摘要:

SummaryStatus epilepticus (SE) remains one of the most serious disorders affecting the central nervous system. Recent progress in understanding the mechanisms of the brain damage produced by SE make even more apparent the need to quickly terminate this condition, prevent its recurrence, and treat its complications. Intracellular calcium concentrations rise, prompting a cascade of excitotoxic consequences. Therapy for SE currently consists of agents which stop seizures (benzodiazepines, phenytoin, barbiturates). This review discusses their use in SE.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

SummaryBecause of substantial evidence for the hyperdopaminergic hypothesis of tardive dyskinesia (TD), animal models, especially rats, treated chronically with neuroleptics continue to be used to study this disorder. The rat model has been criticized because, unlike TD, in rats there is an apparent lack of spontaneous abnormal movements even when striatal D2dopamine receptor (DAr) density is substantially increased. Our data suggest a mechanism by which rats suppress these abnormal movements normally associated with elevated DAr levels. We correlated neurochemical with behavioral changes using several animal models, including nonneuroleptic ones, which elicit varied levels of DAr upregulation. There was (as expected) a robust, significant,positivecorrelation between striatal DAr density and apomorphine-induced stereotypic behaviors. In contrast, there was a significantnegativecorrelation between increased DAr density and synthesis capacity for striatal DA (Vmaxfor tyrosine hydroxylase). We conclude that this decrease in Vmaxis a compensatory adjustment of the nigrostriatal DA tract for the increased DAr density induced in our animal models. Our data further suggest the generalization that an observed increase in receptor density doesn't necessarily predict a functional change (spontaneous behavior, neuropathology) because compensatory neural mechanisms exist. In TD these compensatory neural mechanisms may fail, leading to spontaneous behaviors.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

SummarySeven patients with Parkinson's disease and levodopa-induced motor fluctuations were studied with repeated injections of apomorphine over a 10-h period to explore possible changes in the latency, duration, and quality of motor response with recurrent dopaminergic stimulation. Doses were given when the motor effects induced by the previous dose had just worn off. No significant change in the motor response to repeated boluses of subcutaneous apomorphine was found. Our results do not support the suggestion that rapid changes in receptor sensitivity during repeated intermittent dopaminergic stimulation are a major factor in the pathogenesis of parkinsonian motor fluctuations.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

SummaryThe potent and selective dopamine D-2 agonist, MK-458 [PHNO; ( + )-4-propyl-9-hydroxynaphthoxazine] was administered as monotherapy to nine patients with Parkinson's disease in a double-blind, placebo-controlled 12-week investigation; ten other patients were randomized to placebo. MK-458 was formulated as a controlled-release preparation, using a hydroxypropyl methylcellulose-lactase (HPMC) matrix. Patients receiving MK-458/HPMC improved on a variety of measures of parkinsonism, compared to their baseline scores; in contrast, only trivial improvement was seen within the placebo group. We subsequently compared the anti-Parkinson response to MK-458/HPMC with the response to chronic carbidopa/levodopa monotherapy in an open label trial. Carbidopa/levodopa improved parkinsonism to a significantly greater degree than MK-458/HPMC. Doses of MK-458 used in these studies (up to 60 mg per day) were substantially higher than those in previously reported preliminary studies of this medication. We conclude that monotherapy with MK-458/HPMC results in a significant anti-Parkinson effect; however, the response falls short of that seen with carbidopa/levodopa.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

SummaryL-deprenyl (Eldepryl) added to Sinemet CR in the treatment regimens of seven patients with Parkinson's disease (PD) and therapeutic response fluctuations (RF) allowed a statistically significant reduction in total daily levodopa intake and an increase in the mean interdose interval. Trends were noted towards a reduction in the number of daily “off periods and an increase in the portion of the waking day spent ”on.“ Three patients suffered an increase in the intensity of their dyskinesias, and discontinued taking deprenyl. Four patients, all of whom reported improved functioning during ”off“ periods, have continued taking the combination. Sinemet CR and deprenyl can safely be used together in patients with advanced PD, and the combination may result in improved control of motor fluctuations in selected patients.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

SummaryIt has been proposed that initiation of anti-Parkinson therapy with continuous release formulations of Sinemet might prevent or delay the development of adverse effects associated with chronic levodopa therapy employed in standard formulations. In anticipation of a prospective study comparing Sinemet to Sinemet CR in previously untreated Parkinson's disease patients, we evaluated Sinemet CR as primary therapy in 45 levodopa-naive Parkinson's disease patients in a 12 week, open-label, multi-center study. At the conclusion of the study, optimal results were obtained with levodopa administered as Sinemet CR in a total daily dose of 497 mg divided into 2.4 doses per day. Statistically significant improvement compared to baseline was observed for total Parkinson score as well as each of rigidity, tremor, bradykinesia, gait and postural stability. Statistically significant improvement was also noted in total disability as well as in each of its components. Adverse experiences were mild and transient and no significant laboratory abnormalities were encountered. We conclude that a daily dose of 1 to 1.5 tablets b.i.d. of Sinemet CR as primary therapy for patients with Parkinson's disease is well tolerated and provides effective therapy.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

SummaryWe compared the efficacy of a single dose of an oral solution of levodopa methyl ester (ME) to that of standard levodopa, in the form of a single dose of Madopar, in reversing afternoon “off” periods in 12 patients with Parkinson's disease (PD). The highly soluble ME solution led to a significantly more rapid reversal of “off” periods. This preparation may therefore convey a clinical advantage in patients experiencing motor fluctuations whilst taking multiple daily dosages of levodopa, particularly in those with long or highly variable latency to the next “on” period.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

SummaryBecause of evidence that supports an important role for the 5–HT,1Areceptor subtype in migraine, buspirone—the novel 5–HT1Areceptor agonist with anxiolytic properties—was given to 33 patients suffering from severe migraine exacerbations. Patients took 15–20 mg/daily for 10 weeks; six (18%) patients did not improve. Although buspirone was well tolerated, two additional patients (6%) did not finish the trial, due to undesirable side effects. On the other hand, 25 (76%) patients improved; 17 (52%) exhibited an excellent response; and 8 (24%), a moderate response. Potential reasons for the observed antimigraine effect of buspirone and its possible consequences in migraine pathophysiology are discussed. Our results, at first, seem to support the role of a 5-HT,1Ahypersensitivity in migraine pathogenesis, and warrant further trials to confirm whether buspirone represents an alternative in preventive treatment of migraine exacerbations.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

SummaryFour young patients who developed weight gain induced by carbamazepine therapy are described. The patients received the carbamazepine as anticonvulsant treatment, and soon after starting the drug, abruptly developed an increase in appetite with a concomitant increase in food intake. During a period of 2 months the patients' weights rose by between 7 and 15 kg. Dietary restriction during the carbamazepine treatment was ineffective in promoting weight loss, and loss of the excess weight was achieved only when the drug was discontinued. These patients demonstrate an as yet unpublished adverse effect of carbamazepine. In carbamazepine-induced weight gain, overeating and fat deposition must be taken into consideration as a differential diagnosis to the hitherto described water retention and edema.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

SummaryThe capability of pravastatin and lovastatin, HMG-CoA reductase inhibitors likely to be taken chronically for hypercholesterolemia, to cross the blood-brain barrier was investigated in normal male volunteers. Lovastatin, which is lipophilic, was detected in cerebrospinal fluid (CSF) at concentrations that may have a pharmacologic effect. Pravastatin, which is hydrophilic, was not detected in CSF. It is concluded that pravastatin may have less potential for causing CNS-related side effects than lovastatin.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID