end point trial (PREPIC2) with 6-month follow-up conducted from August 2006 to January 2013. Hospitalized patients with acute, symptomatic pulmonary embolism associated with lower-limb vein thrombosis and at least 1 criterion for severity were assigned to retrievable inferior vena cava filter implantation plus anticoagulation (filter group; n = 200) or anticoagulation alone with no filter implantation (control group; n = 199). Initial hospitalization with ambulatory follow-up occurred in 17 French centers. INTERVENTIONS: Full-dose anticoagulation for at least 6 months in all patients. Insertion of a retrievable inferior vena cava filter in patients randomized to the filter group. Filter retrieval was planned at 3 months from placement. MAIN OUTCOMES AND MEASURES: Primary efficacy outcomewas symptomatic recurrent pulmonary embolism at 3 months. Secondary outcomes were recurrent pulmonary embolism at 6 months, symptomatic deep vein thrombosis, major bleeding, death at 3 and 6 months, and filter complications. RESULTS: In the filter group, the filter was successfully inserted in 193 patients and was retrieved as planned in 153 of the 164 patients in whom retrieval was attempted. By 3 months, recurrent pulmonary embolism had occurred in 6 patients (3.0%; all fatal) in the filter group and in 3 patients (1.5%; 2 fatal) in the control group (relative risk with filter, 2.00 [95%CI, 0.51-7.89]; P = .50). Results were similar at 6 months. No difference was observed between the 2 groups regarding the other outcomes. Filter thrombosis occurred in 3 patients. CONCLUSIONS AND RELEVANCE: Among hospitalized patients with severe acute pulmonary embolism, the use of a retrievable inferior vena cava filter plus anticoagulation compared with anticoagulation alone did not reduce the risk of symptomatic recurrent pulmonary embolism at 3 months. These findings do not support the use of this type of filter in patients who can be treated with anticoagulation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00457158. Copyright 2015 American Medical Association. All rights reserved.
Farges O.,University Paris Diderot |
Regimbeau J.M.,Center Hospitalier University dAmiens |
Fuks D.,Center Hospitalier University dAmiens |
Le Treut Y.P.,Hopital Conception |
And 3 more authors.
British Journal of Surgery | Year: 2013
Background: Indications for preoperative biliary drainage (PBD) in the context of hepatectomy for hilar malignancies are still debated. The aim of this study was to investigate current European practice regarding biliary drainage before hepatectomy for Klatskin tumours. Methods: This was a retrospective analysis of all patients who underwent formal or extended right or left hepatectomy for hilar cholangiocarcinoma between 1997 and 2008 at 11 European teaching hospitals, and for whom details of serum bilirubin levels at admission and at the time of surgery were available. PBD was performed at the physicians' discretion. The primary outcome was 90-day mortality. Secondary outcomes were morbidity and cause of death. The association of PBD and of preoperative serum bilirubin levels with postoperative mortality was assessed by logistic regression, in the entire population as well as separately in the right- and left-sided hepatectomy groups, and was adjusted for confounding factors. Results: A total of 366 patients were enrolled; PBD was performed in 180 patients. The overall mortality rate was 10·7 per cent and was higher after right- than left-sided hepatectomy (14·7 versus 6·6 per cent; adjusted odds ratio (OR) 3·16, 95 per cent confidence interval 1·50 to 6·65; P = 0·001). PBD did not affect overall postoperative mortality, but was associated with a decreased mortality rate after right hepatectomy (adjusted OR 0·29, 0·11 to 0·77; P = 0·013) and an increased mortality rate after left hepatectomy (adjusted OR 4·06, 1·01 to 16·30; P = 0·035). A preoperative serum bilirubin level greater than 50 μmol/l was also associated with increased mortality, but only after right hepatectomy (adjusted OR 7·02, 1·73 to 28·52; P = 0·002). Conclusion: PBD does not affect overall mortality in jaundiced patients with hilar cholangiocarcinoma, but there may be a difference between patients undergoing right-sided versus left-sided hepatectomy. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
Saliou G.,Hopital Nord |
Kocheida E.M.,Hopital Raymond Poincare |
Lehmann P.,Hopital Nord |
Depriester C.,Hopital Nord |
And 4 more authors.
