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Biomedical subjects

J Bonde

Publications and source records attributed to J Bonde.

At least 55 records · Page 3Linked to original sources
PubMed1990

A comparison of systolic time intervals measured by impedance cardiography and carotid pulse tracing.

The purpose of this study was to compare the systolic time intervals (STI) obtained by impedance cardiography and by the conventional carotid technique. This comparison was done with respect to: 1) correlations between variables obtained by the two methods, 2) ability to reflect drug-induced changes, 3) reliability in terms of reproducibility and 4) heart rate dependency of the variables measured. The study included 25 unmedicated patients with ischaemic heart disease and 36 healthy subjects. We obtained significant correlations between STI-variables measured by the two methods (p less than 0.001) and found that left ventricular ejection times were longer when determined by the carotid technique (p less than 0.01). We found a significant correlation between drug-induced changes in STI-variables measured by the two methods (p less than 0.001). Both methods had a high degree of reproducibility and this parameter was significantly better within the same day, when impedance cardiography was used (p less than 0.01). The error due to the reading of STI-tracings obtained by impedance cardiography was very small when performed by the same observer. We found the pre-ejection period to be independent upon heart rate, while the left ventricular ejection time depended upon this parameter. We conclude that impedance cardiography and carotid technique differ with respect to the measurement of left ventricular ejection times, but not with respect to the measurement of other STI-variables. We furthermore conclude that both methods are reliable, but we recommend the use of impedance cardiography because it is easier to apply, it may be more precise and it can be used for simultaneous measurements of other haemodynamic variables.

Cardiac Output↗
PubMed1990

Relative bioavailability of methadone hydrochloride administered in chewing gum and tablets.

Methadone administered in chewing gum in doses of 16.7-22.6 mg to seven patients in a study using an open balanced cross-over design, was compared with 20 mg of methadone given perorally as tablets. There was no significant difference in the AUC/D obtained after administration of chewing gum and tablets (p greater than 0.05). It is concluded that the chewing gum formulation should be considered for further testing with respect to suppression of abstinence syndrome in narcotic addicts.

Adult↗
PubMed1989

Disposition kinetics of disopyramide in human healthy volunteers described by an open three compartment model.

Disposition kinetics of disopyramide was examined in an open randomised cross-over study in 8 healthy volunteers. Disopyramide was randomly administered as a single bolus injection (150 mg) over a period of 5 min. and as an infusion (28.2) mg/h to steady state. Disposition kinetics of disopyramide were most precisely described by an open three compartment model according to Akaike's information criteria. Significant positive correlations (0.909 +/- 0.04, P less than 0.05 (injection study); 0.787 +/- 0.11, P less than 0.05 (infusion study] were observed between total serum concentrations of disopyramide and renal clearance while no significant correlation could be demonstrated between free serum concentrations and renal clearance. This implies a constant value of unbound renal clearance. The results are consistent with non linear kinetics (mainly caused by the variable free fraction of the drug), when based on total serum concentrations. The disposition of unbound disopyramide, however seems to be linear (i.e. the kinetic parameters are independent of dose) in the bolus injection study. Total elimination clearance (free and total), volume of distribution and elimination half-life were significantly higher in the steady state experiment than in the bolus injection study.

Adult↗
PubMed1988

Elimination kinetics and urinary excretion of disopyramide in human healthy volunteers.

Elimination kinetics and the renal handling of disopyramide was examined in 8 healthy volunteers. Approximately 50% of the administered disopyramide undergoes hepatic metabolism (metabolic clearance = 116.1 +/- 42.2 ml/min.), while the rest is excreted by the kidneys (renal clearance = 101.9 +/- 21.6 ml/min.). Total renal excretion rate of disopyramide was 0.676 +/- 0.188 mumol/min. and 0.258 +/- 0.029 mumol/min. was excreted by glomerular filtration leaving a net tubular secretion of 60% of the total renal elimination. A significant positive correlation was observed between total serum concentrations and renal clearance values of disopyramide while no significant correlation could be obtained between serum concentrations of the unbound drug and renal clearance values of disopyramide, implying a constant value of unbound renal clearance. Hepatic blood flow was significantly (P less than 0.005) decreased following disopyramide infusion.

