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Biomedical subjects

A Cailleux

Publications and source records attributed to A Cailleux.

At least 19 recordsLinked to original sources

Mechanisms of the inhibition of human erythrocyte pyridoxal kinase by drugs.

The aim of this study was to investigate the interaction between drugs chosen for their clinical neurotoxicity or chemical structure and vitamin B6 metabolism. After a preliminary screening of drugs to determine their potential inhibitory effect on erythrocyte nonpurified pyridoxal kinase (PLK) (EC 2.7.1.35), additional investigations, including kinetic studies and detection of chemical reactivity between the inhibiting drugs and pyridoxal (PL) or pyridoxal-5'-phosphate (PLP), using UV-visible spectrophotometry and mass analysis, were carried out to specify the mechanism of PLK inhibition. Depending on the results, the inhibiting drugs were divided into three groups. The first group included theophylline and progabide and inhibited PLK using either PL or pyridoxamine (PM) as substrate and thereby were true inhibitors. Moreover, they did not form covalent complexes with PL or PLP. The second group, which included cycloserine, dopamine, isoniazid, and thiamphenicol glycinate, inhibited PLK using PL, but not PM, as substrate. They were able to react with PL or PLP to form covalent complexes, and kinetic studies suggested that the observed PLK inhibition was due to these formed complexes. A third group, which consisted of levodopa, D-penicillamine, and muzolimine, inhibited PLK using PL, but not PM, as substrate. They formed, with PL or PLP, chemical derivatives that probably had no inhibitory effect on PLK. These results and the clinical consequences of such interactions are discussed and compared with results of previous studies.

Drug Interactions

Plasma sialic acid as a marker of the effect of the treatment on metastatic colorectal cancer.

The concentration of total sialic acid (TSA) is increased in the plasma of patients with many types of cancer. The purpose of this study was to assess the usefulness of the TSA marker in predicting the efficacy of the treatment, and to compare TSA with two common markers, carcinoembryonic antigen (CEA) and the carbohydrate antigen 19-9 (CA 19-9). The study was performed on 44 patients treated for advanced colorectal carcinoma by a weekly 8 h continuous infusion of 5-fluorouracil (1300 mg/m2) plus bolus injection of L-folinic acid (100 mg/m2). TSA, CEA and CA 19-9 levels were measured before and after 3 months of treatment and their variations analysed as a function of the response to the treatment. TSA levels of patients with metastatic colorectal carcinoma before treatment (959 +/- 265 mg/l) were significantly higher than those of 32 healthy people (584 +/- 99 mg/l). The percentage of patients with TSA concentration above the cut-off level (782 mg/l) was 73% before treatment and 23% after. All patients who experienced an objective response to the treatment (complete, partial or minor response) (n = 29) had a significant decrease of TSA levels (t = 5.96; P < 0.001). When the disease was considered as stabilised (n = 10), TSA changed slightly, but it increased with progressive disease (4 out of 5 patients). Changes in CEA and CA 19-9 did not correlate as well as TSA to the treatment efficacy. Initial levels of TSA did not permit prediction of the efficacy of the treatment since they were not significantly different between the five response groups. TSA seems to be more likely involved in tumour changes than in tumour volume. Its determination could provide useful information about the spreading and metastatic properties of the tumour. TSA normalisation is an indicator of probable tumour growth arrest and its elevation could be a marker of relapse.

Adenocarcinoma

Decrease of isoprene concentrations in blood during general anesthesia.

Isoprene is present in human breath and in human blood. The fact that isoprene concentrations in breath are linked to states of sleep and wakefulness led us to study its concentration in blood of 12 patients before, during, and after general anesthesia. Isoprene concentrations in blood of patients before anesthesia were 3.3 +/- 1.6 micrograms/liter. During anesthesia, isoprene concentrations decreased to 0.9 +/- 0.5 micrograms/liter. One hour after the end of anesthesia isoprene increased to levels similar to or higher than the preanesthetic ones.

Adult

Is pentane a normal constituent of human breath?

Breath analysis is a non-invasive method for investigation of the volatile compounds produced by humans. Pentane has often been taken as an indicator of lipid peroxidation. Our purpose in this study was to determine its normal concentration in the breath of healthy humans. Using a specific and sensitive gas chromatography-mass spectrometry technique pentane concentrations in breath were lower than 10 pmoles/l. The high levels of pentane found by some authors in healthy humans were probably due to the coelution of pentane with isoprene, a volatile hydrocarbon present in human breath.

Adult

Blood isoprene concentrations in humans and in some animal species.

The concentrations of isoprene, the main hydrocarbon of human breath, were measured in the blood of humans and of different animal species (rat, rabbit, dog, ewe, cow). In human blood, the concentrations of isoprene were between 15 and 70 nmol/liter (mean value of 37 +/- 25 (SD) nmol/liter). In the blood of the different animal species tested, traces of isoprene were unambiguously detected by mass spectrometry, but the levels were always lower than 1 nmol/liter.

Adult

[Iodoform poisoning. 3 cases].

Three cases of iodoform poisoning are described following dressings with 10% iodoform gauze (0.10 x 5 m) on extended wounds. Five, ten and sixteen days after the beginning of dressings, the patients became confuse, hallucinated, and one of them was subsequently comatose. Vomiting, fever, tachycardia with premature ventricular beats and shortening of P-R interval, slight increase of transaminases and proteinuria were observed. Within a few days (3 to 8) after the iodoform dressings were discontinued, the signs of iodoform toxicity disappeared. The toxicity of iodoform is probably unrecognized if the rarity of the observations published and the amount of iodoform gauzes annually sold are compared.

Adult

Severe monochlorobenzene-induced liver cell necrosis.

Benzene derivatives can induce severe liver cell necrosis in animals. A case of a 40-year-old man whose daily consumption of alcohol was 200 g and who had a severe monochlorobenzene-induced liver necrosis is described. Liver biopsy specimen showed centrilobular and mediolobular necrosis, similar to that in mice after experimental bromobenzene administration. Monochlorobenzene serum concentration, assayed from day 3 to day 15 after poisoning, decreased monoexponentially with a half-life of 40.3 hours. Prostaglandin E1 was administered from day 3 to day 8. The patient ultimately recovered. The mechanism of monochlorobenzene-induced liver injury and the possible aggravating role of chronic alcohol consumption are discussed.

Adult

Toxicological screening of drugs by microbore high-performance liquid chromatography with photodiode-array detection and ultraviolet spectral library searches.

We use ultraviolet data, acquired with a photodiode-array detector coupled to a reversed-phase liquid-chromatographic system, to identify unknown drugs in plasma samples of acutely poisoned patients. Both retention time and spectra of the peaks obtained with a microbore Hypersil ODS column under gradient elution are compared with a library of approximately 350 compounds. We present our three-year experience with this system, which identifies drugs in less than 1 h, with a high degree of confidence.

Chromatography, High Pressure Liquid

Uptake of trihalomethanes by patients during hemodialysis.

Trihalomethanes (THM) present in tap water were also found in dialysis fluid because they were not eliminated by water treatment. THM, absorbed through the dialyser membranes, increased considerably in blood and in expired air of patients on hemodialysis during the dialysis sessions. The uptake of THM during each dialysis session was about 1 mg.

Aged

Isoprene and sleep.

Isoprene is one of the main constituents of endogenous origin in exhaled human breath. The concentration of isoprene seems to vary with states of sleep and wakefulness, increasing during sleep and decreasing sharply just after awakening. Thus, isoprene may be involved in in sleep upholding.

Acetone

[Level of urinary phenol and hippuric acid in control subjects and subjects exposed to benzene and toluene].

Two high-performance liquid chromatographic methods are described, one for assay of phenol in urine, the other for assay of hippuric acid. Steam distillation was used to hydrolyse the sample and separate the phenol from the matrix. A dilution was the only pretreatment of urine for assay of hippuric acid. The upper reference limits obtained from 42 non-exposed subjects were 7.09 mmol/mol creatinine for urinary phenol and 1,174 mmol/mol creatinine for hippuric acid. The mean concentration of urinary phenol was higher in 190 exposed workers (7.21 +/- 5.05 mmol/mol creatinine; mean +/- SD) than in control subjects (3.97 +/- 1.56 mmol/mol creatinine).

Benzene

Cyanide and thiocyanate blood levels in patients with renal failure or respiratory disease.

Whole blood cyanide and plasma thiocyanate were measured by a headspace gas chromatographic method and a colorimetric method, respectively, in 16 healthy subjects, in 10 patients with respiratory disease and in 12 patients on chronic dialysis for renal failure. In healthy subjects, whole blood cyanide and plasma thiocyanate concentrations were significantly higher in smokers (1.8 +/- 0.4 mumol/l; 206 +/- 74 mumol/l) than in non-smokers (0.8 +/- 0.4 mumol/l; 74 +/- 19 mumol/l). In renal failure patients on hemodialysis, no difference was noted in cyanide levels (0.6 +/- 0.4 mumol/l), but there was a significant increase in plasma thiocyanate levels during the interdialysis period (62 +/- 24 mumol/l; 91 +/- 24 mumol/l). No difference in cyanide and thiocyanate levels of patients with respiratory disease was seen, in agreement with a weak pulmonary elimination of cyanide.

Cyanides

Screening for neutral and basic drugs in blood by dual fused-silica column chromatography with nitrogen-phosphorus detection.

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.

Chromatography, Gas

[Determination of plasma noradrenaline by automatic high pressure liquid chromatography with electrochemical detection].

A method for the plasma noradrenaline (NA) analysis by reversed-phase liquid chromatography with electrochemical detection is described. The plasma sample preparation includes two-steps: ion-exchange and alumina adsorption. The use of a data system and an automatic sampler enables the injection of samples in series. Using this technique, determination of plasma NA concentration in 34 healthy subjects (27.4 +/- 7.2 years) gave the following results: 0.28 +/- 0.10 micrograms/l after 30 min of resting in the supine position and 0.52 +/- 0.17 micrograms/l after 5 min of upright position.

Adult