IL-2-inducible T-cell kinase deficiency: clinical presentation and therapeutic approach

Mutations in the IL-2-inducible T-cell kinase gene have recently been shown to cause an autosomal recessive fatal Epstein Barr virus (EBV) associated lymphoproliferation. We report 3 cases from a single family who presented with EBV-positive B-cell proliferation diagnosed as Hodgkin's lymphoma. Single nucleotide polymorphism array-based genome-wide linkage analysis revealed IL-2-inducible T-cell kinase as a candidate gene for this disorder. All 3 patients harbored the same novel homozygous nonsense mutation C1764G which causes a premature stop-codon in the kinase domain. All cases were initially treated with chemotherapy. One patient remains in durable remission, the second patient subsequently developed severe hemophagocytic lymphohistiocytosis with multi-organ failure and died, and the third patient underwent a successful allogeneic bone marrow transplantation. IL-2-inducible T-cell kinase deficiency underlies a new primary immune deficiency which may account for part of the spectrum of Epstein Barr virus related lymphoproliferative disorders which can be successfully corrected by bone marrow transplantation.     

德国老年人对替代医学疗法、针刺、顺势疗法及人智学疗法的使用情况

目的：很多有关补充替代医学（complementary and alternative medicine,CAM）的研究表明,CAM的使用情况与患者的社会文化背景、性别、年龄及基础疾病等因素有关。本研究旨在调查分析拥有医疗保险的德国老年人对特定的CAM疗法的使用情况。方法：在一次匿名的德国保险受益人的横断面调查中,对5 830名老年人过去5年里通过医生或非医疗工作者使用CAM的情况的调查数据进行分析。结果：德国老年人最广泛使用的CAM疗法分别为针刺/中医（21%）、顺势疗法（21%）、运动疗法/锻炼（19%）、整骨疗法/脊椎指压疗法（12%）、草药/植物疗法（7%）、节食/特殊食谱（6%）及足底反射疗法（5%）。人智学疗法只被很少数的人使用。针刺与顺势疗法的使用者倾向于同时使用多种CAM疗法,特别是同时使用针刺与顺势疗法。男性患者与女性患者在CAM疗法的使用上有显著的不同。结论：针刺与顺势疗法的使用人数近似,而顺势疗法是源于西欧的一种CAM疗法,这说明针刺这一来自东方的疗法在德国也有其立足之地。很多患者同时使用多种CAM疗法,特别是针刺与顺势疗法同时使用者居多。此外,对于一些将并非CAM疗法的治疗方法纳入其研究之中而得出的结论,应该持谨慎态度。     

Suicidal and self-harm behaviour associated with adolescent attention deficit hyperactivity disorder-A study in the Northern Finland Birth Cohort 1986

Background: Suicidal behaviour, i.e. suicidal ideation and suicidal acts, as well as self-harm behaviour, are relatively common among adolescents. Depression and/or female gender seem to be risk factors for suicidal behaviour. However, the role of attention deficit hyperactivity disorder (ADHD) in these behaviours is still unclear. Aim: To study the effect of ADHD on suicidal or self-harm behaviour in adolescents from a general population sample. Methods: The sample was derived from a population-based Northern Finland Birth Cohort 1986 (n = 9432). Based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version (Kiddie-SADS-PL) interview performed in a subpopulation (n = 457), the associations between suicidal behaviour and deliberate self-harm (DSH) and the diagnosis of ADHD were studied. Results: Compared with adolescents without ADHD (n = 169), those with ADHD (n = 104) had more suicidal ideation (57% vs. 28%, P < 0.001) and DSH (69% vs. 32%, P < 0.001). In binary logistic models, the effect of ADHD on suicidal ideation remained strong (OR = 6.1) after controlling for several other predictors. Other contributing factors in suicidal behaviour included female gender, childhood emotional and behavioural problems, concurrent depression and anxiety, and, specifically in DSH, behavioural disorder, substance abuse and strains in family relations. Discussion and clinical implications: ADHD is a risk factor for suicidal ideation and DSH. These findings in a general population sample speak for a need to target mental health interventions at children and adolescents with relevant symptoms of ADHD.     

XIAP protects oligodendrocytes against cell death in vitro but has no functional role in toxic demyelination

Oligodendroglial damage and loss are typical characteristics of demyelinating diseases such as multiple sclerosis (MS) and the leukodystrophies. Axonal loss is the underlying cause of permanent neurological deficits in MS and it is thought to arise from a combination of immune-mediated axonal damage and the loss of trophic support to axons from myelin sheaths after demyelination. Prevention of oligodendroglial damage or death and demyelination are therefore attractive neuroprotective treatment strategies. However, a better understanding of mechanisms leading to oligodendroglial damage and demyelination is a prerequisite for the development of such treatment options. Here, we demonstrate that X-linked inhibitor of apoptosis (XIAP), the most potent member of the inhibitor of apoptosis proteins (IAP) family is expressed in oligodendrocytes in vivo and in vitro. Increased expression of XIAP is associated with protection against selected cell death pathways, whereas decreased expression increases oligodendroglial cell death in vitro. However, lack of XIAP does not modulate oligodendroglial cell death in toxic demyelination in vivo.