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Biomedical subjects

H Allain

Publications and source records attributed to H Allain.

At least 37 records · Page 2Linked to original sources
PubMed2001

Role of dopaminergic and serotonergic systems on behavioral stimulatory effects of low-dose alprazolam and lorazepam.

Several recent studies have demonstrated that alprazolam and lorazepam, administered at low doses to healthy volunteers, improve cognitive functions and psychomotor performances. Paradoxical effects of low-dose benzodiazepines have been also observed in mice, in experimental pharmacology. The aim of this work was to determine, in rat, the effect of similar low-doses of benzodiazepines on spontaneous locomotor activity and performance in the elevated zero-maze, and to investigate the underlying neurobiological mechanisms. The dose-effect and the time-course of the action were studied for both compounds. Spontaneous locomotor activity was measured using a photoelectric actimeter. The level of anxiety of the animals was assessed in the elevated zero-maze. Dopamine, serotonin, and their metabolites were assayed in the extracellular striatal fluid of the awake rat, obtained by microdialysis, by HPLC--EC. Spontaneous locomotor activity observed in rats given low-dose alprazolam and lorazepam evidenced a stimulatory effect only with alprazolam. The effect was maximum 90 min after administration of 0.0050 mg/kg alprazolam. An anxiogenic-like action was evidenced with the elevated zero-maze for the two compounds. We observed a statistically significant increase in striatal dopamine concentrations only with alprazolam, during the period corresponding to the behavioral stimulatory effects. We also showed a marked trend towards increased levels of serotonin with alprazolam but this modification was not significant, in spite of statistically significant variations of 5-HIAA. In the rat, behavioral stimulatory effects of low-dose benzodiazepines is evidenced with alprazolam but not lorazepam. This effect could be explained, at least in part, by increased extracellular dopamine concentrations in the striatum. Their different structures could explain the different pattern observed for the two benzodiazepines.

Alprazolam↗
PubMed2001

[Long-term treatment of Alzheimer's disease: followup of a cohort of 255 patients treated with lacrine for four years].

We describe the follow-up of a cohort of 255 Alzheimer's disease (AD) patients (81 males, 174 females) treated by tacrine during 4 years. We performed the survey of hepatic, cholinergic and general tolérance. Drug efficacy was measured by MMS examination on weeks 0, 18, 30, 52, 104, 156 and 208. A total of 190 patients (74.5 percent) were dropped out of this study, 75 (29 percent) for adverse events. We found 85 hepatic (33 percent), 79 cholinergic (31 percent), 31 (12 percent) neuropsychiatric and 72 general (28 percent) side effects. In term of drug efficacy we observed a global decline of 2.5 MMS points during the first year and 2 MMS points between W52 and W156. Tacrine's symptomatic efficacy, defined as the number of patients improved or stabilized at W30, was present in 50 patients (46 percent) among the 109 patients reaching W30. The intensity of symptomatic efficacy was expressed by a 2.7 MMS points increase in 37 patients improved on W30. The long term effects of Tacrine, measured by the MMS score at one year, showed a positive impact as the MMS was 2.5 points above the expected score in non treated AD patients. This study raises the practical problem of optimal cholinesterase inhibitors use in AD and the theoretical question of long term action of cholinesterase inhibitors on cerebral lesions of AD.

Aged↗
PubMed2001

[Perspectives for drug treatment in Alzheimer's disease].

The last decade was very fruitful in neuropharmacology and notably in the therapeutic strategies of dementia and Alzheimer's disease (AD). The amount of data, information and breakthroughs is nevertheless difficult to apply in direct relationship with patients. The present review aims at classifying information according to their origins: epidemiology, clinical trials, neurosciences. A guide for drug prescription in Alzheimer's disease is thus warranted and becomes clearer, sure that, in the next future modifications and new strategies will appear. The main goal of the present review is to summarize the state-of-the-art for a non specialist in AD.

Alzheimer Disease↗
PubMed2000

[Psychiatry and clinical research. A dialogue with hospital directors].

Clinical research must be considered as a main and compulsory medical activity which has to be promoted on a European level. Some difficulties appear to be specific to mental diseases and may represent obstacles or a reason not to participate in clinical research. In fact, financing, grants, organizations and research centers do exist and should push forward clinical research in psychiatry. Human and cultural factors may explain why so few breakthroughs have occurred in France in the considered field. Incentive politics as well as avoidance of technical and frequently definitive errors must be proned and issue from a deep analysis of how leading teams are organized and operate.

Ethics, Medical↗
PubMed2000

[Multiconceptual therapy in Alzheimer's disease].

UNLABELLED: SOCIAL AND ECONOMICAL IMPACT: Alzheimer's disease is a neurodegenerative dementia raising major public health concern in industrialized countries. The consequences are not only medical but also social and economical. PERSPECTIVES: It is thus important to establish diagnostic principles, therapeutic goals, and global strategies guiding the behavior of physicians, family and patients faced with this dreaded disease. Currently, only a few rare symptomatic treatments are available, but research in this field points to potentially effective preventive and etiopathogentic therapeutic protocols associating drugs, social support, and psychotherapy.

Alzheimer Disease↗
PubMed2000

[Prescriptions for antidepressants in a population of psychiatrists and non-psychiatrists].

OBJECTIVE: Much proof has been accumulated over the last decade demonstrating that depression is a major public health issue. Use of psychotropics and more precisely antidepressants is considered to be excessive. It is however paradoxical that prescribing antidepressants has become commonplace. The aim of this study was to better assess the process of prescribing antidepressants in the hospital setting. METHODS: An epidemiological study was carried out to examine prescribing practices used by psychiatrists and non psychiatrists working in the Rennes University Hospital. The psychiatrist population was used as the reference population for univariate and multivariate analysis designed to ascertain differences concerning prescription practices. RESULTS: Duration of the clinical examination (shortest for non-psychiatric physicians, p = 0.0001), use of a diagnostic scale (more frequently for psychiatrists, p = 0.0008), reasons for choosing an antidepressant (pharmacological considerations more frequent among psychiatrists, p = 0.0009), and co-therapies (neuroleptic association more frequent among psychiatrists, p = 0.0001) were found to be different between the two prescribing populations. CONCLUSION: All patients with signs of depression are not necessarily given optimal care. Errors in assessing antidepressants is probably a common problem.

Adult↗
PubMed2000

Double blind study of tiapride versus haloperidol and placebo in agitation and aggressiveness in elderly patients with cognitive impairment.

OBJECTIVE: The aim of the present study was to compare the efficacy and safety of tiapride versus haloperidol and placebo in the treatment of agitation and aggressiveness in elderly patients with mild or moderate mental impairment. METHOD: This international, multicentre, randomized, double blind, three parallel groups study compared efficacy and safety of a 21 -day regimen of tiapride 100-300 mg/day versus haloperidol 2-6 mg/day and placebo in 306 elderly patients with mild or moderate dementia according to DSM III R and behavioural troubles with the Multidimensional Observation Scale for the Elderly Subjects (MOSES) irritability/aggressiveness subscore ranging from 16 to 30. RESULTS: The percentage of responders (defined as patients with at least a 25% MOSES irritability/aggressiveness subscore decrease between the inclusion and the end of the treatment) was significantly greater in the tiapride (63%, P=0.04) and haloperidol (69%, P=0.004) groups than in the placebo group (49%), with no significant difference between the active drugs. Similar results were observed for the mean MOSES irritability/aggressiveness subscores on D7, D21 and at D(end) which were significantly smaller in the tiapride and haloperidol groups than in the placebo group. The decrease between D0 and D(end) was significantly greater in the tiapride (6.57, P=0.009) and haloperidol groups (6.75, P=0.005) than in the placebo group (4.71). The global improvement CGI was significantly better in the tiapride and haloperidol groups than in the placebo group (P=0.03 and P=0.02). No significant difference was observed between the two active drugs or among the three treatment groups for the Folstein's Mini Mental Status scale (MMS) total score, and there was no notable change during treatment. The number of patients with adverse events, assessed on the Udvalg Kliniske Undersogelser scale (UKU), and the number of UKU symptoms were smaller in the tiapride group (62 patients, 61%, 212 events) than in the haloperidol group (77 patients, 76%, 305 events) and identical to that observed in the placebo group (69 patients, 67%, 234 events). Of interest, the number of patients with at least one extrapyramidal symptom was significantly lower (P=0.003) in the tiapride group (16 patients, 16%) than in the haloperidol group (34 patients, 34%) and similar to that of the placebo group (18 patients, 17%); the difference observed between the haloperidol and placebo groups was significant (P=0.008). CONCLUSION: Tiapride is not different from haloperidol in the treatment of agitation and aggressiveness in elderly patients and better tolerated, in particular with significantly fewer extrapyramidal symptoms.

