摘要:

Rapid and accurate management of a patient afflicted by cerebral ischemia is crucial for the development of a successful outcome. Yet, it is the understanding of the molecular and clinical presentation of cerebrovascular disease that enables the physician to diagnose and effectively treat cerebral ischemia. Neuronal degeneration can occur at several levels in the ischemic cascade. The free radical nitric oxide (NO) has been clearly linked to ischemic neurodegeneration in both animal models and cell culture systems, but the final cellular pathways that lead from the generation of NO to eventual neuronal death require further investigation. The protective mechanisms of the peptide growth factors basic fibroblast growth factor and epidermal growth factor appear to be linked to the signal transduction pathways of NO, programmed cell death, and protein kinase C. Active modulation of metabotropic glutamate receptor activity also can prevent neuronal injury at or below the level of NO generation. The molecular mechanisms that mediate the protective effects of the metabotropic glutamate receptors are dependent on the modulation of programmed cell death. Further investigation into the molecular signal transduction pathways that are responsible for ischemic neuronal injury will foster the development of efficacious and safe treatments for cerebral ischemia.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

This review examines the features of the 16 randomized controlled trials that have been published on the use of oral tacrine for treating probable Alzheimer's disease and explores the methodologic problems associated with these studies. Patient selection using the standard National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria is now a feature of all studies; however, the specificity of the diagnosis, the severity of the dementia, the heterogeneity of the dementia with respect to disease and patient genotype, and the health status of the patients all are factors that may affect responsiveness to therapy. Most studies use crossover designs; however, because of the progressive nature of the disease and the variability in the rate of decline, parallel group studies over a length of time sufficient to produce worsening in disease severity in a placebo group appear to be most suited to detecting clinically relevant therapeutic effects. The close relation between dose, efficacy, and serious adverse events has been a problem in the tacrine trials, since many studies, titrating to maximum tolerated doses, have used clinically ineffective doses. This problem can be circumvented by the use of fixed-dose regimens. Three broad classes of outcome measures have been used to assess treatment efficacy: 1) performance-based tests of cognitive function, 2) global impressions of change on the part of the clinician or care giver, and 3) functional measures of daily living. Including a limited number of each type of measure provides strong evidence of clinically relevant therapeutic benefit; however, more widely accepted and better validated instruments need to be developed for all three areas.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Behavior disorders frequently are associated with mental retardation. The most common interventions involve psychotropics, behavior modification, or both. Etiologically based treatments, derived from an understanding of underlying disease pathogeneses, are infrequent. However, several genetic diseases are associated with elevated rates of destructive responding. The hyperphenylalaninemias provide an excellent model for alternative interventions that have clear biological plausibility. A literature review is undertaken that provides the biochemical rationale for treatment with a low-phenylalanine diet. Several phenylalanine dietary control studies designed to manage aberrant responding among patients with hyperphenylalaninemia are summarized. Together they provide strong evidence that dietary phenylalanine restriction is the treatment of choice among patients ranging from classic phenylketonuria to milder hyperphenylalaninemia. Corroborating evidence derived from phenylalanine loading, magnetic resonance imaging, and dietary amino acid supplementation studies is presented.