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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.

A Redox Chemistry-based Function for Parkinson Disease-linked Parkin Confers Direct, Anti-oxidant Activities in Mammalian Brain

El Kodsi, Daniel N. 29 September 2020 (has links)
Early-onset Parkinson disease, of which the best studied and most common cause are biallelic mutations in the PRKN gene, is characterized by an age of onset before 40 years. Parkin-deficient patients show slow progression, excellent responsiveness to L-dopa therapy, and are generally spared cognitive decline. At autopsy, PRKN-linked Parkinson disease is further distinguished by relative selectivity in cell loss, namely of dopamine producing neurons in the human brainstem, and the general absence of Lewy body inclusions. Since its discovery two decades ago, the field has focused on the function of parkin as an E3 ubiquitin ligase and its related role in mitophagy. However, its essential, neuroprotective function in ageing human midbrain and the mechanisms by which wildtype parkin preserves dopamine cell health in aged humans are yet to be elucidated. I hypothesized that parkin confers neuroprotection due to a redox function by its many cysteines (7.5%). We first focused on parkin’s biochemistry, reporting a shift from solubility to a nearly insoluble, aggregated state in adult control brain after age 40 years. We detected cysteine-based, post-translational modifications of parkin in response to oxidative stress, and characterized a novel, redox chemistry-based function: Through its own oxidation parkin reduced hydrogen peroxide in vitro. I validated this finding by showing its elevation in parkin-deficient, human brain. Wild-type parkin also participated in dopamine metabolism through the conjugation of reactive radicals at several of its cysteines, which augmented the generation of melanin. (Chapter 2). In addition, we demonstrated parkin’s heretofore unknown, antioxidant function in the cytosol using cellular paradigms and select genetic as well as toxin-based mouse models that featured elevated oxidative stress. Moreover, we uncovered parkin’s contribution to the wider thiol network, namely through an apparent feedback loop with glutathione metabolism (Chapter 3). Lastly, I developed and investigated a bi-genic (prkn-/-//Sod2+/-) model in an attempt to restage the pathogenesis of early-onset parkinsonism in mice; there, we detected a rise in systemic, oxidative stress and in total nitrotyrosination profiles of the brain, but did not observe any dopamine neuron loss in the midbrain. In accordance, the behavioural characterization of these animals did not reveal any motor abnormalities (Chapter 4). Based on this previously unknown function for parkin in redox biology, I envision three future research directions: a) additional studies to delineate the full range of oxidative modifications of parkin versus neutralization of radicals; this, to better define the distinct pathogenesis of parkin-linked Parkinson’s when compared to other forms of the disorder; b) structural studies of its oxidative modifications in vitro and renewed attempts of staging parkin-linked dopamine cell death in vivo; and c) and importantly, the exploration of cause-directed therapy based on parkin’s redox functions to preserve dopamine neurons of the human midbrain throughout adulthood.

Analysis of deep brain stimulation and ablative lesions in surgical treatment of movement disorders : with emphasis on safety aspects /

Blomstedt, Patric, January 2007 (has links)
Diss. (sammanfattning) Umeå : Univ., 2007. / Härtill 6 uppsatser.

Parkinson's disease and depression clinical and neurobiological studies /

Pålhagen, Sven E., January 2009 (has links)
Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009.

The Effects of Deep Brain Stimulation on Deglutition in Parkinson Disease

Ciucci, Michelle Renee January 2006 (has links)
Relatively little is known about the role of the basal ganglia and their pathways in human deglutition. Deep Brain Stimulation (DBS) is a treatment for Parkinson Disease (PD) that stimulates the subthalamic nuclei and affords us a model for examining deglutition in humans with known impairment of the basal ganglia. The purpose of this study was to examine the effects of DBS in the ON versus Off conditions on the oral and pharyngeal stages of deglutition in participants with PD. It was hypothesized that DBS in the ON condition would yield improvement in the following dependent variables: oral total composite score, pharyngeal total composite score, pharyngeal transit time, and maximal hyoid bone excursion. Statistically significant differences (improvement) were found for the pharyngeal composite score and pharyngeal transit time in the DBS ON condition. Findings of this study demonstrated that DBS in the ON condition helps to alleviate some of the bradykinesia and hypokinesia associated with PD on the pharyngeal stage of deglutition, but not the oral stage. These findings suggest that Parkinsonian swallowing dysfunction is not solely related to nigrostriatal dopamine deficiency which is purported to be the primary means of DBS alleviation of motor signs. Rather, it may be due to an additional non-dopamine related system of deglutition found in the brainstem.

Ser du mig? : En litteraturstudie om upplevelsen av att leva med Parkinsons sjukdom utifrån teorin Preserving Self / Do you see me? : The experience of living with Parkinson’s disease based on the theory of Preserving Self

Alsén, Kim, Lagundzija, Marijana January 2019 (has links)
Parkinsons sjukdom är den näst vanligaste neurodegenerativa sjukdomen hos den äldre befolkningen. Sjukdomen påverkar den kroppsliga funktionen negativt på olika sätt och sjukdomens medicinering är betydelsefull för att kunna hantera de olika symtom som uppkommer. Personer med Parkinsons sjukdom lider risk för nedsatt livskvalitet på grund av den begränsning i livet som sjukdomen leder till. Syftet med denna studie var att belysa patientens upplevelse av att leva med Parkinsons sjukdom. Studien utfördes som en allmän litteraturstudie med en deduktiv ansats, där tio resultatartiklar användes. Resultatet kategoriserades och presenterades utifrån Preserving Self teorins fem steg och fyra övergångar. Teorin bidrog till ett brett och detaljerat resultat från resultatartiklarna och tillförde en fördjupad bild av livet med Parkinsons sjukdom. Sjuksköterskans ansvar innefattar att göra patienten delaktig i sin vård och ta tillvara de resurser som finns hos varje individ. Användningen av teorin Preserving Self kan bidra till fördjupad kunskap i vården för personer med Parkinsons sjukdom. / Parkinson's disease is the second most common neurodegenerative disease in the elderly population. The disease adversely affects the bodily function in various ways and the medication of the disease is important in order to handle the various symptoms that arise. People with Parkinson's disease are at risk of impaired quality of life due to the limitations in life that the disease causes. The purpose with this study was to highlight the patient's experience of living with Parkinson's disease. The study was conducted as a general literature study with a deductive approach, in which ten result articles were used. The result was categorized and presented based on the five stages and four transitions in the theory of Preserving Self. The theory contributed to a broad and detailed result from the resultarticles and added an in-depth picture of life with Parkinson's disease. The nurses’ responsibility includes getting the patient to participate in their care and taking advantage of the resources that exist in each individual. Using the theory of Preserving Self can contribute to in-depth knowledge in the care for people with Parkinson's disease.

Características fonoarticulatórias na doença de Parkinson de início na meia idade e tardio / Speech and voice characteristics in middle age and late onset Parkinson\'s disease

