Search PubMed⌕ Search

Biomedical subjects

H Rameis

Publications and source records attributed to H Rameis.

At least 37 records · Page 2Linked to original sources
PubMed1984

Diltiazem and verapamil: functional antagonism of exogenous noradrenaline and angiotensin II in man.

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.

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

The diltiazem-digoxin interaction.

To study the interaction between the calcium antagonist diltiazem and digoxin, a randomized crossover trial under steady-state conditions was carried out in 24 healthy male subjects. Diltiazem with digoxin induced an average increase of steady-state plasma digoxin concentration and AUC over 48 hr of 22.4%. This is caused by the prolongation of elimination t1/2 from 36.2 +/- 11.2 to 44.5 +/- 11.5 hr (means +/- SD) and the impairment of total digoxin clearance, dropping from 146.6 +/- 37.9 to 107.9 +/- 18.4 ml/min. Average reduction in renal clearance (from 102.1 +/- 35.5 to 85.5 +/- 42.7 ml/min) was not statistically reproducible. Apparent volume of distribution was not relevantly altered. Diltiazem kinetics did not change significantly when digoxin was concurrently given.

Adult↗
PubMed1984

[Therapeutic problems in hyperkinetic heart syndrome].

At present beta-blockers are the therapy recommended in hyperkinetic heart syndrome. This therapeutical advice was investigated by two cross over studies: the first trial was a comparison between the circulatory effects of Celiprolol and Pindolol, the second one between Oxprenolol and the calcium antagonist Verapamil. All beta-blockers tested effected a safe reduction in heart rate, which is elevated in hyperkinetic state, but failed to lower diastolic blood pressure by at least 15 mm Hg. Verapamil however, also effected bradycardia but did not reduce heart-rate in the same amount as beta-blockers. Furthermore the calcium antagonist's hypotensive effects are more pronounced by comparison with beta-blockers. According to these findings beta-blockers are not to be seen as therapy of first choice in hyperkinetic heart syndrome, they are only recommended combined with diuretics or vasodilators. As alternative therapy Verapamil could be prescribed, which disadvantage is the necessity of taking it several times per day.

Adrenergic beta-Antagonists↗
PubMed1984

Comparison of gastrointestinal blood loss induced by cloximate in two formulations and by naproxen.

In a double-blind baseline controlled crossover trial gastrointestinal blood loss induced by cloximate in two different formulations (enteric-coated and non-enteric coated) was compared with naproxen. Gastrointestinal blood loss increased more in the naproxen group (0.41 ml/24 h) than in the group treated with non-enteric coated cloximate. The group treated with coated cloximate had a higher mean increase in gastrointestinal blood loss (0.36 ml/24 h) compared with placebo than those treated with non-coated cloximate.

Acetates↗
PubMed1984

Changes in metildigoxin pharmacokinetics in cirrhosis of the liver: a comparison with beta-acetyldigoxin.

In a prospective randomized study 12 patients suffering from cirrhosis of the liver (stable phase) and 12 healthy volunteers were treated daily with either 0.3 mg metildigoxin (Lanitop) or 0.4 mg beta-acetyldigoxin (Novodigal) orally. Every day the total serum digoxin concentrations of the patients and volunteers were measured by radioimmunoassay. Both digoxin and beta-methyldigoxin are measured by this method. In patients receiving metildigoxin therapy the ratio of beta-methyldigoxin/digoxin in the serum was determined by HPLC. The digoxin levels in patients with cirrhosis treated with metildigoxin were statistically significantly higher than in healthy volunteers. In patients with cirrhosis the proportion of serum beta-methyldigoxin averaged 77.7% of the total digoxin concentration, whereas the proportion was only 37.5% in healthy volunteers. With beta-acetyldigoxin there was no statistically significant difference between patients with cirrhosis and healthy volunteers. The higher total serum-digoxin levels in patients with cirrhosis of the liver after moderate saturation with metildigoxin are caused by reduced demethylation of beta-methyldigoxin to digoxin due to impaired liver function. A comparison with healthy volunteers showed that the reduced hepatic metabolism in the cirrhotic patients caused changes in the pharmacokinetics: a reduced metildigoxin clearance and a smaller distribution volume were found. According to our findings there is more danger of digitalis toxicity in patients with cirrhosis of the liver on a standard dosage of metildigoxin than on a standard dosage of beta-acetyldigoxin.