Radiology | Year: 2010
Purpose: To evaluate the feasibility, efficacy, and safety of percutaneous vertebroplasty (PV) in the treatment of pathologic fractures owing to malignancy with epidural involvement, with or without neurologic symptoms of spinal cord or cauda equina compression. Materials and Methods: This study was approved by the local ethics committee;informed consent was obtained from all patients. This retrospective review was performed for 51 consecutive patients with metastatic disease or multiple myeloma treated by means of vertebroplasty, who presented with at least one vertebral lesion with epidural involvement, with or without clinical symptoms of spinal cord or cauda equina compression. All patients with neurologic deficit were terminally ill. A neurologic examination was performed before and after treatment in all patients. All imaging examinations and treatments were reviewed, and x2, Mann Whitney, or Fisher exact testing was performed for univariate analysis of variables. Results: A total of 74 vertebrae were treated in 51 patients, 22 women and 29 men with a mean age of 62.5 years (range, 28-85 years). Fifteen (29%) patients presented symptoms of complete or incomplete spinal cord or cauda equina compression before vertebroplasty and no further clinical deterioration was observed after treatment. The analgesic efficacy of vertebroplasty was satisfactory for 94% (48 of 51) of patients after 1 day, 86% (31 of 36) patients after 1 month, and 92% (11 of 12) patients after 1 year. One patient with no clinical neurologic deficit before treatment experienced symptoms of cauda equina compression 2 days after vertebroplasty. No other major complication was observed. Conclusion: The feasibility, efficacy, and safety of PV were confirmed in patients experiencing pain related to malignant spinal tumors with epidural extension, with a low complication rate. PV should become part of the palliative analgesic treatment for such patients. © RSNA, 2010.
Choucha Snouber L.,CNRS Biomechanical Engineering Laboratory |
Jacques S.,French Institute of Health and Medical Research |
Monge M.,Center Hospitalier University dAmiens |
Legallais C.,CNRS Biomechanical Engineering Laboratory |
Leclerc E.,CNRS Biomechanical Engineering Laboratory
Genomics | Year: 2012
We investigated the behavior of renal cells cultivated in microfluidic biochips when exposed to 50 μM of ifosfamide, an antineoplastic drug treatment. The microarray analysis revealed that ifosfamide had any effect in Petri conditions. The microfluidic biochips induced an early inflammatory response in the MDCK in the untreated cells. This was attributed to cells adapting to the dynamics and micro environment created by the biochips. This led to modulations in the mitochondria dysfunction pathway, the Nrf-2 and oxidative stress pathways and some related cancer genes. When exposed to 50 μM of ifosfamide, we detected a modulation of the pathways related to the cancer and inflammation in the MDCK cultivated in the biochips via modulation of the ATM, p53, MAP Kinase, Nrf-2 and NFKB signaling. In addition, the genes identified and related proteins affected by the ifosfamide treatment in the biochips such as TXNRD1, HSP40 (DNAJB4 and DNAJB9), HSP70 (HSPA9), p21 (CDKN1A), TP53, IKBalpha (NFKBIA) are reported to be the molecular targets in cancer therapy. We also found that the integrin pathway was perturbed with the ifosfamide treatment. Finally, the MYC proto-oncogene appeared to be a potential bridge between the integrin signaling and the anti-inflammatory response. © 2012 Elsevier Inc.
