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Biomedical subjects

G Lagier

Publications and source records attributed to G Lagier.

At least 19 recordsLinked to original sources
PubMed1991

Effects of some chelating agents on bismuth absorption in the rat.

Bismuth encephalopathies appeared in the mid-seventies in France and concerned about 1,000 people and led to a fatal outcome in 70 cases. Responsibility of Bi was clearly confirmed by the disappearance of the intoxication after prescription of drugs containing Bi had been more tightly regulated. Since the implication of a substance increasing the intestinal absorption of Bi has been suspected, we studied the concentrations of Bi in the tissues of rats who had been treated with bismuth nitrate basic 400 mg/kg per d for one month with and without an intake of a chelating agent added to the drinking water at a concentration of 10 mmol/l. The chelating agents tested were ethylenediaminetetraacetic acid (EDTA), nitriloacetic acid (NTA) and tripolyphosphate (TPP), cysteine and diethyldithiocarbamate (DEDTC). Cysteine and DEDTC gave the highest increase of Bi in tissues but with a wide dispersion of levels. However, even in the rats with the highest levels of Bi, there were no behavioral problems. EDTA induced an increase of Bi in kidney, brain and bone and NTA in kidney but there was no obvious sign of toxicity. We did not succeed in reproducing in rats the Bi toxicity observed in patients some years ago.

Animals↗
PubMed1991

Steady-state population pharmacokinetics of sustained release theophylline in adult asthmatic patients.

The steady-state population pharmacokinetics of theophylline were studied in 52 asthmatic adult patients who received sustained-release theophylline as armophylline or euphylline. A total of 92 steady-state plasma theophylline concentration-dosage pairs were analyzed using a nonlinear mixed effects model. The pharmacokinetic model used was a one-compartment open model with single path Michaelis-Menten elimination. Dosage was adjusted to body weight. The effects of age, gender, alcohol consumption, cigarette smoking, dosage form, concurrent treatment with beta-agonists or steroids, outpatient dosing, and plasma caffeine concentration on maximum elimination rate (Vm) and Michaelis constant for theophylline metabolism (Km) were investigated. Hypothesis testing produced a final model in which Km = 0.42 (mg/l), and Vm (mg/kg per day) was based on cigarette smoking and dosage form, with Vm = 7.54 + 2.01 (smoking) + 1.08 (euphylline). Estimated coefficients of variation for interindividual variability in Km and Vm were 162.6% and 48.1%, respectively. Residual variability in dosage rates was estimated as 0.90 mg/kg per day. The identification of factors influencing theophylline disposition should prove useful for the a priori design of theophylline dosage regimens and monitoring of drug levels during therapy.

Adult↗
PubMed1989

[Drug-induced renal insufficiency. Results of consensus meetings].

We report the conclusions of consensus meetings organized by the "Direction de la Pharmacovigilance" of Roussel Uclaf, and attended by University Hospital Nephrologists, members of the National Network of Pharmacovigilance and representatives of Roussel Uclaf Drug Monitoring Department, in order to define more accurately, as regards drug-induced renal failure, the criteria and the terminology proposed by the French method of causality assessment of adverse drug reactions.

Humans↗
PubMed1988

[Presence of benzodiazepines in the serum of patients after accidents. Relation to alcoholism].

In a study of 2.021 injured persons (accidents at home or at work, road accidents), qualitative assays of serum benzodiazepines by the EMIT method were positive in 9.6 per cent of the cases, including 3.2 per cent who had blood alcohol levels in excess of 0.10 g/l. Benzodiazepines were more frequently found in accidents at home and on roads than in accidents at work. These results raise the question of the role played by benzodiazepines as a possible risk factor of accidents, notably road accidents.

Accidents↗
PubMed1988

Detection of blood benzodiazepines in injured people. Relationship with alcoholism.

In 2021 accident victims (household, work and road accidents) the qualitative test for benzodiazepines in the serum by the EMIT method was positive in 9.6% of cases, including 3.2% of subjects who also had a blood alcohol level greater than 0.10 milligram. Benzodiazepines were detected with a particularly high frequency in household accidents and road accidents and rarely in work accidents. These results raise the problem of the role of benzodiazepines as a possible risk factor for accidents, particularly road accidents.

Accidents↗
PubMed1987

Quantitative modifications of major histocompatibility complex (MHC) antigens induced by recombinant gamma interferon in two human breast cancer lines.

