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)

Four cases of transplant to the brain (striatum) of the ventral mesencephalic area (VMA) and three adrenal glands (A) to patients with Parkinson's disease are described as a new alternative for the improvement of this disease. The patients who received VMA showed a very significant improvement in the rigidity, bradykinesia, alterations in walking and posture, as well as the facial expression. Three of the four patients have returned to work. The group that received A tissue, showed a discreet improvement in the rigidity and bradykinesia, but none in the other signs of the disease. These patients are able to accomplish their daily needs, but two are unable to return to work. The differences which we observed between patients receiving VMA and A transplants, might be related to the heterogeneity of the disease, although we believe that the type of graft was responsible of these differences. Our results with the use of VMA, as well as that of other groups, are encouraging, although it is important to clearly establish that it is a procedure which is still in an experimental phase, requiring caution, and should only be practiced in highly qualified centers of clinical research.
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PMID:[Human fetal homograft to the nigrostriatal system for the treatment of Parkinson's disease]. 210 10

Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-L-[18F]fluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the "on-off" phenomenon). The clinical improvement was most marked on the side contralateral to the transplant.
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PMID:Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease. 230 Aug 13

We studied the metabolic anatomy of typical Parkinson's disease (PD) using [18F]fluorodeoxyglucose (FDG) and [18F]fluorodopa (FDOPA) and positron emission tomography (PET). Fourteen PD patients (mean age 49 years) had FDG/PET scans, of which 11 were scanned with both FDOPA and FDG. After the injection of FDOPA, brain uptake and arterial plasma radioactivity were monitored for 2 h. Striatal FDOPA uptake was analyzed with regard to a two-compartment model, and target-to-background ratios (TBRs) and TBR-versus-time slopes were also calculated. Regional patterns of metabolic covariation were extracted from FDG/PET data using the Scaled Subprofile Model (SSM). SSM pattern weights, FDOPA uptake constants (Ki), TBRs, and TBR slopes were correlated with clinical measures for bradykinesia, rigidity, tremor, gait disturbance, left-right asymmetry, dementia, and overall disease severity. In PD patients, rate constants for FDOPA uptake correlated with individual measures of bradykinesia (p = 0.001) and gait disability (p less than 0.05). SSM analysis revealed a distinct pattern of regional metabolic asymmetries, which correlated with motor asymmetries (p less than 0.001) and left-right differences in Ki (p less than 0.01). Our data suggest that in PD patients, FDG/PET and FDOPA/PET may provide unique and complementary information about underlying disease processes.
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PMID:The metabolic anatomy of Parkinson's disease: complementary [18F]fluorodeoxyglucose and [18F]fluorodopa positron emission tomographic studies. 211 6

The possibility of inducing Parkinson's syndrome in cats was investigated in three kinds of lesions: by microinjection of 6-hydroxy dopamine (6-OHDA) into the pars compacta of substantia nigra (SNC), bilateral injection into the SNC and globus pallidus (GP) and into the SNC and caput nuclei caudati (NC). In all three kinds of lesions of the dopaminergic system disturbances of behavior involving specially the motor system were obtained, corresponding to the parkinsonism syndrome--in the form of bradykinesia-akinesia, increased muscle tonus of plastic type, vegetative disorders (sialorrhea, pupils) and psychic disorders such as lack of interest in the surroundings and food. The character of the enhanced muscle tonus typical for extrapyramidal disturbances was confirmed by EMG examination. The parkinsonism-like syndrome induced in the cats was transient and receded after several weeks.
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PMID:Parkinson's syndrome induced in cats by the use of 6-hydroxydopamine. Observations of behavior and motor disorders. 213 Jun 49

