Assessment of interindividual variability of plasma concentrations after administrazion of high doses of intravenous amoxicillin or cloxacillin in critically ill patients.

The aim of the present retrospective observational clinical study was to assess the interindividual pharmacokinetic variability of plasma concentrations of amoxicillin or cloxacillin administered in high doses intravenously in critically ill patients, related to renal function or administration method.Four hundred and two plasma concentrations were measured at steady-state with a high performance liquid chromatography technique in 162 patients treated with 100 - 300 mg/kg/day of intravenous amoxicillin or cloxacillin.For both drugs and administration methods, plasma concentrations were significantly higher for patients with creatinine clearance below 60 ml/min, even though doses were adapted for renal impairment. the correlations calculated between plasma concentrations and creatinine level, creatinine clearance or doses were all low. There were fewer outlying drug concentrations in patients receiving continuous rather than intermittent regimens.Our results are in favor of adapting dosages of these beta-lactam antibiotics based on plasma concentrations, especially in cases of renal impairment.

[Prescription of olanzapine in children and adolescent psychiatric patients]. / Prescription de l'olanzapine chez l'enfant et l'adolescent.

INTRODUCTION: A review of the literature from 1996-2004 on the indications and adverse reactions concerning the use of olanzapine, a second generation antipsychotic agent, in children and adolescents with psychiatric illness is made in this article. Studies lasted for 2 to 3 months and a few had a follow up period up to a year. Olanzapine, dosed from 2.5 to 20 mg/day, is shown to be a useful drug in the treatment of child and adolescent onset schizophrenia, bipolar disorder, anorexia nervosa with delusions, pervasive developmental disorder, tic disorders, and aggression. OPEN AND DOUBLE-BLIND STUDIES: In 4 open labeled studies (26, 34, 39, 43) and 2 case reports (25), 53 patients, aged from 6-18 years old, afflicted by child onset schizophrenia, were treated with olanzapine for 1 1/2 weeks to one year; 19 had treatment resistant childhood schizophrenia and 34 a first episode. In the first group 13/19 showed improvement whereas, in the second group 27/34 were considered responders. Four patients in the first group who had responded to clozapine (stopped because of adverse events) did less well on olanzapine. In 5 studies, 4 open labeled (15, 20, 44) and 1 double blind (27), 59 adolescent onset schizophrenic patients were treated by olanzapine from 8 to 26 weeks; 50/59 patients were considered responders. In the open label study (20) comparing 43 adolescents treated by olanzapine (19 patients), risperidone (17 patients), or haloperidol (7 patients), improvement was significant in the three groups after 4 weeks of treatment and continued after 8 weeks. It is most interesting to mention that 2 months after the end of the study 71% (12/17) of the olanzapine group that had completed the study, 10/15 (67%) of the risperidone group, and 43% (3/7) of the haloperidol group had continued their treatment. Dropouts were for inefficacy and non-compliance in the olanzapine and risperidone groups whereas they were also for adverse events in the haloperidol group (2/4). A final double blind study of 263 adult and adolescent schizophrenic patients (latter are not separated from the former) confirmed the superiority of olanzapine compared to haloperidol and its use for a long period: 67% of the olanzapine and 54% of the haloperidol patients completed the 12-week study. CASE-REPORTS: 12 case reports of children and adolescents diagnosed with acute mania (8, 25, 46, 47) and 23 in an open labeled study (16) were treated by olanzapine; 26/35 were considered to respond well. Some of the patients were on mood stabilizers before adjunction of olanzapine, others on olanzapine monotherapy; 10 case reports of patients with anorexia nervosa associated with psychotic symptomatology, aged from 10-17 years old, relate the use of olanzapine as adjuvant treatment. Improvement was spectacular in these patients who not only gained considerable weight, but were also more compliant to the therapeutic program and their obsessions, delusions, agitation and anxiety became less intense. In this form of anorexia nervosa, olanzapine appears to have an interesting therapeutic role and, in particular, its most important adverse effect, weight gain, became a therapeutic goal. In 2 preliminary studies (24, 30) 31 children and adolescents diagnosed with pervasive developmental disorder were treated by olanzapine from 6 to 13 weeks; 18/25 had good or moderate symptomatic improvement: they were less irritable and hyperactive, and their speech less excessive. In 17 case reports of children and adolescents with aggression (42, 45), associated with tics in 10 patients (49), treatment with olanzapine from 2 weeks to 10 months lowered the presenting symptoms, enhanced the cooperation, and improved the mood of the patients. Only one patient's treatment was changed for inefficacy. DISCUSSION: No matter what the disorder treated, when olanzapine was compared to haloperidol and risperidone, it proved to be as effective as risperidone, and as or more effective than haloperidol; but when compared to clozapine, it was less effective. The most prominent adverse reaction was excessive weight gain, even more so than in adult patients treated with olanzapine. Also weight gain was greater in children and adolescents treated by olanzapine than those treated by risperidone or haloperidol. Though few treatments had to be interrupted because of this side effect, child and adolescent psychiatrists are wary of the long-term disease related to obesity and glucose dysregulation. All should be done to under-stand the process of weight gain better and to prevent or stall excessive caloric intake, encourage activity, and eventually treat by corrector drugs. Secondly, sedation may bother up to 50% of patients even at the end of the study periods, as many as those treated by haloperidol and more than those treated by risperidone. Extrapyramidal symptoms were mild or moderate compared to those that appear with haloperidol, but may be more frequent than in adult patients. Liver enzymes and blood sugar may be slightly elevated. Prolactemia may be elevated but less so with risperidone and haloperidol. CONCLUSION: All the authors emphasized the unfortunate lack of randomized double blind studies for the use of olanzapine in this age group.

