Bedeutung der Endothelinrezeptoren für die Endothelin- und Noradrenalin- induzierte Vasokonstriktion bei Patienten mit Arteriosklerose

Im Endothelinsystem sind verschiedene Rezeptoren an der Signaltransduktion beteiligt. Beim Menschen spielen dabei vor allem ETA-und ETB- Rezeptoren eine führende Rolle. Die ETA-Rezeptoren auf den Gefäßmuskelzellen vermitteln dabei die Endothlin-1 (ET-1) induzierte Vasokonstriktion, während die Stimulation von ETB-Rezeptoren abhängig von ihrer Lokalisation auf Gefäßmuskelzellen oder Endothelzellen eine Vasokonstriktion sowie ein Vasodilatation auslösen kann. Bei Gesunden überwiegen nach Stimulation der ETB-Rezeptoren vasodilatierende Effekte. Nur wenig ist über die Funktion der konstringierend wirkenden ETB-Rezeptoren im Zusammenhang mit kardiovaskulären Erkrankungen und endothelialer Dysfunktion bekannt. Aus Tierversuchen und in vitro-Untersuchungen ist anzunehmen, dass Wechselwirkungen zwischen dem Endothelinsystem und dem Sympathischen Nervensystem zu einer zu einer Potenzierung der sympathisch vermittelten Vasokonstriktion durch ET-1 führen. Zur Identifizierung der Bedeutung von ETB-Rezeptoren und Beschreibung möglicher Interaktionen zwischen ET-1 und Noradrenalin (NA) untersuchten wir in der vorliegenden Arbeit den Einfluss von ETA- und ETB-Rezeptoren auf die ET-1 und NA- induzierte Vasokonstriktion in der Hautmikrozirkulation von 19 Patienten mit Arteriosklerose und 20 gesunden Kontrollen mittels der Triple-Injektionstechnik und eines Laser-Doppler-Imagers. ET-1 und NA induzierten in beiden Gruppen eine signifikante Vasokonstriktion in der Hautmikrozirkulation. Nicht nur die ET-1-, sondern auch die NA- induzierte Vasokonstriktion konnte durch den selektiven ETA-Rezeptorantagonisten BQ123 in beiden Gruppen signifikant reduziert werden. Der selektive ETB- Rezeptorantagonist BQ788 hatte lediglich in der Gruppe der Patienten einen hochsignifikanten inhibitorischen Effekt auf die NA- und ET-1- induzierte Vasokonstriktion. Unsere Ergebnisse im in vivo Modell der Hautmikrozirkulation weisen damit den ETB-Rezeptoren bei Patienten mit Arteriosklerose eine bedeutende Rolle zu. Diese Ergebnisse müssen noch für andere Bereiche der Zirkulation bestätigt werden

Meglers undersøkelses- og opplysningsplikt : En redegjørelse av innholdet og utstrekningen av meglers undersøkelses- og opplysningsplikt etter emgll. § 6-7 (1) og (2)

En redegjørelse av innholdet og utstrekningen av meglers undersøkelses- og opplysningsplikt etter emgll. § 6-7 (1) og (2

Screening for balance disorders in mildly affected multiple sclerosis patients

Multiple sclerosis (MS) patients often complain about balance problems when Romberg's test and tandem gait are normal. The aim of the study was to determine if measures of trunk sway taken during a battery of stance and gait tasks could be used to detect subclinical balance disorders. We recorded trunk angular sway in the pitch and roll directions from 20 MS patients (EDSS 1.4±0.5) and 20 age- and gender-matched healthy controls (HCs), during 12 stance and gait tasks. We filmed 22 subjects simultaneously. Two neurologists assessed the videos, deciding whether task performance was pathological. Sway measures were significantly different between patients and HCs in eight out of 12 balance tasks. The most significant differences between MS patients and HCs were pitch angle range standing on one leg with eyes open on a firm surface (mean 3.13° vs. 2.09°, p=0.005), and on a foam support surface (mean 6.24° vs. 2.96°, p=0.006), pitch velocity range walking 8m with eyes closed (mean 75.5 vs. 50.2°/s, p<0.001) and pitch velocity range walking 3m on heels (mean 85.37 vs. 60.9°/s, p=0.002). Multivariate analysis revealed a model with three tasks which detected balance disorders in 84% of the MS patients and 90% of the HCs correctly. The neurologists achieved accuracies of 30% for the MS patients and 82% for the HCs. Using trunk sway measures during stance and gait tasks is a sensitive screening method for balance problems in MS patients, and is more accurate than assessment by trained neurologist