Aged↗
PubMed2000

Five-year follow-up of early lisuride and levodopa combination therapy versus levodopa monotherapy in de novo Parkinson's disease. The French Lisuride Study Group.

The value of an early initial coadministration of levodopa (L-dopa) and lisuride in Parkinson's disease was the main goal of the present study. Eighty-two patients with recently diagnosed idiopathic Parkinson's disease were randomized into two groups for treatment with L-dopa alone or L-dopa + lisuride. The trial was double-blinded for the first year and open for the following 4 years. Selegiline (10 mg/day b.i.d.) was added in both groups at the end of the first year. Outcome measures were evolution of L-dopa dosage and Unified Parkinson's Disease Rating Scale scores and subscores, and incidence of motor complications. The dropout rate was higher in the L-dopa group (63.4%) than in the combination group. Motor improvement was better (p < 0.01) in the L-dopa + lisuride group. Expected motor complications were rare, moderate and equivalent in the two groups despite a difference in L-dopa dosage (446.7 vs. 387.5 mg/day). Long-term follow-up demonstrated the L-dopa-sparing effect of lisuride (average 1 mg/day), the beneficial effect of early combination therapy on motor status and the paucity of motor complications in both groups.

Adult↗
PubMed2000

[Rating scales and questionnaires in Parkinson's disease].

Rating scales and questionnaires used as measurement tools in Parkinson's disease are carefully constructed with well-defined items. The validity of a scale is its capacity to provide the intended measurement. One can distinguish perceived, content, and criteria-based validity as well as construction and sensitivity to change validity. The reliability of a scale is the capacity of a scale to produce statistically equivalent data in comparable situations. Reliability is composed of the following qualities: interobserver reliability, test-retest reliability, and internal coherence. UPDRES, mood scales (Hamilton, MADRS, CES-D, BDI), scales assessing cognitive disorders (MATTIS, MMSE), and quality of life questionnaires designed specifically for Parkinson's disease (PDQL, PDA-39, PDq-8) or for the general population (SF-36, SIP, NHP) are used in routine practice, and are particularly useful for clinical research. The metrological properties of these scales are analyzed here.

Humans↗
PubMed2000

[The physiopathology of migraine].

Although the neurobiological causative factors are now beginning to be understood, to a large extent the complex mechanisms involved in migraine remain an enigma, with the appearance of a transient unilateral cephalic pain, possibly preceded by a protean aura and associated with several other symptoms. The factors involved include three clinical signs or symptoms, i.e., pain, the aura (focalized neurological and neurosensory signs), and accompanying symptoms (e.g., sensory, psychological, or digestive); and three anatomical sites, i.e., the brain, the meningeal or intracranial vessel and a peripheral cranial nerve, the trigeminus (V). Familial hemiplegic migraine (FHM) has led to a consideration of the genetic origin of ionic channel-dependent pathologies (channelopathies), while certain other arguments which are for the most part indirect favor the hypothesis of abnormalities, again possibly of genetic origin, in the central neurotransmitters (including serotonin), which are involved in the transmission of pain messages and in vasomotor control. However, the main point is that each of the sites involved has its specific pharmacopoeia, which can contribute towards the treatment of migraine.

