Results-A total of 2522 prescriptions were administered to 989 patients; 844 (33%) were used either in an unlicensed (4%) or an oV label (29%) manner. A total of 550 (56%) paediatric patients received one or more oV label prescriptions. Conclusions-OV label prescriptions (that is, outside the terms of the Summary of Product Characteristics) are widespread in oYce based paediatric practice, while unlicensed drug use is rare in our study. New regulations in the licensing process in Europe are needed to allow children to receive drugs that have been fully evaluated in their specific age group. (Arch Dis Child 2000;83:502-505)

SUMMARY1. The effects of bilateral electrolytic lesions within and around the prepositus hypoglossi (p.h.) nucleus on horizontal saccades in the dark and on the horizontal sinusoidal vestibulo-ocular reflex (v.o.r.) in the dark were studied.2. After p.h. lesion, including its rostral part between P 7 and P 8, the v.o.r. showed a phase lead as much as about 90 deg at 0-10 Hz. A significant gain reduction paralleled that phase lead at lower frequencies. A large post-saccadic drift was also observed, the time constant of which ranged from 0 3 to 0-6 s.3. After p.h. lesion extending from P 8 to P 11 (but sparing the rostral part of the p.h.), no significant gain or phase lead change was observed. Post-saccadic drift was either missing or weak.4. A bilateral medial vestibular nucleus (m.v.n.) lesion from P 7 to P 11 produced a marked gain decrease, paralleled by a marked phase advance. A post-saccadic drift was observed (r = 0-6 s).5. A surgical mid-line lesion from P 7 to P 11 (depth: about 2 mm) was followed by no remarkable change in the gain and in the phase of the v.o.r. No post-saccadic drift was observed after such lesion.6. It was concluded that (i) both the horizontal v.o.r. integration processing, and the horizontal saccadic integration processing were destroyed when an electrolytic lesion was made 'in the region of' the rostral part of the p.h. nucleus, and that (ii) the posterior four-fifths of the p.h. was the location of neither the horizontal v.o.r. integrator nor the horizontal saccadic integrator.

1. For horizontal eye movements, previous observations led to the hypothesis that the legendary neural integrator necessary for correct gaze holding, adequate vestibuloocular reflex (VOR), and optokinetic nystagmus, was located in the region of the complex formed by the nucleus prepositus hypoglossi (NPH) and the medial vestibular nucleus (MVN). 2. The aim of the present study was to test the respective contributions of the NPH, of the rostral part of the MVN, which contains most second-order vestibular neurons, and of the central part of the MVN to the horizontal integrator. 3. An injection of muscimol was used to inactivate each of these three zones in the cat's brain. Muscimol is a gamma-aminobutyric acid (GABA) agonist. By binding to GABAA receptors, it induces a hyperpolarization of the neurons that nullifies their activity. Muscimol was injected into the brain stem of the alert cat through a micropipette by an air pressure system. 4. The search coil technique was used to record spontaneous eye movements and the VOR induced by rotating a turntable at a constant velocity. VOR was analyzed by a new method: transient analysis of vestibular nystagmus. 5. A unilateral injection of muscimol into the NPH induced a bilateral gaze-holding failure: saccades were followed by a centripetal postsaccadic drift. A vestibular imbalance was also present but it was moderate and variable. The VOR responses were distorted drastically. Through transient analysis of vestibular nystagmus, that distortion was revealed to be due more to a failure of the neural integrator than to an alteration of the vestibular input to the neural integrator. The responses to a rotation either toward the injected side or in the opposite direction were asymmetrical. The direction of that asymmetry was variable. 6. A unilateral injection of muscimol into the rostral part of the MVN caused a vestibular imbalance: in complete darkness, a nystagmus appeared, whose linear slow phases were directed toward the side of injection. 7. A unilateral injection of muscimol into the central part of the MVN induced a syndrome where a severe bilateral gaze-holding failure was combined with a vestibular imbalance. In the light, saccades were followed by a bilateral centripetal postsaccadic drift. In complete darkness, a nystagmus was observed, whose curved slow phases were directed towards the side of injection. The VOR responses were distorted drastically. Here again, that distortion was revealed by our analysis to be due more to a failure of the neural integrator than to an alteration of the vestibular input to the neural integrator.(ABSTRACT TRUNCATED AT 400 WORDS)

One of the major challenges in alcohol dependence is relapse prevention, as rates of relapse following detoxification are high. Drug-related motivational processes may represent key mechanisms in alcoholic relapse. In the present study, event-related potentials (ERPs) were recorded during a visual oddball task administered to 29 controls (11 females) and 39 patients (9 females). Deviant stimuli were related or unrelated to alcohol. For patients, the task was administered following a 3-week detoxification course. Of these, 19 relapsed during the three months follow-up period. The P3, an ERP component associated with activation of arousal systems in the brain and motivational engagement, was examined with the aim to link the fluctuation of its amplitude in response to alcohol versus non-alcohol cues to the observed relapse rate. Results showed that compared to relapsers, abstainers presented with a decreased P3 amplitude for alcohol related compared to non-alcohol related pictures (p=.009). Microstate analysis and sLORETA topography showed that activation for both types of deviant cues in abstainers originated from the inferior and medial temporal gyrus and the uncus, regions implicated in detection of target stimuli in oddball tasks and of biologically relevant stimuli. Through hierarchical regression, it was found that the P3 amplitude difference between alcohol and non-alcohol related cues was the best predictor of relapse vulnerability (p=.013). Therefore, it seems that a devaluation of the motivational significance of stimuli related to alcohol, measurable through electrophysiology, could protect from a relapse within three months following detoxification in alcohol-dependent patients.