Acetyldigoxins↗
PubMed1983

[Intraocular penetration of netilmicin].

The penetration of netilmicin, a semisynthetic aminoglycosid into the primary human aqueous humor was determined. The antibacterial spectrum of netilmicin is adequate to gentamicin. The efficacy also covers gentamicin resistant strains. After intramuscular injection of 5 mg/kg body weight aqueous levels higher than the minimum inhibitory concentration (MIC) of staphylococcus aureus, Escherichia coli, Klebsiella, Enterobacter, Citrobacter and Proteus morganii were obtained. In the therapy of bacterial endophthalmitis the synergistic effect of netilmicin with beta-Lactam antibiotics in the form of a combined therapy should be made use of. For perioperative prophylaxis the newer aminoglycosids are not indicated because there is the danger of a development of resistant strains.

Aged↗
PubMed1983

[Pharmacokinetics and acute signs of cardiac toxicity during doxorubicin therapy].

Doxorubicin (Adriamycin) has shown impressive activity in the treatment of a broad spectrum of malignant tumours. Chronic irreversible cardiac myopathy is the usual cumulative dose-limiting toxicity with this anthracycline antibiotic. In this study acute cardiac reactions following doxorubicin infusions (60 mg/m2) were registered by means of ECG Holter monitoring and measurement of systolic time intervals. The PEPI as well as the PEP/LVET ratio were found to be significantly increased, with a peak at 6 hours following drug infusion (p less than 0.001). This observation proves the occurrence of transient myocardial dysfunction during doxorubicin treatment. Pharmacokinetic data showed good correlation between the electrocardiographic changes and the tissue distribution of the drug. Doxorubicin-related ventricular arrhythmias were observed in only 2 out of 6 cases. Repeated acute myocardial damage by doxorubicin infusions is considered to be the cause of chronic cardiomyopathy with long-term administration.

Adult↗
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↗
PubMed1983

Acute cardiac toxicity in patients after doxorubicin treatment and the effect of combined tocopherol and nifedipine pretreatment.

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 less than 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.

Adult↗
PubMed1983

Gentamicin monitoring in low-birth-weight newborns.

The pharmacokinetics of gentamicin in premature newborns is influenced by many noncalculable variables. Nevertheless, and despite its narrow therapeutic range, this aminoglycoside antibiotic is usually prescribed according to a fixed schedule. Gentamicin was monitored in 22 severely sick, low-birth-weight newborns on combination therapy of various antibiotics including gentamicin. Dosage regimen of gentamicin was prescribed according to Eichenwald and McCracken [1978]. Serum gentamicin concentrations were measured by radioimmunoassay before infusion, 30 min after, and 3 h after infusion of the antibiotic. In 22 prematures desirable serum gentamicin concentrations with a mean elimination half-life (t 1/2) of 5.3 h; in 2 prematures, levels with a mean t 1/2 of 2.3 h; in 7 prematures, possible toxic levels with a mean t 1/2 of 8.3 h; and in 2 prematures, definite toxic levels with a prolonged t 1/2 up to 17 h were observed. Most of the prematures with possible or definite toxic gentamicin levels were not older than 1 week. This is explained by the immaturity of the kidneys and the retention of aminoglycosides. A satisfactory correlation between postnatal age and gentamicin elimination half-life was found, which might be caused by postnatal maturation of the glomerular function. In prematures in the 1st postnatal week we recommend reducing the daily dose by prolonging the dosage interval, e.g., from 12 to 18 h, or reducing the single gentamicin doses. Gentamicin monitoring seems advisable for detecting toxic serum concentrations and accumulation and for revealing an insufficient dosage of this aminoglycoside antibiotic.

Age Factors↗
PubMed1983

Amikacin levels in human aqueous humor.

Amikacin is one of the newer aminoglycoside antibiotics. The penetration of amikacin into the human primary aqueous humor after intramuscular application was investigated. Comparing our results with reports concerning the blood aqueous permeability of gentamicin and tobramycin we could not find any significantly better penetration of amikacin into the human aqueous humor after i.m. injection. The advantage of amikacin lies in its effectiveness against bacteria resistant to other aminoglycosides.

