[Taking charge of severe brain injuries. Comparison of 2 severity indexes. A study over a year activity at the SAMU 45].
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Biomedical subjects
Publications and source records attributed to P Allain.
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We describe a capillary gas-chromatographic method for detection and quantification of basic and neutral drugs in the plasma of patients thought to be poisoned after dangerous overdose. Without further derivatization, the drugs are extracted from 1 mL of plasma, at basic pH, into diethyl ether. The extracts are injected onto two fused-silica capillary columns of different polarity (Ultra 1 and CP Sil 19 CB) coupled to nitrogen-phosphorus detectors. Under these conditions, drug-free plasmas give blank chromatograms, with a peak only for the internal standard (RN 927, an antihistamine not being marketed). Plasma samples from patients who have taken drugs show additional peaks, the relative retention times (RRTs) of which are used to identify the drugs. Here we list the RRTs of about 200 drugs on the two columns. Analyses are routinely performed with an automatic injector; overall analysis time is about 1 h per sample. During the last six years, more than 1000 plasma samples per year have been analyzed. We find this method a powerful tool for toxicological analysis, especially in cases of multi-drug intoxications.
Plasma norepinephrine concentrations after supine rest and after standing were measured by high-pressure liquid chromatography with electrochemical detection in 49 normotensive controls and in 79 patients with essential hypertension. Twenty-nine hypertensive patients were not treated for hypertension. In normotensive subjects--but not in hypertensive patients--supine plasma norepinephrine levels increased significantly with age. No significant difference in supine plasma norepinephrine levels was found between hypertensive patients (NE = 0.28 +/- 0.16 microgram/l, n = 79 and NE = 0.28 +/- 0.14 microgram/l, n = 29) and normotensive subjects (NE = 0.30 +/- 0.13 microgram/l). When expressed as percentage, the rise in norepinephrine levels when standing was greater in hypertensive patients (127.4 +/- 77.4%, n = 79 and 122.6 +/- 65.6%, n = 29) than in normotensive subjects (93.2 +/- 60.3%). When patients and controls aged less than 40 years were compared, similar results were obtained. Supine plasma norepinephrine levels do not support the theory that sympathetic system activity is enhanced in essential hypertension.
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The single dose pharmacokinetics of ornidazole has been evaluated in 12 neonates or infants (aged 1 to 42 weeks) after the infusion of 20 mg/kg over 20 min. Plasma disposition was described by a two-compartment open model. The distribution phase was short (T1/2 (1) = 0.31 h) and was followed by an elimination phase (t1/2 (2) = 14.67 h). The mean apparent volume of distribution was 0.961/kg-1. These results did not differ from data previous by reported in adults. Total plasma clearance was between 0.4 and 1.4 ml X min-1 X kg-1. The plasma concentration 24 h after the infusion was 7.32 mg X l-1, which was above the minimum inhibitory concentration for clinically significant anaerobic bacteria. Based on the pharmacokinetic results and residual concentrations at 24 h, a single daily infusion of ornidazole 20 mg X kg-1 appears adequate for therapy in neonates and infants.
We have used a new analytical micromethod to study the pharmacokinetics of desferrioxamine and its aluminium chelates in patients with chronic renal failure on haemodialysis. Desferrioxamine (Desferal, CIBA, Basle) was given by 1-h infusion just after the haemodialysis at 20, 40, 80 mg/kg body wt. and during the first and the last hour of the haemodialysis at 40 mg/kg. The concentrations of desferrioxamine during infusions showed a linear increase with increasing doses. The maximum concentrations and the AUC obtained when desferrioxamine was infused during the haemodialysis were not statistically different but slightly lower than those obtained in post dialysis administration. This result indicates that the loss of desferrioxamine by transfer in the dialysate is quite moderate within 1 h. During the interdialysis period, there was a decrease of plasma desferrioxamine concentrations with a mean half-life of 18.7 +/- 5.2 h and an increase in plasma concentrations of aluminium desferrioxamine chelate. In vitro studies show that a lengthy contact between desferrioxamine and plasma is necessary for complete chelation of A1 already present in plasma. During the following dialysis session, there was an important decrease of desferrioxamine and of its iron and aluminium chelates in blood plasma representing their transfer to the dialysis fluid.
1 Desferrioxamine mesylate (DM) (10 mg kg-1 = 15.24 mumol kg-1) was given by intramuscular injection to five healthy subjects and to six patients with haemochromatosis, after informed consent. 2 Desferrioxamine (DFA), ferrioxamine (FeA), aluminoxamine (AlA), aluminium (Al) and iron (Fe) were measured in plasma, before and 10, 20, 30, 60 min and 2, 4, 6, 8, 12 h after DM injection and in urine collected over a 6 h period the day before and the day of administration. 3 The predominant form in plasma from control subjects was DFA whereas FeA predominated in plasma from patients. In controls, rapid and slow phases of decline in plasma DFA concentrations were found, with half-lives of 1.0 h and 6.1 h, respectively. In the patients, only a single phase of decline was observed, with a half-life of 5.6 h. Total clearances of DFA were 296 ml h-1 kg-1 in controls and 239 ml h-1 kg-1 in patients. 4 The amount of FeA eliminated in urine during 6 h was significantly lower in controls (8.0 +/- 4.6 mumol) than in patients (129.2 +/- 40.0 mumol), with respective renal clearances estimated over 6 h of 516 ml h-1 kg-1 and 1,716 ml h-1 kg-1. DFA elimination was similar in both groups and its renal clearance estimated over 6 h was 91 ml h-1 kg-1 in controls and 85 ml h-1 kg-1 in patients. 5 Since there was no overlap in the 1 h DFA/FeA plasma ratio between controls and patients, this might be useful as an index of iron overload.
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Plasma noradrenaline concentrations (NA) were measured in 11 hypothyroid patients, 24 hypothyroid patients and 30 normal subjects after 30 minutes of supine rest and after 5 minutes of standing. Observed noradrenaline levels, after rest as well as after standing, were significantly higher in hypothyroid patients (NA rest = 0.66 +/- 0.35 microgram/l, NA standing = 1.26 +/- 0.70 micrograms/l) and significantly lower in hyperthyroid patients (NA rest = 0.22 +/- 0.13 micrograms/l, NA standing = 0.37 +/- 0.20 microgram/l) than in normal subjects (NA rest = 0.32 +/- 0.13 microgram/l, NA standing = 0.55 +/- 0.20 microgram/l). The increase in noradrenaline with standing, when expressed in percent, was similar for the three groups studied (about 100%). These results suggest that a sympathetic nervous system adaptation occurs in hyperthyroidism and hypothyroidism as a compensatory phenomenon to the direct effect of thyroid hormones on the heart.
Boron and strontium concentrations in blood plasma of controls and hemodialyzed patients from two Centers were determined by inductively coupled plasma emission spectrometry. Boron concentrations in blood plasma were respectively, in controls 2.6 +/- 0.9 mumol/l and in hemodialyzed patients 16.1 +/- 5.6 mumol/l before the dialysis session and 9.5 +/- 3.2 mumol/l at the end. The decrease in blood plasma during the dialysis was concomitant with an increase in the dialysis fluid (1.2 +/- 0.7 mumol/l at the beginning and 4.6 +/- 1.8 mumol/l at the end). Strontium concentrations in blood plasma were respectively, in controls 0.22 +/- 0.06 mumol/l and in hemodialyzed patients 0.62 +/- 0.24 mumol/l before the dialysis session and 0.64 +/- 0.14 mumol/l at the end. The mean concentration of strontium in the dialysis fluid was the same before (0.49 +/- 0.11 mumol/l) and after the dialysis session (0.49 +/- 0.10 mumol/l), but a transfer between plasma and dialysis fluid was shown by individual changes. Some considerations about these results are put forward but their possible clinical consequences are not yet known.
Thirty-four patients received, during laparotomy, a 15-20 Gy localized irradiation from a 10-13 MeV beam of electrons supplied by a linear accelerator and focalized by means of a localizer especially designed for this purpose. This technique is indicated for localized residual tumours of the pelvis and intra-operative irradiation of the lumbar aorta, as part of a chemo-radiotherapeutic programme in patients with advanced cancer of the cervix. It is too early to evaluate the medium-term results, but the technique is very well tolerated immediately.
Blood plasma fluoride was determined in 15 chronic haemodialysed patients (60.2 +/- 7.2 yr old) before and after a 4-h dialysis using dialysates with very low fluoride level, and in two control groups, the first of 20 healthy younger subjects (45.9 +/- 3.4 yr old), the second of 8 healthy older subjects (69.1 +/- 6.8 y old). Before haemodialysis the fluoride concentration (1.31 +/- 0.31 mumol/l; 24.8 +/- 5.9 micrograms/l), was higher than in both control groups (0.35 +/- 0.16 mumol/l; 6.6 +/- 3.1 micrograms/l and 0.44 +/- 0.16 mumol/l 8.4 +/- 3.0 micrograms/l, respectively). During dialysis, the mean fluoride concentration fell to 0.94 +/- 0.26 mumol/l, remaining however, significantly higher than in control subjects. The use of fluoride-free dialysates seems to partially compensate the effect of renal impairment since plasma fluoride is only moderately increased in these patients.
Plasma thiopentone concentrations after a single intravenous dose were determined by high pressure liquid chromatography in female surgical patients (n = 13), in pregnant women at term (n = 13) and in neonates (n = 13). In pregnant women, the apparent volume of distribution (Vd = 10.02 +/- 3.26 l X kg-1), plasma clearance (Cl = 22.03 +/- 7.55 l X h-1) and elimination half-life (t 1/2 (3) = 21.71 +/- 11.12 h) were significantly greater than in the surgical patients (Vd = 4.22 +/- 1.16 l X kg-1; Cl = 12.49 +/- 3.50 l X h-1; t 1/2 (3) = 13.79 +/- 3.09 h). Elimination half-life in neonates (t 1/2(e) = 17.9 +/- 9.7 h) was not different from half-life in mothers or in the surgical group. At delivery, the simultaneous concentrations were 5.3 +/- 1.3 mg X l-1 in venous blood and 3.8 +/- 1.6 mg X l-1 in cord venous blood. Apgar score was 10 in eleven neonates. For two babies, an Apgar score at 6 was explained by a uterine incision-to-delivery time interval greater than 2 min.
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The study of an Algerian family revealed that four of the seven children presented dentinogenesis imperfecta associated with an anomaly of the facial skeleton (maxillary hypoplasia, anterior expansion of skeletal origin due to widening of the angle of the gonion). This type of association and its very unusual type of transmission (no doubt recessive) leads to a discussion of genetic mechanisms of these syndromes.
Follow up 30 months after extensive bone resection of mandible with disarticulation of condyle for widespread tumor of angle in a 9 1/2 year old child showed very satisfactory functional and esthetic bone reconstruction. Favorable elements were: conservation of periosteum made possible from results of histology of fresh specimen (showing eosinophil granuloma); the immediate insertion of a temporary prosthesis in strengthened resin to maintain anatomical relations and spontaneous functions.