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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 106 (1983), S. 143-147 
    ISSN: 1432-1335
    Keywords: Doxorubicin ; Acute cardiac toxicity ; Prevention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In two groups of female patients with metastatic breast cancer who had all been pretreated with doxorubicin (350 mg/m2), acute cardiac effects following i.v. doxorubicin bolus injection (60 mg/m2) were recorded on the basis of systolic time intervals (STI). In six patients who received doxorubicin only the ratio between the heart-beat-corrected preejection period and left ventricular ejection time (PEPI:LVETI) as well as the PEP index were found to be significantly increased with a peak at 6 h following drug infusion (P〈0.001). Another six patients received an identical chemotherapeutic regimen and, in addition, a combination of tocopherol (200 mg i.m. 6 h before treatment) and nifedipine (60 mg p.o. daily from 2 days before doxorubicin infusion). In the pretreatment group, the PEPI: LVETI ration and PEP index remained unchanged during the posttreatment period. Pharmacokinetic analysis of drug concentrations in the plasma revealed a significantly accelerated distribution and elimination of doxorubicin after combined tocopherol and nifedipine pretreatment, although no statistically significant differences could be found in calculated drug levels in the peripheral compartment between both treatment groups. Our results indicate that acute cardiac reactions reflected by changes in STI values can be prevented by combined tocopherol and nifedipine pretreatment.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 303-307 
    ISSN: 1432-1041
    Keywords: diltiazem ; verapamil ; calcium antagonists ; angiotensin II ; plasma catecholamines ; hypotensive effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the possible functional antagonism of the calcium antagonists diltiazem and verapamil of the sympathetic nervous system and the renin-angiotensin system, their influence on blood pressure, heart rate, plasma catecholamines and renin activity (PRA), and on the reaction of these parameters to exogenous noradrenaline (NA) and angiotensin II, was investigated in 8 normotensive volunteers. Intravenous diltiazem or verapamil caused a sharp, shortlasting decrease in systolic and diastolic blood pressure, with a maximum 1–3 min after injection and a duration of 10–15 min. Even a further infusion of the calcium antagonists was unable to maintain the initial hypotensive effect. The cessation of the hypotensive effect was not due to reflex stimulation of the sympathetic nervous system, as indicated by unchanged plasma NA and adrenaline levels in the case of diltiazem, but was associated with an increase in PRA. During the administration of diltiazem and verapamil, the increase in blood pressure in response to the infusion of NA and angiotensin II was attenuated; the increase in diastolic pressure was mainly affected. The inhibition was more pronounced at the higher infusion rate of NA and angiotensin II. On the basis of these findings it is suggest that the hypotensive activity of calcium antagonists can be at least partly attributed to a reduction in vascular tone which is maintained by the postjunctional action of noradrenaline and angiotensin II.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 29 (1985), S. 49-53 
    ISSN: 1432-1041
    Keywords: digoxin ; digoxin serum concentration ; drug interaction ; digoxin clearance ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An open, randomized, single-blind cross over trial to investigate phenytoin-digoxin interactions at steady state was performed in 6 healthy male volunteers. Coadministration of phenytoin caused a significant reduction in the elimination half-life of digoxin from 33.9 to 23.7 h and a diminution in AUC0–48 from 31.6 to 24.4 ng · ml−1 · h. Renal digoxin clearance was not significantly altered from 135.7 to 120.3 ml · min−1. Assuming no change in β-acetyldigoxin absorption, the in decrease time-course the serum digoxin concentration was due to a significantly increased total digoxin clearance from 258.6 to 328.3 ml · min−1. An insignificant reduction in the digoxin distribution volume from 749.4 to 668.0 l was also observed. No relevant change in the pharmacokinetic parameters (elimination half-life, area under the serum concentration time-curve, protein binding) of phenytoin was observed when phenytoin and digoxin were co-administered. The data suggest that with this drug combination the serum digoxin concentration should be carefully monitored and, if necessary, the daily digoxin dose should be increased.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 604 cephalotinresistenten Bakterienstämmen erwies sich Cefotaxim im Agar-Diffusionstest verglichen mit Cefamandol, Cefoxitin und Cefuroxim als die wirksamste Substanz gegen gramnegative Bakterien. 70 Patienten mit akuten Harnwegsinfekten, Septikämie, Pneumonie und anderen schweren Infektionen wurden mit Cefotaxim behandelt. Die Dosierung betrug 2–12 g, je nach Nierenfunktion und Art der Infektion. Bei komplizierten Harnwegsinfektionen konnte eine Heilung bei 20 von 28 Patienten erreicht werden, acht Patienten zeigten keinen Therapieeffekt. Von 15 Patienten mit akuten unkomplizierten Harnwegsinfektionen konnten alle geheilt werden. Bei acht von 14 Patienten mit Sepsis und bei acht von 13 Patienten mit anderen schweren Infektionen konnte ein Erfolg erzielt werden.In vitro empfindliche Keime, die nicht eliminiert werden konnten oder unter der Behandlung neu auftraten, waren:Staphylococcus aureus (3),Escherichia coli (3),Klebsiella sp. (1),Enterobacter sp. (2),Serratia sp. (3),Proteus mirabilis (2),Achromobacter sp. (1) undPseudomonas aeruginosa (9). Nebenwirkungen bestanden in Hautreaktionen wie juckendem Exanthem und Urtikaria bei acht von 70 Patienten, leichter Thrombopenie bei zwei, reversible Granulozytopenie bei einem, Anstieg der Leberenzyme bei zwei und Diarrhöe bei einem Patienten.
    Notes: Summary Susceptibility to cefotaxime of 604 cephalothin-resistant strains was tested with the agar diffusion technique. Compared to cefamandole, cefoxitin and cefuroxime, cefotaxime proved to be the most effective agent againstEnterobacteriaceae. Seventy patients suffering from acute urinary tract infections, septicemia, pneumonia and other severe infections were treated with cefotaxime. The doses were 2–12 g per day, depending on renal function and type of infection. In complicated urinary tract infection (UTI) cure was observed in 20 of 28 patients; failure occurred in eight patients. In uncomplicated acute UTI, all 15 patients responded satisfactorily. Of 14 patients with septicemia eight were cured. Of the remaining 13 patients with severe infections, eight were cured.In vitro susceptible organisms which could neither be eliminated nor which emerged again during treatment were:Staphylococcus aureus (3),Escherichia coli (3),Klebsiella sp. (1),Enterobacter sp. (2),Serratia sp. (3),Proteus mirabilis (2),Achromobacter sp. (1) andPseudomonas aeruginosa (9). Adverse side-effects recorded were skin reactions such as itching exanthem or urticaria in eight of 70 patients. In two patients mild thrombocytopenia, in one patient reversible granulocytopenia and in two patients an increase in liver enzymes was observed. One patient developed diarrhea.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1434-0879
    Keywords: Cytostatic drugs ; Pharmacokinetics ; Tissue concentrations ; Diffusion chambers ; Doxorubicin-hydrochloride ; Methotrexate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
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