MULTIPLE CEREBRAL METASTASES MIMICKING WERNICKE'S ENCEPHALOPATHY IN A CHRONIC ALCOHOLIC

Aims: Alcohol dependent patients in withdrawal display a wide spectrum of neurological and neuropsychological symptoms that complicate diagnosis. We report the case of a 53-year-old male alcoholic with disorientation, ataxia and nystagmus in alcohol withdrawal probably due not to initial supposed Wernicke's encephalopathy (WE) but rather due to multiple cerebral metastases of a non-small cell cancer of the lung. Results: The findings illustrate the importance of initially maintaining a tentative attitude toward causation of symptoms and the role of brain imaging in formulating an accurate diagnosi

Corpus callosum index and long-term disability in multiple sclerosis patients

Prediction of long-term disability in patients with multiple sclerosis (MS) is essential. Magnetic resonance imaging (MRI) measurement of brain volume may be of predictive value but sophisticated MRI techniques are often inaccessible in clinical practice. The corpus callosum index (CCI) is a normalized measurement that reflects changes of brain volume. We investigated medical records and 533 MRI scans at diagnosis and during clinical follow-up of 169 MS patients (mean age 42±11years, 86% relapsing-remitting MS, time since first relapse 11±9years). CCI at diagnosis was 0.345±0.04 and correlated with duration of disease (p=0.002; r=−0.234) and expanded disability status scale (EDSS) score at diagnosis (r=−0.428; p<0.001). Linear regression analyses identified age, duration of disease, relapse rate and EDSS at diagnosis as independent predictors for disability after mean of 7.1years (Nagelkerkes' R:0.56). Annual CCI decrease was 0.01±0.02 (annual tissue loss: 1.3%). In secondary progressive MS patients, CCI decrease was double compared to that in relapsing-remitting MS patients (p=0.04). There was a trend of greater CCI decrease in untreated patients compared to those who received disease modifying drugs (p=0.2). CCI is an easy to use MRI marker for estimating brain atrophy in patients with MS. Brain atrophy as measured with CCI was associated with disability progression but it was not an independent predictor of long-term disabilit

Fatigue and progression of corpus callosum atrophy in multiple sclerosis

Fatigue is one of the most disabling symptoms in multiple sclerosis (MS) patients. There is no or only weak correlation between conventional magnetic resonance imaging (MRI) parameters and level of fatigue. The aim of this study was to investigate the relationship between progression of corpus callosum (CC) atrophy and fatigue in MS patients. This was a cohort study in 70 patients with relapsing form of MS (RRMS) and serial MRIs over a mean follow-up of 4.8years [67% female, mean age 42±11years, mean disease duration 9.7±7.6years, mean Expanded Disability Status Scale (EDSS) 2.8±1.6]. Fatigue was assessed by the Fatigue Severity Scale (FSS). CC size was measured with the CC index (CCI). In total, 40% of the patients suffered from fatigue (mean FSS score 5.3±1.1) and 60% patients had no fatigue (mean FSS score of 2.1±1). Patients with fatigue had higher EDSS scores (p=0.01) and CC atrophy was more pronounced in patients with fatigue (−21.8 vs. −12.1%, p=0.005). FSS correlated with CCI change over time (r=−0.33; p=0.009) and EDSS (p=0.008; r=0.361). The association between annualized CCI change and FSS was independent from EDSS, disease duration, gender and age in a multivariate linear regression analysis (p<0.001). Progression of CC atrophy may play a role in the evolution of MS-related fatigu

Benefits of short-term training with vibrotactile biofeedback of trunk sway on balance control in multiple sclerosis