Aged↗
PubMed1982

[Determination of serum concentrations of aminoglycosides in the monitoring of therapy in neonates. I. Gentamycin].

We studied the serum concentrations of gentamicin by radio-immuno-assay in 22 sick prematures (birth weight 1713 +/- 469 g, prenatal age 33 +/- 3 weeks, postnatal age 12 +/- 9 days) receiving 2.5 mg/kg bid. Bactericidal concentrations were present in 91% but only 50% had normal serum concentrations and gentamicin half-lives. Gentamicin half-life decreased significantly (p less than 0.01) with postnatal age but there was no statistically significant correlation between gentamicin serum concentration and gestational age or birth weight. We therefore recommend 1. gentamicin serum concentrations to be monitored routinely in therapy of prematures especially in the first week of life, 2. to expand the dosage interval up to 18 hours (which is about the threefold half-life) in prematures during the first week of life.

Gentamicins↗
PubMed1982

The bioavailability of spironolactone hydrochlorothiazide combination preparation.

In a single-blind, randomized cross-over study the bioavailability of Spironothiazid (50 mg spironolactone, 50 mg hydrochlorothiazide) was investigated in six healthy male volunteers by comparing the same dose of the well-established drugs Aldactone dragees, 50 mg, and Esidrex tablets, 25 mg. After 6 days treatment with 2 X 1 Spironothiazid or 2 X 1 Aldactone dragees, 50 mg, plus Esidrex tablets, 25 mg daly, orally, the serum concentrations and the cumulative renal excretion of the active substances were measured after the morning dose on the 7th day of the study. Canrenone (the main metabolite of spironolactone) was measured fluorimetrically, hydrochlorothiazide was determined by gas chromatography. There was no statistically significant difference between the investigated drugs, neither in the areas under the curves nor in the cumulative renal excretion, thus indicating an identical bioavailability.

Adult↗
PubMed1981

[Pharmacokinetics of beta-methyldigoxin and beta-acetyldigoxin in patients with cirrhosis of the liver (author's transl)].

In this prospective randomised study 12 patients suffering from cirrhosis of the liver (stable phase) and 12 healthy male volunteers were treated with either 0.3 mg beta-methyldigoxin (Lanitop) or 0.4 mg beta-acetyldigoxin (Novodigal) daily, orally. Every day the total serum digoxin concentrations of the patients and volunteers were measured by radioimmunoassay. Both digoxin and beta-methyldigoxin are measured by this method. In subjects receiving beta-methyldigoxin therapy the ratio of beta-methyldigoxin to digoxin in the serum was determined by liquid chromatography. The digoxin levels in patients with cirrhosis treated with beta-methyldigoxin were statistically significantly higher than in healthy volunteers. In patients with cirrhosis the proportion of serum beta-methyldigoxin averaged 77.7% of the total digoxin concentration, whereas the proportion was only 37.5% in healthy volunteers. With beta-acetyldigoxin there was no statistically significant difference between patients with cirrhosis and healthy volunteers. Alterations in pharmacokinetics may cause the higher total serum digoxin concentrations in cirrhotic patients. The following factors seem to be important: longer elimination half life, changes in distribution volume and reduced renal clearance. There is greater danger of digitalis toxicity in patients with cirrhosis of the liver on standard dosage of beta-methyldigoxin than on standard dosage of beta-acetyldigoxin.

Acetyldigoxins↗
PubMed1981

Digoxin concentration in cerebrospinal fluid-a study carried out after 9 days of treatment of beta-methyldigoxin or beta-acetyldigoxin.

Two groups of seven healthy volunteers were treated for 9 days with either 0.3 mg beta-methyldigoxin or 0.4 mg beta-acetyldigoxin daily, applied orally. On the 10th day, digoxin concentrations in plasma and cerebrospinal fluid (CSF) were determined by radioimmunoassay. After therapy with beta-methyldigoxin the plasma/CSF digoxin concentration ratio was 3.7:1; after therapy with beta-acetyldigoxin it was 3.2:1. There was no significant difference in the plasma/CSF digoxin concentration ratio after 9 days of treatment with equipotent doses of beta-methyldigoxin and beta-acetyldigoxin.

Acetyldigoxins↗