Despite astounding progress in the biochemical management of Parkinson's disease in particular and of other movement disorders, there are still patients disabled by severe tremor and not by bradykinesia in whom thalamotomy remains the treatment of choice. Though the irreducible complications of surgery must be taken into account, the problems of prolonged multiple drug therapy should not be ignored. The same rationale applies to selected patients with essential or familial tremor. For some patients with ataxic tremor caused by multiple sclerosis and other brain lesions, or with dystonia or, rarely, other movement disorders, thalamotomy may offer limited though significant relief from an otherwise intractable disability. Indications for the use of stereotactic destructive lesions in the treatment of nociceptive pain in those cases where cordotomy and intraspinal morphine infusion are unsuitable have contracted with the introduction of lower-risk alternatives such as intraventricular morphine instillation. When destructive lesions are indicated, the choice will lie between mesencephalic tractotomy, with its higher success rate but irreducible mortality and morbidity, and medial thalamotomy, which, though less risky, is also less effective. For central and deafferentation pain, the same two procedures may be considered. However, destructive lesions are seldom effective for the treatment of the most common element of these pain syndromes: steady burning or dysesthetic pain. They may be more promising, though, for the intermittent, often shooting pain and the evoked elements (hyperpathia and allodynia) of central and deafferentation pain. Even so, it is advisable first to carry out a trial of VC and PVG stimulation before considering a destructive lesion, which should be a last resort.
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PMID:Thalamotomy. 213 73

When used to treat patients with Parkinson's disease pergolide acts at dopamine receptors in the corpus striatum to improve locomotor activity, reducing the tremor, gait disturbances, bradykinesia or akinesia and rigidity experienced by such patients. Treatment with pergolide often allows substantial reductions in concomitant levodopa dosage, and occasionally levodopa can be completely replaced by pergolide therapy in short term use. Pergolide has a long duration of action, thus reducing the wearing-off and end-of-dose phenomena frequently seen with long term levodopa therapy, suppressing fluctuations in levodopa response, and increasing total 'on' time. Despite a lack of well controlled studies comparing this drug with other dopamine agonist agents, pergolide appears to result in adverse effects and anti-Parkinson responses similar to those of bromocriptine and lisuride. Thus, pergolide would appear to be at least as useful as other dopamine agonists such as bromocriptine or lisuride for the management of patients with Parkinson's disease when administered in combination with levodopa. Future research should be directed towards establishing which patients are most likely to benefit from pergolide therapy, and clarifying the relative efficacy and safety of the anti-Parkinsonian drugs available to the clinician. If pergolide does provide clinical benefit when substituted for levodopa-adjunct drugs that are producing less than optimal control, this will be an advantage in a disease area which at present has few therapeutic options.
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PMID:Pergolide. A review of its pharmacological properties and therapeutic potential in Parkinson's disease. 218 10

The DATATOP database, which includes clinical information on 800 patients with early untreated Parkinson's disease (PD), is well suited to explore clinical heterogeneity in PD. Patients with early-onset PD (less than or equal to 40 years, N = 33) reached the same level of disability as the late-onset PD (greater than or equal to 70 years, N = 85) group at a significantly slower rate (2.9 vs. 1.7 years). Early-onset PD patients functioned cognitively better than late-onset PD patients. Bradykinesia, and postural instability and gait difficulty (PIGD), were more common at onset in patients with a rapid rate of disease progression ("malignant PD"; duration of symptoms less than 1 year and Hoehn/Yahr stage of 2.5, N = 11) as compared with those with a relatively slow rate of progression ("benign PD"; duration of symptoms greater than 4 years, N = 65). Comparisons of tremor-dominant PD (mean tremor score/mean PIGD score less than or equal to 1.5, N = 441) with the PIGD-dominant type (mean tremor score/mean PIGD score greater than or equal to 1.0, N = 233) provided support for the existence of clinical subtypes. The PIGD group reported significantly greater subjective intellectual, motor, and occupational impairment than the tremor group. Stage II patients had higher depression scores than stage I patients. Among the patients participating in the DATATOP, older age at onset with bradykinesia, or with the PIGD form of PD, is associated with more functional disability than when the symptoms are dominated by tremor or begin at a younger age.
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PMID:Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. 221 43

