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Objective: This study improves the knowledge of early autistic symptomatology and research concerning (i) the significant differences in the behaviors of children with autistic disorder (AD) and children with a developmental delay (DD), and (ii) the influence of the cognitive delay on symptomatology., Method: Two groups of 20 young children (7-42 months) were compared: children with AD, and those with DD. The groups were paired by chronological and developmental age. The comparison was extended to four subgroups composed according to age (younger and older children--<24 months, >24 months) and to the global development quotient (GDQ) (the more and less delayed). Each child was evaluated with the Infant Behavior Summarized Evaluation scale (IBSE)., Results: For the younger AD children, significant differences affected social communication and their adaptation to the environment (intolerance to frustration, resistance to change). For the older children (>24 months), this study showed the rapid progression of the number of distinctive signs between AD and DD children according to age and/or developmental level., Conclusions: Cognitive delay has an important influence on the symptomatology at the moment of initial recognition of an autistic syndrome. This study is a complement for the fuller understanding of the nature and early diagnosis of disorders specific to autism at the earliest phases of development.

The chemical synthesis of pure triacylglycerol (TAG) regioisomers, that contain long chain polyunsaturated fatty acids, such as arachidonic acid (AA) or docosahexaenoic acid (DHA), and saturated fatty acids, such as lauric acid (La) or palmitic acid (P), at defined positions, is described. A single step methodology using (benzotriazol-1-yloxy)-tripyrrolidinophosphonium hexafluorophosphate (PyBOP), an activator of carboxyl group commonly used in peptide synthesis and occasionally used in carboxylic acid esterification, has been developed for structured TAG synthesis. Identification of the fatty acyl chains for each TAG species was confirmed by atmospheric pressure chemical ionisation mass spectrometry (APCI-MS) and fatty acid positional distribution was determined by (1)H and (13)C NMR spectra. The generic described procedures can be applied to a large variety of substrates and was used for the production of specific triacylglycerols of defined molecular structures, with high regioisomeric purity. Combination of MS and NMR was shown to be an efficient tool for structural analysis of TAG. In particular, some NMR signals were demonstrated to be regioisomer specific, allowing rapid positional analysis of LC-PUFA containing TAG.

The ready construction of 24 stereochemically and functionally diverse carbohydrate ligand structures from a core D-glucosamine scaffold has allowed the evaluation of broad ranging structure activity relationships in ligand accelerated zincate additions to aldehydes, with variations in deltadeltaG+/+(R-S) of up to 5650 J mol(-1) that create opposing senses of asymmetric induction and that are consistent with models based on several ligand X-ray structures and molecular mechanics analysis. Factorial analysis of enantioselectivity using key dihedral angles and steric volume on N-2 also highlight the potential for the use of factorial design in ligand construction.

Convenient syntheses were developed to obtain on a multigram scale the novel taste enhancer N-(1-carboxyethyl)-6-(hydroxymethyl)pyridinium-3-ol 1, called alapyridaine, as a racemic mixture and as pure (+)-(S) and (-)-(R) enantiomers, respectively. 5-(Hydroxymethyl)-2-furaldehyde was used as key intermediate and was reacted with l-alanine under alkaline conditions to obtain racemic 1. Alternatively, reductive amination of 5-(hydroxymethyl)-2-furaldehyde with Raney-Ni/hydrogen and l- or d-alanine followed by mild oxidation led to (+)-(S)-1 and (-)-(R)-1, respectively. Racemization was promoted under alkaline and boiling conditions via a carbanion, the formation of which was facilitated by the electron-withdrawing effect of the iminium cation and the resonance-stabilizing capacity of the pyridinium moiety. Under these conditions, 1 was obtained in a 1:1 mixture of the phenol (1) and phenolate (1-H) forms as shown by X-ray diffraction. Racemic 1 formed monoclinic crystals of high molecular organization in which the phenol-type (RS)-1, the phenolate-type (RS)-1-H, sodium cations, and ethanol molecules are present. The crystal structure of [Na(1)(1-H).(C(2)H(6)O)] shows one-dimensional mu(2)-bridging-oxygen polymers stabilized by a three-dimensional network of ionic, hydrogen bond, and pi-stacking interactions with channels occupied by solvent molecules.

Galactosylceramide (GalCer) is a glycosphingolipid (GSL) receptor that allows HIV-1 infection of CD4-negative cells from neural and intestinal tissues. A water-soluble analogue of GalCer that features its polar head and the characteristic galactose-ceramide linkage but lacks the carbohydrate chains was prepared as a single enantiomer from (S)-serine. This analogue was not recognized in binding tests with the HIV-1 surface envelope glycoprotein gp120 in solution, which revealed the crucial importance of the ceramide alkyl chains. Two series of water-soluble GalCer analogues that contained either a hexanoic or a decanoic acyl unit and a saturated nine-carbon sphingosine moiety were designed by using molecular modeling results from natural GSLs and analogues with truncated alkyl chains. The longer chain compounds exhibit the characteristic fundamental conformation of GalCer. Seven analogues were prepared from Garner's aldehyde according to a straightforward and efficient asymmetric synthesis. All of these compounds proved to be water soluble but did not bind to gp120 in a solid-phase binding assay. These analogues were thus tested by using surface pressure measurements on a monomolecular film of GalCer, which served as a model of the plasma membrane. The incorporation of analogues very similar to GalCer into a GalCer monolayer prevented the insertion of gp120, whereas a structurally different derivative was not active. Based on these data, the molecular bases for recognition of GSLs by gp120 were elucidated. The essential importance of the GSL conformation in the primary interaction event and the crucial role of the alkyl chains of the ceramide moiety in the secondary interactions and the insertion process were clearly established.

