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Biomedical subjects

H Allain

Publications and source records attributed to H Allain.

At least 19 recordsLinked to original sources

[Consensus statement on severe dementia].

Under the auspices of the French Society of Gerontology and Geriatrics, a multidisciplinary group of experts, including geriatricians, neurologists, epidemiologists, psychiatrists, pharmacologists, and public health specialists developed consensus recommendations about care for patients with severe dementia. They defined 21 recommendations for general practitioners, long-term care physicians, and specialists, based on the knowledge currently available (2005). The aim of care at all stages is to mitigate the quality-of-life of patient, caregiver, and family insofar as possible, combining care and future planning until the end of life. Management, to take into account problems including nutritional status, behavior disorders, and ability (or inability) to perform activities of daily living, must be global, multidisciplinary, and coordinated and must optimize use of local medical and social resources. The group also stressed the importance of clinical research to improve knowledge of disease course and assess management strategies and recommended specific area for research.

Aged↗

[Consensus statement on severe dementia].

Under the auspices of the French Society of Gerontology and Geriatrics, a multidisciplinary team including geriatritians, neurologists, epidemiologists, psychiatrists, pharmacologists and public health specialists developed a consensus on care for patients with severe dementia. They defined 21 recommendations for general practitioners, long-term care physicians and specialists based on knowledge available in 2005. At all stages of the disease, the objective of care is to improve as much as possible quality-of-life for the patient and his/her family, including a life project until the end of life. It is always possible to do something for these patients and their family: nutritional status, behavior disorders, and incapacities to deal with basic activities of daily life have to be taken in consideration. Resource allocation and proximity care have to be targeted. Research areas necessary to improve the care of patients with severe dementia has been selected.

Aged↗

[Myoclonic encephalopathy associated with proton pump inhibitors].

Two men (66 and 73 Years) with a cardiovascular history were hospitalized for rapid onset encephalopathy associated with myoclonia and an extrapyramidal syndrome. On the basis of the French Pharmacovigilance system, this symptomatology has been attributed to the coadministration of a proton pump inhibitor, lansoprazole (15mg/day) with levodopa. Lansoprazole withdrawal led to a normalisation of the situation.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[NOEMIE: an epidemiological study of migraine at work: results from 17 occupational health centres].

INTRODUCTION: A survey (NOEMIE, Nouvel Observatoire Epidemiologique de la Migraine en Entreprise) was carried out in France in 17 occupational healthcare units in order to identify subjects suffering from migraine headache with the aim of guiding them towards a healthcare program. The data collected in the participating units are presented. METHODS: and patients. NOEMIE was a national cross-sectional, observational, multicentric study with a 6-month follow-up. Two groups of migraine sufferers (according to IHS criteria) were included and divided into two groups: subjects already managed for their migraine (group A) and subjects who had not sought healthcare for migraine for more than 12 months (group B). The main objective was to evaluate changes in the quality-of-life score (QVM) 6 months later. RESULTS: At inclusion, the two groups were comparable for demographic features, history of migraine, and disease severity. A significant difference was observed between the two groups for frequency of attacks, disease management, and evaluation of treatment efficacy and of quality-of-life. At 6 months, patient satisfaction and quality-of-life were significantly improved (6 to 10 point improvement). For the 4753 reported attacks, 12.4 percent of the patients in group A required sick leave versus 10.9 percent in group B. Frequency of sick leave was considerably improved in both groups. CONCLUSION: By identifying subjects suffering from migraine headache who had not sought specific medical care and advising them to seek medical management, the employee healthcare units improved the subjects' quality-of-life, promoted adequate medical management and reduced occupational consequences of migraine headache.

Adult↗

[Mechanisms of chronic cough pathophysiology].

INTRODUCTION: In some situations such as post-virus or post whooping cough, a non productive subacute cough may occur without apparent local inflammation, epithelium abnormalities or bronchoconstriction. This subacute or chronic cough represents a real syndrome (cough disease) due to the central nervous system (CNS) and its ortho and parasympathic outputs. At the CNS level, functional disturbancies and neosynaptogenesis can be described, with the intervention of the NMDA-type glutamatergic receptors. STATE OF ART: The neurons located in the expiratory area of the breathing center (Pre-Boetzinger complex of the lower brainstem) present exagerated responses to stimuli, due to the repetitive stimulation of the NMDA receptors; this phenomenon is similar to long-term-potentiation (LTP), the molecular basis of learning, memory and neosynaptogenesis. The cough reflex is thus amplified and rapidly chronic and would justify any pharmacological intervention at the NMDA-receptors level. PERSPECTIVES: More recently 5TH4 receptors have been implied in the control of respiration; an overexpression of these receptors in the Pre-Boetzinger area could contribute to an increase of the cough reflex. CONCLUSION: The present review aims at summarizing the main rationale target to pharmacologically block the chronic cough.

Antitussive Agents↗

The challenge of chronic insomnia: is non-nightly hypnotic treatment a feasible alternative?

The adverse effects of insomnia on health and quality of life are matters receiving increasing attention. Yet, surveys have consistently shown that most people suffering from insomnia do not seek medical help, perhaps, in part, because of a concern of becoming dependent on hypnotic medication. The treatment of chronic insomnia poses a particular dilemma in that continuous hypnotic treatment is restricted in many countries to a maximum of 4 weeks, and behavioural treatment is not readily available. Non-nightly hypnotic treatment of chronic insomnia offers a promising alternative option for the many patients whose symptoms do not necessitate nightly drug intake, allaying fears of psychological dependence on medication and respecting regulatory constraints on hypnotic use while providing patients with adequate symptom relief. The practical feasibility and efficacy of this approach has been demonstrated with zolpidem using various treatment regimens and study designs. So far, six clinical trials have been completed on over 4000 patients. Published results show effective treatment of insomnia without any evidence of either adverse event associated with a discontinuous regimen or increased hypnotic use over the treatment period.

Humans↗

Effects of risperidone on psychometric and cognitive functions in healthy elderly volunteers.

RATIONALE: Dementia includes not only cognitive deficit but may also include psychiatric and behavioral symptoms. These psychological symptoms of dementia require specific treatment without deleterious effects on cognitive functions. OBJECTIVE: The aim of the present study was to assess the effects of a single dose of risperidone (0.25 or 0.5 mg) on psychomotor performances and cognitive functions compared to a placebo and to a positive control, lorazepam 1 mg, in 12 healthy elderly subjects. METHODS: This study was a randomized, double-blind, four-way crossover clinical trial involving four 8-h long treatment periods. The pharmacodynamic assessment criteria included a battery of psychomotor tests, a subjective evaluation and an electroencephalogram. Safety was evaluated by clinical laboratory tests, electrocardiogram and recording of adverse events. Concentrations of risperidone, 9-hydroxy-risperidone and lorazepam were determined before and 2 h after dosing. RESULTS. Few significant effects were observed on psychomotor tests with risperidone at all dosages. Risperidone was devoid of any deleterious effects on speed of reaction, vigilance and sustained attention, working and long-term memory and increased cortical arousal. Risperidone demonstrated minor impairment on motor activity (decreased finger taping), postural stability, and information processing (impaired digit symbol substitution). Contentedness subjective evaluation was decreased with risperidone 0.5 mg, 6 h after dosing. No significant difference was observed on EEG frequencies and no sedative activity was detected with risperidone. At 2 h after dosing, risperidone plasma concentrations were 1.54+/-0.99 ng/ml and 2.80+/-1.41 ng/ml; 9-hydroxy-risperidone concentrations were 0.77+/-0.46 ng/ml and 1.54+/-0.85 ng/ml after intake of 0.25 mg and 0.5 mg doses, respectively. Well-known detrimental effects of lorazepam on psychomotor performances were observed and sedative effects were confirmed by the EEG findings. At 2 h following lorazepam 1 mg administration, plasma concentrations were 13.40+/-2.17 ng/ml. None of both compounds induced serious adverse events. CONCLUSION: The results of this clinical trial conducted on healthy subjects demonstrated that low doses of risperidone, but not low doses of lorazepam, did not disturb the cognitive functions in the elderly.

Aged↗

[Effect of almitrine/raubasine on cerebral metabolism in the elderly].

Recent neurobiological data has led to renewed interest in oxygen (O2). The discovery of neuroglobin, protein varyingly present in the brain, has been enhanced by the elucidation of the mechanisms through which oxygen intervenes in neuronal metabolism. Almitrine/raubasine activates the metabolism of hypoxic/ischemic neurones by increasing O2 bioavailability. This mechanism supports the effects on behaviour obtained in various animal models and the benefits observed during clinical trials in elderly patients presenting with cognitive defects.

Aged↗

[Evaluation of pendulum testing of spasticity].

