Montpellier, France
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Hamed S.,REMEDOR Biomedical Ltd | Bennett C.L.,Medical University of South Carolina | Demiot C.,University of Limoges | Ullmann Y.,University of Limoges | And 2 more authors.
Wound Repair and Regeneration | Year: 2014

Developing a new drug is expensive: the cost of going from bench to bedside is about US1 billion. Therefore, the repurposing of an approved drug is potentially rewarding because it expands the drug's existing therapeutic profile and preempts additional development costs. As the safety profile of a repurposed drug is already well known, any new investigations could then focus on its efficacy and other therapeutic benefits. Recombinant erythropoietin (EPO) is a potential candidate for repurposing because the results of numerous studies have shown that systemic and topical EPO is therapeutically beneficial when it is administered to healthy and diabetic animals with acute and chronic skin wounds and burns. Moreover, the molecular mechanisms of EPO's actions have been elucidated: EPO acts on those nonhematopoietic cells which are involved in the innate immune response where it promotes cellular proliferation and differentiation, exerts its cytoprotective actions, and inhibits apoptosis. In this review, the mechanism of EPO's action in skin wound healing is reviewed, and its potential for treating acute and chronic skin wounds and stimulating tissue regeneration in diabetic patients is discussed. © 2013 by the Wound Healing Society.


Haller H.,Hannover Medical School | Ito S.,Tohoku University | Izzo Jr. J.L.,State University of New York at Buffalo | Januszewicz A.,Institute of Cardiology | And 8 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease. We investigated whether treatment with an angiotensin-receptor blocker (ARB) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria. METHODS: In a randomized, double-blind, multicenter, controlled trial, we assigned 4447 patients with type 2 diabetes to receive olmesartan (at a dose of 40 mg once daily) or placebo for a median of 3.2 years. Additional antihypertensive drugs (except angio-tensin-converting-enzyme inhibitors or ARBs) were used as needed to lower blood pressure to less than 130/80 mm Hg. The primary outcome was the time to the first onset of microalbuminuria. The times to the onset of renal and cardiovascular events were analyzed as secondary end points. RESULTS: The target blood pressure (<130/80 mm Hg) was achieved in nearly 80% of the patients taking olmesartan and 71% taking placebo; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group. Microalbuminuria developed in 8.2% of the patients in the olmesartan group (178 of 2160 patients who could be evaluated) and 9.8% in the placebo group (210 of 2139); the time to the onset of microalbuminuria was increased by 23% with olmesartan (hazard ratio for onset of microalbuminuria, 0.77; 95% confidence interval, 0.63 to 0.94; P = 0.01). The serum creatinine level doubled in 1% of the patients in each group. Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events - 81 of 2232 patients (3.6%) as compared with 91 of 2215 patients (4.1%) (P = 0.37) - but a greater number had fatal cardiovascular events - 15 patients (0.7%) as compared with 3 patients (0.1%) (P = 0.01), a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with pre-existing coronary heart disease (11 of 564 patients [2.0%] vs. 1 of 540 [0.2%], P = 0.02). CONCLUSIONS: Olmesartan was associated with a delayed onset of microalbuminuria, even though blood-pressure control in both groups was excellent according to current standards. The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern. (Funded by Daiichi Sankyo; ClinicalTrials.gov number, NCT00185159.) Copyright © 2011 Massachusetts Medical Society.


Menne J.,Hannover Medical School | Izzo J.L.,State University of New York at Buffalo | Ito S.,Tohoku University | Januszewicz A.,Institute of Cardiology | And 9 more authors.
Journal of Hypertension | Year: 2012

Background: We have previously demonstrated in the Randomized Olmesartan and Diabetes Microalbuminuria Prevention study that the angiotensin receptor blocker (ARB) olmesartan delays the onset of microalbuminuria in patients with type 2 diabetes. Now, we investigated the effect in the subpopulation with hypertension. Methods: Overall, 4020 patients with type 2 diabetes and hypertension at baseline (defined by a SBP/DBP ≥130/80 mmHg or use of antihypertensive medication) received either 40 mg olmesartan once daily or placebo for a median of 3.2 years in a randomized, double-blind, multicenter, controlled trial. Additional antihypertensive drugs (except angiotensin- converting enzyme inhibitors or ARBs) were used as needed to lower blood pressure (BP) to less than 130/80 mmHg. Results: The average BP was 126.3/74.7 and 129.5/76.6 mmHg, respectively (P < 0.001). Olmesartan delayed the time to onset of microalbuminuria by 25% (hazard ratio = 0.75; 95% confidence interval = 0.61-0.92, P = 0.007). Patients with a baseline SBP above the median of 136.7 mmHg and a SBP reduction above the median of 17.45 mmHg had a lower incidence of microalbuminuria than patients with a SBP reduction of less than 17.45 (8.1 vs. 11.2%, P < 0.0001). Independent from the baseline BP and the degree of BP reduction a 15-39% increase in the time to onset of microalbuminuria was detectable by olmesartan treatment. Cardiovascular events were comparable and occurred in 93 (4.6%) patients taking olmesartan and 86 (4.4%) taking placebo. Conclusion: Patients with a better BP reduction are less likely to develop microalbuminuria. Treatment with olmesartan delayed the onset of microalbuminuria independent of the baseline BP and the degree of BP reduction. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Ritz E.,University of Heidelberg | Viberti G.C.,KCL Guys Hospital | Ruilope L.M.,Hospital 12 Of Octubre | Rabelink A.J.,Leiden University | And 8 more authors.
Diabetologia | Year: 2010