H466-B and T47-D breast carcinoma cell lines were treated with recombinant gamma interferon (r gamma IFN) to study major histocompatibility complex (MHC) class I and class II antigen responses. Untreated H466-B cells released B2 microglobulin (B2M) into the culture medium and expressed B2M and class I heavy chain on 100% of the cells. The expression of class II antigens (DR) was limited to 8 +/- 4% of the cells. This subpopulation was isolated by cell sorting and labelled with 35S methionine. Protein extracts were immunoprecipitated with anti-DR antibody and subjected to two dimensional non-equilibrium pH gradient electrophoresis (2D-PAGE). A normal pattern of expression of invariant, alpha and beta chains was shown. The MHC antigenic expression of H466-B parental cell line was not modified by interferon treatment. Untreated T47-D cells did not release B2M into the culture medium, expressed B2M and class I heavy chain on 100% of the cells but did not express class II molecules using radio-immunoassay or 2D-PAGE. As early as 24 h after r gamma IFN addition, T47-D cells released B2M into the medium, B2M and class I heavy chain were significantly greater than that of untreated cells, and class II antigenic expression was found, all these in a dose dependent manner. 2D-PAGE analysis of class II antigens revealed the profile of human DR molecules but this expression seemed incomplete since only single alpha and beta spots were detected suggesting a possible defect in the sialilation of DR molecules. These results show a heterogeneity in MHC antigenic responses to r gamma IFN and suggest that synthetized class II molecules may be incompletely processed.

Antibodies, Monoclonal↗
PubMed1987

1,25-Dihydroxycholecalciferol induces an increase in PGE1- and forskolin-stimulated cyclic-AMP production in T47D human breast cancer cell line.

The effect of 1,25-dihydroxycholecalciferol [1,25(OH)2D3], the active form of vitamin D3, on cell growth, clonogenicity, and cyclic adenosine monophosphate (cAMP) production was examined in human breast cancer cell line T47D. 1,25(OH)2D3 markedly inhibited proliferation of T47D cells in a time- and concentration-dependent manner. 1,25(OH)2D3 5 X 10(-7) reduced to 70% [3H]thymidine incorporation into DNA. Specific high affinity nuclear receptors for 1,25(OH)2D3 were present in this cell line. The cAMP produced by T47D cells was measured during 10 min stimulation by effectors (prostaglandin E1 or forskolin). Without effector, T47D cells produced similar amounts of cAMP in control and 1,25(OH)2D3-treated cells. After 3 days in the presence of 1,25(OH)2D3, cAMP production was significantly increased compared to control cells when stimulated by 10(-4) M prostaglandin E1 or 5 X 10(-7) M forskolin (3.2- and 2.4-fold increase, respectively). This cAMP increase was concentration dependent within the same range that inhibited cell growth and clonogenicity. These results suggest that 1,25(OH)2D3 may indirectly affect cAMP production by modulating the target cell response to stimulatory agents of cAMP production.

Alprostadil↗
PubMed1977

[Hypoglycemia in 2 patients treated with perhexiline maleate].

Hypoglycaemia occurred in two patients treated with perhexiline maleate. The responsibility of the medication is discussed in each case. Blood insulin levels were increased. Blood perhexiline levels decreased very rapidly in the first patient, though much more slowly in the second.

Aged↗
PubMedDate not supplied

[Inventory of questions posed at a Regional Pharmacovigilance Center. Discussion about a possible coordination of informatics].

All the requests (162) from the 1st to the 31th of december 1988 (a period of one month) are analysed by the Paris Fernand-Widal ADR Monitoring Centre. The requests are classified as following: 74 pharmacological consults (39 about pregnancy, 9 for breast-feeding, 3 neonates or children, 2 about G6PD deficiency, 3 guide-lines after a therapeutic error, 3 requests for treatment of ADR, and 15 miscellaneous). 5 ADRs notified and reported to an other nearest Centre to the caller and 3 diagnosed latter as an ADR 49 ADRs registered turn to a request because of lack of information (age: 15; sex: 18; name: 1; address: 31,) or faithfullness (4) or several reasons (18). 31 general information about drugs. Usually, physicians request the Monitoring Centre but recently patients request directly the Centre; specially during pregnancy. The progressive number of the questions makes computerization necessary. A single system appears to be essential for all the Regional Centres to improve the quality of the answer and for the new ADR's alert.

Computers↗
PubMedDate not supplied

[Drug-induced cutaneous photosensitivity. Results of a consensus meeting].

In France, the use of an official drug adverse reaction assessment method is mandatory since 1984. The method proposes various qualifications for chronologic and semiologic criteria without clear limits. The definitions could vary with the nature of the side-effect. We report here the results of a consensus meeting on drug-induced photosensitivity. Dermatologists and experts in pharmacovigilance studied together how the "French method" could apply to the two variances of drug-induced photosensitivity: phototoxicity and photoallergy.

Drug Eruptions↗
PubMedDate not supplied

[Interstitial pneumopathies: criteria of drug side-effects. Results of consensus meetings].

Since 1984, the use of the official method for determining the responsibility of drugs in side-effects has been compulsory in France. This method offers, but does not define, different qualificatives for chronological and semeiological criteria. Consensus workshops have been set up to define the undesirable side-effects themselves and the different qualificatives in each of the principal fields of pathology. As regards drug-induced interstitial pneumonia, chest specialists from university hospitals, members of the national system of pharmacovigilance and representatives of the Roussel-Uclaf central department of pharmaco-vigilance have determined: the limits of time elapsed between the beginning and end of drug administration and the occurrence of the adverse reaction; how to interpret various courses of the side-effect with and without temporary discontinuation of the drug, and how to interpret a possible readministration. A list of investigations aimed at excluding the main possible causes of interstitial pneumonia has been drawn up.

Chronology as Topic↗