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Biomedical subjects

A Leroy

Publications and source records attributed to A Leroy.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Cross-over study of the pharmacokinetics of cefonicid administered intravenously or intramuscularly to healthy adult humans.

The pharmacokinetics of cefonicid were investigated in eight healthy adults. A one-gram dose was administered either intramuscularly or intravenously in a cross-over design study. Mean peak cefonicid plasma concentrations of 186 to 204 mcg/ml and 88 to 123 mcg/ml were achieved after intravenous and intramuscular injection, respectively, with elimination half-lives of 4.9 h and 5.3 h. Cefonicid concentrations were measured by both microbiological (M.A.) and high-performance liquid chromatography (HPLC) assays. Results were quite similar with the two techniques, except for the urinary recovery of cefonicid in the first 24 hours (83% of the dose with MA - vs 53% with HPLC method). The apparent volume of distribution (Vd area) was 0.18 1/kg; the total body clearance (CT) and the renal clearance (CR) were 24-26 ml/min and 15-19 ml/min, respectively. The kinetic data of cefonicid were not significantly different for the two routes of administration. A one-gram i.v. or i.m. cefonicid dose produced high and prolonged plasma concentrations with a longer half-life than obtained with commonly used cephalosporins.

Adult↗
PubMedDate not supplied

A new essential gene of the 'minimal genome' affecting cell division.

The complete sequencing of bacterial genomes has offered new opportunities for the identification of essential genes involved in the control and progression of the cell cycle. For this purpose, we have disrupted ten E. coli genes belonging to the so-called 'minimal genome'. One of these genes, yihA, was necessary for normal cell division. The yihA gene possesses characteristic GTPase motifs and its homologues are present in eukaryotes, archaea and most prokaryotes. Depletion of YihA protein led to a severe reduction in growth rate and to extensive filamentation, with a block beyond the stage of nucleoid segregation. Filamentation was correlated with reduced FtsZ levels and could be specifically suppressed by overexpression of ftsQI, ftsA and ftsZ, and to some extent by ftsZ alone. We hypothesize that YihA, like the Era GTPase, may participate in a checkpoint mechanism that ensures a correct coordination of cell cycle events.

Amino Acid Sequence↗
PubMedDate not supplied

Cellular and molecular mechanisms of metastasis as applied to carcinomatous meningitis.

Cancer cells as well as bacteria metastasize to the subarachnoidal space (SAS) causing meningitis. Primary brain tumors, although not forming distant metastases, disseminate via the cerebrospinal fluid and occupy the meninges. The multistep process of cancer or bacterial dissemination is regulated through molecular crosstalk between invaders and host cells. Such crosstalks establish invasion-promoter and invasion-suppressor complexes. In carcinomatous and bacterial meningitis, the participation of host cells is prominent since leukocytes and inflammatory cytokines are the major determinants of malignancy. We propose a model in which bacterial breakdown products activate endothelial cells, a process leading to leukocyte extravasation. This initiates a cascade of inflammatory processes opening up the blood cerebrospinal fluid barrier and producing access for new invaders.

Astrocytoma↗
PubMedDate not supplied

Pharmacokinetics of cefoxitin in normal subjects and in patients with renal insufficiency.

The pharmacokinetics of a single intravenous dose of 30 mg of cefoxitin/kg given to normal subjects and to patients with various degrees of chronic renal insufficiency were studied. The serum half-life of cefoxitin was correlated inversely with the rate of creatinine clearance, and the half-life increased exponentially when the creatinine clearance rate fell below 30 ml/min per 1.73 m2. The elimination of cefoxitin into urine was rapid and extensive in patients whose creatinine clearance was greater than 30 ml/min per 1.73 m2. In patients with more severe degrees of renal impairment, renal clearance of drug was diminished markedly (less than 20% of the administered dose was excreted in 4 hr as compared with greater than 60% in the former group). The clearance of cefoxitin can be increased fivefold by hemodialysis in patients with end-stage renal disease.

Adult↗
PubMedDate not supplied

The pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired renal function.

The pharmacokinetics of single doses (15 mg/kg) of cefotaxime and each of its metabolites were examined in six normal subjects and 24 patients who showed various degrees of renal insufficiency. An additional nine patients with renal failure were entered into a multiple-dose study in which cefotaxime (1 g) was given twice daily for five to seven days. After intravenous administration, the levels of cefotaxime in serum declined in two phases. The half-life for the terminal phase was 1.10 +/- 0.78 hr. Cefotaxime administered intramuscularly was well absorbed from the injection site (91% +/- 19%) and produced maximal levels of 25.5 +/- 3.5 microgram/ml in serum at approximately 0.5 hr after injection. The levels of the desacetyl metabolite in serum were comparatively low, and the half-life of this metabolite was 1.3 hr. Microbiologic measurements of cefotaxime showed that the half-life of the drug was lower in normal subjects (1.71 +/- 0.90 hr) than in patients with severe renal impairment (half-life, 10.20 +/- 3.43 hr). However, this difference was due primarily to desacetylcefotaxime. Specific measurement by high-performance liquid chromatography indicated only a slight increase in the half-life of cefotaxime, whereas the increase in half-life of desacetylcefotaxime was greater. The most pronounced increases in half-life of metabolites occurred when values for creatinine clearance in patients were below about 5 ml/min per 1.73 m2. When cefotaxime was administered repetitively, the ratio of maximal serum levels after the last dose to those after the first dose demonstrated minimal accumulation of intact drug. The average accumulation of desacetylcefotaxime in this group of patients was about twofold, and that for metabolites M2 and M3 was approximately fourfold. This accumulation of metabolites was observed only in those patients with severe renal impairment and was not excessive. Hemodialysis caused a significant reduction in the half-life of both cefotaxime and desacetylcefotaxime. Recommendations are made for the adjustment of dosing schedules in patients with renal failure.

Adult↗
PubMedDate not supplied

Pharmacokinetics of aztreonam in patients with chronic renal failure.

The elimination kinetics of aztreonam (SQ 26,776), a new, completely synthetic, monocyclic beta-lactam antibiotic, were studied after the administration of a single 1g intravenous dose. Five healthy volunteers and 20 patients with various degrees of renal insufficiency were enrolled in this study. Concentrations of aztreonam in serum and urine were determined by both microbiological and high pressure liquid chromatography (HPLC) assays. The pharmacokinetic parameters for aztreonam were calculated on the basis of a 2-compartment open model. Serum concentrations of aztreonam at 10 minutes after administration were approximately 100 micrograms/ml in all subjects, regardless of renal function (HPLC assay). The mean serum half-life during the alpha-phase showed no important variation with renal function. The mean serum half-life during the beta-phase was 1.8 hours in normal subjects and 8.4 hours in haemodialysis patients (HPLC assay). There was a linear correlation between the serum clearance of aztreonam and creatinine clearance. The mean cumulative urinary recovery of aztreonam in 48 hours was 60 to 70% of the administered dose in normal subjects but this was reduced in the presence of renal insufficiency. SQ 26,992, the microbiologically inactive metabolite of aztreonam resulting from hydrolytic opening of the beta-lactam ring, was undetectable in the serum of normal subjects but was found in low levels in uraemic patients. Half of a 1g intravenous dose of aztreonam was eliminated during 4 hours of haemodialysis. Guidelines for administration of aztreonam in the presence of renal failure are given.

Adult↗