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Biomedical subjects

A Georgopoulos

Publications and source records attributed to A Georgopoulos.

At least 109 records · Page 6Linked to original sources
PubMed1988

In-vitro activity of fleroxacin.

Fleroxacin is a new synthetic fluorinated quinolone antimicrobial agent. The in-vitro activity of fleroxacin and five comparative quinolones against 541 clinical isolates was studied. Minimum inhibitory concentrations (MIC90) of fleroxacin were less than or equal to 2.0 mg/l for Enterobacteriaceae, less than or equal to 8.0 mg/l for Pseudomonas aeruginosa and 1.0 mg/l for Acinetobacter calcoaceficis and 8 mg/l for streptococci. The activity of fleroxacin was comparable with that of ofloxacin, pefloxacin and norfloxacin, but less than that of ciprofloxacin. All quinolones showed little difference between MIC and minimum bactericidal concentrations (MBCs).

Anti-Infective Agents↗
PubMed1987

In vitro evaluation of teicoplanin and other antimicrobials against streptococci group D bacteria.

In vitro activities of teicoplanin were compared with those of ampicillin, imipenem, rifampicin, coumermycin and vancomycin against clinical isolates of Streptococcus faecalis (n = 100) and Streptococcus faecium (n = 30). Against Str. faecalis, ampicillin and imipenem had an MIC90 and MBC90 of 3.9 micrograms/ml. Coumermycin and rifampicin had poor bactericidal activity with MBC90 values of 31.2 and 62.5 micrograms/ml. Teicoplanin was extremely active with an MIC90 of 0.95 microgram/ml and an MBC90 of 1.86 micrograms/ml.

Anti-Bacterial Agents↗
PubMed1986

[Clinical microbiology and chemotherapy in the spirit of Escherich].

One hundred years ago Billroth and Escherich were engaged with microbiological investigations. They are representative of intimate relationship between clinic and microbiological laboratory. In 1979 the Department of Chemotherapy was founded and this tradition was resumed and continued.

Anti-Bacterial Agents↗
PubMed1986

Synthesis and structure-activity relationships of naftifine-related allylamine antimycotics.

Naftifine (1) is the first representative of the new antifungal allylamine derivatives. Its biological activity is strictly bound to specific structural requirements that are unrelated to those of known antifungals. A tertiary allylamine function seems to be a prerequisite for activity against fungi. By systematic variation of the individual structural elements in 1, detailed structure-activity relationships are defined in which the phenyl ring is the structural feature permitting the widest variations. Versatile synthetic routes to allylamine derivatives and comparative biological data are presented.

Allylamine↗
PubMed1986

Ubiquinone-8 stimulates phagocytosis in macrophages by modulation of the kinetics of the Fc receptor.

The effect of exogenous ubiquinone-8 (Q8) on IgG- and C3b-mediated phagocytosis of sensitized sheep red blood cells and of opsonized Staphylococcus aureus by macrophages was studied by morphological and quantitative methods. Q8 stimulated the initial events of phagocytosis, that is, attachment and ingestion, in which occupancy of the Fc receptor by IgG was shown to be of critical significance. The kinetics of competitive inhibition of phagocytosis of opsonized bacteria by macrophages by using Fc fragments suggested the intimate role of the kinetics of the Fc receptor in the initial events of phagocytosis and, further, the modulation of the kinetics of the Fc receptor by Q8 as the basis of enhanced phagocytosis by Q8.

Animals↗
PubMed1986

The utility of diffusion chambers as models for the description of drug disposition.

Tissue cages were employed to explore the diffusion processes of several cephalosporins into extravascular fluids. Concentrations of cefotaxime in serum and in subcutaneous chambers increased proportionally to the amount of the drug injected. Administration of single equal doses of cephalothin, cephaloridine and cefotaxime resulted in different concentration-time courses in the serum and in diffusion chambers. These observations suggest that diffusion chambers are linked to the tissue at the implantation site. None of the classical compartmental approaches can be applied to evaluate the kinetics of drug diffusion into tissue cages. Correlations of total or non-protein bound drug concentrations in tissue cages to those in the peripheral compartment assumed concentration and time dependent diffusion processes. No specific diffusion constant based on the law of Fick could be derived for the diffusion chambers used in this study. Concentration-time courses in serum and interstitial fluid can be simultaneously evaluated according to pharmacokinetic-pharmacodynamic models. Based on the equation describing the effect site this model can be used to simulate drug concentrations in tissue cages by varying the dose size or the dose interval.

Analysis of Variance↗
PubMed1985

Phospholipase-A1 and -A2 in experimental acute pancreatitis in rats.

