摘要:

Summary:The opsoclonus‐myoclonus syndrome (OMS) is a potentially devastating paraneoplastic or paraviral syndrome. Although it is a rare disorder, it has major implications for cancer, virology, immunology, developmental neurobiology, and molecular pharmacology. The mechanism of brain injury in OMS is unknown, but evidence suggests immune system dysregulation. This article surveys recent clinical and laboratory evidence for the autoimmune theory and discusses how some current therapies for OMS may exert their effects through immunomodulation. Specific testable hypotheses on the immunologic defect in OMS involving both B cells and T cells, the nature and mechanisms of brain injury, and their clinical correlations are proffered. The current therapeutic armamentarium provides a broad spectrum of nonselective immunotherapies, including noncytotoxic and cytotoxic drugs, intravenous immunoglobulins, and plasma exchange, some selected for induction and others for maintenance. The use of combination immunotherapies may allow steroid sparing, targeting of more than one immunologic effector pathway, and a mixture of early‐ and late‐acting drugs. More selective immunotherapies, now available or in preclinical and clinical trials, have great potential for the treatment of OMS but require precise information on the underlying immunological problem. These data provide possible new directions for immunologic research and therapy in OMS.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The basal uptake of radiolabelled45Ca2+into platelets and the effect of 1 mMlithium on uptake was measured in manic (n= 13) and depressed (n= 15) patients with bipolar disorder and in controls (n= 13). Lithium was significantly associated with inhibition of uptake of45Ca2+into platelets in all three groups. There were no significant intergroup differences in either basal levels of calcium uptake or the effects of lithium on calcium uptake (analysis of variance).

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Dopamine agonists have been used with some success in treating cocaine addiction. However, both cocaine and psychostimulants have been reported to produce neurotoxic effects. We evaluated the effect of the stimulant diethylpropion on cognitive performance in a double‐blind, placebocontrolled trial. Forty‐six abstinent crack‐cocaine users received either placebo, 25‐mg, 50‐mg, or 75‐mg doses of diethylpropion. Patients were tested at baseline and again after 9‐14 days of medication. There were no differences between placebo and medication groups on any test, indicating that, within the time frame studied, diethylpropion does not produce neurotoxic effects that can be detected with standardized neuropsychological tests.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The development of tolerance to dopaminergic drugs may be important in the long‐term therapy of Parkinson's disease. In this study, we sought to determine whether tolerance developed during infusions of apomorphine and if there was evidence of any dose dependency. Eight patients with Parkinson's disease received 4‐ to 6‐h infusions of apomorphine at low, medium, and high rates on consecutive days. Before and after each infusion, test boluses of apomorphine were administered to measure sensitivity to the drug. The duration of motor effects after the postinfusion boluses were reduced in comparison to those of the preinfusion boluses, indicating that tolerance developed during the infusions. The infusion rate did not affect the responses to the postinfusion test boluses. Our observations indicate that tolerance develops to the antiparkinsonian effect of apomorphine after several hours of its constant infusion, but is not influenced by the dose of drug administered.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Levodopa ethyl ester (LDEE), a highly soluble prodrug of levodopa, was synthesized and administered to mice and rats subcutaneously or intraperitoneally. Striatal levels of levodopa, dopamine, and the dopamine metabolite 3,4‐dihydroxyphenylacetic acid (DOPAC) were determined using high‐performance liquid chromatography with electrochemical detection and compared with those obtained after intraperitoneal injections of levodopa. LDEE injections produced significant and rapid elevations of striatal levodopa, dopamine, and DOPAC, which were similar to those achieved after levodopa administration, with similar dose‐response curves. The elevations achieved by LDEE given s.c. were higher than those achieved after i.p. administration and lasted for longer periods. In addition, intraperitoneal administration of levodopa or LDEE to rats with unilateral 6‐hydroxydopamine (6‐OHDA) nigral lesions produced similar contraversive circling responses. We suggest that LDEE may be a beneficial antiparkinsonian agent. It has potential pharmacokinetic advantages that are superior to those of levodopa itself, and its subcutaneous administration may become an effective rescue strategy to overcome “off” situations in patients with Parkinson's disease and response fluctuations.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:In a randomized double‐blind study, 20 parkinsonian patients (suffering from the disease for 2‐18 years), chronically treated with levodopa (500‐750 mg/day for 0.5‐12 years), received terguride (1 mg b.i.d) or placebo for 4 weeks. Growth hormone (GH), prolactin (PRL), thyroid‐stimulating hormone (TSH), and insulin‐like growth factor (IGF‐I) secretions were studied before and after the morning dose of levodopa (250 mg p.o.), both before and at the end of study period. At the beginning of the study, basal hormonal levels were within normal limits, and levodopa administration induced a significant suppression in PRL and TSH levels (bothp< 0.01)) and a significant increase in GH (p< 0.01). The same results were observed at the end of the study period in the placebo group. Addition of terguride induced a significant suppression in basal PRL levels (p< 0.01), whereas levodopa‐induced hormonal changes were unaffected. These data suggest that the hypothalamic dopaminergic function that controls anterior pituitary hormones is preserved in parkinsonian patients, regardless of both the duration of the disease and the long‐term treatment with levodopa. The strong additional prolactin‐lowering effect of terguride indicates long‐lasting dopaminergic effects, as is already known from hyperprolactinemic conditions. The dopaminergic effects of levodopa on TSH, GH, and IGF‐I secretion were unchanged by terguride treatment. The antidopaminergic effects of terguride observed in the motor system in animal studies, as well as in levodopa‐induced dyskinesias in parkinsonian patients, could not be observed in the case of the dopaminergic control of anterior pituitary hormones under the conditions of this study.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Twenty patients with Parkinson's disease (PD), who developed delusions and psychotic behavior, underwent electroencephalogram (EEG) recordings before and during treatment with low‐dose clozapine. Resolution of the psychotic features was observed in all cases. The EEG was unaltered in 15, whereas five patients exhibited increased generalized or focal slowing when compared with the pretreatment tracings. These findings contrast with the high incidence of EEG abnormalities, including epileptiform activity, which are observed when larger doses of clozapine are used in schizophrenic patients, but they underscore that even in low doses, clozapine may cause EEG changes.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:In previous studies, we demonstrated that the benzodiazepine (BZP) receptors of the visual system are functionally preserved in Creutzfeldt‐Jakob disease (CJD). We hypothesized that such a functional preservation is not confined to the visual system. In a 74‐year‐old woman suffering from CJD, three consecutive recording sessions of somatosensory cortical evoked potentials (SEPs) by right median nerve stimulation were carried out: (a) basal condition, without any pharmacologic treatment; (b) 1 min after i.v. administration of 10 mg diazepam (DZP); (c) 2.5 min after i.v. administration of 3 mg FMZ, a high‐affinity receptor benzodiazepine antagonist. DZP greatly decreased the amplitude of SEP early components, whereas flumazenil (FMZ) reversed such an effect. The results of this study, paralleling our previous findings on the visual system in CJD, demonstrated functional preservation of BZP receptors in the somatosensory pathways as well.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:To study the analgesic efficacy of enadoline, a selective agonist of the &kgr;‐opioid receptor, a double‐blind, randomized comparison was made of enadoline versus placebo and a combination of acetaminophen‐codeine in patients with pain after surgical extraction of impacted molar teeth. An initial study involving a comparison of enadoline, a combination, and placebo failed to show any analgesic effect of enadoline. Therefore, a second study with the same design but using higher doses of enadoline was conducted. Despite continued safety and tolerability even at the higher doses, enadoline could not be shown to be superior to placebo. The acetaminophen‐codeine combination was significantly more effective than enadoline or placebo. Enadoline did not show analgesic efficacy in this study. Possible reasons for this lack of efficacy are discussed.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID