摘要:

Summary:A dose‐response study of the effects of entacapone on the pharmacokinetics and metabolism of levodopa and on the clinical response to levodopa was carried out in 20 parkinsonian patients with levodopa‐related fluctuations. A randomized, double‐blind, single‐graded‐dose, crossover design of five 1‐day treatment periods each 1 week apart was used. Entacapone (50, 100, 200, or 400 mg) or placebo was given at 8 a.m. with the patient's individual dose of levodopa/dopa decarboxylase inhibitor. The inhibition of soluble catechol‐O‐methyltransferase (S‐COMT) in red blood cells (RBCs) and plasma concentrations of levodopa, its metabolites, and entacapone were measured and motor responses were quantified at 30‐min intervals using the motor part of the Unified Parkinson's Disease Rating Scale. Entacapone brought about a dose‐dependent decrease in S‐COMT activity in the RBCs, maximally by 48% at 400 mg. With a 200‐mg dose of entacapone, the area under the plasma concentration‐time curve (AUC) and half‐life of levodopa increased (p < 0.001); the AUCs of 3‐O‐methyldopa and homovanillic acid decreased (p = 0.01 and p < 0.001, respectively) and that of 3,4‐dihydroxyphenylacetic acid increased (p < 0.001). Entacapone prolonged the duration of the motor response to levodopa by 33 min (p = 0.04) and dyskinesias by 45 min (p = 0.003) without affecting their magnitude; the highest increase in duration of these responses occurred with 200 mg of entacapone. Thus, on pharmacokinetic and clinical grounds, the 200‐mg dose of entacapone was the most effective. Doserelated responses to entacapone demonstrated its value in the treatment of parkinsonian patients with levodopa‐related fluctuations by prolonging the antiparkinsonian response to the levodopa dose.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Thirty‐one patients, aged 12.6 ± 5.6 years, with refractory seizures for 8 ± 4.3 years, were treated with adjunctive vigabatrin. Twenty‐four percent had a >50% reduction in seizure frequency (95% one‐sided confidence interval). Generalized myoclonic, atonic, and tonic clonic and partial, with and without secondary generalization, seizures were all reduced at a mean dose of 70 ± 38 mg/kg/day. Comparison of vigabatrin therapy duration, for partial and generalized seizure groups, utilizing Kaplan‐Meier methodology showed similar survival times. Vigabatrin therapy was ineffective in the four children with tuberous sclerosis. Transient somnolence, ataxia and dizziness were the most frequent side effects. A severe aggressive agitation occurred in three patients, and necessitated discontinuation of vigabatrin in one patient. Vigabatrin was as effective in generalized as in partial seizures in this study. Clinical utility may be limited by unacceptable behavioral side effects in some patients.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Interest in the association of obsessive‐compulsive (OC) symptoms and schizophrenia has been reawakened since the introduction of clozapine for treatment of schizophrenia. We describe the appearance of this disorder and examine the efficacy of adding fluvoxamine to ongoing clozapine treatment of the OC and schizophrenic symptoms. Four patients with DSM‐III‐R schizophrenic disorder, in whom OC symptoms appeared during the course of clozapine treatment, are reported. In two patients, fluvoxamine, a serotonin‐selective reuptake inhibitor (SSRI), was added to clozapine under open‐trial conditions. The patients were serially assessed by using the Brief Psychiatric Rating Scale, Yale‐Brown Obsessive‐Compulsive Scale, and Scale for the Assessment of Negative Symptoms. The de novo occurrence and eventual spontaneous reduction of OC symptoms were noted in two schizophrenic patients treated with clozapine. In the other two patients, one with previous and the other with a family history of OC disorder, the addition of fluvoxamine to clozapine was effective in eliminating the OC symptoms. A concomitant improvement in the schizophrenic symptomatology was seen as well. It appears that disabling OC symptoms may occur as in response to clozapine treatment in chronic drug‐resistant schizophrenic patients. Some of the latter may benefit from the addition of an SSRI to the ongoing clozapine regimen.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Forty‐four patients with disabling writer's cramp (WC) and one with a musician's cramp were treated with botulinum toxin (BT) injections for a mean period of 12 (range, 3‐48) months.The forearm muscles causing the dystonic position were identified by inspection while writing; BT was then administered under electromyographic (EMG) guidance. The degree of improvement in writing and amelioration of pain were rated with self‐assessment scales. Patients reported significant improvement in writing after 56% treatment sessions (TS) and in pain after 62% TS. Mild weakness occurred after 32% TS. Twenty‐nine patients discontinued treatment, generally after the initial BT injection. In 16 patients who remained on treatment with a mean follow‐up of 21 (range, 3‐48) months, the improvement in writing and pain was present after 76 and 79% of the TS, respectively. We conclude that BT injections offered a worthwhile and sustained functional improvement to 36% of our patients with WC.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Previous polysomnographic (PSG) investigations have reported a rhythmic electromyographic (EMG) pattern (0.5‐3.0 cps) of leg movement activity in a subset of patients with neuroleptic‐induced akathisia (NIA). It has been suggested that this EMG pattern may represent a pathophysiological correlate of NIA and thus have clinical utility as an objective marker for this condition. We present preliminary measures of sensitivity and specificity for this EMG pattern as a diagnostic marker for NIA for 26 neuroleptic‐treated patients. The EMG marker yielded a diagnostic sensitivity of 68.9% and a specificity of 70.0%, falling just short of statistical significance (Fisher's exact test p = 0.06). Quantitative analysis of the EMG pattern revealed a significant positive correlation between the percentage of time the NIA marker occurred during wakefulness and corresponding chlorpromazine equivalent levels. Clinical demographic findings for true‐positive, false‐positive, true‐negative, and false‐negative groups are discussed. Overall findings suggest that this particular pattern of EMG marker activity observed in neuroleptic‐treated patients during PSG and EMG studies is valuable in facilitating the diagnosis and monitoring treatment of NIA.