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Biomedical subjects

M Dugas

Publications and source records attributed to M Dugas.

At least 73 records · Page 4Linked to original sources
PubMed1990

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↗
PubMed1990

[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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

[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↗
PubMed1989

[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↗
PubMed1988

[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↗
PubMed1986

[Tics: from Itard to the neuroleptics].

When the six DSM-III (1980) diagnostic criteria are applied to the nine cases reported by Gilles de la Tourette in 1885, six of them are found to be in accordance with the diagnosis of Gilles de la Tourette's syndrome (cases nos 4, 5 and 7 do not involve vocal tics). Gilles de la Tourette deserves credit, not only for having regrouped fragmented observations into one remarkably well described clinical entity which held over time (such as Itard's observations nos 9 and 10 in 1825; the latter is the famous Marquise of D ... seen several times by Charcot and the only one which, along with no 1, appears in Gilles de la Tourette's paper), but also for having described the course of this chronic and fluctuating disease. Why Gilles de la Tourette did not use the term "tic", a term which had been in use for a long time in both veterinary and human medicine, to describe "the motor incoordination" of these patients? Did Charcot take some distance from his student's paper as early as 1885? He viewed tics as the basis of "the disease described by Gilles de la Tourette". In addition to coprolalia and echolalia, he alsa reported the existence of "mental tics". How have French neurologists and psychiatrists been able to perpetuate Brissaud's error who, contrary to Gilles de la Tourette, mentioned that the illness "can be associated with severe mental disorders which often lead to dementia"?(ABSTRACT TRUNCATED AT 250 WORDS)

France↗
PubMed1986

[Psychopharmacology of panic attacks].

A new type of anxiety state has recently been identified: the panic attack. This condition is qualitatively distinct from other anxiety disturbances and its treatment is different. Sodium lactate seems to play an essential role in the triggering of panic attacks through the intermediary of catabolic, physicochemical mechanisms or by alteration of adrenergic neurotransmission. Anxiety may be autonomised into two sub-groups, based on the effects of psychotropic drugs: phobic and anxiety states. The presence or absence of panic attacks is essential as it has diagnostic and therapeutic implications: M.A.D.I. or tricyclic antidepressors have a specific action on panic attacks but are ineffective on anticipatory, chronic, phobic or other forms of anxiety. Which are improved by benzodiazepines which; themselves, have very little effect on panic attacks.

Antidepressive Agents↗
PubMed1986

[Apropos of mother-child hospitalizations: mother-child hospitalization in a child psychology service].

Mother-child hospitalization is still rarely practiced in child psychiatric services. The experience of this kind of care in the child and adolescent psychopathology service in the Herold Hospital (Paris), however, demonstrates its interest. It permits one to respect the bond of attachment and proves to be a useful instrument of psychiatric evaluation of children, particularly in greater diagnostic precision to which the observation of the mother-child unit also contributes. The conjoint hospitalization, however, involves some risks, which can be anticipated in pre-hospitalization work up: repercussion on the family, difficulties in the functioning of the care taking team, and especially the impact on the mother of the hospitalization which creates a real crisis situation which must be handled in order to be able to use the maturative possibilities.

Adolescent↗
PubMed1985

[Panic attacks in adolescents].

Anxiety has been the object of many therapeutic attempts, often in the absence of well-founded indications and often yielding inconclusive results. We obtained good results in two adolescents for whom we used a new classification system based upon the differential action of psychotropic drugs on anxiety. More specifically, this approach singled out the panic disorder by demonstrating that patients with this disorder react specifically to antidepressant drugs. More extensive studies are clearly needed to confirm that these results, well established for adult patients, also apply to an adolescent population.

Acute Disease↗
PubMed1985

[Gilles de la Tourette's syndrome. Current status of tic disease].

Two French physicians, J.M.G. Itard (1774-1838), then G. Gilles de la Tourette (1857-1904), have individualized a syndrome which has now been universally recognized for almost a century. Modern clinical studies conducted in the United States on a large number of patients have confirmed and completed Gilles de la Tourette's excellent description based on 9 cases. Interpreted at first as psychological, these "caricatures of natural acts" (J.M. Charcot) have given rise to numerous experimental studies in search of a possible imbalance of neurotransmitters. The inconstant or contradictory results obtained so far do not provide a coherent explanation. With its bizarre and disconcerting symptoms, the Gilles de la Tourette's syndrome compromises the social life of the patients throughout childhood and adulthood. Physicians should be able to diagnose the syndrome in order to help these patients, whose mental capacities remain unimpaired.

Dopamine↗
PubMed1985

Treatment of childhood and adolescent depression with mianserin.

The efficacy of mianserin in treating adult depression is now well established. Since there are no publications concerning the use of mianserin in children, the authors set up an open pilot study of 110 depressed children and adolescents aged 8-19 years. The average dose of mianserin was 1 mg/kg/day. Efficacy of treatment was noticeable by the end of the first week and was maintained throughout the 60 day study period. Evaluation was based on both clinical observations and changes in scores obtained from 80 subjects. Side-effects were minimal leading to temporary withdrawal of treatment in only seven cases. The profile of mianserin in children and adolescents is similar to that of adults. It is an antidepressant with an anxiolytic component, and has a regulating effect on sleep. In view of its efficacy, compliance, and the very low incidence of side-effects, mianserin appears to be a useful treatment for depression in children and adolescents. The results of this open study justify the development of further controlled studies.

Adolescent↗
PubMed1985

[Haloperidol. Plasma monitoring and hormonal effects of treatment].

Therapeutic plasma monitoring of haloperidol, a major neuroleptic, measured by radioimmunoassay, has shown a rather good correlation between plasma level and dosage but with large interindividual variation in children as in adults; age seems not to have any effect on haloperidol metabolism. 80% of subjects present a concomitant prolactin levels variation, whereas in 20% no prolactin response is found. During acute kinetics of either a 10 mg oral haloperidol administration or a 250 mg intramuscular haloperidol decanoate injection, a parallel elevation of prolactin, cortisol, immunoreactive bêta-endorphin and bêta-lipotropin plasma levels occur, at the same time as haloperidol plasma levels. Those rise with a good equivalence between the two doses of the two forms.

Administration, Oral↗