Extrapyramidal signs, particularly rigidity and tremor, have been reported in a proportion of patients with dementia of the Alzheimer type. To test the hypothesis that these extrapyramidal signs are similar clinically and neurochemically to the extrapyramidal signs of Parkinson's disease, a group of 20 patients satisfying clinical criteria for probable Alzheimer's disease were studied and assessed clinically for the presence of rigidity, tremor, and bradykinesia. In those patients with extrapyramidal signs, qualitative differences were observed between the signs in these patients and in subjects with Parkinson's disease. Fifteen of 20 patients underwent fluoro-18-dopa scans, which showed no significant difference in fluoro-18-dopa uptake into the caudate and putamen between normal subjects and the rigid and nonrigid patients with Alzheimer's disease, in contrast to the marked reduction in fluoro-18-dopa uptake into the putamen that is observed in Parkinson's disease. This provides clinical and in vivo neurochemical support for the hypothesis that extranigral factors may be involved in the pathogenesis of rigidity in Alzheimer's disease.
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PMID:Clinical and positron emission tomographic studies in the 'extrapyramidal syndrome' of dementia of the Alzheimer type. 225 49

Akinesia refers to failure of willed movement to occur, and bradykinesia refers to slowness of movement that is ongoing. One mechanism of bradykinesia is failure to energize muscles up to the level necessary to complete a movement in a standard amount of time. Akinesia may occur for two possible reasons. One is that the movement is so slow (and so small) that it cannot be seen. A second is that the time needed to initiate the movement becomes excessively long; this can be studied by evaluation of reaction time. One simple factor in prolongation of reaction time is present in patients with rest tremor, who appear to have to wait for a beat of tremor in the agonist muscle of the willed movement in order to initiate the movement. Reaction time studies in patients with Parkinson's disease demonstrate that simple reaction time is delayed, while choice reaction time is normal. Additionally, there does not appear to be any slowness of thinking or difficulty with storage of a motor program. Hence, the difficulty with reaction time in these patients appears to be the time that it takes to execute a motor program. Studies with magnetic stimulation of the motor cortex during the reaction time period seem to support this hypothesis. Slowness of activation of the motor cortex to trigger a movement may well be analogous in mechanism to the slowness of bradykinesia.
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PMID:Clinical neurophysiology of akinesia. 226 21

The GABA/benzodiazepine receptor complex in the basal ganglia of primates treated with the neurotoxin n-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been studied by semi-quantitative autoradiography with [3H]flunitrazepam ([3H]FNZ). Systemic treatment with MPTP produced a stable and lasting parkinsonian condition, with pronounced bradykinesia, akinesia and tremor. In the lateral segment of the globus pallidus (GPL) there was a significant reduction of [3H]FNZ binding compared with non-treated animals. There were no significant changes in the [3H]FNZ binding in the caudate nucleus, putamen and medial globus pallidus (GPM). This suggests that MPTP-treatment increases GABA release within the GPL exclusively. In view of the available evidence suggesting increased striatal output, and reduced unit activity within the GPL of the MPTP-treated primate, it seems likely that the striatal GABAergic output to the GPL is overactive in this model of Parkinson's disease. Furthermore, as there is no evidence for a change in GABA function within the GPM using this measure, the striatal neurones which innervate the GPM may be differentially affected by loss of dopamine innervation. In line with structural evidence and extrastriatal dopamine receptor distribution this suggests that the two striatopallidal systems are functionally heterogeneous. A hemi-parkinsonian primate model has also been used in this study. This model was produced by injection of MPTP directly into one carotid artery. The substantia nigra pars compacta (SNc) was destroyed on the injected side alone, and consequently the appearance of parkinsonian symptoms was confined to the contralateral side. [3H]FNZ binding in the GPL appears to be bilaterally reduced in this model, suggesting an interaction between the treated and non-treated side of the brain. In addition there is increased binding in the putamen and GPM with respect to the non-treated side of the brain. The increased [3H]FNZ binding in the GPM of the unilateral model may be due to the greater disruption of the nigropallidal and/or nigrostiatal dopamine neurones relative to the systemic model. The former would have the effect of uncoupling D1 dopamine receptors located on the terminals of striatal efferents from nigropallidal dopamine input, and as D1 dopamine receptors are implicated in the presynaptic control of GABA release from the terminals of striatal efferents, this would consequently reduce the level of GABA release in the GPM. The latter possibility would suggest that striatopallidal neurones projecting to GPM are more resistant to the effects of dopaminergic denervation than those projecting to GPL.
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PMID:The role of striatopallidal neurones utilizing gamma-aminobutyric acid in the pathophysiology of MPTP-induced parkinsonism in the primate: evidence from [3H]flunitrazepam autoradiography. 228 39


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