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Danker-Hopfe H.,ChariteUniversity Medicine Berlin | Gruber G.,The Siesta Group Schlafanalyse GmbH | Olbert E.,Medical University of Vienna | Dorffner G.,The Siesta Group Schlafanalyse GmbH | And 4 more authors.
Somnologie | Year: 2015

Objective: The purpose of the present study was to analyse gender- and age-specific variations in microstructures of rapid eye movement (REM) sleep and to provide reference values for microstructures.Methods: The results are based on Somnolyzer 24 × 7 (The Siesta Group Schlafanalyse GmbH., Vienna, Austria) evaluation of data from the SIESTA database. Data from 160 healthy subjects (74 men and 86 women; age range 20–95 years) were considered and a total of 11 REM sleep-related variables analysed.Results: Some of the variables, i.e., REM and slow eye movement (SEM) density, SEM intensity and the REM sleep arousal index, are fairly constant across ages and do not differ between men and women. The atonia index shows gender-specific differences, but does not vary with age among healthy subjects; whereas REM intensity and the time in tonic REM sleep decrease with age, without differences between men and women. Time in stage R sleep (minutes and percentage of total sleep time, TST) and the time in phasic stage R sleep vary with both age and gender.Conclusion: Given the relevance of sleep microstructures in research and potentially also in clinical studies, there is a need for reference values indicating the range of variation of these variables in healthy subjects. Reference values always have the limitation that they refer to the specific method of assessment. Where different detection algorithms are used, the reference values might vary. The reference values presented here—where necessary for men and women separately and/or stratified by age—refer to microstructures assessed by the feature extraction module of the Somnolyzer 24 × 7. © 2015, Springer-Verlag Berlin Heidelberg.

Strangfeld A.,German Rheumatism Research Center | Richter A.,German Rheumatism Research Center | Siegmund B.,ChariteUniversity Medicine Berlin | Herzer P.,Scientific Advisory Board | And 5 more authors.
Annals of the Rheumatic Diseases | Year: 2016

Objective To investigate the risk of developing lower intestinal perforations (LIPs) in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ). Methods In 13 310 patients with RA observed in the German biologics register Rheumatoid Arthritis: Observation of Biologic Therapy, 141 serious gastrointestinal events possibly associated with perforations were reported until 31 October 2015. All events were validated independently by two physicians, blinded for treatment exposure. Results 37 LIPs (32 in the colon/sigma) were observed in 53 972 patient years (PYs). Only two patients had a history of diverticulitis (one in TCZ). Age, current/ cumulative glucocorticoids and non-steroidal antiinflammatory drugs were significantly associated with the risk of LIP. The crude incidence rate of LIP was significantly increased in TCZ (2.7/1000 PYs) as compared with all other treatments (0.2-0.6/1000 PYs). The adjusted HR (ref: conventional synthetic (cs) diseasemodifying anti-rheumatic drugs (DMARDs)) in TCZ was 4.48 (95% CI 2.0 to 10.0), in tumour necrosis factor-a inhibitor (TNFi) 1.04 (0.5 to 2.3) and in other biologic DMARDs 0.33 (0.1 to 1.4). 4/11 patients treated with TCZ presented without typical symptoms of LIP (acute abdomen, severe pain). Only one patient had highly elevated C reactive protein (CRP). One quarter of patients died within 30 days after LIP (9/37), 5/11 under TCZ, 2/13 under TNFi and 2/11 under csDMARD treatment. Conclusions The incidence rates of LIP under TCZ found in this real world study are in line with those seen in randomised controlled trials of TCZ and higher than in all other DMARD treatments. To ensure safe use of TCZ in daily practice, physicians and patients should be aware that, under TCZ, LIP may occur with mild symptoms only and without CRP elevation. © 2016 BMJ Publishing Group Ltd & European League Against Rheumatism.

