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Biomedical subjects

J Micallef

Publications and source records attributed to J Micallef.

At least 19 recordsLinked to original sources
PubMed2006

Potential biases in estimates of hepatitis C RNA clearance in newly acquired hepatitis C infection among a cohort of injecting drug users.

Estimates of hepatitis C virus (HCV) clearance following acute infection range from 14 to 46%. This wide range is likely to be due to the characteristics of the populations studied and analysis methods. This paper examines how differing definitions of clearance parameters affect estimates of viral clearance in a cohort of 85 injecting drug users with newly acquired HCV infection. Kaplan-Meier estimates of time to HCV clearance were determined using varying definitions of eligible cohort, viral clearance, date of infection and date of clearance. Based on which combinations of definitions were used, the number of subjects eligible for analysis ranged from 27 to 75, clearance rate ranged from 14 to 68% and time to achieving 25% clearance ranged from approximately 5 months to 14 months. Standardized definitions and methodologies are required to enable valid comparisons of rates of clearance across newly acquired HCV infection natural history studies.

Bias↗
PubMed2006

Efficacy of etifoxine compared to lorazepam monotherapy in the treatment of patients with adjustment disorders with anxiety: a double-blind controlled study in general practice.

Adjustment Disorders With Anxiety (ADWA) account for almost 10% of psychologically motivated consultations in primary care. The aim of this double-blind randomised parallel group study was to compare (non-inferiority test) the efficacies of etifoxine, a non-benzodiazepine anxiolytic drug, and lorazepam, a benzodiazepine, for ADWA outpatients followed by general practitioners. 191 outpatients (mean age: 43, female: 66%) were assigned to receive etifoxine (50 mg tid) or lorazepam (0.5-0.5-1 mg /day) for 28 days. Efficacy was evaluated on days 7 and 28 of the treatment. The main efficacy assessment criterion was the Hamilton Rating Scale for Anxiety score (HAM-A) on Day 28 adjusted to Day 0. The anxiolytic effect of etifoxine was found not inferior to that of lorazepam (HAM-A score decrease: 54.6% vs 52.3%, respectively, p=0.0006). The two drugs were equivalent on Day 28. However, more etifoxine recipients responded to the treatment (HAM-A score decreased by >or=50%, p=0.03). Clinical improvement (based on Clinical Global Impression scale CGI, Social Adjustment Scale Self-Report SAS-SR, and Sheehan scores) was observed in both treatment arms, but more etifoxine patients improved markedly (p=0.03) and had a marked therapeutic effect without side effects as assessed by CGI, p=0.04. Moreover, 1 week after stopping treatment, fewer patients taking etifoxine experienced a rebound of anxiety, compared to lorazepam (1 and 8, respectively, p=0.034).

Adjustment Disorders↗
PubMed2006

[Sexual behaviour in schizophrenic patients: the impact of antipsychotics].

In spite of the frequency of sexual dysfunction in schizophrenic patients and antipsychotic-treated schizophrenic patients, few studies have been performed. The relationship of schizophrenia to sexual pathology is variable and complex, and of course different between men and women. Few evaluation methods have been proposed or validated. Antipsychotics may improve some aspects of sexual behaviour in schizophrenic patients. However, sexual dysfunction is also a possible side effect of these drugs. The evaluation of antipsychotics is often restricted to prolactin measurement, the relationship with sexual disorders of which has not been fully established. Preliminary data suggest that the capacity to induce sexual disorders differs from one antipsychotic to another. The available data on the mechanisms of sexual dysfunction, the pharmacological profile and the sexual effects of classical neuroleptics (haloperidol and thioridazine) and second generation antipsychotics available in France (amisulpride, clozapine, risperidone, olanzapine) are reviewed.

Antipsychotic Agents↗
PubMed2004

A randomized clinical trial comparing doses and efficacy of lormetazepam tablets or oral solution for insomnia in a general practice setting.

