RESUMEN
BACKGROUND AND PURPOSE: Although Parkinson's disease (PD) is characterized by typical motor manifestations, non-motor symptoms (NMS) are an outstanding part of the disease. At present, several specific instruments for assessment of NMS are available. The objective of our study was to determine the performance of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part I - Non-Motor Aspects of Experiences of Daily Living (nM-EDL) compared with the Non-Motor Symptoms Scale (NMSS). METHODS: To this purpose, 434 consecutive patients with PD were included in an international, observational, cross-sectional study. The association between scores of both scales was determined by the Spearman rank correlation coefficient. Equations for transformation of total score of a scale to the other were constructed from weighted regression models and both, transformed and observed score, contrasted by means of the Lin's Concordance Correlation Coefficient (LCCC) and Bland-Altman plot. RESULTS: As a whole, the prevalence of the NMS according to each scale was quite similar, and most of the correlations between their corresponding components were high (r(S) > 0.60). The total score correlation of the MDS-UPDRS Part I with the NMSS was high (r(S) = 0.81). Concerning the transformed scores, estimated scores only partially approach the observed ones (sharing about 60-64% of the variance) because residual variance increased with increasing magnitudes of the scores, i.e. the most severe patients (Bland-Altman plot; LCCCâ <â 0.60 for severe patients). CONCLUSIONS: (i) MDS-UPDRS Part I (nM-EDL) and NMSS showed a strong convergent validity; (ii) however, transformed scores using the equations from weighted regression models showed that for patients with the most severe NMS they are not concordant.
Asunto(s)
Actividades Cotidianas , Enfermedad de Parkinson/diagnóstico , Psicometría/instrumentación , Índice de Severidad de la Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND PURPOSE: The Movement Disorder Society sponsored version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a comprehensive instrument for assessing Parkinson's disease (PD). The present study was aimed at determining the relationships between MDS-UPDRS components and health-related quality of life (HRQoL) evaluations in PD patients. METHODS: An international, multicenter, cross-sectional study was carried out of 435 PD patients assessed with the MDS-UPDRS, Hoehn and Yahr (HY), Clinical Impression Severity for PD, EQ-5D and PD Questionnaire - eight items (PDQ-8). Spearman's rank correlation coefficients, exploratory factor analysis and multiple linear regression models (dependent variables EQ-5D and PDQ-8) were performed. RESULTS: The participants' age was 66.71 ± 10.32 years (51.5% men). PD duration was 8.52 ± 6.14, and median HY was 2 (range 1-5). The correlation between the EQ-5D index and the MDS-UPDRS ranged from -0.46 (Part IV) to -0.72 (Part II) and for the PDQ-8 index from 0.47 (Part III) to 0.74 (Part II). In multiple regression models with the MDS-UPDRS domains as independent variables, the main determinant for both the EQ-5D index and the PDQ-8 was Part II followed by Part I. After factorial grouping of the cardinal PD manifestations embedded in the MDS-UPDRS Parts III and IV for inclusion into multiple regression models, a factor formed by M-EDL, nM-EDL and fluctuations was the main determinant for both the EQ-5D and PDQ-8 indexes. CONCLUSIONS: The MDS-UPDRS component most tightly related with the HRQoL measures was a combination of motor and non-motor experiences of daily living.
