Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics and clinical effects of apomorphine after rectal administration were determined in five patients with idiopathic Parkinson's disease (PD). Three different pharmaceutical formulations were tested: a rectal solution of apomorphine (10 or 15 mg), a gelatin suppository (25 and 50 mg), and a Witepsol-H15 suppository (50 and 100 mg). The pharmacokinetics of apomorphine were determined by measuring plasma concentrations using a sensitive and specific high-performance liquid chromatography method. The mean bioavailability varied between 14.7% and 40.2%, which was the bioavailability until the end of clinical benefit. Also, despite the differences in dose, the values of the Cmax were similar, with average values of 12.7-25.6 ng/ml. Wide differences in Tmax were observed, with values varying between 16 min for the enema and 127.5 min for the Witepsol-H15 100-mg suppository. The time course of the clinical effect was determined by assessing the time needed for walking a 25-m course and by calculating a tremor and dyskinesia score. Onset of effect was similar for each of the preparations, with an average onset time of 14-28 min. Significant differences with respect to the duration of the effect were observed. The duration of effect after administration of the Witepsol-H15 100-mg suppository was 156 +/- 43 min versus 50 +/- 13 min after rectal administration of the apomorphine solution. These results show that rectal administration of apomorphine may present an alternative to subcutaneous administration. The sustained-release properties of the Witepsol-H15 suppositories are especially of interest in the treatment of on-off fluctuations in PD.
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PMID:Pharmacokinetics and clinical efficacy of rectal apomorphine in patients with Parkinson's disease: a study of five different suppositories. 756 22

Neuroleptic-induced extrapyramidal side effects (EPS) were evaluated in 92 patients treated with clozapine for the first time and 59 patients treated with haloperidol followed in a drug monitoring program. Side effects were measured by the Columbia University Rating Scale, the Simpson Dyskinesia Scale and the Hillside Akathisia Scale. The cumulative incidence rate for tremor was found to be 24.4% in the clozapine group and 39.3% in the haloperidol group. This did not amount to a statistically significant group difference. Bradykinesia was observed in 21.8% of the patients treated with clozapine and in 47.7% of the patients of haloperidol (P = 0.011). In the clozapine group the akathisia incidence rate was 5.6%, whereas haloperidol patients showed a higher rate of 31.7% (P = 0.005). Our results show higher incidence rates of tremor and bradykinesia during clozapine treatment than previous studies. We conclude that clozapine is not entirely free of EPS, but they are usually less severe and of a different quality than side effects induced by typical antipsychotics.
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PMID:Extrapyramidal side effects of clozapine and haloperidol. 759 22

Determinations of biopterin (BP), homovanilic acid (HVA), glutamic acid (GTA), and glutamine (GT) levels in cerebrospinal fluid (CSF) obtained through a lumbar tap were performed in 20 parkinsonian patients in different stages of evolution and without medication. In patients with motor symptoms not related to Parkinson's disease (dystonia, dyskinesia and essential tremor) (n = 4). In 7 other neurological patients subjected to spinal tap for diagnostic procedures neurotransmitters were also determined and taken as control groups. In 14 of the patients with Parkinson's disease, the symptoms were evaluated using conventional scales (UPDS, NYPDS, NWPDS, Schwab and England, and Hoehn and Yahr scale). The amplitude and the frequency of tremor were quantitatively evaluated through a single plane accelerometer Grass SP-1, akinesia was measured through reaction time to auditory stimuli, and rigidity through the speed of lineal movement. Evaluations were performed with the patient not on any medication for 1 week and repeated 1 h after the intake of 250 mg of 200/50 L-dopa/carbidopa preparation (Sinemet) and on a different day after the intake of biperiden (Akineton) 6 mg/day. Differences in neurotransmitter or metabolites levels between Parkinson's disease and control groups were determined through an independent Student's t test. Correlation between severity of symptoms in the scales and for each individual symptom measured through the quantitative tests and the levels of neurotransmitters in CSF were evaluated through the Pearson correlation analysis test. Modifications in the motor performance after administration of Sinemet and Akineton, and the levels of neurotransmitters were indirectly determined. RESULTS. (1) There were significant differences between the levels of BP and GT in patients with Parkinson's disease and control groups, (2) lower GTA levels correlated with more severe rigidity and akinesia, and with the best response to the administration of L-dopa and may be an important marker for prognosis, and (3) lower levels of GT correlated with least akinesia, but not with tremor, which may indicate that the akinesia depends on other biochemical abnormalities besides dopamine depletion.
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PMID:Neurotransmitter levels in cerebrospinal fluid in relation to severity of symptoms and response to medical therapy in Parkinson's disease. 763 Oct 94

In the past, stereotactic surgical intervention for Parkinson's disease was considered indicated only in those patients with active motor manifestations that were refractory to pharmacological therapy, manifestations such as tremor, rigidity, dystonia, and dyskinesia. With the reintroduction and refinement of Leksell's posteroventral pallidotomy, both akinetic and hyperkinetic symptoms are now amenable to surgical treatment. We have analyzed the results of 126 patients who underwent either unilateral (n = 58) or bilateral (n = 68) posteroventral pallidotomies. The Unified Parkinson's Disease Rating Scale and Hoehn and Yahr Staging Scale were used for preoperative and postoperative objective assessments. Postoperative follow-up evaluation occurred initially at 1 week and subsequently at intervals between 1 and 12 months (mean = 4.5 months) after surgery. Although individual motor subscores on the Unified Parkinson's Disease Rating Scale were significantly reduced (n = 126, P < or = 0.01), the most dramatic findings were the reversal of akinetic symptoms and the elimination of dyskinesia and profound "off" periods. These clinical results, combined with intraoperative microelectrode records revealing pallidal neuronal hyperactivity, suggest a reconsideration of the pathophysiology of akinesia and point to possible mechanisms of akinesia improvement by posteroventral pallidotomy in some parkinsonian subgroups.
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PMID:The results, indications, and physiology of posteroventral pallidotomy for patients with Parkinson's disease. 764 96

Two adult men, aged 86 and 63, with essential tremor and Parkinson's-disease-related tremor, respectively, were provided Behavioral Relaxation Training in reclined and upright seated positions. Multiple measures were recorded, including the Behavioral Relaxation Scale (BRS), clinical and self-rated tremor severity, informant ratings, ratings of disability in activities of daily living (ADL), and forearm EMG. Results showed increased relaxation skills on the BRS, with reductions in EMG, tremor ratings, and some ADL disabilities. Upright BRS scores did not change during reclined training, but improved rapidly during upright training. The second man was found to suffer from dyskinesia when he relaxed during baseline, which declined markedly during training. A two-week follow-up indicated that most improvements were maintained by both men. Statistical analyses of data for each man showed significant changes. These results suggest that relaxation may be useful in the treatment of idiopathic and pathologic tremor disorders in older adults.
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PMID:Behavioral relaxation training for tremor disorders in older adults. 766 49

Motor disorders affecting the orofacial musculature include bruxism, chronic orofacial muscle pain affecting the jaw and neck muscles and the involuntary waking period disorders such as orofacial dyskinesia, oral mandibular dystonia, tremor and others. Research at UCLA has touched these and many other areas. Current results have indicated the usefulness of contingent afferent electrical stimulation of the lip to control bruxism; provided information regarding the fatigue, endurance and recovery faculties of the protrusive jaw muscles; explored the issue of chronic muscle hyperactivity inducing headache pain; and worked with botulin toxin as a method to treat orofacial dystonia and dyskinesia.
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PMID:Oral motor disorders in humans. 768 5