Humans↗
PubMed1999

Free radical involvement in endothelium-dependent responses of the rat thoracic aorta in moderate hypoxic conditions.

This study investigates the effects of agents which act on the production or efficacy of free radicals on the hypoxic responses of rat aorta rings. Under moderate hypoxic conditions, the resting tension of the rings was not changed but in rings precontracted with 5-hydroxytryptamine, there was a relaxation followed by a contraction. Removal of the endothelium with saponin suppressed relaxation to acetylcholine and abolished the contractions produced by hypoxia. In rings with a functional endothelium, hypoxic vasoconstriction was strongly inhibited by mannitol and exifone, but was not reduced by N(G)-nitro-L-arginine methyl ester, superoxide dismutase + catalase, or deferoxamine. Hypoxic vasodilatation was only partially inhibited by mannitol. To conclude, hypoxic constriction of the rat thoracic aorta is largely endothelium-dependent and involves free radicals whereas hypoxic dilatation is partially endothelium-dependent and partially involves free radicals. There is also indirect evidence for lack of direct involvement of nitric oxide/endothelium-derived relaxing factor (NO*/EDRF), hydroxyl radical (OH*) and superoxide anion in the hypoxic constriction and relaxation of the rat aorta.

Animals↗
PubMed1999

Effects of tiapride on electroencephalograms and cognitive functions in the elderly.

Tiapride is a substituted benzamide with selective dopamine D2 and D3-antagonist properties which appears to have preferential affinity for extra-striatal dopamine receptors. Tiapride is used in the treatment of agitation, aggressiveness and anxiety in the elderly. To define the effects of a single dose of tiapride 100 mg on psychomotor performance and cognitive functions and electroencephalogram (EEG), a randomized, double-blind, three-way crossover, placebo-controlled study using lorazepam 1 mg as a positive control was carried out in 12 elderly individuals (six women and six men, mean age +/- SD: 69 +/- 3 years). A 1-week wash-out interval was allowed between each administration. Psychomotor and cognitive functions were assessed using both objective [EEG, critical flicker fusion, simple reaction time, tapping, body sway, continuous performance task (CPT), digit symbol substitution test, Sternberg memory scanning and a learning memory test using word lists] and subjective (visual analogue scales) measures before and up to 6 h after dosing. Tiapride was devoid of any detrimental or sedative effects on EEG and all of the performance tasks used and did not impair memory compared with-placebo. In contrast, a single dose of lorazepam produced significant deleterious effects on psychomotor performance (decrease in tapping and in sustained attention (CPT) and an increase in reaction time and body sway), and sedative effects on EEG (significant increase in delta and decrease in alpha waves) as well as significant impairment in working memory (Sternberg) and anterograde amnesia (decrease in immediate and delayed free recall) up to 6 h after dosing compared with placebo and tiapride. In conclusion, the present study showed that in contrast to lorazepam 1 mg there is no evidence to suggest that a single dose of tiapride 100 mg has any sedative and amnestic effects in the elderly which may interfere with everyday life activities.

Aged↗
PubMed1999

Effects of 50mg amisulpride on EEG, psychomotor and cognitive functions in healthy sleep-deprived subjects.

