摘要:

We found low levels of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) in a subgroup of children with opsoclonus-myoclonus, a pervasive neurological disorder that disables previously normal infants and children. As part of a systematic study to define the neuropharmacologic basis of opsoclonus-myoclonus, five chronically affected children were enrolled in an open, randomized, two-period, dose-ranging, double-blind, cross-over pilot clinical trial designed to compare the antimyoclonic properties of oral 5-hydroxy-L-tryptophan (L-5-HTP) with placebo. Subjects received an increasing L-5-HTP dose from 2 to 15 mg/kg/day as well as oral carbidopa throughout the study but were on no other drugs. Subjective improvement was reported in two subjects, but none showed significantly improved scores on rating scales for myoclonus, opsoclonus, and ataxia, even after further treatment with L-5-HTP for 1–3 months. After treatment, three patients had worse emotional and behavioral problems, and the electroencephalograms of two showed mild slowing but normalized during washout. Blood tests to evaluate hematologic, renal, and hepatic systems showed no changes and no evidence of the eosinophiliamyalgia syndrome. None of the subjects exhibited seizures or worsening of myoclonus. Two patients had very low predrug CSF 5-HIAA levels, but CSF 5-HIAA did not appear to correlate with response to L-5-HTP. The data suggest that L-5-HTP with carbidopa can be used safely in children using our dosing schedule. However, behavioral side effects, which tended to be exacerbations of severe baseline difficulties, though reversible, were prohibitive. Serotonin may play a role in the chronic neurobehavioral problems of opsoclonus-myoclonus. The data support our hypothesis of biochemical subgroups of opsoclonus-myoclonus based on CSF neurochemical studies.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We performed a double-blind, randomized, controlled study of levodopa withdrawal or dosage reduction in 11 patients with advanced Parkinson's disease (PD). Entry criteria were inadequate response to levodopa plus dose-limiting drug-induced side effects. In place of levodopa, subjects were randomly assigned to receive either (a) 100% placebo (complete drug holiday) or (b) 50% levodopa and 50% placebo (50% drug reduction) for 6 days. After subsequent open-label levodopa dose optimization, subjects were followed until entry criteria were again satisfied or for a maximum of 1 year. Improvement occurred with both interventions. The distribution of survival time to endpoint was longer for the drug holiday group (182 vs. 100 days), but the difference was not statistically significant. Aspiration pneumonia occurred in two patients undergoing complete drug holiday while no significant morbidity occurred with drug reduction. We observed no significant alterations of pharmacokinetic or pharmacodynamic properties of levodopa after drug holiday or reduction. Thus, subject to the limitations of our small sample size, we found no significant clinical or pharmacologic evidence that drug holiday results in dopamine receptor resensitization in patients with advanced PD. Temporary drug reduction is a therapeutic strategy with short-term benefit and no serious morbidity.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We evaluated patient acceptance and adverse effects when patients with Parkinson's disease (PD) stabilized on standard carbidopa-levodopa (Std-CL; Sinemet) were converted to controlled-release carbidopa-levodopa (CR-CL; Sinemet CR). The rational for the use of CR-CL is that continuous dopamine stimulation may delay the onset of motor fluctuations. Data were analyzed on 40 patients with PD who were on Std-CL and then were converted to CR-CL. Parkinsonian evaluations were done utilizing the Unified Parkinson's Disease Rating Scale (UPDRS), the Mini-Mental State Examination, and the Hamilton Depression Scale (HDS) while the patients were on Std-CL and following conversion to CR-CL. The median number of daily doses on Std-CL was four; on CR-CL it was two. The daily dose of levodopa during treatment with CR-CL was 29% higher than the dose during the treatment with Std-CL. A statistically significant difference existed in the dosages of Std-CL and CR-CL between stable PD patients and those with motor fluctuations. Statistically significant differences in scores on HDS and on items I, II, and III of UPDRS existed between Stages I–II and III–IV. The difference in adverse effects of CR-CL compared with those of Std-CL was insignificant. Forty percent of patients preferred CR-CL over Std-CL; 37.5% had no preference. Selection of the initial dosage of CR-CL is an important factor in therapeutic management of parkinsonism. The initial dose of CR-CL should be equivalent to 130% of the Std-CL dose. The patient acceptance rate of conversion to CR-CL was high.