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Biomedical subjects

O Blin

Publications and source records attributed to O Blin.

At least 55 records · Page 3Linked to original sources

Serotonin and human information processing: fluvoxamine can improve reaction time performance.

Fluvoxamine is a specific serotonin reuptake inhibitor. Recent evidence suggests that this antidepressive drug shortens the reaction time (RT) of healthy volunteers. The first objective of the present study was to decipher whether this effect is due to an improvement in information processing per se or to the adoption of an error-prone strategy. The second objective was to locate the effect of fluvoxamine within the series of information processing stages by means of Sternberg's additive factor method. After administration of a single oral dose of fluvoxamine (100 mg) or a placebo (randomized double-blind, cross-over design), eight healthy volunteers performed a choice RT task in which stimulus intensity, stimulus-response compatibility and response repertoire were manipulated. Fluvoxamine shortened RT without decreasing the accuracy of the responses. This demonstrates that fluvoxamine improves information processing per se. The effect of fluvoxamine was additive on RT with the respective effects of stimulus intensity and stimulus-response compatibility. This result suggests that fluvoxamine spares the processing stages of stimulus preprocessing and response selection.

Adult↗

Olanzapine versus haloperidol: acute phase results of the international double-blind olanzapine trial.

A 6-week acute phase of an international 1-year double-blind study was conducted comparing three dose ranges of olanzapine (5 +/- 2.5 mg/day, 10 +/- 2.5 mg/day, and 15 +/- 2.5 mg/day) with a fixed dose of olanzapine (1.0 mg/day) and with a dose range of haloperidol (15 +/- 5 mg/day) in the treatment of 431 patients with schizophrenia. The purpose was to determine whether olanzapine demonstrated a dose-related ability to decrease overall psychopathology with minimal associated extrapyramidal symptoms in patients with schizophrenia. The high-dose olanzapine group showed statistically significantly greater improvement in overall psychopathology based on mean change in the CGI Severity score and statistically significantly greater improvement in positive psychotic symptoms based on mean change in both the BPRS positive score and the PANSS positive score compared with the 1.0-mg/day olanzapine group. Analyses indicated that an increasing dose-response curve was observed across the range of all olanzapine dose groups. Acute extrapyramidal syndromes were reported less frequently among all olanzapine groups compared with the haloperidol group. Endpoint mean change on both the Simpson-Angus Scale and the Barnes Akathisia Scale reflected improvement for all olanzapine treatment groups compared with worsening for the haloperidol group. Olanzapine was associated with weight gain but did not appear to have any clinically meaningful effect on vital signs. Although olanzapine was associated with some increase in prolactin concentrations, increases were transient, occurred less often, and were of lesser magnitude than those observed with haloperidol.

Adult↗

Effects of lorazepam on film-induced differentiated emotions in healthy volunteers.

We studied the effects of lorazepam, a benzodiazepine, on differentiated emotions in healthy volunteers. In order to induce differentiated emotions, film excerpts were selected on the basis of the type of emotion they induced (fear, anger and for affective tone neutral film). For 6 days (D1 to D6), ten healthy volunteers received lorazepam (1 mg bid) or placebo in a randomized cross-over double-blind trial. During each treatment period, emotional induction occurred on D4, D5 and D6. One film excerpt (fear, anger or neutral) was presented each morning after relaxation. Evaluation was performed before and after each emotional induction and included questionnaires (Differential Emotions Scale and physical activation visual analog scales), and neurophysiological parameters (systolic and diastolic blood pressure, heart rate and norepinephrine levels). Globally, the film excerpts induced the predicted emotions. An analysis of variance was undertaken and revealed a significant effect of lorazepam versus placebo. On the Differential Emotions Scale and during fear induction, lorazepam induced a significantly higher increase in fear, anxiety and disgust emotions than placebo, whereas no effect was observed after anger induction. Lorazepam also induced a significantly higher increase in diastolic and systolic blood pressure with no change in heart rate, and physical activation items ("tears" and "faster breathing") without no significant change in norepinephrine. In conclusion, our results are consistent with an overall increase in emotional reactivity with lorazepam (1 mg bid) as compared to placebo. The pertinence of film-induced differentiated emotions has to be confirmed for clinical pharmacological use.

