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Biomedical subjects

P Kozlovskis

Publications and source records attributed to P Kozlovskis.

11 recordsLinked to original sources
PubMed1995

Selective removal of plasma low density lipoprotein with the HELP system: biweekly versus weekly therapy.

PURPOSE: Biweekly (once every 2 weeks) heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) therapy was evaluated for safety and efficacy in selectively reducing LDL cholesterol levels compared with weekly HELP therapy. PATIENTS AND METHODS: Biweekly treatments were given to high-risk, diet/drug resistant hypercholesterolemic patients (n = 23) after 6 months of weekly HELP therapy. Lipids, lipoprotein cholesterol, apolipoproteins A-I and B, and fibrinogen were measured on plasma samples before and after treatment. RESULTS: Mean plasma volume treated was 2.8 l and mean treatment duration 1.7 h. Therapy complications were minimal. In 98% of 268 biweekly HELP treatments, LDL cholesterol levels were reduced by > 30%. For patients completing 6 months of biweekly therapy following 6 months' weekly therapy (n = 23), mean LDL cholesterol levels were reduced 138.5 mg/dl (111.2 mg/dl weekly) with a time-averaged decrease from mean pre-apheresis levels of 33% for biweekly therapy (39% weekly). Mean total cholesterol (161.2 mg/dl biweekly versus 132.9 weekly) and apolipoprotein B (104.6 mg/dl versus 92.6) levels were also reduced with each treatment. Mean HDL cholesterol was reduced only 6.1 mg/dl (6.3 mg/dl weekly). CONCLUSIONS: Biweekly HELP treatments can safely reduce LDL cholesterol levels as consistently as weekly HELP treatments. However, the higher pre-treatment LDL cholesterol levels with biweekly treatments may produce less therapeutic benefit than with weekly therapy.

Blood Component Removal↗
PubMed1993

Weekly treatment of diet/drug-resistant hypercholesterolemia with the heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) system by selective plasma low-density lipoprotein removal.

Heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) weekly therapy was evaluated for safety and efficacy in selectively reducing LDL cholesterol levels. Weekly treatments (25) were given to high-risk hypercholesterolemic patients (n = 33) with screening LDL cholesterol levels > 160 mg/dl despite prior diet and drug therapy. Lipids, lipoprotein cholesterol, apolipoproteins A-l and B, and fibrinogen were measured on plasma samples before and after treatment. Mean plasma volume treated was 2.66 liters and mean treatment duration 1.7 hours. Therapy complications were infrequent and were primarily vascular access problems or hypotension. Treatment goals were > 30% LDL cholesterol reduction with each treatment. In 98% of 686 HELP treatments, LDL cholesterol levels were reduced > or = 30%. Mean LDL cholesterol levels were reduced 111.0 mg/dl (54%) with a time-averaged decrease of 39% over a 25-week course. Mean HDL cholesterol was reduced only 6.2 mg/dl (15%). Total cholesterol (134.4 mg/dl; 47% decrease) and apolipoprotein B (88.7 mg/dl; 53% decrease) levels were also reduced. Fibrinogen decreased 158.2 mg/dl (58%) without bleeding complications. HELP therapy can safely and selectively remove plasma LDL cholesterol, producing consistent reductions in LDL cholesterol, total cholesterol and apolipoprotein B levels.

Apolipoproteins B↗
PubMed1991

Paired comparisons of efficacy of intravenous and oral procainamide in patients with inducible sustained ventricular tachyarrhythmias.

Thirty-eight patients who had inducible sustained ventricular tachycardia during baseline programmed electrical stimulation underwent electrophysiologic testing after both intravenous and oral administration of procainamide. Each had presented clinically with documented sustained ventricular tachycardia or out of hospital cardiac arrest not associated with acute myocardial infarction. In 23 patients (61%) (Group I) the arrhythmia became noninducible during an intravenous infusion of procainamide. Oral procainamide was subsequently administered and retesting was carried out after dose titration to match plasma concentration at the end of the intravenous study. Among the 23 patients in Group I the mean (+/- SD) plasma procainamide level was 7.2 +/- 2.8 micrograms/ml after intravenous dosing and 7.9 +/- 2.5 micrograms/ml after oral dosing (p = 0.09). In 15 (65%) of the 23 patients, sustained ventricular arrhythmia was inducible on oral therapy with comparable plasma procainamide levels (intravenous = 6.3 +/- 2.1 micrograms/ml, oral = 7.5 +/- 2.1 micrograms/ml). The other eight patients (35%) had concordant responses to repeat testing with comparable intravenous (mean 9.0 +/- 3.3 micrograms/ml) and oral (8.8 +/- 3.1 micrograms/ml) plasma procainamide levels. In the additional 15 patients (Group II) sustained ventricular tachyarrhythmia remained inducible on intravenous procainamide therapy and the patients were retested on oral therapy with similar plasma concentration (p = 0.05). In seven patients (47%) sustained ventricular tachyarrhythmia was noninducible on treatment with oral procainamide (mean plasma level 7.6 +/- 2.7 micrograms/ml) after failure of intravenous procainamide (mean plasma level 10.3 +/- 2.3 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

QRS morphology-dependent, concordant frequency distribution of single and repetitive forms of ventricular ectopic activity.

We tested the relationship between the frequency of single premature ventricular complexes (PVCs) of specific QRS morphologies and repetitive forms (RF) of greater than or equal to 2 PVCs. Fourteen patients with multiform PVCs and RFs underwent 8-hour, two-channel continuous electrocardiographic monitoring. After a 2-hour baseline, procainamide was administered intravenously at 25 mg/min until PVC suppression or 1000 mg. Multiple regression analysis was used to relate the frequencies of repetitive forms initiated by PVCs of the most frequent QRS morphology (M1) and the second most frequent QRS morphology (M2) to the frequency of M1 and M2 single PVCs. Parallel changes in the frequency of M1 RFs and M1 PVCs occurred in 9 of 14 patients and parallel changes in the frequency of M2 RFs and M2 PVCs occurred in 7 of 14 patients (i.e., the relationships were concordant). In two patients, M1 RFs related to M2 PVC frequency; in three patients, M2 RFs related to M1 PVC frequency (i.e., the relationships were discordant). Thus concordant frequency distributions were present in 16 of 28 (57%) comparisons, while a discordant relationship occurred in only 5 of 28 (18%) comparisons (p less than 0.005). In conclusion, there is frequent concordance in the frequency distribution of single multiform PVCs and of RFs initiated by PVCs of the same QRS morphology during a pharmacologic intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Complexes, Premature↗
PubMed1989

The clinical implication of changing unbound quinidine levels.

Pharmacodynamic and pharmacokinetic aspects pertinent to the potential clinical application of unbound quinidine levels were studied. Following heparin administration during electrophysiologic testing in 10 patients receiving quinidine, there were significant increases in the mean (+/- SD) right ventricular effective refractory period (266 +/- 24 versus 279 +/- 23; p less than 0.025), free fatty acid concentration (515 +/- 213 versus 1071 +/- 359 mmol/L; p less than 0.001), and unbound quinidine concentration (0.3 +/- 0.1 to 0.6 +/- 0.1 microgram/ml; p less than 0.001) but no changes in heart rate, corrected QT interval, or total plasma quinidine concentration. Ten control patients showed no change in the right ventricular effective refractory period following heparin administration. These findings were consistent with a heparin-induced increase in unbound drug concentration and activity that was limited to the vascular compartment. Eleven patients studied on day 3 (+/- 1) and day 10 (+/- 3) during an acute myocardial infarction showed a significant decrease in unbound quinidine fraction (12 +/- 4% versus 9 +/- 4%; p less than 0.02) accompanied by a decrease, rather than the predicted increase, in half-life (7.1 +/- 2.7 versus 6.3 +/- 2.1 hours; p less than 0.02). Volumes of distribution remained stable while the mean quinidine clearance tended to increase. Half-life correlated with albumin changes (r = -0.71; p less than 0.02). Apparently, improvement in clinical status (assumed) and drug clearance (measured) negated the direct effects of the decrease in unbound quinidine fraction. Although unbound drug concentrations should correlate best with drug dynamic and kinetic information, full knowledge of the clinical context of such measurements is needed for appropriate interpretation.

Adult↗
PubMed1988

QRS morphology-dependent pharmacodynamics in multiform ventricular ectopic activity.

The effect of an infusion of intravenous procainamide on the frequency of ventricular premature complexes (VCPs) of differing QRS morphologies was studied in 20 patients with multiform ectopic activity. In 17 of 20 patients, there was differential suppression of single VPCs with different QRS morphologies. VPCs of the most frequent QRS morphology and the second most frequent QRS morphology were compared with respect to the procainamide level at the escape of VPCs from 85% suppression and the duration of suppression measured from the onset of the procainamide infusion. In 8 patients, VPCs of the most frequent QRS morphology remained suppressed at lower procainamide concentrations and for longer times than did VPCs of the second most frequent QRS morphology (escape procainamide concentration = 2.8 +/- 1.7 versus 5.4 +/- 2.3 micrograms/ml, p less than 0.025; time to escape 244 +/- 138 versus 98 +/- 114 min; p less than 0.05). In 9 other patients, VPCs of the second most frequent QRS morphology remained suppressed at lower procainamide concentrations and for longer times than did VPCs of the most frequent QRS morphology (escape procainamide concentration 2.9 +/- 1.4 versus 8.3 +/- 6.3 micrograms/ml, p less than 0.025; time to escape 317 +/- 114 versus 63 +/- 80 min; p less than 0.001). Thus, in individual patients there are specific patterns of suppression of VPCs of different QRS morphologies which are independent of the frequency of each morphology. There is apparently a differential pharmacologic effect of procainamide on the foci or pathways responsible for the different QRS morphologies of multiform VPCs.

Arrhythmias, Cardiac↗
PubMed1984

Dynamic variability of binding of antiarrhythmic drugs during the evolution of acute myocardial infarction.

We tested the hypothesis that the changes in free fatty acid and alpha 1-glycoprotein concentrations, which occur during acute myocardial infarction, exert asynchronous and opposing influences on the serum protein binding of selected drugs. Free drug fractions of two antiarrhythmic agents with contrasting binding characteristics, quinidine and procainamide, were related to free fatty acid and alpha 1-glycoprotein concentrations on days 1 through 5 and 10 in 20 patients with acute myocardial infarction. The mean free quinidine fraction was elevated on day 1 (9.0 +/- 4.4% vs 6.7 +/- 2.7% in patients with stable heart disease; p less than .05) and fell progressively to day 10 (4.0 +/- 2.8%; p less than .0002) as free fatty acid concentration decreased (day 1 = 464 +/- 272 meq/liter; day 10 = 264 +/- 155 meq/liter; p less than .01) and alpha 1-glycoprotein concentration increased (day 1 = 98 +/- 31 mg/dl; day 10 = 141 +/- 47 mg/dl; p less than .02). Multiple stepwise regression showed a major influence of changing alpha 1-glycoprotein concentration on the observed sequential changes in the free quinidine fraction (p less than .005). In contrast, no serial changes in procainamide binding were noted. In conclusion, metabolic changes during the course of acute myocardial infarction sequentially alter free quinidine fraction and, consequently, may influence pharmacodynamics.

Aged↗