Goethes Wahlverwandtschaften wurden schon unter vielen Aspekten untersucht, eine eingehende Betrachtung ihrer raffinierten bis arglosen Gesprächskunst stand bisher jedoch noch aus. Gerhard Bauer ...untersucht dieses Zureden und Abwehren, auch Sticheln, die meist frei fließende, manchmal aber auch stockende Rede, mit Untertönen, wo sie ans Unerlaubte rührt - und macht deutlich: Goethes Dichtkunst erweist sich in der Ausgestaltung dieser Gesprächsverläufe nicht weniger als in der Konzeption und Durchführung der ruhigen - und unversehens dramatisch zugespitzten - Handlung.
Summary
Nonconvulsive status epilepticus (NCSE) in a comatose patient cannot be diagnosed without electroencephalography (EEG). In many advanced coma stages, the EEG exhibits continuous or periodic ...EEG abnormalities, but their causal role in coma remains unclear in many cases. To date there is no consensus on whether to treat NCSE in a comatose patient in order to improve the outcome or to retract from treatment, as these EEG patterns might reflect the end stages of a dying brain. On the basis of EEG, NCSE in comatose patients may be classified as generalized or lateralized. This review aims to summarize the ongoing debate of NCSE and coma and to critically reassess the available literature on coma with epileptiform EEG pattern and its prognostic and therapeutic implications. The authors suggest distinguishing NCSE proper and comatose NCSE, which includes coma with continuous lateralized discharges or generalized epileptiform discharges (coma‐LED, coma‐GED). Although NCSE proper is accompanied by clinical symptoms suggestive of status epilepticus and mild impairment of consciousness, such as in absence status or complex focal status epilepticus, coma‐LED and coma‐GED represent deep coma of various etiology without any clinical motor signs of status epilepticus but with characteristic epileptiform EEG pattern. Hence coma‐LED and coma‐GED can be diagnosed with EEG only. Subtle or stuporous status epilepticus and epilepsia partialis continua–like symptoms in severe acute central nervous system (CNS) disorders represent the borderland in this biologic continuum between NCSE proper and comatose NCSE (coma‐LED/GED). This pragmatic differentiation could act as a starting point to solve terminologic and factual confusion.
Adult stem cell therapies have provided success for more than 50 years, through reconstitution of the hematopoietic system using bone marrow, umbilical cord blood, and mobilized peripheral blood ...transplantation. Mesenchymal stem cell (MSC)‐mediated therapy is a fast‐growing field that has proven safe and effective in the treatment of various degenerative diseases and tissue injuries. Since the first derivation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), there has been impressive progress toward developing safe clinical applications from PSCs. Recent successes in transgene‐free iPSC reprogramming have brought attention to the potential of clinical applications of these pluripotent cells, but key hurdles must be overcome, which are discussed in this review. Looking to the future, it could be advantageous to derive MSC from iPSC or human ESC in cases where genetic engineering is needed, since in the PSCs, clones with “safe harbor” vector integration could be selected, expanded, and differentiated. Here, we describe the status of the progress of the use of MSC and PSCs in clinical trials and analyze the challenges that should be overcome before iPSC‐derived MSC therapy can be used widely in the clinic. STEM CELLS 2012;30:42–47
The promise of stem cell (SC) therapies to restore functions of damaged tissues and organs brings enormous hope to patients, their families, loved ones, and caregivers. However, limits may exist for ...which indications SC therapies might be useful, efficacious, and safe. Applications of innovative therapies within regulatory boundaries and within the framework of controlled clinical trials are the norm in the scientific and medical community; such a system minimizes patient risk by setting a clear and acceptable safety and efficacy profile for new therapeutics before marketing authorization. This careful clinical validation approach often takes time, which patients suffering from terminal or debilitating diseases do not have. Not validated, unproven stem cell interventions (SCI) that promise a working treatment or cure for severe diseases have therefore found their way into the patient community, and providers of such treatments often take advantage of the public's willingness to pay large amounts of money for the misguided hope of a reliable recovery from their illnesses. We conducted a review of scientific publications, clinical case reports, and mass media publications to assess the reported cases and safety incidents associated with unproven SCI. The review also analyzes the main factors that were identified as contributing to the emergence and global rise of the “stem cell tourism” phenomenon. Stem Cells Translational Medicine 2018;1–10
The clinical use of unproven stem cell interventions is a complicated, multifactorial problem. A balance should be struck between accelerating the development of stem cell‐based treatments and compiling a well‐characterized benefit‐risk profile based on available safety and efficacy data for such products, ultimately benefiting patients.
