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Biomedical subjects

O Blin

Publications and source records attributed to O Blin.

At least 109 records · Page 6Linked to original sources
PubMed1990

Quantitative analysis of walking in patients with knee osteoarthritis: a method of assessing the effectiveness of non-steroidal anti-inflammatory treatment.

Most therapeutic tests of osteoarthritis treatments are assessed by criteria based either on fundamental data or on clinical data, which is often subjective. A quantified analysis of locomotion can be used to determine the spatiotemporal indices (stride length and duration), kinematic indices (walking speed, velocity peak), and symmetry criteria that are relevant to the assessment of locomotor handicaps in patients with osteoarthritis. This study examined the progression of locomotor abilities in 11 subjects aged 49-69 (mean 60.9) years with knee osteoarthritis before and after treatment with a non-steroidal anti-inflammatory drug. Naproxen sodium (1100 mg) was given once a day for seven days. The condition before and after treatment was evaluated by quantitative analysis of locomotion, estimation of pain on a visual analogue scale, and assessment of the degree of functional disability. Significant improvement in locomotor indices (proportional increase in walking speed 17.8%) and in degree of pain (proportional decrease 27%) as estimated on the analogue scale was found after non-steroidal anti-inflammatory drug treatment. The lack of a significant correlation between the decrease in pain experienced by the patients and the objective improvement of their functional capabilities emphasises the need in further studies of new treatments to accompany the patients' own assessments of self improvement with a quantitative analysis of the way in which they walk.

Aged↗
PubMed1990

Spatiotemporal contrast sensitivity differs in normal aging and Parkinson's disease.

We measured contrast sensitivity for static and laterally drifting vertical gratings in 12 young adults, 7 normal elderly adults, and 8 patients with Parkinson's disease (PD). We compared static and motion contrast sensitivity for spatial frequencies of 0.25, 1, and 4 cycles per degree (cpd), and temporal frequencies of 1, 3, and 9 Hz. Results show that normal aging leads to a reduction of motion sensitivity for the spatial frequency of 0.25 cpd. Compared with elderly controls, PD patients do not present specific abnormalities in this domain. However, for spatial frequencies of 1 and 4 cpd and temporal frequencies of 1 and 3 Hz, motion sensitivity is worse than static sensitivity in PD patients and not in elderly controls. These findings suggest a specific deficit of motion perception in PD, and possible dopaminergic involvement in the control of visuospatial behavior.

Adult↗
PubMed1990

[A new method of quantitative analysis of parkinsonian gait: report of 6 patients].

A simple quantitative method of gait analysis in parkinsonism is presented. In this method, spatial and temporal parameters (stride length and duration, stance duration and double support duration) and cinematic parameters (velocity) were evaluated. A pilot trial performed in 6 patients highlighted the pathological aspect of the parkinsonian gait as compared to the gait of healthy elderly subjects. A significant degradation (reduced speed, diminished stride length, short duration of the double support stage) was noted, even when parkinsonians were compared with the oldest of the control subjects.

Aged↗
PubMed1990

[Congenital blepharoptosis. Diagnosis and treatment].

The congenital blepharoptosis is the most frequent palpebral abnormality. The anatomical, physiological and clinical aspects of the congenital blepharoptosis are successively discussed. Clinical and anatomopathological studies support the hypothesis of a myogenic basis for congenital genuine blepharoptosis and the hypothesis of a neurogenic basis for the ptosis with synkinetic phenomena. The different surgical methods are then described and their results compared.

Blepharoptosis↗
PubMedDate not supplied

[Use of antidepressant drugs in schizophrenic patients with depression].

