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D Dutoit

Publications and source records attributed to D Dutoit.

5 recordsLinked to original sources

[Anxiety disorders and unexplained syncopes of presumed vaso-vagal origin].

The impact of anxiety neurosis on the diagnosis and treatment of patients with unexplained syncope (S) was assessed in 178 patients (91 women and 87 men) with an average age of 36.5 +/- 20 years, presenting with 10.7 +/- 24 episodes of S). None had evidence of underlying cardiac disease apart from 7 patients with mild hypertension. All patients underwent a tilt test (TT) at 60 degrees for 45 minutes. A bolus of isoproterenol was injected intravenously in subjects with negative TT. After the test, the patients were classified according to the presence (n = 38) or absence (n = 140) of anxiety neurosis based on the DSM III-R diagnostic. The TT was positive in 76 patients, 9 of whom had a cardioinhibitory reaction with prolonged asystole. Patients with anxiety had more episodes of S (24 +/- 43 versus 7 +/- 13; p = 0.001), a shorter interval between S (11.5 +/- 23 months versus 12.5 +/- 20 months, p = 0.02) but more negative TT (27/38 versus 75/140; p = 0.05). One hundred and sixty-eight patients were followed up : 10 were lost to follow-up. Preventive treatment was undertaken in 59 patients who were representative of the whole group with respect to age (30 +/- 18 years 39 +/- 21 years : p = 0.004). After an average follow-up of 24.5 +/- 15 months, 26 patients (15%) experienced a recurrence of S. The recurrence rate was identical in patients with positive and negative TT and in treated and untreated cases. On the other hand, recurrence was higher in those with anxiety (12/25 versus 14/117; p = 0.001) who also had less improvement of symptoms (12/15 versus 74/120; p = 0.001). The "anxiety" variable was therefore identified as being the only predictive factor for recurrence of syncope. The authors conclude that in patients referred for investigation of unexplained syncope, some suffer from anxiety neurosis, in whom the TT is usually negative, and have a higher risk of recurrence. They justify a specific therapeutic management.

Adolescent↗

[Erythrocyte superoxide dismutase (eSOD) determination in positive moments of psychosis].

Dysregulation of free radical metabolism has been supposed to be involved in schizophrenia etiopathogeny. Recently, Wang et al. showed a red blood cell super oxide dismutase increase in positive schizophrenia (Crow's type I), but neither in negative schizophrenia (Crow's type II) nor in controls. The study included 28 in-patients suffering from acute positive psychosis who were compared with 15 controls. We confirmed the results of Wang. We found a significantly red blood cell Super oxide dismutase increase in positive psychosis, in comparison to negative psychosis and controls (p = 0.0001). This SOD increase was in relationship with the degree of clinical psychomotor excitement. After 21 days of neuroleptic treatment, SOD activity decreased and reached standard values. These results support the hypothesis of striking relationships between catecholaminergic hyper-metabolism and SOD increase, in positive psychosis. These could account for psychotic positive symptoms improvement with neuroleptic treatment, which blocks dopamine pathways.

Adult↗

[Value of the determination of erythrocyte haloperidol ketone reductase activity in the evaluation of haloperidol therapy].

Serum levels of haloperidol and reduced haloperidol as well as the reduced haloperidol/haloperidol ratios were determined in nine acute schizophrenics on oral haloperidol medication and correlated over 21 days with psycho pathology and extra-pyramidal symptom scores. We have investigated red blood cells haloperidol reductase activity in the group of patients. Significant correlations were found between haloperidol plasma levels and positive sub scale for each patient (r = 0.86 and p < 0.01; r = 0.70 and p < 0.05). We found a correlation between red blood cells reductase activity and the improvement of the psychotic anxiety scale (r = 0.64/and p < 0.05; r = 0.67 and p < 0.05), but not with reduced haloperidol/haloperidol ratios in plasma. The knowledge of reductase activity could predict the treatment response in acute schizophrenic patients. We suggest that the reported inter individual and inter ethnic differences in haloperidol and reduced haloperidol and in clinical response and adverse effects may be a reflection of genetic control of the two oxidative pathways mediated by cytochrome P450 isozyme and/or the reductase pathway mediated by haloperidol reductase in individual subject.

Adult↗

[Erythrocyte ketone reductase activity, total plasma haloperidol and acute psychoses].

Haloperidol (HAL) is a widely used and clinically effective neuroleptic. Its metabolism differs in various animal species. In humans, reduced haloperidol (RHAL), a hydroxy metabolite of HAL, is produced by a cytosolic ketone reductase. Interconversion is known to occur whereby HAL is found in the plasma after administration of RHAL in vivo. Interconversion of HAL and RHAL has been observed in man. However, the capacity for reductive HAL is greater than its oxidation back from RHAL. RHAL, the resulting metabolite of HAL, is reported to be about 10-25% as active as HAL in an animal model. Large intersubject variation has been observed in the pharmacokinetics of HAL and RHAL. A wide variation in reductive drug-metabolizing has been observed in schizophrenic patients treated with HAL. Both high and low RHAL/HAL ratios or RHAL levels were reported to be linked to poor response in HAL-treated patients and might be correlated with the therapeutic window effect of HAL treatment. It is conceivable, therefore, that subjects with high reductive capacity relative to oxidative capacity may have less therapeutic response from the same dose of HAL than those with a low reductive capacity relative to oxidative capacity. This aim of this study was to investigate the HAL reduction among a sample of HAL-treated schizophrenic patients. Because ketone reductases are generally not tissue specific, we investigate the reductase activity in Red blood cells (as described by Inaba), before and during the treatment. Steady-state plasma drug levels during 2 weeks of treatment were quantified. We examined the relationships between fixed doses of HAL treatment, Red blood cells ketone reductase activity, plasma HAL and RHAL levels and the percentage of change of the Positive and Negative Syndrome Scale for Schizophrenia. The participants in this study were 15 inpatients consecutively being treated in the adult psychiatric wards of the University of Lille. All subjects met DSM III-R criteria for schizophrenia (paranoid form). Upon induction subjects were evaluated clinically by trained raters using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Subjects were required to score 40 or higher on the general psychopathology subscale of the PANSS to continue participation. All subjects were drug free. Haloperidol was administered orally at three times daily dose. Patients were randomized to treatment at three orally fixed doses: 6 mg per day, 10 mg per day and 15 mg per day. Patients were treated for 2 periods of one week. At the end of each period, dosages could be modified according to the clinic evolution of the patient. PANSS was repeated by the same raters blinded to the haloperidol dosage, plasma concentration and Rbc haloperidol ketone reductase activity, at the beginning and at the end of each period. Blood samples were collected on the same day that clinical assessment were made. Multiple regression analysis (forward stepwise) revealed that Red blood cells reductase activity at D0 is an important variable predicting haloperidol plasma levels at week 2. Similarly Red blood cells reductase activity at D0 and D7 predicted Reduced haloperidol plasma concentrations at week 2. In this sample, no parameter was found to be consistency predicted the percentage change in the PANSS positive subscale from baseline, at week 2. Nevertheless, Red blood cells reductase activity at D0, Reduced haloperidol/haloperidol ratio at week 2, haloperidol plasma levels at week 2 and the dose of haloperidol at week 1 were important variables predicting the percentage change in the PANSS general subscale from baseline at week 2. These results suggest that the knowledge of reductase activity could predict the treatment response in acute schizophrenic patients.

Acute Disease↗