Amisulpride, a substituted benzamide, binds selectively to the dopamine D2- and D3-receptors. It has higher affinity for limbic compared to striatal dopamine receptors in vivo. At low doses, amisulpride facilitates dopamine transmission via a selective blockade of presynaptic D2- and D3-receptors. Amisulpride is an active antipsychotic compound effective at low doses for negative symptoms and at high doses for positive symptoms of schizophrenia. The CNS profile of multiple doses of a low dosage regimen of amisulpride (50 mg once daily for 4 days) was assessed in a randomised, double-blind, 3-way crossover, placebo-controlled study carried out in 12 young sleep-deprived (for 36 h) subjects, using EEG and various measures of psychomotor and cognitive functions. Caffeine slow release (600 mg) was used as a positive reference. Multiple doses of 50 mg amisulpride once daily were devoid of any detrimental effects on EEG and psychomotor performance and cognitive function after total sleep deprivation. In addition, 50mg amisulpride partially antagonized the deleterious effects of sleep deprivation on EEG and subjective sedation as shown by trends, and a significant increase in EEG relative beta power and a decrease in subjective sedation. These effects were more pronounced at the end of sleep deprivation, suggesting possible alerting effects of amisulpride at this dose level. Caffeine significantly antagonized the detrimental effects of sleep deprivation on vigilance (increase in EEG beta waves, speed of reaction, sustained attention and reduction in subjective sedation). In conclusion, the present results demonstrate that 50 mg amisulpride is devoid of detrimental effects on EEG, psychomotor and cognitive performance after sleep deprivation, a situation well-known to amplify such effects if they exist. Moreover, some data suggest possible alerting effects of this low dosage regimen of amisulpride.

Adult↗
PubMed1999

Fecal incontinence with normal anal canal pressures: where is the pitfall?

OBJECTIVE: One third of subjects who suffer from fecal incontinence are found to have values within the normal range when anal manometry is performed. For these patients, one hypothesis is that impaired rectal adaptation to distension may occur. The aim of our study was to analyze anorectal responses to rectal isobaric distension in this population. METHODS: This was a prospective study conducted in 51 consecutive incontinent patients (45 female, six male) divided into two groups according to their functional anal state: absence (19 patients aged 55 +/- 6 yr) or presence of manometric anal weakness (32 patients aged 59 +/- 2 yr). The subjects were submitted to two randomized modes of rectal isobaric distension (tonic, phasic) with an electronic barostat. Anal pressures, perception, and volumes of the rectum were recorded at six different preselected pressures. RESULTS: As compared with those having anal weakness, patients with no anal weakness retained higher mean pressures at both upper (36.9 +/- 2.2 vs 22.9 +/- 1.4 mm Hg; p = 0.01) and lower parts (41.0 +/- 2.0 vs 23.3 +/- 1.4 mm Hg; p = 0.002) of the anal canal, similar perception scores, but much lower rectal volumes (68.5 +/- 5.5 vs 121.8 +/- 7.0 ml; p = 0.008) in response to rectal isobaric distension. CONCLUSION: A decrease in rectal adaptation could be involved in fecal leakage in patients with no anal manometric weakness.

Adaptation, Physiological↗
PubMed1999

Perception of and adaptation to rectal isobaric distension in patients with faecal incontinence.

BACKGROUND: Perception of, and adaptation of the rectum to, distension probably play an important role in the maintenance of continence, but perception studies in faecal incontinence provide controversial conclusions possibly related to methodological biases. In order to better understand perception disorders, the aim of this study was to analyse anorectal adaptation to rectal isobaric distension in subjects with incontinence. PATIENTS/METHODS: Between June 95 and December 97, 97 consecutive patients (nine men and 88 women, mean (SEM) age 55 (1) years) suffering from incontinence were evaluated and compared with 15 healthy volunteers (four men and 11 women, mean age 48 (3) years). The patients were classified into three groups according to their perception status to rectal isobaric distensions (impaired, 22; normal, 61; enhanced, 14). Anal and rectal adaptations to increasing rectal pressure were analysed using a model of rectal isobaric distension. RESULTS: The four groups did not differ with respect to age, parity, or sex ratio. Magnitude of incontinence, prevalence of pelvic disorders, and sphincter defects were similar in the incontinent groups. When compared with healthy controls, anal pressure and rectal adaptation to distension were decreased in incontinent patients. When compared with incontinent patients with normal perception, patients with enhanced perception experienced similar rectal adaptation but had reduced anal pressure. In contrast, patients with impaired perception showed considerably decreased rectal adaptation but had similar anal pressure. CONCLUSION: Abnormal sensations during rectal distension are observed in one third of subjects suffering from incontinence. These abnormalities may reflect hyperreactivity or neuropathological damage of the rectal wall.

Adaptation, Physiological↗