1. The aim of this study was to characterize the signals transmitted by the neurons of the nucleus prepositus hypoglossal (NPH) to the middle zone of the flocculus of the cat. The methods, the behavioral testing, and the animals used in this study were the same as those used in the accompanying paper on medial vestibular nucleus neurons. 2. The rostral two-thirds of the NPH was explored in alert animals with microelectrodes during stimulation of the middle zone of both flocculi. Discharges of neurons were analyzed during spontaneous eye movements (head fixed) and during horizontal vestibuloocular reflex (VOR) activity elicited by sinusoidal stimulation (10, 20, 30, or 40 degrees at 0.1 Hz). Forty neurons were found to be antidromically activated from only one or the other of the two flocculi (latency: 0.99 +/- 0.17 ms, mean +/- SD): 37 from the contralateral flocculus and 3 from the ipsilateral one. None of the neurons could be activated antidromically from both flocculi. Floccular stimulation never resulted in direct inhibition of these NPH neurons. 3. Of the 37 units antidromically activated from the contralateral flocculus, 26 were recorded sufficiently long to allow full quantitative analysis. Most of these (20 neurons) were classified as burst-tonic (BT) neurons. The BT neurons exhibited during each saccade made in one direction (the ON direction) a burst of spikes, and during postsaccadic fixation a tonic activity that increased with gaze displacement in the ON direction. The mean sensitivity of the neurons to eye velocity during the "ON" saccades was 3.3 +/- 1.6 spikes.s-1.deg-1.s-1. During intersaccadic fixation, the mean sensitivity to eye position was 3.6 +/- 2.5 spikes.s-1.deg-1. During the VOR, the majority showed modulation in relation to both eye position and eye velocity. The mean sensitivity to eye position during the VOR was 3.4 +/- 2.6 spikes.s-1.deg-1 (range: 0.2-8.1 spikes.s-1.deg-1). The mean sensitivity to eye velocity during the VOR was 2.1 +/- 1.3 spikes.s-1.deg-1.s-1. The mean phase lead of with respect to eye position was 16.4 +/- 6.8 degrees (range: 6.0-28.9 degrees). Eighty percent of the BT neurons behaved as type I neurons. Forty-seven percent of the BT neurons also presented some head velocity sensitivity (1.48 +/- 0.6 spikes.s-1.deg-1.s-1, mean +/- SD). 4. Other NPH cells antidromically activated from the contralateral flocculus were classified in two groups: bidirectional burst (BB) neurons (n = 4) and burst-driving (BD) neurons (n = 2). The BB neurons were characterized by a burst discharge during every horizontal saccade or VOR quick phase, irrespective of the direction. The mean sensitivity of the BB neurons to eye velocity during saccades was 3.3 +/- 7.8 (SD) spikes.s-1.deg-1.s-1. Both BD neurons increased their firing rate during the slow VOR phases induced by an ipsilateral rotation (type I neurons) and exhibited high-frequency bursts in association with ipsilaterally directed quick phases. 5. The results indicate that the main projection of the NPH onto the middle zone of t...

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1. Properties of nucleus incertus (NIC) neurons projecting to the cerebellar flocculus were studied in alert cats by using chronic unit and eye movement recording and antidromic activation. Projection of these neurons onto the flocculus was verified with retrograde transport of horseradish peroxidase after injections in the flocculus. 2. Bipolar stimulation electrodes were implanted into the "middle" zone of each flocculus because this zone is known to be involved in the control of horizontal eye movements. The dorsomedial aspect of the pontine tegmentum was explored with microelectrodes during stimulation of both flocculi. The majority of neurons antidromically activated from the flocculus were found in the caudal part of the NIC. 3. Of the 69 neurons activated from the flocculus, 44 were classified as burst-tonic (BT) neurons; 34 discharged in relation with horizontal movements of the eye, 10 in relation with vertical movements. Of the 14 remaining neurons, 6 were not related to eye movements and 8 were classified as burst neurons. The BT neurons of the NIC displayed a great sensitivity to both horizontal eye position and horizontal eye velocity. 4. This study demonstrates the presence of a new group of horizontal eye movement related BT neurons situated in the NIC. The fact that they project to the horizontal floccular zone emphasizes the importance of the functional specialization of the different Purkinje cell zones.