ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The mortality risk associated with cardiovascular disease is significantly increased in patients with major depression and panic disorder. The mechanism of this phenomenon is unclear. Thrombin is responsible for platelet aggregation and shape change, and it plays a significant role in the development of thromboembolic events. In this study, we examined the platelet second messenger intracellular calcium response to thrombin stimulation in patients with major depression (n= 13), major depression after response to electroconvulsive therapy (ECT;n= 13), subsyndromal depression (n= 16), schizophrenia (n= 15), and control subjects (n= 65). Patients with major depression had significantly higher intracellular calcium responses to thrombin stimulation than control subjects, patients with subsyndromal depression, and patients with schizophrenia (p< 0.05). Elelctroconvulsive therapy did not significantly change this supersensitivity. This suggests that the platelet response to activation in patients with major depression is supersensitive. This study suggests a possible mechanism for the increased risk of cardiovascular disease that is seen in these two psychiatric disorders. The lack of difference between the control and subsyndromal depression groups appears to validate current diagnostic thresholds in depression. The failure of nonpharmacologic treatment to alter this marker suggests that it may be a trait marker of depression.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Mexiletine is an antiarrhythmic drug that has been reported to exert antidystonic properties. We performed an open-label study to collect further evidence of the antidystonic effect of mexiletine in spasmodic torticollis (ST) and to evaluate its possible use in generalized dystonia. We administered mexiletine to six patients with dystonia (three with generalized dystonia and three with ST) who had failed to respond to previous pharmacotherapy. The drug was started at a dose of 200 mg/d by mouth and increased up to a maximum dose of 800 mg/d. Patients were evaluated at regular intervals over a 6-week period with use of the Fahn & Marsden Dystonia Scale and the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and videotaped. At the end of the trial, the videotapes were reviewed and scored by a blind observer. Patients were then followed for at least 1 year and evaluated every 3 months at the dose reached during the study period. No adverse effects were reported in five patients; in one patient, dizziness developed at the dosage of 800 mg/d, requiring a reduction of the dose. At the end of a 6-week period, a significant improvement in the rating scale for dystonia and in videotape ratings was observed after mexiletine treatment (p< 0.01). Our data indicate that mexiletine is a useful drug in dystonia treatment.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

To determine whether dopamine metabolism is abnormal in HIV infected patients and whether dopamine metabolism abnormalities are related to specific neuropsychologic characteristics in HIV-infected patients, we measured cerebrospinal fluid (CSF) levels of homovanilic acid (HVA), the primary dopamine metabolite, in 10 HIV-infected patients and compared it to HVA levels in CSF in a group of 13 healthy control subjects. HIV-infected patients were also assessed with a battery of neuropsychologic tests and HVA levels were then correlated with performance on specific neuropsychologic tests. The mean (±SD) HVA level in CSF was 100.9 ± 29.3 nmol/L in the HIV-infected study group and 230.5 ± 50.0 nmol/L in the non-HIV-infected control group (p< 0.0001). The decrease in concentrations of HVA in CSF correlated with impairment on performance on neuropsychologic testing (Spearman r = 0.67;p= 0.03). When the relationship between HVA levels and specific cognitive domains was evaluated, we observed trends for positive correlation between HVA levels and tests that measure motor speed (r = 0.59;p= 0.074) and those testing attention, concentration, and executive control (r = 0.54;p= 0.108). There was no relationship between performance on memory tests and CSF HVA levels (r = −0.0061;p= 0.987). These results further support the hypothesis that dopaminergic dysfunction plays an important role in the pathogenesis of AIDS dementia complex (ADC) and suggest that specific motor and cognitive abnormalities may be related to depressed dopaminergic activity. This may have important implications for the development of treatments or preventive strategies for ADC.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The pathophysiology of L-Dopa-induced dyskinesias (LID), a common problem after long-term use of L-dopa in the treatment of Parkinson's disease (PD), is not completely understood. Oscillations in L-Dopa concentrations in the brain are believed to be responsible, at least in part, for their pathogenesis. This study was aimed at verifying whether chronic administration of cabergoline, a long-acting dopamine D2-like receptor agonist, can reverse established LID. Four MPTP-treated cynomolgus monkeys with long-standing and stable parkinsonian syndrome and reproducible dyskinesias to L-Dopa, were used in this study. We compared the antiparkinsonian and dyskinetic responses of L-Dopa methyl ester (62.5 mg and 125 mg), given with benserazide (50 mg) (L-Dopa/benserazide), administered before and after a 6-week period during which the animals were treated only by daily administration of cabergoline (doses ranging from 0.125 to 0.185 mg/kg, subcutaneous). During cabergoline treatment, the monkeys initially showed marked dyskinesias, which were reduced significantly after 4 weeks of treatment. However, there was no tolerance to its antiparkinsonian effect. L-Dopa/benserazide given 4 days after cabergoline withdrawal produced a significant antiparkinsonian effect, but dyskinesias were dramatically reduced compared to what had been seen before chronic cabergoline treatment. The duration of the L-Dopa response was not increased after chronic administration of cabergoline. Our data suggest that sustained dopamine D2receptor stimulation could be of value when trying to reduce or to reverse LID in patients with fluctuating advanced PD.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

We performed a prospective study in 21 patients to evaluate the cost of treatment of spasmodic torticollis (cervical dystonia) before and after botulinum toxin type A (BTA) treatment and to assess the impact of BTA treatment on quality of life. Data were recorded for the analysis over a period starting 8 months before and ending 7.2 ± 0.2 months (mean ± SEM) after the first injection of BTA. All patients received at least two BTA injections (2.9 ± 0.2 injections per patient). We studied direct medical costs (drugs, outpatient and inpatient visits, diagnostic procedures, physiotherapy), clinical effects of BTA (clinical rating scale and patient's global assessment), quality of life (French version of the Nottingham Health Profile [NHP]), and adverse reactions. Costs associated with the treatment of spasmodic torticollis before the first BTA injection were 479 ± 143 French Francs (FF)/patient/month (97 ± 29 US $/pt/mo). During BTA treatment, costs were 1,126 ± 147 FF/pt/mo (228 ± 30 US $/pt/mo), including a mean cost of BTA of 771 ± 131 FF/pt/mo (157 ± 27 US $/pt/mo). Treatment with BTA significantly decreased clinical symptoms of spasmodic torticollis and improved the emotional, social, and pain-related domains of the quality of life assessment. Botulinum toxin type A treatment increases the cost of treating spasmodic torticollis but improves quality of life in terms of pain, social, and psychologic functioning in patients with spasmodic torticollis.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

We studied the effect and temporal profile of deep brain stimulation (DBS) of the globus pallidus and subthalamic nucleus on the motor signs of Parkinson's disease (PD). Four patients with bilateral deep brain stimulators of the globus pallidus and four patients with bilateral deep brain stimulators of the subthalamus were studied while taking no medication and at 15 and 30 minutes and 1, 2, 4, and 6 hours after turning stimulation on. An immediate (15 minutes) and sustained (6 hours) benefit was observed for all the motor manifestations of PD for both stimulation sites. Deep brain stimulation of the globus pallidus and subthalamus is highly effective in reducing all the cardinal motor features of PD.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

There are several reports regarding the efficacy of vitamin B6in the treatment of tardive dyskinesia (TD). Vitamin B6plays a key role in the synthesis of several neurotransmitters, including serotonin, dopamine, norepinephrine, and gamma-aminobutyric acid, all of which have been proposed to be involved in the development of TD. The purpose of this study was to examine whether there are special markers to distinguish long-term neuroleptic exposure patients who have TD from those patients who do not develop this side effect. In view of the pivotal role of vitamin B6in the synthesis of all neurotransmitters believed to take part in the pathogenesis of TD, we decided to examine whether basal levels of vitamin B6might explain the difference between these two groups. Such a finding could provide a predictive marker for vulnerable patients. The active metabolite of vitamin B6is pyridoxal phosphate (PP). Pyridoxal phosphate blood levels were measured in 15 schizophrenic and schizoaffective patients with TD and compared with 15 patients without evidence of TD (matched by sex, age, smoking, and diagnosis). We found that, although patients in the TD group were exposed to neuroleptic drugs for significantly longer periods of time, there were no differences in serum PP levels between the groups. The reports of the effectiveness of vitamin B6supplementation in the treatment of TD could therefore be explained by the assumption that central nervous system or intracellular vitamin B6levels, which are involved in the pathogenesis of TD, are not the same as vitamin B6peripheral serum levels. There is need for further studies, which will clarify the relationship between vitamin B6and TD.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Neurologic manifestations of HIV infection are quite diverse and can develop into seizures. Because new drug therapies have been developed, it is important to know the interactions between antiretroviral and antiepileptic agents. A 36-year-old patient with HIV developed a set of progressive left hemiparesis and secondarily generalized partial seizures related to progressive multifocal leukoencephalopathy. Phenytoin and carbamazepine were necessary to control the seizures. Instead of diverse antiretroviral therapies, the viral load was increased. Protease inhibitors (ritonavir and saquinavir) were added to the treatment and the patient developed progressive ataxia related to carbamazepine toxicity. Carbamazepine was discontinued and the patient remained asymptomatic. The patient was diagnosed with carbamazepine toxicity related to the introduction of ritonavir. Ritonavir is a potent inhibitor of hepatic cytochrome P450, mainly the CYP3A4 isoform. Carbamazepine is metabolized by this subsystem. Ritonavir acted as a CYP3A4 inhibitor, diminishing carbamazepine metabolism and provoking an increase in serum levels and clinical toxicity. We present a case of interaction between ritonavir and carbamazepine. Interaction between antiepileptic and antiretroviral agents is an emergent problem caused by the increasing association of the two therapies. We recommend strict monitoring of serum antiepileptic drug (AED) levels to avoid toxicity and inadequate seizure control.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Carbamazepine (CBZ) is an antiepileptic drug frequently used to treat a variety of neurologic diseases or symptoms. In addition, the drug is used as a mood stabilizer in patients with affective or schizophrenic disorders. Among its adverse effects, auditory disturbance is described rarely. In this report, we describe a 25-year-old woman who noted falsely higher pitch perception after starting CBZ treatment for schizoaffective disorder. We also review the literature reporting CBZ-associated abnormal pitch perception.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID