Da Costa L.,Hopital University Robert Debre
Blood | Year: 2013
In this issue of Blood Garçon et al describe successful derivation of induced pluripotent stem cells (iPSs) from fibroblasts of Diamond Blackfan anemia (DBA) patients with 2 distinct ribosomal defects. Using these cells the authors showed that they not only exhibit defective erythropoiesis but also globally impaired hematopoiesis affecting multipotent progenitors. © 2013 by The American Society of Hematology.
Coghill D.R.,University of Dundee |
Banaschewski T.,University of Heidelberg |
Lecendreux M.,Hopital University Robert Debre |
Zuddas A.,University of Cagliari |
And 7 more authors.
Journal of the American Academy of Child and Adolescent Psychiatry | Year: 2014
Objective In this phase 3 extension study, the long-term maintenance of efficacy of lisdexamfetamine dimesylate (LDX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) was evaluated using a randomized-withdrawal study design. Method European and US patients (6-17 years; N = 276) with ADHD were entered into a 26-week open-label trial of LDX treatment. Those who completed the open-label period (n = 157) were randomized 1:1 to their optimized dose of LDX (30, 50, or 70 mg per day) or placebo for a 6-week randomized-withdrawal period (RWP). The primary efficacy measure was the proportion of patients meeting treatment failure criteria (≥50% increase in ADHD Rating Scale IV total score and ≥2-point increase in Clinical Global Impressions-Severity of Illness [CGI-S] score, compared with RWP start point). Safety and tolerability were also evaluated. Results During the RWP (LDX, n = 78; placebo, n = 79), significantly fewer patients receiving LDX met treatment failure criteria (15.8%) compared with those receiving placebo (67.5%; difference = -51.7%; 95% confidence interval = -65.0, -38.5; p <.001). Most treatment failures occurred at or before the week 2 visit after randomization. Treatment-emergent adverse events were reported in 39.7% and 25.3% of patients receiving LDX and placebo, respectively, during the RWP. Conclusions These data demonstrate the maintenance of efficacy of LDX during long-term treatment in children and adolescents with ADHD. The rapid return of symptoms on LDX withdrawal demonstrates the need for continuing treatment. The safety profile of LDX was consistent with that of other stimulants. Clinical trial registration information - Double-Blind, Placebo-Controlled, Randomized Withdrawal, Extension, Safety and Efficacy Study of LDX in Children and Adolescents Aged 6-17; http://clinicaltrials.gov; NCT00784654.
Quoc E.B.,Hopital University Robert Debre
Revue Francophone d'Orthoptie | Year: 2014
Meridian amblyopia or amblyopia induced by astigmatism is a unilateral or bilateral amblyopia resulting from a significant astigmatism that was not corrected during the sensitive period of visual development: unilateral meridian amblyopia is possible with a 0.75 diopter cylindrical anisotropy; bilateral meridian amblyopia is possible in the case of bilateral astigmatism of more than 2 diopters. An oblique axis of astigmatism is more amblyogenic than an orthogonal axis. The prevalence of meridian amblyopia is difficult to assess because the spherical factors are often associated with cylindrical factors, but an asymmetrical astigmatism is clearly a risk factor for amblyopia. Meridian amblyopia would be the consequence notably of a bias in the selectivity in orientation of visual neurones. Treatment of meridian amblyopia resides in total optical correction of the cylindrical ametropia and of the spherical ametropia as well as occlusion of the healthy eye. © 2014 Elsevier Masson SAS. All rights reserved.
Baudouin V.,Hopital University Robert Debre
Medecine Therapeutique Pediatrie | Year: 2015
More than 90% of children with idiopathic nephrotic syndrome (INS) experience remission with steroid treatment. However, 80% experience relapses and around 60% require long-term corticotherapy to remain in remission. Prolonged use of corticotherapy leads to a number of side effects and in order to avoid them, immune modulators or immune suppressors may be prescribed. Traditionally, cyclosporine and cyclophosphamide have been used as immunosuppressive treatment strategies in such cases, but toxicity limits their use. For more than 10 years, numerous clinical reports have demonstrated the efficacy of mycophenolate mofetil (MMF) in steroid-dependent nephrotic syndrome (NS). Due to the lack of nephrotoxicity, cyclosporine is now considered only in the event of MMF treatment failure. More recently, rituximab has emerged as a new treatment option in cases of calcineurin inhibitor dependency. However, while treatment of the primary course of INS is well established, steroid-dependent NS management continues to pose challenges and there is a need to define appropriate treatment depending on patients' individual characteristics.
Lemaire M.,Yale University |
Fremeaux-Bacchi V.,Assistance Publique Hopitaux de Paris |
Schaefer F.,University of Heidelberg |
Choi M.,Yale University |
And 29 more authors.
Nature Genetics | Year: 2013
Pathologic thrombosis is a major cause of mortality. Hemolytic-uremic syndrome (HUS) features episodes of small-vessel thrombosis resulting in microangiopathic hemolytic anemia, thrombocytopenia and renal failure. Atypical HUS (aHUS) can result from genetic or autoimmune factors that lead to pathologic complement cascade activation. Using exome sequencing, we identified recessive mutations in DGKE (encoding diacylglycerol kinase É) that co-segregated with aHUS in nine unrelated kindreds, defining a distinctive Mendelian disease. Affected individuals present with aHUS before age 1 year, have persistent hypertension, hematuria and proteinuria (sometimes in the nephrotic range), and develop chronic kidney disease with age. DGKE is found in endothelium, platelets and podocytes. Arachidonic acid-containing diacylglycerols (DAG) activate protein kinase C (PKC), which promotes thrombosis, and DGKE normally inactivates DAG signaling. We infer that loss of DGKE function results in a prothrombotic state. These findings identify a new mechanism of pathologic thrombosis and kidney failure and have immediate implications for treating individuals with aHUS. © 2013 Nature America, Inc. All rights reserved.