Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The long term effects of a de novo treatment with levodopa versus bromocriptine were compared in respectively 13 and 15 previously untreated patients with Parkinson's disease in a prospective randomised trial. Thirteen patients were treated with levodopa alone (mean dose 444, SEM 63 mg daily) whereas 15 others received bromocriptine alone (mean dose 50, SEM 6 mg daily) during 37, SEM 4 and 32, SEM 4 months respectively. For a similar decrease in the Columbia rating scale, the nature of long term side effects was different in the two groups: three patients on levodopa developed peak-dose dyskinesias and one other dystonia. With bromocriptine, one patient developed a severe psychosis whereas 3 others suffered from primary lack of efficacy (1 case) or late decrease in efficacy (2 cases). These results demonstrate the potential of D2 dopamine agonists (like bromocriptine) in the de novo treatment of Parkinson's disease; however, their use is limited by their lack of efficacy and/or the occurrence of neuropsychiatric side effects.
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PMID:A randomised controlled study of bromocriptine versus levodopa in previously untreated Parkinsonian patients: a 3 year follow-up. 266 89

We reviewed the frequency of spontaneous remissions in spasmodic torticollis (ST). One hundred sixteen patients with idiopathic ST (72 F, 44 M) were examined. The age at onset ranged from 9 to 69 (mean, 38.1 +/- 1.3). Twenty-one patients (18%) were Jewish. Eleven patients (9%) had a history of familial dystonia. Remissions longer than 1 year unrelated to treatment were observed in 14 patients (12%) (9 F, 5 M). They occurred in the first year of ST in 13 patients (93%) and in the eighth year in 1. Duration of remissions ranged from 1 to 20 years (mean, 6.5 +/- 1.6). Two patients had three remissions, and another had two. The mean age at the onset of ST in patients with remission was 26.4 +/- 3.3 (SEM) and ranged from 9 to 49. The age at the onset in the patients without remissions was 39.7 +/- 1.4, ranging from 10 to 69 (p less than 0.01). In the remission group, 3 patients were Jewish (21%); in the non-remission group, 18 (18%) were Jewish. There was a familial history in 1 case with remission (7%) and in 10 cases (10%) without remission. Spontaneous remissions in the course of ST seem to be more frequent in patients with early onset, and they occur usually during the first year.
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PMID:Spontaneous remissions in spasmodic torticollis. 395 8

Although trihexyphenidyl has been used effectively for many years in the treatment of Parkinson's disease, little is known about its pharmacokinetics. Using a sensitive radioreceptor assay for anticholinergic drugs, we assayed trihexyphenidyl in human serum and studied its pharmacokinetics following short-term and long-term administration to patients with dystonia. Previously untreated patients had a biphasic semilogarithmic plot of serum concentration-time consisting of an initial rapid distribution phase and a later slower elimination phase. Patients on long-term treatment showed only the slower elimination phase. Elimination followed first-order kinetics and was rapid, with a half-life of 3.7 +/- 0.4 (SEM) hours. There was no relationship between half-life and peak serum level, age, duration of therapy, or etiology or severity of dystonia. Although acute anticholinergic side effects paralleled the rise and fall of serum anticholinergic levels, the response of dystonia did not.
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PMID:Pharmacokinetics of trihexyphenidyl after short-term and long-term administration to dystonic patients. 403 49

A single dose of haloperidol and reduced haloperidol has been found to exacerbate the dystonic response produced by U50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) -cyclohexyl]-benzeacetamide methane sulphonate) in guinea-pigs [8]. The present study sought to correlate the behavioural effect of haloperidol and reduced haloperidol with their effect on inhibition of sigma binding sites in guinea-pig brain using receptor binding and semi-quantitative autoradiography. In the first experiments, groups of guinea-pigs were injected with saline (control, n = 12), haloperidol (0.1 and 1 mg/kg i.p., n = 5) or reduced haloperidol (0.1 and 1 mg/kg i.p., n = 5) 1, 3 and 10 days before, followed by U50,488H (10 mg/kg s.c.) and the effect on the dystonic response rated using a behavioural rating scale [8]. In the second experiments, animals (n = 5) were injected with saline, haloperidol and reduced haloperidol as above and killed 1, 3 and 10 days later, their brains removed, dissected and tissue sections processed for sigma binding site autoradiography using [3H]3-(3-hydroxyphenyl)-N-(n-propyl)piperidine ([3H]-3-PPP). Triplicate tissue sections were wiped using GF/C filters and radioactivity counted. Injection of haloperidol and reduced haloperidol 1, 3 and 10 days earlier exacerbated the dystonic response by decreasing the latency to maximal dystonia and increasing the duration of the response at each dose tested compared with saline-treated animals. These effects of haloperidol and reduced haloperidol on latency and duration were time-related since the effect at 1 > 3 > 10 days. In addition, [3H]-3-PPP binding was inhibited by haloperidol and reduced haloperidol in a dose-and time-related manner. For example, % inhibition of [3H]-3-PPP binding for haloperidol (1 mg/kg) > haloperidol (0.1 mg/kg) and % inhibition of binding (mean +/- SEM) produced by haloperidol (0.1 mg/kg) at 1 (96.1 +/- 2.4) > 3 (74.8 +/- 4.8) > 10 days (36.2 +/- 1.6). Similar results were obtained for haloperidol (1 mg/kg) and reduced haloperidol (0.1 and 1 mg/kg). [3H]-3-PPP autoradiography confirmed these binding data. The results indicate that the exacerbation by sigma ligands of the dystonia produced by U50,488H was associated with the degree of inhibition of [3H]-3-PPP binding.
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PMID:Haloperidol and reduced haloperidol-induced exacerbation of the dystonia produced by the kappa opioid U50,488H in guinea-pigs is associated with inhibition of sigma binding sites: behavioural and autoradiographical studies. 758 12

Preclinical data indicated that seroquel (ICI 204 636), a dibenzothiazepine with 5-HT2 and D2-like receptor antagonistic properties, might be an effective antipsychotic agent, causing fewer extrapyramidal side effects than typical neuroleptics. In the present study, 12 patients suffering from schizophrenia or schizophreniform disorder with predominantly positive symptomatology were treated in an open clinical trial for 4 weeks with seroquel at a maximum dosage of 750 mg/day. The drug was generally well tolerated, and virtually no adverse extrapyramidal side effects such as acute dystonia, parkinsonism or akathisia were observed. Total scores for BPRS (item score 0-6; baseline: 42.0 +/- 2.3; mean +/- SEM), SAPS (64.5 +/- 4.8) and SANS (55.0 +/- 4.3) showed a moderate decrease at the end of treatment (BPRS: 30.0 +/- 3.5; SAPS: 36.1 +/- 6.7; SANS: 42.5 +/- 5.9), when intention-to-treat analysis was applied. There were considerable interindividual differences in treatment response, with some subjects showing almost full remission of positive symptoms, in contrast to about half of the patients who showed no satisfactory clinical improvement. Interestingly, patients showing good antipsychotic response reported slight initial side effects like mild sedation. Prolactin and TSH levels were not altered during seroquel administration. As to pharmaco-EEG investigations, seroquel caused a moderate increase of the absolute power in the alpha, theta, and beta frequency bands, paralleled by a decrease of delta activity. There were no signs of paroxysmal EEG activity under seroquel.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Seroquel (ICI 204 636), a putative "atypical" antipsychotic, in schizophrenia with positive symptomatology: results of an open clinical trial and changes of neuroendocrinological and EEG parameters. 765 71

We performed a prospective study in 21 patients to evaluate the cost of treatment of spasmodic torticollis (cervical dystonia) before and after botulinum toxin type A (BTA) treatment and to assess the impact of BTA treatment on quality of life. Data were recorded for the analysis over a period starting 8 months before and ending 7.2 +/- 0.2 months (mean +/- SEM) after the first injection of BTA. All patients received at least two BTA injections (2.9 +/- 0.2 injections per patient). We studied direct medical costs (drugs, outpatient and inpatient visits, diagnostic procedures, physiotherapy), clinical effects of BTA (clinical rating scale and patient's global assessment), quality of life (French version of the Nottingham Health Profile [NHP]), and adverse reactions. Costs associated with the treatment of spasmodic torticollis before the first BTA injection were 479 +/- 143 French Francs (FF)/patient/month (97 +/- 29 US $/pt/mo). During BTA treatment, costs were 1,126 +/- 147 FF/pt/mo (228 +/- 30 US $/pt/mo), including a mean cost of BTA of 771 +/- 131 FF/pt/mo (157 +/- 27 US $/pt/mo). Treatment with BTA significantly decreased clinical symptoms of spasmodic torticollis and improved the emotional, social, and pain-related domains of the quality of life assessment. Botulinum toxin type A treatment increases the cost of treating spasmodic torticollis but improves quality of life in terms of pain, social, and psychologic functioning in patients with spasmodic torticollis.
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PMID:A pharmacoeconomic evaluation of botulinum toxin in the treatment of spasmodic torticollis. 1102 Jan 24

Deep brain stimulation (DBS) is used to treat a variety of severe medically intractable movement disorders, including Parkinson's disease, tremor and dystonia. There have been few studies examining the effect of chronic DBS on the brains of Parkinson's disease patients. Most of these post mortem studies concluded that chronic DBS caused mild gliosis around the lead track and did not damage brain tissue. There have been no similar histopathological studies on brains from dystonic patients who have undergone DBS. In this study, our objective was to discover whether tissue would be attached to DBS electrodes removed from patients for routine clinical reasons. We hoped that by examining explanted DBS electrodes using scanning (SEM) and/or transmission (TEM) electron microscopy we might visualize any attached tissue and thus understand the electrode-human brain tissue interaction more accurately. Initially, SEM was performed on one control DBS electrode that had not been implanted. Then 21 (one subthalamic nucleus and 20 globus pallidus internus) explanted DBS electrodes were prepared, after fixation in 3% glutaraldehyde, for SEM (n = 9) or TEM (n = 10), or both (n = 2), according to departmental protocol. The electrodes were sourced from two patients with Parkinson's disease, one with myoclonic dystonia, two with cervical dystonia and five with primary generalized dystonia, and had been in situ for 11 and 31 months (Parkinson's disease), 16 months (myoclonic dystonia), 14 and 24 months (cervical dystonia) and 3-24 months (primary generalized dystonia). Our results showed that a foreign body multinucleate giant cell-type reaction was present in all TEM samples and in SEM samples, prewashed to remove surface blood and fibrin, regardless of the diagnosis. Some of the giant cells were >100 microm in diameter and might have originated from either fusion of parenchymal microglia, resident perivascular macrophage precursors and/or monocytes/macrophages invading from the blood stream. The presence of mononuclear macrophages containing lysosomes and sometimes having conspicuous filopodia was detected by TEM. Both types of cell contained highly electron-dense inclusions, which probably represent phagocytosed material. Similar material, the exact nature of which is unknown, was also seen in the vicinity of these cells. This reaction was present irrespective of the duration of implantation and may be a response to the polyurethane component of the electrodes' surface coat. These findings may be relevant to our understanding of the time course of the clinical response to DBS in Parkinson's disease and various forms of dystonia, as well as contributing to the design characteristics of future DBS electrodes.
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PMID:Electron microscopy of tissue adherent to explanted electrodes in dystonia and Parkinson's disease. 1532 56