OBJECTIVES: To identify valid measurements of spasticity derived from the pendulum test of the leg in a representative population of spastic patients. MATERIAL AND METHODS: Pendulum testing was performed in 15 spastic and 10 matched healthy subjects. The reflex-mediated torque evoked in quadriceps femoris, as well as muscle mechanical parameters (viscosity and elasticity), were calculated using mathematical modelling. Correlation with the two main measures derived from the pendulum test reported in the literature (the Relaxation Index and the area under the curve) was calculated in order to select the most valid. RESULTS, DISCUSSION: Among mechanical parameters, only viscosity was found to be significantly higher in the spastic group. As expected, the computed integral of the reflex-mediated torque was found to be larger in spastics than in healthy subjects. A significant non-linear (logarithmic) correlation was found between the clinically-assessed muscle spasticity (Ashworth grading) and the computed reflex-mediated torque, emphasising the non-linear behaviour of this scale. Among measurements derived from the pendulum test which are proposed in the literature for routine estimation of spasticity, the Relaxation Index exhibited an unsuitable U-shaped pattern of variation with increasing reflex-mediated torque. On the opposite, the area under the curve revealed a linear regression, which is more convenient for routine estimation of spasticity. CONCLUSION: The pendulum test of the leg is a simple technique for the assessment of spastic hypertonia. However, the measurement generally used in the literature (the Relaxation Index) exhibits serious limitations, and would benefit to be replaced by more valid measures, such as the area under the goniometric curve, especially for the assessment of therapeutics.

Adult↗

Lack of effect of single and repeated doses of levocetirizine, a new antihistamine drug, on cognitive and psychomotor functions in healthy volunteers.

AIMS: Levocetirizine (R-cetirizine), is the active enantiomer of cetirizine, an antihistamine indicated in the treatment of allergic rhinitis and chronic idiopathic urticaria. The purpose of this trial was to analyse the effects of levocetirizine single and multiple doses on CNS using integrated measures of cognitive and psychometric performance. METHODS: A battery of psychometric tests was used: critical flicker fusion (CFF), choice reaction time (CRT), body sway (BS), learning memory test (LMT) and subjective assessments of alertness compared with placebo. Nineteen (19) healthy male volunteers received either levocetirizine 5 mg (therapeutic dose), diphenhydramine 50 mg or placebo once daily for 5 consecutive days (3-way cross-over). Diphenhydramine was used as a positive control. CFF tests were performed on days 1 and 5 at baseline and up to 24 h following drug intake. Subjects used the Bond-Lader visual analogue scales (VAS) to assess their mood and vigilance. RESULTS: In contrast to diphenhydramine, when compared with placebo, levocetirizine did not modify the CFF (primary endpoint), regardless of the dosing scheme (-1.62 Hz [-2.61, -0.64] and -0.81 Hz [-1.80, 0.19], respectively, 3 h after dosing on day 1). CRT was decreased with both levocetirizine and placebo up to 5 h after dosing on day 1 and up to 3 h after dosing on day 5. Body sway data were similar with levocetirizine and placebo but increased with diphenhydramine. LMT was similar in all three groups. No relevant difference between placebo and levocetirizine was recorded by the subjects on their assessment of alertness using the VAS, whilst decreased alertness was reported following diphenhydramine 50 mg. CONCLUSIONS: This study showed that levocetirizine does not produce any deleterious effect on cognitive and psychometric functions compared with placebo in healthy male volunteers.

Central Nervous System↗

Effects of nicardipine and clonidine on cognitive functions and electroencephalography in hypertensive patients.

The aim of this study was to investigate the cognitive and electroencephalography (EEG) short-term effects of a calcium antagonist, nicardipine, compared to placebo and clonidine (which, having known sedative effects, acted as a negative control) for 15 days in elderly hypertensive patients with memory complaints. Nicardipine and clonidine were compared with placebo in a double-blind, randomized, three-way cross-over controlled study after a 2-week placebo run-in period. This was a phase II clinical study carried out on out-patients in a single research centre. Fifteen elderly (63 +/- 10 years) hypertensive patients, without dementia but with memory complaints, were included. Psychomotor performance and cognition were assessed using both an extensive battery of validated psychometric tests (which evaluated attention and vigilance, body sway and memory) and an EEG profile. Cardiovascular parameters measured were blood pressure and heart rate. No detrimental effects of nicardipine were found on attention, vigilance, body sway or memory. Nicardipine produced a significant increase in alpha EEG energies, which may indicate possible alerting effects. In contrast, clonidine induced well-known deleterious sedative effects in psychometric tests and in EEG analysis (decrease in alpha and increase in delta and theta waves). The two drugs produced equivalent decreases in blood pressure at steady state. In conclusion, clonidine induced well-known sedative effects, while nicardipine did not impair central nervous system activity and may have had some short-term alerting effects in elderly hypertensive patients with memory complaints. This study supports the hypothesis of a dissociation between blood pressure and direct drug effects on the central nervous system.

Aged↗

[Study of the real situation of improvement by Zopiclone in treatment of insomnia among persons working during night shifts].

UNLABELLED: We investigated the effect of adapted management of sleep on the duration and quality of sleep in shift workers working the night shift. Twenty-nine shift workers suffering from insomnia were included and treated with zopiclone (7.5mg/day) or placebo according to a random double-blind protocol. Patients completed a sleep diary and a wrist actigraph was used to evaluate episodes of rest/activity. A self-administered subjective sleep questionnaire was filled out just after awakening. Zopicone was found to increase the duration of sleep significantly (p<0.05) over the baseline duration after the first and second night on duty. Subjective estimation of sleep was better in patients taking zopiclone who exhibited a smaller number of shorter awakening episodes. IN CONCLUSION: zopiclone improves the quality and duration of sleep in shift workers suffering from insomnia.

Adult↗

[Mild Cognitive Impairment: potential therapeutics].

Mild Cognitive Impairment (MCI) is an emerging concept used to describe memory decline and probably attention disturbances in otherwise intellectually intact individuals. MCI may be considered in 12 to 15 p. 100 of the cases as announcing an Alzheimer's Disease (AD). Although still speculative, the debate concerning the drugs susceptible to normalize symptoms of MCI or to stop conversion to AD must be raised. For that purpose, several long term clinical trials are running (antioxidants, nootropics, anticholinesterasics.) and new molecules in the pipe-line should be assessed in patients with the diagnosis of MCI.

Aged↗

A comprehensive model of spastic hypertonia derived from the pendulum test of the leg.

We propose a comprehensive model of spastic hypertonia based on clinical neurophysiology and validated using experimental data obtained from the pendulum test of the leg in 8 healthy volunteers and 15 spastic patients. This nonlinear computational model includes mechanical parameters and a stretch reflex representation involving three neural parameters: a threshold coefficient, the gain of the stretch reflex, and a time lag accounting for the reflex loop latency and the electromechanical coupling delay. Variation of the threshold coefficient alone allowed an overall reproduction of experimental data obtained from spastic and healthy subjects. We propose that this parameter could represent the supraspinal drive, supposed to be preserved in control subjects and decreased in spastic patients. No subsequent variation of the reflex gain was required to simulate spastic traces. Adjustment of the time lag influenced the duration of the swinging phase and oscillatory phenomena possibly occurring during the pendulum test. It could be related to the involvement of either short- or long-latency stretch reflex loops. With respect to current neurophysiological concepts of motor control, this modeling approach may help in understanding mechanisms underlying spastic hypertonia, and in predicting the clinical effect of antispasticity agents.

Adult↗

Clinical management of agitation in the elderly with tiapride.

Agitated behaviors such as uncooperativeness with necessary care, motor hyperactivity, and verbal or physical aggression are some of the most commonly reported complications in dementia and organic disorders in elderly subjects. These symptoms present greater clinical challenges and management issues than the cognitive deficits. Antipsychotics are the most commonly used psychotropic agents for treating these types of symptoms. The aims of this article are to review clinical studies with tiapride, a substituted benzamide, and more specifically to present recent data coming from two double-blind, randomized studies in elderly subjects. The first study versus melperone was conducted in Germany, with over 176 hospitalized demented patients, and indicated that tiapride was as effective and safe as melperone. More recently, a multicentre, international, double-blind, three-parallel group study compared a 21-day treatment of tiapride to haloperidol and placebo and included 306 demented elderly patients with agitation and aggressiveness. The results showed that tiapride and haloperidol were significantly effective in the treatment of agitation and aggressiveness compared to placebo. The tiapride safety profile was found to be better than haloperidol for clinical acceptability, particularly for significantly fewer extrapyramidal symptoms in the tiapride group.

Aged↗

Comparative effects of pharmacotherapy on the maintenance of cognitive function.

The quality of human cognitive performance appears today as one of the main components of quality of life, whatever the age. Ageing by itself and most of the diseases affecting the central nervous system alter higher brain functions such as memory, vigilance and attention. Dementia is the most acute example, with a cascade of behavioral and psychological consequences (BPSD), which are the main cause of the caregiver's burden and need specific pharmacotherapy. In this respect, the problem will be the choice of the best drug in situations such as wandering, agitation, violence, and screaming. The psychotropics, however, should not deteriorate the already disturbed cognition of the patients. This is the reason why we propose to establish for each drug, and notably for the antipsychotics, a precise and exact "cognitive mapping"; in other words, to measure the effects of drugs on the different components of cognition. The results of such studies will be predictive of the future phase III clinical trials and therapeutic responses. As an illustration of this approach we shall relate two studies, TIATEM (phase I) and TIAGE (phase III/IV), leading to the determination of a good cognitive safety profile of an atypical neuroleptic drug, tiapride.

Alzheimer Disease↗