摘要:

We tested a novel preparation of sublingual apomorphine hydrochloride (APO) in 10 patients with advanced Parkinson's disease complicated by motor fluctuations and dyskinesias. After dose titration, patients underwent a blinded comparison of APO versus placebo, and an unblinded comparison of APO versus optimally dosed carbidopa/levodopa using timed tapping and walking paradigms. APO was significantly better than placebo in both measures: Tapping speed was 30.8% faster than with placebo (p< .0005), and ambulation speed was 45.2% faster than with placebo (p< .05). Ambulation speed with APO was also 15.9% faster than that with optimal doses of carbidopa/levodopa (p< .05). The latency to onset of clinical improvement with each APO dose was 10 to 40 minutes, and the duration of effect was 60 to 130 minutes. Adverse events included nausea, orthostatic hypotension, and disagreeable taste in the patient's mouth. Aside from the bitter taste, all other side effects resolved with continued use and did not limit dosing in any case. We feel that the good short-term efficacy and tolerability demonstrated in this study warrant further study of this new preparation, as there are several potential advantages of sublingual administration compared with traditional APO preparations.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Three-hundred fifty-two randomly selected residents, aged over 65 years, of 42 representative long-term care institutions in a defined geographic area of southwestern France, were assessed for demographic characteristics, drug intake, and motor and cognitive status. Neuroleptic drug intake is described and demographic variables and motor and cognitive status are analyzed according to exposure to neuroleptics and presence of parkinsonism. Exposure to neuroleptics was considered as a “risk factor” for parkinsonism, and the risk (proportion) of parkinsonism attributable to neuroleptics calculated. Twenty-one percent of subjects were exposed to neuroleptics, of whom 27% took more than one. Subjects taking neuroleptics were significantly younger and more cognitively impaired. About 30% of subjects taking neuroleptics had parkinsonism (6.25% of the sample). Postural and action tremors were more frequent than resting tremor, and asymmetry of parkinsonian signs was found in 25%. The mean dosage taken by exposed subjects with parkinsonism was found to be twice that of those without. The proportion of cases of parkinsonism attributable to neuroleptics in institutions was 19%. Our results clearly show that neuroleptic drug use in institutionalized elderly persons is associated with a high risk for parkinsonism.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The present study was undertaken to investigate whether or not radical scavengers can inhibit platelet aggregation in humans. Toward this end, nicaraven was selected for this study because it has been shown to specifically scavenge hydroxyl radicals that are implicated in platelet aggregation. Ten healthy volunteers and 10 patients with cerebral thrombosis were enrolled in this study. The antiplatelet activitiesin vitroof nicaraven were examined. The concentrations of nicaraven tested were 3.50 ± 10−5mol/L, 1.75 10−4mol/L, 3.50 ± 10−4mol/L, and 1.75 ± 10−3mol/L, respectively. The maximum aggregation rate induced by adenosinc diphosphate (ADP) was significantly inhibited by nicaraven at concentration ranges of 3.50 ± 10−4mol/L or higher in the healthy volunteer platelets. The maximum aggregation rate induced by collagen was significantly inhibited by 1.75 ± 10−3mol/L of nicaraven. Using platelets from patients with cerebral thrombosis, the maximum aggregation rate induced by ADP was significantly inhibited by 1.75 ± 10−3mol/L of nicaraven. Furthermore, the maximum aggregation rate induced by collagen were significantly reduced by 1.75 ± 10−3mol/L of nicaraven. Nicaraven induces dose-dependent inhibition of platelet aggregation in both healthy volunteers and patients with cerebral thrombosis.