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Biomedical subjects

P Mahieu

Publications and source records attributed to P Mahieu.

At least 19 recordsLinked to original sources

Cytogenetic observations following thallium poisoning.

Observations have been performed on peripheral blood lymphocytes from a patient having ingested 200 mg thallium sulfate, in order to evaluate the ability of the compound to produce cytogenetic damage in vivo in humans. Our results demonstrate that neither the yield of structural chromosome aberrations nor sister chromatid exchanges were significantly modified. The drastic increase of binucleated cells with micronuclei indicates that thallium sulfate has in common with many metallic compounds the ability to interfere with chromosome distribution.

Cell Nucleus

A rapid high-performance liquid chromatographic method for the measurement of midazolam plasma concentrations during long-term infusion in ICU patients.

A new high-performance liquid chromatographic method was developed for quantification of midazolam in plasma samples from intensive care unit patients on long-term intravenous infusion of this benzodiazepine. Plasma samples (0.5 ml) were mixed with 1 microgram flurazepam (internal standard), alkalinized with 2.5 N NaOH, and extracted with toluene. The organic phase was evaporated to dryness, and the residue was dissolved in the mobile phase (acetonitrile/0.05 M phosphate buffer pH 4.5) and injected into the analytical column (C18 Nova-Pak 3.9 x 150 mm, 4 microns, maintained at room temperature; mobile phase flow rate: 1.2 ml/minute). The eluate was monitored at 207 nm, which reduced the risk of interferences from concurrent medications. Retention times of flurazepam, 1'-hydroxymidazolam (an active metabolite) and midazolam were approximately 4.5, 6.1 and 13.5 minutes, respectively. The assay was linear over the range 100 to 3000 ng/ml. The coefficients of variation of the within-day and between-day assay for the 100 to 3000 ng/ml range were < 5% and < 7%, respectively. The developed method is fast, reproducible, and well suited to monitor steady state midazolam plasma concentrations in clinical samples.

Anesthetics, Intravenous

Neurotoxicity to the basal ganglia shown by magnetic resonance imaging (MRI) following poisoning by methanol and other substances.

OBJECTIVE: To define specific brain magnetic resonance features in methanol intoxicated patients and to evaluate the clinical relevance of monitoring these features. BACKGROUND: During the past decade magnetic resonance imaging has proven to be an exquisitely sensitive modality in depicting subtle water changes in diseased areas of the brain, allowing the definition of high-risk structures in numerous pathological conditions. METHOD: Four patients admitted to our institution for acute methanol intoxication were repeatedly evaluated by brain magnetic resonance imaging or a combination of computed tomography and magnetic resonance imaging. Common features of initial brain status were shown in all four cases and compared to those of patients presenting with other intoxications or critical deprivation states. RESULTS: Preferential localization of methanol-induced lesions within the putamina was observed in all four cases. This finding is specific compared to intoxication by other substances like carbon monoxide, or in the critical phase of metabolic disorders. The striking regression of the putaminal lesions on follow-up magnetic resonance examinations correlated with complete neurological recovery and the absence of extrapyramidal disturbance. Two patients exhibited discrete symmetric additional lesions in the medial areas of the parieto-occipital lobes. In a third one, the occipital lesions were severe. All three suffered from permanent visual impairment. The fourth patient, in whom magnetic resonance examinations failed to reveal any occipital lesion, never complained of visual disturbance though signs of optic neuropathy were detected in the visual evoked potentials. CONCLUSION: Magnetic resonance imaging appeared as a well suited neuroimaging modality in methanol intoxicated patients both in revealing a specific pattern of brain lesions and in demonstrating valuable correlation between evolution of brain changes on magnetic resonance images and clinical outcome.

Adult

Methanol poisoning during late pregnancy.

CASE REPORT: A 26-year-old woman ingested 250 to 500 mL methanol during the 38th week of pregnancy. The initial serum methanol concentration was 230 mg/dL and formate was 33.6 mg/dL. A mild metabolic acidosis was present. As gynecologic examination and fetal monitoring failed to detect fetal distress, it was decided to give tocolytic therapy until the treatment of methanol poisoning could be achieved in the mother. Therapy included ethanol infusion, bicarbonate administration and three courses of hemodialysis. Delivery occurred six days after methanol exposure, when methanol was no longer detected in maternal blood. No further complications were noted in the mother and her newborn. To our knowledge, there is no other case of methanol poisoning during pregnancy in the literature.

Adult

Carvedilol overdose.

Carvedilol is a non selective beta-adrenoceptor antagonist which also causes peripheral vasodilation primarily via alpha 1-adrenergic blockade (Strein et al., 1987, McTavish et al., 1993). It has been shown effective in the treatment of mild-to-moderate hypertension and angina, and is currently under investigation in patients with congestive heart failure.

Adrenergic beta-Antagonists

Evaluation of the ability of paracetamol to produce chromosome aberrations in man.

The ability of paracetamol to induce structural chromosome aberrations in human peripheral blood lymphocytes in vivo was evaluated in volunteers who had been administered a single oral dose of 3 g paracetamol, in patients who had received 2 g of propacetamol by intravenous infusion every 6 h for at least 7 days, and in self-poisoned patients who, for suicidal reasons, had ingested more than 15 g paracetamol. In addition to the in vivo observations, the effectiveness of paracetamol to interfere with fusorial microtubule polymerisation was assayed in vitro in order to detect a possible effect of paracetamol on the distribution of chromosomes during cell division. The negative results obtained in all those assays strongly suggest that paracetamol has no mutagenic properties in human. There was, indeed, no significant difference in the percentage of abnormal cells before and after application of paracetamol in volunteers (0.2% before ingestion of 3 g paracetamol, 0.12% after 24 h, 0.04% after 72 h and 0.04% after 168 h) and in patients (0.5% of abnormal cells before treatment versus 0.44% after intravenous infusion of a total of 28 g paracetamol). Moreover, the yield of abnormal cells was not modified in self-poisoned persons (0.24%), in spite of an important decrease in the mitotic index of the PHA stimulated lymphocytes. In the in vitro assay, no inhibition of microtubule polymerisation was detected with concentrations of 2.5, 5 and 10 mM paracetamol.

Acetaminophen

Sister chromatid exchanges in human peripheral blood lymphocytes after ingestion of high doses of arsenicals.

OBJECTIVE: To evaluate the cytogenetic effects following the ingestion of high doses of arsenicals. METHODS: Determination of the mean sister chromatid exchange (SCE) frequency and the population of high-frequency cells (HFC, cells with a high SCE frequency) in the peripheral blood lymphocytes in four patients who ingested 150 mg KAsO2, 1 g, 10 g and 20 g As2O3 respectively. RESULTS: Doses of 10 g and 20 g significantly increased the HFC frequency and produced a shift in the distribution of the cells in accordance with the number of SCEs. The mean frequency of SCEs/cell was affected only after the highest dose (20 g). CONCLUSION: These results strongly suggest that cytogenetic methods are inappropriate for biomonitoring people occupationally exposed to arsenicals.

Adolescent

Increased hepatocytic mitotic activity as a diagnostic marker of acute arsenic intoxication. A report of two cases.

We report two patients in whom acute arsenic poisoning was associated with a very peculiar increase in hepatocytic mitotic activity. The recognition of such an unusual picture which is likely to be related to the mitogenic properties of arsenic may be of help in the identification of acute arsenic intoxication, a life-threatening condition which is difficult to diagnose.

Acute Disease

Decrease in systemic tolerance to fed ovalbumin in indomethacin-treated mice.

The oral administration of non-steroidal anti-inflammatory drugs (NSAID) to animals induces a quick increase in intestinal permeability and secondary inflammatory lesions of the intestine. The mechanisms leading to the inflammatory lesions are hypothetical. The increased intestinal permeability could allow a greater mucosal and systemic penetration of fed antigens and bacterial products leading to an abnormal mucosal and systemic immune and inflammatory response toward these materials. We examined the effect of oral dosing with indomethacin on ovalbumin serum levels and the systemic immune response to ovalbumin in mice fed with ovalbumin. The ovalbumin serum level was higher in indomethacin-treated mice and the increase was proportional to the dose of indomethacin. It was associated with epithelial and subepithelial lesions. Moreover, the systemic humoral and, to a lesser extent, the cellular tolerance were partially abrogated in the treated mice. These findings suggest that the oral administration of indomethacin in mice induces an increased passage of fed antigen through the intestinal epithelium associated with a decrease in systemic tolerance to this antigen. The reason for this decrease remains unclear. Besides a disequilibrium between systemic and mucosal immune responses, a loss of integrity of the intestinal epithelial cells and a direct immunomodulating effect of indomethacin may also be involved. This decrease in systemic tolerance to luminal antigen could be involved in the development of NSAID enteropathy.

Administration, Oral

Intracardiac injection of T-61, a veterinary euthanasia drug.

CASE REPORT: We report a suicidal attempt by intracardiac injection of T-61, a veterinary euthanasia drug containing embutramide, mebezonium and tetracaine in dimethylformamide. The main complications were reversible acute renal failure and pericardial effusion. There was a delayed abnormality of the liver function tests possibly related to the dimethylformamide solvent. A liver biopsy on day 16 showed a normal hepatic architecture with lipid-containing lysosomes and prominent vesicular endoplasmic reticulum noted on electron microscopy.

Acute Kidney Injury