Background and Aims: Patients with multiple sclerosis (MS) suffer from diminished balance control. We examined whether 4 sessions of training with vibrotactile biofeedback (VTfb) of trunk sway could improve their balance control and provide a carry-over effect. Methods: Baseline trunk sway was first measured for 15 MS patients. Then they received head mounted VTfb of trunk sway which was directionally active when trunk sway exceeded limits set using the baseline assessments. Stance and gait tasks were trained 2 times weekly for 2 weeks with VTfb. Assessments with VTfb were performed at the end of each week. Two weeks later balance was assessed without VTfb to determine if a carry-over effect was present. Results: Assessments with VTfb showed a significant decrease in trunk sway after 1 and 2 weeks of VTfb training (p<0.02). Carry-over improvements were also present (p<0.02). The greatest effects were found for tests of standing eyes closed stance on foam which resulted in a 59% decreased pitch sway angle (p=0.002) with VTfb and a 51% reduction (p=0.03) carry-over effect. Conclusions: This study indicates that balance control in MS patients improves rapidly after one week of training with VTfb and more slowly subsequently. The carry-over effect lasted at least 2 weeks. Future studies should determine, with more weeks of VTfb training, the time course of the slower balance and carry-over improvements following the first rapid improvement in balance control. We conclude that training with VTfb of trunk sway significantly improves balance control in MS patients, and could possibly reduce falls

Characteristics of improvements in balance control using vibro-tactile biofeedback of trunk sway for multiple sclerosis patients

Background and aims: Previously, we determined that training with vibrotactile feedback (VTfb) of trunk sway improves MS patients’ balance impairment. Here, we posed 5 questions: 1) How many weeks of VTfb training are required to obtain the best short-term carry over effect (CoE) with VTfb? 2) How long does the CoE last once VTfb training terminates? 3) Is the benefit similar for stance and gait? 4) Is position or velocity based VTfb more effective in reducing trunk sway? 5) Do patients’ subjective assessments of balance control improve? Methods: Balance control of 16 MS patients was measured with gyroscopes at the lower trunk. The gyroscopes drove directionally active VTfb in a head-band. Patients trained twice per week with VTfb for 4 weeks to determine when balance control with and without VTfb stopped improving. Thereafter, weekly assessments without VTfb over 4 weeks and at 6 months determined when CoEs ended. Results: A 20% improvement in balance to normal levels occurred with VTfb. Short term CoEs improved from 15 to 20% (p ≤0.001). Medium term (1–4 weeks) CoEs were constant at 19% (p ≤0.001). At 6 months improvement was not significant, 9%. Most improvement was for lateral sway. Equal improvement occurred when angle position or velocity drove VTfb. Subjectively, balance improvements peaked after 3 weeks of training (32%, p ≤0.05). Conclusions: 3–4 weeks VTfb training yields clinically relevant sway reductions and subjective improvements for MS patients during stance and gait. The CoEs lasted at least 1 month. Velocity-based VTfb was equally effective as position-based VTf

Learn to Ignore: Domain Adaptation for Multi-Site MRI Analysis

The limited availability of large image datasets, mainly due to data privacy and differences in acquisition protocols or hardware, is a significant issue in the development of accurate and generalizable machine learning methods in medicine. This is especially the case for Magnetic Resonance (MR) images, where different MR scanners introduce a bias that limits the performance of a machine learning model. We present a novel method that learns to ignore the scanner-related features present in MR images, by introducing specific additional constraints on the latent space. We focus on a real-world classification scenario, where only a small dataset provides images of all classes. Our method \textit{Learn to Ignore (L2I)} outperforms state-of-the-art domain adaptation methods on a multi-site MR dataset for a classification task between multiple sclerosis patients and healthy controls

Magnetization transfer ratio measures in normal-appearing white matter show periventricular gradient abnormalities in multiple sclerosis

In multiple sclerosis, grey matter pathology occurs mostly next to or near the outer surface of the brain. Using quantitative MRI, Liu et al. reveal that white matter abnormalities are also greatest near the surface of the brain, suggesting common elements in the genesis of grey and white matter patholog