Lormetazepam is a short-acting benzodiazepine hypnotic which is beneficial in shortening the time to onset of sleep. The aim of the study was to assess a new formulation of lormetazepam (oral solution) in comparison with lormetazepam tablets in out-patients with insomnia. This trial was an open randomized parallel group study conducted by 30 general practitioners. One hundred and eight patients took 0.5 mg on the first night and were allowed to increase their dosage by 0.25 mg (for oral solution) and 0.5 mg (for tablets), respectively, each day and every 2 days. The patients assessed the efficacy, acceptability and tolerance of lormetazepam using a diary card and a set of visual analogue scales assessing their sleep. Over 14 days of treatment, the mean daily dose of lormetazepam was lower in the oral solution group than in the tablets group (0.78 mg versus 0.97 mg). The cumulated dose of lormetazepam was lower with the oral solution (18% reduction). No significant difference between the two groups was found in the assessment of sleep characteristics. The occurrence of side effects did not differ between the two groups. These results suggest that a unitary dose as achieved by an oral solution of lormetazepam allows easier determination of the minimal individual effective dose.

Administration, Oral↗
PubMed2004

A longitudinal study of the evolution of cognitive function and affective state in patients with amyotrophic lateral sclerosis.

OBJECTIVES: The study aimed to evaluate cognitive function and emotional reactivity in 18 patients with ALS, compared to 19 matched controls, and assess their evolution over a 12-month period. METHODS: 18 ALS patients and 19 matched controls were included, and assessed at inclusion, six months and twelve months later. Depression was evaluated with the Geriatric Depression Scale, and cognitive function with the Folstein Mini Mental State. A battery of psychometric tests (Wisconsin Card Sorting Test (WCST), the numerical Empan test, the Trail-making test, the Boston Naming Test, the 15-word Rey memory test, the Benton visual retention test and the Raven Progressive Matrix) was used to measure frontal processing and non-frontal function. Emotional reactivity was measured with the film-evoked emotions test. RESULTS: ALS patients were significantly more depressed than controls, as measured on the Geriatric Depression Scale, and depression increased over the study period. There was a very mild defect in cognitive function, and a performance deficit in the Trail-making test, a measure of frontal processing. These deficits, unlike neuromuscular function and depression, did not aggravate over the 12 months of the study. There was no observable change in non-frontal function. Emotional reactivity did not differ significantly between ALS patients and controls. CONCLUSIONS: This study provides further evidence for a mild defect in frontal cognitive processing in ALS patients that evolves only slowly, if at all, with time.

Adolescent↗
PubMed2004

Amphetamine-like stimulant cessation in an abusing patient treated with bupropion.

OBJECTIVE: Bupropion sustained release is considered to be a weak inhibitor of dopamine and serotonin reuptake. METHOD: We report the case of an amphetamine-abusing patient who self-administered bupropion. RESULTS: Since 30 years, a 52-year-old women used amphetamine derivates. She explained her need for amphetamine use in order to perform daily activities. Recently, she decided to experiment with bupropion. She abruptly stopped taking clobenzorex and simultaneously started taking bupropion (150 mg/day). The seventh day she reported a concomitant intake of clobenzorex; this induced adverse effects. Whilst taking bupropion, she described experiencing an euthymic state without any compulsion to take amphetamine drugs and was able to perform daily activities. After stopping it, no symptoms of withdrawal were reported by the patient. CONCLUSION: This observation supports an another report suggesting that bupropion may be of help in weaning from amphetamine users and should be confirmed by clinical trials.

Amphetamine-Related Disorders↗
PubMed2003

[Effects of a subanaesthetic dose of ketamine on emotional and behavioral state in healthy subjects].