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Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/psicología , Calidad de Vida/psicología , Índice de Severidad de la Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Análisis de RegresiónRESUMEN
BACKGROUND: We recently demonstrated that decline in fluid intelligence is a substantial contributor to frontal deficits. For some classical 'executive' tasks, such as the Wisconsin Card Sorting Test (WCST) and Verbal Fluency, frontal deficits were entirely explained by fluid intelligence. However, on a second set of frontal tasks, deficits remained even after statistically controlling for this factor. These tasks included tests of theory of mind and multitasking. As frontal dysfunction is the most frequent cognitive deficit observed in early Parkinson's disease (PD), the present study aimed to determine the role of fluid intelligence in such deficits. METHOD: We assessed patients with PD (n=32) and control subjects (n=22) with the aforementioned frontal tests and with a test of fluid intelligence. Group performance was compared and fluid intelligence was introduced as a covariate to determine its role in frontal deficits shown by PD patients. RESULTS: In line with our previous results, scores on the WCST and Verbal Fluency were closely linked to fluid intelligence. Significant patient-control differences were eliminated or at least substantially reduced once fluid intelligence was introduced as a covariate. However, for tasks of theory of mind and multitasking, deficits remained even after fluid intelligence was statistically controlled. CONCLUSIONS: The present results suggest that clinical assessment of neuropsychological deficits in PD should include tests of fluid intelligence, together with one or more specific tasks that allow for the assessment of residual frontal deficits associated with theory of mind and multitasking.
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Función Ejecutiva/fisiología , Inteligencia/fisiología , Enfermedad de Parkinson/fisiopatología , Anciano , Humanos , Persona de Mediana Edad , Teoría de la Mente/fisiologíaRESUMEN
Study of the nongenetic causes of Parkinson's disease (PD) was encouraged by discovery of a cluster of parkinsonism produced by neurotoxic pyridine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the 1980s. Since that time, epidemiologic investigations have suggested risk factors, though their results do not establish causality. Pesticide exposure has been associated with increased risk in many studies. Other proposed risks include rural residence and certain occupations. Cigarette smoking, use of coffee/caffeine, and non-steroidal antiinflammatory drugs (NSAIDs) all appear to lower risk of PD, while dietary lipid and milk consumption, high caloric intake, and head trauma may increase risk. The cause of PD is likely multifactorial. Underlying genetic susceptibility and combinations of risk and protective factors likely all contribute. The combined research effort by epidemiologists, geneticists, and basic scientists will be needed to clarify the cause(s) of PD.
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Enfermedad de Parkinson/genética , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/efectos adversos , Humanos , Exposición Profesional , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/epidemiología , Enfermedad de Parkinson Secundaria/patología , Plaguicidas/efectos adversosRESUMEN
OBJECTIVES: To assess the role of coronary vasa vasorum (VV) spatial distribution in determining the location of early atherosclerotic lesion development. METHODS AND RESULTS: Six, 3-month-old, female, crossbred swine were fed 2% high-cholesterol (HC) diet for 3 months prior to euthanasia. Six other pigs were fed normal diet (N) for the entire 6 months. Right coronary arteries were harvested and scanned intact with micro-CT (20mum cubic-voxel-size). After scanning, randomly selected cross-sectional histological sections were stained for nuclear-factor kappaB (NF-kappaB), hypoxia-inducible factor-1alpha (HIF-1alpha), macrophages, von-Willebrand-factor, dihydroethidium (DHE), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). The number of positive stained cells, as well as intima-to-media ratio, were compared with VV density (#/mm(2)) obtained from micro-CT images (which closely matched the location of the histological sections) in each of four equal quadrants of the coronary vessel wall. In normal, as well as HC pigs, the number of NF-kappaB (r=0.73 and 0.70), HIF-1alpha (r=0.74 and 0.77), TNF-alpha (r=0.58 and 0.72) and IL-6 (r=0.70 and 0.72) positive cells as well as the expression of DHE (Kendall tau coefficient -0.64 and -0.63) inversely correlated with VV density. In HC the VV density also inversely correlated with intima/media ratios (r=0.65). CONCLUSIONS: Our data suggest that low VV density territories within the coronary vessel wall are susceptible to hypoxia, oxidative stress and microinflammation and may therefore be starting points of early atherogenesis.
