Reinhard Dengler

Bio: Reinhard Dengler is an academic researcher from Hannover Medical School. The author has contributed to research in topics: Amyotrophic lateral sclerosis & Sodium channel. The author has an hindex of 43, co-authored 207 publications receiving 6902 citations. Previous affiliations of Reinhard Dengler include Leibniz University of Hanover & Hochschule Hannover.

Recombinant Human Erythropoietin in the Treatment of Acute Ischemic Stroke

Abstract: Background and Purpose— Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ischemic stroke. Although EPO has been considered to be a safe and well-tolerated drug over 2 decades, recent studies have identified increased thromboembolic complications and/or mortality risks on EPO administration to patients with cancer or chronic kidney disease. Accordingly, the double-blind, placebo-controlled, randomized German Multicenter EPO Stroke Trial (Phase II/III; ClinicalTrials.gov Identifier: NCT00604630) was designed to evaluate efficacy and safety of EPO in stroke. Methods— This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40 000 IU each). Sys...

Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study.

Abstract: Objective To evaluate the effect of different treatment strategies on enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome. Design Multicentre retrospective case-control study. Setting 23 hospitals in northern Germany. Participants 298 adults with enterohaemorrhagic E coli induced haemolytic uraemic syndrome. Main outcome measures Dialysis, seizures, mechanical ventilation, abdominal surgery owing to perforation of the bowel or bowel necrosis, and death. Results 160 of the 298 patients (54%) temporarily required dialysis, with only three needing treatment long term. 37 patients (12%) had seizures, 54 (18%) required mechanical ventilation, and 12 (4%) died. No clear benefit was found from use of plasmapheresis or plasmapheresis with glucocorticoids. 67 of the patients were treated with eculizumab, a monoclonal antibody directed against the complement cascade. No short term benefit was detected that could be attributed to this treatment. 52 patients in one centre that used a strategy of aggressive treatment with combined antibiotics had fewer seizures (2% v 15%, P=0.03),fewer deaths (0% v 5%, p=0.029), required no abdominal surgery, and excreted E coli for a shorter duration. Conclusions Enterohaemorrhagic E coli induced haemolytic uraemic syndrome is a severe self limiting acute condition. Our findings question the benefit of eculizumab and of plasmapheresis with or without glucocorticoids. Patients with established haemolytic uraemic syndrome seemed to benefit from antibiotic treatment and this should be investigated in a controlled trial.

High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebo-controlled double-blind study

Abstract: Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS. The current study, a double blind, placebo-controlled, randomised, stratified, parallel-group clinical trial, was designed to determine whether vitamin E (5000 mg per day) may be efficacious in slowing down disease progression when added to riluzole. Methods. 160 patients in 6 German centres with either probable or definite ALS (according to the El Escorial Criteria) and a disease duration of less than 5 years, treated with riluzole, were included in this study and were randomly assigned to receive either alpha-tocopherol (5000 mg per day) or placebo for 18 months. The Primary outcome measure was survival, calculating time to death, tracheostomy or permanent assisted ventilation, according to the WFN-Criteria of clinical trials. Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales, manual muscle testing (BMRC), spasticity scale, ventilatory function and the Sickness Impact Profile (SIP ALS/19). Patients were assessed at entry and every 4 months thereafter during the study period until month 16 and at a final visit at month 18. Vitamin E samples were taken for compliance check and Quality Control of the trial. For Safety, a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 18. Height and weight were recorded at baseline and weight alone at the follow-up visits. A neurological examination as well as vital signs (heart rate and blood pressure), an ECG and VEP’s were recorded at each visit. Furthermore, spontaneously reported adverse experiences and serious adverse events were documented and standard laboratory tests including liver function tests performed. For Statistical Analysis, the population to be considered for the primary outcome measure was an “intent-to-treat” (ITT) population which included all randomised patients who had received at least one treatment dose (n = 160 patients). For the secondary outcome measures, a two way analysis of variance was performed on a patient population that included all randomised patients who had at least one assessment after inclusion. Results. Concerning the primary endpoint, no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test. The functional assessments showed a marginal trend in favour of vitamin E, without reaching significance. Conclusion. Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol. Larger or longer studies might be needed. However, administration of this megadose does not seem to have any significant side effects in this patient population.

Widespread sensorimotor and frontal cortical atrophy in Amyotrophic Lateral Sclerosis

Abstract: Widespread cortical atrophy in Amyotrophic Lateral Sclerosis (ALS) has been described in neuropathological studies. The presence of cortical atrophy in conventional and scientific neuroimaging has been a matter of debate. In studies using computertomography, positron emission tomography, proton magnetic resonance spectroscopy and conventional T2-weighted and proton-weighted images, results have been variable. Recent morphometric studies by magnetic resonance imaging have produced conflicting results regarding the extent of grey and white matter involvement in ALS patients. The authors used optimized voxel-based morphometry as an unbiased whole brain approach to detect differences between regional grey and white matter volumes. Seventeen patients with a diagnosis of ALS according to El-Escorial criteria and seventeen age-matched controls received a high resolution anatomical T1 scan. In ALS patients regional grey matter volume (GMV) reductions were found in the pre- and postcentral gyrus bilaterally which extended to premotor, parietal and frontal regions bilaterally compared with controls (p < 0.05, corrected for the entire volume). The revised ALS functional rating scale showed a positive correlation with GMV reduction of the right medial frontal gyrus corresponding to the dorsolateral prefrontal cortex. No significant differences were found for white matter volumes or when grey and white matter density images were investigated. There were no further correlations with clinical variables found. In ALS patients, primary sensorimotor cortex atrophy can be regarded as a prominent feature of the disease. Supporting the concept of ALS being a multisytem disorder, our study provides further evidence for extramotor involvement which is widespread. The lack of correlation with common clinical variables probably reflects the fact that heterogeneous disease processes underlie ALS. The discrepancy within all published morphometric studies in ALS so far may be related to differences in patient cohorts and several methodological factors of the data analysis process. Longitudinal studies are required to further clarify the time course and distribution of grey and white matter pathology during the course of ALS.

Voltage-dependent block of neuronal and skeletal muscle sodium channels by thymol and menthol.

Abstract: SummaryBackground and objective:Thymol is a naturally occurring phenol derivative used in anaesthetic practice as a stabilizer and preservative of halothane, usually at a concentration of 0.01%. Although analgesic effects have long been described for thymol and its structural homologue menthol, a mo

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Principles of Neural Science

Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Abstract: Background and Purpose—The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audienc...

Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

Abstract: Background and Purpose- The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods- Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers' comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results- These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions- These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

Neuroscience 細胞死：最近の知見

Abstract: 中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．