Summary
The diagnosis of nonconvulsive status epilepticus (NCSE) relies largely on electroencephalography (EEG) findings. The lack of a unified EEG terminology, and of evidence‐based EEG criteria, ...leads to varying criteria for and ability to diagnose NCSE. We propose a unified terminology and classification system for NCSE, using, as a template, the Standardised Computer‐based Organised Reporting of EEG (SCORE). This approach integrates the terminology recently proposed for the rhythmic and periodic patterns in critically ill patients, the electroclinical classification of NCSE (type of NCSE) and the context for the pathologic conditions and age‐related epilepsy syndromes. We propose flexible EEG criteria that employ the SCORE system to assemble a database for determining evidence‐based EEG criteria for NCSE.
Mesenchymal stem cells (MSC) are known to facilitate healing of ischemic tissue related diseases through proangiogenic secretory proteins. Recent studies further show that MSC derived exosomes ...function as paracrine effectors of angiogenesis, however, the identity of which components of the exosome proteome responsible for this effect remains elusive. To address this we used high‐resolution isoelectric focusing coupled liquid chromatography tandem mass spectrometry, an unbiased high throughput proteomics approach to comprehensively characterize the proteinaceous contents of MSCs and MSC derived exosomes. We probed the proteome of MSCs and MSC derived exosomes from cells cultured under expansion conditions and under ischemic tissue simulated conditions to elucidate key angiogenic paracrine effectors present and potentially differentially expressed in these conditions. In total, 6,342 proteins were identified in MSCs and 1,927 proteins in MSC derived exosomes, representing to our knowledge the first time these proteomes have been probed comprehensively. Multilayered analyses identified several putative paracrine effectors of angiogenesis present in MSC exosomes and increased in expression in MSCs exposed to ischemic tissue‐simulated conditions; these include platelet derived growth factor, epidermal growth factor, fibroblast growth factor, and most notably nuclear factor‐kappaB (NFkB) signaling pathway proteins. NFkB signaling was identified as a key mediator of MSC exosome induced angiogenesis in endothelial cells by functional in vitro validation using a specific inhibitor. Collectively, the results of our proteomic analysis show that MSC derived exosomes contain a robust profile of angiogenic paracrine effectors, which have potential for the treatment of ischemic tissue‐related diseases. Stem Cells 2016;34:601–613
Mesenchymal stem cells (MSCs) exposed to peripheral arterial disease‐like (PAD) conditions increase expression of a diverse profile of angiogenic proteins which are subsequently packaged into exosome for secretion and induce angiogenesis in endothelial cells.
Purpose
Patellofemoral instability is influenced by ligamentous, boney and neuromuscular factors. The most important variables are trochlea geometry, medial patellofemoral ligament (MPFL), patella ...height, tibial tuberosity–trochlea groove distance (TT–TG) and the extensor muscles. Treatment is complicated by these multifactorial conditions. This prospective study examined the influence of risk factors on clinical results and athletic activities where treatment was confined to ligamentous procedures only.
Methods
Fifty patients with chronic patellofemoral instability were treated with MPFL reconstruction using an autologous gracilis tendon. Clinical data, radiographs and magnetic resonance imaging (MRI) were prospectively evaluated pre- and postoperative (minimum follow-up 12 month) to detect existing risk factors for patellofemoral instability and to evaluate clinical and sport ability scores (Kujala, Valderrabano).
