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Biomedical subjects

M Dugas

Publications and source records attributed to M Dugas.

At least 91 records · Page 5Linked to original sources

[Psychotic symptoms during the evolution of dementia in muco- polysaccharidosis of Hurler-Scheie phenotype].

The case reported concerns a 17 1/2 year-old adolescent presenting with complete alpha-L-iduronidase deficiency. Its phenotype intermediate between Hurler's and Scheie's syndromes and the occurrence of a delirious and hallucinatory condition evolving with acute exacerbations on a constant subdelirious and excited state made this case particular. This case report is compared to the 30 in the Anglo-Saxon literature which shows, in addition to the rarity of psychiatric symptoms (one single case), the multiplicity of the possible phenotypes, reinforcing the hypothesis of a polyallelic or even non allelic mutation.

Adolescent↗

[The dexamethasone suppression test in child and adolescent psychiatry].

The dexamethasone suppression test was performed on 67 children and adolescents who were hospitalized in the child psychopathology unit of Herold Hospital (Paris). We used the DSM-III diagnostic criteria. After 10 preliminary trials using 2 mg/1.73 m2 of dexamethasone, 63 trials were conducted with a dosage of 1 mg/1.73 m2. In 19 cases of anorexia nervosa, non-suppression was associated with the weight reduction, with no other significance attached to the results. In 30 pubertal cases, 11 out of the 20 depressed patients escaped from dexamethasone suppression while none of the 10 non-depressed patients did. Those 5 adolescents who were categorized as depressed with psychotic features all escaped suppression. Criteria of specificity and more specifically the role of weight loss, are discussed. In 8 prepubertal patients (under Thirteen) the 4 depressed cases showed no escape response but this response was noted in 2 out of the 4 other children. These results suggest the presence of neuroendocrinological alterations in depressed pubertal children similar to those observed in some depressed adults. We could not find similar alterations in our small sample of non pubertal children.

Adolescent↗

Therapeutic drug monitoring of psychotropic drugs in children.

In several areas of medicine, therapeutic drug monitoring (TDM) has been proven to be a very useful tool for optimizing the therapeutic potential of various drugs and for minimizing the risk of adverse events. In pediatrics the value of TDM is generally accepted for drugs such as Theophylline and/or antiepileptics, but it is still strongly questioned for classes of drugs such as neuroleptic and tricyclic antidepressants. However, in the last 5 years evidence has been produced indicating that TDM may be a very useful tool in pediatric neuropsychiatry too. In fact, if on the one side therapeutic windows have been defined for major neuroleptics and tricyclic antidepressants, on the other side clear relationships between drug plasma concentrations and the incidence and severity of adverse reactions have been reported. Data derived from our own experience of 5 years of TDM in pediatric neuropsychiatry will be described together with data from the literature. It appears that at least for four major drugs, Haloperidol, Chlorpromazine, Imipramine, and Chlorimipramine, drug plasma levels monitoring during chronic treatment does help in a significant manner in optimizing the treatment.

Adolescent↗

[The Landau-Kleffner syndrome. Infantile "acquired" aphasia, paroxysmal electroencephalographic changes and epileptic seizures].

Since the initial description by Landau and Kleffner, in 1957, of a syndrome occurring exclusively in children and consisting of aphasia, paroxysmal changes in E.E.G. and, frequently, epileptic seizures, 80 cases have been reported. The acquired speech disorder, sometimes associated with auditory agnosia, differs in symptomatology and development from the usual forms of infantile aphasia. The prognosis, based on the regression or persistence of the aphasia, is favourable in 60% of the cases and unfavourable in 40%. None of the various antiepileptic drugs is consistently effective. The cause of the syndrome remains unknown.

Aphasia↗

[Plasma level monitoring of psychotropic drugs in children. II -- Antidepressants (author's transl)].

Children and young adolescents with either depressive syndromes or enuresis were treated with clomipramine for periods of 1 to 9 months. Plasma concentrations of the drug and of its demethylated metabolite were monitored and compared with clinical effects. In children, clomipramine proved rapidly absorbed by the oral route, and its rate of distribution seemed to be related to age since the dose-concentration ratio was lower in the youngest subjects. There was a clear correlation between side-effects and clomipramine levels but not demethyl-chlorimipramine levels. In enuresis, a therapeutic effect was obtained with clomipramine levels of 20 to 60 ng/ml; lower levels were associated with ineffectiveness and higher levels with side-effects. The relationship between daily doses and plasma concentrations varied considerably from one patient to another but was almost constant in the same individual. The results obtained underline the usefulness of routinely monitoring antidepressant plasma levels in children.

Adolescent↗

[Plasma level monitoring of psychotropic drugs in children. I-Haloperidol (author's transl)].

Monitoring of haloperidol plasma levels during long-term treatment is not commonly practised in adults and even less in children. In this study, haloperidol plasma levels were measured in children and teenagers with psychotic episodes or abnormal movements. Steady state concentrations ranged from 0.7 to 19 ng/ml. They were apparently unrelated to the doses administered (15-285 micrograms/kg/day), and variations of up to 15-fold were observed with the same dosage. In contrast, a significant correlation (p less than 0.02) was determined between age and dose-concentration ratio. Side-effects also seemed to be significantly related to plasma levels (p less than 0.01); they occurred at concentration higher than 6 ng/ml. Therapeutic response was observed with plasma concentrations of 1 to 4 ng/ml in cases with abnormal movements, but no dose-effect relationship was found in patients with psychotic episodes.

Adolescent↗

A program for training physician-investigators.

A decreasing number of physicians are selecting careers in clinical investigation. In order to aid in reversing this trend, the Physician Investigator Training Program for residents and postdoctoral fellows was developed within the Department of Medicine at the University of Pittsburgh School of Medicine. Ph. D.s with broad-based research experience serve as the core faculty. The trainees are not assigned clinical duties during the two-year period of the program. The first nine months of the curriculum consist of formal lectures and laboratory training encompassing basic laboratory techniques, cell and tissue culture, separation techniques, advanced instrumental techniques, kinetics, enzymology and receptors, membrane structure and transport, radioimmunoassay, statistical analysis, computer programming, mathematics, microbiology, animals in research, immunology, epidemiology, teaching methods, and manuscript and grant-writing. The last 15 months are devoted to a supervised laboratory research project. The program may serve as a model to train increased numbers of physician-investigators.

Curriculum↗

Haloperidol plasma level monitoring in neuropsychiatric patients.

The available data on haloperidol pharmacokinetics and haloperidol plasma level monitoring in neuropsychiatric patients are reviewed and compared with authors' personal observations. It appears that although haloperidol disposition can be described by linear kinetics in volunteers, this is not the case in patients in whom a 7--10-fold variability in plasma levels is observed for the same dosage together with the possibility of saturation kinetics and/or first pass effect. Anticholinergics may interfere with haloperidol absorption, and significant differences in disposition rate and binding have been observed in children and cirrhotic patients. A clear correlation appears to exist between plasma concentrations and side effects or adverse reactions with threshold levels for extrapyramidal syndromes of 6--9 ng/ml. Threshold levels for therapeutic effects vary with syndromes and age. In Gilles de la Tourette syndrome, active levels are of the order of 1--3 ng/ml, whereas in psychotic syndromes levels of 10--15 ng/ml are requested. In mania, a good therapeutic effect has been observed with plasma levels of 2.5--4.5 ng/ml. In general, children require lower plasma levels for the same therapeutic effects. In chronic unresponsive schizophrenic patients, poor drug bioavailability is not the major factor for the lack of response, and the possibility that these patients constitute a nosological subgroup is suggested. Therapeutic drug monitoring of haloperidol appears justified because (a) no direct relationship exists between daily doses and haloperidol steady-state plasma levels; (b) there is a possibility of saturation kinetics at higher doses; (c) commonly associated drugs or diseases may alter the kinetic profile of the drug; (d) drug disposition is faster in children than in adults; (e) optimal plasma concentration appears to differ in various pathological syndromes and age groups; and (f) side-effects and adverse reactions are clearly related to haloperidol plasma levels.

Chronic Disease↗