[Medico-economic assessment of the Pontoise Hospital stroke unit]. / Évaluation médico-économique de l'unité neurovasculaire du centre hospitalier de Pontoise.

INTRODUCTION: Annually, approximately 120,000 people in France have a stroke. Various controlled studies have pointed out the benefits of treatment in a stroke unit (SU). The objective of this study was to evaluate, from a medical point of view, the economic impact of the Pontoise Hospital SU. PATIENTS AND METHODS: Based on the national cost study (NCS [étude nationale des coûts: ENC]) we analyzed data of five diagnosis related groups (DRG) which have a principle diagnosis in relation with stroke. This work was limited to strokes and transient ischemic events in adults and excluded sub-arachnoid hemorrhage. Medical and economic parameters were collected over the period from January to October 2006 and compared with those of the same period in 2005, that is to say before the opening of the SU. RESULTS: Three hundred and twenty-three hospital stays occurred between January 1st and October 31st, 2006 and 216 during the same time period before the opening of the SU, an increase of approximately 50% of all stroke-related admissions in our hospital. The number of stays carried out in the neurology unit increased by 29%. There was no significant difference between the two periods regarding age (median 69 versus 70 years) and sex- ratio. Average length of stay (ALS) was the same (9 days). There were no significant differences concerning the death rate (5.6% versus 6.2%) and that of discharge to home (44.6% versus 44.4%). The cost by stay in 2006 was 3534 euros [median; min 664-max 57,542] versus 3541 euros in 2005 [681-35,149] (p=0.57). Analysis by DRG highlighted an increase in the cost for serious strokes, cerebral infarctions and hemorrhages. For transitory ischemic events, the cost and the ALS decreased. CONCLUSION: After the opening of the SU, there was an increase in the activity without an increase in the total cost. This could be related in part to the limited means allocated to the stroke unit at its opening (in particular medical staff). The NCS can be used to evaluate the activity of a stroke unit. This work could be completed on a larger number of units or in several units of different size.

A numerical study of the blocking of migraine by Rolando sulcus.

Migraine with aura is a complex phenomena, which remains still not completely understood. A striking fact is that its clinical manifestations may change from one patient to another. Migraine with aura may only consist in visual hallucinations, but may as well go on to temporary aphasy. However, for all the patients it always stops before it goes from area 3 to area 4, thus just before crossing Rolando sulcus. In this paper, we give arguments showing that the detailed geometry of Rolando sulcus in human cortex may by itself explain that migraine attack never crosses Rolando sulcus.

Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease.

Dyskinesia is a frequent and disabling side effect in patients with Parkinson's disease treated with chronic dopa-therapy. Preclinical data in the 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) monkey suggest that alpha-2 antagonists may reduce dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. We assessed, in a pilot randomised placebo-controlled study, the effects of single oral doses (10 mg, 20 mg, and 40 mg) of idazoxan, an alpha-2 antagonist, on motor parkinsonian disability and L-DOPA-induced dyskinesia following an acute oral challenge of L-DOPA in 18 patients with Parkinson's disease. The severity of L-DOPA-induced dyskinesia improved after 20 mg idazoxan pretreatment, while there was no concommittant deterioration in the antiparkinsonian response to L-DOPA. These results suggest that blocking alpha-2 receptors in patients with Parkinson's disease might improve L-DOPA-induced dyskinesia without the cost of a return of parkinsonian symptomatology. Further studies are required to assess whether this property could have potential therapeutic applications in the long-term management of dyskinetic patients with Parkinson's disease.

Dual-release formulation, a novel principle in L-dopa treatment of Parkinson's disease.

A single morning dose of dual-release formulation was compared with a slow-release formulation of L-dopa plus benserazide in a randomized, double-blind, cross-over study in 16 fluctuating patients with PD. The mean time to "on" was shorter with the dual-release formulation (43 +/- 31 minutes) than with the slow-release formulation (81 +/- 39 minutes) (p < 0.001), whereas the mean time to relapse to "off" was similar for both formulations. The dual-release formulation had a significantly shorter time to reach peak concentration (t(max)) and greater maximum concentration (C(max)) and area under the plasma concentration time curve (AUC(0--5 h)) than the slow-release formulation, whereas apparent elimination half-life (t(1/2)) was similar for both formulations.

Amitriptyline treatment in chronic drug-induced headache: a double-blind comparative pilot study.

OBJECTIVE: To assess the effects of amitriptyline and sudden analgesic withdrawal on headache frequency and quality of life in patients suffering from chronic daily headache related to analgesics abuse. METHODS: Seventeen nondepressed patients with chronic drug-induced headache were included in a 9-week, parallel-group, randomized, double-blind, placebo-controlled study. After abrupt analgesic withdrawal, amitriptyline or an active placebo (trihexyphenidyl) was started. The primary efficacy variable was headache frequency recorded on a headache diary in the last 4 weeks of each treatment. The secondary efficacy variable was quality of life (Nottingham Health Profile). RESULTS: Headache frequency decreased by 45% in the amitriptyline group and by 28% in the trihexyphenidyl group. Amitriptyline enhanced all the dimensions of quality of life and significantly improved emotional reaction and social isolation. CONCLUSION: This pilot study suggests a beneficial effect of amitriptyline on headache frequency and quality of life for patients with chronic drug-induced headache.

Differential bicuculline-induced epileptogenesis in rat neonatal, juvenile and adult CA3 pyramidal neurons in vitro.

The GABA(A) receptor antagonist bicuculline methiodide (BMI, 10 microM) transformed the evoked synaptic responses, recorded intracellularly from the CA3 area of neonatal (postnatal days 3-7, P3-P7), juvenile (P8-P20) and adult hippocampal slices, into long-lasting paroxysmal depolarizations (PDs), with repetitive action potentials (APs). In the same preparation, GABA(A)-mediated fast-IPSPs were depolarizing at resting membrane potential (RMP), with a reversal potential shifting to a hyperpolarizing direction with age (n=15, P6-P17). BMI provoked also spontaneous PDs in juvenile (20/30) and adult (7/10) but not in neonatal (0/12) neurons. PDs were depressed by either the NMDA receptor antagonist CPP (10 microM) or the non-NMDA antagonist CNQX (10 microM), but were blocked only by the combination of the two (n=6), indicating that activation of either NMDA or non-NMDA receptors can independently sustain PDs in immature hippocampus. In conclusion, these findings show that endogenous GABA tonically inhibits CA3 synaptic responses in neonatal life despite the depolarizing nature of GABA(A)-mediated potentials. Moreover, they suggest that during the 1st postnatal week, disinhibition alone is not sufficient to provoke spontaneous epileptiform discharges in CA3 hippocampal area.

Epileptiform activity generated by endogenous acetylcholine during blockade of GABAergic inhibition in immature and adult rat hippocampus.

We tested the effects of the acetylcholinesterase inhibitor eserine (10 microM), an indicator of the activity of endogenous ACh, on the generation of epileptiform discharges during blockade of inhibitory GABA(A)-mediated potentials by bicuculline (10 microM), in the CA3 area of hippocampal slices from postnatal days 4-20 (P4-P20) immature and adult rats. Eserine provoked or significantly increased the frequency of spontaneous synchronous epileptiform discharges, in 6/22 (27%) P4-P10 slices, 34/35 P11-P20 slices and 18/18 adult slices, an epileptogenic effect. In immature slices, spontaneous discharges showed a stable frequency throughout perfusion with eserine, while in 5/11 adult slices an initial fast frequency was followed by a slower steady-state one. The cholinergic agonist carbachol (CCh, 25 microM) provoked only transient or no spontaneous synchronous discharges in adult slices (n=8), thus suggesting that massive activation of cholinergic receptors may lead to suppression of epileptiform activity in adult brain. Stimulus-induced excitatory CA3 responses, were depressed by eserine in approximately half of 20 P4-P10, 45 P11-P20 and 11 adult slices. The depression consisted of a decrease in the amplitude, duration, and number of population spikes of the field potentials by about 30%, a minor neuroprotective effect, which did not change with maturation. The different developmental profiles of the epileptogenic and neuroprotective effects of endogenous ACh suggest that they are mediated by different mechanisms. These experiments demonstrate that, endogenous ACh is sufficient to induce epileptogenesis during a decrease or failure of GABAergic inhibition, in both >/=P10 immature and in adult hippocampus. We therefore suggest that clinical or behavioral conditions which raise the concentration of endogenous ACh may lower the threshold to seizures.

ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson's disease.

Studies in animal models show a selective D1 receptor agonist with full functional efficacy compared with dopamine to have antiparkinsonian efficacy of similar magnitude to levodopa, without the same propensity for inducing dyskinesia. To date, no such agent has been tested in humans. ABT-431 is the prodrug of A-86929, a full, selective D1 receptor agonist. Subjects (n = 14) with levodopa-responsive Parkinson's disease received five doses of ABT-431 (5, 10, 20, 30, and 40 mg) and one of placebo after a 12-hour levodopa holiday. Response was assessed by using the Unified Parkinson's Disease Rating Scale motor subsection. Dyskinesia was separately graded. ABT-431 showed efficacy significantly superior to placebo at doses of 10 mg and more, and of similar magnitude to that seen with levodopa. Dyskinesia was reduced in several patients after receiving ABT-431. There were no serious adverse events, the most common minor events being nausea and emesis, dizziness, and hypotension. Assuming that ABT-431 is not transformed in humans into an unknown active D2 metabolite, and remains selective for D1 receptors, it is the first dopamine D1 receptor agonist to demonstrate a full antiparkinsonian effect in patients with Parkinson's disease. These preliminary findings also suggest that it may exhibit a reduced tendency to provoke dyskinesia. The emergence of a well-tolerated D1 agonist should allow for the development of a better understanding of the relation between motor efficacy and dyskinesia in Parkinson's disease.

A comparison of the adenosine-mediated synaptic inhibition in the CA3 area of immature and adult rat hippocampus.

We compared the effects of the adenosine A1 receptor activation on the postsynaptic potentials (psps) recorded from the CA3 area of immature (postnatal days 10-20) and adult rat hippocampal neurons in vitro. The adenosine A1 receptor agonist 2-phenyl-isopropyl-adenosine (PIA, 1 microM) depressed the stimulus-induced psps less in immature and more in adult neurons. In the presence of the GABAA receptor antagonist bicuculline methiodide (BMI, 10 microM), PIA reduced the duration and number of action potentials of the stimulus-induced paroxysmal depolarizations (PDs) in immature neurons, while it blocked PDs in adult neurons. Spontaneous BMI-induced PDs, were blocked by PIA in less than half (5/12) immature and all (6/6) adult neurons. The adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 microM) enhanced the stimulus-induced psps in immature and adult neurons alike; this effect did not lead to stimulus-induced bursting in immature neurons. DPCPX induced spontaneous bursts (proconvulsant effect) in only 2/16 immature but in all adult (12/12) neurons. In BMI, DPCPX increased the duration and number of action potentials of the stimulus-induced PDs in immature and adult neurons alike (by about 30%), but it increased the rates of occurrence of spontaneous PDs in significantly more adult neurons. In conclusion, our results suggest that adenosine, acting via A1 receptors, is a more effective endogenous anti-epileptic in adult than in immature hippocampus, a fact which may contribute to the susceptibility of the latter to epileptogenesis.

Reliability of a paralleling instrument for dental radiographs.

The reliability of a paralleling instrument for dental radiographs was retrospectively evaluated in the course of a 6-month clinical study. The angular variation between successive exposures was precisely quantified. Ninety-one percent of the angular variations were below a 1.4 degree threshold, but some paired images were found unsuitable for quantitative analysis. A mathematic procedure to assess the global angular projection error of any similar coupled x-ray cone-film holder device is proposed. This mathematic procedure should be routinely used to check superimposability of serial radiographs before density quantification or subtraction.