Results
There was a low rate of redislocation (2 %) and an average Kujala score of 87 ± 13 points postoperative. The MRI showed good integration of the reconstructed MPFL and a positive effect regarding the decrease of patella tilt (16.1° to 11.2°). A negative relationship was found between the degree of trochlear dysplasia and outcomes. 80 % of all patients returned to the same or higher level of physical activity.
Conclusions
Addressing only ligamentous factors through MPFL reconstruction leads to satisfying clinical results and low redislocation rates in most patients. In cases with a high degree of trochlear dysplasia and enlarged TT–TG, additional procedures such as trochleaplasty and tibial tuberosity transfer should be considered as well.
Level of evidence
IV.
Huntington's disease (HD) is a fatal degenerative autosomal dominant neuropsychiatric disease that causes neuronal death and is characterized by progressive striatal and then widespread brain ...atrophy. Brain-derived neurotrophic factor (BDNF) is a lead candidate for the treatment of HD, as it has been shown to prevent cell death and to stimulate the growth and migration of new neurons in the brain in transgenic mouse models. BDNF levels are reduced in HD postmortem human brain. Previous studies have shown efficacy of mesenchymal stem/stromal cells (MSC)/BDNF using murine MSCs, and the present study used human MSCs to advance the therapeutic potential of the MSC/BDNF platform for clinical application. Double-blinded studies were performed to examine the effects of intrastriatally transplanted human MSC/BDNF on disease progression in two strains of immune-suppressed HD transgenic mice: YAC128 and R6/2. MSC/BDNF treatment decreased striatal atrophy in YAC128 mice. MSC/BDNF treatment also significantly reduced anxiety as measured in the open-field assay. Both MSC and MSC/BDNF treatments induced a significant increase in neurogenesis-like activity in R6/2 mice. MSC/BDNF treatment also increased the mean lifespan of the R6/2 mice. Our genetically modified MSC/BDNF cells set a precedent for stem cell-based neurotherapeutics and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis, Alzheimer's disease, and some forms of Parkinson's disease. These cells provide a platform delivery system for future studies involving corrective gene-editing strategies.
Case-control observational study.
Determination of dimensional changes in the lumbar spines of athletes between supine and stand-up position in MRI, concerning the lordosis, spinal canal ...cross-sectional area (SCCA), dural sac cross-sectional area (DSCA), sagittal dural sac diameter (SDSD), the lateral recess and the neural foramina.
The development of positional MRI allows the examination of spine segments under a true weight-bearing situation.
About 35 athletes (20m/15f, Ø: 28a) were examined using a 0.25 T open MRI-Scanner (G-Scan, ESAOTE, Italy). In all cases, axial and sagittal SE-T1 + SSE-T2 images were recorded in supine and true standing position. All measurements were performed using MEDIMAGE software (Vepro AG, Germany). The blinded measurements were performed 3 times by 2 independent examiners. Sagittal images were used to determine the lordosis and the narrowing of the left/right foramen at all levels between L1/2 and L5/S1. Axial images were used to determine the SDSD, the SCCA and the DSCA at L3/4, L4/5, L5/S1, and narrowing of the left/right recessus lateralis of L4, L5 and S1.
The lordosis showed a significant increase of 6.3 degrees (14%) from supine to true standing position (P < 0.001). The SDSD is significantly smaller in true standing position, than in supine position at the level of L3/4 and L4/5 (P < 0.001). Narrowing of the foramen occurred in true standing position in 13.4% at L4/L5 and in 26.7% at level L5/S1. No significant differences were observed at the recessus lateralis, the SCCA and the DSCA.
The measurement method in supine and true standing position is excellent for depicting the anatomical regions relevant for spinal canal stenosis in healthy individuals. Measuring the lumbar lordosis angle in both positions is an important requirement for interpreting the relevant anatomical regions. Of particular importance here is the DSCA and the SDSD.
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