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)

"Wearing-off" effect, the most common form of levodopa-induced fluctuations, seems to be related to the short plasma half-life of the drug. More sustained plasma levodopa levels may be achieved with a new controlled-release formulation of carbidopa/levodopa, Sinemet CR4. We studied 20 patients, 12 men and 8 women, with Parkinson's disease complicated by "wearing-off" phenomenon. Mean age was 61.1 +/- 8.1 years, duration of symptoms 8.3 +/- 2.4 years, and the Hoehn-Yahr stage 3.0 +/- 0.9. In a 12-week double-blind study, the average number of tablets administered per day decreased from 5.7 +/- 1.2 to 3.8 +/- 0.7 when Sinemet CR4 (50/200) was substituted for the standard Sinemet (25/100) (p less than 0.001). However, this was at the expense of reducing the "on" time (without dyskinesia) from 9.3 +/- 4.6 to 7.5 +/- 4.3 (p less than 0.05), although the total "on" time did not significantly change. In a long-term follow-up of 18 patients, the "on" time with dyskinesia and morning dystonia significantly increased (p less than 0.05). There was no significant change in the total daily dosage of levodopa, but the daily number of doses and tablets significantly decreased (p less than 0.001). Despite increased dyskinesia, most patients preferred taking fewer tablets and have elected to continue taking Sinemet CR4 instead of standard Sinemet. Sinemet CR4 seems to offer a new and effective strategy for the management of levodopa-related fluctuations.
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PMID:Comparison of Sinemet CR4 and standard Sinemet: double blind and long-term open trial in parkinsonian patients with fluctuations. 268 15

Twenty-one patients with Parkinson's disease and motor fluctuations who completed a double-blind study comparing controlled-release carbidopa/levodopa (Sinemet CR4) with standard Sinemet (SS) were evaluated one year following completion of the study. Five patients remained on CR4 alone; 16 continued on CR4 plus SS, and one also required addition of bromocriptine. Patients were significantly worse (p less than 0.05) at one year compared with double-blind CR4 phase (DBCR) for nine parameters of the motor exam, six activities of daily living (ADL), Hoehn & Yahr staging, and physician's global assessment. Compared with baseline SS, patients were worse at one year for four points of the motor exam, two of mentation, behavior, and mood, and 11 parameters of ADL. Improvement at one year was noted for less action and postural tremor and decreased duration of dyskinesias for both comparison periods. There was elimination of early morning dystonia at one year over the DBCR period and more hours "on" without dyskinesias and fewer hours "on" with dyskinesias compared with baseline SS. Total levodopa dosage was not significantly changed over the year. These data suggest that, in long-term use, CR4 remains more efficacious than SS alone for Parkinson's patients experiencing motor fluctuations, although disease progression continues despite optimal medication.
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PMID:Long-term efficacy of controlled-release carbidopa/levodopa in patients with advanced Parkinson's disease. 269 Jul 30

Two siblings of juvenile parkinson's disease dystonic type (JPA Yokochi type 3) and hereditary progressive dystonia with marked diurnal fluctuation (Segawa, HPD) were reported. The family had consanguinity. The elder brother suffered from resting tremor of legs, left foot dystonia and left pes equinovarus at the age of 12 years and 5 months. At the age of 15, he developed tremor and rigidity of upper extremities. These symptoms did not show diurnal fluctuation and markedly responded to L-dopa treatment. He implicated wearing-off phenomenon at the age of 16, and on-off phenomenon and L-dopa-induced dyskinesia at the age of 18. He was diagnosed as JPA Yokochi type 3. The younger brother suffered from left pes equinovarus, right scoliosis and foot dystonia at the age of 8 years. These symptoms showed remarkable diurnal fluctuation, which ameliorated after sleep or rest and worsened afternoon. He noticed fine postural tremor of upper extremities at psychological tense state and right pes varus at the age of 16. He received L-dopa at the age of 17 and became to be remission. He was diagnosed as HPD. Since these two disorders related to basal ganglia show similar clinical symptoms mainly consisting of foot dystonia and similar clinicopharmacological response to L-dopa, it has been assumed that shared abnormalities in pathomechanism can exist between them. This study indicates that the same gene-regulated abnormality may participate in the development of these two disorders.
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PMID:[Two siblings of juvenile Parkinson's disease dystonic type (Yokochi type 3) and hereditary progressive dystonia with marked diurnal fluctuation (Segawa)]. 280 13

"Extrapyramidal" reactions to antipsychotic drugs include acute dystonias, akathisia, Parkinson's syndrome, and tardive dyskinesia. Recent research suggests efficacy of prophylactic antiparkinson drugs in diminishing the incidence of acute dystonia in high-risk patients, although the use of lower neuroleptic doses also might lower the risk and cause fewer unwanted effects. New in the treatment of akathisia is the use of beta-blockers, specifically propranolol (Inderal and others). Many patients require maintenance antiparkinson drug therapy during prolonged antipsychotic drug treatment. There is no effective treatment for tardive dyskinesia, the prevalence of which may be growing, with an estimated annual incidence of new cases of 3%-4%; the elderly and patients with affective illness may be at greatest risk. Clinicians are also attending to the related syndrome of tardive dystonia.
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PMID:Treating extrapyramidal reactions: some current issues. 288 54