Al-Salameh A.,Center Hospitalier Of Creil |
Cohen R.,Center Hospitalier Of Saint Denis |
Desailloud R.,Center Hospitalier University dAmiens
Application of Clinical Genetics | Year: 2014
Primary aldosteronism is the most common cause of secondary hypertension. The syndrome accounts for 10% of all cases of hypertension and is primarily caused by bilateral adrenal hyperplasia or aldosterone-producing adenoma. Over the last few years, the use of exome sequencing has significantly improved our understanding of this syndrome. Somatic mutations in the KCNJ5, ATP1A1, ATP2B3 or CACNA1D genes are present in more than half of all cases of aldosterone-producing adenoma (~40%, ~6%, ~1% and ~8%, respectively). Germline gain-of-function mutations in KCNJ5 are now known to cause familial hyperaldosteronism type III, and an additional form of genetic hyperaldosteronism has been reported in patients with germline mutations in CACNA1D. These genes code for channels that control ion homeostasis across the plasma membrane of zona glomerulosa cells. Moreover, all these mutations modulate the same pathway, in which elevated intracellular calcium levels lead to aldosterone hyperproduction and (in some cases) adrenal cell proliferation. From a clinical standpoint, the discovery of these mutations has potential implications for patient management. The mutated channels could be targeted by drugs, in order to control hormonal and overgrowth-related manifestations. Furthermore, some of these mutations are associated with high cell turnover and may be amenable to diagnosis via the sequencing of cell-free (circulating) DNA. However, genotype-phenotype correlations in patients harboring these mutations have yet to be characterized. Despite this recent progress, much remains to be done to elucidate the yet unknown mechanisms underlying sporadic bilateral adrenal hyperplasia. © 2014 Al-Salameh et al.
Andrejak C.,Aarhus University Hospital |
Andrejak C.,Center Hospitalier University dAmiens |
Thomsen V.O.,Statens Serum Institute |
Johansen I.S.,Statens Serum Institute |
And 7 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2010
Rationale: Few population-based data are available regarding nontuberculous mycobacteria (NTM) pulmonary disease epidemiology and prognosis. Objectives: To examine NTM pulmonary colonization incidence, disease incidence, and prognostic factors. Methods: All adults in Denmark with at least one NTM-positive pulmonary specimen during 1997 to 2008 were identified using national medical databases and were categorized as having possible or definite NTM disease or colonization. Measurements and Main Results:We calculated annual age-standardized NTM incidence rates and adjusted hazard ratios (HR) of death associated with patient age, sex, comorbidity, NTM species, and NTM disease status. Of 1,282 adults with 2,666 NTM-positive pulmonary specimens, 335 (26%) had definite NTM disease, 238 (19%) possible disease, and 709 (55%) colonization only. NTM incidence rates decreased until 2002, followed by an increase from 2003 to 2008 (mean annual rate per 100,000 person-years: NTM colonization, 1.36; NTM disease, 1.08). Five-year mortality after definite NTM disease was 40.1%. After controlling for potential confounders, 5-year mortality for definite NTM disease was slightly higher than for NTM colonization (adjusted hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.90-1.51). Mycobacterium xenopi was associated with worse prognosis (adjusted HR, 1.51; 95% CI, 0.99-2.33) than the reference Mycobacterium avium complex. High comorbidity level (HR, 2.97), age greater than or equal to 65 years (HR, 9.17), and male sex (female sex HR, 0.73) were predictors of death. Conclusions: NTM disease incidence has remained unchanged in Denmark over the past 12 years. Patients with NTM colonization and disease have similarly poor prognosis. Negative prognostic factors include high levels of comorbidity, advanced age, male sex, and M. xenopi.
Mitchell L.,Stollery Childrens Hospital |
Lambers M.,University of Munster |
Lambers M.,Radboud University Nijmegen |
Flege S.,University of Munster |
And 9 more authors.