Heinz A.,ChariteUniversity Medicine Berlin | Muller D.J.,University of Toronto | Krach S.,University of Marburg | Cabanis M.,Center for Mental Health | Kluge U.P.,ChariteUniversity Medicine Berlin
Frontiers in Human Neuroscience | Year: 2014

The aim of this Hypothesis and Theory is to question the recently increasing use of the “race” concept in contemporary genetic, psychiatric, neuroscience as well as social studies. We discuss “race” and related terms used to assign individuals to distinct groups and caution that also concepts such as “ethnicity” or “culture” unduly neglect diversity. We suggest that one factor contributing to the dangerous nature of the “race” concept is that it is based on a mixture of traditional stereotypes about “physiognomy”, which are deeply imbued by colonial traditions. Furthermore, the social impact of “race classifications” will be critically reflected. We then examine current ways to apply the term “culture” and caution that while originally derived from a fundamentally different background, “culture” is all too often used as a proxy for “race”, particularly when referring to the population of a certain national state or wider region. When used in such contexts, suggesting that all inhabitants of a geographical or political unit belong to a certain “culture” tends to ignore diversity and to suggest a homogeneity, which consciously or unconsciously appears to extend into the realm of biological similarities and differences. Finally, we discuss alternative approaches and their respective relevance to biological and cultural studies. © 2014 Heinz, Müller, Krach, Cabanis and Kluge.

Eckstein J.,ChariteUniversity Medicine Berlin | Berndt N.,ChariteUniversity Medicine Berlin | Holzhutter H.-G.,ChariteUniversity Medicine Berlin
PLoS Computational Biology | Year: 2015

The bile fluid contains various lipids that are secreted at the canalicular membrane of hepatocytes. As the secretion mechanism is still a matter of debate and a direct experimental observation of the secretion process is not possible so far, we used a mathematical model to simulate the extraction of the major bile lipids cholesterol, phosphatidylcholine and sphingomyelin from the outer leaflet of the canalicular membrane. Lipid diffusion was modeled as random movement on a triangular lattice governed by next-neighbor interaction energies. Phase separation in liquid-ordered and liquid-disordered domains was modeled by assigning two alternative ordering states to each lipid species and minimization of next-neighbor ordering energies. Parameterization of the model was performed such that experimentally determined diffusion rates and phases in ternary lipid mixtures of model membranes were correctly recapitulated. The model describes the spontaneous formation of nanodomains in the external leaflet of the canalicular membrane in a time window between 0.1 ms to 10 ms at varying lipid proportions. The extraction of lipid patches from the bile salt soluble nanodomain into the bile reproduced observed biliary phospholipid compositions for a physiologi-cal membrane composition. Comparing the outcome of model simulations with available experi-mental observations clearly favors the extraction of tiny membrane patches composed of about 100–400 lipids as the likely mechanism of biliary lipid secretion. © 2015 Eckstein et al.

Busch J.,ChariteUniversity Medicine Berlin | Stephan C.,ChariteUniversity Medicine Berlin | Stephan C.,Berlin Institute for Urological Research | Herold A.,ChariteUniversity Medicine Berlin | And 9 more authors.
BJU International | Year: 2012

OBJECTIVE • To investigate biochemical recurrence (BCR) rates and data on postoperative incontinence in a large laparoscopic radical prostatectomy (LRP) cohort with extended follow-up. MATERIALS AND METHODS • BCR and independent predictors of BCR were identified using Kaplan-Meier and Cox regression analysis of 1845 patients who underwent LRP from 1999 to 2007. • Urinary incontinence was evaluated by pads per day and stratified as follows: 0-1 pad: no incontinence; 2-3 pads: mild incontinence; and ≥ 3 pads: severe incontinence. RESULTS • Organ-confined disease, extraprostatic extension, seminal vesicle invasion and lymph node metastasis were present in 71.3%, 20.5%, 6.7% and 3.2% of patients, respectively. The positive surgical margin rate was 29.2%. • Postoperatively, 74.9% of the patients were continent, while 9.2% had mild and 15.9% severe incontinence. • The mean follow-up was 5 years with a maximum follow-up of 11.3 years. • There were 51 overall deaths and six deaths from prostate cancer. The 5-year, 8-year and 10-year BCR-free survival rates were 83.9%, 78.6% and 75.6%, respectively. • On univariate analyses preoperative D'Amico risk classification, pathological tumour stage, postoperative Gleason sum and surgical margin status were predictors of BCR ( P < 0.001). • On multivariable analysis, D'Amico classification, Gleason sum ( P < 0.001), postoperative tumour stage ( P < 0.001), nodal status ( P < 0.001) and surgical margin status ( P =0.002) were independent predictors of BCR. CONCLUSIONS • LRP offers excellent long-term functional and oncological results with a low incidence of BCR for patients with localized disease. • These results could be used for patient counselling before robot-assisted laparascopic prostatectomy (RALP) until long-term follow-up data for RALP is available. © 2012 THE AUTHORS.

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