Effect of training and detraining on catecholamine responses to sprint exercise in adolescent girls.

Training is well known to influence catecholamine responses to exercise. In women, this training effect is still not well characterized and has been studied mostly in adults. Hence, we investigated in this longitudinal study, the effects of a 6-month sprint training program followed by 5 months of detraining on plasma catecholamine responses to a sprint exercise in young female subjects. Twelve healthy adolescent girls [training group (TG), n=6; control group (CG), n=6] took part in our study. TG participated in 6 months of supervised sprint training program (3 days/week) and has no training past whereas, CG continued with it's normal activity. A 6s-sprint test was performed on a cycle ergometer before training (P1) and after training (P2) in both the groups. TG only realized a 6s-sprint test after 5 months of detraining (P3). Blood lactate concentrations (La) as well as plasma adrenaline (A) and noradrenaline (NA) concentrations were measured at rest, immediately after the warm-up and the 6s-sprint and during recovery. Peak power W peak), expressed both in absolute and relative values, were significantly increased in TG in P2 (P<0.01) but did not change in CG. After the sprint-training period, the warm-up and the 6s-sprint induced plasma A increase and the maximal A concentrations were significantly higher than in P1 and P3 for TG only (P<0.05). Plasma A did not change in CG after 6 months. In P3, W peak and maximal lactate concentrations ([La]max) were significantly greater compared to P1 and P2 in TG (P<0.05). In CG, [La]max were significantly increased in P2 (P<0.05). The present study demonstrates that 6 months of sprint training in adolescent girls induce both an increase in performances and in A responses to sprint exercise. This adrenergic adaptation disappears after 5 months of detraining whereas the gain in performance is maintained. These new data may lead to practical considerations.

[Mechanisms of chronic cough pathophysiology]. / Passage à la chronicité d'une toux: quels mécanismes?

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.

[NOEMIE: an epidemiological study of migraine at work: results from 17 occupational health centres]. / NOEMIE: un observatoire de la migraine en entreprise. Résultats obtenus dans dix-sept centres de médecine du travail.

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.

[Myoclonic encephalopathy associated with proton pump inhibitors]. / Encéphalopathie myoclonique: rôle des inhibiteurs de la pompe à protons.

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.

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.

[Drug distribution systems in hospitals]. / Le circuit du médicament à l'hôpital.

Any drug generally made and marketed by drug companies must respect the quality standards conferred by New Drug Approval regarding both safety and efficacy. Once prescribed by a doctor, inside a hospital, the drug, or more precisely the decision of its prescription will follow a complex circuit, involving numerous intermediates (human and technical) leading to drug dispensation and follow-up. Regulatory guidelines and rules harmonise and standardise this drug pathway in hospitals. Any weakness in this distribution system will be the source of nosocomial drug iatrogeny. The present review aims at describing the different steps and stages from the prescription to an individual patient to drug administration and follow-up. The evaluation of this system will be mentioned in the perspective of optimisation. The computerised system is essential allowing tracking of a drug, and providing help for decision-making (by confrontation with data bases) and a research tool (i.e, pharmacoepidemiology). Different experiences of assessment of the performance of such a drug distribution system inside hospitals will be presented, trying to check the quality reference: the right drug, the right patient, the right moment, in good conditions. The challenge is to optimise and secure all steps of the process. This goal needs assessment and quality control of the different phases, opening the discussion between hospital policy and regulatory and technical considerations.