Adult↗

Long term follow up of multifocal motor neuropathy with conduction block under treatment.

Eighteen patients (15 men, three women; age range 30 to 71 years, mean 45.8 years) with multifocal motor neuropathy treated with high dose intravenous immunoglobulin (IVIg) were evaluated for nine to 48 months (mean follow up 25.3 months). The median time between onset of multifocal motor neuropathy and treatment was 5.8 years. The dose of IVIg was 0.4 g/day for three to five days. The interval between each treatment was determined for each patient by the evaluation of the effect of the first course. Muscle strength was evaluated by a computerised analyser. Clinical improvement was seen in 12 patients treated with IVIg (67%). Isometric strength increased from 32% to 97% (mean 54.5%) of the initial value. Functional scales corroborated these findings. No clear predictive factors of response to IVIg was found except the presence of high titres of IgM anti-GM1 antibodies. Often, patients needed repeated courses of IVIg to maintain the improvement. In two patients, IVIg infusions were stopped without signs of relapse after one year. Four patients were initially treated with prednisone (1 mg/kg/day), without any clear improvement. Five patients with no response to IVIg or who were IVIg dependent were treated with cyclophosphamide, but only one showed improvement. These results show the long term benefits and safety of IVIg in multifocal motor neuropathy but also the transient effect of this expensive treatment in most patients.

Adult↗

[Dopamine D2 and serotonin 5HT2 receptors: functions, interactions and clinical consequences in schizophrenia].

This didactic paper reviews the different receptors families, the principal characteristics of the dopaminergic and serotoninergic receptors and their role in the aetiology and pathophysiology of schizophrenia. The current knowledge on interactions between serotoninergic and dopaminergic systems is also summarized. The theoretical and potential interests of these interactions in alleviating neuroleptic-induced extrapyramidal symptoms and improving negative signs in schizophrenia are also examined.

Antipsychotic Agents↗

Plasma concentrations and pharmacokinetics of idebenone and its metabolites following single and repeated doses in young patients with mitochondrial encephalomyopathy.

OBJECTIVE: The pharmacokinetics and tolerance of idebenone after single or repeated doses have been studied in young patients with mitochondrial encephalomyopathy. RESULTS: No significant adverse effects were noted. In 3 out of 7 patients idebenone induced overall stimulation and improvement in arousal. Plasma concentrations of idebenone and its main metabolites were determined and the pharmacokinetic parameters of idebenone after single and repeated doses were estimated. During the single dose study, the mean plasma concentrations of idebenone and its main metabolites and mean pharmacokinetic parameters were comparable to published results (Cmax = 452.2 ng.ml-1, tmax = 2.3 h, AUC = 26 micrograms. ml-1.h, t1/2 beta = 16.5 h). During the repeated doses study, no significant difference was found between mean residual plasma concentrations of idebenone on Day 2 (47 ng.ml-1) and Day 5 (70.6 ng.ml-1), and mean t1/2 beta of idebenone after the single and after repeated dose studies, i.e., there was no evidence of accumulation. Although idebenone did not appear to accumulate during this study, the coadministration of anticonvulsants, often prescribed during mitochondrial encephalomyopathy, can affect its pharmacokinetics.

Adolescent↗

A controlled one-year trial of dextromethorphan in amyotrophic lateral sclerosis.

In a one-year parallel group double-blind placebo-controlled study of dextromethorphan (1.5 mg/kg) in amyotrophic lateral sclerosis, no significant differences were observed in the rate of progression (Norris scale) in comparing 24 patients randomly assigned to the dextromethorphan group and 25 patients randomly assigned to the placebo group. Of the 24 patients in the dextromethorphan group, 17 had limb onset and 7 had bulbar onset disease; average duration of disease was 12.5 +/- 6 months and sex ratio (M:F) was 1.4:1. Of the 25 patients in the placebo group, 18 had limb onset and 7 had bulbar onset disease; average duration of disease was 9.9 +/- 6 months and sex ratio (M:F) was 1.55:1. Dextromethorphan is a weak noncompetitive N-methyl-D-aspartate (NMDA) antagonist and higher doses or other potent NMDA receptor antagonists should be tested.

Adult↗

Antipsychotic and anxiolytic properties of risperidone, haloperidol, and methotrimeprazine in schizophrenic patients.

The subjects were 62 patients hospitalized for acute exacerbations of schizophrenia and were randomly assigned to receive risperidone (mean dose, 7.4 mg/day), haloperidol (7.6 mg/day), or methotrimeprazine (100 mg/day) for 4 weeks. Clinical improvement, defined a priori as a 20% reduction in total Positive and Negative Syndrome Scale (PANSS) scores at end point, was attained by 81% of the risperidone patients, 60% of the haloperidol patients, and 52% of the methotrimeprazine patients (p < 0.05). The reductions in total PANSS and Clinical Global Impression Scale severity scores from baseline to end point were significantly greater in the risperidone patients than in the other two groups. Reductions in scores on the Psychotic Anxiety Scale were significantly greater in the risperidone patients than the methotrimeprazine patients; the difference between haloperidol and methotrimeprazine was not significant. Extrapyramidal symptoms (scores on the Extrapyramidal Symptom Rating Scale) were more severe in the haloperidol patients than in the other two groups, but few differences were apparent between risperidone and methotrimeprazine patients. It is concluded that risperidone is an effective antipsychotic and anxiolytic agent in schizophrenic patients.

Adolescent↗

[Automatic motion analysis of gait in patients with Parkinson disease: effects of levodopa and visual stimulations].

Gait analysis of 13 patients affected by Parkinson's disease (PD) and 7 healthy elderly volunteers was performed with a fully automatic motion analyser. The recording included stride parameters for walking velocity, stride length, stride duration and swing time. Maximal amplitudes of rotation of the hip, knee and ankle were also recorded. The analysis was performed for the PD's patients before and after L-Dopa intake. All the patients walked with and without transversal stripes on the floor. The contrasting white lines were 45 cm apart. After medication, the stride length, the velocity and the swing phase duration were significantly increased. The movements around the hip, knee and ankle joints that were initially reduced, poorly increased after L-Dopa intake. When stripes were placed on the floor, no significant changes occurred for the overall group of patients. Seven parkinsonian patients did improve with visual guidance, increasing their stride length and their speed. Some rotations of hip and knee were also influenced by stripes. This sub-group of patients was characterized by older age, a slower walking velocity, a smaller stride length and a shorter swing time. We correlated the sensitivity to visual cues to the defect of the visual contrast sensitivity that has been established in PD by several recent works. Locomotion on the transverse lines might have produced a motion perception at a rate determined by the speed of the patient. For appropriate intervals between stripes, one can hypothesise that the resulting visual stimuli belonged to a range of spatio-temporal frequencies that are decreased in patients with PD.

Aged↗

Evaluation of saccadic eye movements as an objective test of recovery from anaesthesia.

