Plasma levels and membrane transports in red blood cell of tyrosine and tryptophane in depression. Evaluation at baseline and recovery

The erythrocyte membrane transports (MT) of L-tyrosine and L-tryptophan, as well as their plasma levels, were measured in 143 depressed patients after a wash-out period of one week and before any antidepressant treatment, and then at regular intervals until they recovered. 49 normal subjects served as a control group. The perturbations of these biologic variables at baseline were different according to diagnostic groups (DSM III), compared to controls: significant decrease of the two MT in depressed bipolar disorders; significant decrease of MT in depressed bipolar disorders; significant decrease of MT tyrosine and significant increase of MT tryptophan in recurrent major depressions; no significant changes of MT in dysthymic disorders. The plasma levels of tyrosine and total tryptophan show a significant diminution in the 3 groups. The study of the evolution of these same variables after antidepressant treatment show a return to normal of the MT at recovery, as well as the plasma levels of tyrosine. The plasma levels of tryptophan stay low in depressed bipolar disorders and recurrent major depressions.     

Glutathione ester protects against hydroxynonenal-induced loss of auditory hair cells.

OBJECTIVE: Test the ability of glutathione monoethyl ester (GSH(e)) to protect auditory hair cells against the ototoxic effects of 4-hydroxy-2,3-nonenal (HNE). STUDY DESIGN AND SETTING: Organ of Corti explants were either untreated or treated with one of a series of four concentrations of GSH(e) for one day, then exposed to HNE. Counts of FITC-phalloidin-labeled hair cells determined both HNE ototoxicity and GSH(e) otoprotection. RESULTS: HNE was toxic to hair cells at physiologically relevant levels, eg, 400 muM, and GSH(e) provided a significant level of protection against HNE ototoxicity (P < 0.05) at all levels tested, ie, 1.16 to 9.3 mM. CONCLUSION: GSH(e) protects auditory hair cells from damage and loss initiated by a naturally occurring ototoxic molecule, ie, HNE (a by-product of oxidative stress). SIGNIFICANCE: Treatment with GSH(e) may be an effective therapy to protect the cochlea against the adverse effects of traumas (eg, electrode insertion) that generate oxidative stress.     

Low molecular weight heparin compared with unfractionated heparin in prevention of postoperative thrombosis

Three consecutive randomized open studies have been carried out to determine the optimal dosage of low molecular weight heparin (LMWH) in the prevention of postoperative thrombosis in general surgery (892 patients). All patients undergoing abdominal, gynaecological, thoracic or urological surgery were over 40 years old and presented at least one of the following risk factors for thrombosis: previous thromboembolism, obesity, varicose veins, malignancy (30 per cent), pre-operative hospitalization over 5 days, oestrogen therapy, chronic cardiac disease or bronchitis. Isotopic venous thrombosis and bleeding complications were assessed after subcutaneous administration of a LMWH fragment (LMWH, Enoxaparine) or unfractionated heparin (UH). The three studies compared 3 X 5000 units UH daily with 1 X 60 mg, 1 X 40 mg, 1 X 20 mg LMWH daily. Thromboembolic events rates were not significantly different from group to group (UH: 3.8 per cent, 2.7 per cent, 7.6 per cent respectively compared with LMWH: 2.9 per cent, 2.8 per cent, 3.8 per cent). Bleeding episodes including wound haematoma formation, perioperative blood losses and systemic haemorrhage were not significantly different in patients receiving LMWH or UH. Significant decreases in haematocrit and haemoglobin were only observed in patients receiving 60 mg Enoxaparine (as compared to UH). An analysis using the 'intention to treat' approach gave results consistent with those of an analysis of good compliers. An overview of isotopic thromboses in the three studies gave no evidence of differences amongst the effects of the three doses of LMWH (P = 0.20), and pooling the results of the three studies using the Mantel-Haenszel procedure gave no evidence of a global difference between Enoxaparine and UH (P = 0.54). These results suggest that an optimal dosage of 20 mg/day of Enoxaparine is safe and effective in the prevention of postoperative thrombosis in this population.     

Clonality of cold agglutinins in patients with hemolytic anemia: an analysis by high-resolution two-dimensional gel electrophoresis.

High-resolution two-dimensional gel electrophoresis (2-DGE) was used to analyse plasma samples and partially purified cold agglutinins (CA) obtained from two selected patients. Both presented an acute hemolytic anemia with CA of high thermal amplitude, normal immunoglobulin levels, no detectable paraproteinemia, and no clinical evidence of a malignant B-cell disorder. The electrophoretograms of their plasma showed evident alternations of the "normal" protein profile, which were directly related to hemolysis (absence of the spots of haptoglobin and in one case of those of hemopexin), but no monoclonal gammopathy. The electrophoretograms of their purified CA revealed two clearly different spot patterns respectively corresponding to a monoclonal IgM and to polyclonal IgM. These results show that the clonality of CA associated with hemolytic anemia can be easily determined by 2-DGE. This technique may be very useful to discriminate chronic cold agglutinin disease in the early phase from "parainfectious" CA.     

Validity and reliability of the infant Behavioral Summarized Evaluation (IBSE): A rating scale for the assessment of young children with autism and developmental disorders

The Infant Behavioral Summarized Evaluation (IBSE) is a rating scale adapted from the Behavioral Summarized Evaluation (BSE) and specifically related to the assessment of behaviors of young children having autistic disorders. Content validity and reliability studies described in the paper were made from behavior ratings of videotapes for 89 children aged from 6 to 48 months. Results show a significant group of 19 items including some characteristic early autistic behaviors (communicative and social abnormalities) and some that are less commonly described in the syndrome (attentional, perceptive, and adaptive disorders). The value of the use of this scale for clinicians and professionals involved in behavioral evaluations and treatment of young children with developmental disorders and the necessity for further psychometric investigations are discussed.This study was supported by INSERM U.316 Nervous System from the Foetus to the Child. Development, Circulation, Metabolism, L. Pourcelot, INSERM, Network INSERM No. 489001, Grant INSERM No. 911182 (D. Savrage) No. 911008 (L. Hameury) MRT. No. 9906 Fondation Langlois. Gratitude is expressed to Professor G. Lelord who initiated and supervised this study. The authors thank Professor J. Fermanian, Department of Biostatistics, CHU Necker, Paris, for his helpful suggestions and assistance. They also thank Dr. Larmande, Dr. Leddet, Dr. Glorion, and Dr. Garreau for their medical participation in the study and C. Richard, C. Fillatre, J. Rabant, and F. Etourneau for the psychological assessments of children. Special thanks to G. Calzas, M. Barré, A. Lardeux, and D. Lioret for their technical assistance.     

Cortical auditory processing and communication in children with autism: electrophysiological/behavioral relations.

The purpose of the present study was to investigate the relations between late auditory evoked potentials (AEPs) recorded at temporal sites (the N1c wave or Tb) and verbal and non-verbal abilities in children with autism. The study was performed in 26 mentally retarded children with autism (AUT) aged 4-8 years (mean age +/- S.E.M. = 71 +/- 2 months; mean verbal and non-verbal developmental quotient +/- S.E.M. = 36 +/- 4 and 48 +/- 3). The stimuli used were 750 Hz tone bursts of 200 ms duration delivered binaurally at different intensity levels (50, 60, 70, 80 dB SPL) with 3-5 s interstimulus intervals. Temporal AEPs were first compared to those of a group of 16 normal children (NOR) in the same age range (mean age +/- S.E.M. = 69 +/- 3 months). We then focused on the AUT group and considered relations between temporal AEPs and the severity of disorders of verbal and non-verbal communication assessed using a behavior rating scale. AEPs recorded on left and right temporal sites were of smaller amplitude in the AUT group than in the NOR group. Increasing intensity-related amplitude was observed on both sides in NOR and only on the right side in AUT. The lack of intensity effect on the left side resulted in a particular pattern of asymmetry at the highest level of intensity (80 dB SPL) with greater N1c amplitude on the right than on the left side (the reverse was found in the NOR group). Electro-clinical correlations indicated that the greater the amplitude of the right temporal N1c responses, the higher the verbal and non-verbal communication abilities. This suggests a developmental reorganization of left-right hemisphere functions in autism, with preferential activation of the right hemisphere for functions usually allocated to the left hemisphere, particularly those involving the secondary auditory areas situated on the lateral surface of the superior temporal gyrus where the N1c/Tb wave is generated.     

Regulation of cognitive activity and early communication development in young autistic, mentally retarded, and young normal children

Based on the Piagetian framework, this study examined regulation of cognitive activity and developmental communication profiles and their interrelationship in groups of autistic, mentally retarded, and normal children of comparable overall, verbal, and oculo-manual developmental ages (from 6 to 24 months). Regulation of activity was assessed with both an object permanence test and an original behavior grid, and development of communication skills with the Guidetti-Tourrette scales (French adaptation of the Seibert-Hogan scales). The results showed evidence of certain types of dysregulation of cognitive activity and a general delay in communication ability in autistic children compared to the other two groups. Moreover, although the intensity of some of these disorders decreased in relation to the developmental levels of social interaction and joint attention in normal children, they were related to both high and low levels of development of social interaction only in autistic children. These findings raise the hypothesis of a relationship between a disorder of disengaging from an activity and developmental levels of social interaction noted at two transitory periods of early development (12 and 24 months) only in children with autism. Developmental and neuropsychological interpretations of this particular pattern are proposed.