PubMed Health⌕ Search

Biomedical subjects

F Peters

Publications and source records attributed to F Peters.

At least 73 records · Page 4Linked to original sources
PubMed1983

Possible contribution of encainide metabolites to the long-term antiarrhythmic efficacy of encainide.

To establish long-term efficacy and the relation between drug plasma concentration and antiarrhythmic response, 12 patients with encainide-responsive frequent complex ventricular ectopic activity underwent 1 year of therapy with encainide. Twenty-four hour ambulatory electrocardiograms were obtained at baseline and every 2 months. Drug withdrawal with concomitant plasma sampling and electrocardiographic monitoring was performed at 6 and 12 months. Average group premature ventricular contraction (PVC) suppression during the year was 97 to 99%, with nearly total suppression of pairs and salvos. The most common adverse effects were transient visual disturbances and dizziness or lightheadedness. During a dose interval (6 to 12 hours) the concentration of encainide metabolites exceeded that of encainide by several-fold. The median time of arrhythmia return after drug withdrawal was 12 to 14 hours. At the time of arrhythmia return encainide was generally no longer detectable but the average concentration of O-demethylencainide and 3 methoxy-O-demethylencainide was 72 +/- 49 and 172 +/- 74 ng/ml, respectively. It is concluded that encainide therapy is extremely effective for continuous long-term suppression of complex ventricular arrhythmias and its metabolites contribute significantly to its antiarrhythmic action during chronic oral therapy.

Adult↗
PubMed1983

The influence of tracers on insulin binding to human erythrocytes.

We studied insulin binding to human erythrocytes using two different 125I-insulin-tracers. Erythrocytes of 8 normal subjects were examined using [mono-125II-(Tyr A 14)insulin as tracer. Three of these erythrocyte preparations were examined simultaneously using [125I]insulin, which was randomly iodinated by the chloramine-T-method. Data were analysed by a computerized non-linear least-squares procedure both on the basis of one and two class receptor models. Only the one class receptor model yielded consistent results. When the two class receptor model was applied the low affinity branch of the Scatchard plot was not reproducible. On the basis of the one class receptor model the number of receptor sites was lower (R0 = 0.046 +/- 0.006 nmol/l equivalent to 6.3 +/- 0.8 receptors/erythrocyte) with [mono-125I-(Tyr A 14)]insulin as compared to [125I]insulin randomly iodinated by the chloramine-T method (R0 = 0.070 +/- 0.008 nmol/l equivalent to 9.6 +/- 1.1 receptors/erythrocyte). Conversely, the affinity of the [mono-125I-(Tyr A 14)]insulin was higher (Ka = 2.6 +/- 0.3 x 10(9) l . mol-1 vs. 1.9 +/- 0.2 x 10(9) l . mol-1.

Adult↗
PubMed1982

A critical interpretation of experiments on binding of peptide hormone to specific receptors by computer modelling.

Many investigations dealing with the interaction of peptide hormones and specific cell membrane receptors imply the existence of two classes of independent binding sites. On class is characterized by high affinity and low capacity, the other one by low affinity and high capacity. This conclusion has been derived from the fact that the Scatchard plots of binding data show a significant upward curvature. Using a more precise and critical method of evaluation these findings probably must be revised in some cases. Other conclusions taken from linear plots concerning the regulation of hormone receptors should be discussed more carefully. Some sources of errors caused by an uncritical interpretation of Scatchard plots are demonstrated.

Animals↗
PubMed1982

A quantitative analysis of glucagon binding to isolated intact neonatal and adult rat hepatocytes on the basis of two different binding models.

The interaction of glucagon with specific receptors has been studied in isolated intact neonatal and adult rat hepatocytes. The hormone binding measured directly with 125I-labelled glucagon was saturable and reversible. The 125I-labelled glucagon binding was inhibited by unlabelled homologous hormone at concentrations ranging from 0.5 nM to 50 microM. Two different binding models were assumed to analyse the binding data by a nonlinear least-squares procedure: (I) a single class of independent sites and (II) two classes of independent sites. The comparison of the fitted theoretical curves reveals that both binding models are in fact compatible with these data. Adult hepatocytes have a considerably higher affinity for glucagon than neonatal hepatocytes; the binding capacity of neonatal liver cells from 1-7-days-old rats proved to be markedly reduced compared with the cells from adult rats. The glucagon-induced intracellular cyclic AMP production was measured at various hormone concentrations under conditions identical to those for the determination of extracellular hormone binding. The correlation of both parameters indicates a direct connection between receptor-occupancy and adenylate cyclase stimulation of both parameters indicates a direct connection between receptor-occupancy and adenylate cyclase stimulation. These results suggest that a decreased receptor concentration in neonatal hepatocytes is responsible for the decreased cyclic AMP production.

Age Factors↗
PubMed1982

Randomized double-blind placebo controlled crossover trial documenting oral lorcainide efficacy in suppression of symptomatic ventricular tachyarrhythmias.

Lorcainide, a new antiarrhythmic drug, was given to 10 patients with frequent (greater than 1/min) premature ventricular contractions (PVCs) on a baseline 24-hour Holter monitor. Each patient received lorcainide, 100 mg twice daily, and an identical placebo, in a randomized double-blind crossover trial, with 1 week in each treatment period. Before the trial and at the end of each period, routine laboratory, clinical evaluation, 12-lead ECG's, and 24-hour ambulatory ECG recordings were performed. Trough drug plasma concentration measurements were done at the end of each treatment period. All patients had reduction in PVCs, comparing drug to placebo, averaging 82.3 +/- 19.7% (mean +/- SD, p less than 0.01 by Wilcoxin ranked sum), and there was also significant decrease in the number of ventricular pairs and runs. Levels of the major metabolite, norlorcainide, ranged from 34 to 254 ng/ml (mean 160 ng/ml) and exceeded those for lorcainide, range 6 to 169 ng/ml (mean 79 ng/ml). Prolongation of PR, QRS, and QTc intervals was evident during drug therapy, as was decrease in heart rate, but these changes were minimal. The major adverse effect noted was sleep disturbance, which was often initially severe, but improved during the week of therapy.

Administration, Oral↗
PubMed1982

Antiarrhythmic efficacy of amiodarone in recurrent ventricular tachycardia evaluated by multiple electrophysiological and ambulatory ECG recordings.

Thirty-three patients with recurrent drug-refractory ventricular tachycardia were treated with oral amiodarone during an average period of 6.1 months. In-hospital monitoring for two weeks or more, electrophysiological tests and ambulatory ECG were used to evaluate the results. Twenty patients are still using the drug with complete control of the arrhythmia. Eleven have failed the drug, ten due to recurrence of documented ventricular tachycardia. Only three patients failed after the first month of therapy. Two patients died, one suddenly. The drug was discontinued in a further two patients due to side-effects. Other side-effects were tolerable or manageable by dose adjustments alone. Five patients showed evidence of inadequate arrhythmia control between days 15 and 32 of therapy but subsequently responded to the drug for 4-9 months, giving further support to the concept that in some patients at least 30 days of therapy is necessary for the full effect of the drug to appear. In 16 of the 20 patients tested by arrhythmia induction study while on the drug, ventricular tachycardia could still be induced. Seven (44%) of these eventually failed the drug. Arrhythmia recurred in one of those four in whom tachycardia could not be induced. Amiodarone is a valuable drug in the management of recurrent ventricular tachycardia, refractory to other antiarrhythmic drugs.

Adult↗
PubMed1982

Interactions between psychosomatic conflicts and gonadotropin secretion.

This present paper represents an attempt to correlate hormonal patterns and psychoanalytical data in 30 patients with secondary amenorrhea. Based on psychoanalytical data and the maximal LH response to GnRH, which were obtained independently, the patients were divided into two groups presenting differing psychosomatic symptomatologies. Patients with severe psychosomatic disease (group A) complaining predominantly of somatic discomfort, exhibited a weak pituitary response to GnRH. Patients presenting mainly mental symptoms were found to be less affected by the psychosomatic disease (group B). The LH responses to GnRH were only moderately impaired in these patients. Seven patients of group A underwent psychotherapy, resulting in a resumption of regular menses in 4 patients. Eight untreated controls of this group who remained amenorrheic exhibited unaltered gonadotropin in levels. All patients of group B being treated by psychotherapy resumed regular menses, while 5 of 7 control patients developed spontaneous menstruation. The progress of sexual maturation in these patients is correlated with increasing pituitary LH response to GnRH. The present study provides evidence that the degree of a psychosomatic disturbance resulting in secondary amenorrhea is reflected by the pattern of plasma LH after GnRH stimulation.

Adult↗
PubMed1981

Electrophysiologic effects of N-acetylprocainamide in human beings.

The electrophysiologic properties of N-acetylprocainamide (NAPA) were studied in 10 patients undergoing cardiac catheterization. Each patient received two successive intravenous infusions: one loading infusion over 15 minutes and one maintenance infusion at a slower rate for 30 minutes. Eight patients received 10.5 mg/kg body weight and two received larger doses (16 and 21 mg/kg, respectively). NAPA plasma concentration was measured at 5 minute intervals from 0 to 25 minutes, and then at 15 and 30 minutes of the second infusion. Mean blood pressure and electrophysiologic data obtained by programmed stimulation were recorded before drug administration and at 15 and 30 minutes of the infusion when the concentration of NAPA was nearly constant in each patient (range 12 to 35 microgram/ml). NAPA decreased blood pressure (p less than 0.005), increased corrected Q-T interval (p less than 0.01) and increased the atrial and ventricular effective refractory periods from 267 +/- 40 to 307 +/- 41 ms (p less than 0.01) and from 278 +/- 37 to 301 +/- 32.8 ms (p less than 0.05), respectively. NAPA did not significantly change sinus cycle length or sinus nodal recovery time, conduction intervals (A-H, H-V, P-R, QRS), atrioventricular nodal functional refractory period or nodal Wenckebach cycle length. The patient receiving the largest dose experienced mild nausea when the plasma concentration was above 35 microgram/ml. These data show that the electrophysiology of NAPA in human beings is different from that reported for procainamide. At the plasma concentrations studied NAPA increases atrial and ventricular refractory periods without increasing cardiac conduction times

Acecainide↗
PubMed1981

Clinical pharmacology and antiarrhythmic efficacy of N-acetylprocainamide.

Eleven patients with chronic ventricular arrhythmias took part in a study of N-acetylprocainamide (NAPA), the major metabolite of procainamide, in order to characterize further NAPA's clinical pharmacology and antiarrhythmic action. The frequency of ventricular arrhythmia on 24 hour ambulatory electrocardiographic recordings was comparable on recordings obtained in a prestudy screening, during treatment with placebo before administration of NAPA and after treatment with NAPA. The initial dosage of NAPA was 500 mg every 8 hours, which was increased by 500 mg increments every few days until 90 percent suppression of arrhythmia or intolerable adverse effects occurred. Only two patients achieved 90 percent suppression of ventricular ectopic complexes. The mean plasma concentration associated with 90 percent suppression of arrhythmia in these two patients ws 12.6 and 32.3 mg/ml, respectively. One of these two patients was unable to continue long-term therapy with NAPA because of a rash. Other adverse effects included gastrointestinal symptoms in seven patients with visual symptoms in four patients at plasma concentratons as low as 6.9 mg/ml. NAPA obeyed linear pharmacokinetics over the range of dosages studied (500 to 2,500 mg every 8 hours) and had a half-life of 10.7 +/- 1.98 hours (mean +/- standard deviation). There was no change in the P-R or QRS intervals and there was a dose-dependent prolongation of the Q-Tc interval. It is concluded that in this patient group, NAPA suppressed chronic ventricular ectopic complexes without adverse effects in only a minority of patients.

Acecainide↗
PubMed1981

Characterization of ventricular tachyarrhythmias on ambulatory ECG recordings in post-myocardial infarction patients: arrhythmia detection and duration of recording, relationship between arrhythmia frequency and complexity, and day-to-day reproducibility.