Aims/hypothesis: In contrast to microalbuminuric type 2 diabetic patients, the factors correlated with urinary albumin excretion are less well known in normoalbuminuric patients. This may be important because even within the normoalbuminuric range, higher rates of albuminuria are known to be associated with higher renal and cardiovascular risk. Methods: At the time of screening for the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) Study, the urinary albumin/creatinine ratio (UACR) was 0.44 mg/mmol in 4,449 type 2 diabetic patients. The independent correlates of UACR were analysed. Results: Independent correlates of UACR during baseline were (in descending order): night-time systolic BP (r s=0.19); HbA1c (r s=0.18); mean 24 h systolic BP (r s=0.16); fasting blood glucose (r s=0.16); night-time diastolic BP (r s=0.12); office systolic BP, sitting (r s=0.11), standing (r s=0.10); estimated GFR (r s=0.10); heart rate, sitting (r s=0.10); haemoglobin (r s=-0.10); triacylglycerol (r s=0.09); and uric acid (r s=-0.08; all p≤0.001). Significantly higher albumin excretion rates were found for the following categorical variables: higher waist circumference (more marked in men); presence of the metabolic syndrome; smoking (difference more marked in males); female sex; antihypertensive treatment; use of amlodipine; insulin treatment; family history of diabetes; and family history of cardiovascular disease (more marked in women). Conclusions/interpretation: Although observational correlations do not prove causality, in normoalbuminuric type 2 diabetic patients the albumin excretion rate is correlated with many factors that are potentially susceptible to intervention. Trial registration:: ClinicalTrials.gov ID no.: NCT00185159 Funding:: This study was sponsored by Daichii-Sankyo.


Guillaume S.,Montpellier University Hospital Center | Guillaume S.,Hospital Lapeyronie | Gorwood P.,University of Paris Descartes | Gorwood P.,French Institute of Health and Medical Research | And 5 more authors.
Psychological Medicine | Year: 2015

Impaired decision-making is a potential neurocognitive phenotype of eating disorders. It is therefore important to disentangle the decision-making deficits associated with the eating disorder subtypes and determine whether this putative impairment is a state or trait marker of the disease or more related to starvation. We systematically reviewed the literature on decision-making in eating disorders and conducted a meta-analysis to explore its role in anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder (BED). Method. A search of the Medline and EMBASE databases and article references was performed. A total of 23 studies (2044 participants) met the selection criteria. When the Iowa gambling task (IGT) was used in at least three of the studies, a meta-analysis was run. Results. IGT performance was significantly worse in patients with an eating disorder diagnosis (AN, BN or BED) compared with healthy controls, indicating that eating disorders have a negative effect on decision-making. Hedges' g effect sizes were moderate to large (-0.72 in AN,-0.62 in BN, and-1.26 in BED). Recovered AN patients had IGT scores similar to those of healthy controls. Restrictive AN patients had significantly lower IGT net scores than purging AN patients, and both AN subtypes had worse performances than healthy controls. Age and body mass index did not explain results. Conclusions. Decision-making was significantly altered in patients with eating disorders. Poor decision-making was more pronounced during the acute phase than in the recovered state of AN. Nutritional status during the acute phase of the disease did not seem to influence decision-making skills. © 2015 Cambridge University Press.


Courtet P.,Hospital Lapeyronie
Correspondances en MHND | Year: 2012

Depression and diabetes are strongly related with bidirectional links and when together they are associated with a poor prognosis of both disorders. Depression should not be considered as a normal suffering in patients presenting a chronic illness. Informing patients and their family about the depressive risk and a regular screening of depression would be helpful to diagnose the disorder earlier and better in diabetic patients. The adequate treatment of depression would be beneficial for both depressive disorder and glycaemic control. Collaborative care for patients presenting chronic medical illness and depression represent a promising strategy.