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Aterosclerosis/patología , Túnica Íntima/patología , Vasa Vasorum/patología , Animales , Colesterol en la Dieta/farmacología , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/patología , Femenino , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Interleucina-6/metabolismo , FN-kappa B/metabolismo , Superóxidos/metabolismo , Porcinos , Factor de Necrosis Tumoral alfa/metabolismo , Túnica Íntima/metabolismoRESUMEN
The main goal in the treatment of obstructive atherosclerotic renovascular disease (ARVD) is to preserve or recover renal function. The ARVD kidney continues to deteriorate in 20-40% of cases despite restoration of blood flow. Holden et al. report that renal function stabilized or improved in up to 97% of patients with the use of a distal embolic protection device.
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Angioplastia de Balón/métodos , Aterosclerosis/complicaciones , Aterosclerosis/terapia , Embolia/prevención & control , Obstrucción de la Arteria Renal/terapia , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/instrumentación , Cateterismo/instrumentación , Cateterismo/métodos , Progresión de la Enfermedad , Humanos , Riñón/irrigación sanguínea , Riñón/fisiopatología , Flujo Sanguíneo Regional/fisiología , Obstrucción de la Arteria Renal/fisiopatología , StentsRESUMEN
Patients with chronic kidney disease (CKD) have increased risk for cardiovascular events. However, the association between these pathophysiological processes is unclear. Therefore, this study was designed to determine the association between early CKD and coronary microvascular disease in patients with normal or mildly diseased coronary arteries. A total of 605 patients with normal or mildly diseased coronary arteries based on angiography underwent coronary flow reserve (CFR) evaluation using intracoronary adenosine. Patients were divided based on glomerular filtration rate (GFR). CKD was defined as calculated GFR<60 ml/min/1.73 m(2). Patients with normal GFR (> or =60 ml/min/1.73 m(2), n=481) had higher CFR compared to those with CKD (n=124, CFR=3.0+/-0.8 vs 2.6+/-0.6, P<0.001, respectively). Patients with abnormal GFR were more likely to be older and of female gender, with greater prevalence of hypertension. Multiple logistic regression analysis adjusted for the aforementioned risk factors further supported the observed relationship. The current study shows that reduced renal function is associated with attenuated coronary vasodilator capacity in patients without obstructive coronary artery disease. The correlation between low GFR and reduced CFR may suggest parallel alterations in the renal and coronary microcirculation at the early stage of disease. Impairment in both microcirculatory beds may reflect an unmeasured risk factor induced by blunted renal function and add a burden to the increased propensity for cardiovascular events in CKD.
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Circulación Coronaria , Enfermedad Coronaria/fisiopatología , Insuficiencia Renal/fisiopatología , Adulto , Anciano , Enfermedad Crónica , Femenino , Humanos , Masculino , Microcirculación , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Experimental models have enhanced our understanding of atherothrombosis pathophysiology and have played a major role in the search for adequate therapeutic interventions. Various animal models have been developed to simulate thrombosis and to study in vivo parameters related to hemodynamics and rheology that lead to thrombogenesis. Although no model completely mimics the human condition, much can be learned from existing models about specific biologic processes in disease causation and therapeutic intervention. In general, large animals such as pigs and monkeys have been better suited to study atherosclerosis and arterial and venous thrombosis than smaller species such as rats, rabbits, and dogs. On the other hand, mouse models of arterial and venous thrombosis have attracted increasing interest over the past two decades, owing to direct availability of a growing number of genetically modified mice, improved technical feasibility, standardization of new models of local thrombosis, and low maintenance costs. To simulate rupture of an atherosclerotic plaque, models of arterial thrombosis often involve vascular injury, which can be achieved by several means. There is no animal model that is sufficiently tall, that can mimic the ability of humans to walk upright, and that possesses the calf muscle pump that plays an important role in human venous hemodynamics. A number of spontaneous or genetically engineered animals with overexpression or deletion of various elements in the coagulation, platelet, and fibrinolysis pathways are now available. These animal models can replicate important aspects of thrombosis in humans, and provide a valuable resource in the development of novel concepts of disease mechanisms in human patients.