The local concentration of 6-[18F]fluoro-L-dopa(18F) reflects the activity of aromatic acid decarboxylase (AADC), the enzyme that generates dopamine from its precursor amino acid, L-dopa. In young healthy adults, the local concentration of 18F, and hence AADC activity, is constant in coronal slices taken in a rostrocaudal direction. With increasing age a gradient representing decreasing activity in the putamen develops. This decrease is less marked than was expected from the literature. In five children with primary dystonia, the striatal distribution of 18F resembled that seen in the normal older adults. In established clinical Parkinson's disease the rostrocaudal gradient becomes steep; the putamen is more damaged.
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PMID:A rostrocaudal gradient for aromatic acid decarboxylase in the human striatum. 311 81

Positron emission tomography provides a method for the quantitation of regional function within the living human brain. Studies of cerebral metabolism and blood flow in patients with Huntington's disease, Parkinson's disease and focal dystonia have revealed functional abnormalities within substructures of the basal ganglia. Recent developments permit assessment of both pre-synaptic and post-synaptic function in dopaminergic pathways. These techniques are now being applied to studies of movement disorders in human subjects.
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PMID:Positron emission tomography in movement disorders. 315 62

The experience that the supplementation of depleted dopamine in the nigro-striatal system of parkinsonian patients with L-dopa improves the clinical triad, akinesia, rigidity and tremor, mainly applies to long-term treatment in the early phase of Parkinson's disease. Complications in motor performance, like on-off response, wearing-off phenomena, peak-dose dyskinesia, biphasic dyskinesia, off-period dystonia and others, after more than 3 to 5 years following the onset of treatment indicate fluctuations in the dopaminergic feedback control system. It is suggested that these complications are due to progressive presynaptic degeneration and late changes in postsynaptic receptor amplification. However, as fluctuations are not imperative in all patients, an important additional aspect seems to be the topography of denervation, which involves different portions of the striatum to varying degrees. Location and extent of denervation are criteria which appear to have predictive value for the malignancy of the disease, the therapeutic response of drugs and complications in long-term treatment.
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PMID:Factors contributing to fluctuations of the dopaminergic nigro-striatal feedback system in Parkinson's disease. 316 34

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 39 normal subjects, 32 neurological controls, 66 patients with progressive ataxic disorders, 32 with multiple system atrophy, 40 with Parkinson's disease, eight with Steele-Richardson-Olszewski syndrome, eight with juvenile Parkinsonism and four with the dystonia-Parkinsonism syndrome. GDH activity was reproducible to within 10% in leukocyte pellets stored at -70 degrees C for up to 9 months, and did not vary with sex or age in control subjects. There was marked variation in the relative proportions of heat stable and heat labile forms of GDH between control subjects and on repeated assay in the same subject. Total leukocyte GDH activity was similar in normal subjects and neurological controls. Mean total GDH activity was reduced in all patient groups by between 15 to 29% compared with controls. Fourteen patients had total GDH activity below 50% of the control mean, but low values were not specific for any one disease (five had ataxic disorders, four Parkinson's disease, three multiple system atrophy, one juvenile Parkinsonism, and one dystonia-Parkinsonism). The heat labile fraction of GDH represented about 20% of total activity in control subjects, and 27% in the patients with reduced total GDH activity. Thus low GDH activity was not disease-specific in this study, and the heat-labile GDH fraction was not selectively affected. "Reduced" leucocyte GDH activity in some patients may represent no more than the lower end of a normal distribution.
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PMID:Leukocyte glutamate dehydrogenase activity in patients with degenerative neurological disorders. 320 97

Anismus, or constipation due to functional obstruction at the pelvic outlet by paradoxical contraction of the striated sphincter muscles during defaecation straining, is described in ten constipated patients and four patients with Parkinson's disease and constipation. The dysfunctional pattern of muscle recruitment resembled that characteristic of dystonia elsewhere in the body and was indistinguishable in patients with idiopathic anismus and those with extrapyramidal motor disturbance due to Parkinson's disease. These findings suggest that anismus may be a focal dystonic phenomenon.
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PMID:Constipation and paradoxical puborectalis contraction in anismus and Parkinson's disease: a dystonic phenomenon? 322 Dec 17

In this review, the authors present a critical overview of the historical development, indications, complications, operative techniques, and results of procedures for the alleviation of the major dyskinesias. Emphasis is placed upon recent refinement of technique, particularly stereotaxis, as well as neurophysiologic stimulation and recording, computerized tomographic scanning (CT) and magnetic resonance imaging (MRI). Specific disorders that may be amenable to surgical therapy include spasticity secondary to spinal cord pathology, cerebral palsy, and multiple sclerosis; the tremor and rigidity of Parkinson's disease; essential tremor; dystonia; spasmodic torticollis; post-traumatic and postinfarction intention tremor; cerebral palsy with tremor; hemiballismus; myoclonus; and dyskinesias induced by L-DOPA.
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PMID:Neurosurgical management of spasticity, rigidity, and tremor. 332 80


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