Schizophrenic patients suffer from positive (delusions, hallucinations) and negative signs (social withdrawal) as well as emotional disturbance that included quantitative (blunted affect) and qualitative impairments (discordance of emotional level). Ketamine, a phencyclidine derivative, is a non competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist. In healthy subjects its administration induces some positive symptoms (perceptual distortions.), negative symptoms (emotional deficit, apathy, social withdrawal) and cognitive changes (memory impairments and perseverations) that resemble some aspects of the symptoms of schizophrenia. A double blind cross over, placebo controlled was performed in 12 normal subjects with 2 sessions separated by one week of wash-out to determine ketamine-induced effects on behavioral and emotional responses. During each session, subjects received either ketamine or placebo (saline) infusion. A subanesthetic dose of ketamine (0,5 mg/kg) was administered by constant perfusion over 60 min. Behavioral and cognitive responses were assessed using positive and negative symptoms scales (BPRS, items from SAPS and SANS), vigilance and mood visual analog scale, subjective feelings using the Addiction Research Center Inventory (ARCI) and the Profile of Mood States (POMS). Using Philippot's method, emotions were elicited by films segments which induce a diversity of predictable emotions (fear, anger, sadness, joy, disgust and neutral state) and emotional responses were assessed by the Differential Emotions Scale (DES Izard). Low dose of ketamine induced significant effects on 7-items BPRS score (positive and negative items) and significant effects on positive and negative symptoms from SANS and SAPS. This was associated with emotional blunting of visually-induced responses that resemble aspects of schizophrenic emotional impairments. Ketamine impaired ARCI subscales (benzedrine subscale, pentobarbital-chlorpromazine subscale and LSD subscale). The recent findings of ketamine's pharmacology and imaging studies allow to draw several hypothesis related to neurotransmitter systems (glutamate, dopamine, serotonin interactions) and cerebral areas (particularly prefrontal cortex, anterior cingulate cortex, hippocampus) underlying some of these ketamine-induced effects.

Adult↗
PubMed2003

Weight gain profiles of new anti-psychotics: public health consequences.

Anti-psychotic medications are an important therapeutic option for many individuals with schizophrenia. Recently, a growing interest has been observed on weight gain, which is now a well-known adverse effect of many anti-psychotics. As obesity is frequently a comorbid condition with schizophrenia, patients with schizophrenia are inherently at increased risk of developing obesity-related conditions such as cardiovascular disease and type 2 diabetes. The consequences of excessive weight gain (obesity) associated with anti-psychotic drugs are likely to include adverse effects on health, social burden and poor compliance or even discontinuation of therapy by the patients. In this article, we focus on different aspects of weight gain induced by anti-psychotics. This review comprises the following sections: (i) the pharmacological basis of anti-psychotic-induced weight gain and metabolic effects with a review of all anti-psychotics that can be used in patients with schizophrenia; (ii) the clinical impact of the body weight gain (morbidity, psychatric consequences, mortality); (iii) the management of obesity (identification of risk factors including pharmacogenetics, diet, behavioural therapies, pharmacological approach). An understanding of these aspects is important for those who prescribe anti-psychotics in order to provide the patient the best therapeutic management.

Antipsychotic Agents↗
PubMed2003

[Treatment of non-dopamine-dependent signs in parkinsonian syndromes: evaluation and results].

With dopaminergic systems, non dopaminergic neurotransmission probably plays a major role in parkinsonian syndromes (Multiple System Atrophy, Progressive Supranuclear Palsy, Pure Autonomic Failure, Cortical basal degeneration, Lewy Body Disease). A better understanding of the pathophysiology of these syndromes led to the development of molecules that interact with non dopaminergic systems. Thus, freezing, gait and balance disorders, dysautonomia and neuropsychiatric disorders are likely to benefit from specific treatments. However, due to methodological difficulties related to the evaluation of such molecules, controlled trials are rather rare and the results are often partial and sometimes unclear.

Anti-Dyskinesia Agents↗
PubMed2002

Buprenorphine prescription by general practitioners in a French region.

Since 1996 French general practitioners (GPs) may prescribe sublingual buprenorphine tablets as maintenance treatment for opiate dependence. The computerised data management of the main French health reimbursement system now allows surveillance of the use of this drug, and how it is prescribed. The purpose of this study is to determine the profile of maintained patients, prescribed doses, associated psychotropic treatments and how practitioners prescribe these treatments. This study analyses the 11186 buprenorphine prescriptions electronically transmitted for reimbursement between September and December 1999 in a specific French region. It was found that the 2078 treated patients consumed a mean of 11.5 mg of buprenorphine per day and 12% of them procured prescriptions from more than two prescribers. 43% of maintained patients had an associated benzodiazepine prescription, mainly flunitrazepam, often on the same prescription form. 61% of patients had regular follow-up, others had occasional consultations (21%) and another 18% had deviant maintenance treatment (more than two prescribers or more than 20 mg per day of daily buprenorphine dose). Benzodiazepine consumption was much higher in the 'deviant group' (71.4%). 85% of buprenorphine prescriptions were made by GPs. 21% of GPs prescribed buprenorphine and 61% of those had only one or two maintained patients. Buprenorphine prescription by French GPs is a procedure with no particular requirements, allowing many patients to easily access maintenance treatments. However, a high risk of abuse exists, which demands extensive investigation and evaluation of these practices.

Administration, Sublingual↗
PubMed2001

N-methyl-D-aspartate receptors and information processing: human choice reaction time under a subanaesthetic dose of ketamine.

Ketamine is an N-methyl-D-aspartate antagonist that induces cognitive dysfunctions. The purpose of the present study was to investigate the effects of a subanesthetic dose of ketamine on human information processing, using the additive factor method. During perfusion of a subanesthetic dose of ketamine (0.5 mg/kg over 60 min) or a placebo (randomized double-blind, cross-over design), eight adults (aged 22-33, mean=27) performed a two-choice visual reaction time (RT) task. Signal intensity, stimulus-response mapping, and foreperiod duration were manipulated. The effects of these three variables were found to be additive on RT, indicating that three independent stages - namely, stimulus preprocessing, response selection and motor selection- were manipulated. Ketamine altered RT performance in a specific way: it interacted with foreperiod duration but its effect was additive with those of signal intensity and stimulus-response mapping. These results show that ketamine specifically affects the stage of motor adjustment, which suggests that the glutamatergic system plays an important role in motor processes.

Acoustic Stimulation↗
PubMed2001

Recent evolution in opiate dependence in France during generalisation of maintenance treatments.

Two maintenance drugs had been used in France since 1996, methadone and high-dosage buprenorphine. This study aimed to examine changes in drug use from observations gathered between 1995 and 1997, within the framework of the French program for the monitoring of drug dependence (OPPIDUM). This annual survey studies psychoactive substances consumed by drug addicts attending specialised drug care centres. During the last three surveys, 16 centres collected a total of 1597 patient-files. This study shows an increase in the number of patients undergoing maintenance treatment (from 14 to 69%), a reduction in the number of intravenous drug users (from 55 to 22%) and a reduction in consumption of psychoactive substances. However, poly-drug addiction behaviour continues and high-dose buprenorphine subjects frequently use the substance intravenously and in association with benzodiazepines.

Adult↗
PubMed2001

Comparison of methadone and high dosage buprenorphine users in French care centres.

AIMS: In France, maintenance programmes for opiate users were adopted later than in other countries. Two maintenance treatments are available: methadone is only delivered in specialized centres while high dosage (HD) buprenorphine can be prescribed by all general practitioners and in specialized centres. The aim of this study was to compare the socio-demographic profiles, the practices and drug consumption patterns of the two groups attending specialized centres. METHODOLOGY: The Oppidum Programme (observation of illegal drugs and misuse of psychotropic medications), a multi-centric survey, surveys drug-dependent subjects attending specialized care centres throughout France annually. Data were collected by questionnaire on socio-demographic variables and drug use during the preceding week. RESULTS: During October 1998, 46 centres took part in the survey. The methadone group (n = 424) was older, with a better economic situation; 16% used cocaine regularly. The HD buprenorphine group (n = 616) consumed more heroin (12% vs. 8%) and engaged in more misuse, such as intravenous use, illicit acquisitions or irregular consumption. These practices were more frequent for patients consuming the drug "outwith protocol" or for patients obtaining the drug from a general practitioner. CONCLUSION: Our results suggest that patterns of consumption of methadone and buprenorphine are different in several respects: concomitant use of licit or illicit psychoactive substances, route of administration, and illegal acquisition. They also suggest that the behaviours of maintenance treatment users depend less on the nature of the maintenance drug (methadone or high dosage buprenorphine), than the nature of the delivery and monitoring practices.

Adult↗
PubMed2001

A double blind parallel group placebo controlled comparison of sedative and mnesic effects of etifoxine and lorazepam in healthy subjects [corrected].

This paper describes the psychomotor and mnesic effects of single oral doses of etifoxine (50 and 100 mg) and lorazepam (2 mg) in healthy subjects. Forty-eight healthy subjects were included in this randomized double blind, placebo controlled parallel group study [corrected]. The effects of drugs were assessed by using a battery of subjective and objective tests that explored mood and vigilance (Visual Analog Scale), attention (Barrage test), psychomotor performance (Choice Reaction Time) and memory (digit span, immediate and delayed free recall of a word list). Whereas vigilance, psychomotor performance and free recall were significantly impaired by lorazepam, neither dosage of etifoxine (50 and 100 mg) produced such effects. These results suggest that 50 and 100 mg single dose of etifoxine do not induce amnesia and sedation as compared to lorazepam.

