Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our study aims were: 1) to determine whether assisted weight bearing or additional weight bearing is more beneficial to the improvement of function and increased stability in gait and dynamic balance in patients with Parkinsonism, compared with matched controls (treadmill alone). Twenty-three men and women participants (M +/- SD = 74.5 +/- 9.7 yrs; Males = 19, Females = 4) with Parkinsonism were in the study. Participants staged at 1-7 (M +/- SD = 3.96 +/- 1.07) using the Hoehn & Yahr scale. All participants were tested before, after the intervention (within one week), and four weeks later on: 1) dynamic posturography, 2) Berg Balance scale, 3) United Parkinson's Disease Rating Scale (UPDRS), 4) biomechanical assessment of strength and range of motion, and 5) Gaitrite force sensitive gait mat. Group 1 (treadmill control group), received treadmill training with no loading or unloading. Group 2 (unweighted group), walked on the treadmill assisted by the Biodex Unweighing System at a 25% body weight reduction. Group 3 (weighted group), ambulated wearing a weighted scuba-diving belt, which increased their normal body weight by 5%. All subjects walked on the treadmill for 20 minutes per day for 3 days per week for 6 weeks. Improvements in dynamic posturography, falls during balance testing, Berg Balance, UPDRS (Motor Exam), and gait for all groups lead us to believe that neuromuscular regulation can be facilitated in all Parkinson's individuals no matter what treadmill intervention is employed.
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PMID:The effects of loading and unloading treadmill walking on balance, gait, fall risk, and daily function in Parkinsonism. 1640 97

Dementia with Lewy bodies (DLB) is characterized by progressive dementia with two of three core symptoms; Parkinsonism, visual hallucinations or disturbances of consciousness/fluctuating attention. Dementia in Parkinson's disease (PDD) has similar neuropsychiatric characteristics. Reduced nigrothalamic dopamine and altered thalamic D2 receptors may mediate some of the non-motor symptoms of DLB and PDD. The study aims were to ascertain whether thalamic D2 density was altered in Parkinson's disease (PD), PDD and DLB, and whether D2 density was related to core symptoms. Thalamic D2 receptor binding was measured by post-mortem autoradiography in 18 cases of DLB, 13 PDD, 6 PD and 14 normal elderly controls. Highest D2 density in control cases was in the intralaminar, midline, anterior and mediodorsal nuclei. In PD without dementia D2 binding was elevated above controls in all thalamic regions, significantly in reticular, laterodorsal, centromedian, ventral centromedian, parafascicular, paraventricular, ventroposterior, ventrolateral posterior, and ventrointermedius nuclei. Compared to controls, DLB cases with Parkinsonism (DLB+EPS) had significantly elevated D2 receptor density in laterodorsal and ventrointermedius nuclei; PDD cases had significantly raised density in the ventrointermedius, and DLB cases without Parkinsonism (DLB-EPS) did not show increased D2 density in any areas. In DLB and PDD cases with disturbances of consciousness, cases treated with neuroleptics had higher D2 binding in all thalamic regions, significantly in the mediodorsal and ventrolateral posterior nuclei. D2 receptor binding did not vary with cognitive decline (MMSE) or visual hallucinations, but was significantly higher with increased extrapyramidal symptoms.
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PMID:Thalamic D2 receptors in dementia with Lewy bodies, Parkinson's disease, and Parkinson's disease dementia. 1644 81

Medicated patients with Parkinsonism and parkin gene mutations have been reported to show a significant decrease in striatal dopamine D2 receptors (D2R) in comparison to medicated idiopathic Parkinson's disease (IPD) patients with similar age and disease severity. The aim of this study was to verify whether the genetic defect per se is responsible for this decrease. We have studied with [11C]raclopride (RAC) positron emission tomography (PET) in a group of 14 sporadic patients with parkin-linked Parkinsonism, 6 of whom had never received levodopa or dopamine agonists. The remaining 8 patients had been treated with levodopa for at least 5 years. Presynaptic striatal [18F]dopa storage was not significantly different between these two groups of patients. In untreated parkin-positive patients, significant putaminal increases in RAC-binding potential (BP) were found in comparison to an age-matched healthy control group by using a classical region of interest approach and statistical parametric mapping. In contrast, levodopa-treated parkin-positive patients showed significant decreases in RAC-BP in the caudate and putamen when compared to an age-matched healthy control group. The RAC PET findings revealed that striatal D2R upregulation occurs in dopaminergic drug-naive parkin-positive patients, in a similar fashion to the upregulation reported in drug-naive IPD. D2R downregulation observed in medicated parkin-positive patients, therefore, is not caused primarily by the genetic defect itself. Parkin-positive patients appear to have a greater susceptibility to the exposure to dopaminergic medication than IPD patients, which in turn might be an indirect effect of their genetic mutation.
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PMID:Upregulation of dopamine D2 receptors in dopaminergic drug-naive patients with Parkin gene mutations. 1651 56

