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1.
Qual Life Res ; 25(10): 2417-2427, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27038054

RESUMEN

PURPOSE: Huntington disease (HD) is an autosomal dominant neurodegenerative disease which results in several progressive symptoms, including bulbar dysfunction (i.e., speech and swallowing difficulties). Although difficulties in speech and swallowing in HD have a negative impact on health-related quality of life, no patient-reported outcome measure exists to capture these difficulties that are specific to HD. Thus, we developed a new patient-reported outcome measure for use in the Huntington Disease Health-Related Quality of Life (HDQLIFE) Measurement System that focused on the impact that difficulties with speech and swallowing have on HRQOL in HD. METHODS: Five hundred and seven individuals with prodromal and/or manifest HD completed 47 newly developed items examining speech and swallowing difficulties. Unidimensional item pools were identified using exploratory factor analysis and confirmatory factor analysis (EFA and CFA, respectively). Item response theory (IRT) was used to calibrate the final measures. RESULTS: EFA and CFA identified two separate unidimensional sets of items: Speech Difficulties (27 items) and Swallowing Difficulties (16 items). Items were calibrated separately for these two measures and resulted in item banks that can be administered as computer adaptive tests (CATs) and/or 6-item, static short forms. Reliability of both of these measures was supported through high correlations between the simulated CAT scores and the full item bank. CONCLUSIONS: CATs and 6-item calibrated short forms were developed for HDQLIFE Speech Difficulties and HDQLIFE Swallowing Difficulties. These measures both demonstrate excellent psychometric properties and may have clinical utility in other populations where speech and swallowing difficulties are prevalent.


Asunto(s)
Computadores/estadística & datos numéricos , Trastornos de Deglución/terapia , Enfermedad de Huntington/psicología , Trastornos del Habla/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Perfil de Impacto de Enfermedad , Encuestas y Cuestionarios , Adulto Joven
2.
Qual Life Res ; 25(10): 2441-2455, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27522213

RESUMEN

PURPOSE: Huntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL-Quality of Life in Neurological Disorders and PROMIS-Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS methodology to develop new, HD-specific content. METHODS: New item pools were developed using cognitive debriefing with individuals with HD, and expert, literacy, and translatability reviews. Existing item banks and new item pools were field tested in 536 individuals with prodromal, early-, or late-stage HD. RESULTS: Moderate to strong relationships between Neuro-QoL/PROMIS measures and generic self-report measures of HRQOL, and moderate relationships between Neuro-QoL/PROMIS and clinician-rated measures of similar constructs supported the validity of Neuro-QoL/PROMIS in individuals with HD. Exploratory and confirmatory factor analysis, item response theory, and differential item functioning analyses were utilized to develop new item banks for Chorea, Speech Difficulties, Swallowing Difficulties, and Concern with Death and Dying, with corresponding six-item short forms. A four-item short form was developed for Meaning and Purpose. CONCLUSIONS: HDQLIFE encompasses both validated Neuro-QoL/PROMIS measures, as well as five new scales in order to provide a comprehensive assessment of HRQOL in HD.


Asunto(s)
Enfermedad de Huntington/psicología , Perfil de Impacto de Enfermedad , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
3.
Int J Neurosci ; 121(8): 472-6, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21663381

RESUMEN

Hallucinations, delusions, and compulsive behaviors are frequent iatrogenic complications of the treatment of motor dysfunction in Parkinson's disease (PD). Although these have been studied, and the phenomenology described, there are few detailed descriptions of the various psychiatric problems our treated PD patients live with that allow physicians who do not have a great deal of experience with PD patients to appreciate the extent of their altered lives. This report is a compilation of vignettes describing these behavioral problems that the treating neurologist or psychiatrist attributed to the medications used for treating PD.


Asunto(s)
Antiparkinsonianos/efectos adversos , Carbidopa/efectos adversos , Conducta Compulsiva/inducido químicamente , Deluciones/inducido químicamente , Alucinaciones/inducido químicamente , Levodopa/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/tratamiento farmacológico , Escalas de Valoración Psiquiátrica
4.
J Mot Behav ; 45(5): 423-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23971968

RESUMEN

Mild to moderate Parkinson's disease shows more denervation in the posterodorsal striatum and sparing of the anteroventral striatum. Dopaminergic medications can interfere with anteroventral striatum function by overdosing this relatively intact structure. The authors determined how regional striatal denervation affects medication-associated sequence learning impairment in Parkinson's disease. Eighteen Parkinson's patients performed motor sequence learning on and off levodopa. Patients underwent (11)C-dihydrotetrabenazine positron emission tomography scans to measure nigrostriatal denervation. Patients with more preserved putamen were more likely to exhibit levodopa-associated sequence learning impairments. Furthermore, the ratio of denervation in the anterior to posterior dorsal putamen predicted the level of learning differences on and off levodopa. These results demonstrate that the spatial pattern of nigrostriatal dopaminergic denervation predicts medication responsiveness for motor sequence learning.


