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Biomedical subjects

H Lode

Publications and source records attributed to H Lode.

At least 289 records · Page 16Linked to original sources

[Pharmacologic studies or aminoglycoside antibiotics (amikacin, gentamicin, sisomicin, tobramycin)].

In a randomized study of 12 healthy subjects, the pharmacokinetics of gentamicin, sisomicin and tobramycin were determined after a one-hour infusion of each drug (1.0 mg/kg body-weight). There were no pharmacokinetic differences of therapeutic significance between the three drugs. The mean serum concentrations at the end of infusion were 3.85 microgram/ml for gentamicin and 4.66 microgram/ml for sisomicin, falling to 0.12 and 0.26 microgram/ml, respectively, after eight hours. The biological half-life varied between 96 and 122 min and the apparent volumes of distribution corresponded closely to the size of the extracellular space.--The pharmacokinetic data of amikacin were determined after a one-hour constant infusion, the mean amikacin serum concentration was 37.5 microgram/ml and, 8 hours later, decreased to an average of 1.3 microgram/ml. The biological half-life amounted to a mean of 114.2 +/- 16.7 min, and the apparent volume of distribution could be calculated with 18.1 +/- 1.81/100 kg body weight.

Adult↗

[Bacterial endocarditis. Clinical picture, treatment and course in 37 patients (author's transl)].

Between March 1971 and April 1976 37 patients were seen with manifest bacterial endocarditis. The main signs were high temperature and cardiac murmurs whereas other "classical" signs such as splenomegaly, anaemia, leucocytosis, and positive anti-streptolysin titres were much less frequent. In 35 cases bacteriological proof was possible. As causative organism a total of 30 gram-positive organisms (of which 15 were Streptococcus viridans and 8 were Staphylococcus species) and 10 gram-negative bacteria (4 of which were Pseudomonas aeruginosa) could be demonstrated. Treatment was mainly with beta-lactam and/or aminoglycoside antibiotics. Use of the combination of penicillin and streptomycin or gentamicin was based on the results of in-vitro bactericidal activity. The main complications were emboli, penicillin allergies, pulmonary involvement and cardiac complications. 13 patients died; the main cause was cardiac failure which was irreversible even despite operative valve replacement during the acute infection in two cases.

Adult↗

[A multi-centre study of reproterol, a bronchodilator (author's transl)].

Reproterol (Bronchospasmin), a monomolecular combination of catecholamine and theophylline, was tested in 81 patients with bronchial asthma or chronic obstructive bronchitis after a single oral dose, and compared with orciprenaline by intra-individual cross-over test. Five pulmonary-function laboratories cooperated in the study. A statistically significant bronchodilator effect, as measured by airway resistance and volume-corrected resistance, was obtained with 20 mg reproterol, having its onset after about 30 minutes, reaching its peak after 2-3 hours, and lasting for at least 4 hours. Comparing the area under the time-effect curves, the total effect was greater than that after 20 mg orciprenaline, pO2 rose higher after reproterol than after orciprenaline, but only by a few mm Hg. Neither heart rate nor blood pressure changed significantly after reproterol.

Airway Resistance↗

[Azlocillin and mezlocillin: two new semisynthetic acylureido-penicillins (author's transl)].

The pharmacokinetic parameters of two new ureido-penicillins (azlocillin and mezlocillin) were determined in 12 healthy subjects after a half-hour continuous infusion of 5,000 mg. The agar diffusion test (test strain Bacillus subtilis ATCC 6633) was used for the microbiological assays. The mean azlocillin serum concentration after the half-hour infusion was 431.0 +/- 75.0 microgram/ml; after eight hours it had fallen to a mean value of 4.7 +/- 2.6 microngram/ml. The mean elimination half-life was 77.5 +/- 10.4 minutes, and the relative distribution volume was 19.4 +/- 1.9% of the bodyweight. At the end of the infusion, mezlocillin showed a mean serum concentration of 426.0 +/- 61.0 microgram/ml and after eight hours an average of 1.1 +/-0.9 microgram/ml; the half-life was shorter (56.9 +/- 9.9 minutes) and the distribution volume lower (14.8 +/- 3.1%) than that of azlocillin. The renal clearance values measured in three subjects during a four-hour continuous infusion were: azlocillin 111.6 ml/min/1.73 m2, mezlocillin 121.5 ml/min/1.73 m2. The kinetic behaviour of the two ureido-penicillins was essentially very similar to that of ampicillin and carbenicillin, 38 patients with bronchopneumonia, cholangitis or urinary tract infections, which in some instances were severe, were treated for an average of 10 days with an average daily dosage of 3X4.0 g azlocillin or 3X5.0 g mezlocillin. 30 patients showed clinical improvement, and in 17 of these the pathogen was eliminated. These therapeutic results appear more favourable than those obtained with the newer aminoglycoside antibiotics (amikacin, sisomicin); in particular the drug was well tolerated.

Adult↗

[Indications for the monitoring of aminoglycoside serum concentrations in internal medicine (author's transl)].

Numerous factors in the human body can influence and cause variations in the pharmacokinetics of aminoglycoside antibiotics. As a result of these observations it has been demanded that all treatments with aminoglycosides be monitored. This would only appear to be justified for a limited number of indications, however, which involve very high dosages, long-term therapy and impaired renal function. The advantages of monitoring treatment are demonstrated in a patient with endocarditis.

Adult↗

[Pharmacokinetics and clinical experience with amikacin. A new aminoglycoside antibiotic].

The pharmacokinetic data of amikacin were determined after a 1 hr constant infusion with a dosage of 7.5 mg/kg body weight in 12 healthy test subjects. Microbiological bioassay was performed by the agar diffusion test. After the infusion, the mean amikacin serum concentration was 37.5 mug/ml and, 8 hours later, decreased to an average of 1.3 mug/ml. The biological half-life amounted to a mean of 114.2 min, the area below the concentration-time-curve was calculated to an average of 140.4 hr - mug/ml. The renal clearance of amikacin was determined during a 4 hr constant infusion in 3 test individuals; the average clearance was 84.3 ml/min - 1.73 m2. 38 patients with severe bronchopulmonary, urinary and peritoneal infections were treated with an average daily dose of 10-15 mg of amikacin per kg body weight during a mean period of 10 days. 32 patients showed clinical improvement, 17 of them with complete elimination of the pathogenic bacteria.

Adult↗

Pharmacokinetic and clinical studies with amikacin, a new aminoglycoside antibiotic.

Pharmacokinetic parameters of amikacin were determined in 12 healthy volunteers after a 1-hr continuous intravenous infusion of 7.5 mg of the drug/kg. The serum concentration rose rapidly to a peak of 37.5 +/- 4.9 mug/ml at the termination of the infusion and declined to 1.3 +/- 0.5 mug/ml 8 hr later. The mean half-life was 114 +/- 16.7 min, and the apparent volume of distribution was 18.1% +/- 1.8% of body weight. During a 4-hr constant intravenous infusion in three subjects, amikacin was cleared from the kidney at a mean rate of 84.3 ml/min per 1.73 m2, and from the serum at a mean rate of 129.7 ml/min per 1.73 m2. Of the administered dose, 93.5% was recovered from the urine in 24 hr (81.7% during the first 6 hr). After single intramuscular injections of 5 mg/kg in 30 patients, serum levels peaked at 1 hr (21.4 +/- 5.4 mug/ml) and declined to 2.4 +/- 0.9 mug/ml by 8 hr. Of 33 patients with serious urinary or bronchopulmonary infections (usually superimposed on chronic organic pathology) treated with amikacin (10 or 15 mg/kg per day for eight to 17 days), 27 had a clinical remission, and in 15 of these patients the pathogen was eradicated.

Adult↗

[Enzymatic quick determination of aminoglycoside antibiotics in serum].

The therapeutic range of aminoglycoside antibiotics is relatively narrow; therefore short-term controls of serum concentrations can be recommended, particularly for high-dosage therapy and for renal insufficiency. For the aminoglycosides Amicacin, Gentamycin, Sisomicin and Tobramycin an enzymatic quick-determination test within 2 hrs is being described, which is based on the pH-deviation of a medium containing urea by hydrolytic activity of proteus mirabilis-bacteriae. In more than 180 measurements of patients' sera as well as of sera with known concentrations the method was tried out and compared with the conventional agar diffusion procedure. In strict compliance with the methodical directions, reproducable results could be achieved at any time within the range of1.0-30.0mug/ml; the number of faults in the quick-determination test was with +/- 8.4% about the same as in the agar diffusion test. In comparison with other microbiological or biochemical quick-procedures, the simplicity of the described method must be emphasized, thus it can be performed, too, in non-bacteriological laboratories.

Agar↗

[Pharmacokinetics and clinical observations of sisomicin, a newly developed aminoglycoside derivative (author's transl)].

In a randomized study of 12 healthy subjects the pharmacokinetics of gentamicin, sisomicin and tobramycin were determined after a one-hour infusion of each drug (1.0 mg/kg body-weight) four weeks apart. There were no pharmacokinetic differences of therapeutic significance between the three drugs. The mean serum concentrations at the end of infusion were 3.85 mug/ml for gentamicin and 4.66 mug/ml for sisomicin, falling to 0.12 and 0.26 mug/ml, respectively, after eight hours. The biological half-life varied between 96 and 122 min and the apparent volumes of distribution corresponded closely tothe size of the extracellular space. The antibacterial effectiveness, tolerance and modes of application were studied in 24 patients, most of them with urinary infection, at a dosage of 1.0 mg per kg body-weight two to three times daily. Good clinical results were achieved in 15, satisfactory ones in three, and in 16 the causative bacteria were eradicated. Sisomicin was well tolerated, except for minor and reversible renal (2 patients), hepatic (3 patients), and hearing (1 patient) disturbances.

Adult↗

[Studies on the in vitro effects of cephalothin and gentamicin, alone and in combination, on proteus mirabilis and enterococci (author's transl)].

A combined antibiotic therapy is only useful in a few precisely defined clinical pictures where testing of the chemotherapeutics administered is required to determine their characteristics of action (antagonism, indifference, synergism) on the isolated organism. For the initial therapy of critical acute infections, simultaneous administration of cephalothin and gentamicin proved to be valuable. In the present study, the efficiency of these chemotherapeutics alone and in combination was investigated in a quantitative serial dilution test and with the membrane-filtration method. Thirty strains of Proteus mirabilis and enterococci showed only low sensitivity to the antibiotic alone. In combination, whereby gentamicin was at a constant level comparable to in vivo serum levels, an increase of bacteriostatic and bactericidal action could be demonstrated, especially for Proteus mirabilis. The antibacterial spectrum, the molecular-biological mode of action, clinical experience and possible side-effects of the cephalotin-gentamicin combination are discussed.

Cephalothin↗

[Comparative clinical pharmacology of gentamicin, sisomicin, and tobramycin].

Using a randomized crossover design involving 12 normal subjects, we studied comparatively the pharmacokinetics and tolerance of three aminoglycoside antibiotics, gentamicin, sisomicin, and tobramycin. Serum concentrations were determined during 8 h and the urine recovery rate was determined within 24 h after a 1-h intravenous infusion of the respective antibiotic in a dose of 1 mg/kg of body weight. Microbiological assay was performed with the agar diffusion test (Bacillus subtilis); pharmacokinetic calculations were performed by means of a digital computer on the basis of a mathematical model of an open, two-compartment system. Of the three antibiotics studied, gentamicin showed the lowest concentration in serum after termination of the 1-h infusion (3.85 +/- 0.67 mug/ml), and the serum-regression curve steadily lay below those of the two other antibiotics. Sisomicin had the highest serum concentrations (4,66 +/- 1.24 mug/ml) and the serum-level curve exceeded that of the two other antibiotics. Tobramycin occupied a position between sisomicin and gentamicin in form of its serum level characteristics. Corresponding to the serum kinetics we also found slight differences in the pharmacokinetic parameters, especially in serum half-lives, elimination constants, and areas under the serum level curves. The test of liver and kidney functions and the hematological systems, as well as the function of the stato-acusticus nerve, showed no pathological changes by any of the three antibiotics tested.

Adult↗

Comparative pharmacokinetics and clinical experience with a new cephalosporin-derivative: cefazolin.

In a cross-over study in 12 normal individuals, the pharmacokinetic parameters of cefalotin, cefradine and cefazolin were determined after intravenous injection of 1,000 mg of each substance. The microbiological activities in urine and serum were determined using the agar diffusion test; the pharmacokinetic data were calculated by a computer system on the basis of a Fortran programme. Cefazolin has significantly higher serum concentrations than the other two cephalosporins, distinctly longer serum half-lives, higher protein binding, and smaller apparent volumina of distribution. In 36 inpatients with mainly chronical and acute infections of the urinary tract, we tested the antibacterial effectivity, the compatibility, and the application modalities of cefazolin. In 29 patients we had a satisfactory clinical result, in 25 cases we achieved the elimination of bacteria by the end of the therapy. The compatibility of cefazolin was good; apart from a minor, reversible, liver-specific increase in enzymes in 6 patients, no side effects could be detected.

Adult↗