摘要:

SummaryImmunotherapy is frequently employed in treatment of patients with myasthenia gravis. Different regimens are not based entirely on controlled or comparative studies. There are few clear guidelines for choosing a particular immunomodulating agent and timing of its introduction. In this article, we have tried to summarize known information about the immunopharmacologic agents used for the treatment of patients with myasthenia gravis.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryThe clinical development of immunomodulatory agents for the treatment of autoimmune diseases is an arduous process. This can be explained by the fact that the true pathogenic mechanism of the disease(s) is unknown. Moreover, the properties and pharmacokinetic profile of these immunomodulatory agents are different from other classic therapeutic compounds. The aim of this brief review is to discuss a number of general aspects of the clinical pharmacology of i.v. immune globulin as well as more recent immunotherapeutic approaches such as anticytokine therapy, which are currently being applied in the immunotherapy for neurologic and rheumatic autoimmune disorders such as my asthenia gravis, chronic inflammatory demyelinating polyneuropathy, and rheumatoid arthritis. A better understanding of the interaction of the therapeutic compound and the host immune response, the knowledge of its kinetic profile, and the development of surrogate markers of clinical efficacy should help in designing randomized and blinded clinical trials that will ultimately determine the optimal therapeutic regimen.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryWe performed a crossover study of apomorphine-induced motor response reproducibility in 10 parkinsonian patients with the “on-off‘ phenomenon. On 2 separate days, each patient received two successive identical s.c. apomorphine injections, the second injection being randomly administered either 10 or 80 min after the end of the first apomorphine-induced motor benefit. Latency (12.3 ± 4.5 min) and duration (61.9 ± 13.3 min) of motor effects were similar in all tests. A transient worsening of the parkinsonian state after a motor improvement induced by apomorphine occurred in most of the patients. Therefore, the duration and severity of the ”off period after a motor improvement does not seem to influence the efficacy of a second apomorphine administration.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryBromocriptine, a preferential D2 receptor agonist, was administered to six human narcoleptic patients during a double-blind, cross-over study. Laboratory sessions consisted of two all-night polysomnographic recordings and three daytime tests of vigilance: the Analogue Vigilance Scale (AVS), the Maintenance of Wakefulness Test (MWT), and the Four-Choice Reaction Time Test (FCRTT). No change in nocturnal sleep organization, daytime somnolence, or psychomotor performance was observed during bro-mocriptine administration. Periodic limb movements in sleep (PLMS) were significantly reduced during bromocriptine condition. These results suggest that D2 receptors are unlikely to play a major role in the physiopathology of human narcolepsy, and support the hypothesis that dopaminergic mechanisms are involved in PLMS.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryThe effects of the psychotropic drug etoperidone on the response to laboratory Stressors was investigated in a controlled study. Cardiovascular and hormonal (catecholamines, corticotropin, and cortisol) measurements were made in a group of young, healthy volunteers during a cold pressor test (CPT), a mental arythmetic test (MAT), and insulin-induced hypoglycaemia (ITT). One-week treatment with etoperidone (ETO) (150 mg/day, orally) reduced basal and stress-induced values of systolic and diastolic blood pressure (BP) on CPT, while it did not alter catecholamine output in response to the stressor. Cardiovascular response was also attenuated after ETO on MAT, in the absence of any hormone changes. Adrenocorticotropic hormone (ACTH) and cortisol secretions were markedly reduced on ITT after ETO, whereas catecholamine outflow and cardiovascular parameters were substantially unaffected. These findings on ITT suggest that the anti-serotoninergic and anti-α1adrenergic activities of ETO may be used in the pharmacological control of the potentially detrimental consequences of the stress response.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryA poor response to L-DOPA in addition to parkinsonian, cerebellar, and autonomic signs is commonly regarded as indicative of clinical multiple system atrophy (MSA). We compared the motor response to a single oral administration of 250 mg L-DOPA/25 mg carbidopa in eight MSA patients and eight Parkinson's disease (PD) patients with the “on-off‘ phenomenon, evaluating L-DOPA peripheral pharmacokinetics. Motor response was consistently good in all PD patients, but only four MSA patients had a (moderate) response. Pharmacokinetic parameters did not differ between the groups. The varying extent of putaminal damage could be responsible for the differing motor response to L-DOPA in MSA patients.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryWe studied the effect of inhibiting the enzyme catechol-O-methyltransferase (COMT) by a novel COMT inhibitor, entacapone, on the pharmacokinetics and metabolism of levodopa in 12 healthy male volunteers. Single increasing oral doses of entacapone (50–400 mg) were administered concomitantly with a single oral dose of levodopa/carbidopa (100/25 mg). The subjects were treated with carbidopa (100 mg t.i.d.) for 1 day prior to the administration of study drugs. Plasma concentrations of levodopa; its metabolites 3-O-methyldopa (3-OMD), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA); as well as carbidopa and entacapone were determined for pharmacokinetic calculations. Entacapone dose-dependently increased the area under the plasma concentration-time curve (AUC) of levodopa; the increase was 65% after the 400 mg dose of entacapone. NeitherCmaxnorTmaxof levodopa was statistically significantly influenced by entacapone. Entacapone dose-dependently decreased the AUC of 3-OMD, maximally by 58%. The AUC of DOPAC was statistically significantly increased but no change in the AUC of HVA was observed after entacapone. No drug-related adverse events or hemodynamic effects were observed. The in vivo biochemical effects of entacapone indicate that it is an orally active COMT inhibitor and that it may improve the therapeutic efficacy of levodopa in Parkinson's disease.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryApomorphine was administered sublingually in two single doses (0.3 and 0.6 mg/kg) to seven patients with idiopathic Parkinson's disease (PD) to assess the relation between clinical efficacy, dosage, and pharmacokinetic parameters of apomorphine. On day 1 and day 3, patients were given 0.3 mg/kg and 0.6 mg/kg of apomorphine, respectively (3 mg tablets). Before apomorphine administration and during the following 4 h, motor score was assessed by measuring tremor, akinesia scores, rising from a chair, and walking speed. The delay to turn on was not different between the two doses but after the 0.3 mg/kg dose, only three patients turned on, whereas all the patients treated with 0.6 mg/kg turned on. Apomorphine (0.3 mg/kg) induced a shorter duration of the “on” period than 0.6 mg/kg (0.3 mg/kg: 24.2 ± 14.6 min; 0.6 mg/kg: 86.7 ± 14.9 min). The time to obtain the peak plasma concentration (tmax) obtained with the two doses were not different (0.3 mg/kg: 31.5 ± 3.4 min; 0.6 mg/kg: 38.3 ± 2.8 min). Peak plasma concentrations (Cmax) and areas under the curve (AUC) were significantly higher after 0.6 mg/kg than 0.3 mg/kg (Cmax: 0.3 mg/kg: 7.5 ± 3.2 ng/ml; 0.6 mg/kg: 22.7 ± 3.6 ng/ml;p< 0.01; AUC: 0.3 mg/kg: 929 ± 109 ng/ml/min; 0.6 mg/kg: 2,277 ± 209 ng/ml/min;p< 0.01). There was a significant linear correlation between the duration of therapeutic effect, AUC, andCmax(r= 0.86,p< 0.01 for AUC;r= 0.63,p< 0.05 forCmax). These results show that sublingual apomorphine could be of interest in the treatment of “off phases in parkinsonian patients with motor fluctuations.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryWe carried out a double-blind, randomized, parallel-groups clinical trial of fluoxetine (20–40 mg/day) and placebo in 11 children with Tourette's syndrome (TS) and associated obsessive-compulsive symptoms (OCS). The treatment period lasted 4 months. No significant differences between treatment groups were observed for measures of OCS. Fluoxetine therapy, however, was associated with a trend toward some improvement in tic severity, attentional abilities, and social functioning. Given these observations and the limitations of this pilot study, which include selection biases, small sample size, and significant placebo effects, the efficacy of fluoxetine in children with TS deserves further larger-scale investigation.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryA 74-year-old man developed paranoid ideation, memory impairment, and defective gustatory and olfactory function while on bismuth subgallate therapy for use as a colostomy deodorant. Twenty-four-hour urine bismuth was elevated at 889 μg/day, and whole blood bismuth concentration was 67 (μg/L. The patient improved after discontinuation of bismuth subgallate; there was resolution of paranoid behavior and gustatory and olfactory functions improved. Follow-up whole blood bismuth concentration was 21 μg/L 4 weeks after cessation. Altered gustatory and olfactory function have not been previously reported with bismuth intoxication.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID