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Strasbourg, France

Hochane M.,French Institute of Health and Medical Research | Hochane M.,University of Strasbourg | Raison D.,French Institute of Health and Medical Research | Raison D.,University of Strasbourg | And 10 more authors.

Glomerulonephritis is characterized by the proliferation and apoptosis of mesangial cells (MC). The parathyroid-hormone related protein (PTHrP) is a locally active cytokine that affects these phenomena in many cell types, through either paracrine or intracrine pathways. The aim of this study was to evaluate the effect of both PTHrP pathways on MC proliferation and apoptosis. In vitro studies were based on MC from male transgenic mice allowing PTHrP-gene excision by a CreLoxP system. MC were also transfected with different PTHrP constructs: wild type PTHrP, PTHrP devoid of its signal peptide, or of its nuclear localization sequence. The results showed that PTHrP deletion in MC reduced their proliferation even in the presence of serum and increased their apoptosis when serum-deprived. PTH1R activation by PTHrP(1-36) or PTH(1-34) had no effect on proliferation but improved MC survival. Transfection of MC with PTHrP devoid of its signal peptide significantly increased their proliferation and minimally reduced their apoptosis. Overexpression of PTHrP devoid of its nuclear localization sequence protected cells from apoptosis without changing their proliferation. Wild type PTHrP transfection conferred both mitogenic and survival effects, which seem independent of midregion and C-terminal PTHrP fragments. PTHrP-induced MC proliferation was associated with p27Kip1 down-regulation and c-Myc/E2F1 up-regulation. PTHrP increased MC survival through the activation of cAMP/protein kinase A and PI3-K/Akt pathways. These results reveal that PTHrP is a cytokine of multiple roles in MC, acting as a mitogenic factor only through an intracrine pathway, and reducing apoptosis mainly through the paracrine pathway. Thus, PTHrP appears as a probable actor in MC injuries. Copyright © 2013 by The Endocrine Society. Source

Background: To evaluate different techniques of physiotherapy performed after lung resection via thoracotomy, thanks to a medical literature survey. Material and methods: A bibliographic search (Pubmed, Pascal, Cochrane, PEDro) for English language articles dating from 1980 yielded 32 articles. There were 24 studies (among which 18 were prospective randomized controlled; 5 were case series without controls and 1 was based from a cohort) and 8 synthesis reviews (among which 5 were systematic; 1 was non-systematic; 1 were based from a consensus conference and 1 were based from evidence-based clinical practice guidelines). Results: 1. Definite benefit validated by the scientific search: Transcutaneous electrical nerve stimulation, non invasive ventilation. 2. Benefit non validated by the scientific search because methodology (p or sample size): chest physiotherapy, High frequency percussive ventilation, Positive expiratory pressure. 3. Benefit non validated by the scientific search because methodology (trial without control group): nebulisation, massage, chest wall compression. 4. No benefit validated by scientific search: incentive spirometry. Conclusion: A little techniques of physiotherapy are validated in the framework of pulmonary resection. However, a lot of studies are still to be done in order to enhance the scientific quality of the techniques used by the physiotherapist, to better outcomes after lung resection. © 2010. Elsevier Masson SAS. Tous droits réservés. Source

Penard-Morand C.,French Institute of Health and Medical Research | Penard-Morand C.,University Pierre and Marie Curie | Penard-Morand C.,Agro ParisTech | Raherison C.,Center Francois Magendie | And 7 more authors.
European Respiratory Journal

The aim of this study was to evaluate the impact of urban air pollution, assessed through reliable indicators of exposure, on asthma and allergies in schoolchildren. A validated dispersion model combining data on traffic conditions, topography, meteorology and background pollution was used to relate 3-yrs averaged concentrations of major urban pollutants at the sites of schools to skin prick tests, exercise-induced asthma and reported asthma and allergies in 6,683 children (9-11 yrs) attending 108 schools randomly selected in six French communities. For the 4,907 children who had resided at their current address for the past 3 yrs, asthma (exercise induced, past year and lifetime) was significantly positively associated with benzene, SO2, particles with a 50% cut-off aerodynamic diameter of 10 μm (PM10), nitrogen oxides (NOx) and CO. In the same children, eczema (lifetime and past year) was significantly positively associated with benzene, PM10, NO2, NOx and CO, lifetime allergic rhinitis with PM10 and sensitisation to pollens with benzene and PM10. Among the 2,213 children residing at their current address since birth, the associations persisted for lifetime asthma with benzene (adjusted OR per interquartile range (95% CI) 1.3 (1.0-1.9)) and PM10 (1.4 (1.0-2.0)), and for sensitisation to pollens with volatile organic compounds (1.3 (1.0-1.9)) and PM10 (1.2 (1.0-1.9)). Accurately modelled urban air pollution was associated with some measures of childhood asthma and allergies. Copyright©ERS 2010. Source

Neel A.,University of Nantes | Hello M.,University of Nantes | Cottereau A.,Roche Holding AG | Graveleau J.,University of Nantes | And 10 more authors.

Aim: To investigate the presentation, disease course and long-term outcome of a western cohort of idiopathic granulomatous mastitis (IGM) and to analyse the impact of different therapeutic strategies. Methods: Multicentre retrospective study of 23 women followed over an extended period. Patients were recruited in nine French internal medicine departments. Results: The median follow-up was 6 years. IGM presented commonly as a single inflammatory unilateral extra-areolar lump of varying size. Clinical course was heterogeneous and frequently remitting/relapsing. Most patients had at least one recurrence (18/23, 78%). The mean number of recurrences was 1.3 ± 1.5. Seven women had a bilateral evolution. Twelve women received steroids (corticosteroids). Only two of these did not respond to corticosteroids, whereas six relapsed when dose was tapered off. Nine patients received colchicine and/or hydroxychloroquine. First-line treatment consisted of excisional surgery in eight cases. At the date of last interview, 91% of the patients declared to be healed, 15 being free of treatment. However, 12/21 (57%) reported significant sequelae (unsightly scars: eight and/or lasting pain: six). Unsightly scars were not more prevalent in patients who had received steroids whereas they tended to be more frequent after breast excisional surgery. In addition, we found that excisional surgery did not prevent recurrences more successfully than a conservative approach. Conclusions: Despite its retrospective nature, this Caucasian series provides novel information regarding long-term outcomes in IGM and argues in favour of conservative approaches. The value of immunomodulatory drugs such as colchicine or hydroxychloroquine deserves further investigation. © The Author 2013. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. Source

Mertes P.M.,Nancy University Hospital Center | De Blay F.,Nouvel Hopital Civil | Dong S.,Nancy University Hospital Center
Presse Medicale

Anaphylactic reactions may be either of immune (allergy, usually IgE-mediated, sometimes IgG-mediated) or non-immune origin. The incidence of anaphylactic reactions during anaesthesia varies between countries ranging from 1/1250 to 1/13,000 per procedure. In France, the estimated incidence of allergic reactions is 100.6 [76.2-125.3]/million procedures with a high female predominance (male: 55.4 [42.0-69.0], female: 154.9 [117.2-193.1]). This predominance is not observed in children. In adults, the most frequently incriminated substances are neuromuscular blocking agents, followed by latex and antibiotics. The estimated incidence of allergic reactions to neuromuscular blocking agents is 184.0 [139.3-229.7]/million procedure. In most cases there is a close reaction between clinical symptoms and drug administration. When the reaction is delayed, occurring during the surgical procedure, a reaction involving latex, a vital dye, an antiseptic or a volume expanding fluid should be suspected. Reaction severity may vary. The most frequently reported initial symptoms are pulselessness, erythema, increased airway pressure, desaturation or decreased end-tidal CO2.Clinical symptoms may occur as an isolated condition, making proper diagnosis difficult. In some cases a cardiovascular arrest can be observed. Reaction mechanism identification relies on mediators (tryptase, histamine) measurement at the time of the reaction. In case of allergic reaction, the responsible drug can be identified by the detection of specific IgE using immunoassays or by skin tests performed 6 weeks after the reaction. Predictive allergy investigation to latex or anaesthetics in the absence of history of reaction should be restricted to at-risk patients. Premedication cannot prevent the onset of an allergic reaction. Providing a latex-free environment can be used for primary or secondary prevention. Treatment is based on allergen administration interruption, epinephrine administration in a titrated manner based on symptoms severity, and on volume expansion. © 2012 Elsevier Masson SAS. Source

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