Barrot A.,Hospital Lapeyronie | Dupuy A.M.,Hospital Lapeyronie | Badiou S.,Hospital Lapeyronie | Bargnoux A.S.,Hospital Lapeyronie | Cristol J.P.,Hospital Lapeyronie
Clinical Laboratory | Year: 2012

Background: To compare the results of HbA1c determination obtained through immunoassays versus the HPLC method currently used routinely in our laboratory. Methods: We evaluated immunoturbidimetric assays for the HbA1c measure on three analyzers, specifically the Roche Cobas Integra 400+®(Roche Diagnostics, Indianapolis, IN, USA), Ortho Clinical Diagnostics Vitros 5.1 FS®(Ortho Clinical Diagnostics, NY, USA), and Siemens Dimension RxL®(Siemens Healthcare Diagnostics, NY, USA), in comparison with the HPLC Menarini HA 8140®(Menarini Diagnostics, Rungis, France) currently used in our laboratory. Results: Analytical performances including precision, analytical range, recovery, carryover, erythrosedimentation and comparison studies were acceptable leading to results with a level of exactitude in accordance with the recommendations of the National Glycohemoglobin Standardization Program (NGSP). Conclusions: The three immunoassays tested can be used interchangeably and will be satisfactory for laboratories who cannot invest in a HPLC analyzer.


Dimeglio A.,Hospital Lapeyronie | Canavese F.,Hospital Lapeyronie | Charles P.,Hospital Lapeyronie
Journal of Pediatric Orthopaedics | Year: 2011

Growth in childhood and in puberty has a major influence on the evolution of spinal curvature. The yearly rate of increase in standing height and sitting height, bone age, and Tanner signs are essential parameters. Additionally, biometric measurements must be repeated every six months. Puberty is a turning point. The pubertal diagram is characterized by two phases: the first two years are a phase of acceleration, and the last three years is a phase of decelaration. Thoracic growth is the fourth dimension of the spine. Bone age is an essential parameter. Risser 0 covers two third of the pubertal growth. On the acceleration phase, olecranon evaluation is more precise than the hand. On the deceleration phase, the Risser sign must be completed by the hand maturation. A 30 degree curve at the very beginning of puberty has 100% risk of surgery. Any spinal, if progression is greater than 10 degree per year on the first two years of puberty the surgical risk is 100%. © 2010 by Lippincott Williams & Wilkins.


Dupuy A.M.,Hospital Lapeyronie | Badiou S.,Hospital Lapeyronie | Elong-Bertard C.,Hospital Lapeyronie | Bargnoux A.S.,Hospital Lapeyronie | Cristol J.P.,Hospital Lapeyronie
Clinical Laboratory | Year: 2014

Background: As the implementation of POC analyzers in clinical department is growing and HbA1c has been included in diagnostics, it appears mandatory to evaluate the accuracy of the POC method to be used. The aim of our study is to evaluate the analytical performance and usefulness of the Afinion® analyzer, and the impact of HbF, hemoglobin variants, and changes of reagent lots. Methods: The Afinion® analyzer (Axis-Shield, Oslo, Norway) is based on affinity separation methodology. Analytical performances including imprecision studies and correlation with currently used HPLC were performed on Biochemistry laboratory. We evaluated the effects of presence of variants on the results of HbA1c. Two reagent lots were evaluated on samples without variant as well as on samples with in the presence of hemoglobin variants HbA/S. The practicability of the system was also tested installing the instrument on pediatric consultation. Results: Imprecision studies of Afinion® were acceptable. Linear regression analysis indicated good correlation between HbA1c values with Afinion® (r > 0.97) in comparison with HPLC method. Overall, the Afinion® overestimated the HbA1 compared to the MenariniHA8140®. These differences were confirmed when the estimated average glucose was calculated. In addition, the variance of cartridge lots requires its use with caution and the problem of lot number instability must be resolved, requiring an adjustment of the calibration by the manufacturer. Conclusions: The Afinion® analyzer met the acceptance criteria of analytical performance, requires minimal operator interaction and presents good correlation with the laboratory method. Beyond the analytical performance, the different regression lines for different lots is a matter of concern. The reproductibility of the production of the different reagent lots for POC devices appears inadequate for its use in a clinical department. HbA1c, POC, precision, lot variability.


PubMed | Hospital Lapeyronie
Type: Journal Article | Journal: Journal of pediatric orthopedics | Year: 2010

Growth in childhood and in puberty has a major influence on the evolution of spinal curvature. The yearly rate of increase in standing height and sitting height, bone age, and Tanner signs are essential parameters. Additionally, biometric measurements must be repeated every six months. Puberty is a turning point. The pubertal diagram is characterized by two phases: the first two years are a phase of acceleration, and the last three years is a phase of decelaration. Thoracic growth is the fourth dimension of the spine. Bone age is an essential parameter. Risser 0 covers two third of the pubertal growth. On the acceleration phase, olecranon evaluation is more precise than the hand. On the deceleration phase, the Risser sign must be completed by the hand maturation. A 30 degree curve at the very beginning of puberty has 100% risk of surgery. Any spinal, if progression is greater than 10 degree per year on the first two years of puberty the surgical risk is 100%.

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