Eighteen patients with medically intractable Parkinson's disease that was characterized by bradykinesia, rigidity, and marked "on-off" fluctuations underwent stereotactic ventral pallidotomy under local anesthesia. Targeting was aided by anatomic coordinates derived from the MRI, intraoperative cell recordings, and electrical stimulation prior to lesioning. A nonsurgically treated group of seven similarly affected individuals was also followed. Assessment of motor function was made at baseline and at 3-month intervals for 1 year. Following the lesioning, patients improved in bradykinesia, rigidity, resting tremor, and balance with resolution of medication-induced contralateral dyskinesia. When compared with preoperative baseline, all quantifiable test scores after surgery improved significantly with the patients off medications for 12 hours: UPDRS by 65%, and CAPIT subtest scores on the contralateral limb by 38.2% and the ipsilateral limb by 24.2%. Walk scores improved by 45%. Medication requirements were unchanged, but the patients who had had surgery were able to tolerate larger doses because of reduced dyskinesia. Ventral pallidotomy produces statistically significant reduction in parkinsonism and contralateral "on" dyskinesia without morbidity or mortality and with a short hospitalization in Parkinson's disease patients for whom medical therapy has failed.
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PMID:Stereotactic ventral pallidotomy for Parkinson's disease. 772 66

L-Dopa pioneered the symptomatic therapy of Parkinson's disease. While this treatment proved effective in the treatment of parkinsonian akinesia, rigidity and tremor, prolonged L-dopa treatment was often noted to result in dyskinesia, psychosis and 'on-off' phenomena. This increasing disability of L-Dopa-treated parkinsonian patients, however, is not correlated with the duration of L-dopa treatment. Mortality due to Parkinson's disease has decreased significantly after the introduction of L-dopa treatment. The development of D1-selective dopamine agonists and the introduction of neuroprotective rather than symptomatic therapy are required for treating Parkinson's disease.
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PMID:Dilemma in the treatment of Parkinson's disease with L-dopa. 782 30

The diagnosis and treatment of juvenile parkinsonism (JP) is described. There was a high incidence of familial JP (58.1%), and its inheritance pattern was usually an autosomal recessive type. The patients with JP presented with improvement of parkinsonian symptoms following sleep and dystonic posture of the feet as specific signs. The tremor was a fine postural, and impairment of postural reflex was prominent. In the treatment of JP, it is important to control the wearing-off phenomenon and the dopa-induced choreic dyskinesia usually occurring in the extremities. A small dose of levodopa with decarboxylase inhibitor has to be carefully administered several times a day. The clinical course of JP is very slowly progressive compared with that of Parkinson's disease.
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PMID:[Progress in diagnosis and treatment of juvenile parkinsonism]. 790 87

To determine whether tolerance to the antiparkinsonian actions of levodopa develops during longterm levodopa therapy, we compared the response to 2-hour levodopa infusions before and after 2- to 4-day levodopa holidays using tapping and walking speeds and tremor/dyskinesia scores as measures of response in 17 parkinsonian patients with a fluctuating response to levodopa. As expected, motor function deteriorated during the levodopa holiday, but the maximum motor tapping and walking speeds and dyskinesia scores produced by the levodopa infusion before the holiday were the same as those produced by the infusion after the holiday. Because the baseline motor function was lower after the holiday, the increment in tapping and walking speeds (ie, the difference between the baseline and the maximum response) was larger with the postholiday infusion (p < 0.01). The postholiday infusion produced a longer response than did the preholiday infusion as measured by tapping score (p = 0.047), walking speed (p = 0.02), and tremor or dyskinesia scores (p = 0.02). The prolongation of the response was greater in patients receiving larger daily doses of levodopa (r = 0.55; p = 0.03). These changes in the duration of response suggest that progressive shortening of the response to levodopa during long-term therapy is partially caused by development of tolerance to levodopa and not just by loss of dopamine storage sites. Tolerance to levodopa should be considered in establishing oral dosing regimens and in developing new strategies for drug delivery.
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PMID:Effect of brief levodopa holidays on the short-duration response to levodopa: evidence for tolerance to the antiparkinsonian effects. 793 85


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