摘要:

Introduced on the market in 1989, pergolide, a D1/D2 dopamine receptor agonist, is still widely prescribed for the treatment of patients with early and advanced Parkinson's disease (PD). Initially, pergolide was introduced as an adjunct therapy to levodopa treatment in patients exhibiting fluctuating motor responses and dyskinesias. Results of recent randomized controlled clinical trials inde novopatients with PD show that pergolide is able to improve parkinsonian symptoms when used as monotherapy. Moreover, preliminary results of a long-term monotherapy study in early PD suggest that pergolide is as effective as levodopa, and that a significant delay in the time of the onset of levodopa-induced motor complications can be obtained. A number of randomized studies have shown that pergolide is more effective than bromocriptine as adjunct therapy to levodopa in patients with advanced PD; the greater benefit found with pergolide could be ascribed to its action on both D1 and D2 dopamine receptors. However, controlled comparative studies with new dopamine agonists, such as ropinirole, cabergoline, and pramipexole, have not been performed yet. Interestingly, few open studies in patients with complicated PD have shown that high doses of pergolide (> 6 mg/d) are able to improve motor fluctuations and dyskinesias through a dramatic reduction of levodopa dosage. The side-effect profile of pergolide is similar to that of other dopamine agonists, and complications such as sleep attack and serosal fibrosis have been rarely reported.

ISSN:0362-5664    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Daily 20-mg doses of Copolymer 1 have been shown to significantly decrease the relapse rate in patients with multiple sclerosis (MS). In the present open-label study, patients with relapsing MS were treated with the same dose of Copolymer 1 administered on alternate days. Sixty-eight patients were recruited: fifty-one and forty-one patients completed 1 and 2 years of treatment respectively. The relapse rate during the 2 years of treatment decreased by 80.8% compared with the 2 years before treatment (means, 0.56 ± 1.02 versus 2.91 ± 1.10, respectively;p< 0.0001). This lower rate is comparable with that obtained with daily open-label administration previously reported by the authors. The score on the Expanded Disability Status Scale did not differ from that at baseline after the first year of treatment, although it increased somewhat at the end of the second year (baseline = 2.72 ± 1.55, 1 year = 2.71 ± 1.59, 2 years = 2.97 ± 1.80;p< 0.008). The drug was very well tolerated. This preliminary open-label study suggests that alternate-day therapy has beneficial effects and is well tolerated, comparing favorably with the effects of daily injections of Copolymer 1 in patients with relapsing MS. These results should be confirmed by randomized double-blind examinations.

ISSN:0362-5664    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Wernicke–Korsakoff's disease (WKD) is cognitively an amnestic state resulting from strategic lesions in the limbic system subserving the episodic memory network and resulting from thiamine deficiency. Neurochemical deficits have been implicated in the pathophysiology of amnesia based on the pathologic observations that various brainstem and basal forebrain nuclei are also affected. Previous treatment attempts with serotoninergic, noradrenergic, and cholinergic drugs have given controversial results. The objective of this study was to assess the effects of a cholinesterase inhibitor, donepezil, on memory, attention, and executive functions in patients with nonalcoholic WKD. Seven patients who developed WKD after a hunger strike were included in this single, blind, placebo-controlled, one-way, crossover study. The patients were administered donepezil during the first 30 days, and were administered placebo during the following 30 days. Neuropsychological tests to evaluate verbal and visual memory, and attention and executive function were performed on days 0, 31, and 61. All patients completed both phases of the study. There were no statistically significant differences between the three evaluations, except for a difference between active treatment and the placebo phase during recall of the Rey–Osterrieth complex figure, which was in favor of the placebo phase. There were no significant changes in favor of the active treatment. Cholinergic treatment with the cholinesterase inhibitor donepezil does not seem to provide marked beneficial effects in patients with WKD in this small, descriptive study. This may be because pathways mediating channel and state-dependent functions are impaired in this disease, and enhancement of state-dependent cholinergic transmission may not be sufficient. Subtle benefits, however, cannot be excluded because of the small sample size and the relatively short duration of the treatment.

ISSN:0362-5664    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Idiopathic Parkinson's disease (IPD) is characterized by motor signs such as akinesia, rigidity, and often tremor at rest. In addition to these symptoms, depression is a common finding affecting 40% of patients with IPD. This study evaluates the effect of the selective serotonin reuptake inhibitor, citalopram, on motor and nonmotor symptoms of depressed and nondepressed patients with IPD. Forty-six nondemented patients with IPD (24 men, 22 women; mean age 64 ± 5.3 years; mean ± SD disease duration, 6.4 ± 3.2 years; mean ± SD Hoehn-Yahr stage, 2.8 ± 1.2) were included in the study. Patients were divided in two subgroups: depressed (n= 18) and nondepressed (n= 28). Citalopram was added in an unblinded manner, starting with 10 mg/d, and, after a week, increased up to 20 mg/d in the depressed subgroup (n= 18) and in half of the nondepressed subgroup (n= 14). Parkinsonian and depressive symptoms were evaluated before and after 1 and 4 months of treatment. Statistical evaluation was made by analysis of variance for repeated measures. Citalopram did not worsen motor performance in IPD, but improved bradykinesia and finger taps after 1 month and 4 months of treatment both in patients with and without depression (p< 0.05 versus baseline). A clear improvement in mood was also observed in 15 of 16 patients with depression. Although case reports indicate that citalopram can potentially worsen the motor symptoms in patients with PD, to date this effect has not been confirmed. Many of the symptoms, typically associated with depression, can be observed in nondepressed patients with IPD, because signs thought to represent depression can be produced by Parkinson's disease. In this study, we observed that when combined with levodopa, citalopram induces an improvement of motor performance, in particular of subscores 23 and 31 of Unified Parkinson's Disease Rating Scale both in depressed and in nondepressed patients with IPD.

ISSN:0362-5664    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Blockade of the adenosine A2Areceptor potentiates the effects of levodopa in experimental animals and may offer a novel nondopaminergic target for drug therapy in Parkinson's disease (PD). Open-label trials suggest that the nonspecific adenosine antagonist theophylline improves parkinsonian symptoms and increases ON time in advanced patients with PD. In a double-blind, crossover, placebo-controlled trial, the authors investigated the ability of stable plasma levels of theophylline (between 10–20 &mgr;g/mL after 15 days of treatment) to modulate the long-duration response and the short-duration response of levodopa in 10 patients with PD. Although theophylline induced a longer duration of the effect of levodopa in all Unified Parkinson's Disease Rating Scale variables considered, including dyskinesias, maximal levodopa-induced improvement and the duration of the effect of levodopa did not differ significantly from placebo. Only the secondary variable “akinesia” showed a statistical tendency to a more prolonged beneficial response with theophylline during an acute levodopa test (short-duration response), and tremor worsened with theophylline during levodopa withdrawal (long-duration response). No differences were observed during the subacute course of study medication added to levodopa. During this exploratory study, the effects of theophylline were not strong enough to potentiate clearly the antiparkinsonian action of levodopa or to increase ON time in patients with advanced PD.

ISSN:0362-5664    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The binding of imipramine to plasma proteins was studied in 20 adult patients with endogenous depression, with the purpose of assessing the effect produced by its simultaneous administration with an analgesic. Patients were administered 150 mg/day imipramine for 5 days and the binding to plasma proteins was determined. This was repeated 2 days later, after simultaneous administration of imipramine with 1,000 mg/day acetylsalicylic acid (ASA). Adverse effects for each patient were registered during both phases and were classified as mild, moderate, or severe. Results showed 84.4 ± 7.07% of imipramine bound to plasma proteins and 72.18 ± 6.5% when imipramine was administered with ASA (p< 0.05). When imipramine was administered alone, 1.95 mild adverse events per patient were registered. When imipramine was administered with ASA, the mild adverse events increased to 3.1 (p< 0.01) and the severe adverse events increased from 0.6 to 1.5 (p< 0.01). The levels of free imipramine increased when ASA was administered, indicating a displacement on the binding to plasma proteins. When adverse events were compared for each treatment, the accumulation of the free fraction of imipramine caused an increase in adverse events as well as in their clinical severity.

ISSN:0362-5664    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Oxygen-free radicals play an important role in several physiologic and pathophysiologic processes. In pathologic circumstances, they can modify and damage biologic systems. Because oxygen-free radicals are involved in a wide range of diseases (cerebrovascular, cardiovascular, etc.), scavenging these radicals should be considered as an important therapeutic approach. In ourin vitrostudy, we investigated the antioxidant capacity of three drugs: pentoxiphylline (Sigma Aldrich, St. Louis, MO, USA) piracetam (Sigma Aldrich), and vinpocetine (Richter Gedeon RT, Budapest, Hungary). Phenazine methosulphate was applied to generate free radicals, increasing red blood cell rigidity. Filtration technique and potassium leaking were used to detect the cellular damage and the scavenging effect of the examined drugs. According to our results, at human therapeutic serum concentration, only vinpocetine (Richter Gedeon RT) had significant (p< 0.01) scavenging activity with a protective effect that increased further at higher concentrations. Pentoxiphylline (Sigma Aldrich) and piracetam (Sigma Aldrich) did not have significant antioxidant capacity at therapeutic concentrations, but increasing their concentrations (pentoxiphylline at 100-times, and piracetam at 10-times higher concentrations) led to a significant (p< 0.01) scavenger effect. Our findings suggest that this pronounced antioxidant effect of vinpocetine and even the milder scavenging capacity of pentoxiphylline and piracetam may be of value in the treatment of patients with cerebrovascular disorders, but merits further investigations.

ISSN:0362-5664    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The objective of this study was to develop a Parkinson's disease diary that evaluates a patient's difficulties in performing activities as a substitute for the amount of “on”- and “off”-time and to assess its clinimetric qualities. In this study, 84 patients with Parkinson's disease kept a diary for 2 or 3 periods of 5 days. Daily, five items were recorded across 11 time periods. Patients simultaneously recorded “on-off” in the traditional way. The diary was easily understood, and median recording time was 5–10 minutes a day. Clinimetric analysis showed that the diary could be reduced successfully to 3 days, in which five items (walking, transfers, manual activities, dyskinesias, and sleep) with four response options (no, slight, moderate, and severe difficulty) were assessed seven times daily. Sumscores of the first three items accurately predicted being “on” or “off” in 93% of the cases, making separate scoring of “on” and “off” unnecessary. The diary was internally consistent and showed good reproducibility. Construct validity with external measures was adequate, and comparisons between patients grouped by disease severity and by degree of fluctuations revealed significant differences in the expected directions. Taken together, this Parkinson's disease diary has a sound clinimetric basis, provides information on the extent of perceived disability, and thereby accurately reflects the severity of “off”-periods and the variability of motor fluctuations.

ISSN:0362-5664    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

A human immunodeficiency virus–positive patient receiving indinavir therapy developed a slowly progressive paraparesis. Magnetic resonance imaging findings were consistent with epidural lipomatosis. On discontinuing indinavir, symptoms gradually remitted. Although indinavir, a protease inhibitor, is known to cause abnormal fat accumulation, to the best of our knowledge this is the first report of epidural lipomatosis.

ISSN:0362-5664    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Depressive disorders are frequently managed with long-term use of antidepressant medication. Even though the newer generation of selective serotonin reuptake inhibitor antidepressants exhibits a more favorable short-term, side-effect profile, effects of chronic use of such drugs remain unknown. Considering the limited data available on long-term, selective serotonin reuptake inhibitor management, we report for the first time on two cases of late-onset adverse effects occurring 6 and 10 years after chronic-fluoxetine treatment in which patients experienced symptoms of restlessness, tension, agitation, and sleep disturbances. Symptoms resolved after reduction or cessation of the medication. Our case reports suggest the existence of a late-onset side-effect profile, which appears similar to acute side-effect symptomatology. Super sensitivity of the serotonin-related receptors may develop over the long-term and account for the phenomenon. Careful clinical monitoring is recommended to detect any late-onset, medication-related side effects.

ISSN:0362-5664    

出版商:OVID    

年代:2002

数据来源: OVID