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M Kettner

Publications and source records attributed to M Kettner.

At least 37 records · Page 2Linked to original sources

Clinical experience with simvastatin compared with cholestyramine.

Simvastatin (MK733), derived from lovastatin by substituting CH3 for H at the 2' position, is a potent hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor. Its cholesterol-lowering effect in 40 patients with heterozygous familial hypercholesterolaemia was more pronounced (an LDL-cholesterol reduction of 43%) than that of cholestyramine monotherapy in a matched group of 20 patients (30% reduction). The combination of the 2 drugs for 50 patients who tolerated cholestyramine was even more effective (a 54% reduction of LDL-cholesterol). The other changes were as follows: total cholesterol (simvastatin [S] -36%, cholestyramine [C] -23%, both drugs in combination [S + C] -45%); HDL-cholesterol (S +16%, C +9%, S + C +20%); triglyceride (S -21%, C +11%, S + C -17%); and the apolipoprotein B/apolipoprotein A ratio (S -51%, C -39%, S + C -67%). Cholestyramine caused more gastrointestinal adverse effects (12 of 20 patients), whereas a transaminase increase was seen both with cholestyramine (2 of 20 patients) and simvastatin (3 of 40 patients) and with the combination (6 of 50 patients). Treatment with simvastatin decreases the atherogenic potential of plasma more than cholestyramine monotherapy and causes fewer adverse effects. For those patients who tolerate cholestyramine, the combination of the drugs is even more potent.

Adult↗

Development of gentamicin resistance in gram-negative bacteria in Czechoslovakia and correlation with its usage.

Widespread use of gentamicin in Czechoslovakia began in 1975 when it became more available, although its use remained restricted until 1986. Starting in 1980 a remarkable increase in gentamicin resistance was observed in Pseudomonas aeruginosa, Klebsiella, Enterobacter and several Proteus species, especially Proteus rettgeri. A large proportion of gentamicin-resistant strains came from the urine of hospitalized patients. In spite of infection control measures and restrictive antibiotic policy, gentamicin resistance has increased over the last years. In 1985 gentamicin resistance of bacteria in Czechoslovakia represented 18.2% and was higher than in Austria or the Federal Republic of Germany, for example, but lower than in Hungary, France, Greece and Italy. The usage of gentamicin has also increased. During the years 1982-1987 gentamicin usage in Czechoslovakia increased by one-half. In a representative collection of 69 gentamicin-resistant Gram-negative strains from seven regions of Czechoslovakia, the mechanisms of resistance to gentamicin, netilmicin, tobramycin and amikacin were studied. Production of acetyltransferases (AAC) and adenylyltransferases (ANT) was observed in 84% of strains. The majority of isolates produced AAC(3) enzymes (55%); production of ANT(2") represented the second most observed resistance mechanism (35%); only 14% of isolates produced AAC(6'). This resistance pattern correlates with patterns reported recently for Central and Southern Europe. Due to dissemination of plasmids coding for the AAC(3)-II enzyme, the majority of Czechoslovak gentamicin-resistant Gram-negative strains were also tobramycin- (87%) and netilmicin-resistant (68%). Amikacin remains the most effective aminoglycoside against multiresistant bacterial strains.

Acetyltransferases↗

Aminoglycoside resistance patterns in clinical isolates of Enterobacteriaceae from Czechoslovakia.

Multi-resistant Enterobacteriaceae isolated mainly from urine specimens from patients at the Department of Urology, Kramáre Hospital, Bratislava, were characterized for resistance phenotype. Seventeen gentamicin-resistant isolates were further studied for the presence of aminoglycoside-modifying enzymes. Five enzymes were detected: AAC(2'), AAC(3)-II, AAC non-characterized, ANT(2") and APH(3')-I. The substrate range of these enzymes was found to correlate with the resistance phenotype in most isolates. In our collection the AAC(3)-II enzyme that inactivates gentamicin, sisomicin, tobramycin and netilmicin was predominant. Predominance of this type of modifying enzyme has been observed also in resistant Gram-negative strains in Belgium, The Netherlands and Chile, in contrast to the United States, Federal Republic of Germany, Switzerland, Greece and Turkey, where ANT(2") has been the most common enzyme.

Acetyltransferases↗

Enzymatic modification of aminoglycoside antibiotics in gentamicin-resistant gram-negative bacteria.

An in vitro evaluation of 32 gentamicin-resistant, Gram-negative bacteria from hygiene-centres in Berne, Switzerland and Bratislava, Czechoslovakia, revealed that 24 strains produced gentamicin-modifying enzymes. Occurrence of acetyltransferases (AAC) was confirmed in 16 strains, adenylyltransferase (AAD) /2''/ was observed in 13 strains while 5 of the gentamicin-resistant strains produced both enzymes. All Czechoslovak strains were amikacin-susceptible, in amikacin-resistant Pseudomonas aeruginosa strains from Switzerland the presence of AAC/6'/ was found. In the majority of gentamicin-resistant, netilmicin-susceptible strains the occurrence of AAD/2''/ was observed. Gentamicin-resistance in the modifying enzymes producing strains was due either to production of an acetyltransferase or the adenylyltransferase except Swiss strains of Serratia marcescens where a simultaneous production of both types of the enzymes was noted. Twenty eight strains produced an enzyme modifying aminoglycosides of any kind.

Acetyltransferases↗

Hepatic and plasma lysosomal enzyme activity in shock-like state following administration of polysaccharide-protein complex isolated from Candida albicans.

Polysaccharide-protein complex (PPC) derived from the cell walls of Candida albicans exerts several pathophysiological effects in laboratory animals similar to the symptoms of shock found at acute disseminated candidiasis. The present study evaluated the presumed fragility of hepatic lysosomes in rats in shock-like state following a single dose of PPC (25 mg/kg) administered intravenously, in terms of temporal changes in lysosomal enzymatic activity (cathepsin D, N-acetylglucosaminidase) in four sedimentable fractions and supernatant of liver homogenate after differential centrifugation, as well as in plasma. A reduction of sedimentable lysosomal activity (13,000 X g) was observed during the first hours (3-5 h) after administration of PPC with both lysosomal hydrolases, accompanied by a concomitant increase in the unsedimentable activity that represented the enzymatic activity released from disrupted lysosomes. Plasma levels of cathepsin D and N-acetylgucosaminidase had the same pattern of changes, reaching the maximum level 2-3 h after administration of PPC with a tendency of returning to the control levels by 12 h. Thus PPC from Candida albicans appears to have similar effects upon integrity of hepatic lysosomes as bacterial endotoxins have by labilizing the lysosomal membrane.

Acetylglucosaminidase↗

Antitrichomonadal and other biological effects of sugar hydrazones and phenylosazones.

When investigating the possible antitrichomodal effect of 41 phenylsazones, nitro- and dinitro-phenylhydrazones a significant inhibitory effect on multiplication of Trichomonas foetus could be detected in 14 derivatives; eight derivatives were ineffective, other derivatives exhibited only a slight effect. The inhibitory effect of most compounds increased after acetylation. Toxicity of seven effective compounds was determined in vivo. Mutagenicity of these compounds was followed with microorganisms and their cytotoxicity with tumor EAC cells. Two of the effective compounds exhibited also a significant mutagenic effect, three of eight compounds had a pronounced cytotoxic effect, three of eight compounds had a pronounced cytotoxic effect in vitro on the EAC cells, in which they inhibited mainly the incorporation of adenine.

Animals↗

Radiation-induced changes in gentamicin pharmacokinetics.

Decreased clearance of i.v. or intratracheally administered gentamicin was observed in rats following single whole-body irradiation. 6 Gy 60Co. reaching its lowest rate on the 7th post-irradiation day. Simultaneously the absorption rate of gentamicin from the lungs was found to be increased.

Animals↗

Inhibition of Tritrichomonas foetus by vermiculine in vitro.

The macrolide aglycosidic antibiotic vermiculine, added to the cultivation medium to a concentration of 30 micogram/ml, has an in vitro inhibitory effect on Tritrichomonas foetus. The agent interacts rapidly with the cells, causing irreversible changes after several hours of action. The changes are not repaired on removing the agent; the cells suffer from a rapid inhibition of nucleic acid synthesis, the protein synthesis remaining intact.

Animals↗

Pharmacokinetics of gentamicin administered intratracheally to rats.

The pharmacokinetics of intratracheally instilled and intravenously injected gentamicin were compared in the rat and analyzed by a one-compartment open model. The maximum concentration of gentamicin in plasma occurred within 10 min after intratracheal instillation. Considerable amounts of gentamicin were absorbed from lungs after intratracheal instillation, as shown by its concentrations in plasma and elimination in urine. The data suggest that the absorption of gentamicin from the pulmonary system would be sufficient to maintain therapeutic levels of this agent in plasma.

Animals↗

R plasmids coding for gentamicin, tobramycin, and carbenicillin resistance in Serratia, Klebsiella and Escherichia coli strains from a single clinical source.

Serratia marcescens, Klebsiella sp. and Escherichia coli strains bearing transferable resistance to aminoglycoside antibiotics, namely, gentamicin, tobramycin, kanamycin, streptomycin, lividomycin, and carbenicillin, as well as to a series of more classical drugs, began to emerge in materials from the Frankfurt University Hospital. Plasmids from Serratia, Klebsiella, and E. coli exhibit a broad host range in that they are transferable to E. coli, Proteus mirabilis and Salmonella typhimurium receipients. They are not transferable to Pseudomonas aeruginosa, although in that species plasmids of gentamicin and tobramycin resistance, was well as of resistance to further drugs, were detected in that area as early as in 1973. High-level carbenicillinase has been identified in Serratia and Klebsiella plasmids associated with drug resistance to aminoglycoside antibiotics.

Anti-Bacterial Agents↗