Training status (endurance or sprint) and catecholamine response to the Wingate-test in women.

The aim of this study was to verify if, as for men, training status induces different catecholamine responses to exercise. To do this, we investigated the effect of training status (sprint or endurance) on plasma catecholamine response to a supramaximal exercise in women. Nineteen subjects took part in our study: six untrained subjects (UT), seven endurance trained subjects (ET) and six sprint trained ones (ST). The trained subjects (ET and ST) were all competing at a high national level. The maximal power (W max ) and the mean power (W) were determined from the Wingate-test. Blood lactate, adrenaline (A) and noradrenaline (NA) were analysed at rest (La 0, A 0 and NA 0 ), immediately at the end of the exercise (A max and NA max ) and after 5 min recovery (La max [3 min in arterialized blood], A 5 and NA 5 ). The disappearance of A and NA was judged by the ratio (A max -A 5 )/A max and (NA max -NA 5 )/NA 5. The ratio A max /NA max was considered as an index of the adrenal medulla responsiveness to the sympathetic nervous activity. As expected, during the Wingate-test ST exhibited significantly higher performances compared to UT and ET. But in contrast to the men's data no difference was observed between the three groups both for La max (13.1 +/- 0.8 mmol x L (-1); 14.8 +/- 1.0 mmol x L (-1) and 11.2 +/- 0.5 mmol x L (-1) respectively for ET, ST and UT), NA max (22.1 +/- 1.2 nmol x L (-1); 13.1 +/- 2.4 nmol x L (-1) and 20.2 +/- 7 nmol x L (-1)respectively for ET, ST and UT) and A max (4.1 +/- 0.8 nmol x L (-1); 2.6 +/- 0.6 nmol x L (-1); 13.1 +/- 0.6 nmol x L (-1) respectively for ET, ST and UT). Consequently the ratio A max /NA max was similar in UT, ET and ST (respectively 0.2 +/- 0.03; 0.2 +/- 0.04; 0.17 +/- 0.04), These results indicated, in contrast to the men's data, that the catecholamine response to the Wingate-test did not differ between female subjects of different status of training. In conclusion this study did not find any significant effect of training status on the catecholamine response to supramaximal exercise and so argues in favour of sex differences in response to training.

[Effect of almitrine/raubasine on cerebral metabolism in the elderly]. / Effet de l'almitrine/raubasine sur le métabolisme cérébral du sujet âgé.

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.

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.

[Mild Cognitive Impairment: potential therapeutics]. / Le déclin cognitif modéré ou le mild cognitive impairment (MCI): perspectives thérapeutiques.

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.

Effect of training status on the sympathoadrenal activity during a supramaximal exercise in human.

BACKGROUND: The study investigated the concentrations of plasma catecholamine, adrenaline (A) and noradrenaline (NA), and the adrenal medulla responsiveness to the sympathetic nervous activity in sprinters (S), endurance runners (E) and untrained subjects (U) during a supramaximal exercise (the Wingate-test). METHODS: A group of 19 men took part in the tests: 6 S (20.5+/-0.7 years), 6 E (21.0+/-1.0 years) and 7 U (20.9+/-0.4 years). The maximal power (Wmax) and the mean power (W) were determined from the Wingate-test on a cycle ergometer. The plasma lactate, A and NA were analysed at rest (La0, A0 and NA0), immediately at the end of the exercise (Amax and NA(max)) and after 5 min recovery (La(max), A5 and NA5). The disappearance of A and NA was judged by the difference between the maximal values and those determined after 5 min recovery (Amax-A5 and NA(max)-NA5) and the ratio A/NA was considered as an index of the adrenal medulla responsiveness to the sympathetic nervous activity. RESULTS: During the Wingate-test S exhibited higher performances and higher La(max) than the two other groups. At the end of the Wingate-test the NA(max) values were similar in the three groups whereas the Amax values were significantly higher in S than in E and U (8.00+/-0.5 nmol x l(-1) in S vs 3.47+/-0.30 nmol x l(-1) and 3.29+/-1.14 nmol x l(-1) respectively in E and U). This leads to a higher Amax/NA(max) ratio for S compared to the other two groups (0.77+/-0.10 in S vs 0.23+/-0.03 and 0.28+/-0.05, respectively in E and U). As the disappearance of A (Amax-A5) was significantly higher in S (6.80+/-0.47 nmol x l(-1) in S vs 2.64+/-0.19 nmol x l(-1) and 1.64+/-1.37 nmol x l(-1), respectively in E and U), the higher values of Amax in S could be explained by an increase of the adrenal medullary secretory capacity in this group. CONCLUSIONS: It was concluded that essentially short term and intense exercises as sprint ones or interval-training may alter the adrenal medulla responsiveness to supramaximal exercise but not long duration exercises.