Saccadic eye movements have been previously used to assess residual effect of anaesthetics, but this test is seldom compared to other psychomotor tests. The aim of the present study was to validate saccades as a recovery index in relation to frequently referred subjective and psychometric tests. Eight healthy subjects were tested before and after intra-muscular injection of either placebo or 0.15 mg.kg-1 of midazolam. Each session consisted of a saccadic test (recorded by electro-oculography), a choice-reaction-time test (CRT), a subjective state-of-alertness test (11 visual analogic scales) and blood sampling (to monitor midazolam plasma concentration), before and 30 (t30), 60 (t60), 120 (t120), 180 (t180), 240 (t240) minutes after drug administration. In the placebo group, there was no change in subjective assessment, saccade characteristics (latency, peak velocity and duration) or CRT results. In the midazolam group, 6 subjective items changed with different time-courses, when compared to baseline: from t30 to t120 (drowsy, in shape, tired, clumsy, strong) and t120 (woolly). Saccade latency and duration were significantly different from t30 to t120 and until t180 for peak velocity. CRT performance was significantly altered from t30 to t120. Midazolam plasma concentration decreased from 177 +/- 33 ng.ml-1 at t30 to 47 +/- 12 ng.ml-1 at t240. At this latter time, sensorimotor functions returned to the baseline. All subjects fulfilled the clinical conditions for home discharge 4 hours after administration. These results suggest that a saccadic eye movement test is a sensitive and reliable tool for the assessment of residual effect of anaesthetics. This test was found to be more sensitive than CRT test since peak saccadic velocity was the last psychometric parameter to be returned to baseline after midazolam injection. This study also confirms the poor reliability of subjective assessment, as subjects tended to underestimate the alteration of their performance immediately following drug injection.

Adult↗

[Psychopharmacologic approaches to schizophrenic psychoses].

The dopaminergic hypothesis in schizophrenia has progressively shifted to a bipolar hypothesis. Furthermore, there are numerous interactions between dopaminergic systems and other neurotransmission systems. Therefore, several pharmacological approaches are possible either through the specific antagonism of different dopaminergic receptors subclasses, partial dopaminergic agonists or indirect modulation or through the combined blockade of dopaminergic and serotoninergic, cholinergic or adrenergic receptors. The challenge today is to link a given clinical effect to one specific pharmacological property.

Antipsychotic Agents↗

Naltrexone, an opiate antagonist, fails to modify motor symptoms in patients with Parkinson's disease.

One month of adjunct treatment with naltrexone (100 mg/day) was compared with placebo in a double-blind, randomized, cross-over design in two groups of patients with Parkinson's disease. The first group was composed of 10 patients with a moderate motor impairment insufficiently controlled by monotherapy with bromocriptine. The second group was composed of eight patients with L-dopa-induced peak-dose dyskinesia. Naltrexone as compared with placebo did not demonstrate any significant change in motor function in either group. These negative clinical results do not support a significant role of endogenous opioid systems in the pathophysiology of motor impairment in Parkinson's disease.

Aged↗

The quinolone, flumequine, has no effect on theophylline pharmacokinetics.

The kinetics of a single i.v. dose of theophylline given either alone or with flumequine was studied in eight healthy volunteers. No statistically significant differences were observed in the pharmacokinetic parameters of theophylline (volume of distribution, elimination half-life, AUC, plasma clearance) following the two treatments. Pretreatment for 5 days with oral flumequine (400 mg, three times daily) had no significant effect on the disposition of a single i.v. dose of theophylline in healthy volunteers.

Adult↗

Contrast sensitivity improvement with sulfamethoxazole and trimethoprim in a patient with Machado-Joseph disease without spasticity.

A double-blind, placebo controlled, cross-over trial of sulfamethoxazole and trimethoprim was performed in a 62-year-old male patient who suffered from Machado-Joseph disease for 25 years. The patient, with cerebellar ataxia, akinetic-rigid syndrome and motor weakness but without any pyramidal features, had been chair-bound for 3 years before the trial. Bactrim therapy markedly improved performance on a physical examination which tested standing and gait, as compared to placebo session. Walker-assisted gait was possible again. For the first time, evaluation of spatio-temporal contrast sensitivity was performed and also revealed an improvement after Bactrim therapy as compared to placebo. These results suggest that Bactrim may be effective in degenerative neurological diseases and that Bactrim may have an overall effect on neurotransmission rather than solely possessing antispastic properties.

Analysis of Variance↗