INTRODUCTION: Depression is common in people with schizophrenia and is associated with substantial morbidity explaining also the considerable attention and recognition of this entity as suggested by the inclusion of the post-psychotic depression in DSM IV and ICD 10. The prevalence of this disorder varies according to the type of approach used (range between 7% to 75%). Prescription of antidepressants plus antipsychotic treatment is frequent in clinical practice (11 to 43%). BACKGROUND: Pharmacokinetic and metabolic interactions have been identified. The cytochrome P450 has been identified as being implicated in the metabolism of most psychotropics, mainly through the CYP1A2, CYP2C19, CYP2D6, CYP3A4 isoenzymes. Tricyclic antidepressants are likely to increase chlorpromazine plasma levels. Similarly, antipsychotics such as perphenazine, chlorpromazine or haloperidol can increase antidepressant plasma levels, through the inhibition of CYP 450 isoenzymes (CYP2D6). Most of the Specific Serotonin Recapture Inhibitors (SSRIs) are likely to inhibit one or several CYP450 isoenzymes. The inhibition is moderate to marked for CYP1A2 (fluvoxamine and fluoxetine), CYP2C19 (fluoxetine, fluvoxamine and sertraline), CYP2D6 (paroxetine, fluoxetine and sertraline), and CYP3A4 (fluvoxamine, fluoxetine and sertraline). In the US, one-fourth of psychiatrists report the use of depression-rating scales in schizophrenic patients. Non specific scales (Hamilton Depression Rating Scale or Beck Depression Inventory) are the most commonly used in spite of the fact that these scales do not allow the distinction of depressive from negative symptoms in schizophrenic patients. LITERATURE FINDINGS: Due to these limitations, more specific assessment tools for depressive symptoms in schizophrenia are required. Two specific scales for assessing depressive symptoms in schizophrenic patients have been constructed and validated. The Calgary Depression Scale (CDS) is a nine item scale, each item scored from 0 to 3. This scale was derived from the HDRS and the Present State Examination. Factor analysis showed that the CDS is unidimensional, has high internal consistency, and significant strong correlation with scores on the HDRS, Beck and BPRS depression scales. The CDS has been validated in different languages (Brazilian, Danish, French...). It has been shown that there is no overlap between negative or extrapyramidal and depressive symptoms assessed by the PDS in schizophrenic patients. The Psychotic Depression Scale (PDS) is a 32 item scale derived from the HDRS, PANSS, CPRS and AMDP, each item being rated from 0 to 7. A principal component analysis of the PDS items using a Varimax rotation disclosed 8 orthogonal components that account for 71% of the variance. These components involved the following dimensions : depressive mood, inhibition, vegetative signs, paranoid signs, strangeness of thought, inverse vegetative signs, guilt feelings and cognitive signs. The analysis revealed that the 'depressive mood' factor of the PDS was correlated with the 'depressive' factor and was slightly correlated with the cognitive factor of the PANSS. This first factor was not correlated with either the "negative" factor of the PANSS, or the Positive or Excitement factor of the PANSS. Hence, this PDS, factor distinguished depressive signs from negative symptoms. Due to their metrologic properties, specific scales should be preferred. However, only one open trial (of an antipsychotic) and two double blind controlled trials (one comparison of 2 antipsychotics and one comparison of an cholinesterase inhibitor versus placebo) have been published using the CDS. Likewise, only one double blind controlled trial using the PDS (comparison of 2 antipsychotics) has been published. No study of the effect of antidepressants in depressed schizophrenic patients has been published, using either the CDS or the PDS assessment criteria. DISCUSSION: These specific scales are rarely used in clinical practice. Only about 1% of the US psychiatrists reported the use of the Calgary Depression Scale. Several open clinical trials have assessed the efficacy of antidepressant agents added to antipsychotic in patients with schizophrenia. They have produced inconsistent results but have suffered from methodological limits (short duration of the studies, non homogeneous inclusion criteria, heterogeneous assessment methods...). Due to the lack of a reference drug, double blind placebo-controlled trial are necessary. A recent meta-analysis has been performed on results of trials that have investigated the clinical efficacy of antidepressant medication (either tricyclics, SSRIs or others) in the treatment of depression in schizophrenic patients. In a subset of 5 trials (209 patients), the proportion improved in the antidepressant group was 26% (95% CI 10 to 42) higher than in the placebo group. The estimated number needed to treat was 4. In a subgroup of 6 studies (267 patients), the standardized mean difference on the HDRS score was -0.27 (95% CI - 0.7 to -0.2). There was no evidence that antidepressant treatment induced a deterioration of psychotic symptoms in these trials. CONCLUSION: The results provide weak evidence for the efficacy of antidepressants in patients with schizophrenia and depression. Today, the only SSRI tested in the treatment of depression in schizophrenic patients is sertraline. One study led to positive results. Since the meta-analysis, one additional study has been performed comparing sertraline to placebo. No difference between the 2 treatment groups was demonstrated but the power of the trial was rather low. Further research is required to determine the best approach towards treating depression in patients with schizophrenia, with clinical trials performed for longer periods, using appropriate assessment criteria such as depressive symptoms and quality of life.

Antidepressive Agents↗
PubMedDate not supplied

Pharmacokinetic and pharmacodynamic analysis of sedative and amnesic effects of lorazepam in healthy volunteers.

