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Biomedical subjects

L Xerri

Publications and source records attributed to L Xerri.

122 records · Page 7Linked to original sources

Experimental infections for the evaluation of beta-lactamase resistance.

The antibacterial activity and pharmacokinetics of the beta-lactamase-stable cephalosporin cefuroxime and the gram-negative beta-lactamase-susceptible cephalosporin cefazolin were compared in two contrasting infection models in which Proteus morganii 82, which produces chromosomally mediated beta-lactamase, was the pathogen. In the rat paw model, characterized by high numbers of localized bacteria, cefazolin was destroyed at the site of infection and consequently did not produce a therapeutic response. In the mouse intraperitoneal model cefazolin was also inactive, despite peritoneal concentrations being unaffected by high counts of the beta-lactamase-producing P. morganii in the body cavity. In contrast the pharmacokinetics of cefuroxime was unaffected by the presence of the beta-lactamase-producing P. morganii, and good therapeutic responses were seen in both models.

Animals↗

The kinetics of cefuroxime in ascitic and pleural fluid.

Adequate drug concentration at the infection site is a very important objective of antibiotic therapy. In this study we investigated the pharmacokinetics of the new methoximine, cefuroxime, in peritoneal and pleural fluids in 16 patients. After a 1-g dosage of cefuroxime, its concentration reaches a peak in ascitic fluid within 4-5 h. With a 2-g dose the peak level is reached in 2-3 h. After 5 h, cefuroxime concentration in ascites exceeds that in serum. Cefuroxime diffuses readily into the peritoneal space, where high concentrations (8-10 mcg/ml) are maintained for at least 6 h. Data on the kinetics in pleural fluid also seem to show high antibiotic diffusion rates, even if concentrations are never as high as those in blood at the same time following 1 g i.v. These favorable kinetic properties are probably due to low serum protein binding and to slow renal excretion.

Ascitic Fluid↗

Pharmacokinetic studies of cefuroxime in patients with liver cirrhosis.

Blood levels and urinary excretion of 6R,7R-3-carbamoyloxy-methyl-7-(2Z)-2-methoxyimino-(fur-2-yl)-acetamido-ceph-3-em-4-carboxylate sodium salt (cefuroxime) were determined in cirrhotic patients without ascites and in healthy volunteers after an i.m. injection of 750 mg and an i.v. injection of 1 g. An average peak serum level of 23.9 micrograms/ml in the case of cirrhotic patients and 22.5 micrograms/ml in the case of volunteers was reached 0.5 h after the i.m. dose, followed by a gradual decrease. An average serum level of 78.8 micrograms/ml in the case of cirrhotic patients was obtained 5 min after i.v. injection. During the first 6 h after administration of the 750 mg i.m. dose and the first 4 h after the administration of the 1 g i.v. dose, 90% of the administered dose were excreted in the urine, in the case of both cirrhotic patients and volunteers. These results show that the pharmacokinetic features of cefuroxime are not affected in cirrhotic patients without ascites; therefore the antibiotic is particularly suitable for acute infections in hospital, and also for cirrhotic patients without ascites without any difference in the dosage.

Adult↗

Pharmacokinetics of intravenous and intraperitoneal cefuroxime during peritoneal dialysis.

We investigated the pharmacokinetics of cefuroxime sodium, a new parenteral beta-lactam antibiotic, in 15 patients with stable chronic renal failure during intermittent peritoneal dialysis (IPD). Eight patients were administered 1 g cefuroxime as an intravenous bolus 1 h before the start of dialysis. Mean plasma levels of cefuroxime fell from 80 mcg/ml at 1 h to 40 mcg/ml at 6-8 h. At 24 h, concentrations were higher than 20 mcg/ml. In peritoneal fluid cefuroxime reached 16.7 mcg/ml at 1 h and 7.55 mcg/ml at 6 h. Seven patients received cefuroxime added to the dialysis solution at a dose of 2.5 g/10 liters. After 6 h of dialysis, cefuroxime reached plasma levels of 60 mcg/ml; after 24 h, concentrations were 37.5 mcg/ml. These results demonstrate that cefuroxime, administered by the i.v. route, easily diffuses from blood to peritoneal fluid and, from peritoneal fluid to blood when added to the dialysis solution. In both cases concentrations reached by cefuroxime are sufficient to treat peritoneal infections associated with peritoneal dialysis.

Adult↗

Lymphocyte functions in the rat spleen at various times after urethan administration.

The effect of urethan on various spleen-lymphocyte functions was studied in the rat for 45 days after administration of the carcinogen. For 3 days following the last injection of urethan, the total cell number and LPS reactivity were greatly reduced. Certain reactivities, probably T-cell dependent functions, such as responsiveness to the in vitro mitogenic effect of PHA, Con A, and primary stimulation by histocompatibility alloantigens in the one-way reaction, were selectively enriched during the first 2 days. Thereafter several dissociations of these lymphocyte functions can be observed: i.e., various intervals succeed during which one function may be enriched and other(s) diminished. It seems that the kinetics of enrichment, decay and recovery of the T-cell subsets involved in the reactions investigated follow a distinctive profile for each one of them. It is suggested, as a working hypothesis, that the unbalanced situations derived from the time-course discordance of the quantitative changes in the various lymphocyte functions may allow, or even enhance, tumor development.

Animals↗

Mos oncogene expression in human ovarian tumors.

The expression of the mos proto-oncogene was investigated in frozen sections from 15 ovarian adenocarcinomas, 1 seminoma, 1 immature teratoma and 2 benign stromal tumors by in situ RNA/RNA hybridization with a [35S] labeled mos probe. The presence of mos transcripts was detected in one germ cell tumor and three ovarian carcinomas. The putative role of the mos proto-oncogene activation is discussed.

Adenocarcinoma↗