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)

Patients with Parkinson's disease were compared during two 15-year periods before and after the introduction of levodopa. With levodopa treatment: The duration of illness at each stage of severity was 3 to 5 years longer; at every duration of illness, death and disability were reduced 1.5- to 3-fold, except in patients whose treatment had been delayed; abnormal involuntary movements that interfered with function occurred in 24% of patients; severe fluctuations that required rescheduling of activities occurred in 29% of patients; severe AIMs and fluctuations were rare during the first 3 years of treatment, but remained constant thereafter, without progressive increase; prevalence of severe fluctuations was related only to age of onset of disease: If under 50, severe fluctuations developed in 66%, if age 50 to 59 at onset, they developed in 30%, if over age 60, in only 6%; average age at death was 6 years older; and observed/expected mortality was 1.2, not significantly different from the unaffected population.
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PMID:Parkinson's disease: progression and mortality. 382 26

Thirty-six patients with Parkinson's disease, on levodopa, were admitted to a double-blind, parallel, 40-week study of adjunct bromocriptine in dosages increased by 2.5 mg every 4 weeks. A 37% improvement of the mean neurologic deficit score was obtained at the maximal daily dosage of 20 mg. Improvement was greatest in patients with mild disease. The wearing-off effect, off-dose abnormal involuntary movements, and leg pains, associated with levodopa, improved in over 70% of patients at an average dosage of 13 mg. Only 15% of patients had adverse reactions severe enough to necessitate discontinuance of the drug. Abnormalities of mental state were less severe than expected, but two patients had exacerbations of angina pectoris.
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PMID:Low dosages of bromocriptine added to levodopa in Parkinson's disease. 396 7

Research in Parkinson's disease has given little attention to the reliability of subjective-qualitative assessment, or to the empirical aggregation of physical signs to supraordinate indexes of motor disturbance. We illustrate methods for examining observer reliability and discuss the importance of reliability to the interpretation of results. Observers rated patients (n = 70) for physical signs (selected Columbia Scale scores), disability stages, and abnormal involuntary movements. Observer agreement was achieved for Columbia scores and disability stages (range of Spearman rho = 0.67-0.95), but not for dyskinesias or dystonic postures. A factor analysis of Columbia scores revealed two indexes of motor disturbance: motor deficiency and tremor.
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PMID:Qualitative assessment of Parkinson's disease: study of reliability and data reduction with an abbreviated Columbia Scale. 397 53

15 years' experience with Parkinson's disease treated with levodopa was compared to the 15 years before the advent of levodopa. Progression to severe disability and death was prolonged, at each stage of severity, by 3 to 5 years. At each duration of illness, the percentage of patients with severe disability was reduced significantly. There was some indication that independence was prolonged by early treatment. Life expectancy was increased to approximately that of the unaffected population. However, especially with patients with onset of disease before the age of 50, fluctuations of therapeutic response and severe abnormal involuntary movements interfered with satisfactory therapeutic results. Supplemental bromocriptine produced a smoother therapeutic response and decreased "off" period dystonia and leg pains in over 70% of patients. At dosages below 20 mg daily, it was not particularly effective in severely affected disabled patients. Adverse reactions prevented the use of bromocriptine in less than 20% of patients.
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PMID:Result of chronic levodopa therapy and its modification by bromocriptine in Parkinson's disease. 398 85

The last 10 years have seen great activity in the investigation of cerebral catecholamines, particular attention having been paid to dopamine. The low dopamine content in the basal ganglia and in the urine of patients with Parkinson's disease led to the logical use of the precursor DOPA in the treatment of this disorder. Between 1961 and 1966, both the oral and the intravenous routes were utilized and some effects were noted upon akinesia and rigidity. The doses then used were low and the results remained somewhat controversial. When higher oral levels of L-dopa were introduced, the beneficial action of L-dopa upon parkinsonian symptoms and signs was proved beyond doubt, but there came to light a number of troublesome side effects, the worst of which were hypotension and a variety of abnormal involuntary movements. Recently, new approaches to the therapy have been tried and the sum total of these observations is to challenge our peace of mind regarding a seemingly logical chain of events. We are convinced that such second thoughts will eventually result in better and safer methods of treating this too frequent and disabling neurological disorder.
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PMID:L-dopa therapy in Parkinson's disease: a critical review of nine years' experience. 490 90

The authors report their experience, over a 26-month period, in the management of 60 parkinsonian patients with the combination of levodopa and an inhibitor of peripheral dopa-decarboxylase, Ro 4-4602. This approach to Parkinson's disease is useful, safe, and at least as effective as levodopa alone. To date there have been no recognizable toxic effects attributable to Ro 4-4602. This agent appears to prolong the duration of action of levodopa, smoothing out its therapeutic effects. The percentage of patients obtaining a very good and excellent response is slightly increased. There is a possible diminution in the late-occurring bradykinetic and hypotonic freezing episodes. Nausea and cardiac arrhythmias are lessened, as are the incidence and severity of hypotension. Abnormal involuntary movements remain the limiting adverse side effect.
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PMID:Levodopa combined with peripheral decarboxylase inhibition in Parkinson's disease. 503 97

