The aim of this study was to examine global functioning, health-related quality of life (HRQOL), and clinical outcome in children and adolescents with bipolar I disorder, schizophrenia, or ...schizoaffective disorder following ziprasidone treatment.
Sixty-three subjects (aged 10-17 years) received open-label ziprasidone, titrated from 10 to 40 mg twice a day (b.i.d.) (low-dose group) or from 20 to 80 mg b.i.d. (high-dose group); fixed doses were used until week 3, followed by flexible doses for 6 months. The Children's Global Assessment Scale (CGAS) characterized functional impairment at baseline and following treatment. The Child Health Questionnaire (CHQ) assessed HRQOL at baseline.
Baseline CHQ showed greater impairment in psychosocial functioning than in physical health. Baseline mean CGAS scores were substantially below normal (i.e., <70), indicating functional impairment. Improvement in CGAS scores occurred as early as the first week of treatment. The low correlations between both CHQ and CGAS and the efficacy measures at baseline indicate that these scales measure different constructs. Nevertheless, there was good correlation between improvements in the CGAS and changes in Brief Psychiatric Rating Scale-Anchored (BPRS-A) and Young Mania Rating Scale (YMRS) during ziprasidone treatment.
CHQ and CGAS scales may be useful together with standard efficacy measures for children and adolescents with these disorders.
ZK 200775 is a selective competitive AMPA receptor antagonist. It has demonstrated neuroprotective efficacy in experimental models of stroke and tolerability in healthy volunteers. We tested the ...safety and tolerability of ZK 200775 in patients with acute ischaemic stroke.
In a multicentre double-blind, randomised, placebo-controlled phase II trial, 61 ischaemic stroke patients were treated with either placebo or active drug in a dose finding design. Twenty-five patients received placebo, 12 patients received a total dose of 262.5 mg in 48 h (group 1) and 13 patients received a total dose of 525 mg in 48 h (group 2), and 11 patients received a total dose of 105 mg over a period of 6 h (group 3). We studied the pharmacokinetics of the compound and the effect of the infusion on the neurologic and haemodynamic parameters of the patients. The study was not powered to detect neuroprotective efficacy.
In group 2 there was a significant transient worsening in the mean NIH stroke scale score 14- 18 h after the start of treatment. This was due to reduction of consciousness (stupor and coma) in 8 out of 13 patients. Level of consciousness improved approximately 6 h after cessation of infusion. No significant haemodynamic responses were observed. Even after reduction of the administered dose and duration of infusion to 6 h (group 3), 2 patients experienced a reduction in level of consciousness. The effect of ZK 200775 on level of consciousness gave cause for concern and the trial was stopped prematurely for safety reasons.
The AMPA antagonist ZK 200775 reversibly worsened the neurological condition in patients with acute ischaemic stroke. Our results suggest that ZK 200775 exerts significant sedative effects in patients with acute stroke which preclude its further development as a neuroprotective agent in this indication.
S-100B and neuron-specific enolase (NSE) serum concentrations can be used as peripheral markers of glial cell and neuronal damage, respectively. We investigated these markers in a clinical trial with ...the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) antagonist ZK200775 in acute ischemic stroke patients.
In a multicenter, double-blind, randomized, placebo-controlled phase 2 trial, 61 ischemic stroke patients were treated with either placebo or active drug in a dose-finding design. Twenty-five patients received placebo, 12 patients received a total dose of 262.5 mg in 48 hours (dose group 1), and 13 patients received a total dose of 525 mg in 48 hours (dose group 2). Eleven patients received a total dose of 105 mg over a period of 6 hours (dose group 3; reduction of total dose and infusion time because of adverse events in group 2). Serum concentrations of S-100B and NSE were analyzed with the use of a monoclonal sandwich immunoluminometric assay. Neurological outcome was assessed with the National Institutes of Health Stroke Scale (NIHSS).
In group 2 there was a significant transient worsening in the mean NIHSS score 48 hours after the start of treatment. The mean increase was 11 points. This was due to reduction of consciousness (stupor and coma) in 8 of 13 patients. Neurological deterioration in group 2 was associated with a higher increase of S-100B concentrations, but not of NSE concentrations, than in the placebo group. The trial was stopped prematurely for safety reasons.
The AMPA antagonist ZK200775 transiently worsened the neurological condition in patients with acute ischemic stroke. Our results suggest that in addition to neuronal dysfunction, glial cell toxicity may have occurred. It may be useful to introduce monitoring of serum markers of brain damage in phase 2 trials with glutamate receptor antagonists.
Abstract Objective To compare the efficacy, safety and tolerability of sumanirole with placebo in patients with idiopathic restless legs syndrome (RLS). Methods In this double-blind, ...placebo-controlled, randomized, parallel-group, dose–response study, 270 patients with idiopathic RLS were enrolled and randomized to receive sumanirole 0.5, 1.0, 2.0, or 4.0 mg, or placebo. The primary efficacy endpoint was mean change of the total score of the International Restless Legs Scale (IRLS-10), a 10-item scale, from baseline to end of maintenance. Secondary assessments included polysomnography (PSG) variables. Results Treatment with sumanirole was well tolerated. Mean change in IRLS-10 showed no statistically significant change compared with placebo at any dose, although the mean change with the 4.0-mg dose was numerically greater than the other doses and placebo. PSG variables, specifically the periodic leg movements during sleep, showed statistically significant dose-related improvement in favor of sumanirole. Consistent with earlier multinational, multicenter studies in RLS, high placebo response rates were seen with IRLS-10 but not with PSG variables. Conclusions Given data published in Parkinson’s disease, the dose range of sumanirole selected here may have been too low. Alternatively, dopamine D2 selective agents could be intrinsically less effective than agonists with combined D2 /D3 activity. Sumanirole demonstrated an excellent safety profile.
Single cells were recorded in area 17 of anaesthetized and paralyzed cats and their responses to curved stimuli and chevrons compared. Striate cells exhibited three different response patterns. A ...first group responded optimally to a straight line (i.e. zero curvature) and responded similarly to chevrons and to curved lines. A second group responded to all curvatures and was broadly tuned for the straight line when tested with chevrons. A third group responded only to large curvatures, many (2/3) to both signs of curvature and a number (1/3) to only one sign. Cells in this group responded differently to chevrons and curved lines. Cells in these three classes differed both in length-response curve and in width of orientation tuning. Laminar analysis revealed that the three classes are distributed differently across cortical layers. These data shed new light on the finding of Malpeli and coworkers that orientation is extracted at least twice in a cortical column.
The purpose of this study was to validate a computerised psychometric test system by demonstrating the change of the test variables of the Bochum Diagnostic System after administration of alcohol. ...Twenty-four healthy young male or female volunteers participated in a doubleblind, randomised, placebo-controlled study in a 3-way cross-over design. The volunteers took single doses of placebo, 0.4 and 0.7 g alcohol/kg body weight (females: 10% less) in a random sequence. Psychometric tests were performed before as well as 1 and 3 h after the administration of alcohol. The effects of alcohol on the psychometric performance were most pronounced 1 h after administration. At this time a significant dose-dependent impairment of performance in the concentration test, the simple and complex reaction tests, the vigilance test and the coordination test was observed. 3 h after administration, significant effects were only observed in the complex reaction test and the concentration test. Maximal alcohol serum concentrations of 0.47 +/- 0.05 % per thousand and of 0.90 +/- 0.15 % per thousand were reached after administration of 0.4 g/kg and 0.7 g/kg, respectively. The correlations between individual serum alcohol concentrations and differences of psychometric variables from baseline were significant. It is concluded that the tests of the Bochum Diagnostic System can quantitatively measure the effects of alcohol. The most sensitive tests are the complex reaction test and the concentration test.
197 native, drug-free healthy young volunteers performed psychometric tests on a single occasion, using a new multi-user computerized test system which consists of tests of simple reaction time, ...complex reaction time, vigilance, concentration, motor coordination, short-term memory (word pairs or figures) and abstract language-free reasoning (2 versions). Normality of distribution of all psychometric variables was checked. For the reasoning tests and the memory tests, internal consistency and parallel test reliability were determined. Cross-correlations between the variables and factor analysis were done to evaluate whether different tests measure different brain functions. Multivariate variance analysis was carried out to test the effect of the independent factors school education, gender and age on the performance in the psychometric tests. Subjects with a lower school education level performed worse in the reasoning tests, the concentration test and the memory tests. Females were slower in the coordination test and made fewer correct solutions in the concentration test. Older subjects performed worse in the reasoning tests and had a longer working time in the memory tests than younger ones. The results show the necessity of psychometric screening of volunteers before recruitment for clinical pharmacological psychometric studies in order to reduce-individual variability.
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