[Fatal case of enterovirus A71 hand, foot, and mouth disease infection]. / Décès d'un nourrisson dans un contexte de syndrome pieds-mains-bouche associé à l'entérovirus A71.

Hand, foot, and mouth disease associated with enterovirus (EV) infections is a common pediatric pathology that is usually considered as benign. However, neurological complications of varying severity, sometimes fatal, are possible, particularly when EV-A71 is involved. Several Asian countries are regularly affected by large-scale epidemics of EV infections with substantial morbidity and mortality, where early screening and appropriate therapeutic management are a public health challenge. In 2016, Europe experienced an epidemic of unusual magnitude, associated with increasing cases of severe neurological complications in Spain and France, mainly affecting children. Virological diagnosis is based on EV genome detection in peripheral clinical specimens (vesicles or oral ulcerations, throat, nasopharyngeal aspirate, stool) in addition to cerebrospinal fluid and blood. EV-A71 is rarely detected in cerebrospinal fluid, which renders the diagnosis of EV-A71-associated encephalitis challenging. We report the case of a 27-month-old child with hand, foot, and mouth disease turning into rapidly progressive and fatal cardiopulmonary failure associated with EV-A71 infection, in France in 2016. EV infections associated with hand, foot, and mouth disease warrant specific epidemiological surveillance outside the Asian region.

Acute inescapable stress exposure induces long-term sleep disturbances and avoidance behavior: a mouse model of post-traumatic stress disorder (PTSD).

The experience of traumatic stress often leads to long-lasting alteration in sleep quality and behavior. The objective of the present experiment was to investigate the short- and long-term effects of acute inescapable stress (i.e. two electric foot-shocks of 1.5 mA; 2s) on sleep/wakefulness parameters and behavior in Swiss mice using electroencephalographic (EEG) analysis. Baseline EEG recording was performed in the home cage for 6h prior to the application of the foot-shocks in the presence of an object (i.e. a plastic prism). One, 7, 14 or 21 days later, a second 6h EEG recording session was performed after mice had been exposed or not to the same object for 5 min in their home cage. Results showed that at day 1, 7, 14 and 21 post-stress, shocked mice displayed sleep fragmentation as shown by an increase in the number of sleep episodes, regardless the presence of the object or not. In animals exposed to the object, the total duration of wakefulness over 6h was significantly increased at days 7, 14 and 21 post-stress, and rapid eye movement (REM) sleep was significantly decreased at day 14 post-shock. Moreover, in the behavioral experiment, conditioned avoidance to a shock-paired object, which appeared as soon as 24h after shock application, turned into generalized avoidance towards an unknown object 21 days after stress. These findings demonstrate that an acute inescapable stress exposure may cause long-lasting alterations in sleep patterns and behavior. Such modifications may be reminiscent of the profound changes observed in patients suffering from post-traumatic stress disorder.

[Impact of CRP rapid test in management of febrile children in paediatric emergency units of Ile-de-France]. / Impact de la protéine C-réactive (CRP) en microméthode sur la prise en charge des enfants fébriles aux urgences pédiatriques en Ile-de-France.

OBJECTIVE: Fever is a common cause of children visits to emergency units. Clinical evaluation does not always eliminate a bacterial infection. Among blood markers, several publications showed the interest of CRP. This study was undertaken to evaluate correlation between two techniques of CRP, one by usual technique at the laboratory and the other by a rapid test, and to evaluate the impact of this rapid test for febrile children at the emergency room, when a hospitalization was not immediately decided. MATERIAL AND METHODS: The study was undertaken in 2004-2005 in eight emergency paediatric units in Ile-de-France concerning febrile children during two periods. In period A, children had at the same time a CRP dosage through two methods, whereas in period B, only a rapid CRP test was first managed. The test used was NycoCard CRP Single test (Progen Biotechnique). RESULTS: Between September 2004 and June 2005, 572 children were included, 268 in period A and 304 in period B. Comparison of CRP results by the two methods showed for 247 children (93%) a fairly good linear correlation (r: 0.929). Blood cell count was the most often prescribed test (99.4 vs 10.5%). Conversely to chest radiography, blood culture, fibrinogen and urinary test were significantly most frequent in period A. The average cost of the additional examinations was 2.6 times more important during the first period. Duration of children management in the units was approximately two times shorter when rapid CRP test was used (199.7+/-92.8 vs 103.5+/-98.6 min). CONCLUSION: This study shows the interest of rapid CRP test for febrile children in the emergency units, and has to be confirmed in ambulatory paediatric practice.

SL651498: an anxioselective compound with functional selectivity for alpha2- and alpha3-containing gamma-aminobutyric acid(A) (GABA(A)) receptors.

SL651498 [6-fluoro-9-methyl-2-phenyl-4-(pyrrolidin-1-yl-carbonyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-1-one] is a novel pyridoindole derivative that displays high affinity for rat native GABA(A) receptors containing alpha(1) (K(i) = 6.8 nM) and alpha2 (K(i) = 12.3 nM) subunits, and weaker affinity for alpha5-containing GABA(A) receptors (K(i) = 117 nM). Studies on recombinant rat GABA(A) receptors confirm these data (K(i), alpha1beta2gamma2 = 17, alpha2beta2gamma2 = 73, alpha5beta3gamma2 = 215 nM) and indicate intermediate affinity for the alpha3beta2gamma2 subtype (K(i) = 80 nM). SL651498 behaves as a full agonist at recombinant rat GABA(A) receptors containing alpha2 and alpha3 subunits and as a partial agonist at recombinant GABA(A) receptors expressing alpha1 and alpha5 subunits. SL651498 elicited anxiolytic-like activity similar to that of diazepam [minimal effective dose (MED): 1-10 mg/kg, i.p.] in three conflict models, in the elevated plus-maze, the light/dark test, and the defense test battery in rats and mice. Results from activity tests and electroencephalogram analysis indicated that SL651498 induced muscle weakness, ataxia, or sedation at doses much higher than those producing anxiolytic-like activity (MED > or = 30 mg/kg, i.p.). Repeated treatment for 10 days with SL651498 (30 mg/kg, i.p., b.i.d.) in mice was not associated with the development of tolerance to its anticonvulsant effects or physical dependence. Furthermore, SL651498 was much less active than diazepam in potentiating the depressant effects of ethanol in mice. The "anxioselective" profile of SL651498 points to a major role for GABA(A) alpha2 subtype in regulating anxiety and suggests that selectively targeting GABA(A) receptor subtypes can lead to drugs with increased clinical specificity.

Mizolastine, a novel selective histamine H1 receptor antagonist: lack of sedative potential on the EEG in the rodent.

The sedative potential of mizolastine, a new, potent and selective antagonist of histamine H1-receptors, has been evaluated in the rodent with EEG techniques. In chronically implanted rabbits, sedation was observed in ECoG recordings after intravenous injection of terfenadine (1-10 mg/kg) and loratadine (0.3-3 mg/kg) but not after intravenous injection of astemizole or mizolastine (1-10 mg/kg). In freely moving implanted rats, mizolastine and cetirizine (10 mg/kg i.p.) did not modify the sleep-wakefulness pattern recorded during the dark period nor did mizolastine alter the sleep architecture recorded in rats during the light period. In contrast, during the dark-period recording, astemizole, loratadine and terfenadine (10 mg/kg i.p.) increased the total duration of slow-wave sleep; this sleep-facilitating effect had a late onset of action, beginning 3 h after drug injection. In conclusion, the results obtained with astemizole, cetirizine, loratadine and terfenadine demonstrate their low sedation potential in the rat, and suggest that the absence or low incidence of sedation seen in humans with these drugs may be due to their limited ability to cross the blood brain-barrier, especially at recommended therapeutic doses. Mizolastine appears to be devoid of sedative effects in our experimental models irrespective of the route of administration used. These results predict a lack of sedative action in humans with mizolastine at therapeutic doses.

Hypnotics: clinical value of pharmaco-EEG methods.

The central effects of sedative-hypnotic drugs were defined through the use of electroencephalographic (EEG) techniques in two species (rat and cat). In immobilized rats, spectral and visual electrocorticogram analysis provides a means of studying and comparing different profiles of sedative-hypnotic drugs. As with spectral analysis, Hjorth's descriptors allow one to detect the sedative effects of drugs and to study drug interactions in acute preparations. We have evaluated the action of hypnotics on the sleep-wakefulness cycle in freely implanted rats during their maximally active period because it is easier to estimate the duration of the sedative effect. We have also examined the action of sedative-hypnotic agents in rats and cats because of the different species reactivity to drugs such as benzodiazepines. These EEG methods are of value in the development of new hypnotic agents.

Drug effects on the EEG of various species of laboratory animals.

The analysis of the results obtained in different tests--sleep studies, cortical and hippocampal EEG activity, PGO-R spikes--in rats or in cats allows the characterization of different classes of drugs and to establish the relative efficacy of psychoactive drugs in these models. Moreover, the sequential spectral analysis of cortical EEG recordings in curarized rats allows the assessment of EEG modifications, of the presence of hypersynchronized rhythms, of the induction and duration of drug action, of topographic drug effects and interactions between different agents. Thus, the use of EEG techniques in various animal species allows a better classification and definition of the central action of drugs.