Using a standardized model of bile-induced acute pancreatitis, the reaction of phospholipase-A1 activity was investigated in parallel to that of phospholipase-A2, as well as their relationship to the pathomorphological spread of pancreatitis. While the measurement of the total free fatty acids (FFA) in serum as metabolites of phospholipase-A activity indicated variable reactions with the average remaining the same (0.186 +/- 0.15 to 0.192 +/- 0.153 mEq/l), phospholipase-A2 exhibited a highly significant increase from 9.6 +/- 2.2 to 18.2 +/- 5.4 nmol/ml/min (P less than 0.01). It was demonstrated that in parallel phospholipase-A1 also showed a highly significant increase from 2.5 +/- 1.2 to 6.7 +/- 3.1 nmol/ml/min (P less than 0.01). In relation to the pathomorphological score, both phospholipases showed a small increase at a low score (edema to focal necrosis), whereas in groups with a larger spread of the pancreatitis, score 5 or 6 (extended necrosis to retroperitoneal necrosis), the increase was substantially clearer. As a result of these findings, we conclude that phospholipase-A1 could possibly be used as phospholipase-A2 as an indicator of the severity of acute pancreatitis and that it should be taken into consideration in the very promising therapy with phospholipase-A-antagonists.

Acute Disease↗
PubMed1985

Methicillin- and gentamicin-resistant Staphylococcus aureus: susceptibility to fosfomycin, cefamandole, N-formimidoyl-thienamycin, clindamycin, fusidic acid and vancomycin.

The in vitro activity of fosfomycin against 90 strains of methicillin- and gentamicin-resistant Staphylococcus aureus was studied in an in vitro microtitre system using Mueller-Hinton broth supplemented with glucose-6-phosphate. In parallel the antistaphylococcal activity of cefamandole, N-formimidoyl-thienamycin, clindamycin, fusidic acid and vancomycin was determined with the same organisms. The following MIC50 (MIC95) values were obtained: fosfomycin 8 (128) mg/l, cefamandole 8 (greater than 64) mg/l, clindamycin 0.25 (16) mg/l, fusidic acid less than 0.25 (less than 0.25) mg/l, vancomycin 1 (2) mg/l and N-formimidoyl-thienamycin 4 (16) mg/l. A high MIC/MBC ratio was noted for cefamandole, in contrast to fosfomycin.

Cefamandole↗
PubMed1984

[Biology and clinical aspects of intracellular resistance to infection].

Normal functioning of phagocytic cells depends upon the integration of chemotaxis, phagocytosis, degranulation and oxidative metabolism. The availability of in vitro assays for the separate quantitative evaluation of each function has permitted the definition of specific congenital and acquired abnormalities of phagocytic cells which are associated with defective mechanisms of host resistance. The appreciation of complex and often adverse effects of certain systemic diseases and pharmacological agents on the phagocytes, as well as the use of new approaches to therapy underline the importance of assessing the role of phagocytic cells in states of impaired host defence. In addition, cellular immune mechanisms involving the interaction of T-cells and macrophages contribute essentially to the proper functioning of intracellular host defence, as indicated by the delayed type hypersensitivity reaction.

Antigens, Bacterial↗
PubMed1984

[Perioperative cefamandole prevention in aortocoronary bypass operations: the course of serum levels in extracorporeal circulation].

Antibiotic prophylaxis with 2 g Cefamandole at induction of anaesthesia was performed in 12 male patients undergoing aortocoronary bypass surgery. Caused by hemodilution, there was a marked decrease of serum concentration at the beginning of extracorporeal circulation, from 110.96 +/- 40.29 mcg/ml to 70.89 +/- 34.65 mcg/ml within 10 min. During extracorporeal circulation, elimination was as fast as before and after perfusion. 240 min after application, mean serum concentrations of 16.80 +/- 9.32 mcg/ml were measured. Failure of antibiotic prophylaxis in operations exceeding 4 h might be due to unadaequate antibiotic concentrations, beyond the minimal inhibitory concentration for the pathogens, reported to cause infections after cardiac operations.

Adult↗
PubMed1984

Concentrations of doxorubicin in renal interstitial fluid after peripheral intravenous and intrarenal artery infusion in dogs.

Concentrations of doxorubicin-hydrochloride in renal interstitial fluid were compared following peripheral and intrarenal artery infusion of 2 milligrams per kilogram body weight using a diffusion chamber model. After intra-arterial application, the mean peak concentration in renal interstitial fluid was approximately 30 times higher than that after intravenous infusion (66.49 and 2.38 nanograms per milliliter respectively). After peripheral application, the concentrations in serum and renal interstitial fluid, as well as the cumulative urinary excretion, were measured until day 7 of the experiment, and the pharmacokinetic parameters were calculated. The diffusion chamber model used proved itself to be suitable for simultaneous and continuous measurement of cytostatic drug concentrations in serum and renal interstitial fluid.