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Recently, we have shown that ingestion ofVicia fababeans improved substantially the clinical features in parkinsonian patients. However, the supply of the beans is season-dependent and their digestion can be quite unpleasant due to flatulence. In the present study, we verified that the L-Dopa content ofV. fabaseedlings is 20-fold higher than that of the fruit. Moreover, the germination of the seedlings is easy and not season-dependent, and their ingestion does not cause any adverse digestive effects. In the present study, seven Parkinson's disease (PD) patients and nine healthy controls ingestedV. fabaseedlings. Plasma L-Dopa and dihydroxyphenylacetic acid (DOPAC) levels were measured by a high performance liquid chromatography with electrochemical detection (HPLC-ECD) method. Plasma L-Dopa increased in both populations, and a substantial clinical improvement was observed in the patients according to the Webster scale.Vicia fabaseedling ingestion is a useful tool in the treatment of PD patients, especially those in low-income societies where limited resources do not allow the purchase or manufacture of expensive drugs. This treatment might also appeal to those people who prefer natural treatment in PD and in other conditions for which L-Dopa is prescribed.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

An effect model is proposed for the prediction of individual motor response in “on-off‘’ parkinsonian patients following a single-dose administration of levodopa/carbidopa. The process does not involve any iterative method (in order to minimize hysteresis). For an examination of the model, previously published data of Deleu et al. are used. Following administration of a duodenal bolus of the drug to on-off responders, individual motor score is linearly related to drug concentration in the effect compartment. Linear transformation constants were fairly similar in the four patients examined. If this behavior is generally the case, individual motor response can be predicted from plasma concentration following administration of a duodenal bolus to on-off patients. Following oral administration, a linear relationship between motor score and levodopa effect compartment concentration was found in one patient. With the other patient, a linear relationship persisted for 2 hours only following drug administration. Later, an unpredictable decrease in response was observed. This decrease was unrelated to (the calculated) drug concentration in the effect compartment. Following administration of a duodenal bolus, an on-off responder may react more like a “wearing-off‘’ responder by exhibiting less unpredictable fluctuations. The use of a one-compartment open model to describe levodopa pharmacokinetics reveals absorption and elimination rate constants of a comparable magnitude, following an ingestion of a Sinemet tablet. A double flip-flop model is proposed to account for this fact. In order to explain the linear relationship between motor effect and levodopa concentration in the effect compartment, the following relations between enzymatic first-order rate constants, in the effect compartment of on-off responders, are proposed:kMAO≤KDecarboxylase,kCOMT≤kMAO, wherekMAOrefers to dopamine as a substrate, whereaskDecarboxylaseandkCOMTrefer to levodopa. The above relations between rate constants imply also that [dopamine] ≤ [levodopa] in the effect compartment following levodopa administration to on-off responders.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Continuous epileptiform discharges (CEDs) are often an unanticipated finding on an electroencephalogram (EEG) at times occurring after presumedly successful treatment of convulsive status epilepticus. Often no clinical seizures are evident. Implications for treatment are unclear and not necessarily the same as for convulsive status. We reviewed anticonvulsant use in 53 patients with CEDs. Clinical seizures occurred in just 21 following the EEG and were usually readily controlled. Mental status improved with anticonvulsant treatment in 16 of 20 stuporous or confused patients but in only 2 of 33 comatose patients. Benzodiazepines often controlled clinical seizures or suppressed EEG discharges but rarely led to improved alertness. Phenytoin and phenobarbital were the most useful medications in improving level of consciousness. Carbamazepine and valproic acid were almost never helpful, but drug levels were often subtherapeutic. The medication effect during the EEG did not predict which medication would produce a cognitive improvement. Recurrence of CEDs was common following tapering of medication, and most patients had complications attributed to anticonvulsants. Some patients with CEDs appear to benefit from long-acting anticonvulsants but require prolonged clinical and EEG follow-up.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

An open-label, dose run-up clinical trial of diethylpropion, a mild psychostimulant medication with an approved indication for the short-term treatment of exogenous obesity, was conducted in 10 cocaine dependent patients. A “cocaine agonist” strategy has been proposed as a potential pharmacotherapy to assist in the initiation of cocaine abstinence in severely dependent patients. Diethylpropion exhibits many of the desirable properties of a medication with cocaine agonist properties. The current trial was conducted to obtain preliminary data on the safety, tolerability and efficacy of diethylpropion in cocaine dependent patients. Moreover, the study was conducted to obtain guidelines for dosing in future clinical trials. The results of this preliminary study suggest possible anti-craving efficacy and mood elevating properties for diethylpropion in this population. However, side effects were noted. Although most were not of a serious nature, one involved the precipitation of a manic episode. Nevertheless, because of diethylpropion's potential clinical efficacy in this population, further cautious investigation of the efficacy of this medication for the treatment of cocaine dependence is indicated.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

This study used a prospective, double-blind placebo-controlled study to determine the minimal dose of botulinum toxin (BTX) necessary to eliminate sternocleidomastoid (SCM) muscle activity in cervical dystonia (CD). Twelve patients with CD were randomized to receive 0, 20, 40, 60, 80, or 100 IU of BTX (diluted to a total volume of 1 cc) into the most clinically active SCM. Quantitative Eletromyographic (EMG) measures, clinical rating, and subjective patient assessments were obtained before and four weeks after BTX.A single injection of BTX into the SCM virtually eliminated muscle activity with all BTX doses administered (Manova, F[1,6] = 26.76, p = 0.002). Despite this marked reduction in SCM muscle activity, no significant clinical or subjective improvements were observed. Neck flexor weakness occurred in 59% and postinjection dysphagia occurred in 25%. Neither of these side effects were dose-related. We conclude that, with the injection techniques used in this study, even small doses of BTX can eliminate SCM muscle activity in CD and cause dysphagia and neck weakness. However, since CD is a disorder involving multiple muscles, more than one muscle must be injected with BTX for clinical efficacy. Similar studies of other cervical muscles may determine the minimum and the optimal effective doses of BTX for each muscle.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The first generation monoamine oxidase inhibitors (MAOI's) acted as antidepressants by increasing presynaptic stores of all monoamines and caused both the reaction with tyramine and psychosis. The newer selective, reversible inhibitors of the MAO-A system that are currently undergoing trials aim to act more specifically through noradrenaline and serotonin, and might be expected not to involve the same problems. This article describes a case of psychosis precipitated by the MAO-A inhibitor brofaromine and suggests possible mechanisms to explain it.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The influence of chronic antiepileptic treatment on total and conjugated bilirubin, lipid profile, and calcium and magnesium plasma levels was investigated in 294 adult epileptic outpatients undergoing different antiepileptic therapies. A comparison was made with an age- and sex-matched control group. All the antiepileptic groups, excluding the sodium valproate group, showed a significant reduction in total and conjugated bilirubin and a significant increase in total cholesterol and low-density lipoprotein (LDL) cholesterol levels in comparison to the controls. The high-density lipoprotein (HDL) level in the valproic acid group was significantly lower than that in the controls, although no difference was found between the therapeutic groups and the controls for triglycerides, calcium, and magnesium. Our findings indicate that before beginning any antiepileptic treatment, the lipid profile should always be taken into consideration and should be regularly checked throughout the treatment.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID