ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Neuroimaging studies have been conducted with increasing frequency in recent years in attempts to identify structural and functional abnormalities in the brains of persons with attention deficit/hyperactivity disorder. Although the results of these studies are frequently cited in support of a biologic etiology for this disorder, inconsistencies among studies raise questions about the reliability of the findings. The present review shows that no specific abnormality in brain structure or function has been convincingly demonstrated by neuroimaging studies. Implications regarding stimulant treatment for attention deficit/hyperactivity disorder are discussed.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

A randomized, placebo-controlled, double-blind study was performed as a pilot study to examine the benefit of the administration of magnesium sulfate given intravenously as a protective substance during the first 24 hours following a stroke. Patients who had cortical infarction in the middle cerebral artery territory with moderate to severe neurologic deficits lasting for more than 15 minutes with onset less than 24 hours were included. The patients were treated with magnesium sulfate or placebo for 5 days and examined by a blinded investigator. Patients had follow-up for 30 days. The primary efficacy variable was the proportion of patients reaching mild to moderate neurologic deficit on the Orgogozo scale (80 points) and relative functional independence on the Barthel index (60 points). Orgogozo scale and Mathew scale values were obtained on admission and days 2, 4, 8, and 30 after stroke. Barthel activities of daily living index and Rankin disability score were obtained on day 30. Forty-one patients (22 given treatment and 19 given placebo) demonstrated significant beneficial effects on the Orgogozo scale (84 ± 11 vs. 64 ± 10,p< 0.0001) and (83 ± 14 vs. 70 ± 15,p< 0.009), respectively. At the end of 1-month follow-up, the Barthel ADL index was nonsignificantly higher and the Rankin disability score was marginally significantly lower in the magnesium-treated group (84 ± 26 vs. 71.8 ± 26,p< 0.143) than in control subjects (2.3 ± 1.1 vs. 3 ± 1.3,p< 0.077). Intravenous magnesium sulfate had significant positive effect on the outcome in patients with acute stroke. Further studies on a larger scale are needed to confirm these findings.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Lanepitant is effective in the formalin analgesic model suggesting efficacy in painful neuropathy. This study was designed to evaluate the dose-response effect of lanepitant in patients with daily moderate to severe, bilateral, distal neuropathic pain. After a 1-to 3-week lead-in period, patients were randomly allocated to double-blind, parallel treatment with lanepitant 50 mg daily (n= 27), 100 mg daily (n= 27), 200 mg twice daily (n= 13), or placebo (n= 26) over 8 weeks. Patients reported average daytime pain and average nighttime pain intensity. Plasma concentrations and amount of adjunctive analgesic medication were obtained at all visits after baseline. Patient global evaluation and clinician global impression were obtained at weeks 3 and 8. Safety was assessed by adverse events, vital signs, laboratory analytes, and electrocardiogram. No dosage of lanepitant differed significantly from placebo. Efficacy did not increase with lanepitant dosage, and higher plasma concentrations were no more effective than lower plasma concentrations. The adverse event diarrhea was more frequent for lanepitant-treated patients. Although well tolerated, lanepitant was ineffective in relieving pain of diabetic neuropathy.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

In patients with epilepsy the older antiepileptic drugs induce distinct electroencephalographic changes and may also alter visual function. Although the effects of the newer antiepileptic drugs on the electroencephalogram remain less clear, long-term treatment with vigabatrin (VGB) has been reported to induce severe and permanent visual impairment. Our aim in this study was to investigate the effects of a single oral dose of VGB and carbamazepine (CBZ) on visual function in normal healthy volunteers randomly assigned to three groups according to a single-blind, placebo-controlled design. All subjects underwent color visual evoked potential tests and color perimetry at baseline and after receiving placebo, VGB (2,000 mg) or CBZ (400 mg). Whereas CBZ induced a mild overall impairment of the chromatic and achromatic systems, VGB induced a selective blue impairment. The differential changes the two antiepileptic drugs induced in visual tests presumably depend on their different mechanisms of action. The selective blue impairment in color visual tests in VGB-treated healthy subjects is consistent with gamma-aminobutyric acid (GABA)–ergic inhibition also at retinal level. Hence, color visual tests may be suitable to detect initial visual abnormalities in VGB-treated patients with epilepsy.