Animals↗
PubMed1984

Absorption of doxorubicin-hydrochloride and mitomycin-C after instillation into noninfected and infected bladders of dogs.

The described investigations were carried out in order to determine the degree of absorption of doxorubicin, and mitomycin-C after intravesical instillation into noninfected or Staphylococcus aureus-infected bladders in beagle dogs. The drug concentrations in the bladder wall were determined using diffusion chambers with permeable membranes. Two hours after end of instillation of 10 mg. doxorubicin, a concentration of 1.4 ng. per ml. was measured in the bladder wall of noninfected animals, and 3.75 ng. per ml. in that of infected animals (p less than 0.05). The simultaneously measured serum concentration reached mean peak levels after 30 minutes. The concentrations in infected animals were 3 times higher (1.9 ng. per ml.) than in noninfected animals (0.6 ng. per ml.) (p less than 0.05). After instillation of 1 mg. per kg. bw. mitomycin-C the concentration in both groups of animals was below 0.06 micrograms per ml. Doxorubicin concentrations were determined with a radioimmunoassay and mitomycin-C with a micro-agar diffusion method.

Animals↗
PubMed1984

Cefotaxime and desacetyl-cefotaxime blood levels in hepatic dysfunction.

Serum levels of cefotaxime and desacetyl-cefotaxime were studied in 18 patients with hepatic cirrhosis after an intravenous bolus injection of 2 g of cefotaxime. Blood levels were independent of the degree of hepatic dysfunction and did not differ from those reported in normal individuals.

Adult↗
PubMed1984

Therapeutic relevance of penicillin-induced hypersensitivity of Staphylococcus aureus to killing by polymorphonuclear leukocytes.

There is an overwhelming body of evidence that certain Staphylococcus aureus strains become more sensitive to killing by polymorphonuclear leukocytes after their growth in media containing subinhibitory concentrations of penicillin. However, it is not clear to what extent this phenomenon contributes to the curative effect of penicillin in vivo. To explore its therapeutic relevance, we evaluated the interaction of staphylococci pretreated with penicillin in vitro with leukocytes in cell-proof diffusion chambers (porosity, 0.22 micron) implanted subcutaneously in rabbits. Under this in vivo environment, staphylococci pretreated with penicillin remained hypersensitive to leukocyte killing as under in vitro conditions. Furthermore, when the staphylococci were mixed with the leukocytes in chambers implanted intraperitoneally in mice which subsequently received intravenously a suboptimal dose of penicillin, they also became hypersensitive to leukocytic killing. However, because the staphylococcal growth rate was considerably reduced in vivo, the degree of penicillin-induced sensitivity to leukocytic killing was smaller than that obtained in test tube cultures; nevertheless, the enhanced killing was significant. Additional support that the curative effect of penicillin partly depends on its synergistic action with the leukocytes was provided by the relative decrease in virulence of staphylococci pretreated with penicillin in mice in which the cellular host defenses were already recruited at the focus of inoculation. These observations indicate that penicillin-induced hypersensitivity of staphylococci to leukocytic killing is not only an in vitro phenomenon, but an effect which has therapeutic relevance.

Animals↗
PubMed1983

Pharmacokinetics of high-dose methotrexate in dogs. An experimental model with diffusion chambers.

The usefulness of a diffusion chamber method for determination of concentrations of cytostatic drugs in the interstitial fluid of tissues was tested. Chambers with a permeable membrane (pore size: 0.45 micrometer) were implanted in the liver, kidney, bladder wall, and prostate of dogs. After administration of high doses of methotrexate (100 mg/kg body wt) the concentrations in the chamber fluid and in serum were measured simultaneously and repeatedly for 72 h. The method proved to be effective for collecting data on the distribution of drugs in different organs. The results show that knowledge of the serum concentration does not permit predictions of the drug concentration in the interstitial fluid of various tissues to be made.

Animals↗
PubMed1983

Evaluation of cytostatic drug concentrations in the kidney, bladder wall, and prostate by means of the diffusion chamber technique in dogs.

The usefulness of a diffusion chamber model for measurement of concentrations of cytostatics in the interstitial fluid of tissues was tested. Chambers (pore size of the membranes: 0.45 mcm) were implanted in the kidney, bladder wall, and prostate of dogs. The concentrations after application of Doxorubicin-hydrochloride (2 mg/kg body wt.) and high doses of Methotrexate (100 mg/kg body wt.) were measured simultaneously and continuously in serum and in the above organs. The investigations showed that knowledge of the plasma level alone does not permit a prediction of the concentrations in the organs to be made. The diffusion chamber technique proved itself to be relatively simple to perform, economical, and it provides reproducible values.

Animals↗