Freezing of gait (FOG) is a disabling episodic gait disturbance that is common among patients with Parkinsonism. FOG typically lasts a few seconds and is associated with a unique sensation: the patient feels that his feet are glued to the ground, causing him to remain in place despite making a concerted effort to overcome the motor block and move forward. Traditionally, FOG has been viewed as a motor symptom of advanced Parkinson's disease. Here we describe evidence which demonstrates that mental conditions also likely play an important role in the pathogenesis of FOG. Stress, anxiety, depression and cognitively challenging situations are associated with FOG, and may set the stage for and increase the likelihood that FOG occurs. A conceptual model that explains how mental conditions may modulate FOG is developed.
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PMID:The role of mental function in the pathogenesis of freezing of gait in Parkinson's disease. 1678 Aug 86

Gaucher disease is the most frequent lysosome storage disease and presents an autosomal recessive mode of inheritance. It is caused by mutations at the GBA gene leading to deficient activity of the glucocerebrosidase enzyme. This report describes 12 new mutations [c.38A>G (K-27R), c.220G>A (G35S), c.448G>A (E111K), IVS4+1G>A, c.746C>T (A210V), c.776A>G (Y220C), c.793delC (Q226_fs4X), c.1102C>T (R329C), c.1300C>T (R395C), c.1309G>A (V398I), c.1324-1326delATT (delI403) and c.1583T>C (I489T)] and 4 novel silent alterations [c.342C>T (F75), c.528C>T (D137), c.1011C>T (D298) and c.1092G>A (G325)] detected among 40 unrelated Brazilian type 1 Gaucher disease patients by a combination of RFLP, dHPLC and DNA sequencing procedures. The R329C mutation, previously described in a Parkinson's disease patient (A. Lwin, E. Orvisky, O. Goker-Alpan, M.E. LaMarca, E. Sidransky. Glucocerebrosidase mutations in subjects with Parkinsonism. Mol. Genet. Metab. 81 (2004) 70-73), is described here for the first time in a Gaucher disease patient. Several genotype-phenotype correlations could be established, contributing significantly to the panel of reported mutations and conferring predictive value to their detection.
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PMID:Detection of 12 new mutations in Gaucher disease Brazilian patients. 1705 88

The choice of agents to treat psychotic symptoms in Parkinson's disease is important given the potential for antipsychotics to worsen Parkinsonism. The purpose of this study was to estimate the incidence of psychotic symptoms requiring treatment in individuals with Parkinson's disease after starting dopaminergic medications, and to describe the agents being selected as initial antipsychotic therapy. Using the administrative health care databases of Ontario, Canada, individuals 66 years of age or older with Parkinson's disease who were newly treated with dopaminergic agents were identified. Subsequent prescriptions for antipsychotic medications were then identified. A total of 10,347 older adults were newly started on dopaminergic agents between 1998 and 2003. The Kaplan-Meier estimate for the cumulative probability of requiring an antipsychotic at 7 years was 35%; 499 individuals (4.8%; 5.2/100 person-years) were prescribed an antipsychotic within 1 year of starting dopaminergic therapy. The proportion of initial antipsychotic prescriptions for typical antipsychotics decreased from 56% (42 of 75) in 1998 to 9% (8 of 88) in 2002. Antipsychotic use is common in individuals with Parkinsonism newly treated with dopaminergic medication. Typical antipsychotics are still commonly being chosen as first-line agents for older patients, indicating a need for interventions to improve practice.
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PMID:Antipsychotic use in older adults with Parkinson's disease. 1714 18

Recently, the introduction of 3 tesla (3T) magnetic resonance (MR) system for more sophisticated clinical applications has yielded in important benefits, especially in neuroradiology. The aim of this article is to illustrate the practical scientific applications of the 3T system in the neuroradiological filed. From the clinical point of view, we focused on the usefulness of 3T system for the diagnosis of several neurological disorders, such as brain tumors, vascular lesions, hemorrhagic lesions, acute cerebral infarcts and degenerative diseases. The greatest advantage of high-field MR system is a higher signal to noise ratio. This higher spatial resolution can provide precise anatomical information for brain tumor itself and its surrounding structures. Diffusion weighted imaging (DWI) also benefits from the higher signal to noise ratio and offers useful information for tumor characteristics. Navigation system with diffusion tensor tractgraphy is also available for surgical operation of brain tumors. Parallel imaging enables to improve the quality of tractgraphy by reducing susceptibility artifacts. 3T TOF (time-of-flight) MR angiography (MRA) demonstrates superior depiction of intracranial aneurysms compared with that of 1.5T TOF MRA. 3T TOF MRA is also useful for the evaluation and follow-up of stenoocclusive diseases including moyamoya disease. Susceptibility weighted imaging (SWI) is a BOLD (blood oxygenation level dependent)-sensitive method for visualizing anatomical features such as small cerebral veins in high detail. Therefore, 3T system has advantages for obtaining detailed, high spatial resolution images of the venous network. SWI is useful for detection of hemorrhagic lesions and early diagnosis of acute hemorrhagic infarcts. SWI also can detect embolus and evaluate functional changes showing dilatation of medullary veins in the area of acute cerebral infarcts. Neuromelanin imaging using 3T system can directly demonstrate the locus ceruleus and substantia nigra by the neuromelanin content and have the potential to become a powerful tool in Parkinson's disease and other neurodegenerative disorders with Parkinsonism. Hyperintense putaminal rim can be often observed in clinically normal subjects on fast spin echo T2-weighted images at 3T system. This finding should not be mistaken for multiple system atrophy. 3T MR system indeed offers new potential because of a substantial increase in signal intensity provided by the higher magnetic field. Routine neuroradiologic imaging would benefit from higher magnetic field. However, It is required that extended knowledge of clinical data in comparison with 1.5T system to elucidate the efficacy of 3T system in the neuroradiology.
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PMID:[Clinical applications of 3.0 T magnetic resonance system in the neuroradiological field]. 1753 73

Most cases of Parkinson's disease (PD) are sporadic, suggesting an environmental influence on individuals affected by this neurodegenerative disorder. Environmental stresses often lead to changes in the regulation of splicing of pre-mRNA transcripts and this may lead to the pathogenesis of the disease. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid mouse model was used to examine the changes in the splicing of the fosB and rgs9 transcripts. The ratio of DeltafosB/fosB transcript was decreased in the substantia nigra and unchanged in the striatum after acute MPTP treatment. The DeltafosB/fosB transcript ratio decreased initially and then increased in the striatum of chronically MPTP-treated animals due to different degrees of reduction for the splice variants over time, whereas the ratio was unchanged in the substantia nigra. The ratio of rgs9-2/rgs9-1 transcript decreased in the substantia nigra of mice after acute MPTP treatment and increased temporarily in the striatum after chronic MPTP treatment. There was an increase in the DeltaFosB/FosB and RGS9-2/RGS9-1 protein ratios 3 weeks and 3 days post-treatment, respectively, in chronically treated mice. The data indicate that the pattern of splice isoforms of fosB and rgs9 reflects the brain's immediate and long-term responses to the physiological stress associated with Parkinsonism.
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PMID:MPTP administration in mice changes the ratio of splice isoforms of fosB and rgs9. 1793 34

Clinical features that are prognostic indicators of placebo response among dyskinetic Parkinson's disease patients were determined. Placebo-associated improvements occur in Parkinsonism, but responses in dyskinesia have not been studied. Placebo data from two multicenter studies with identical design comparing sarizotan to placebo for treating dyskinesia were accessed. Sarizotan (2 mg/day) failed to improve dyskinesia compared with placebo, but both treatments improved dyskinesia compared with baseline. Stepwise regression identified baseline characteristics that influenced dyskinesia response to placebo, and these factors were entered into a logistic regression model to quantify their influence on placebo-related dyskinesia improvements and worsening. Because placebo-associated improvements in Parkinsonism have been attributed to heightened dopaminergic activity, we also examined the association between changes in Parkinsonism and dyskinesia. Four hundred eighty-four subjects received placebo treatment; 178 met criteria for placebo-associated dyskinesia improvement and 37 for dyskinesia worsening. Older age, lower baseline Parkinsonism score, and lower total daily levodopa doses were associated with placebo-associated improvement, whereas lower baseline dyskinesia score was associated with placebo-associated worsening. Placebo-associated dyskinesia changes were not correlated with Parkinsonism changes, and all effects in the sarizotan group were statistically explained by the placebo-effect regression model. Dyskinesias are affected by placebo treatment. The absence of correlation between placebo-induced changes in dyskinesia and Parkinsonism argues against a dopaminergic activation mechanism to explain placebo-associated improvements in dyskinesia. The magnitude and variance of placebo-related changes and the factors that influence them can be helpful in the design of future clinical trials of antidyskinetic agents.
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PMID:Placebo influences on dyskinesia in Parkinson's disease. 1817 37

Mitochondrial DNA (mtDNA) deletions have been investigated in a number of neurodegenerative diseases. This study aimed to investigate the characteristics of mtDNA deletions found in single substantia nigra neurons from three patient groups: controls, Parkinson disease patients, and a patient with Parkinsonism due to multiple mtDNA deletions. We have identified 89 deletions from these neurons and examined the breakpoint characteristics of them. There was no difference in the types of mtDNA deletions detected in these neurons. These results suggest that the mechanism leading to the formation of these deletions in these three distinct groups could be the same.
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PMID:Nature of mitochondrial DNA deletions in substantia nigra neurons. 1817 4


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