Dias, Alice Estevo 15 August 2006 (has links)
Alterações fonoarticulatórias caracterizam a disartria hipocinética e podem ocorrer ao longo da evolução da doença de Parkinson (DP). No entanto, não existem estudos que evidenciem a influência da idade nessas alterações. Objetivo: Comparar e correlacionar selecionadas características fonoarticulatórias em pacientes com DP de início na meia idade e tardio. Método: Participaram 50 pacientes que constituíram dois grupos. O Grupo I foi composto por 30 (60%) pacientes com idade de início da DP entre 40 e 55 anos e o Grupo II, por 20 (40%) pacientes com início da doença após os 65 anos, ambos com a duração da doença variando de 2 a 18 anos. Todos foram submetidos à avaliação neurológica a partir da Parte III da Escala Unificada para a Doença de Parkinson (UPDRS) e Escala Modificada de Hoehn & Yahr e, fonoaudiológica, realizada por meio de análise perceptivo-auditiva (velocidade, inteligibilidade e tipo articulatório da fala e qualidade da voz) e acústica computadorizada (freqüência fundamental e intensidade da voz). Resultados: Não houve diferença estatisticamente significativa entre os dois grupos no que diz respeito ao estágio da doença, aos escores da escala UPDRS e às análises fonoaudiológicas. As análises de correlação não mostraram diferença estatisticamente significativa entre a qualidade, a freqüência fundamental e a intensidade da voz, bem como a velocidade da fala e o estágio da doença. Contudo, houve diferença estatística significativa entre a articulação e a inteligibilidade da fala e o estágio da doença. Os escores da escala UPDRS não revelaram diferença estatisticamente significativa quando comparados com a qualidade, a freqüência fundamental e a intensidade da voz e a velocidade da fala. Diferença estatisticamente significativa foi encontrada na correlação entre a articulação e os acometimentos axiais e também entre a velocidade da fala e os escores dos acometimentos axiais, da rigidez e da bradicinesia. Conclusões: A idade de início da DP não se relacionou com as características fonoarticulatórias analisadas. A função articulatória (articulação e inteligibilidade da fala) estava prejudicada sobremaneira nos estágios mais avançados da DP e foi associada ao maior tempo de duração da doença e aos escores mais elevados de manifestações axiais, de rigidez e de bradicinesia. A função fonatória (freqüência fundamental, qualidade e intensidade da voz) apresentou-se com características semelhantes em todos os estágios da DP e não se associou com a duração da doença e tampouco com os escores motores analisados. / Parkinson\'s disease (PD) patients may develop speech and voice abnormalities during the course of their illness, typically hypokinetic dysarthria. There are no studies to date describing the influence of age on these abnormalities. Objective: To describe and to correlate selected speech and voice characteristics in PD patients with middle-age and late-onset disease and compare each group\'s findings. Methods: Fifty PD patients were enrolled in this study and subsequently divided into two groups. Group I included 30 (60%) patients with PD onset between 40 and 55 years old and Group II consisted of 20 (40%) patients with disease onset after the age of 65. In both groups disease duration ranged from 2 to 18 years. All patients were submitted to neurological evaluation based on the motor Unified Parkinson\'s Disease Rating Scale (UPDRS - part III) and the Modified Hoehn and Yahr Staging Scale plus speech and voice evaluation, performed through perceptual analysis (speech velocity and intelligibility, articulatory speech type and voice quality) and computerized acoustic (fundamental frequency and voice intensity). Results: There was no statistically significant difference between the groups concerning disease stage, UPDRS scores and speech and voice analysis. Disease stage was not associated to quality, fundamental frequency and intensity of voice. There was also no difference between speech velocity and disease stage. On the other hand, there was statistically significant difference between articulation and speech intelligibility and disease stage. UPDRS scores did not reveal a statistically significant difference when compared to quality, fundamental frequency and voice intensity and speech velocity, but there was a difference in the correlation between articulation and axial symptoms and also between speech velocity and scores for axial symptoms, rigidity and bradykinesia. Conclusion: The age of onset of PD was not associated with speech and voice characteristics analysed. Articulatory function (speech articulation and intelligibility) was remarkably affected in advanced PD and was associated with not only with longer disease duration, but also with more axial symptoms, rigidity and bradykinesia. Phonatory function (fundamental frequency, quality and intensity of voice) disclosed similar characteristics in all PD stages and was not associated with disease duration or with motor scores analysed.

"Análise comparativa das funções neuropsicológicas de portadores de doença de Parkinson em estágios inicial e avançado: uma determinação de padrões para diagnóstico em população brasileira" / Comparative analysis of the neuropsychological functions of patients with Parkinson disease in the initial and advanced stages: a determination of patterns to the diagnosis in the Brazilian population.

Pinto, Kátia Osternack 28 October 2005 (has links)
A avaliação neuropsicológica de portadores de doença de Parkinson (DP) tem sido de fundamental importância para definição de resultados em procedimentos clínicos, cirúrgicos experimentais ou para diagnóstico de demência nestes doentes. No entanto, ainda não existe consenso quanto aos testes neuropsicológicos necessários e padrões de comprometimento esperados. Este estudo objetivou comparar a produtividade das funções neuropsicológicas entre portadores da Doença de Parkinson, em diferentes estágios da doença, em relação aos indivíduos normais. Foram analisados 60 sujeitos (32 homens e 28 mulheres), emparelhados em relação à idade (média de 65,6 +-9,2) e instrução (média de 5,9 =- 4,0), distribuídos entre normais (n=20) e portadores de DP ambulatoriais, nos estágios leve a moderado (n=20) ou moderado a grave (n=20), de acordo com a escala Hoehn & Yahr. A bateria utilizou 24 testes neuropsicológicos abrangendo as funções de raciocínio, percepção visuoespacial, visuoconstrução, linguagem, memória, atenção e função executiva. Os resultados apontaram diferenças significantes (p < 0,01) entre vários testes e em todas as funções, exceto linguagem. Alguns instrumentos se mostraram mais adequados e outros se mostraram pouco indicados para avaliar estes doentes. Diferenças entre os estágios da doença só se evidenciaram nos testes que exigiam destreza motora. Este trabalho estabelece a adequação dos instrumentos e propõe uma bateria específica para avaliação destes doentes. A investigação de estados situacionais (nível cultural, sintoma afetivo e/ou limitações funcionais), manifestos na avaliação, permitiu estabelecer parâmetros para discriminar o modo como estas variáveis interferem na produção dos doentes de Parkinson. E conclui-se apresentando um método inovador de classificação para subsidiar com objetividade o diagnóstico neuropsicológico diferencial na DP. / The neuropsychological assessment of patients with Parkinson disease (PD) has been very important to define the results in clinical, experimental surgeries procedures or in the diagnostic of dementia of these patients. However, there is no consensus about the necessary neuropsychological tests and about the expected commitment patterns. This study aimed to compare the productivity of the neuropsychological functions among patients with Parkinson Disease, in different stages of the disease, in relation to normal people. Sixty subjects were assessed (32 men and 28 women), pared in relation to the age (average of 65.6 +- 9.2) and age of study (average of 5.9 +- 4.0), distributed among normal (n=20) and outpatients with PD, in the mild to moderate stages (n=20) or moderate to severe (n=20), according to Hoehn & Yahr Scale. The battery used 24 neuropsychological tests comprising the thinking, visuospatial perception, visuoconstruction, language, memory, attention and executive function. The results showed significant differences (p < 0.01) among many tests and in all the functions, except language. Some instruments were more suitable and others proved to be less indicated to assess these patients. Differences in the stages of the disease were highlighted in the tests that required motor ability. This work establishes the adequacy of the instruments and proposes a specific battery to assess these patients. The investigation of the situational state (cultural level, affective symptom and/or functional limitations), that appeared in the assessment, allowed to establish parameters to find out the way that these variables interfered in the Parkinson patients’ production. The work concludes presenting an innovative classification method to objectively subside the neuropsychological differential diagnosis for PD.

Efeito de um programa sistematizado de atividades rítmicas e dança nas funções cognitivas, aspectos neuropsiquiátricos e andar de pacientes com doença de Parkinson : um estudo controlado e randomizado /

Lirani-Silva, Ellen. January 2018 (has links)
Orientador: Lilian Teresa Bucken Gobbi / Banca: Carolina Rodrigues Alves Silveira / Banca: Renato de Moraes / Banca: Carla da Silva Batista / Banca: Luciane Aparecida Pascucci Sande de Souza / Resumo: Introdução: A presente tese de Doutorado é composta por dois estudos. O objetivo do Estudo #1 foi investigar a associação entre domínios do andar (com e sem tarefa dupla) e domínios cognitivos e neuropsiquiátricos de pacientes com DP (DP). O objetivo do Estudo #2 foi investigar os efeitos de uma intervenção de atividades rítmicas e dança no andar, funções cognitivas e aspectos neuropsiquiátricos de pacientes com DP e a manutenção de benefícios após um período de follow up (5 meses). Materiais e método: O Estudo #1 contou com a participação de 87 pacientes com DP. Após avaliação clínica e anamnese, os pacientes foram avaliados quanto ao andar (com e sem tarefa dupla), funções cognitivas e aspectos neuropsiquiátricos. A partir das avaliações, dois modelos foram elaborados: i) modelo do andar formado por 16 características espaço-temporais do andar, distribuídos em cinco domínios (pace, variabilidade, ritmo, assimetria e controle postural); ii) modelo de aspectos cognitivos e neuropsiquiátricos formado por 10 testes, distribuídos em sete domínios (cognição global, memória, função executiva, atenção, memória de trabalho, habilidade visuoespacial, neuropsiquiátrico ). O Estudo #2 contou com a participação de 86 pacientes com DP que foram distribuídos randomicamente em dois grupos: grupo de atividades rítmicas (DPd) e dança e grupo convívio (DPc). As atividades do grupo DPd foram realizadas com base em diferentes estilos, com progressão tanto em mudanças do ambiente como em complex... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: This PhD thesis consists of two studies. The aim of the Study #1 was to investigate the association between gait domains (with and without dual task) and cognitive and neuropsychiatric domains of patients with Parkinson's disease (PD). The aim of the St udy #2 was to investigate the effects of a rhythm activities and dance intervention on gait, cognitive function and neuropsychiatric aspects of patients with PD, as well as the retention of benefits after a follow up period (5 months). Methods: Study #1 in volved the participation of 87 patients with PD. A fter clinical assessment, gait (with and without dual task), cognition and neuropsychiatric aspects were assessed. Gait, cognition and neuropsychiatric aspects were summarized in two models: i) a gait model with 16 spatial - temporal gait characteristics, described by five domains (pace, variability, rhythm, asymmetry and postural control); ii) a cognitive and neuropsychiatric model with 10 assessments organized in seven domains (global cognition, memory, exec utive function, attention, working memory, visuospatial ability and neuropsychiatric). Study #2 involved 86 patients with PD which were allocated in two groups: rhythm activities and dance intervention group (PDd) and socializing group (PDs). Activities of the PDd group were structured based on different styles of dance, with progression in the environment and movement complexity. Activities of t he PDs group were organized in three phases: i) talks and d... (Complete abstract click electronic access below) / Doutor

Optimised dose titration for Duodopatreatment based on simulation experiments– implementation in a decision supportsystem

CHen, Canghai January 2009 (has links)
The aim of this work was to design a set of rules for levodopa infusion dose adjustment in Parkinson’s disease based on a simulation experiments. Using this simulator, optimal infusions dose in different conditions were calculated. There are seven conditions (-3 to +3)appearing in a rating scale for Parkinson’s disease patients. By finding mean of the differences between conditions and optimal dose, two sets of rules were designed. The set of rules was optimized by several testing. Usefulness for optimizing the titration procedure of new infusion patients based on rule-based reasoning was investigated. Results show that both of the number of the steps and the errors for finding optimal dose was shorten by new rules. At last, the dose predicted with new rules well on each single occasion of majority of patients in simulation experiments.

Women with Parkinson's disease : circadian function /

Dowling, Glenna Annette, January 1989 (has links)
Thesis (Ph. D.)--University of Washington, 1989. / Vita. Includes bibliographical references (leaves [62]-66).

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