This study describes for the first time the pharmacokinetic and pharmacodynamic modeling of the psychomotor and amnesic effects of a single 2-mg oral dose of lorazepam in healthy volunteers. Twelve healthy volunteers were included in this randomized, double-blinded, placebo-controlled two-way crossover study. The effect of lorazepam was examined for a battery of tests that explored mood, vigilance, psychomotor performance, and memory. The pharmacokinetic and pharmacodynamic modeling of these tests was performed using the indirect response model. Vigilance and psychomotor performance were significantly impaired. Short-term memory was not affected, but a paradoxical tendency to improvement of the score was observed 0.4 hours after drug intake. Significant impairment was observed for immediate and delayed cued verbal recall, for immediate and delayed free recall, and for picture recognition as well as for visual-verbal recall, but not for cued visual-spatial recall or priming. Globally, the different effects were greatest between 0.4 to 3 hours after dosing. However, the time course profile of the recovery period suggests a possible dissociation between the kinetics of the effects of lorazepam on vigilance, psychomotor performance, and visual episodic memory, on the one hand, and on verbal episodic memory, on the other. The pharmacokinetic and pharmacodynamic model used two compartments with first-order absorption to describe the lorazepam concentrations and an indirect response model with inhibition or stimulation of Kin to describe the effects. The mean values for calculated median effective concentration (EC50) derived from the pharmacokinetic and pharmacodynamic modeling of the different tests ranged from 11.3 to 39.8 ng/mL. According to these EC50 values, lorazepam seemed to be more potent on the delayed-recall trials than on the immediate-recall trials; similar observations were made concerning the free-recall versus cued-recall trials. The previously stated results suggest that the tests performed in this study represent sensitive measurements of the effects of lorazepam on the central nervous system. Moreover, the parameter values derived from pharmacokinetic and pharmacodynamic modeling, especially, the EC50 values, may provide sensitive indices that can be used to compare the central nervous system effects of benzodiazepines.

Adolescent↗
PubMedDate not supplied

Levodopa-induced drowsiness in healthy volunteers: results of a choice reaction time test combined with a subjective evaluation of sedation.

The aim of the present study was to assess levodopa (L-Dopa)-induced drowsiness in healthy volunteers using two parameters: choice reaction time and a subjective rating of sedation. Sixteen subjects participated in a randomized, double-blinded, crossover study. A single dose of 200 mg L-Dopa or placebo was administered at 9:00 AM. To limit peripheral side effects connected with L-Dopa, subjects were treated with 20 mg domperidone three times daily. Subjective rating of sedation consisted of visual analogue scale. Reaction time was measured by means of responses to two light-emitting diodes. The illumination of one of these diodes constituted the imperative signal. Manual responses were performed on two buttons located under the right and left index fingers. Results demonstrated a positive correlation between sedation level and reaction time (r = 0.70, p = 0.0026). Adverse events of L-Dopa were nausea (four cases) and excitation (one case). Subjects who did not develop adverse events were faster under L-Dopa than under placebo (p = 0.02), whereas subjects who had nausea or excitation were slower. A single dose of L-Dopa either deteriorated or improved choice reaction time in healthy volunteers according to whether it was sedative and whether it generated disruptive adverse events.

Adult↗
PubMedDate not supplied

Neurobiology and clinical pharmacology of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a brain disorder with recognizable periods of onset, course, familial occurrence, epidemiology, phenomenology, and treatment response. Several manifestations of pathophysiology are beginning to be defined, although they may represent intermediate pathophysiology rather than primary etiology. Positron emission tomography studies have consistently identified hypermetabolism in the orbitofrontal cortex, caudate nucleus, and, sometimes, anterior cingulate cortex. Neuropsychologic testing frequently identifies abnormalities in visuospatial function. Abnormal levels of cerebrospinal fluid neurotransmitters and neuromodulators are identifiable in untreated patients with OCD and return toward normal levels after effective treatment. The most consistent pathophysiologic finding in OCD points toward an abnormality in serotonin neurotransmission. Therapeutic response to selective serotonin reuptake inhibitors and the absence of improvement with norepinephrine reuptake inhibitors and dopamine antagonists argue strongly for a role of serotonin in the pathophysiology and treatment of OCD. Despite this clear indication from treatment trials, probes and manipulations of the serotonin system and its specific receptors have not provided a useful understanding of specific abnormalities. Clomipramine or potent selective serotonin reuptake inhibitors are the pharmacotherapy of choice for OCD, with a more limited role reserved for monoamine oxidase inhibitors. If one selective serotonin reuptake inhibitor is ineffective, others may be beneficial, in addition to the different proserotonergic and nonserotonergic augmentation strategies that could be useful in treatment of resistant OCD patients. Nondrug therapies are also important in OCD: behavioral therapy is frequently helpful and neurosurgery is sometimes helpful when other treatments fail.

Animals↗
PubMedDate not supplied

[Construction and validation of visual analogue scale for risk assessment].

This paper describes the factor structure and validity of a visual analogue scale designed to rate risk proneness: EVAR (EVAluation of Risk). Risk behaviors and sensation seeking are related, therefore we correlated EVAR (24 100 mm items) with Zuckerman Sensation Seeking Scale (SSS) (40 conventional items) in a population of 199 volunteers. Subjects had an age range of 18-68 years (mean age of 31), and 49 were females. Factor analysis using a principal component solution and an orthogonal rotation of the factor matrix were computed. Five factors were selected, accounting for 46 per cent of the total variation: F1 "self control", F2 "danger seeking", F3 "energy", F4 "impulsiveness", F5 "invincibility". F1, F2 and F3 from EVAR were correlated with SSS factors "general", "danger seeking", "experience seeking" and "boredom susceptibility". F4 was correlated with "general", "boredom susceptibility" and "disinhibition" whereas F5 was not correlated with any of SSS factors. This visual analogue scale is likely to reveal change in subjects, regarding risk proneness, when submitted to various stressors (sleep deprivation, fatigue...).

Adolescent↗
PubMedDate not supplied

[Public health networks: practical aspects and contribution to clinical research. Round table no. 2. XV].

A public health network involves several and different health professionals who work in synergy to achieve a common objective: to improve the management of a given disease. Per se, this objective could not be achieved by each of these professionals if working separately. In practice, existing public health networks ensue from very different legal frameworks and come up against various impediments. They have been developed mainly for the management of chronic and serious diseases (e.g. asthma, diabetes, virus C hepatitis, Parkinson's disease, drug abuse). Public health networks can be a very valuable source of data for clinical and epidemiological research, mainly because patients are followed up over a very long period and information coming from various health professionals (general practitioners, specialists, nurses, etc.) is centralized and recorded in a common database. It can also be useful for pharmacovigilance purposes (assessment of Type A and delayed reactions). In any case, the relative interest of such networks should be regularly assessed by an ad hoc methodology, e.g. an experimental or pseudo-experimental design vs. a reference. Despite the fact that there are relatively few operational networks, they can be of great interest for clinical research.

Community Networks↗
PubMedDate not supplied

[Pharmacological modulation of the effects induced by ketamine at subanesthetic doses].

The similarity between ketamine effects and endogenous psychoses has created interest in the capacity of antipsychotic medications to block ketamine effects. In healthy subjects, a sub-anaesthetic single dose of lorazepam, typical neuroleptics, such as haloperidol, and atypical neuroleptics, such as clozapine and olanzapine, failed to block ketamine-induced positive and negative symptoms resembling schizophrenia. However, haloperidol is able to decrease ketamine-induced impairment in executive cognitive functions. Recently, lamotrigine reduced ketamine-induced psychotic symptoms, perceptual alterations, and cognitive impairments. In schizophrenic subjects, single doses of olanzapine do not decrease the effects of ketamine. However, long term treatment with clozapine has been reported to decrease ketamine-induced positive symptoms. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia.

Anesthetics, Dissociative↗
PubMedDate not supplied

[Role of pharmacokinetic-pharmacodynamic relationships in drug development].

An important part of drug development relies on the analysis of the relationships between drug doses and therapeutic and/or side effects. This analysis implies an in-depth understanding of the pharmacokinetics (PK) and pharmacodynamics (PD) of the drug and of the relationship which links them (PK-PD relationship). The aim of this round table was to define the place of the study of PK-PD relationships in drug development. After reviewing the definitions of PK models, PD models, and of integrated PK-PD models, the article highlights the importance of studying the PK-PD relationship during the successive phases of drug development (pre-clinical, phase I/II, phase III) and in specific populations (children, elderly people). A number of examples taken from pharmaceutical development or international literature are given. They show the methodology used and the type of information which can be drawn at each step of drug development. The article also presents the difficulties which prevent a more systematic application of this kind of approach during drug development. Scientific limits, problems in relation with the misunderstanding of the approach both in academic institutions and in pharmaceutical companies, and difficulties related to the lack of specific guidelines are discussed. The conclusion emphasizes the importance of using PK-PD modeling all along drug development and presents a number of actions which could further broaden its use.

Clinical Trials as Topic↗