Blood | Year: 2010
Among risk factors for developing thromboembolism (VTE) in children with acute lymphoblastic leukemia were Escherichia coli asparaginase, concomitant steroid use, presence of central venous lines, and thrombophilic abnormalities. Developing a predictive model for determining children at increased risk would be beneficial in targeting interventional studies to high-risk groups (HRGs). Predictive variables were incorporated into a risk assessment model, which was evaluated in 456 children and then validated in 339 patients. VTE risk by score was no greater than 2.5 for low-risk group (LRG) and greater than 2.5 for HRG. VTE rates at 3.5 months (validation cohorts) were 2.5% in LRG and 64.7% in HRG. In multivariate analysis adjusted for age, duration of asparaginase administration, enoxaparin prophylaxis, and T-immunophenotype, the HRG was significantly associated with VTE compared with the LRG (hazard/95% confidence interval [CI], 8.22/1.85-36.53). Model specificity was 96.2% and sensitivity was 63.2%. As secondary objective we investigated the use of enoxaparin for VTE prophylaxis in the HRG. HRG patients without enoxaparin prophylaxis showed a significantly reduced thrombosis-free survival compared with children on low-molecular-weight heparin (LMWH). On the basis of the high specificity, the model may identify children with leukemia at risk of VTE. LMWH may help prevent VTE in the HRG; this warrants assessment in larger cooperative clinical trials. © 2010 by The American Society of Hematology.
Popescu C.-I.,University of Lille Nord de France |
Popescu C.-I.,Institute of Biochemistry of the Romanian Academy |
Callens N.,University of Lille Nord de France |
Trinel D.,Lille University of Science and Technology |
And 8 more authors.
PLoS Pathogens | Year: 2011
Growing experimental evidence indicates that, in addition to the physical virion components, the non-structural proteins of hepatitis C virus (HCV) are intimately involved in orchestrating morphogenesis. Since it is dispensable for HCV RNA replication, the non-structural viral protein NS2 is suggested to play a central role in HCV particle assembly. However, despite genetic evidences, we have almost no understanding about NS2 protein-protein interactions and their role in the production of infectious particles. Here, we used co-immunoprecipitation and/or fluorescence resonance energy transfer with fluorescence lifetime imaging microscopy analyses to study the interactions between NS2 and the viroporin p7 and the HCV glycoprotein E2. In addition, we used alanine scanning insertion mutagenesis as well as other mutations in the context of an infectious virus to investigate the functional role of NS2 in HCV assembly. Finally, the subcellular localization of NS2 and several mutants was analyzed by confocal microscopy. Our data demonstrate molecular interactions between NS2 and p7 and E2. Furthermore, we show that, in the context of an infectious virus, NS2 accumulates over time in endoplasmic reticulum-derived dotted structures and colocalizes with both the envelope glycoproteins and components of the replication complex in close proximity to the HCV core protein and lipid droplets, a location that has been shown to be essential for virus assembly. We show that NS2 transmembrane region is crucial for both E2 interaction and subcellular localization. Moreover, specific mutations in core, envelope proteins, p7 and NS5A reported to abolish viral assembly changed the subcellular localization of NS2 protein. Together, these observations indicate that NS2 protein attracts the envelope proteins at the assembly site and it crosstalks with non-structural proteins for virus assembly. © 2011 Popescu et al.
Desnos-Ollivier M.,Institute Pasteur Paris |
Desnos-Ollivier M.,French National Center for Scientific Research |
Moquet O.,Center Hospitalier Of Beauvais |
Chouaki T.,Center Hospitalier University dAmiens |
And 3 more authors.
Journal of Clinical Microbiology | Year: 2011
Clavispora lusitaniae is an opportunistic human pathogen responsible for 0.6 to 2% of candidemia. This species is intrinsically susceptible to echinocandins. Nevertheless, in this study, development of echinocandin resistance in C. lusitaniae isolates was observed during caspofungin treatment. This resistance resulted from missense mutation in the echinocandin target Fks1 gene. Copyright © 2011, American Society for Microbiology. All Rights Reserved.