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Zolpidem was evaluated in this double‐blind, randomized, placebocontrolled study for efficacy and safety in patients with short‐term insomnia related to problems with work, marriage, family, or financial matters. One hundred and thirty‐eight patients ranging in age from 20 to 55 years were evaluated for safety. Of these, 136 patients were included in the analysis of efficacy. Patients received zolpidem 10 mg or placebo nightly for 7‐10 nights. Patients completed a morning questionnaire daily, reported their global impressions of therapy, and completed a Profile of Mood States (POMS) at the start and end of the study. Nine patients (three zolpidem and six placebo) discontinued before completing the study; three (one zolpidem and two placebo) due to adverse events. Compared to placebo, zolpidem significantly reduced subjective latency to sleep on all nights of treatment and patients rated that falling asleep was easier with zolpidem than with placebo (p < 0.01) throughout the study. Compared to placebo, the zolpidem‐treated patients reported longer total sleep time, fewer awakenings after sleep onset, shorter time spent awake after sleep onset and better quality of sleep. All of these differences were significant during at least part of the study. No morning sleepiness or impairment in the ability to concentrate were recorded among patients taking zolpidem. Each item on the patient's global impression of zolpidem therapy was rated significantly better than that of placebo. No changes in mood (including anxiety) were detected using the POMS scale. Side effects occurred with a similar frequency in the zolpidem and placebo groups. Zolpidem was found to be more effective than placebo and was well tolerated in the management of stress‐induced short‐term insomnia.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Histaminergic projections innervate brain areas implicated in the pathophysiology of schizophrenia. In a previous open‐label study, there was the suggestion that famotidine, an H2histamine‐receptor antagonist, possessed adjuvant therapeutic properties when added to the stable neuroleptic medication regimens of 10 treatment‐refractory patients. In that study, the maximal dosage of famotidine was limited to 40 mg/day, the recommended maximal dosage for the treatment of peptic ulcer disease. In this study, we examined 18 patients fulfilling DSM‐III‐R criteria for schizophrenia and schizoaffective disorder who had famotidine (100 mg/day) added to their stable neuroleptic medication regimen. Patients were rated on baseline, weekly thereafter, and 1 week after famotidine discontinuation, by using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Assessment of Negative Symptoms (SANS), and the Clinical Global Impression (CGI). On all of these outcome measures, statistically significant improvements suggestive of a beneficial adjunctive effect of famotidine were found. Famotidine (100 mg/day) was well tolerated by the study subjects. There was a wide range of famotidine blood levels achieved at the end of 3 weeks of famotidine adjunctive treatment, but these blood levels did not correlate with BPRS or SANS scores changes. However, the patients with the greatest improvement in BPRS scores (and without concomitant deterioration in SANS scores) had some of the higher famotidine levels found in the study. Double‐blind studies further assessing the potential adjunctive benefit of famotidine in the treatment of schizophrenia are indicated.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Asterixis (flapping tremor) can be induced by treatment with psychopharmacologic agents. We observed 10 cases of asterixis in psychiatric inpatients, most with affective spectrum disorders being treated with combination therapy. The drugs most often used were clozapine (eight cases), lithium (seven cases), and carbamazepine (seven cases). There were neither metabolic disorders nor structural brain lesions that might explain the occurrence of asterixis. Because dosage in general was moderate and serum levels were within therapeutic boundaries in most cases, the symptom seemed to have been caused by an interaction of drugs rather than by a single agent. Therefore clozapine, carbamazepine, and lithium should be combined with each other only with great care.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:A 67‐year‐old man with bipolar disorder developed a Creutzfeldt‐Jakob like syndrome during lithium carbonate treatment. Lithium serum level was within the therapeutic range. Complete clinical‐electroencephalographic recovery was achieved after lithium therapy was discontinued. Several cases of lithium‐induced Creutzfeldt‐Jakob syndrome have been reported to date; all of them were elderly patients and a half had “therapeutic” lithium serum levels. Patients in this age group receiving antimanic maintenance treatment should keep lithium serum levels as low as possible. Lithium neurotoxicity should be considered in Creutzfeldt‐Jakob disease differential diagnosis, serial electroencephalograms being the most valuable.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Oxidant stress resulting from excess dopamine (DA) may contribute to the development and progression of Parkinson's disease (PD). Free radicals resulting from the enzymatic metabolism of DA are most often discussed in this regard. However, levodopa (L‐DOPA) and DA can also undergo autooxidation, producing free radicals as well as cytotoxic metabolites. We evaluated the neurotoxic effects of the two stereoisomers of L‐DOPA to differentiate between enzyme‐mediated and autooxidation mechanisms. Various concentrations of D‐ or L‐DOPA (1 mMthrough 10 nM) were added to freshly harvested rostral mesencephalic tegmentum cultures. After 72 h, the cultures were fixed and stained for tyrosine hydroxylase (TH). The number of THimmunoreactive (THir) neurons was then assessed and used as an index of DA neuron survival. Both D‐ and L‐DOPA induced a dose‐dependent loss of THir neurons (F10,21= 135.75, p < 0.0001 andF10,21= 142.53, p < 0.0001, respectively) with ED50values of 10‐5.3and 10‐5.2M, respectively. The doseresponse curves for each drug were not significantly different from one another (F1,43= 0.09, p > 0.05). Moreover, both drugs killed THir as well as non‐THir cells at high concentrations, suggesting a nonspecific toxic effect. These data are most consistent with an enzyme‐independent, autooxidation‐mediated mechanism for DA neuron loss.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID