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Biomedical subjects

E Tiula

Publications and source records attributed to E Tiula.

26 records · Page 2Linked to original sources

Factors affecting serum protein binding of phenytoin, diazepam and propranolol in acute renal diseases.

The effect of acute renal disease on the serum free fraction of phenytoin, diazepam and propranolol was examined in vitro among 37 patients with acute renal insufficiency of varying etiology and 10 healthy control subjects, men and women equally. The free fractions were separated at 37 degrees C using a pressure ultrafiltration method. The free fraction of phenytoin varied from about 14% to 45% and that of diazepam from 2% to 10%. The free fraction did not correlate significantly with either the serum urea or creatinine concentrations or the creatinine clearance within the acutely uremic group. The free fractions of propranolol varied considerably in the uremic patients but did not correlate significantly with the above parameters either. The mean free fractions of propranolol in the acutely uremics (11.9 +/- 1.0%, mean +/- SE) and controls (8.9 +/- 0.5%) did not differ significantly. The free fractions of both phenytoin and diazepam had a significant inverse correlation with the serum albumin level and that of propranolol with the alpha 1-acid glycoprotein (alpha, AGP) level. The correlations were similar irrespective of the etiology of renal failure. In practice, the variable best predicting the phenytoin and diazepam free fractions in acute renal insufficiency is the serum albumin concentration, and for propranolol the serum alpha 1-AGP concentration.

Acute Kidney Injury↗

Effect of total drug concentration on the free fraction in uremic sera.

The effect of total drug concentration on the free fraction was studied in vitro using sera of uremic and nonuremic subjects. Both therapeutic and toxic concentrations of radiolabeled phenytoin, diazepam, and propranolol were used. The free fraction was separated by a pressure ultrafiltration method at 37 degrees C and determined from 200-microliters aliquots of serum and the ultrafiltrate. Sera from 11 acutely uremic and 10 chronically uremic patients and from 10 healthy control subjects were used. Only slight increases in the free fraction were found over the concentration range studied in both nonuremic and uremic subjects. The concentration-dependent increases in the unbound fraction of phenytoin and diazepam were quite negligible compared with the two- to threefold increases caused by uremia itself. Thus, variation in total concentrations of phenytoin, diazepam, and propranolol does not change the free fractions to a clinically significant degree even in uremic patients with a compromised binding capacity.

Adult↗

A pressure ultrafiltration method for serum free drug determination. Comparison with equilibrium dialysis using normal and uraemic sera.

The clinical methods most frequently used for serum free drug determinations are equilibrium dialysis and ultrafiltration. Both methods have usually been considered equal when comparisons have been made on normal sera. The purpose of the study was to develop a reliable and rapid method for serum free drug determinations especially for disease states where there is an increased free fraction. This modification of the pressure ultrafiltration method proved to meet these demands. The method was tested in vitro by adding radiolabelled phenytoin in different concentrations to normal and uraemic sera. The within-run and between-run variation coefficients were both under 5%. In comparison with equilibrium dialysis the values obtained by the ultrafiltration method were 0.65% lower (p less than 0.001, Student's paired t-test) in normal and 0.37% lower (non-significant) in uraemic sera. There are some theoretical grounds to presume that the results obtained by means of the pressure ultrafiltration method would better reflect the real values than those obtained by means of equilibrium dialysis.

Dialysis↗

Disturbances in the function of cardiac pacemaker caused by short wave and microwave diathermies and pulsed high frequency current.

The effect of short wave diathermy, pulsed high frequency current (Diapulse, Curapuls) and microwave diathermy on the function of an implantable cardiac pacemaker and its leads was examined by measuring the output (voltage) and rate of the pacemaker under various experimental conditions. It appeared that all these devices had a decreasing effect on the output and an increasing effect on the rate of the pacemaker. When therapeutic doses (power) were applied the greatest changes in output and rate were caused by microwave diathermy and the slightest by Curapuls. The clinical precautionary measures based on these observations are discussed.

Arrhythmias, Cardiac↗