Adult↗
PubMed1987

Immediate haemodynamic effects of a novel partial agonist, beta 1-adrenoceptor blocking drug ICI 141,292 after intravenous administration to healthy young volunteers and patients with ischaemic heart disease.

ICI 141,292 is a new beta 1-adrenoceptor blocking drug. The beta 1-adrenoceptor antagonistic effect of ICI 141,292 was examined in a double-blind, randomised crossover study in eight healthy young volunteers and compared with atenolol. Three doses of ICI 141,292 (1, 2 and 4 mg) and atenolol 5 mg were administered intravenously. The attenuation in exercise induced tachycardia varied between 16.0 and 21.2% (P less than 0.01). A significant reduction in blood pressure could be demonstrated following all three doses of ICI 141,292 and atenolol during exercise. At rest in the sitting position HR decreased approximately 8% following all three doses of ICI 141,292 and 14.9% after atenolol 5 mg. No changes in blood pressure were observed under resting conditions after any of the drugs. In six patients with ischaemic heart disease the intrinsic sympathomimetic activity following intravenous administration of four sequential doses (0.5, 0.5, 1.0 and 2.0 mg) of ICI 141,292 was examined. HR decreased 7% (P less than 0.05) following ICI 141,292 1 mg with no further decrease following the succeeding doses. Cardiac output decreased 5.2% (P less than 0.05) following a cumulative dose of 4 mg. No significant changes were observed in mean arterial blood pressure, stroke volume or total peripheral resistance whereas an increase in supine resting mean pulmonary arterial pressure of 3.4 mm Hg (P less than 0.05) could be demonstrated. ICI 141,292 seems to be a potent (at least five times as potent as atenolol) beta 1-adrenoceptor blocking agent possessing moderate intrinsic sympathomimetic activity.

Adrenergic beta-Antagonists↗
PubMed1987

Quantitative and qualitative binding characteristics of disopyramide in serum from patients with decreased renal and hepatic function.

Protein binding of disopyramide, binding capacities, affinity constants and serum concentrations of alpha 1-acid glycoprotein (AAG) were studied in five groups of patients. A: young healthy volunteers (n = 8); B: elderly patients with minor symptoms of ischaemic heart disease (n = 9); C: patients with cirrhosis of the liver and normal values of coagulation factors (II, VII and X), albumin and immunoglobulin G (n = 8); D: patients with cirrhosis and at least two abnormal of the previously mentioned values (n = 9) and E: eleven patients with severely impaired renal function. Subfractions of AAG (Fr1, Fr2 and Fr3) were determined by affinoimmunoelectrophoresis. AAG concentration was significantly (P less than 0.005) elevated in group E patients and decreased (P less than 0.025) in group D patients. Fr2 is probably associated with the high affinity, first binding site of disopyramide to AAG. Earlier observations of a reduced qualitative binding of disopyramide in patients with cirrhosis can be explained by a significant decrease in Fr2 (P less than 0.001) in group D patients. The protein binding of disopyramide in patients with uraemia was significantly increased due to a significant (P less than 0.005) increase in AAG concentration in spite of a smaller (P less than 0.025) affinity constant. Suggestions for therapeutic drug monitoring based on total serum concentrations are given.

Adult↗
PubMed1987

The influence of hepatic insufficiency due to alcoholic cirrhosis on the erythrocyte transketolase activity (ETKA).

