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Saint-André-lez-Lille, France

Karila L.,University Paris - Sud | Megarbane B.,French Institute of Health and Medical Research | Megarbane B.,University of Paris Descartes | Megarbane B.,University Paris Diderot | And 2 more authors.
Current Neuropharmacology | Year: 2015

New psychoactive substances (NPS) have completely modified the drug scene and the current landscape of addiction. Synthetic substances, such as substituted or synthetic cathinones, also known as « legal highs », are often produced and used to mimic the effects of controlled drugs such as cocaine, methylenedioxymethamphetamine (MDMA, ecstasy), and methamphetamine. The overwhelming majority of synthetic cathinones are produced in China and South East Asian countries. The Internet has emerged as the new marketplace for NPS, playing a major role in providing information on acquisition, synthesis, extraction, identification, and substance use. All these compounds are intentionally mislabeled and sold on-line under slang terms such as bath salts, plant food, plant feeders and research chemicals. They are sometimes labeled « not for human use » or « not tested for hazards or toxicity ». The rapid spread of NPS forces member countries of the European Union to adapt their response to the potential new dangers that may cause. To date, not only health actors but also the general public need to be clearly informed and aware of dangers resulting from NPS spread and use. Here, we review the major clinical effects of synthetic cathinones to highlight their impact on public health. A literature search was conducted from 2009 to 2014 based on PubMed, Google Scholar, Erowid, and governmental websites, using the following keywords alone or in combination: “new psychoactive substances”, “synthetic cathinones”, “substituted cathinones”, “mephedrone”, “methylone”, “MDPV”, “4-MEC”, “addiction”, and “substance use disorder”. © 2015 Bentham Science Publishers. Source

Dubuquoy L.,French Institute of Health and Medical Research | Colombel J.-F.,The New School | Jouret-Mourin A.,Cliniques Universitaires | Delos M.,CHU UCL Mont Godinne | And 5 more authors.
Inflammatory Bowel Diseases | Year: 2013

Background: Increased lymphatic vessel (LV) density has been found in uninflamed intestinal wall of patients with Crohn's disease (CD). The goal of the study was to search for an association between LV density in the proximal ileal resection margin at the time of surgery and endoscopic recurrence. Methods: Ileocolonic resection specimens were obtained from 28 CD patients and 10 control subjects. The ileal proximal uninflamed section was used for the histological quantification of LV using immunohistochemistry with D2-40 antibody in the mucosa and submucosa. Quantification of LV was performed in 8 consecutive fields and was blinded to recurrence score. Patients were divided into 2 groups based on the presence (Rutgeerts score, i3/i4) (R+) or absence (Rutgeerts score, i0/i1) (R-) of endoscopic recurrence 1 year after the surgery. All patients were free of immunomodulators or biologics between surgery and postoperative endoscopy. Results: Median LV density was lower in control subjects than in CD patients in the mucosa (4.5%; interquartile range [IQR], 3.6-5.3 versus 5.9%; IQR, 4.2-8.5; P = 0.04) and submucosa (2.4%; IQR, 1.9-3.6 versus 5.7%; IQR, 4.3-6.9; P < 0.01). R-patients had a higher LV density in the proximal resection margin at surgery than R+ patients, both in the mucosa (8.5%; IQR, 6.5-10.3 versus 4.4%; IQR, 3.1-6.1; P < 0.01) and in the submucosa (6.3%; IQR, 5.5-9.3 versus 5.3%; IQR, 3.4-5.9; P = 0.03). Mucosal LV density greater than 7% predicted the absence of endoscopic recurrence at 1 year, with a sensitivity of 81% and a specificity of 75%. Conclusions: Decreased LV density is associated with high risk of endoscopic recurrence after surgery. Therapies that improve lymphatic flow in the gut may reduce the incidence of endoscopic recurrence. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc. Source

Tallet A.,French Institute of Health and Medical Research | Tallet A.,University of Paris Descartes | Nault J.-C.,French Institute of Health and Medical Research | Nault J.-C.,University of Paris Descartes | And 17 more authors.
Oncogene | Year: 2014

Malignant pleural mesothelioma (MPM) is a very aggressive tumor with no known curative treatment. Better knowledge of the molecular mechanisms of mesothelial carcinogenesis is required to develop new therapeutic strategies. MPM, like all cancer cells, needs to maintain telomere length to prevent senescence. Previous studies suggested that the telomere lengthening mechanism in MPM is based mainly on telomerase activity. For this reason, we focused on the key catalytic enzyme, TERT (telomerase reverse transcriptase), by analyzing its gene expression in MPM and by studying the mechanism underlying its upregulation. We used our large collection of MPM composed of 61 MPM in culture and 71 frozen MPM tumor samples. Evaluation of TERT mRNA expression by quantitative RT-PCR showed overexpression in MPM in culture compared with normal mesothelial cells, and in MPM tumor samples compared with normal pleura. We identified a 'hot spot' of mutations in the TERT gene core promoter in both MPM in culture and in MPM tumor samples with an overall frequency of 15%. Furthermore, data clearly identified mutation in the TERT promoter as a mechanism of TERT mRNA upregulation in MPM. In contrast, gene copy number amplification was not associated with TERT overexpression. Then, we analyzed the clinicopathological, etiological and genetic characteristics of MPM with mutations in the TERT promoter. TERT promoter mutations were more frequent in MPM with sarcomatoid histologic subtype (P<0.01), and they were frequently associated with CDKN2A gene inactivation (P=0.03). In conclusion, a subgroup of MPM presents TERT promoter mutations, which lead to TERT mRNA upregulation. This is the first recurrent gain-of-function oncogenic mutations identified in MPM. © 2014 Macmillan Publishers Limited. Source

Lemyze M.,Schaffner Hospital | Mallat J.,Schaffner Hospital | Duhamel A.,CHRU Lille | Pepy F.,Schaffner Hospital | And 5 more authors.
Critical Care Medicine | Year: 2013

OBJECTIVE: To evaluate the extent to which sitting position and applied positive end-expiratory pressure improve respiratory mechanics of severely obese patients under mechanical ventilation. DESIGN: Prospective cohort study. SETTINGS: A 15-bed ICU of a tertiary hospital. PARTICIPANTS: Fifteen consecutive critically ill patients with a body mass index (the weight in kilograms divided by the square of the height in meters) above 35 were compared to 15 controls with body mass index less than 30. INTERVENTIONS: Respiratory mechanics was first assessed in the supine position, at zero end-expiratory pressure, and then at positive end-expiratory pressure set at the level of auto-positive endexpiratory pressure. Second, all measures were repeated in the sitting position. MEASUREMENTS AND MAIN RESULTS: Assessment of respiratory mechanics included plateau pressure, auto-positive end-expiratory pressure, and flow-limited volume during manual compression of the abdomen, expressed as percentage of tidal volume to evaluate expiratory flow limitation. In supine position at zero end-expiratory pressure, all critically ill obese patients demonstrated expiratory flow limitation (flow-limited volume, 59.4% [51.3-81.4%] vs 0% [0-0%] in controls; p < 0.0001) and greater auto-positive end-expiratory pressure (10 [5-12.5] vs 0.7 [0.4-1.25] cm H2O in controls; p < 0.0001). Applied positive end-expiratory pressure reverses expiratory flow limitation (flow-limited volume, 0% [0-21%] vs 59.4% [51-81.4%] at zero end-expiratory pressure; p < 0.001) in almost all the obese patients, without increasing plateau pressure (24 [19-25] vs 22 [18-24] cm H2O at zero end-expiratory pressure; p = 0.94). Sitting position not only reverses partially or completely expiratory flow limitation at zero end-expiratory pressure (flow-limited volume, 0% [0-58%] vs 59.4% [51-81.4%] in supine obese patients; p < 0.001) but also results in a significant drop in auto-positive end-expiratory pressure (1.2 [0.6-4] vs 10 [5-12.5] cm H2O in supine obese patients; p < 0.001) and plateau pressure (15.6 [14-17] vs 22 [18-24] cm H2O in supine obese patients; p < 0.001). CONCLUSIONS: In critically ill obese patients under mechanical ventilation, sitting position constantly and significantly relieved expiratory flow limitation and auto-positive end-expiratory pressure resulting in a dramatic drop in alveolar pressures. Combining sitting position and applied positive end-expiratory pressure provides the best strategy. Copyright © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Source

Hochart V.,CHRU Lille | Verpillat P.,CHRU Lille | Langlois C.,EA | Garabedian C.,CHRU Lille | And 4 more authors.
European Radiology | Year: 2014

Methods: We reviewed fMRI performed because of sonographic suspicion of an OA. The signs reviewed included stomach size, “pouch sign”, bowing of the trachea and visualization of the lower oesophageal lumen. The fetuses were assigned by consensus as having or not having EA, as well as having a tracheaoesophageal fistula (TOF). All findings were correlated with postnatal data. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated.Results: Se, Sp, PPV and NPV of the technique were respectively 91 %, 100 %, 100 % and 88 %. The presence of the pouch sign yielded corresponding values of 82 %, 100 %, 100 % and 78 %. Mid-tracheal bowing was correlated positively with EA. The type of atresia was correctly evaluated in 90 % of patients.Conclusion: fMRI is useful for the diagnosis of EA through the visualization of the oesophageal pouch or through associated signs such as tracheal bowing. Visualization of the lower oesophageal lumen seems to be a good sign of TEF.Key Points: • Challenges are to improve the prenatal diagnosis of EA and associated malformations.• fMRI is able to diagnose EA through demonstration of the pouch sign.• Tracheal bowing is a promising indirect sign of EA.• Tracheoesophageal fistula can also be suspected thanks to fMRI.• Obstetrical US, fMRI and fetal CT are complementary for assessing associated malformations.Objective: Present challenges are to improve the diagnosis rate of oesophageal atresia (OA) and evaluate as completely as possible a fetus affected by OA, specifically the type of OA and the length of the gap. Our aim was to evaluate the accuracy of fetal MR imaging (fMRI) for diagnosis of OA. © 2014, European Society of Radiology. Source

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