Asunto(s)
Antiparkinsonianos/uso terapéutico , Desnervación , Levodopa/uso terapéutico , Neostriado/patología , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/psicología , Aprendizaje Seriado/fisiología , Anciano , Interpretación Estadística de Datos , Femenino , Radioisótopos de Flúor , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos , Tetrabenazina/análogos & derivados
5.
Behav Brain Res ; 245: 128-36, 2013 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-23439215

RESUMEN

Variants in genes regulating dopamine transmission affect performance on tasks including working memory and executive function as well as temporal processing and sequence learning. In the current study, we determined whether a dopamine D2 receptor DNA sequence polymorphism interacts with L-DOPA during motor tasks in patients with Parkinson's disease (PD). Forty-five PD patients were genotyped for the DRD2 polymorphism (rs 1076560, G>T). Patients performed an explicit motor sequence learning task and the grooved pegboard test in both ON and OFF L-DOPA states. For motor sequence learning, DRD2 genotype mediated L-DOPA effects such that L-DOPA associated improvements were only observed in the minor T allele carriers (associated with lower D2 receptor availability, t10=-2.71, p=0.022), whereas G homozygotes showed no performance change with L-DOPA. For the grooved pegboard test, performance improved with L-DOPA independent of patients' DRD2 genotype. Collectively these results demonstrate that common DRD2 allelic differences found in the human population may explain how dopamine differentially contributes to performance across tasks and individuals.


Asunto(s)
Antiparkinsonianos/uso terapéutico , Levodopa/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , Polimorfismo Genético/genética , Receptores de Dopamina D2/genética , Anciano , Alelos , Interpretación Estadística de Datos , Dopamina/metabolismo , Femenino , Genotipo , Heterocigoto , Humanos , Aprendizaje/fisiología , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Desempeño Psicomotor/fisiología
6.
Front Syst Neurosci ; 6: 52, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22783172

RESUMEN

Analysis of the amplitude of low frequency BOLD signal fluctuations (ALFF) in the resting state has recently been used to study the dynamics of intrinsic neural activity. Several studies have also suggested its potential as a biomarker for neuropsychiatric disease. In the current study, we quantified ALFF to determine changes in intrinsic neural oscillations in patients with Parkinson's disease (PD) on and off L-DOPA. Twenty-four PD patients and 24 healthy age-matched controls participated in the study. PD patients underwent two resting state fMRI sessions, either ON a controlled dose of L-DOPA or following a placebo pill (OFF). Control participants underwent one test session. We found that there was increased amplitude of low frequency BOLD signal oscillations for PD patients OFF L-DOPA in the primary and secondary motor areas, and in the middle and medial prefrontal cortices. L-DOPA significantly reduced the amplitude of low frequency oscillations within these regions. The degree of ALFF in the premotor cortex predicted patients' motor performance as measured by the Grooved Pegboard task, such that greater ALFF was associated with poorer performance. These results are in line with the pathophysiology of PD, which shows changes in neural oscillations. Thus, frequency domain analyses of resting state BOLD fMRI signals may provide a useful means to study the pathophysiology of PD and the physiology of the brain's dopaminergic pathways.

7.
J Hum Evol ; 39(1): 1-22, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10896810

RESUMEN

This analysis investigates the ancestry of a single modern human specimen from Australia, WLH-50 (Thorne et al., in preparation; Webb, 1989). Evaluating its ancestry is important to our understanding of modern human origins in Australasia because the prevailing models of human origins make different predictions for the ancestry of this specimen, and others like it. Some authors believe in the validity of a complete replacement theory and propose that modern humans in Australasia descended solely from earlier modern human populations found in Late Pleistocene Africa and the Levant. These ancestral modern populations are believed to have completely replaced other archaic human populations, including the Ngandong hominids of Indonesia. According to this recent African origin theory, the archaic humans from Indonesia are classified as Homo erectus, a different evolutionary species that could not have contributed to the ancestry of modern Australasians. Therefore this theory of complete replacement makes clear predictions concerning the ancestry of the specimen WLH-50. We tested these predictions using two methods: a discriminant analysis of metric data for three samples that are potential ancestors of WLH-50 (Ngandong, Late Pleistocene Africans, Levant hominids from Skhul and Qafzeh) and a pairwise difference analysis of nonmetric data for individuals within these samples. The results of these procedures provide an unambiguous refutation of a model of complete replacement within this region, and indicate that the Ngandong hominids or a population like them may have contributed significantly to the ancestry of WLH-50. We therefore contend that Ngandong hominids should be classified within the evolutionary species, Homo sapiens. The Multiregional model of human evolution has the expectation that Australasian ancestry is in all three of the potentially ancestral groups and best explains modern Australasian origins.


Asunto(s)
Cefalometría , Hominidae/anatomía & histología , Animales , Australia , Evolución Biológica , Análisis Discriminante , Fósiles , Humanos
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