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The purpose of this study was to examine the effects of 3-O-methylation by catechol-O-methyltransferase (COMT) on the toxicity of levodopa in neuronal cultures. High concentrations of levodopa are toxicin vitro.Therefore, there is concern that long-term treatment with levodopa in patients with Parkinson's disease might accelerate the rate of degeneration of nigrostriatal neurons. However, recent studies have suggested that, while levodopa is harmfulin vitro,it may not be toxicin vivo.A possible defense mechanism is by means of metabolic shunting of levodopa excess to 3-O-methyldopa by COMT in peripheral and central nervous system tissues. In this study we examine whether the use of COMT inhibitor, which reduced the levels of 3-O-methyldopa, affect levodopa toxicity. Mice cerebellar granule neurons, PC12, and neuroblastoma cells were used, and their viability following exposure to levodopa and COMT with and without tolcapone, a COMT inhibitor, was measured by neutral red staining. Auto-oxidation of levodopa was evaluated using a spectrophotometer (690 nm). We found that 3-O-methyldopa, unlike levodopa, was not toxic to all cells examined. Addition of purified COMT to levodopa prevented its auto-oxidation and markedly attenuated its cytotoxicityin vitro.Additional tolcapone reversed the protective effect of COMT. The agent 3-O-methyldopa is not toxic to cell cultures. Catechol-O-methyltransferase attenuates toxicity of levodopain vitroby its metabolism to nontoxic 3-O-methyldopa.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The latency of P300 “cognitive” event-related potentials changes if cholinergic activities of the central nervous system are pharmacologically manipulated. We tested the hypothesis that the new cholinesterase inhibitors donepezil (DPZ) and rivastigmine (Riv) may have an effect on the frequently abnormal P300 component in patients with Alzheimer disease (AD), thereby allowing a significant evaluation of cholinesterase inhibitors. We evaluated 60 patients with mild to moderately severe probable AD, in comparison with 60 age-matched control subjects, with P300 recordings and neuropsychologic examinations. Forty patients were randomly assigned in a double-blinded trial to 5–10 mg/d DPZ versus 2,000 IU/d vitamin E, and 20 patients were instead treated in an open trial with 1.5 to 12 mg/d Riv. In patients treated with vitamin E, we observed latency increments (7.4 ± 3.5 msec) correlated with worsening neuropsychologic test scores. In patients treated with DPZ and Riv, we found significant P300 latency reductions (15.3 ± 3.2 msec and 22.0 ± 3.3 msec). Shorter P300 latencies were associated with higher Wechsler Adult Intelligence Scale scores and with lower AD Assessment Scale–cognitive subscale (ADAS-cog) scores (R= 0.72). Correlations between ADAS-cog changes and P300 changes significantly separated patients treated with DPZ and Riv from those treated with vitamin E. Administration of DPZ and Riv reduced the latencies of P300 components proportionately to neuropsychologic test improvements. Combined P300 and neuropsychologic test evaluation significantly separated DPZ-treated patients and Riv-treated patients from vitamin E-treated patients.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

A revision of an “excitotoxic hypothesis” of schizophrenia is summarized. The hypothesis suggests that in, at least, a subtype of patients with schizophrenia, progressive excitotoxic neuronal cell death in hippocampal and cortical areas occurs via “disinhibition” of glutamatergic projections to these areas. Patients who have excitotoxic damage would be expected to have poor outcomes characterized, perhaps, by anatomic evidence of progressive neurodegeneration, pronounced negative symptoms and cognitive deficits, and profound psychosocial deterioration. Disinhibited glutamatergic activity could result from inhibition of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission and a consequent failure to stimulate inhibitory gamma-aminobutyric acid (GABA)–ergic interneurons, and/or anatomic degeneration of inhibitory GABAergic interneurons. The result of these hypothesized mechanisms is excessive stimulation of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate class of glutamate receptor complexes. In turn, this excessive stimulation of AMPA/kainate receptors could lead to disruption of ionic gradients, depletion of energy reserves expended in an attempt to restore and maintain the ionic disequilibrium across neuronal membranes, generation of reactive oxygen species, and cell death from apoptotic and other mechanisms. The postulated existence of disinhibited glutamatergic neurotransmission and the subsequent cascade of excitotoxic events resulting from NMDA receptor hypofunction (NRH), anatomic degeneration of inhibitory GABAergic interneurons, or a combination of the two has suggested a diverse variety of experimental therapeutic interventions for schizophrenia. These interventions include facilitation of NMDA receptor-mediated neurotransmission, potentiation of GABAergic neurotransmission, antagonism of AMPA/kainate receptors, and “quenching” of locally generated reactive oxygen species. In fact, several of these approaches have already been pursued or are proposed as part of a systematic clinical investigation of the revised excitotoxic hypothesis of schizophrenia.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We have compared the effects of entacapone, a peripherally acting catechol-O-methyltransferase (COMT) inhibitor, and placebo on cardiovascular autonomic responses in L-Dopa/dopa decarboxylase inhibitor–treated patients with Parkinson's disease (PD). In a double-blind, randomized, crossover study with two consecutive 1-week treatment periods, a battery of cardiovascular reflex tests (orthostatic, Valsalva, deep breathing, and isometric hand grip tests) was performed in a group of 15 patients with idiopathic PD. The first set of tests was performed after withholding L-Dopa overnight (control, “off” stage). The second and third sets of tests were performed in “on” stage after 1-week treatment with either entacapone 200 mg or placebo administered with each dose of L-Dopa/dopa decarboxylase (DDC) inhibitor. Valsalva, deep breathing, and orthostatic tests demonstrated no statistically significant differences in the ratio of the longest and shortest electrocardiographic R-to-R wave (R-R) intervals between entacapone and placebo or between study treatments and control. Blood pressure responses to both orthostatic challenge and prolonged isometric work (hand grip test) were similar between treatments. Systolic orthostatic hypotension was observed in only one patient during the control test, but it occurred more frequently after L-Dopa/DDC inhibitor, regardless of concomitant administration of either entacapone (n= 3) or placebo (n= 4). Peripheral COMT inhibition with entacapone does not significantly alter cardiovascular autonomic responses in L-Dopa-treated patients with PD.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The objective of the study was to investigate the effects of estrogen on severity and duration of myoclonus in the rat cardiac arrest model of posthypoxic myoclonus. Female sex hormones affect a variety of movement disorders and alter dopaminergic and serotonergic pharmacology. Although women represented three-fourths of patients from the original report of Lance and Adams and 80% of the largest published series, the impact of estrogens on myoclonus has never been studied. Twelve previously ovariectomized female rats underwent 8 minutes of mechanically induced cardiac arrest and were resuscitated according to a standardized protocol. On the same day, they were randomly assigned to subcutaneous treatment with a 21-day, 0.5-mg, 17 &bgr;-estradiol or matching placebo pellet. Animals were tested daily with 7 sets of 45 auditory stimuli for 10 days, and myoclonus scores were obtained using a 5-point interval scale. Comparisons were based on two-sample Wilcoxon rank-sum tests. Estrogen treatment significantly enhanced myoclonus intensity and duration: mean peak myoclonus score, 210.2 ± 18.0 versus 180 ± 28.5 (p= 0.031); mean number of days above baseline, 9.2 ± 0.4 versus 5.7 ± 2.3 (p= 0.004); mean score on day 10, 90.7 ± 38.7 versus 27.0 ± 20.6 (p= 0.016). All estrogen-treated animals were above baseline on day 10 compared with none in the placebo group. Estrogen enhances and prolongs posthypoxic myoclonus, suggesting that female gender and estrogen status may play a pivotal role as a risk factor for human posthypoxic myoclonus.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID