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K Sack

Publications and source records attributed to K Sack.

At least 109 records · Page 6Linked to original sources
PubMed1979

Experimental investigations of the renal tolerance of cefazedone.

Renal tolerance tests in Wistar rats (n = 40) over 12 days showed that the tubulotoxic threshold dose of the cephalosporin antibiotic (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid acid (cefazedone, Refosporen) is 2000 mg/kg/day when the cell excretion rates in the urine are used as the parameter of toxicity. It is concluded that cefazedone and cefazolin are similar in respect of their nephrotoxicity.

Animals↗
PubMed1979

Clinical study on the tolerance of cefazedone.

Tolerance of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen) (3X1 g or 3X2 g/day; dosage interval 8 hours; duration of treatment 1 week) was examined in i.v. administration to 20 patients using numerous parameters. In 2 patients treatment was stopped sooner on account of the development of a morbilliform rash; a causal relation between this and the chemotherapy seemed probable in one case and possible in the other. 1 patient developed a transitory thrombocytosis without clinical symptoms, in 2 female patients yeasts were found in the mid-stream urine. Changes in the red or white blood count, in serum electrolytes, in bilirubin or increases in the activity of serum enzymes were not found. Indications of disturbances in renal function could be ruled out by examinations of endogenous creatinine clearance; repeat analyses of excretion of erythrocytes, nucleated cells and various urinary enzymes did not provide any indication of even slight renal lesions. Local tolerance of the substance was good.

Adult↗
PubMed1979

[Animal studies on nephrotoxicity of seven aminoglycoside antibiotics during long-term treatment (author's transl)].

In studies on female Wistar rats (n = 133) the nephrotoxicity and kidney concentrations of amikacin, butirosin, gentamicin, kanamycin, bekanamycin, sisomicin, and tobramycin were examined during four weeks therapy and four weeks convalescence. Maximum doses recommended for human therapy were administered i.m. at 12-h intervals. For evaulation of the tubulotoxic effect the excretion rates of tubular cells were determined daily. At weekly intervals animals were sacrificed for determination of the kidney aminoglycoside concentration, which was assayed microbiologically. The application of all aminoglycosides resulted in an increase of excreted tubular cells, but the extent and course of cell excretion varied for the different aminoglycosides. An initial peak after different periods of therapy and later on a decrease of cell excretion was found for all aminoglycosides. These periods of high and low loss of tubular cells corresponded to aminoglycoside accumulation and saturation in the kidneys. During the first week of treatment only gentamicin was tolerated without signs of renal damage. Initially the nephrotoxic effect was strongest for bekanamycin, but at the end of the first week kanamycin and sisomicin produced similar distinct side effects. Thereafter the highest cell excretion rates were continuously caused by sisomicin.

Aminoglycosides↗
PubMed1979

[Netilmicin and tobramycin: comparative evaluation of pharmacokinetics, nephrotoxicity, and therapeutic efficacy in animal studies (author's transl)].

Pharmacokinetics, nephrotoxicity, and therapeutic efficacy of (2S-cis)-4-O-[3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]-2-deoxy-6-O-[3-deoxy-4-C-methyl-3-(methyl-amino)-beta-L-arabinopyranosyl]-N1-ethyl-D-streptamine sulfate (netilmicin) and tobramycin were investigated in rats. The excretion rates of tubular cells and of the urinary enzyme malic dehydrogenase served as parameter of nephrotoxicity. Both compounds were, similar to other aminoglycosides, tubulotoxic within the range of dosages used for human therapy. Netilmicin, however, produced less renal damage than did tobramycin in all dosages applied. Pharmacokinetic studies revealed lower renal concentrations of netilmicin after repetitive administration. Experimental chemotherapy of the chronic E. coli pyelonephritis in rats with both aminoglycosides resulted in a significant reduction of the renal bacterial counts. In spite of approximately identical serum concentration curves and in vitro activity, especially the low dosage of netilmicin led to more favourable therapeutic results than equal doses of tobramycin. These animal experiments suggest higher renal tolerance and efficacy of netilmicin.

Animals↗
PubMed1978

[Therapeutic studies on two different models of experimental pyelonephritis (author's transl)].

By transurethral instillation of a suspension of a serum resistant E. coli strain (serotype O25:19:12), chronic pyelonephritis is induced in rats, if systemic and local defense mechanisms are impaired by estradiol application. Without hormonal treatment a similar infection can be achieved with a more virulent E. coli strain (serotype O2:1:4). Due to the chronic course of the renal infection in either model, beginning of therapy may be delayed (e.g., 10 days after infection) thus imposing difficult therapeutic conditions on the efficacy of antibiotics to be tested. Evaluation of antibiotics in both models produced differential therapeutic results. In spite of equal MIC's for the applied E. coli strains, gentamicin and particularly cefazolin treatment was less effective in the estradiol treated rats than in those without hormone application. Cefuroxime therapy produced favourable results in either model. The different therapeutic efficacy in both models is to be explained by differences in host resistance to infection. It is suggested that by simultaneans testing of antibiotics in either model, it will be possible to estimate to what extent the therapeutic efficacy of antibiotics depends on the support of intact host defense mechanisms.

Animals↗
PubMed1978

[Amikacin and kanamycin. Comparative experimental studies on nephrotoxicity].

The nephrotoxicity of amikacin and kanamycin was investigated in 110 female albino Wistar rats. The drugs were administered i.m. in different dosages (2.5; 5; 10; 20; 100 and 500 mg/kg/day; dosage interval: 12 h) over a period of 5 days. The excretion of tubular cells and urinary enzymes (MDH, LDH and GOT) was assessed before, during and after administration of the antibioitcs. In addition, the concentration of serum urea was analysed and the kidneys were investigated histologically. These investigations show that both the aminoglycosides are tubulotoxic, in higher dosages glomerulotoxic, too. The toxic threshold doses were found to be within the range of human therapeutic dosages: amikacin: 10 mg/kg/day, kanamycin: 5 mg/kg/day.

Amikacin↗
PubMed1978

[The differentiation of potential nephrotoxicity of various aminoglycosides in animal experiments].

Experimental differentiation in the animal of nephrotoxicity of various aminoglycosides. Animal experiments showed that all aminoglycosides cause similar toxic tubular and glomerular damage when investigated by qualitative morphology. Quantitative differences in tubular nephrotoxicity of gentamicin, tobramycin, sisomicin, kanamycin, kanendomycin, amikacin, and butirosin were demonstrable by evaluation of the excretion rates of tubular cells and urinary enzymes in rats. By this means dose-effect-relationships were found resulting in reproducible different toxic threshold doses for each antibiotic, and thus in a scale of increasing nephrotoxicity. The aminoglycosides differed by their affinity to kidney tissue as measured by determination of the accumulating renal concentrations of the drugs at different times during multiple-dose administration. This had a modifying influence on excretion rates of cells and enzymes affecting the scale of toxicity in long-term studies. Comparative investigations on nephrotoxicity in rats and guinea pigs gave similar results. In addition, a study in man suggested that the test results of nephrotoxicity are not species-specific. For human therapy it is concluded that even more caution should be practised with the new aminoglycosides than with gentamicin in order to avoid renal damage.

Aminoglycosides↗
PubMed1977

[Experimental studies on the renal tolerance of cefuroxime (author's transl)].

The potential renal tolerance of cefuroxime was investigated in 80 female albino Wistar rats and compared with that of cephacetrile. The drugs were administered i.m. in different dosages (1000, 2000, 3000 and 5000 mg/kg/day; dosage interval: 12 h) over a period of five days. The excretion of tubular cells and urinary malic dehydrogenase was assessed before, during and after administration of the antibiotics. In addition, the concentration of serum urea was analysed and the renal histology was examined. The following toxic threshold doses were estimated: cefuroxime 5000 mg/kg/day, cephacetrile 3000 mg/kg/day. In comparison with other cephalosporines cefuroxime belongs to those antibiotics with which a high degree of renal tolerance is demonstrated.

Animals↗
PubMed1976

[Side effects of aminoglycosides: nephrotoxicity (author's transl)].

Animal experiments showed that all aminoglycosides cause similar toxic tubular and glomerular damage when investigated by qualitative morphology. Quantitative differences in the tubular nephrotoxicity of gentamicin, tobramycin, sisomicin, kanamycin, kanendomycin, amikacin, and butirosin can be demonstrated experimentally by evaluation of the excretion rates of tubular cells and urinary enzymes in rats. By this means dose-effect relationships were established resulting in varying reproduceable toxic threshold doses for each antibiotic, and thus in a scale of increasing nephrotoxicity. The aminoglycosides differed in their affinity to kidney tissue as measured by determination of the accumulating renal concentrations of the drugs at different times during multiple-dose administration. This had a modifying influence on excretion rates of cells and enzymes affecting the scale of toxicity in long-term studies. Comparative investigations on nephrotoxicity in rats and guinea pigs gave similar results. In addition, a study in man suggested that the test results of nephrotoxicity are not species-specific. For human therapy it is concluded that even more caution should be practised with the new aminoglycerides than with gentamicin in order to avoid renal damage.

Amikacin↗
PubMed1976

Comparative assessment of cylacillin and ampicillin by experimental therapy and by serum level determinations in rats and mice.

Therapy of chronic E. coli pyelonephritis in rats was equally effective with cyclacillin and oral ampicillin, whereas intramuscular ampicillin had a significantly higher therapeutic activity than oral cyclacillin. Serum concentrations in rats and mice were consistently higher with cyclacillin than with ampicillin and showed great variations depending on the animal species. It was concluded that there is a good correlation between in vivo and in vitro activity of both antibiotics, provided that the serum levels are taken into consideration. On this basis it may be predicted that a man cyclacillin will exhibit lower therapeutic activity in gram-negative infections than ampicillin.

Administration, Oral↗
PubMed1975

The diagnostic value of enzymuria, cell excretion, and proteinuria in experimental renal diseases.

Enzymuria, urinary cell excretion and proteinuria were simultaneously determined in renal diseases of female Wistar rats in order to investigate the diagnostic value of urinary enzymes. Investigations were carried out on rats with E. coli-pyelonephritis facilitated by oestradiolundecylate, aminonucleoside nephrosis, aminoglycoside induced renal lesions and pyelonephritic animals treated with therapeutic and toxic doses of tobramycin. --From the results of these studies it was concluded that the main diagnostic value of urinary enzymes is detection of drug induced tubular lesions in individuals with preexisting renal diseases.

Animals↗
PubMed1975

[Experimental study in rats on the renal compatibility of cephalothin and cephalothin-aminoglycoside combinations (author's transl)].

The possible nephrotoxity of cephalothin and the antibiotic combinations cephalotin-gentamicin and cephalothin-tobramycin was investigated in standardized animal experiments. Toxicity parameters were blood-urea concentration, the urinary enzymes GOT, LDH, MDH and the cell excretion rate, supplemented by histological investigations of the kidneys. Compared with other cephalosporine derivates, the antibiotic cephalothin in a toxic threshold-dose of 3000 mg/kg/day proved to be realtively well tolerated by the kidneys. On comparison with the respective monotherapy, the renal tolerance for cephalothin-aminoglycoside combinations was reduced. The clinical value of these findings is discussed.

Aminoglycosides↗