Brief report: a double-blind study of naltrexone in infantile autism.
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Adolescent↗
Biomedical subjects
M Dugas
Publications and source records attributed to M Dugas.
An event-related potential study of controlled and automatic processes in 6-8-year-old boys with attention deficit hyperactivity disorder.
Event-related potentials (ERPs) were recorded from 2 groups (attention deficit hyperactivity disorder (ADHD) and normal control) of 12 boys aged from 6 to 8 years. Subjects were submitted to 2 different types of categorization tasks (with rare targets and frequent standards) implying either the use of a verbal class or that of an ordered series. Each type of task was performed twice, the first with reading and the second without. Amplitudes and latencies of a fronto-central N150-P250 complex, a parieto-occipital N250-P350 complex and a parieto-occipital P500 were measured. Regardless of the task, hyperactive children showed larger fronto-central P250, larger parieto-occipital N250 and smaller parieto-occipital P350s and P500s; moreover, the latencies of their parieto-occipital P350s were shortened. When the categorization depended on the use of a verbal class, ERP reading effects were significantly smaller in hyperactives than in normal controls for the parieto-occipital waves only. Alternatively, the target effects were significantly larger in hyperactive children but for the fronto-central P250 only. These results suggest that in ADHD automatic processes were enhanced when higher-order controlled processes were inadequate.
Aging↗
Relation between veratridine reaction dynamics and macroscopic Na current in single cardiac cells.
Veratridine modification of Na current was examined in single dissociated ventricular myocytes from late-fetal rats. Extracellularly applied veratridine reduced peak Na current and induced a noninactivating current during the depolarizing pulse and an inward tail current that decayed exponentially (tau = 226 ms) after repolarization. The effect was quantitated as tail current amplitude, Itail (measured 10 ms after repolarization), relative to the maximum amplitude induced by a combination of 100 microM veratridine and 1 microM BDF 9145 (which removes inactivation) in the same cell. Saturation curves for Itail were predicted on the assumption of reversible veratridine binding to open Na channels during the pulse with reaction rate constants determined previously in the same type of cell at single Na channels comodified with BDF 9145. Experimental relationships between veratridine concentration and Itail confirmed those predicted by showing (a) half-maximum effect near 60 microM veratridine and no saturation up to 300 microM in cells with normally inactivating Na channels, and (b) half-maximum effect near 3.5 microM and saturation at 30 microM in cells treated with BDF 9145. Due to its known suppressive effect on single channel conductance, veratridine induced a progressive, but partial reduction of noninactivating Na current during the 50-ms depolarizations in the presence of BDF 9145, the kinetics of which were consistent with veratridine association kinetics in showing a decrease in time constant from 57 to 22 and 11 ms, when veratridine concentration was raised from 3 to 10 and 30 microM, respectively. As predicted for a dissociation process, the tail current time constant was insensitive to veratridine concentration in the range from 1 to 300 microM. In conclusion, we have shown that macroscopic Na current of a veratridine-treated cardiomyocyte can be quantitatively predicted on the assumption of a direct relationship between veratridine binding dynamics and Na current and as such can be successfully used to analyze molecular properties of the veratridine receptor site at the cardiac Na channel.
Animals↗
Mutually exclusive action of cationic veratridine and cevadine at an intracellular site of the cardiac sodium channel.