The erythrocyte transketolase activity (ETKA), the stimulated erythrocyte transketolase activity (ETKAS), and the thiaminepyrophosphate effect (TPPE) were measured in 21 alcoholic patients with cirrhosis and hepatic insufficiency, 13 alcoholic patients without cirrhosis and 21 non-alcoholic persons before and after oral treatment with 100 mg of thiamine daily for 2 weeks in order to investigate the influence of hepatic insufficiency on these variables. A statistically significant rise in ETKA and fall in TPPE were found in all three groups. ETKA, ETKAS and TPPE did not differ from each other in alcoholic patients with and without cirrhosis, but TPPE was significantly higher in these patients than in the non-alcoholic persons. The conclusions are that severe cirrhosis does not affect the erythrocyte transketolase apoenzyme, the ability of the tissues to convert thiamine to thiaminepyrophosphate for use in the erythrocytes or the absorption of thiamine from the gastrointestinal tract. Besides alcoholism seems to dispose to thiamine deficiency to a higher degree than cirrhosis, and the role of the liver as a thiamine store appears to be of minor importance in the development of thiamine deficiency. Finally, ETKA, ETKAS, and TPPE are considered to be usable as thiamine deficiency indicators in patients with cirrhosis as well as in patients without cirrhosis.

Adult↗
PubMed1987

The prognostic significance of bacteremia in hepatic cirrhosis.

In order to investigate whether bacteremic cirrhosis patients generally have a more serious prognosis than non-bacteremic cirrhosis patients the survival rates of 43 bacteremic and 43 matched non-bacteremic cirrhosis patients were compared. No difference in survival existed between the two groups from the time of cirrhosis diagnosis. However, the survival rate of the bacteremic patients calculated from the onset of bacteremia was significantly shorter than the survival rate of the non-bacteremic cirrhosis patients calculated from the time of random selection (p less than 0.05). Thus the bacteremic patients at the time of bacteremia were generally in a later phase of their disease than the controls at the time of selection. Therefore, bacteremia when it occurs in cirrhosis is a severe prognostic sign, not because of its influence on survival but because of its occurrence late in the course of cirrhosis.

Aged↗
PubMed1987

Displacement of lidocaine from human plasma proteins by disopyramide.

Displacement from human plasma proteins of lidocaine by disopyramide was investigated in serum from nine patients receiving lidocaine treatment because of severe ventricular arrhythmias. From each patient disopyramide in concentrations of 5.9 and 14.7 mumol/l was added to three different serum concentrations of lidocaine and the displacement was examined. At a serum concentration of disopyramide of 14.7 mumol/l the percentage of unbound lidocaine increased from 30.4 +/- 0.2 to 36.3 +/- 0.2% (mean +/- S.E.M., P less than 0.001) at an average total serum concentration of lidocaine of 22.7 mumol/l. The study implies a stronger binding affinity of disopyramide than lidocaine to alpha-1-acid glycoprotein. We recommend caution when using disopyramide immediately after an infusion of lidocaine. With the dosage regimen used serum concentrations considerably above the suggested therapeutic level were achieved in the majority of patients.

Aged↗
PubMed1987

Haemodynamic effects of disopyramide using a new model of intravenous administration.

Intravenous treatment with disopyramide is usually performed by administration of a bolus injection of 150 mg given over 5 min. followed by a continuous infusion of 18-24 mg hour-1. A decrease in cardiac output is associated with this rapid bolus injection. Seven patients with ischaemic heart disease entered an open randomised cross-over trial to elucidate if an extension of the bolus injection time to 20 min. resulted in a smaller decrease in cardiac output. Cardiac index decreased significantly (P less than 0.001) in both situations, with maximum decrease observed at time 5 and 20 min., respectively (equivalent to the ending of the administration of 150 mg disopyramide). The decrease in Cardiac index (mean +/- S.E.M.) was identical in the two situations (2.56 +/- 0.23 to 1.78 +/- 0.21 l/min. X m2 (30%) and 2.66 +/- 0.17 to 1.94 +/- 0.19 l/min. X m2 (27%], respectively. Blood pressure was unchanged, while heart-rate (P less than 0.025) and preejection period index (P less than 0.005) increased significantly and to the same extent in the two situations. Significant correlations between the log free and log total serum concentration of disopyramide and the relative change in preejection period index of r = 0.840 (P less than 0.01) and 0.919 (P less than 0.01), respectively, were observed giving disopyramide over 5 min. A significant anticlockwise hysteresis was observed extending the time of administration to 20 min. As no haemodynamic advantages are achieved by the slower way of administration we would still recommend the bolus injection to be given over 5 min.

Disopyramide↗
PubMed1986

Haemodynamic effects and kinetics of concomitant intravenous disopyramide and atenolol in patients with ischaemic heart disease.

The haemodynamic effects of concomitant intravenous administration of disopyramide (Norpace) and atenolol (Tenormin) were studied in a cross-over trial in 7 patients with ischaemic heart disease. Following 150 mg disopyramide i.v. the cardiac index (CI) and stroke volume index (SVI) decreased by 14% and 26%, respectively and the heart rate (HR) and preejection period index (PEPI) increased by 13% and 19%, respectively. A decrease in CI of 14% and HR of 21%, respectively were noted after intravenous administration of 7.5 mg atenolol; PEPI increased by 10% whereas SVI remained unchanged. The cardiac Index (CI) fell by 33% following the administration of both drugs. The effect on CI of the two drugs was additive. The effect of disopyramide and atenolol on HR, SVI and PEPI was not significantly modified by coadministration of the other drug. No change in blood pressure was observed after disopyramide or atenolol. A correlation (rho) of 0.540 and 0.387 was observed between the change in PEPI and the log free and total serum concentrations of disopyramide, respectively. Combined intravenous use of the two drugs in patients with incipient or overt heart failure is not recommended, unless it is due to the arrhythmia to be treated.

Aged↗
PubMed1986

Kinetics of disopyramide in decreased hepatic function.

The elimination kinetics of disopyramide was studied in 9 patients with decreased hepatic function (DHF) due to histologically verified cirrhosis of the liver, and in 11 patients with ischaemic heart disease (IHD). Disopyramide 100 and 150 mg was given intravenously as a bolus to the patients with IHD and DHF, respectively, followed by a continuous infusion of disopyramide 0.3 (DHF group) and 0.4 mg X min-1 (IHD group) until steady-state was achieved. A significant (p less than 0.001) positive correlation between the percentage unbound and total serum concentration of disopyramide was demonstrated in both groups. The percentage of unbound disopyramide at a total serum concentration of 5.9 mumol X l-1 was 45.5% and 19.4% in the DHF and IHD groups, respectively. A negative correlation (r = -0,751, p less than 0.05, and r = -0.827, p less than 0.01 in the IHD and DHF patients, respectively) between the free fraction of disopyramide and alpha 1-acid glycoprotein was observed. The serum concentration of alpha 1-acid glycoprotein, the major binding protein of disopyramide, was significantly lower in the patients with DHF. The clearance of unbound disopyramide and its total volume of distribution and half-life were significantly lower in the DHF patients. No difference in total elimination clearance could be demonstrated. The clinical implication of the present findings appear to be that the dosage of disopyramide should be reduced by 25% when it is given intravenously to patients with decreased hepatic function.

Adult↗
PubMed1986

Immunostimulation of blood monocyte function by RU 41.740 (Biostim) in patients with chronic bronchitis.

RU 41.740 (Biostim), a glycoprotein extract from Klebsiella pneumoniae, which is effective in heightening resistance to experimental infections in animals, was examined with regard to influence on human blood monocyte function in vitro after administration to patients with chronic bronchitis in a randomized, double-blind clinical trial. Twelve patients were given Biostim orally (seven patients received 8 mg daily and five patients received 2 mg daily) while eight patients received placebo. In the Biostim group monocyte phagocytosis increased from 1.4 yeast cells per monocyte before therapy to 3.1 yeast cells per monocyte after 1 month (P less than 0.05) with no further increase after 3 months. Monocyte candidacidal activity increased in the Biostim group from 51% before therapy to 69% after 1 month (P less than 0.05) with a decrease to 57% after 3 months. As expected, placebo had no significant effect on monocyte functions. There was no difference between the improvement in the high dose vs the low dose group. These results suggest that Biostim exerts part of its immunostimulatory property by stimulating blood monocyte antimicrobial function.

Adjuvants, Immunologic↗