The antiparkinsonian activity of several dopamine agonists was investigated in an animal model and clinically in parkinsonian patients. The semisynthetic ergoline, pergolide, the partial ergoline, LY 141865 and the 8-alpha-aminoergoline, CU 32-085 were found to be effective antitremor agents in monkeys with ventromedial tegmental lesions. The administration of pergolide or LY 141865 results in a relief of tremor with a concomitant occurrence of severe abnormal involuntary movements, while the administration of CU 32-085 results in a relief of tremor with the occurrence of only minor abnormal involuntary movements. Clinical studies have revealed that pergolide is an effective drug in patients with advanced Parkinson's disease, and it reduces the "on-off" phenomena. The possible regulation of dopamine neurotransmission by the norepinephrine neuronal systems was reviewed. Preliminary data suggest that clonidine may interact with presynaptic dopamine receptors.
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PMID:Therapeutic potentials of centrally acting dopamine and alpha 2-adrenoreceptor agonists. 613 44

One hundred ninety L-dopa-treated parkinsonian patients have been studied according to the age at onset and to age at last examination. The frequency of major mental disturbances was significantly higher in patients older than 60 years, whereas abnormal involuntary movements and on-off phenomenon were more frequent in patients with onset before age 60. The association of normal aging and of Parkinson's disease may be responsible for the prevalence of mental disease in older patients.
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PMID:L-dopa long-term treatment in Parkinson's disease: age-related side effects. 641 13

In this study the author's experience of Parkinson Disease treatment with long-term Bromocriptine (Br) administration, is summarized. Br, which acts directly on dopaminergic receptors, was introduced in combination with L-Dopa and peripheral decarboxylase inhibitors (PDI). The reasons for this association were: 1) the reduced effectiveness of the current treatment (L-Dopa + PDI) 2) onset of AIM (abnormal involuntary movements). 3) patient's desire to try new drugs. Only the patients who had been on the triple association for at least a year, were considered. Therefore of 50 patients originally considered only 19 were included in this study. The addition of Br allowed a reduction of the mean daily dose of L-Dopa(30%) and the therapeutic efficacy of the drug remained unchanged even after more than 4 years treatment. The "on-off" effect and AIM, are reduced by Br especially in the first months of treatment. The triple association is regarded at present as the best treatment for Parkinson disease.
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PMID:"Long term evaluation of combined treatment of Parkinson disease with L-dopa, peripheral decarboxylase inhibitors and bromocreptine". 733 24

The "off" painful dystonia (OPD), usually concerning the feet, is a type of abnormal involuntary movement, induced by the chronic use of levodopa. It is mostly observed in the advanced stage of Parkinson's disease (PD), particularly in the early morning, in the evening, and late at night. Indeed, some patients have experienced OPD also during "on" periods when dystonic posture of the foot alternates with dyskinesia. The pain probably is due to sustained muscle contraction, which causes prolonged muscle spasm, as in primary dystonia or torticollis. Dopaminergic drugs like bromocriptine, pergolide, and especially apomorphine (s.c. infusions, or bolus), can dramatically improve the OPD. Anticholinergics baclofen and lithium are alos used in the management of OPD with some benefit. On the other hand, clinical experience shows that in many cases, these therapeutic procedures are not always enough to produce the expected results. Thirty PD patients (22 men and eight women) with OPD of the foot were treated with botulinum toxin (Botox, Btx) using electromyograms to guide injections. Dystonia was evaluated using a quantitative rating scale. The selection of the muscles for Btx treatment was carried out on the basis of foot posture. We injected Btx into tibialis posterior, tibialis anterior, gastrocnemius, flexor digitorum longus, and extensores hallucis longus with a median dose 40 IU for each muscle, distributed in two sites. In all patients, the pain improved within 10 days, whereas in 21 patients, the pain disappeared completely for 4 months (range, 3-7 months); a concomitant improvement in intensity of the dystonic spasm was also observed. No side effects were reported. Seven patients with associated "on" foot dystonia described an improvement of foot posture on walking. In conclusion, in this uncontrolled study, the use of Btx in OPD seemed a promising tool to improve pain linked to foot dystonia; however, because of the well-known underlying dopaminergic defect in OPD, the Btx therapy should be considered only if the dopaminergic treatment established for the management of OPD has failed.
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PMID:"Off" painful dystonia in Parkinson's disease treated with botulinum toxin. 765 52


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