Veratridine modification of Na current was examined in single dissociated ventricular myocytes from late-fetal rats by applying pulses to -30 mV for 50 ms every 2 or 5 s from a holding potential of -100 mV (20 degrees C) and measuring amplitude, Itail, and time constant, tau tail, of the post-repolarization inward tail current induced by the alkaloid. Increasing the pH of a 30 microM veratridine superfusate from 7.3 to 8.3 (which increases the fraction of uncharged veratridine molecules from 0.5 to 5% while decreasing that of protonated molecules from 99.5 to 95%) increased Itail by a factor of 2.5 +/- 0.5 (mean +/- SEM; n = 3). Switching from 100 microM veratridine superfusate at pH 7.3 to 10 microM at pH 8.3 did not affect the size of Itail (n = 4). Intracellular (pipette) application of 100 microM veratridine at pH 7.3 or 8.3 produced small Itail's suggesting transmembrane loss of alkaloid. If this was compensated for by simultaneous extracellular application of 100 microM veratridine at a pH identical to intracellular pH, Itail (measured relative to the maximum amplitude induced by a combination of 100 microM veratridine and 1 microM BDF 9145 in the same cell) at pHi 7.3 did not significantly differ from that at pHi 8.3 (84 +/- 4 vs. 70 +/- 6%; n = 3 each). Results from six control cells and five cells subjected to extra- and/or intracellularly increased viscosity by the addition of 0.5 or 1 molal sucrose showed that increasing intracellular viscosity 1.6- and 2.5-fold increased tau tail 1.5- and 2.3-fold, respectively, while a selective 2.5-fold increase of extracellular viscosity did not significantly affect tau tail.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Chiari malformation type I in a child with velopharyngeal insufficiency.
A five-year-old girl was referred for chronic and stable velopharyngeal insufficiency. Pharyngoplasty was performed, without significant improvement, and further neurological investigation was undertaken. Clinical examination and electromyography led to a suspicion of denervation of the IX, X and XI cranial nerves. Magnetic resonance imaging revealed a type 1 Chiari malformation.
Arnold-Chiari Malformation↗
[Specific disorders of mental development].
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Child↗
[Evoked potentials and the mode of cognitive development in boys 6 to 8 years of age presenting hyperactivity with attention deficit].
Event-related potentials were recorded in 2 groups (attention deficit hyperactivity disorder--ADHD--and normal controls) of 12 male children aged between 6-8 years during 4 categorization tasks. Each task was performed with a different type of visual stimulus; pictures, words, geometrical figures or digits. The amplitudes and latencies of a fronto-central P250 and a parieto-occipital P350 were examined. The overall amplitude of the fronto-central P250 was larger in the ADHD group. However, the overall latency of the parieto-occipital P350 decreased with age; coincidentally, in the control group, the P350 latency measured in the left hemisphere became shorter with age for the words than for the pictures. This was not the case in the ADHD group. These results are discussed in relation to the level of the orienting reaction and the modes (general or differentiated) of cognitive development.
Attention Deficit Disorder with Hyperactivity↗
Subclinical alveolitis in immunological systemic disorders. Transition between health and disease?
A subclinical inflammatory alveolitis as assessed by BAL cell analysis may be present in a high proportion of symptomless patients with immunological systemic disorders and with normal chest roentgenogram. Subclinical alveolitis can be characterized by the relative proportions of the different cell populations comprising the alveolitis and by the activated state of the cells. Thus, subclinical alveolitis can be classified into two major groups: lymphocyte and neutrophil alveolitis. Lymphocyte alveolitis is frequently found in patients with extrathoracic granulomatosis (Crohn's disease, primary biliary cirrhosis, extrathoracic sarcoidosis) or with some collagen vascular diseases (Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus). Neutrophil alveolitis is a main finding in collagen vascular diseases, especially progressive systemic sclerosis, dermatopolymyositis and mixed connective tissue disease. In addition, alveolar macrophages may be spontaneously activated and release various mediators that could be relevant to the pathogenesis of interstitial lung disease. On the other hand, some other alveolar macrophage functions (antibacterial activity may be severely impaired in some diseases, for example systemic lupus erythematosus). Alveolar inflammation is associated with an increase in the permeability of the alveolar membrane responsible for an increased influx of blood proteins in the alveolar spaces. Although subclinical inflammation may also be detected by high resolution computed tomography (HRCT) scan and/or lung permeability scintigraphic studies, the significance and prognostic value remains unclear and clearly differs according to both the disease and the pattern of alveolitis.
Humans↗
Interaction between DPI 201-106 enantiomers at the cardiac sodium channel.
The modification of cardiac sodium channels by DPI 201-106, its S-enantiomeric form (S)-DPI, and its R-enantiomeric form (R)-DPI was investigated with whole-cell voltage-clamp recording in single cultured ventricular myocytes obtained from late-fetal rats. From a holding potential of -100 mV, depolarizing pulses to -30 mV of 50-msec duration were applied at 0.2 Hz. Extracellular [Na] was reduced to 70 mM; temperature was 20 degrees. Drugs were administered directly on the cell by a double-barrelled microsuperfusion system. Sodium current inactivation was progressively slowed when the concentration of DPI 201-106 was increased from 0.3 to 3 microM. At 10 microM DPI 201-106, this effect was followed by a blocking effect on peak inward sodium current (INa), and at 30 microM inward sodium current was fully blocked within 2 min. The slowing of inactivation was produced by (S)-DPI (maximally effective at 3 microM), whereas (R)-DPI had little effect on inactivation at 3 microM. Conversely, (R)-DPI reduced INa at 10 microM, whereas (S)-DPI did not reduce INa at 3 microM. The effects of both (S)-DPI and (R)-DPI were partially reversed by washout. (R)-DPI retained its blocking activity on INa when the interval between depolarizing pulses was prolonged to 90 sec. In order to test whether the different sodium channel modifications produced by (S)-DPI and (R)-DPI were mutually exclusive, the INa-reducing activity of (R)-DPI was measured in the absence of (S)-DPI and after equilibration with a maximally effective (S)-DPI concentration. In the absence of (S)-DPI, 3 microM (R)-DPI reduced INa by 35% and in the presence of 3 microM (S)-DPI, by 51%. Thus, modification by (S)-DPI of sodium channels did not prevent their block by (R)-DPI. The INa-reducing activity of (R)-DPI was even significantly augmented by (S)-DPI after a 1-sec depolarization to -30 mV. During such prolonged pulses, (R)-DPI accelerated the monoexponential decay of the (S)-DPI-induced slow phase of sodium current inactivation. The results are consistent with an irreversible binding reaction between (R)-DPI and (S)-DPI-modified open sodium channels (association rate constant, 4.7 x 10(5) M-1sec-1). We conclude that (R)-DPI reduces INa by interacting both with resting sodium channels and with (S)-DPI-modified open sodium channels. The corresponding receptor site is stereoselective and distinct from and allosterically coupled to the (s)-DPI receptor that mediates slowing of inactivation.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Sodium channel comodification with full activator reveals veratridine reaction dynamics.
Veratridine association and dissociation rates were determined at single sodium channels in outside-out patches of cultured ventricular myocytes obtained from late-fetal rat hearts. In single cardiac sodium channels depolarized from -110 to -30 mV, intracellular veratridine induced a long lasting (tau = 0.48 sec) open state with small current amplitude (-0.3 pA, i.e., 1/4 of normal) and frequent closing transitions, giving it a burstlike appearance, in agreement with reports on other types of sodium channel. Veratridine-associated and veratridine-free states of a single sodium channel were monitored by comodifying it with an allosteric activator, BDF 9145 (1 microM), that induced a burst with normal open channel current amplitude (-1.2 pA at -30 mV) upon veratridine dissociation. Veratridine and BDF 9145 interacted with reciprocal synergism at the single sodium channel such that veratridine-induced bursts (called P-bursts for partially activated) alternated with BDF 9145-induced bursts (called F-bursts for fully activated) many times following a single depolarization to -30 mV. P-bursts and F-bursts within such trains of bursts had exponentially distributed durations. The reciprocal time constant for F-bursts, tau F-1, increased linearly with veratridine concentration (0.3-30 microM), whereas tau P was insensitive. We conclude, therefore, that P-bursts reflect veratridine occupancy and F-bursts reflect the veratridine-free state; if veratridine and BDF 9145 bind to a sodium channel simultaneously, veratridine exerts conformational dominance, i.e., retains its property to reduce channel conductance. For the single cardiac sodium channel activated (i.e., deprived of inactivation) by BDF 9145, we have determined a veratridine association rate constant k1 = 4.3 x 10(6) M0-1 sec-1, dissociation rate constant K-1 = 2.2 sec-1 and equilibrium dissociation constant KD = 5.1 x 10(-7) M (20 degrees, -30 mV membrane potential).
Allosteric Regulation↗
[Sexual identity disorders in children].
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Adolescent↗
[Latent alveolitis in systemic disease. The transition between the normal and the pathological].
Alveolitis, an accumulation of inflammatory and immune cells in the alveolar structures, is the essential anatomical lesion associated with the development of pulmonary fibrosis. Broncho-alveolar lavage enables the detection of an alveolitis in patients without any respiratory disorder but having known pathology which can frequently lead to interstitial pneumonia, (certain systemic diseases). The cellular analysis of the bronchoalveolar lavage enabled two types of latent alveolitis to be identified: a lymphocytic alveolitis is very frequent during the course of extra-thoracic sarcoidosis, Crohn's disease, primary biliary cirrhosis, Sjögren-Gougerot syndrome, acute systemic lupus erythematosus and rheumatoid disease. A polymorphonuclear neutrophil alveolitis with or without an associated lymphocytosis which confirmed the almost exclusive attribute of either scleroderma, dermatopolymyositis or Sharp's syndrome. The role of alveolar macrophages is shown to be essential by the secretion of free oxygen radicals, chemotactic factor for polymorphonuclear neutrophils and for fibroblasts proliferation factors (fibronectin, fibroblastic growth factor). The significant and prognostic value of latent alveolitis remains poorly understood. A prolonged follow up of patients shows that the existence of a polymorpho-nuclear alveolar neutrophilia or of secretions containing fibronectin and free oxygen radicals from the alveolar macrophages is associated with a progressive deterioration of respiratory function. In summary the evidence of latent alveolitis in asymptomatic patients leads to the hope that in the future early therapeutic intervention may be instituted before the development of irreversible anatomical lesions.
Disease↗
Tetrodotoxin block of single germitrine-activated sodium channels in cultured rat cardiac cells.
1. The open time of single Na+ channels in excised (outside-out) patches from cultured late-fetal rat ventricular myocytes was prolonged to several minutes by germitrine (0.5 mM) in order to analyse tetrodotoxin (TTX) blocking kinetics. 2. The germitrine modification appeared during depolarizing pulses that activated normal Na+ channels. Following repolarization to -100 mV, the modified Na+ channel remained activated for 136 +/- 186 s (mean +/- S.D., n = 54) with an open-channel current amplitude of -0.5 pA. The predominant open state with a mean open time of 0.13 s was interrupted by brief closing events lasting for milliseconds. Replacing extracellular Na+ by Cs+ decreased the current amplitude to -0.1 pA. 3. Extracellular superfusion with TTX (3 x 10(-7) M) of a single germitrine-activated Na+ channel induced full channel closures lasting seconds (blocked events) separated by channel reopenings (unblocked events) that were indistinguishable in terms of amplitude and gating kinetics from the germitrine-activated state in the absence of TTX. 4. Cumulative probability histograms of blocked and unblocked events (n greater than 140) collected during long-lasting germitrine modifications at 10(-7) and 3 x 10(-7) M-TTX are well described by single exponentials. The 3-fold increase in [TTX] decreased the time constant of the unblocked state, tau o, from 11.9 to 4.7 s, while the time constant of the blocked state, tau c, was not significantly altered from 8.6 to 9.7 s. A microscopic association rate constant of 7.7 x 10(5) M-1 s-1, dissociation rate constant of 0.11 s-1, and equilibrium dissociation constant of 1.4 x 10(-7) M (at -100 mV) were calculated (20 degrees C). 5. Increasing [TTX] to 10(-5) M decreased tau o to 86 ms. This argues against the existence of a slower conformational step interposed between the binding of TTX to an open channel and the resultant channel closure. 6. Setting the membrane potential to -50 or 0 mV subsequent to a germitrine modification at -100 mV did not significantly alter TTX (3 x 10(-7) M) blocking kinetics: tau o was 6.7 s at -50 mV and 5.2 s at 0 mV; tau c was 8.9 and 8.1 s, respectively. 7. These results suggest that blocked events correspond to the random times that a TTX molecule resides on the Na+ channel before it dissociates, and unblocked events correspond to the random waiting times of an unoccupied channel before it binds another toxin molecule.(ABSTRACT TRUNCATED AT 400 WORDS)
Action Potentials↗
From subclinical alveolitis to granulomatosis. Sequential evaluation of pulmonary involvement in extrathoracic sarcoidosis.
Follow-up of patients with subclinical inflammatory alveolitis associated with systemic diseases may represent the best opportunity to study the mechanisms responsible for the development of interstitial lung disease. We report a seven-year sequential pulmonary evaluation of one patient with clinically isolated gastric sarcoidosis, treated by gastrectomy, without evidence of clinical, radiologic or functional lung impairment and with chronic subclinical lymphocyte alveolitis. Five years later, she developed an overt interstitial lung disease characterized by fine crackles, diffuse parenchymal opacities and impaired diffusing capacity, preceded by an expansion of polymorphonuclear neutrophils in the lower respiratory tract, raising the hypothesis that these cells may be implicated in the pathogenesis of pulmonary derangement in sarcoidosis. This observation illustrates the importance of pulmonary follow-up of unaffected patients with systemic diseases and with subclinical inflammatory alveolitis, and the potential predictive value of neutrophil alveolitis in the pulmonary outcome of these patients.
Adult↗
[Use of speech therapy in pediatric practice].
Prescription of speech rehabilitation is now an act often performed by pediatricians. We attempt to define the implications of this act by successively describing the specific features of the training of speech specialists, the main childhood disorders for which their help is sought, and the key principals of rehabilitation. We underline the need for an improved clinical definition of learning disabilities in children in order to propose optimal therapeutic strategies.
Child↗
[Pulmonary sarcoidosis simulating primary acute interstitial fibrosis at presentation. Clinical, radiologic, functional and bronchoalveolar cytologic study in 3 cases].
Sarcoidosis very rarely progresses towards severe subacute respiratory failure. We report three observations of recent atypical cases of pulmonary sarcoidosis which were proven by open lung biopsy and developed severe diffuse pulmonary granulomatosis in a few weeks with an associated interstitial fibrosis. In these patients there were diffuse crepitant rales, a dramatic reduction in lung function of 30-60% of lung volumes and diffusion capacity accompanied by major hypoxemia (m +/- DS: 63.3 +/- 4.0 mmHg) without hypercapnia. Bronchoalveolar lavage showed an alveolar neutrophil leucocytosis (7.3 +/- 5.5%) without a lymphocytosis (4.3 +/- 11.5%). In the three cases under study, the clinical picture, the radiological and lung function studies, as well as the data from the bronchoalveolar lavage, were more suggestive of an acute diffuse interstitial fibrosis than of sarcoidosis.
Adult↗
Effects on naltrexone on infantile autism.
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Autistic Disorder↗
[Nosology and systems for data recording in child and adolescent psychiatry].
Thanks to a system of classification acceptable to a majority of child psychiatrists, recording mental problems has been a necessity since the 1960's. The two main classifications currently being used are that of the World Health Organization (CIM-9) and that of the American Association of Psychiatry (DSM-III), both of which categorize, with categories proper to children. There are also classifications dealing with dimensions which show child psychopathology better to psychologists. A system of French classification is being studied. The merits of a good classification are well set out. No existing system of classification has them completely. The CIM-9 and DSM-III are being fine-tuned. Whichever system used, date gathering on a particular patient must be rigorous. Studies carried out in Great Britain and the United States have led to the formulation of semi-structured interviews, an evaluation scale and questionnaires that now cover most child and adolescent psychiatry.
Adolescent↗