School refusal anxiety is a pathopsychological disorder which touches the young child, between 8 and 13 years. Even if the school refusal is studied for a long time, there is not still consensus as for the specific definition of this disorder or on the best way of treating it. Nevertheless, accountable of long-lasting difficulties in school integration, its short and medium term consequences are serious and well known: school desertion, mood disorder and behavioral problems. Speed and quality of the medico-psychological and educational interventions represent a important factor for evolution and prognosis. Although, psychological interventions remain essential, sometimes the interest of an associated psychotropic medication should be discussed. This one can indeed either improve their results or supporting their installations. Despite more than twenty controlled trials in the pediatric population, no definitive psychopharmacological treatment data exist for anxiety disorder in childhood and especially for school refusal disorder. The majority of the studies stress as well the interest of benzodiazepines as tricyclic antidepressants but without being able to specify the possible superiority of a chemical on the other. On the other hand, the side effects of each one are well-documented, in particular for the benzodiazepines (potential abuse, sedation, potential desinhibition, mnemonic disorder), limiting thus their uses in child. In this work, we would like to emphasize the interest of propranolol in the treatment of somatic symptoms usually met in school refusal anxiety. Although beta-blockers have been used in the treatment of neurovegetative symptoms associated with situational anxiety disorders, there is no controlled data and only some open data to guide pediatric use for anxiety disorders in children. Nevertheless, prescribed with low posology and in substitution of benzodiazepine, this medication enabled us in three severe clinical cases to shorter notably the time of school rehabilitation. Well tolerated on the clinical level, with a greater efficiency on the somatic signs related to anxiety than benzodiazepines and with not having their side effects, this therapeutic can constitute a significant support in the psychological treatment of these children. However, these present results require to be confirm by other observations, which will be lead perhaps to a controlled study.

Hyperkinetic syndrome may be either secondary to an organic disease or a psycho-effective disorder (mood and/or anxiety disorder), or primary as part of an attention deficit hyperactivity disorder. Precise diagnosis is essential before any therapeutic decision; this requires a complete anamnestic, behavioural, psychological, sensorial, and neurological evaluation. It is only when a reliable diagnosis has been made that a relevant therapeutic project can be proposed. An evaluation procedure and a decisional tree are presented.

School refusal mainly affects 11-13-year-old children but may be observed at any age from 5 to 15 years. It has two main clinical varieties: 1) school phobia in which the refusal attitude is directed toward school itself or an aspect of school environment; 2) separation anxiety in which the refusal of going to school is related to the separation with attached relatives, frequently the mother. Early recognition and intervention are determining factors for the prognosis. Hospital management and/or medication (imipramine) may be necessary in severe forms.

Although the concept of child depression is today well admitted, the diagnosis of childhood depression remains difficult due to the variety of its symptoms, many of them being non specific, and the frequency of masked depression. For each period of child development, ie: infancy, early childhood, late childhood and adolescence, depression has particular clinical characteristics which are important to be known for its early recognition. Depression in a child frequently appears to result from the conjunction of a constitutional predisposing ground, one or several losses, and an inappropriate parental response. One must be concerned about the major risk of deleterious effects on psychoaffective, intellectual and somatic development of neglected depression, so that its prevention, early recognition, and treatment are mandatory. According to the cases, treatment requires individual or familial psychotherapy and chemiotherapy, and in particular cases care in a medico-educative establishment.

Although there has been concern about the use of psychoactive drugs in children, evidence is accumulating that these drugs are beneficial. The various groups of currently available drugs are reviewed with their pharmacological characteristics, adverse effects, dosages, and uses in children. Benzodiazepines, both widely used and severely criticized, are effective when used correctly, in particular for the shortest possible length of time. Antidepressants are indicated in many conditions including depression, obsessive-compulsive disorders, and anxiety; some of their indications are specific to children, such as separation anxiety, enuresis, and school phobia. Neuroleptics have a less well defined role and are usually given as symptomatic treatment, although their use is limited by their side effects. This is also true of lithium, despite fairly good tolerability in children. Carbamazepine was introduced in psychiatry too recently to allow valid evaluation. Psychostimulants are viewed with fear in France despite their documented efficacy in hyperkinetic children. A few other drugs used in other fields of medicine are currently being investigated in psychiatry (beta-blockers, clonidine, naloxone). A debate on drugs used in child psychiatry is much needed in particular to overcome the methodological and ethical problems raised by controlled trials of which few have been conducted to date. Drug therapy should be combined with psychotherapy to place the target symptoms in perspective with regard to the child's overall make-up.

Dysfunctions of the serotonergic system are implicated in psychiatric disorders, and there is evidence that a familial element may be significant in childhood autism. The concentrations of platelet 5-HT and free and total plasma tryptophan were determined in healthy pregnant women at each month of pregnancy and, at delivery, in both maternal and umbilical cord blood. A significant rise in the level of platelet 5-HT occured during month 3 and 4 followed by a retum to normal from month 5 until the delivery. The level of total plasma tryptophan remained equal to that in normal healthy non pregnant women until the 6th month. By month 7, it had decreased significantly and remained low until the month 9. At delivery the level fell significantly by -41%. The concentration of free tryptophan varied widely from one month to another but there was a trend towards a progressive increase from month 1 to 9, and at delivery the level returned to basal values. The concentration of 5-HT in the umbilical cord blood was about half that of the maternal blood. Inversely the concentrations of both free and total plasma tryptophan in the umbilical cord blood were nearly twice that of the maternal blood.

High platelet serotonin concentrations have been reported in children with early infantile autism. However, as yet there are no reference values regarding platelet serotonin in normal infants and young children so that it remains difficult to define the exact significance of this finding. We report here with the platelet serotonin concentration found in 57 infants and children (20 girls, 37 boys) ranging in age from 10 days to 5 years old. Our results show that mean platelet serotonin concentrations in infants and young children are significantly greater than mean values obtained in older children (+11%) and neonates in the umbilical cord (+64%). No significant variations were found relating to sex, leucocyte count and platelet count. There therefore appears to be a physiological elevation of platelet serotonin concentration in infants and young children, and this has to be taken into consideration in the interpretation of the elevated values found in cases of infantile autism.

From a biological study of 8 patients with anorexia nervosa and an analysis of the daily profiles of gonadotropins, cortisol and melatonin, the authors discuss the possible relationship between anorexia nervosa and affective disorders. At the initial phase of the illness, plasmatic levels of FSH, LH and oestradiol were very low. 24-hour plasma cortisol values were comparable with those of a depressive population; when weight loss was equal to or higher than 25% of the initial weight, there was no suppression by dexamethasone. The daily profile of melatonin was maintained, with melatonin plasma levels significatively higher than in a control group of depressed patients.

The effects of fenfluramine were studied in a group of 44 children with the autistic syndrome and in 26 non autistic children with behavior abnormalities, mostly hyperkinetic children, as a control group. The mean daily dosage was 0.65 mg/kg/day. There were 75% positive results in the autistic children and 77% in the control group. The clinical improvement appears to be mainly related to the control of the hyperactive behavior in the autistic children. Platelet serotonin levels were studied in both groups, showing a clear cut decrease during fenfluramine therapy with no significant differences between the 2 groups and no correlation between the clinical effects and the magnitude of the decrease.

Among disorders of sleep in children, pavor nocturnus ("night terrors") is common and considered harmless. Yet the clinical picture, the child's personality and the polygraphic electroencephalographic recordings suggest that it should be treated sooner and more often than is usually done. Somnambulism ("sleep walking") also is very frequent. It has no consequences in most cases, but it may be the cause of serious events such as falling out of a window which is rare but may result in death or disablement. Some children have repeated attack of somnambulism, and these constitute a true pathology of sleep requiring a specific treatment that will cure or improve. All this must be known to the practitioner who will inform the parents.

According with experiments, it appears that hormonal environment plays a major role on anatomical, neuroendocrinological and behavioral sexual differentiation in animals. This environment occurs at a critical period, which is specific for each specie, either during fetal life or soon after birth. Sexually dimorphic behavior appears to be influenced by androgens who act either directly or after chemical modification on specific central receptors. In the absence of androgens during the critical specific period, these central structures and consequent behavior differentiate in a feminine pattern. In the presence of androgens during this period, structures and behavior differentiate in a masculine pattern. But this influence of androgens require a double component, defeminization and masculinization, variable among species, as it is observed in rats and mice when defeminization can not be obtained in primates. In human beings, "nature experiments" such as congenital adrenal hyperplasia in feminine foetuses and abnormalities in testosterone metabolism in masculine foetuses are more difficult to study. Fetal hyperandrogenization is responsible of an anatomical and perhaps behavioral masculinization. Neuroendocrine and behavioral defeminization seems not to occur as ovulatory menstrual cycles are possible with a regular treatment, and as sexual identity is feminine when sex of rearing is feminine even if some aspects of sexual roles are unusual. Moreover, these peculiar behavioral traits and changes in sexual orientation in a masculine way at puberty are difficult to explain : fetal hyperandrogenization seems to play a role, as it is observed in animals and as seem to demonstrate Dr J. Imperato-Mc Ginley's observations, but other factors seem to predominate, such as parental attitude in regard with sexual ambiguity and psychological consequences of the acknowledgment of ambiguous genitalia.