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Incidental case reports suggest that some parkinsonian patients treated with dopamincrgic drugs complain of drowsiness but few controlled data are available. We compared the sedative effects of L-Dopa (200 mg + 50 mg benserazide, PO), triazolam (0.125 mg) and placebo in a randomized double-blind cross-over design in 22 healthy volunteers pretreated with domperidonc (60 mg/day). Drowsiness was assessed using a visual analog scale (VAS), a computerized choice reaction time test (CRT) and an electro-oculogram (EOG). L-Dopa and triazolam induced significant drowsiness, compared to placebo, on VAS, CRT and some EOG parameters. After this first evaluation session, all subjects were chronically treated for 11 days with 600 mg/d of L-Dopa. Drowsiness induced by L-Dopa, triazolam or placebo was then tested again on three consecutive days to assess putative dopaminergic tolerance. After chronic L-Dopa treatment, triazolam-induced sedation remained unchanged while L-Dopa sedative effects were no longer significant except on the VAS, preventing the conclusion that tolerance occurred. These data suggest that an acute dose of L-Dopa induces sedation in L-Dopa-naive subjects. This sedative effect must be considered in clinical practice and when studying the effects of L-Dopa on motor or neuropsychological performance, especially in acute tests.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Tolcapone, a central and peripheral catechol O-methyltransferase (COMT) inhibitor, reduces the conversion of L-Dopa into 3-O-methyl-Dopa (3-OMD), thus leading to more stable and sustained L-Dopa plasma levels. This study was designed to evaluate the effects of acute and 6-week tolcapone administration on L-Dopa pharmacokinetics and pharmacodynamics in Parkinson's disease (PD) patients with predictable motor fluctuations. Tapping test, walking time, and tremor, as well as L-Dopa and 3-OMD plasma levels, were assessed before and for 5 hours after the administration of a single L-Dopa dose, alone or in combination with 200 mg tolcapone, in seven patients with PD. This clinical and pharmacokinetic study was repeated after 6 weeks of tolcapone therapy (200 mg three times daily). It was observed that tolcapone, after both acute and chronic administration, prolonged the motor improvement induced by L-Dopa. As a result, at week 6 of tolcapone therapy, the daily hours spent “off were significantly decreased. Tolcapone significantly increased the area under the curve of L-Dopa plasma levels by slowing down the elimination of L-Dopa from plasma, whereas the maximal concentration of L-Dopa was not modified. 3-OMD levels decreased significantly after acute tolcapone administration, and after 6 weeks of tolcapone therapy, they were approximately one sixth of pre-tolcapone values. The data confirm that tolcapone decreases L-Dopa clearance and prolongs motor response in PD patients with motor fluctuations, and that this effect is maintained after 6 weeks of tolcapone therapy.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The purpose of this pilot study was to determine whether rimantadine, the alpha-methyl derivative of amantadine, might have any antiparkinsonian properties. In an open-label trial, 14 patients (12 de novo and 2 on levodopa treatment) with Hoehn and Yahr stage 2 to 3 Parkinson's disease were placed on rimantadine at doses of 100 to 300 mg/d. No patients had dyskinesias or motor fluctuations. Ten of 14 (71%) reported a mean subjective response of 33% (range 10%-60%) to rimantadine. After treatment, there was a 13% improvement in Hoehn and Yahr staging (p= .01) and a 20% improvement in mean motor Unified Parkinsons Disease Rating Scale scores (p= .02). Rigidity was the most consistently improved feature among the responders. Mean effective dose was 256 mg/d (range 200–300 mg/d). Side effects were mild and transient, with nausea being most common (4/14). We conclude that rimantadine has some motor benefits in Parkinson's disease. A double-blind placebo-controlled study is warranted to validate our findings.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

We report ease of conversion, effect on equivalent efficacy and frequency of dosing when immediate-release carbidopa/levodopa (Sinemet, IR-CL, DuPont Pharma, Wilmington, DE, U.S.A.) is replaced with controlled-release carbidopa/levodopa (Sinemet CR, CR-CL, DuPont Pharma, Wilmington, DE, U.S.A.) in patients with Parkinson's disease (PD). One-step conversion through the application of a mathematical formula was utilized. Fifty-two patients (35 men, 17 women) with a mean ± SD age of 72 ± 8 years participated in this open-label study. All patients were taking IR-CL prior to conversion. The Unified Parkinson's Disease Rating Scale (UPDRS) was used for efficacy assessment. Pharmacokinetic studies were undertaken in five patients while they were on IR-CL, and repeated after they were switched to CR-CL. Dosage adjustment was not required either immediately after converting or during the 6-month follow-up. No significant changes occurred in efficacy scores during follow-up visits, indicating the effectiveness of the conversion. There were substantial differences in the levels of plasma DOPA, dopamine, 3-O-mcthyldopa, homovanillic acid, and dihydroxyphenylacetic acid between patients receiving IR-CL and those receiving CR-CL, but the differences did not correlate with clinical changes, suggesting that plasma levels do not reflect tissue levels at the site of action for levodopa. This study demonstrates that conversion from IR-CL to CR-CL for optimal dosing may be achieved in one step through the application of a mathematical formula with case of conversion and reduction of number of doses.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Kleptomania is characterized by an irresistible impulse to steal objects not needed for personal use or for their monetary value. Several recent case reports have shown that Serotonin Specific Reuptake Inhibitors (SSRIs) could be effective in the treatment of kleptomania just as it is in other obsessive-compulsive spectrum disorders. We report five cases of kleptomania patients who were successfully treated with fluoxetine or paroxetine in combination with a psychotherapeutic intervention. In one case, the discontinuation of the medication repeatedly led to the resurgence of the kleptomanic behavior. Our case series illustrates the effectiveness of SSRIs in kleptomania. It thus supports the assumption that this syndrome involves a dysfunctional serotoninergic mechanism.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The Bayley Scales of Infant Development II (1) is a well established standardized test for assessing the mental ability of infants and young children. It provides an age-adjusted standard score as a summary measure, but for very low (or very high) functioning children the raw scores on this test may not allow the calculation of a standard score. The manual provides for the transformation of raw scores into age-equivalents but this translation is not unique and results in a step function. The availability of a unique and continuous transformation of raw scores to age-equivalents is critical when evaluating longitudinal mental development, particularly in the environment of controlled clinical trials or natural history studies. We compared two methods for deriving unique age equivalents: a local regression method, with estimates restricted to age-equivalents within the age range of the test, and a linear method, which also allows extrapolation outside the age range of the test. The linear method was found to be most useful and the values, which are provided in table format, can be used for assigning age equivalent scores to individual children. They are also useful in clinical trials which use the Bayley to assess the safety and efficacy of treatments with potential cognitive effects, when conducted in populations where the children are likely to record scaled scores below the limits of the test.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Visual motor control (VMC) of arm movements is disturbed in patients with Parkinson's disease. The effect of antiparkinsonian medications on VMC is unknown. To assess the effect of deprenyl, a monoamine oxidase type B inhibitor, on VMC in the early stages of parkinsonism. Fourteen recently diagnosed, unmedicated patients with primary degenerative parkinsonism, mean age 61.9 ± 2.8 years, were assessed by a computerized VMC system for tracking and tracing on a sine wave, circle, and square. Score was given for total time of test performance, directional error, arm velocity, and number of interruptions in tracking. All patients performed the first VMC test at baseline, prior to any antiparkinsonian treatment. The second test was performed after a month of treatment with 2.5 mg/d of deprenyl, and the third test was done after an additional month of treatment with 10 mg/d of deprenyl. Results were compared with 15 healthy volunteers with a mean age of 63.1 ± 1.2 years. Parkinsonian patients performed significantly poorer on the VMC when compared to controls. Tracing was more affected than tracking. Tracing total time was almost twice as long as for controls (p< .0005). Treatment with 2.5 mg/d and 10 mg/d of deprenyl improved performance significantly (p< .05 andp< .005, respectively). Velocity of arm movement was not affected by deprenyl treatment in either dose. Directional control (tracing), severely disturbed in the parkinsonian group, improved back to the performance of healthy controls after 10 mg/d of deprenyl. In recently diagnosed parkinsonian patients internally guided VMC tasks were disturbed more than externally guided ones. Deprenyl treatment selectively improved directional control of arm movement in a dose related manner.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID