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Biomedical subjects

A Arvidsson

Publications and source records attributed to A Arvidsson.

At least 19 recordsLinked to original sources
PubMed1992

Digoxin-interactions in man: spironolactone reduces renal but not biliary digoxin clearance.

The possibility of an inhibitory effect of spironolactone on the biliary clearance of digoxin has been investigated in 6 healthy subjects. Plasma clearance and the renal and biliary clearance of digoxin were determined twice at steady state (digoxin 0.5 to 1 mg.d-1 p.o. for 6 days), alone or in combination with spironolactone 200 mg daily, after an intravenous dose of digoxin (0.7 x oral dose) on Day 7. Plasma and urine were collected for 48 h. Biliary clearance of digoxin was determined on Day 8 by a duodenal perfusion technique. During spironolactone treatment plasma digoxin clearance tended to be lower (255 vs 224 ml/min; P = 0.057) and renal clearance significantly lower (166 vs 144 ml/min), while the biliary clearance of digoxin remained unchanged (106 vs 103 ml/min). Thus, spironolactone reduced the renal clearance of digoxin by an average of 13%, without affecting its biliary clearance.

Adult↗
PubMed1991

Digoxin-verapamil interaction: reduction of biliary but not renal digoxin clearance in humans.

The interaction between digoxin and verapamil was studied in six patients (mean age +/- SD, 61 +/- 5 years) with chronic atrial fibrillation. The effects of adding verapamil (240 mg/day) on steady-state plasma concentrations and renal and biliary clearances of digoxin were studied in a crossover manner. The biliary clearance of digoxin was determined by a duodenal perfusion technique. Verapamil induced a 44% increase in steady-state plasma concentrations of digoxin, from 0.80 +/- 0.24 to 1.15 +/- 0.40 nmol/L (p less than 0.01). The biliary clearance of digoxin decreased by 43%, from 187 +/- 89 to 101 +/- 55 ml/min (p less than 0.05), in the presence of verapamil, whereas the renal clearance was unaffected (153 +/- 31 versus 173 +/- 51 ml/min; difference not significant). Our results indicate that the main inhibitory effect of verapamil on digoxin elimination is on the biliary route.

Bile↗
PubMed1991

No effect of probenecid on the renal and biliary clearances of digoxin in man.

1. The cardiac glycoside digoxin is subject to a number of pharmacokinetic interactions. This study concerns the influence of the anionic transport inhibitor probenecid on the steady-state kinetics of digoxin. 2. Six healthy young men were enrolled in the study. After an administration period of 6 days with digoxin only (0.5 to 1 mg p.o. day-1) or digoxin in combination with probenecid (2 g p.o. day-1; 8 days), digoxin was administered intravenously (0.7 oral dose) on day 7. Plasma and urine samples were taken over 48 h. The biliary clearance of digoxin was measured during day 8 by a duodenal perfusion technique. 3. Probenecid did not affect the plasma clearance (mean +/- s.d.: 255 +/- 80 vs 266 +/- 40 ml min-1), renal clearance (166 +/- 17 vs 155 +/- 10 ml min-1), biliary clearance (106 +/- 40 vs 111 +/- 50 ml min-1), elimination half-life (34.4 vs 35.2 h) or volume of distribution (538 +/- 241 vs 566 +/- 60 l) of digoxin. 4. Our results suggest that different systems exist in man for the renal and biliary secretion of probenecid and digoxin.

Administration, Oral↗
PubMed1990

Interactions in the renal and biliary elimination of digoxin: stereoselective difference between quinine and quinidine.

The interactions between digoxin and quinine and quinidine that affect the renal and biliary clearances of digoxin were investigated in eight healthy subjects. Digoxin (0.5 to 0.75 mg/day) was given alone and with concomitant administration of quinine (750 mg/day) to reach a steady-state level. In four of the subjects, the study was repeated by administration of equimolar doses of the diastereoisomer quinidine together with digoxin, enabling a within-subject comparison of the effects of the two isomers on digoxin clearance. The biliary excretion of digoxin was studied by use of a modified duodenal marker perfusion technique. A marked reduction was found in the steady-state biliary clearance of digoxin from control value 134 +/- 57 ml/min (mean +/- SD) to 87 +/- 39 ml/min during treatment with quinine (p less than 0.05) and from 95 +/- 24 to 55 +/- 27 ml/min during treatment with quinidine (p less than 0.01; n = 4). Quinidine reduced the renal clearance of digoxin (155 +/- 26 versus 110 +/- 21 ml/min) (p less than 0.05; n = 4), whereas quinine had no such effect (177 +/- 40 versus 185 +/- 53 ml/min; not significant). These findings explain the difference in magnitude between quinidine and quinine in regard to the interaction with digoxin and imply a different degree of stereoselectivity for these isomers in the renal and biliary secretory systems of digoxin.

Adult↗
PubMed1990

Non-invasive assessment of left ventricular diastolic function in patients with systemic sclerosis.

To evaluate the extent of left ventricular (LV) diastolic impairment in systemic sclerosis, we examined 30 consecutive patients (15 men and 15 women) with this condition, and compared the findings with the data for 48 age- and sex-matched randomly sampled controls. All patients were investigated by phonocardiography, pulse curve recording, and M-mode echocardiography. Twenty-three of 30 (77%) patients had LV hypertrophy and/or diastolic impairment. Interventricular septum (P = 0.0001), LV posterior wall (P less than 0.05), and the wall thickness to cavity dimension ratio (P less than 0.001) were increased in patients compared to controls, as was LV mass index (P less than 0.002). Five patients had asymmetric septal hypertrophy. LV end-diastolic dimension did not differ between groups. LV distensibility was impaired, as judged from apexcardiographic a/H ratio (P less than 0.05) and from an increased left atrial index (P less than 0.005). LV early filling was impaired, with a reduced left atrial emptying index (P = 0.0001), and a reduced rate of dimension increase in digitized M-mode (P less than 0.02). We found no evidence of impaired LV relaxation. Blood pressure did not differ between patients and controls. With longer duration of the disease, left atrial dimension appeared to increase (r = 0.42, P less than 0.05), while other variables were not related to disease duration. The impaired LV filling was not secondary to systolic dysfunction. We conclude that systemic sclerosis patients have an increased LV wall thickness, with impaired early filling properties and LV distensibility.

Body Composition↗
PubMed1990

Increased renal clearance of cefsulodin due to higher glomerular filtration rate in cystic fibrosis.

The steady-state renal clearance of cefsulodin was studied in 6 patients with cystic fibrosis and 8 healthy controls. The drug was administered by constant rate infusion to obtain 2 values of plasma concentration, 2 and 30 mg/L. As an estimate of the glomerular filtration rate, the renal clearance of inulin was measured simultaneously. The results showed the figures for inulin clearance to be approximately 30% higher in cystic fibrosis patients than in healthy controls at both concentrations, and a corresponding increase in the renal clearance of cefsulodin was seen in patients over controls. The ratio between the renal clearances of the 2 substances was on average 0.9 in both groups. The correlation found between the 2 renal clearances (r = 0.75; p less than 0.001) indicates that glomerular filtration rate has considerable influence on the renal elimination of cefsulodin. This finding emphasises the importance of glomerular filtration rate for the renal clearance of drugs in cystic fibrosis.

Adolescent↗
PubMed1990

Plasma and renal clearance of iohexol--a study on the reproducibility of a method for the glomerular filtration rate.

The reproducibility of iohexol clearance as a determination of the glomerular filtration rate was assessed in 12 healthy subjects during triplicate constant-rate infusions. Renal and plasma clearance of iohexol demonstrated a total within-subject variation (CV) ranging between 0% and 16%. The inter-individual variation in renal clearance was about 10%, the clearance values being (mean +/- SD) 116 +/- 10, 117 +/- 9 and 110 +/- 12 ml/min 1.73 m2 in the three experiments and corresponding figures for the plasma clearance were 120 +/- 17, 118 +/- 12 and 112 +/- 14 ml/min 1.73 m2. The renal clearance (CLR) and the plasma clearance (CL) showed good correlation (regression equation CL = 11.80 + 0.93 CLR, rs = 0.67). The method is simple and reproducible; thus, it is suitable for both clinical examinations and research.

Adult↗
PubMed1990

Recombinant leukocyte interferon alpha-2a and medroxyprogesterone in advanced renal cell carcinoma. A randomized trial.

In a randomized study of advanced renal cell carcinoma 60 patients were allocated to treatment with either recombinant interferon alpha-2a or medroxyprogesterone acetate. Correlation between the dose of interferon alpha-2a and plasma-concentration indicated linear kinetics. Survival was similar in the two treatment groups. Only one complete and one partial response were seen in the interferon group and only one complete response in the medroxyprogesterone group, indicating a low therapeutic potential of both interferon and medroxyprogesterone. Interferon influenced the serum liver enzyme levels; increased transaminases were seen in 17 patients treated with interferon but in only four patients in the medroxyprogesterone group. Two patients had very high serum liver-enzyme levels concomitant with intolerable tiredness, in both patients the symptoms disappeared and the enzymes normalized after discontinuation of the interferon treatment. Antibodies to interferon developed frequently in patients receiving high dose oligomeric interferon therapy but rarely in patients receiving low dose monomeric interferon treatment.

Adult↗
PubMed1988

Interindividual variability in biliary excretion of ceftriaxone: effects on biliary lipid metabolism and on intestinal microflora.

Ceftriaxone is a broad spectrum parenteral cephalosporin that is eliminated through renal as well as biliary excretion. In order to characterize factors influencing the biliary excretion of ceftriaxone, and possible effects of this organic anion on biliary lipid transport, we studied six healthy volunteers before and during ceftriaxone infusion. The biliary secretion rates of cholesterol, bile acids, phospholipids and ceftriaxone were determined using a duodenal perfusion technique, and the biliary lipid composition and cholesterol saturation of stimulated hepatic bile were determined. Changes in the intestinal microflora induced by ceftriaxone treatment were also analysed. There was a three-fold interindividual variation in biliary excretion of ceftriaxone, and this was correlated with the secretion rate of bile acids (rs = 0.83, P = 0.05). During ceftriaxone infusion, the secretion rate of cholesterol was reduced by 32% (P less than 0.05), which resulted in a reduction of cholesterol saturation of bile, from 107 +/- 11 to 75 +/- 12% (SEM, P less than 0.05). The suppression of intestinal Escherichia coli and Bacteroides, and the proliferation of enterococci and lactobacilli were related to the biliary excretion of ceftriaxone. We conclude (i) that biliary excretion of ceftriaxone is of major importance for its effects on intestinal microflora, (ii) that secretion of this organic anion into bile is largely dependent on bile acid secretion, and (iii) that ceftriaxone inhibits the biliary secretion of cholesterol.

Adult↗
PubMed1988

Dyspnoea of cardiac origin in 67 year old men: (2). Relation to diastolic left ventricular function and mass. The study of men born in 1913.

The relation of cardiac dyspnoea to diastolic left ventricular dysfunction was examined in a sample of 67 year old men from the general population of Gothenburg, Sweden. Forty two men with cardiac dyspnoea and 45 controls were selected from the screened cohort of 644 men. M mode echocardiography, apexcardiography, and phonocardiography were used to evaluate heart sounds, diastolic time intervals, aortic root motion (atrial emptying index); peak rate of change in left ventricular dimension, left atrial and ventricular size; and left ventricular mass. There was a significant relation between dyspnoea grade and left ventricular mass and posterior wall thickness. Dyspnoea grade also correlated significantly with the amplitude of the rapid filling wave and the third heart sound, atrial emptying index and left atrial size, the pulmonary component of the second heart sound, and the dimension of the right ventricle. In mild to moderate dyspnoea fractional shortening was normal, but posterior wall thickness and left atrial dimension were increased. The time from the second heart sound to the O point of the apexcardiogram, adjusted for heart rate, was significantly prolonged in mild to moderate dyspnoea, but not in severe dyspnoea. There was a significant decrease of rate adjusted isovolumic relaxation time, probably secondary to altered loading conditions, in severe dyspnoea, but not in mild to moderate dyspnoea. When the effect of systolic function was excluded multivariate analyses showed that the relation between dyspnoea grade and left atrial dimension persisted. The finding that diastolic abnormalities of the heart contributed to the generation of cardiac dyspnoea may have implications for treatment.

Aged↗
PubMed1988

Influence of the glomerular filtration rate on renal clearance of ceftazidime in cystic fibrosis.

The renal handling of ceftazidime was studied in 8 patients with cystic fibrosis and 10 healthy controls. The renal clearance of ceftazidime (CLRcz) was measured after an intravenous single dose and during low and high plasma concentration steady-state infusions. The glomerular filtration rate (GFR) was simultaneously estimated by inulin clearance (CL inul). The average CLRcz (mean +/- SD) was higher in cystic fibrosis patients (125 +/- 20 ml/min/1.73 m2) than in healthy controls (100 +/- 9 ml/min/1.73 m2) [p less than 0.005]. Also CL inul (mean +/- SD) was increased in cystic fibrosis patients (132 +/- 30 ml/min/1.73 m2) compared with healthy controls (103 +/- 8 ml/min/1.73 m2) [p less than 0.02]. The mean renal clearance ratios of ceftazidime to inulin were close to unity after both the single dose and low and high dose steady-state infusions both in cystic fibrosis patients and in controls. These findings suggest that the glomerular filtration rate is the principal determinant of the elimination rate of ceftazidime. However, in all cystic fibrosis patients with a CL inul exceeding 125 ml/min/1.73 m2 the clearance ratio was below unity, indicating tubular reabsorption of ceftazidime occurs in these individuals. The results demonstrate a higher but also more variable GFR in cystic fibrosis patients (74 to 174 ml/min/1.73 m2), resulting in increased and accordingly variable ability to eliminate ceftazidime in cystic fibrosis. However, these pharmacokinetic changes are not large enough to call for special dosage considerations for ceftazidime in cystic fibrosis.

Adolescent↗
PubMed1987

Quinidine reduces biliary clearance of digoxin in man.

Quinidine is known to reduce the renal clearance of digoxin, but this effect does not completely explain the influence of quinidine on the total clearance of digoxin. We therefore studied the effect of quinidine administration on biliary clearance of digoxin in five patients with atrial fibrillation. Biliary clearance of digoxin under steady state conditions before and during treatment with quinidine was investigated using a duodenal-marker-perfusion technique. Quinidine caused an average 42% (range 21-65%, P less than 0.02) reduction of the measured biliary clearance of digoxin. We conclude that the biliary effect adds to the previously demonstrated inhibitory effect of quinidine on the renal clearance of digoxin and helps to explain the decrease in total clearance of the drug. This is the first demonstration in man of a pharmacokinetic drug interaction at the level of biliary excretion.

Aged↗
PubMed1985

Pharmacokinetic studies of cefoxitin in continuous ambulatory peritoneal dialysis.

The pharmacokinetics of cefoxitin was examined in 9 patients undergoing peritoneal dialysis for chronic renal failure. Cefoxitin was administered intraperitoneally in the dialysate fluid every 6 h for 24 h, in two different concentrations, 50 micrograms/ml and 100 micrograms/ml. The plasma half-life of cefoxitin was 20.2 h. The major route of elimination was non-renal, with a clearance of 8.0 ml/min. Peritoneal clearance was 4.1 ml/min. As expected, renal clearance was negligible. The peak plasma concentrations of cefoxitin at the two dose levels used were 7 micrograms/ml and 15 micrograms/ml, respectively, when assayed by HPLC, and 12 micrograms/ml and 24 micrograms/ml when determined by a microbiological assay. The cefoxitin concentration in the dialysate decreased from 50 micrograms/ml to 14 micrograms/ml and from 100 micrograms/ml to 37 micrograms/ml during the 6 h of its retention in the peritoneal cavity.

Adult↗
PubMed1984

Automatic selection of uncontaminated electromyogram as applied to respiratory muscle fatigue.

An automatic procedure for detecting artifacts in the electromyogram (EMG) has been developed and applied to a study of respiratory muscle fatigue. Signal segments are characterized by a set of features, the normal variations of which have been estimated in a training session. From the features are calculated a classification variable, which expresses the degree of deviation from normal conditions. A deviation larger than a certain threshold value designates a segment as disturbed. The study deals with the choice of features, the selection of a suitable segment length, and the determination of an optimal classification threshold. The four features chosen include measures of amplitude symmetry, extreme excursions in the signal tracing, the signal-to-noise ratio, and the shape of the EMG power spectrum. Recordings from three subjects were used for the evaluation of the method. The results indicate that a segment length of 250 ms is appropriate. Accepting a 10% rate of false detections, the average rate of missed detections was 2.2%.

Diaphragm↗
PubMed1983

Effect of cephapirin on tubular reabsorption of amino acids, uric acid and beta 2-microglobulin in man.

Cephapirin, a beta-lactam antibiotic, was administered intravenously to five healthy subjects in a dose of 1 g. Renal clearances of cephapirin, beta 2-microglobulin, uric acid and amino acids were measured during the experiment and compared to timed control data, i.e. when no cephapirin was given. Renal clearance of cephapirin decreased when plasma concentrations declined. As protein binding of cephapirin is constant over a wide plasma concentration range, this finding may indicate that cephapirin is reabsorbed in the kidney by a saturable process. Renal clearance of endogenous amino acids, particularly those belonging to the basic group increased after cephapirin. There was no change in renal clearance of beta 2-microglobulin which excludes a general toxic effect on tubular reabsorption of endogenous substances caused by cephapirin. A flow dependent increase of uric acid clearance was observed. Our results are suggestive of a competition between cephapirin and amino acids for some common step in the tubular reabsorption process.

Amino Acids↗
PubMed1982

Optimal conditions for assay of cytochrome-c-oxidase activity in human skeletal muscle tissue.

Conditions for the assay of cytochrome-c-oxidase in human skeletal muscle tissue were studied, including an evaluation of the optimal conditions during the in vitro assay as well as the optimal conditions for storage and treatment of the tissue before the assay. The activity of cytochrome-c-oxidase was assayed polarographically with a Clark oxygen electrode. Optimal oxygen consumption rates were obtained at a cytochrome-c-concentration above 0.2 mmol/l, in the presence of TMPD, 2.2 mmol/l and ascorbic acid, 4.4 mmol/l as reducing agents. Enzyme proportionality was obtained after correction of the oxygen consumption rates for a blank reaction according to one of three alternatives presented. Variations in the homogenizing technique and the degree of dilution of the homogenate (1:11-1:88) had only moderate effects on the enzyme activity. Optimal storage conditions were evaluated by comparing the enzyme activities measured in fresh muscles, frozen muscles and homogenates prepared from fresh muscles. During all storage conditions significantly higher activities were obtained when sucrose buffer (0.25 mol/l) was used as homogenizing medium as compared to phosphate buffer (0.1 mol/l). Freezing and thawing of the muscle tissue before the assay caused an average decrease in the enzyme activity of 50% (P less than 0.005) as compared to the activity obtained in fresh tissue. This untoward effect of the freezing and thawing was reduced when the enzyme activity was analysed in frozen homogenates prepared from fresh muscles. Thus, an average decrease in the enzyme activity of 15% (P less than 0.05) was found in frozen homogenates prepared in sucrose buffer as compared to the activity obtained in the fresh tissue. These findings emphasize the importance of evaluating the effects of the tissue treatment for comparative studies of maximum enzyme activities in vitro.

Electron Transport Complex IV↗
PubMed1979

Renal excretion of cephapirin and cephaloridine: evidence for saturable tubular reabsorption.

Drug concentrations in plasma and urine were determined in 5 healthy subjects after intravenous infusion of 1 gm cephapirin and cephaloridine. Sampling of blood and urine was frequent and prolonged. Specimens were analyzed by high-pressure liquid chromatography (HPLC). Renal clearance of cephapirin decreased to less than 5% of control in all subjects when drug concentrations in plasma and urine declined. Cephaloridine clearance decreased to a lesser extent. Our findings suggest that, besides tubular secretion and glomerular filtration, a saturable and probably active tubular reabsorption is also involved in the renal handling of these two cephalosporins. The saturable reabsorption process was characterized by its Michaelis-Menten constant Km and its maximum transport capacity Tm.

Absorption↗