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Biomedical subjects

H Mattie

Publications and source records attributed to H Mattie.

At least 73 records · Page 4Linked to original sources
PubMed1989

Cefsulodin for the treatment of Pseudomonas infections--a study comparing cefsulodin and ticarcillin.

The efficacy of cefsulodin against infections caused by Pseudomonas aeruginosa was investigated first in an open trial and then in a controlled comparative study in which ticarcillin was used. The first trial consisted of 16 patients with proven Pseudomonas aeruginosa infections, 9 of whom also received an aminoglycoside. In the second trial 28 such patients were evaluated (14 on cefsulodin 1 g 4 times daily and 14 on ticarcillin 5 g 4 times daily); all patients also received an aminoglycoside. The results of the two trials were similar in that 75% of the patients of the first trial and 86% of the second group exhibited an excellent or good response to cefsulodin. For the ticarcillin group a similar response was noted. In the first trial the sensitivity of P. aeruginosa did not change markedly, whereas one strain of the cefsulodin group became resistant in the second trial. Pharmacokinetic data were in agreement with those reported in the literature. Side effects were rare.

Adult↗
PubMed1988

The effects on ventilation of ketorolac in comparison with morphine.

We have compared the effect on ventilation of ketorolac, an injectable non-steroidal analgesic, with that of morphine in a randomized, double-blind, cross-over study, using two doses of ketorolac (10 and 90 mg i.m.) and one of morphine (10 mg i.m.). The effect on ventilation was measured with a CO2 rebreathing technique. As a measure of the effect we studied the increase in PETCO2 (CO2 shift) that caused a respiratory minute volume (RMV) equal to the RMV in the control period at 8 kPa PETCO2. Ketorolac caused insignificant CO2 shifts of about 0.10 kPa, while morphine caused a significant CO2 shift of 0.86 kPa. We conclude that ketorolac in analgesic and supra-analgesic doses has no effect on the ventilatory response to CO2 under circumstances in which significant effects are seen with morphine.

Adult↗
PubMed1988

The relative efficacies of tobramycin and ciprofloxacin against Pseudomonas aeruginosa in vitro and in normal and granulocytopenic mice.

Ciprofloxacin was studied in vitro and in an experimental thigh infection model in mice to evaluate its efficacy against Pseudomonas aeruginosa in comparison with that of tobramycin. The in vivo experiments were carried out in normal mice as well as mice rendered granulocytopenic by irradiation. The MIC of ciprofloxacin for two Pseudomonas strains was 0.125 mg/l and 0.25 mg/l and that of tobramycin 0.25 mg/l and 4.0 mg/l, respectively. In vitro short-term growth experiments revealed that as far as initial killing rate is concerned, ciprofloxacin was 2.20 times as potent as tobramycin against the first strain and 45.4 times as potent against the second strain. The in vivo experiments were performed by injecting the micro-organism into the thigh muscle and counting colony forming units (CFUs) after several hours of exposure to the antibiotics. The results for irradiated mice indicate that ciprofloxacin was 2.0 times as potent as tobramycin against the first strain and 37.8 times as potent against the second strain, when related to dosage. For normal mice these values were 2.0 and 16.0, respectively, which is more than would be expected from the in vitro experiments because the mean plasma concentrations of tobramycin were about four times higher than those of ciprofloxacin.

Agranulocytosis↗
PubMed1988

Effects of tissue-type plasminogen activator (t-PA) on Streptococcus sanguis-infected endocardial vegetations in vitro.

The effects were studied of in-vitro exposure to tissue-type plasminogen activator (t-PA) on endocardial vegetations isolated from rabbits with Streptococcus sanguis endocarditis as well as on Str. sanguis-infected plasma clots. For both vegetations and clots t-PA induced lysis of the infected fibrin matrix, demonstrated by a release of streptococci into the incubation medium and by an increase in the concentration of fibrin degradation products. The clots decreased in weight, whereas only partial lysis of the vegetations was obtained. Addition of plasminogen to the incubation medium did not enhance the effect of t-PA on vegetations. Fibrinolysis by t-PA did not interfere with the antimicrobial action of benzylpenicillin on the bacteria in a fibrin matrix. It is concluded that t-PA can degrade the fibrin matrices of infected endocardial vegetations and plasma clots. Reduction of vegetation size by t-PA may prove to be useful in the treatment of bacterial endocarditis.

Animals↗
PubMed1988

A prospective study of the efficacy of fluconazole (UK-49,858) against deep-seated fungal infections.

Fluconazole (UK-49,858) is a new bis-triazole antifungal drug that can be administered both orally and intravenously. We conducted an open clinical trial on the efficacy of fluconazole (50-100 mg) once daily in 20 non-neutropenic patients with deep-seated fungal infections. Seventeen patients (eight females, nine males, median age 56 years) could be evaluated clinically. All patients had an underlying disease, while eight also received immunosuppressive therapy. The median duration of treatment was 33 days (range 8-194 days). Clinical cure or improvement was achieved in 14 of 17 patients (82%). Nine patients were both clinically and microbiologically cured. Fluconazole was especially effective in patients with candidal infections. Two patients with cryptococcal meningitis were clinically cured; one of the two was also microbiologically cured. No serious side effects of fluconazole were encountered.

Adolescent↗
PubMed1988

Errors in the prediction of creatinine clearance in patients with rheumatoid arthritis.

The accuracy of two equations used to predict creatinine clearance was assessed in 27 patients with rheumatoid arthritis (RA) and 34 controls. Both equations were accurate in controls, but overestimated the clearance in RA patients. The degree of overestimation was not related to patient characteristics. Uncritical use of these equations in RA patients may lead to serious error.

Adult↗
PubMed1988

Saturation of the tubular excretion of beta-lactam antibiotics.

1 The saturability of the tubular excretion of cloxacillin, benzylpenicillin and cephradine was investigated. 2 Volunteers received a continuous infusion of one of the antibiotics at increasing infusion rates in order to maintain constant plasma concentrations at three different levels. Blood and urine samples were taken every 30 min. Sufficient urinary flow was ensured by a saline infusion (500 ml h-1). 3 Renal clearance of the antibiotic was calculated for the non-protein bound fraction of the drug. 4 Tubular clearance and tubular excretion rate were estimated by using the renal clearance of the antibiotic minus the glomerular filtration rate; the latter was considered to be equal to creatinine clearance. 5 Data were fitted to a Scatchard transformation and, by nonlinear methods, to a Michaelis-Menten equation. 6 Parameters of saturability, i.e. EC50 and maximal tubular excretion rate, were established. The values found for EC50 were 7.7, 93.0 and 266 mg l-1 for cloxacillin, benzylpenicillin and cephradine, respectively. The values calculated for the maximal tubular excretion rate were 1017, 5535 and 4537 mg h-1, respectively.

Adolescent↗
PubMed1988

The effect of probenecid on the renal tubular excretion of benzylpenicillin.

1 The aim of this study was to establish whether the renal tubular excretion of benzylpenicillin is saturable and whether the effect of probenecid on the tubular excretion of benzylpenicillin is dose-dependent. 2 Each of four volunteers underwent three experiments. In each experiment benzylpenicillin was administered by continuous infusion, such that three different consecutive concentration levels were reached. In the first experiment no probenecid was given; in the second and third experiments, probenecid was administered by continuous infusion at a low and higher rate, respectively. 3 Plasma and urinary concentrations of benzylpenicillin were determined at 30 min intervals by high performance liquid chromatography. 4 By fitting the equation Rtub = Rtub,max.Cp/(EC50 + Cp) to the values of the tubular excretion rate found for benzylpenicillin (Rtub) vs the free plasma concentration (Cp), the values of Rtub,max and EC50 could be calculated: 3350 (+/- 606) mg h-1 for Rtub,max and 48.0 (+/- 17.8) mg l-1 for EC50 (in the absence of probenecid). 5 The EC50 for benzylpenicillin increased significantly with increasing doses of probenecid. 6 The dose of probenecid at which 50% of the excretory system is occupied by probenecid in the absence of benzylpenicillin (ED50) ranged from 13.2 to 108.5 mg h-1. 7 The EC50 of probenecid in one subject could actually be measured: 52.3 mg l-1. 8 Extrapolating these results to the clinical situation, the commonly used daily dose of 2 g of probenecid is likely to be close to the maximal effective dose for inhibition of the tubular excretion of benzylpenicillin.

Adult↗
PubMed1988

Antibacterial effect of etoposide in vitro.

Etoposide, an antitumor drug, had an effect in vitro against all strains of gram-positive bacteria studied but not against three gram-negative bacteria. The MICs ranged between 6.2 and 50 micrograms/ml. In short-term-growth experiments, etoposide had a bactericidal efficacy that was 10 to 50 times lower than that of cloxacillin.

Etoposide↗
PubMed1988

Clinical pharmacokinetics of aztreonam.

