Association between DRD2 and DRD3 gene polymorphisms and gastrointestinal symptoms induced by levodopa therapy in Parkinson's disease.

Levodopa is the most used drug to treat motor symptoms in Parkinson's disease (PD). However, dopaminergic side effects such as nausea and vomiting may occur. Several evidences indicate a major role for dopamine receptors D2 (DRD2) and D3 (DRD3) in emetic activity. The aim of this study was to investigate the relationship of DRD2 rs1799732 and DRD3 rs6280 gene polymorphisms with gastrointestinal (GI) symptoms induced by levodopa in PD patients. Two hundred and seventeen PD patients on levodopa therapy were investigated. DRD2 rs1799732 and DRD3 rs6280 polymorphisms were genotyped by PCR-based methods. Multiple Poisson regression method with robust variance estimators was performed to assess the association between polymorphisms and gastrointestinal symptoms. The analyses showed that DRD2 Ins/Ins (prevalence ratio (PR)=2.374, 95% confidence interval (CI): 1.105-5.100; P=0.027) and DRD3 Ser/Ser genotypes (PR=1.677, 95% CI 1.077-2.611; P=0.022) were independent and predictors of gastrointestinal symptoms associated with levodopa therapy. Despite all the efforts to alleviate GI symptoms, this adverse effect still occurs in PD patients. Pharmacogenetic studies of GI symptoms induced by levodopa therapy have the potential to display new ways to better understand the molecular mechanisms involved in these side effects.

Classifying trunk strength impairment according to the activity limitation caused in wheelchair rugby performance.

International Federations in Paralympic sports should develop evidence-based classification, based on the relative strength of association between impairment and activities that determine sport-specific performance. The purpose of the current study was to assess the relationship between trunk strength impairment and three activities that determine performance in wheelchair rugby, and to determine whether this relationship supports the concept of "natural classes." Trunk muscle strength and three determinants of performance were assessed in 27 athletes. The correlations between lateral trunk muscle strength and the determinant tilting the chair, and between forward trunk muscle strength and the determinants 1 m acceleration and sprint momentum were calculated. To group athletes based on impairment, K-means cluster analysis was used to group athletes according to how much trunk muscle strength affected the activities. There were significant, moderate to strong correlations between left-right strength and chair tilting (r=.50), between forward strength and 1 m acceleration (r=.59), and between forward strength and sprint momentum (r=.79). Cluster analysis indicated at least one cut-point in performance with a decrease in impairment in all three wheelchair activities, supporting the concept of "natural classes."

The impact of trunk impairment on performance-determining activities in wheelchair rugby.

In Paralympic sport, classification of impairment is needed to prevent a one-sided and predictable outcome of competition, in which the least impaired athlete has the best chance to win. To develop evidence-based classification in wheelchair rugby, the impact of trunk impairment, measured by the Trunk Impairment Classification (TIC), on performance-determining activities was assessed. Arm impairment was analyzed as a covariant. Fifty-five athletes, 21 with TIC score 0, 13 with TIC score 0.5, 11 with TIC score 1.0, and 10 with TIC score 1.5 performed standardized sport-specific activities. A multiple step forward regression analysis was performed for all activities to assess the relative impact of trunk and arm impairment on performance. Trunk impairment was the most important factor for tilting the chair and acceleration in the first 2 m. The explained variance of the performance by trunk and arm impairment ranged from 23% for acceleration in the first meter, to 37% for sprint momentum, the tilt test left, and the time to cover 3 and 4 m. This study shows that athletes with limited trunk impairment are more proficient in wheelchair rugby than athletes with severe trunk impairment.

Association of common genetic variants of HOMER1 gene with levodopa adverse effects in Parkinson's disease patients.

Levodopa is the most effective symptomatic therapy for Parkinson's disease, but its chronic use could lead to chronic adverse outcomes, such as motor fluctuations, dyskinesia and visual hallucinations. HOMER1 is a protein with pivotal function in glutamate transmission, which has been related to the pathogenesis of these complications. This study investigates whether polymorphisms in the HOMER1 gene promoter region are associated with the occurrence of the chronic complications of levodopa therapy. A total of 205 patients with idiopathic Parkinson's disease were investigated. Patients were genotyped for rs4704559, rs10942891 and rs4704560 by allelic discrimination with Taqman assays. The rs4704559 G allele was associated with a lower prevalence of dyskinesia (prevalence ratio (PR)=0.615, 95% confidence interval (CI) 0.426-0.887, P=0.009) and visual hallucinations (PR=0.515, 95% CI 0.295-0.899, P=0.020). Our data suggest that HOMER1 rs4704559 G allele has a protective role for the development of levodopa adverse effects.

Reliability of the revised wheelchair rugby trunk impairment classification system.

STUDY DESIGN: Observational, cross-sectional. OBJECTIVES: A new classification system for trunk impairment in wheelchair rugby was introduced in 2010. It consists of 10 tests, arranged in an algorithm, to assign four different trunk scores (0, 0.5, 1.0 or 1.5) to athletes. The purpose of this study was to assess the inter-rater reliability of this classification system. SETTING: National competition for wheelchair rugby and wheelchair basketball in the Netherlands and Belgium. METHODS: Three experienced wheelchair rugby classifiers independently assigned trunk scores to wheelchair rugby and wheelchair basketball athletes in two sessions. After each session, test descriptions were adjusted. The inter-rater reliability was evaluated by determining the agreement and Fleiss Kappa. RESULTS: In the first session, all classifiers agreed on the trunk score in 13 out of 16 athletes; the overall Kappa was 0.76 (P<0.001). The Kappa per trunk score ranged from 0.29 to 1. Four test descriptions were adjusted after the first session. In the second session, there was an agreement in trunk score between the classifiers in 15 out of 21 athletes. The overall Kappa was 0.75 (P<0.0001), and the Kappa per trunk scores ranged from 0.58 to 0.92. After the second session, two test descriptions were improved. CONCLUSION: The revised classification system for trunk impairment in wheelchair rugby showed a adequate inter-rater reliability for the allocation of trunk scores.

[Cell mediated immunity in sarcoidosis patients]. / Zellvermittelte Immunität bei Sarkoidosekranken

In vitro tests, lymphocyte transformation tests, and leukocyte migration inhibition tests were carried out on nineteen patients with different stages of sarcoidosis. In all patients there was found a defect of cell-mediated immunity, which was most strongly pronounced in the remission phase of the disease. It is believed that the disturbance of cell-mediated immunity is a result of the disease. It is possible for such a disturbance to be intensified in the further course of disease. It appears that this disturbance may be compensated for by the system of B lymphocytes, through humoral antibodies, because clinical phenomena manifest in the patients and corresponding to the deficiency of immunity demonstrated in vitro could not be observed.