Adolescent↗
PubMed2001

Yawning.

YAWNING IS A COMMON PHYSIOLOGICAL EVENT THAT CAN BE DIVIDED INTO THREE DISTINCT PHASES: a long inspiratory phase, a brief acme and a rapid expiration. The aim of yawning is not yet well defined. However this semi-voluntary event increases vigilance and aims to alert when drowsiness occurs. Yawning probably has an important role for social communication as well. Yawning can be responsible for pain, luxation or even transient ischaemic attack. Abnormal yawning is present in various pathologies: migraine, Parkinson's disease, tumours, psychiatric diseases, infections or iatrogenic pathologies. The neuro-pharmacology of yawning is complex and knowledge of its mechanisms is incomplete. While under the control of several neurotransmitters, yawning is largely affected by dopamine. Dopamine may activate oxytocin production in the paraventricular nucleus of the hypothalamus. Oxytocin may then activate cholinergic transmission in the hippocampus and, finally, acetylcholine might induce yawning via the muscarinic receptors of the effectors. This is an over-simplification; many other molecules can modulate yawning, such as nitric oxide, glutamate, GABA, serotonin, ACTH, MSH, sexual hormones and opium derivate peptides. Dopamine involvement in yawning could have practical applications in the study of new drugs or the exploration of neurological diseases such as migraine or psychosis. 2001 Harcourt Publishers Ltd

Journal Article↗
PubMed2001

Pharmacokinetics of sabeluzole and dextromethorphan oxidation capacity in patients with severe hepatic dysfunction and healthy volunteers.

AIMS: The primary objective of this study was to determine how the pharmacokinetics of sabeluzole, an investigational drug with specific effects on memory and learning abilities, are affected by chronic liver disease. Since sabeluzole is metabolised by CYP2D6, a secondary objective was to study the correlation between CYP2D6 activity (as assessed by the dextromethorphan dextrorphan metabolic ratio) and hepatic dysfunction. METHODS: The single-dose pharmacokinetics of sabeluzole (10 mg) was compared in 10 healthy Caucasian subjects and 10 patients with severe hepatic dysfunction. The urinary dextromethorphan/dextrorphan (DMP/DRP) metabolic ratio was determined after intake of 20 mg dextromethorphan (NODEX capsules). RESULTS: The terminal half-life of sabeluzole was significantly prolonged in subjects with severe hepatic dysfunction vs healthy subjects (respectively 39.3 +/- 11.5 h; 17.5 +/- 10.2 h (mean +/- s.d.)). The areas under the curve (AUC) were significantly higher in subjects with severe hepatic dysfunction than in healthy volunteers (681 +/- 200 ng ml(-1) h vs 331 +/- 282 ng ml(-1) h). There was a significant correlation between the AUC(0,infinity) and the DMP/DRP metabolic ratio in healthy volunteers and subjects with severe hepatic dysfunction. AUC was greater and elimination of sabeluzole slower in poor metabolizers compared with extensive metabolizers. CONCLUSIONS: These results suggest that a) sabeluzole dose should be reduced in patients with severe hepatic dysfunction and b) the AUC of sabeluzole is linked to individual CYP2D6 activity.

Adult↗
PubMed2001

Observation of psychoactive substance consumption: methods and results of the French OPPIDUM programme.

This study presents a French programme designed to observe and evaluate psychoactive substance dependence and abuse. Annual surveys lasting 4 weeks are performed with drug users in drug centres. Its usefulness is discussed using examples from the study: potential for antidepressant dependence (amineptine), monitoring benzodiazepine use and consumption associated with maintenance treatments. Flunitrazepam is the most consumed benzodiazepine and often got by deal (29%). There are important differences between buprenorphine consumption in a maintenance treatment context (9/10) and beyond this context (1/10). The main methodology problems encountered are representativeness and validity of data. The limits of the programme and its role in the French health care system are discussed.

Adolescent↗