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Selfotel (CGS 19755), a competitivey N-methyl-D-aspartate antagonist, is neuroprotective in experimental models of ischemic cerebral injury. We studied the safety and tolerability of a single intravenous dose (0.5 to 2.0 mg/kg) of selfotel in neurosurgery patients. Thirty-two neurosurgical patients undergoing intracranial surgery were given ascending doses of selfotel 2 to 14 h before surgery. Serum selfotel levels were measured over a period of 24 h. Cerebrospinal fluid (CSF) levels were measured 1.5 to 18 h after dosing. Frequent side effects included psychomimetic symptoms such as hallucinations, abnormal dreaming, agitation, and paranoia among 20 (66%) patients. Ataxia was seen among five (16%) and dizziness among eight (25%). Symptoms occurred 38 min to 40 h from administration and persisted 5 min to 4 days. Symptom severity worsened with increasing area under the curve measurements and doses above 1.0 mg/kg. All symptoms were reversible and easily treated with intravenous haloperidol. Modest elevations of hepatic enzymes were observed among four patients. No patient had severe adverse reactions. Maximum selfotel levels attained were 143 μmol (serum) and 4.76 umol (CSF). Peak serum levels among six patients were within potentially neuroprotective ranges. CSF levels remained detectable up to 18 h after dosing. No obvious relationship was seen between CSF drug levels and symptoms. Selfotel in doses of 0.5 to 2.0 mg/kg can be administered safely to neurosurgical patients. Maximum serum levels attained were within the range shown to be neuroprotective in experimental studies. Side effects even at the highest levels are tolerable and reversible. Selfotel use in patients at risk for cerebral injury should be further explored.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BAM-1110 [(5R,8R,10R)-6-methyl–8–(1,2,4-triazol-l-ylmethyl) ergoline maleate] is a newly synthesized dopamine agonist that produces little anorexic side effects (nausea and vomiting). The current study examines the effects of BAM-1110 on parkinsonian symptoms in l-methyl–4–phenyl-l,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, an animal model of Parkinson's disease. First, a significant antiparkinsonian effect of apomorphine hydrochloride (0.3 mg/kg given subcutaneously) was confirmed in these animals. BAM-1110 (0.1, 0.3, and 1 mg/kg subcutaneously) relieved parkinsonian symptoms in a dose-dependent manner. Significant effects were observed at doses of 0.3 and 1 mg/kg and lasted for at least 3 h. BAM-1110, at a dose of 0.3 mg/kg that produced the submaximal antiparkinsonian effect, did not induce significant abnormal behaviors such as hyperactivity and stereotyped behaviors. Significant stereotyped behaviors were observed at 1 mg/kg of BAM-1110. Apomorphine induced hyperactive and stereotyped behaviors in parallel with its antiparkinsonian effect. BAM-1110 appears to be a potentially useful dopamine agonist to treat Parkinson's disease because of its relatively weak drug-induced hyperactive disturbances and anorexic side effects.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The effect of lamotrigine (LTG) as add-on therapy on electroencephalogram (EEG) background activity was studied in 11 patients with refractory partial seizures with or without secondary generalization. The computerized EEG study was performed at rest with eyes closed (EC), during blocking reaction (BR), fixation (FIX), and mental arithmetic (MA) tasks. EEG spectral values were analyzed statistically using three-way ANOVA. The neuropsychological evaluation included a battery of six tests. Epileptic patients before LTG therapy, compared with control subjects, displayed at rest condition EEG changes consisting of higher delta and theta relative power coupled with lower alpha and beta power. During performance of attentive (BR) and cognitive (FIX) tasks, a decrease in alpha reactivity associated with a decrease of beta1 and beta2 power was found. The addition of LTG to previous therapy induced changes, although subtle, consisting of an increase in both alpha reactivity and beta power to attentive task. Neuropsychological evaluation did not evidence any impairment of cognitive functions. During LTG therapy, a decrease in seizure frequency occurred in 9 of the 11 patients whereas no changes were observed in the remaining 2. On the basis of these neurophysiologic and neuropsychological findings, LTG as add-on therapy does not seem to produce adverse side effects on mental activity; moreover, EEG data indicate a slight improvement in attentional processes.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Although therapy with acetylsalicylic acid (aspirin, ASA) is well established in secondary prevention of stroke, efficacy and side effects of this substance in acute stroke treatment are undetermined. ASA may be useful in acute cerebral ischemia because of its potential to prevent thrombus propagation and neuronal damage. A total of 268 patients with an acute cerebral ischemia, who were admitted to our stroke unit within 24 hours after stroke, were treated with intravenously administered ASA (0.5 g/day) in combination with low-dose heparin. The functional status of the patients was assessed after 1 month using the modified Rankin Scale. Eighteen (6.7%) patients died during the observation period. The functional status according to Rankin Scale was classified as stage 0 in 76 (28.3%), 1 in 59 (22.0%), 2 in 39 (14.6%), 3 in 32 (12.3%), 4 in 36 (13.4%), and 5 in 7 (2.6%) patients. A symptomatic secondary intracerebral hemorrhage was seen in one patient. Gastrointestinal symptoms were observed in 13 (4.8%) patients, including five instances of gastrointestinal bleeding. Further complications were allergic reactions to aspirin (one) and hematuria (one). Recurrent cerebral ischemia occurred in nine (3.3%) patients (five with transient ischemic attack or minor stroke) during the observation period. We conclude that treatment of acute ischemic stroke with intravenously applied aspirin in combination with low-dose heparin is safe. Efficacy of this therapy should be elucidated in a controlled trial.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Serum levels of sex-hormones, sex-hormone binding globulin, gonadotropin, and prolactin were evaluated during the follicular and the luteal phases in 65 women with epilepsy and in 20 healthy controls. Twenty-one patients were treated with sodium valproate (VPA), 21 with phenobarbital (PB), and 23 with carbamazepine (CBZ). VPA does not stimulate liver microsome enzymes, whereas PB and CBZ do. Patients on VPA therapy showed higher body weight and body mass index, but no significant differences in hirsutism score, or in ovary volume or polycystic ovary prevalence (at ultrasound examination). Estradiol levels were lower in all patient groups than in healthy controls in the follicular but not in the luteal phases. VPA affected luteal progesterone surge in 63.6% of cases. This effect was significantly lower in the CBZ and PB groups. Furthermore, increases in testosterone and δ4-androstenedione levels and in free androgen index, along with a higher luteinizing hormone-follicle-stimulating hormone ratio in the luteal phase, were observed in women treated with VPA. Although sex-hormone binding globulin levels were higher in CBZ and PB than in VPA-treated patients, the differences were not significant because of the wide dispersion of the carrier protein levels. Inducer antiepileptic drugs decreased dehydroepiandrosterone sulfate levels, which remained unchanged during VPA treatment. No significant differences occurred in basal gonadotropin and prolactin levels.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Sertraline (Zoloft) is a selective serotonin reuptake inhibitor that is commonly used in adults in the treatment of mood and anxiety disorders. Whereas it also is used to treat these illnesses in children, it is not currently approved by the Food and Drug Administration for use in this population. Sertraline use has been increasing secondary to its efficacy and its more tolerable side effect profile than the tricyclic antidepressants. It is also much safer in overdose than the tricyclic antidepressants. Although there have been numerous reports of sertraline overdose in adults, reports in the pediatric population are much less common. We review the literature regarding sertraline overdose in children, describe a case of sertraline ingestion in a 22-month-old infant, and discuss the treatment of such an overdose.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Disturbance of metabolism of trace elements and antioxidants are investigated in epileptic patients with long-term therapy of anticonvulsants. One hundred and fifteen subjects including healthy controls, untreated epileptic patients, and phenytoin (PHT)- or carbamazepine (CBZ)-treated epileptic patients were recruited in this study. Serum malondialdehyde was measured as an index of extracellular lipid peroxidation. The levels of serum copper (S-Cu), serum zinc, copper/zinc superoxide dismutase (CuZn-SOD), and reduced glutathione in the serum were monitored simultaneously. The results showed that malondialdehyde, S-Cu, and CuZn-SOD levels in the serum all were significantly increased, but the glutathione level was significantly decreased, in all the epileptic patients with PHT monotherapy compared with those of the controls. However, no significant differences of these parameters in the epileptic patients with CBZ monotherapy were found except for a mild elevation of the activity of serum CuZn-SOD. We conclude that compared with PHT monotherapy, the CBZ monotherapy induced less disturbance in trace element metabolism, antioxidants, and lipid peroxidation in the serum of epileptic patients.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID