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Hôpital-Camfrout, France

Rinaudo M.,Biomaterials Applications | Lardy B.,Joseph Fourier University | Grange L.,Center Hospitalier University Amichallon | Conrozier T.,Center Hospitalier Of Belfort Montbeliard
Polymers | Year: 2014

In this paper, we propose the evaluation of the mannitol's ability to reduce hyaluronic acid (HA) degradation using two different models of oxidative stress. Firstly, a solution of hyaluronan and a solution of the same HA including mannitol in PBS buffer were submitted to an oxidative stress generated by the addition of xanthine + xanthine oxidase generating oxygen free radicals. Different enzyme concentrations were used and the HA properties were studied after 24 h of contact at ambient temperature. Decreases of the viscosity of the solution were assessed by rheometry (viscous and elastic module) and that of HA molecular weight was determined by steric exclusion chromatography. Rheologic behavior was assessed on identical HA solutions subjected to another model of oxidative stress imposed by addition of hydrogen peroxide. The influence of mannitol concentration on HA degradation was also demonstrated. Whatever the stress applied, it appears very clearly that mannitol protects hyaluronic acid from mediated oxygen free radicals degradation. These in vitro results suggest that mannitol could be a simple way to significantly increase the intra-articular residence time of the injected hyaluronic acid and therefore might improve viscosupplementation effectiveness. © 2014 by the authors. Source

Purpose: The diagnosis of fever or inflammation of unknown origin (FUO/IUO) is guided by the search of clinical clues. Lymphadenopathy is thought to be helpful but its actual contribution has never been tested, and little is known about the main causes of FUO/IUO with lymphadenopathy. The aim of this study was to clarify these issues from the experience of two departments of internal medicine. Methods: We retrospectively studied a cohort of 69 consecutive inpatients with FUO or IUO and lymphadenopathy, hospitalized from January 2002 to February 2008. The patients were coded according to the final diagnosis and age. Recorded data included lymph node location, fever, CRP level, lymphocyte and platelet counts, presence of hyperbasophilic cells, hypogammaglobulinemia, monoclonal gammopathy, LDH level, and the results of histological and or cytological lymph node examination. Results: Malignancy accounted for 54%, granulomatosis for 23%, mainly of infectious (60%) or malignancy-related origin (18%), the group classified as non-specific adenitis represented 17% of the cases and systemic diseases 4%. Diagnosis was obtained by histological examination of a lymph node biopsy in 80% and by cytology alone in 13% of the patients; no correlation was found between anatomic location, clinical and biological data and any pathological group. Univariate age-independent analysis showed significant correlation between intra-abdominal lymphadenopathy (P = 0.05), increased serum CRP (P = 0.01) and LDH levels (P = 0.05) and malignancy, whereas superficial unique lymph node location (P< 0.05), absence of deep site location (P< 0.01), and presence of hyperbasophilic cells (P< 0.01) were all related to benign non specific adenitis. Conclusion: FUO/IUO with lymphadenopathy must be considered as a separate entity, mostly represented by malignancies and granulomatosis, mainly of infectious or malignancy related origin. Fever, intra-abdominal lymphadenopathy, serum CRP and LDH levels and hyperbasophilic cells are relevant indicators. © 2011 Société nationale française de médecine interne (SNFMI). Source

Quoix E.,University of Strasbourg | Ramlau R.,Regional Center for Lung Disease | Westeel V.,University of Franche Comte | Papai Z.,Pulmonologiai Osztaly | And 15 more authors.
The Lancet Oncology | Year: 2011

Background: Chemotherapy is the standard of care for advanced stages of non-small-cell lung cancer (NSCLC). TG4010 is a targeted immunotherapy based on a poxvirus (modified vaccinia virus Ankara) that codes for MUC1 tumour-associated antigen and interleukin 2. This study assessed TG4010 in combination with first-line chemotherapy in advanced NSCLC. Methods: 148 patients with advanced (stage IIIB [wet] or IV) NSCLC expressing MUC1 by immunohistochemistry, and with performance status 0 or 1, were enrolled in parallel groups in this open-label, phase 2B study. 74 patients were allocated to the combination therapy group, and received TG4010 (108 plaque forming units) plus cisplatin (75 mg/m2 on day 1) and gemcitabine (1250 mg/m2 on days 1 and 8) repeated every 3 weeks for up to six cycles. 74 patients allocated to the control group received the same chemotherapy alone. Patients were allocated using a dynamic minimisation procedure stratified by centre, performance status, and disease stage. The primary endpoint was 6-month progression-free survival (PFS), with a target rate of 40% or higher in the experimental group. Analyses were done on an intention-to-treat basis. This study is completed and is registered with ClinicalTrials.gov, number NCT00415818. Findings: 6-month PFS was 43·2% (32 of 74; 95% CI 33·4-53·5) in the TG4010 plus chemotherapy group, and 35·1% (26 of 74; 25·9-45·3) in the chemotherapy alone group. Fever, abdominal pain, and injection-site pain of any grade according to National Cancer Institute Common Toxicity Criteria were more common in the TG4010 group than in the chemotherapy alone group: 17 of 73 patients (23·3%) versus six of 72 (8·3%), 12 (16·4%) versus two (2·8%), and four (5·5%) versus zero (0%), respectively. The most common grade 3-4 adverse events were neutropenia (33 [45·2%] of patients in the TG4010 plus chemotherapy group vs 31 [43·1%] in the chemotherapy alone group) and fatigue (18 [24·7%] vs 13 [18·1%]); the only grade 3-4 events that differed significantly between groups were anorexia (three [4·1%] vs 10 [13·9%]) and pleural effusion (none vs four [5·6%]). 38 of 73 patients (52·1%) in the TG4010 plus chemotherapy group and 34 of 72 (47·2%) in the chemotherapy alone group had at least one serious adverse event. Interpretation: This phase 2B study suggests that TG4010 enhances the effect of chemotherapy in advanced NSCLC. A confirmatory phase 2B-3 trial has been initiated. Funding: Transgene SA, Advanced Diagnostics for New Therapeutic Approaches (ADNA)/OSEO. © 2011 Elsevier Ltd. Source

Wagner S.,Center Hospitalier Of Belfort Montbeliard | Vianey-Saban C.,Lyon University Hospital Center | Salomons G.-S.,VU University Amsterdam | Schmitt E.,Nancy University Hospital Center | Feillet F.,Nancy University Hospital Center
Archives de Pediatrie | Year: 2014

L-2-hydroxyglutaric aciduria is a rare genetic neurometabolic disease. It occurs in childhood with mental retardation, cerebellar ataxia, and epilepsy. Macrocephaly is present in half of the cases. Diagnosis is based on clinical symptoms, biological and radiological findings, and molecular testing. Specific treatments can improve the spontaneous progression of the disease. We examined two independent patients who presented with L-2-hydroxyglutaric aciduria. Clinical presentation led to cerebral MRI and urinary organic acid chromatography. The genetic analysis confirmed the diagnosis. Under specific treatment, the progression of the disease was subsequently stopped. L-2-hydroxyglutaric aciduria shares common symptoms with other genetic and metabolic diseases. However, the association of a distinct phenotype and typical MRI abnormalities (such as a high signal in the subcortical white matter, pallidum, and dentate nuclei) should draw the clinician's attention to this diagnosis. It can easily be suspected with a simple urinary analysis and can then be confirmed by genetic testing. With this case report, we show the importance of genetic identification to begin treatment with riboflavin. Early detection of L-2-hydroxyglutaric aciduria based on MRI abnormalities can enable rapid initiation of treatment and prevent disease progression. © 2013 Elsevier Masson SAS. Source

Veauthier C.,Center Hospitalier Of Belfort Montbeliard | Paul F.,Charite University Medicine Berlin and Max Delbrueck Center for Molecular Medicine | Paul F.,Charite - Medical University of Berlin
Sleep Medicine | Year: 2014

Treatment of multiple sclerosis (MS)-related fatigue is still a challenging task, given that no proven therapies exist and its mechanisms are not known. Our review highlights the relationship between MS-related fatigue and sleep disorders (SD). Although many studies suggest a higher overall prevalence of SD in MS, there are no valid and robust data to confirm this hypothesis until now except for restless legs syndrome (RLS): the prevalence of RLS in MS patients-especially in those with severe pyramidal and sensory disability-seems to be four times higher than in controls subjects. RLS is sometimes difficult to distinguish from spasticity and in case of doubt, probatory dopaminergic therapy or polysomnographic (PSG) investigations may be helpful. Nocturia may impact MS-related fatigue and should be considered. The treatment of underlying SD led to an improvement of MS-related fatigue. From a scientific point of view, SD should be examined in all studies investigating MS-related fatigue and be considered as a relevant confounder. © 2013 Elsevier B.V. Source

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