Glucose tolerance during moderate prolonged exercise in women with oral contraceptives as compared to non-users.

BACKGROUND: The purpose of this study was to assess gluco-se tolerance during exercise in women on oral contraceptives. METHODS: To this end, we investigated the effects of glucose ingestion on glucose and hormonal responses in 7 women on oral contraceptives (OC(+); 21.3+/-1.3 yrs) and 7 normally menstruating (OC(-); 22.6+/-1.3 yrs) during an ergocycle test (30 min, 60% VO2max). Venous blood samples were withdrawn at 0, 3, 5, 10, 15 and 30 min exercise and at the 30th min postexercise. Glucose was ingested per os (0.5 g x kg(-1) b.w) between the 2nd and the 3rd min of the exercise. RESULTS: Under resting condition, plasma glucose and catecholamine concentrations were similar in both groups whereas plasma GH and insulin levels were greater in OC(+) (p<0.05). Glucose/insulin ratio (G/I), used as an indicator of insulin resistance, suggested a reduced insulin sensitivity at rest in the OC(+) (p<0.05). No significant differences were observed between OC(+) and OC(-) in plasma glucose, insulin, and catecholamine concentrations during exercise. Plasma GH values were greater in OC(+) from the 15th min of the exercise and during the recovery period (p<0.01). CONCLUSIONS: This study indicated that oral glucose ingestion at the onset of prolonged submaximal exercise induced similar glucose tolerance in women taking or not oral contraceptives.

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.

[Perspectives for drug treatment in Alzheimer's disease]. / Perspectives médicamenteuses dans la maladie d'Alzheimer.

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.

[The physiopathology of migraine]. / Physiopathologie de la 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.

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.

Effects of glucose ingestion at the onset of moderate-intensity, prolonged exercise in women as compared to men.

To test glucose tolerance during exercise, the effects of oral glucose ingestion (0.5 g x kg(-1)) on plasma glucose and hormonal responses (insulin, catecholamines) were investigated in 11 women [mean (SEM) age 21.6 (1.3) years] and 10 men [22.0 (0.3) years] during cycle ergometer exercise (30 min at 60% maximum oxygen consumption, VO(2max)). The two groups exhibited similar VO(2max) values, when expressed per kg of lean body mass. Venous blood samples (5 ml) were withdrawn immediately before the exercise, during the exercise (at 3, 5, 10, 15 and 30 min) and at the 30th min of the recovery period. Glucose was ingested orally between the 2nd and the 3rd min of the exercise. As compared to men, plasma glucose concentrations were lower in women during exercise (P < 0.05 at 3, 15 and 30 min) and at the 30th min of the recovery period (P < 0. 001), while plasma insulin concentrations were higher in women during exercise (P < 0.05 at 3, 15 and 30 min). The ratio of the area under the curve for glucose over the area under the curve for insulin was lower in women during exercise (P < 0.0002). A linear relationship between glucose and insulin concentrations was found only for women during exercise (r = 0.615, P < 0.0001). No gender difference was observed for the catecholamine concentration during exercise. In conclusion, this study postulates that an oral glucose load given at the onset of a prolonged and moderate exercise bout induced lesser plasma glucose and greater insulin concentrations in women as compared to men. These data argue in favour of a greater glucose tolerance in women during exercise.