ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The spinocerebellar ataxias (SCAs) are diseases characterized by the progressive degeneration and subsequent loss of neurons accompanied by reactive gliosis, degeneration of fibers from the deteriorating neurons, and clinical symptoms reflecting the locations of the lost neurons. The degenerative changes affect specific neuronal groups while others remain preserved, and these diseases can therefore be viewed as system degenerations. The SCAs result from either genetically transmitted diseases with dominant inheritance or unknown causes with sporadic occurrence. Most of these disorders affect the cerebellum and its pathways, resulting in progressive deterioration of cerebellar function manifested by increasing unsteadiness of gait, incoordination of limb movements with impairment of skilled movements such as handwriting, and a distinctive dysarthria. Other neuronal systems are affected in some of these disorders, notably the corticospinal pathway, basal ganglia, and autonomic nuclei of the brain stem and spinal cord.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Chronic hepatic encephalopathy (HE) is a neuropsychiatric syndrome that arises in liver-impaired subjects. Patients with HE display various neuropsychiatric symptoms including affective disturbances and may therefore likely receive treatment with novel thymoleptics like citalopram (CIT). The simultaneous pharmacokinetic and pharmacodynamic outcome of the commonly used serotonin-selective thymoleptic drugs in liver-impaired subjects with pending chronic HE is far from understood today. We therefore investigated the effects of chronic, body-weight-adjusted (10 mg · kg-1· day-1), treatment with CIT in rats with and without portacaval shunts (PCS). Open-field activity was monitored. The 5-HT, 5-HIAA, noradrenaline (NA), and dopamine (DA) output were assessed in the frontal neocortex. The racemic levels of CIT and its metabolites DCIT and DDCIT, including the S- and R-enantiomers, were determined in serum, brain parenchyma, and extracellular fluid. The rats with PCS showed higher (2–3-fold) levels of CIT than rats undergoing a sham treatment with CIT in all compartments investigated. The PCS rats also showed elevated levels of DCIT and DDCIT. No major differences in the S/R ratios between PCS rats and control rats could be detected. The CIT treatment resulted in neocortical output differences between PCS rats and control rats mainly within the 5-HT and DA systems but not within the NA system. For the 5-HT system, this change was further evidenced by outspoken elevation in 5-HT output after KCl-depolarizing challenges. Moreover, the CIT treatment to PCS rats was shown to “normalize” the metabolic turnover of 5-HT, measured as a profound lowering of a basal elevation in the 5-HIAA levels. The CIT treatment resulted in an increased or “normalized” behavioral activity in the PCS group. Therefore, a dose-equal chronic treatment with CIT in PCS rats produced pharmacokinetic and pharmacodynamic changes not observed in control rats. The results further support the contention of an altered 5-HT neurotransmission prevailing in the chronic HE condition. However, the tentatively beneficial behavioral response also seen following chronic CIT treatment to PCS rats in this study has to be viewed in relation to both the pharmacokinetic and pharmacodynamic changes observed.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Cisternal samples of cerebrospinal fluid (CSF) were analyzed for protein, albumin, sodium (Na), potassium (K), and calcium (Ca) content in 21 control subjects and 64 patients who had experienced acute stroke. A second cisternal CSF sample was taken in 37 of the stroke patients after 2–3 weeks treatment with the calcium antagonist nimodipine. Increased permeability of the blood-brain barrier was reflected by the significantly higher CSF/serum ratio of albumin in stroke patients than in control subjects (0.0046 vs. 0.0028,p= 0.0012). Serum and CSF concentrations of Na, K, and Ca did not differ between control subjects and stroke patients. In control subjects and in stroke patients, concentration of calcium in cisternal CSF ([Ca]) was smaller than values reported by others in lumbar samples. In stroke patients, the pH of CSF was lower than that of simultaneously taken blood (7.38 vs. 7.44,p< 0.001). No differences between stroke patients and control subjects were found for the cisternal CSF/serum ratios of Na (1.0 and 0.99), K (0.61 and 0.63), and Ca (0.25 and 0.24). When patients and controls were pooled together, CSF total [Ca] correlated weakly with serum total [Ca] (Spearman r = 0.28,p= 0.014) and with serum ionized [Ca] (Spearman r = 0.27,p= 0.016). After 2–3 weeks of nimodipine treatment, CSF [Ca] was significantly lower in the subgroup treated with 60 mg nimodipine four times daily (240 mg/d) than with 30 mg four times daily. A nimodipine dosage of 30 mg four times daily (120 mg/d) did not affect CSF [Ca]. A 240 mg daily dosage, but not a 120 mg daily dosage, of nimodipine may affect the Ca transport system in humans at the choroid plexus.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Rasagiline mesylate (TVP-1012) is a potent, selective, non-reversible MAO-B inhibitor, without the tyramine-potentiating effect and with neuroprotective activities. The benefit of rasagiline as monotherapy in patients with early Parkinson's disease (PD) has already been reported. To evaluate the safety, tolerability, and clinical effect of rasagiline as adjunctive therapy to levodopa, a multicenter, double-blind, randomized, placebo-controlled, parallel-group study (0.5, 1, and 2 mg/d) was conducted for 12 weeks in 70 patients with PD (mean age, 57.4 y; mean disease duration, 5.7 y; 32 patients had motor fluctuations). A beneficial clinical effect was observed in fluctuating patients treated with rasagiline (all doses), expressed as a decrease in total Unified Parkinson's Disease Rating Scale (UPDRS) score (23.0% vs 8.5% in the placebo group). The treatment effect was still evident 6 weeks after drug discontinuation (in all doses). The safety and tolerability of rasagiline were good. Adverse events were no different than those of patients taking placebo. Almost complete platelet MAO-B inhibition was obtained at all rasagiline doses. This study has demonstrated that rasagiline (up to 2 mg/day) has a good safety profile and a beneficial clinical effect in fluctuating patients with PD when given as an add-on to chronic levodopa therapy.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The objective of this study was to define risk factors for depression in patients with idiopathic Parkinson's disease (PD) and to evaluate the correlation of depression with cognitive function and the primary domains of parkinsonian motor dysfunction tremor, bradykinesia, rigidity, gait and balance impairment. The risk factors for depression in patients with PD remain controversial. Several investigators have demonstrated a significant association between cognitive dysfunction and depression, but motoric and disease variables can confound this evaluation and have shown an inconsistent relation to depression. A consecutive series of 88 patients with PD were examined using the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRSm), Hoehn-Yahr stage (HY), and Hamilton Rating Scale for Depression (HRSD). Major depression was diagnosed according to the criteria in theDiagnostic and Statistic Manual of Mental Disorders, 4th edition. Gender, age, handedness, PD duration, side of PD onset, motor fluctuations, UPDRSm total score, daily Levodopa dose, and Mini-Mental State Examination score (MMSE) were analyzed using multivariate and univariate logistic regression, Fisher's Exact test, and Pearson correlations. Major depression was diagnosed in 12 patients (7.3%). Low MMSE score, axial bradykinesia, gait and balance impairment were strongly significant predictors of depression. In conclusion, depression and physical function are important factors impairing the quality of life for patients with PD, and regular depression screening and treatment should focus on patients with PD who have cognitive impairment, high axial bradykinesia, gait and balance impairment.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Risperidone has been primarily marketed for the treatment of schizophrenia. There are reports about its potential role for the treatment of affective illness. We report here another case of a patient with psychotic depression who was treated successfully with risperidone as monotherapy. This case report suggests that risperidone can be an efficient treatment mode for psychotic depression; however, it needs more data based on controlled study.

ISSN:0362-5664    

出版商:OVID    

年代:2000

数据来源: OVID