ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The etiology of Alzheimer disease (AD) is not well understood; therefore, neither prevention strategies nor long-term effective treatment modalities are available for this disease. Based on laboratory and clinical studies, it appears that reactive oxygen species (ROS) and reactive nitrogen species (RNS) that are generated extracellularly and intracellularly by various mechanisms are among the major intermediary risk factors that initiate and promote neurodegeneration in idiopathic AD. Therefore, multiple antioxidant supplements could be useful in the prevention of AD, and as an adjunct to standard therapy in the treatment of AD. The products of inflammatory reactions such as prostaglandins (PGs; PGE1and PGA1), free radicals, cytokines, and complement proteins are neurotoxic. Nonsteroidal antiinflammatory drugs (NSAIDs), which inhibit the synthesis of PGs, reduce the rate of deterioration of cognitive functions in patients with advanced AD. Cholinergic drugs are routinely used in the treatment of AD to improve cognitive functions. Therefore, we propose that a combination of multiple antioxidants and NSAIDs may be more beneficial in the prevention of AD, and that this combination taken together with cholinergic drugs may be more effective in the treatment of AD than the individual agents alone. We also hypothesize that, in idiopathic AD, epigenetic components of neurons such as mitochondria, membranes, other membranous structures, and protein modifications—rather than the genes of neurons—are the primary targets for the action of neurotoxins including free radicals. In some familial AD, mutations in amyloid precursor protein and presenilins are associated with the risk of early onset of this disease; however, their mechanisms of action are not fully understood.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

We reviewed 36 reported psychiatric patients who were treated with a combination of electroconvulsive therapy (ECT) and clozapine. The indication of the ECT-clozapine treatment was resistance to classical antipsychotic agents, clozapine, or ECT alone. Sixty-seven percent of the patients benefited from the combined treatment. In most of the patients, the combined treatment was safe and well tolerated. Adverse reactions occurred in 16.6% of the patients and included prolonged ECT-induced seizures (one case), supraventricular (one case) and sinus tachycardia, and blood pressure elevation. It seems that combined ECT-clozapine treatment is effective and safe. This strategy may be a therapeutic option in treatment-resistant patients.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The present randomized, double-blind, placebo and active-drug controlled, crossover study assessed residual sedation after zaleplon 10 mg, flurazepam 30 mg (as an active control), and placebo, taken during a nocturnal awakening in patients with sleep maintenance insomnia. Twenty-two healthy sleep maintenance insomniacs (11 men; mean age, 42 y) received zaleplon, flurazepam, or placebo after an experimental awakening 3.5 hours after bedtime on two consecutive nights in each of three conditions. Residual sedation was measured with sleep latency testing (5 and 6.5 h postdrug), digit symbol substitution, symbol copying, and subjective sleepiness by visual analog scale, each twice each morning. Zaleplon did not differ from placebo on any measure of residual sedation; flurazepam showed significant sedation on all measures. No residual sedative effects were detected 5 or 6.5 hours after ingestion of zaleplon during the middle of the night by sleep maintenance insomniacs.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The goal of this study was to examine the multiple-dose pharmacokinetics of selegiline and its metabolites desmethylselegiline, l-methamphetamine, and l-amphetamine after oral administration of selegiline HCl. Twelve healthy volunteers received 10 mg of selegiline HCl once daily for 8 days. The pharmacokinetic profiles of selegiline and the metabolites were examined from serum samples for 24 hours (i.e., the dosing interval, &tgr;) on days 1, 4, and 8. The results indicated significant apparent accumulation of selegiline and desmethylselegiline during the 8-day period of selegiline administration. The AUC&tgr;s of selegiline and desmethylselegiline were increased 2.7 fold (p< 0.001) and 1.5 fold (p< 0.001), respectively, from day 1 to day 8. However, the half-lives of selegiline (range, 1.5–3.5 h) and desmethylselegiline (range, 3.4–5.3 h) were found to be relatively short. Accordingly, the short half-lives of these compounds failed to predict the apparent accumulation. With both of the l-amphetamine metabolites of selegiline, steady state was reached by day 4. We suggest that the most likely explanation for the apparent accumulation of selegiline and desmethylselegiline was the saturation of the MAO-B binding sites in tissues, although decreased first-pass metabolism of selegiline cannot be ruled out. The observed increase in selegiline and desmethylselegiline concentrations on multiple dosing is not likely to significantly increase the pharmacodynamic effect or adverse effects of selegiline compared with what has been found after a single 10-mg dose.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Patients with Parkinson's disease (PD) in long-term levodopa therapy often complain of worsening of motor symptoms in the afternoon and evening. The pathophysiology of this phenomenon is not known. We evaluated the motor response to repeated doses of levodopa during a 12-hour period in 52 parkinsonian patients (19de novo,20 stable, and 13 wearing-off). On the day of the study, all patients received standard doses of levodopa/carbidopa at 8:00 a.m., 12:00 noon, and 4:00 p.m. Motor measurements such as tapping test, walking time, and tremor score, and blood samples for levodopa and 3-O-methyldopa (3OMD) plasma analysis, were performed hourly. Mean motor scores and pharmacokinetic data, evaluated for a period of 3 hours after each levodopa dose, were compared. Inde novopatients, we did not observe diurnal changes in motor score, whereas a progressive daytime worsening was visible in stable and wearing-off patients. No significant difference in levodopa pharmacokinetics after each levodopa dose was observed within each patient group, whereas 3OMD plasma levels significantly increased with repeated levodopa administrations. However, no significant correlation between motor scores and 3OMD plasma levels was observed, suggesting that the diminishing motor response to afternoon and evening doses of levodopa in patients in long-term levodopa therapy does not relate to the pharmacokinetics of the drug. It is possible that this phenomenon may be an expression of the occurrence of tolerance to repeated doses of levodopa.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

CALM-PD (Comparison of the agonist pramipexole with levodopa on motor complications of Parkinson's disease) is a randomized, multicenter, double-blind, controlled clinical trial designed to compare the policy of initial treatment of pramipexole with the policy of initial treatment with levodopa in early, symptomatic Parkinson's disease with regard to the development of dopaminergic motor complications. At 22 American and Canadian sites, 301 eligible subjects requiring antiparkinsonian therapy to treat emerging disability were enrolled in CALM-PD and randomized to (i) active pramipexole and placebo levodopa or (ii) placebo pramipexole and active levodopa. Subjects are being evaluated systematically at regular intervals during a 23.5-month period to determine if and when dopaminergic motor complications (wearing off, dyskinesias, “on-off” effects) occur. In addition, quality-of-life outcomes, economic outcomes, and functional imaging outcomes are being assessed in standard fashion with [123I]&bgr;-CIT and SPECT imaging throughout the trial. The study design contains many provisions to approximate routine clinical practice and to produce data about clinical effectiveness, tolerability, and cost to facilitate the evidence-based practice of neurology.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

To evaluate the efficacy and safety of gabapentin in the treatment of muscle cramps, we engaged an open-label trial with a group of 30 patients with frequent (>5 cramps/week), stable, long-lasting cramps, associated with different diseases. Gabapentin was effective in reducing the frequency and severity of muscle cramps and associated sleep disturbances (clinical outcome measures) within the first 2 weeks of medication at 600 mg/d. At the 1 month control (mean dosage, 825 ± 35 mg), almost every patient had responded to treatment and two thirds experienced a total remission of symptoms. After 3 months of therapy (mean dosage, 892 ± 180 mg), cramps disappeared in 100% of patients and this benefit persisted as long as 6 months. Additionally, we evaluated in 10 patients the Cramps Threshold Frequency (CTF) (neurophysiological outcome measure) before and during gabapentin treatment. Gabapentin significantly increased the CTF, returning it to normal values. With the limitation of an open-label methodology, our clinical and neurophysiologic experience suggests that a gabapentin dose of 600–1200 mg/d would be helpful in the treatment of muscular cramps.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Huntington's disease (HD) is characterized by the presence of hyperkinesias, but bradykinesia is also present in most patients. We studied the motor performance of 18 patients with genetically proven HD (age, 38.5 ± 10 y; clinical stage, 1.7 ± 1.7; (CAG) triplet length, 49.2 ± 6.8 triplets; all but three patients were free from neuroleptics) and compared with a control group (n = 18) and with a typical Parkinson's disease (PD) group (n = 20). Motor study included the four timed tests commonly used for PD : Pronation-supination (PS), finger dexterity (FD), movement between two points (MTP) and walking test (WT). Tests were done at 9 AM. The PD group was studied in “off” condition, with no medication given for 12 hours. The HD group was slower than the controls on all tasks (all tests significant,p< 0.01, Mann-Whitney U test) and even slower than PD group (for FD,p< 0.05). A significant correlation was found between each test and clinical stage (for PS, r = 0.84; for FD, r = 0.75; for MTP, r = 087, and for WT, r = 0.77, Pearson). Severe bradykinesia was present in HD, and motor impairment is related to clinical stage.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

We report the case of a patient with postherpetic neuralgia who developed asterixis while being treated with gabapentin. We discuss the possible mechanism of asterixis in this patient.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID