Parkinson's disease: quantification of disability based on the Unified Parkinson's Disease Rating Scale.

OBJECTIVES: To develop a simple measure for quantification of the disability (dependency) due to Parkinson's disease (PD). PATIENTS: 65 nondemented PD outpatients, stage 1 to 5 of the Hoehn and Yahr Classification (HY). ASSESSMENT: HY, Schwab and England Scale, Northwestern University Disability Scale, Columbia University Rating Scale, Webster Scale, Barthel's Index, finger tapping, and timed "Up & Go" test. Six items from the ADL Section of the Unified PD Rating Scale (UPDRS)--as representative of the most basic ADL--were chosen to compose the UPDRS disability score (UDS), that was simultaneously rated by three observers. Global evaluations of disability by patient and physician were also recorded. STATISTICS: Descriptive, Cronbach alpha, kappa of Fleiss, Spearman rank correlation coefficients, Kruskal-Wallis test, and factor analysis. RESULTS: Internal consistency (Cronbach alpha = 0.86-0.87) and interobserver reliability (kappa = 0.84-0.98) were satisfactory. Convergent validity of the UDS with the applied PD rating scales (R = 0.76-0.92), global evaluations (R = 0.84-0.88), and timed tests (R = 0.47-0.65) was highly significant (all, p < 0.001). Distribution of UDS values across the HY categories showed significant trends (Kruskal-Wallis test, p < 0.001). A single factor explaining over 64% of the variance was identified. CONCLUSION: A simple and valid instrument for standardized evaluation of disability in PD is embedded in the UPDRS.

Highly glycated oxyhaemoglobin impairs nitric oxide relaxations in human mesenteric microvessels.

AIMS/HYPOTHESIS: It has been recently shown that glycated human haemoglobin induces endothelial dysfunction in rat vessels by generating superoxide anions that interfere with nitric oxide mediated responses. Our study analysed the effect of glycated human haemoglobin on the endothelium-dependent relaxations of human vessels. METHODS: Omental microvessels were obtained from patients (without diabetes, hypertension or vascular disease) during surgery and mounted in a small vessel myograph to study their vasoactive responses (vessels from 3-7 patients for each set of experiments). RESULTS: Cumulative vasodilatory responses to bradykinin (10 nmol/l to 3 mumol/l) were induced in vessels precontracted with 35-50 mmol/l potassium chloride. Addition of 100 mumol/l NG-nitro-L-arginine methyl ester reduced the relaxation evoked by bradykinin, but preincubation with both NG-nitro-L-arginine methyl ester and 10 mumol/l indomethacin was needed to abolish it. Bradykinin-induced responses were inhibited by 1 mumol/l non-glycated oxyhaemoglobin whereas no effect was obtained with 10 nmol/l oxyhaemoglobin. At these low concentrations (10 nmol/l), glycated human oxyhaemoglobin caused an impairment of bradykinin-induced relaxation when the percentage of glycation was 10% or higher. This effect was prevented by preincubating the vessels with ascorbic acid (10 mumol/l), superoxide dismutase (100 U/ml) and gliclazide (1 and 10 mumol/l), but not with indomethacin (10 mumol/l), catalase (400-600 U/ml), dimethylthiourea (1 mmol/l) or glibenclamide (10 mumol/l). In vessels preincubated with NG-nitro-L-arginine methyl ester (100 mumol/l), glycohaemoglobin did not add any additional effect. CONCLUSION/INTERPRETATION: Highly glycated human oxyhaemoglobin, at physiological plasmatic concentrations, impairs nitric oxide-mediated responses by a mechanism involving superoxide anions but not cyclooxygenase derivatives.