Aztreonam (azthreonam) is practically completely absorbed after intramuscular injection. After intravenous injection plasma concentrations follow a 2-compartment open model, with a t1/2 alpha of 0.20 hours. Volume of distribution at steady-state (Vdss) after intravenous or intramuscular injection is about 0.16 L/kg (0.42 L/kg for the free drug). After oral administration less than 1% of the drug is absorbed. Over a large dosage range plasma concentrations increase linearly with dose. No accumulation occurs after multiple dosing. Plasma binding in healthy subjects is about 56% and is not concentration dependent. Diffusion into tissues is generally slow, and the ratio between mean tissue and plasma concentration seems to depend mainly on the composition of the tissue. In inflamed meninges, penetration of aztreonam into CSF is more rapid than with uninflamed meninges. Diffusion through the placenta is poor, as is diffusion into breast milk. The main route of elimination of aztreonam is by the kidney, partly by active tubular excretion, but this can be inhibited by probenecid. Extrarenal clearance is probably due to excretion by the liver. Metabolism occurs to a very limited extent. Total plasma clearance in healthy adults is about 140 ml/min (8.4 L/h) or 2 ml/min/kg (0.12 L/h/kg), and terminal half-life is 1.7 hours. In children clearance is similar to that in adults when expressed as a function of bodyweight, but in neonates, especially in low birthweight infants, it is less [about 1 ml/min/kg (0.06 L/h/kg)]. In various disease states the Vdss of aztreonam is not appreciably different from that found in healthy individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

The efficacy of rifampicin against Staphylococcus aureus in vitro and in an experimental infection in normal and granulocytopenic mice.

The effect of rifampicin on Staphylococcus aureus in vitro was assessed as the difference between the logarithms of the numbers of colony forming units (CFU) with and without 3 h of exposure to the drug. The efficacy was expressed as the EC50, i.e. the concentration at which 50% of the maximal effect was obtained, calculated according to the Hill equation. The value found for the EC50 was 3.8 micrograms/l and the mean maximal effect was a log ratio of 5.03 (SEM 0.33). In vivo experiments were performed in normal mice and in mice made granulocytopenic by irradiation. The effect of rifampicin was assessed as the CFU count 5 h after the injection of a suspension of bacteria into the thigh muscle and 4 h after the administration of rifampicin. The efficacy was expressed as the ED50, i.e. the dose at which 50% of the maximal effect is obtained. This value was 0.18 mg/kg for the normal mice and 0.15 mg/kg for the granulocytopenic mice. The corresponding mean plasma concentrations of non-protein-bound drug were 28 and 24 mg/l, respectively. Thus, the EC50 was found to be much higher in vivo than that in vitro. This difference should be taken into account when parameters of in-vitro efficacy are applied to establish dosage schedules.

Agranulocytosis↗
PubMed1987

The activity of ciprofloxacin against Pseudomonas aeruginosa in normal and granulocytopenic mice.

Ciprofloxacin was studied in vitro and in an experimental thigh infection model in mice to evaluate its efficacy against Pseudomonas aeruginosa in comparison with that of tobramycin. The in vivo experiments were carried out in normal mice as well as mice rendered granulocytopenic by irradiation. The MIC of ciprofloxacin for two Pseudomonas strains was 0.125 mg/l and 0.25 mg/l and that of tobramycin 0.25 mg/l and 4.0 mg/l, respectively. In vitro short-term growth experiments revealed that as far as initial killing rate is concerned, ciprofloxacin was 2.20 times as potent as tobramycin against the first strain and 45.4 times as potent against the second strain. The in vivo experiments were performed by injecting the micro-organism into the thigh muscle and counting colony forming units (CFUs) after several hours of exposure to the antibiotics. The results for irradiated mice indicate that ciprofloxacin was 2.0 times as potent as tobramycin against the first strain and 37.8 times as potent against the second strain, when related to dosage. For normal mice these values were 2.0 and 16.0, respectively, which is more than would be expected from the in vitro experiments because the mean plasma concentrations of tobramycin were about four times higher than those of ciprofloxacin.

Agranulocytosis↗
PubMed1987

The use of ciprofloxacin in the treatment of patients with cystic fibrosis.

The use of ciprofloxacin for the treatment of pulmonary infection in cystic fibrosis patients was investigated. Therapy was successful in six patients and unsuccessful in three patients. In one patient therapy had to be stopped because serum transaminase levels showed a 5- to 8- fold increase. During therapy resistance developed in Haemophilus influenzae, Staphylococcus aureus and Pseudomonas aeruginosa.

Adult↗
PubMed1987

Predictability of serum concentrations of aminoglycosides after haemodialysis.

The study was undertaken to look for a correlation between the measured elimination rate constants (k) of aminoglycosides and creatinine during haemodialysis. The pharmacokinetics of aminoglycosides were studied during 44 courses of haemodialysis in 21 patients. The measured k of gentamicin and tobramycin from the start until 30 min after the end of haemodialysis (mean 0.18 h-1; t1/2 = 3 h 51 min) was significantly correlated with the measured k of creatinine (mean 0.13 h-1; t1/2 = 5 h, 20 min), and also with the gentamicin and tobramycin k during haemodialysis (mean 0.20 h-1, t1/2 = 3 h, 28 min), as predicted by a computer program. Thus, serum concentrations of aminoglycosides 30 min after haemodialysis can be estimated by simple regression equations. However, because the measured and predicted values may diverge considerably in the individual patient, monitoring of aminoglycoside concentrations in serum after haemodialysis remains necessary.

Adult↗
PubMed1987

Penetration of praziquantel into cerebrospinal fluid and cysticerci in human cysticercosis.

Two patients with cysticercosis received praziquantel (PZQ) 75 mg/kg/day orally together with 30 mg prednisone daily for 3 weeks. The first patient presented with grand-mal seizures, a pyramidal tract syndrome and subcutaneous cysticerci, and the other had internal hydrocephalus necessitating drainage. Serial plasma samples were taken after the first dose of PZQ. Lumbar CSF was obtained from the first patient and ventricular CSF from the second. Subcutaneous cysticerci were removed from the first patient. PZQ in the specimens was assayed by GLC. For distribution between plasma and CSF a rate constant of 4.9 h-1 for free PZQ, corresponding to a t1/2 of 8 min or less for the non-protein bound fraction was calculated for Patient 1. In the second patient the distribution was so rapid that the rate constant could not be calculated. The difference in distribution rate might have been due to use of different sampling times or to a time lag in the entry of PZQ between the ventricles and the lumbar sac. The rate constant for distribution of the drug between plasma and parasites was 1.4 h-1, corresponding to a t1/2 of 30 min or less. Thus PZQ penetrates rapidly into the CSF. It enters the parasite more slowly, although still more rapidly than the plasma half-life of PZQ (1-1 1/2 h).

Adult↗
PubMed1987

The relation between plasma and tissue concentrations of antibiotics. Description of a method.

A mathematical approach to calculate rate constants of the distribution of antibiotics between plasma and tissue is described. The calculations are based on the assumption that the drug moves between plasma and tissue passively according to the law of diffusion. Corrections can be made for binding to tissue and to plasma proteins. Two mathematical procedures are compared, one based on multiple regression analysis of areas under the curves of the plasma and tissue concentrations and the other on simultaneous curve-fitting to plasma and tissue concentration curves. The method is illustrated for amoxycillin and erythromycin in murine thigh muscle. The half-life of distribution to this tissue is less than 2 min for amoxycillin and about 10 min for erythromycin, and the ratio between the free extracellular tissue concentration and the total tissue content is 4.25 for the former and 0.35 for the latter.

Amoxicillin↗
PubMed1987

Effects of tissue-type plasminogen activator on Staphylococcus epidermidis--infected plasma clots as a model of infected endocardial vegetations.

The ability of tissue-type plasminogen activator (t-PA) to enhance the effect of antibiotics in the treatment of bacterial endocarditis was studied using plasma clots infected with Staphylococcus epidermidis as a model of infected endocardial vegetations. A concentration-dependent lysis of the infected plasma clots was induced by t-PA, as shown by the decrease in the weight of the clots, a decrease in the amount of incorporated 125I fibrin, as well as the release of staphylococci from the clots into the incubation fluid. The addition of cloxacillin to the incubation medium in various concentrations led to a concentration-dependent decrease of the number of S. epidermidis in the clots. The presence of t-PA did not enhance the antibacterial effect of cloxacillin. It is concluded that the lysis induced by t-PA might enhance the effect of treatment of endocarditis by reducing the size of endocardial vegetations but not by enhancement of the effect of antibiotics on the bacteria embedded in the vegetations.

Animals↗
PubMed1987

The penetration of erythromycin into human bronchial mucosa.

1 In this paper the pharmacokinetic relation between concentrations of erythromycin in plasma and in bronchial mucosa was established. 2 Sixteen patients undergoing bronchoscopy received 1 g erythromycin by continuous infusion in 30 min. 3 Two bronchial mucosal samples were taken from each patient sometime after drug administration. Concentrations were determined in the mucosal sample and in several plasma samples collected at different times before the mucosal sample. 4 Rate constants for the distribution between plasma and tissue were calculated on the basis of the assumption of passive diffusion of the free drug. 5 Mean values of the distribution rate constants, calculated by a nonlinear curve fitting procedure, were 2.40 h-1 for distribution from plasma to tissue and 1.28 h-1 for that from tissue to plasma. 6 These values correspond to a half-life for the distribution of the free drug of 33 min and a free fraction of the drug in mucosal tissue of 0.20.

Bronchi↗