We performed three consecutive 24-hour ECG recordings in 57 ambulatory patients approximately 8 to 11 days of post-myocardial infarction. There was considerable additional detection of each type of complex ventricular ectopic beat (VEB) with recordings beyond 24 hours. Multiform, R-on-T, pairs, and bigeminy were often first detected from 24 to 48 hours and 5 of 12 patients with ventricular tachycardia had this rhythm detected only after 48 hours of monitoring. Complex forms were deleted with short recording durations primarily in patients who had complex forms present during a large number of hours during the 72-hour recording session. The occurrence of each type of complex ectopic beat was strongly related to PVC frequency and some type of complex form was seen in virtually all 24-hour recordings with greater than a total of 100 VEBs. Sixty-five percent of 24-hour recordings with infrequent VEBs (2 to 10 per 24 hours) also had complex forms present. The day-to-day reproducibility of VEB frequency and complexity was reasonable, but was largely accounted for by the fact that most recordings were free of frequent ectopic beats and a given type of complex PVC. These data suggest that for longer ECG recording period, the frequency of occurrence of complex forms rather than simply their presence or absence may be important for identifying high risk subgroups.

Adult↗
PubMed1981

Clinical pharmacology and antiarrhythmic efficacy of encainide in patients with chronic ventricular arrhythmias.

We determined the pharmacokinetics, efficacy and therapeutic plasma concentration of encainide, a new antiarrhythmic drug that affects His-Purkinje conduction but not ventricular refractoriness. Nine patients with frequent and complex premature ventricular complexes were studied in a 3-day double-blind protocol. Each day, each patient received 75 mg of i.v. or oral encainide or placebo. Frequent blood samples for encainide plasma concentration determination and continuous ambulatory ECGs were obtained. There was a marked intersubject variation in bioavailability (mean 42 +/- 24%, range 7.4-82%), clearance (13.2 +/- 5.6 ml/min/kg, range 3.75-22.1 ml/min/kg) and half-life (3.4 +/- 1.7 hours i.v., 2.5 +/- 0.8 hours oral). Eight of nine patients had more than 90% suppression of premature ventricular complexes for 3-36 hours. Minimal antiarrhythmic plasma concentration was higher (39 +/- 54 ng/ml, range 3.5-170 ng/ml) after i.v. dosing than after oral dosing (14 +/- 16 ng/ml, range 1.5-48 ng/ml), suggesting an active metabolite after oral dosing in many patients. Minimal side effects were seen despite high peak plasma concentrations (range 794-1556 ng/ml i.v., 36-495 ng/ml oral). The minimal ratio of toxic to therapeutic plasma concentration ranged from 4.3-326 (median 23) after oral dosing. Antiarrhythmic action was associated with an 11-44% widening of the QRS complex that was not associated with other adverse effects. We conclude that encainide effectively suppresses ventricular arrhythmias. Despite a variable bioavailability, high clearance and short half-life, its wide ratio of toxic to therapeutic concentration and probable active metabolite permit a long duration of action, which should allow a reasonable dose schedule in most patients during chronic oral dosing.

Aged↗
PubMed1980

Plasma levels of FSH and LH in patients with gonadal dysgenesis during sequential estrogen and progestogen therapy.

We describe the plasma levels of FSH and LH in ten patients with gonadal dysgenesis during treatment with a low dosage sequential estrogen-progestogen preparation. The daily dose of mestranol ranged from 12.5--50 microgram. Norethisterone was administered from day 16 onwards, the dose ranging between 0.75 and 1.5 mg. It was shown that 25 microgram mestranol was effective in lowering the elevated FSH levels significantly (alpha < 0.001). LH levels remained unaffected. The combination of 25 microgram mestranol and 1 mg norethisterone produced an increase of FSH and LH within 12 h, maximum levels being reached within 36 h after which there was a progressive decline. Low doses of estrogen and progestogen appeared capable of evoking physiological hypothalamic and pituitary responses in patients with gonadal dysgenesis. The doses employed were sufficient to induce breast development, growth of sexual hair, and withdrawal bleeding and were probably not high enough to induce rapid bone maturation and consequent stunting of growth.

Adolescent↗