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Biomedical subjects

N A Klitgaard

Publications and source records attributed to N A Klitgaard.

At least 55 records · Page 3Linked to original sources
PubMed1989

Circadian variation in the pharmacokinetics of verapamil.

Circadian variation in the metabolism of verapamil was investigated in 10 patients with stable angina pectoris during treatment with sustained-release verapamil 360 mg at 08.00 h or 22.0 h. No major difference in exercise parameters was found. During the evening dosage schedule a significantly greater bioavailability (AUC) and a prolonged time to peak concentration was found. During the night (24.00 h-06.00 h) the half-life of verapamil was significantly longer than during the day (16.00 h-22.00 h). These differences in pharmacokinetics may be due to reduced hepatic blood flow at night or to circadian variation in hepatic microsomal metabolism.

Angina Pectoris↗
PubMed1989

Sustained-release and instant-release verapamil in treatment of angina pectoris.

The efficacy of a sustained-release preparation of verapamil (verapamil-SR) has been compared with that of a conventional instant-release formulation (verapamil-IR) in 10 patients with stable angina pectoris treated for 3 weeks with both preparations. The diurnal serum concentrations of verapamil and norverapamil did not differ significantly during treatment with verapamil-IR 120 mg t.i.d. and verapamil-SR 360 mg once daily, but verapamil-SR 240 mg produced significantly lower serum concentrations. The differences did not affect the exercise capacity or the occurrence of ST-segment depression during maximal exercise. Verapamil-SR was well tolerated. A multiple instant-release dosage regime can now be replaced by once daily administration of the sustained-release preparation.

Angina Pectoris↗
PubMed1989

Increased 22Na+-influx in lymphocytes from offspring of essential hypertensive patients.

Lymphocytes were used as a cellular model for the in vitro measurements of 22Na+-influx during sodium pump inhibition by ouabain. The measurements were made using lymphocytes from young men at increased risk of developing essential hypertension in order to assess any changes and to analyse whether any such changes were associated to borderline hypertension and/or heredity. Four groups were evaluated: 28 normotensive and 20 borderline hypertensive offspring of hypertensives, 12 borderline hypertensives and 28 normotensives with normotensive parents. 22Na+-influx was significantly increased in offspring of hypertensive parents especially in the normotensive offspring of hypertensive parents. The association between heredity and increased 22Na+-influx found by us in vitro may be caused by either an increased passive sodium-influx and/or an increased sodium-sodium exchange mechanism.

Adolescent↗
PubMed1989

Increased number of ouabain binding sites in lymphocytes from borderline hypertensives.

Lymphocytes were used as a cellular model for the in vitro measurements of maximal ouabain binding sites in order to assess any changes in young men at increased risk of developing essential hypertension, and to analyse whether any such changes were associated to borderline hypertension and/or heredity. Four groups were evaluated; 28 normotensive (NTO) and 20 borderline hypertensive (BHO) offspring of hypertensives. Twelve borderline hypertensives (BH) and 28 normotensive subjects (NT) with normotensive parents. The number of ouabain binding sites were significantly increased in the borderline hypertensives irrespective of heredity. The borderline hypertensives were heavier than the normotensives. A stepwise multiple regression model was therefore used in order to control confoundings by body mass index (BMI) and other factors such as age, gamma glutamyl transferase, 24 h sodium excretion, serum triglyceride, and serum cholesterol, which may influence the number of ouabain binding sites. Only BMI entered the stepwise model. These results indicate the presence of an increased number of sodium-potassium pumps in lymphocytes from borderline hypertensives. This difference may be attributed to the blood pressure disease or increased body mass.

Adolescent↗
PubMed1989

Prevalence of surreptitious laxative abuse in patients with diarrhoea of uncertain origin: a cost benefit analysis of a screening procedure.

The costs and medical benefits of an early, routine laxative screening test in patients with diarrhoea of uncertain origin was evaluated. During a two year period 200 consecutive, unselected patients complaining of diarrhoea were considered for the study in whom a three day faecal collection was undertaken. Fifty four patients denying laxative consumption had diarrhoea (mean daily stool weight greater than 200 g) of uncertain origin at their initial visit of whom 47 were screened to detect ingestion of anthraquinones, bisacodyl, phenolphthalein, and magnesium salts. Seven patients had positive tests. No single clinical feature could have predicted the outcome of the test. The possible cost savings of the programme were estimated by not releasing the results of the test to the clinicians until the patient's investigations were complete. The seven patients with laxative abuse spent a total of 35 days in hospital and were seen on 29 occasions in the outpatient clinic after the laxative screening test was positive. The cost of the screening programme was cheaper than the costs of the diagnostic procedures in patients with laxative abuse. We recommend the use of a comprehensive, early laxative screening programme in all patients with diarrhoea of uncertain origin as a cost effective procedure.

Adult↗
PubMed1989

Lymphocytic sodium and potassium pump function in Bartter's syndrome.

Bartter's syndrome is characterized by chronic hypokalaemia, activation of the renin-angiotensin system and normal blood pressure. To investigate whether a generalized disturbance of sodium-potassium pump function might be of pathogenetic importance, lymphocytic sodium-potassium homeostasis was examined in 5 patients suffering from Bartter's syndrome. Two of the patients were treated with potassium chloride supplementation, the others were without medical treatment when studied. All were severely hypokalemic (serum potassium 2.8 +/- 0.24 mmol/l, mean +/- SEM). Lymphocyte sodium and potassium concentration (14.4 +/- 0.37 and 94.4 +/- 7.7 mmol/l, respectively), ouabain sensitive 22Na-efflux rate constant (2.68 +/- 0.25 h), and absolute ouabain sensitive efflux rate (38.16 +/- 4.2 mmol l-1 h) did not differ from matched controls. Ouabain binding capacity was 126 900 +/- 23 500 sites/cell in patients vs 50 400 +/- 17 900 in controls (p less than 0.05). In conclusion, patients with Bartter's syndrome may have an intrinsic abnormal pump function, characterized by an increased pump density and a low cation turn-over rate per pump unit.

Adult↗
PubMed1988

Alterations in sodium-potassium regulation in mononuclear leucocytes from young borderline hypertensive and offspring of hypertensive patients.

Membrane ion transports were investigated in lymphocytes from young normotensive and borderline hypertensive offspring with and without heredity for hypertension. Borderline hypertension per se was associated with an enhancement of sodium-potassium pump activity. Heredity per se was associated with increased sodium influx and ouabain-resistant sodium efflux.

Adolescent↗
PubMed1988

86Rubidium uptake in mononuclear leucocytes from young subjects at increased risk of developing essential hypertension.

This study was designed to assess any changes in mononuclear leucocytes from young men at increased risk of developing essential hypertension and to determine whether any changes found were associated with borderline hypertension and/or heredity. To this end we used mononuclear leucocytes as a cellular model for in vitro measurement of total 86rubidium uptake to give an index of sodium-potassium pump activity. Four groups of subjects were evaluated, 28 normotensive and 20 borderline hypertensive offspring of hypertensives, and 12 borderline hypertensives and 28 normotensives with normotensive parents. 86Rubidium uptake was significantly increased in the borderline hypertensive subjects, especially in the borderline hypertensive offspring of hypertensive patients. Our results indicate that the sodium-potassium pump is activated in mononuclear leucocytes from borderline hypertensives, and especially in those borderline hypertensives with at least one hypertensive parent. The latter group was also the group at greatest risk of developing essential hypertension.

Adolescent↗
PubMed1987

24-hour antiarrhythmic effect of conventional and slow-release verapamil in chronic atrial fibrillation.

Twenty-four-hour heart rate control by verapamil given as conventional tablets t.d.s., or as a new slow release formulation once daily, has been compared in an open cross-over trial. Eight patients with chronic atrial fibrillation and one with chronic atrial flutter were studied outside hospital. Trough serum concentration of verapamil did not differ during the two dosage regimens (59 ng/ml - conventional formulation and 49.3 ng/ml - slow release tablet). The average serum concentration of digoxin in the patients was not changed. Compared to the control phase, both dosage regimens significantly and equally reduced individual and average heart rates throughout the entire 24-h period. A positive correlation between the serum concentration of verapamil and the relative increase in average R-R interval was demonstrated. It is concluded that dosage t.d.s. with conventional tablets of verapamil or once daily with the slow release formulation gave the same antiarrhythmic efficacy over 24 h, and was associated with equal trough serum concentrations of verapamil.

Adult↗
PubMed1987

Volume, sodium content and sodium efflux of human mononucleated cells: characteristics and methodological problems.

New methods for determining the volume and sodium content of human mononucleated cells are presented and the kinetics of sodium efflux are characterized. Sodium efflux obeyed first-order kinetics with a half-life of about 9 min. The ouabain-sensitive sodium pump is responsible for about 60% of the total turnover of this cation. Reliable measurement of cell volume and sodium content requires pre-incubation at physiological conditions. Determination of sodium efflux should be based on the initial (less than 15 min) cellular delay of 22Na-activity in preloaded cells. In normal subjects (n = 34), mean cell volume was 635 +/- 138 nl/10(6) cells and sodium content averaged 14.6 +/- 2.8 mmol/l cell. Total and ouabain-sensitive efflux rate constants were 4.56 +/- 0.66 h-1 and 2.70 +/- 0.47 h-1. Corresponding absolute sodium efflux averaged 65.1 +/- 14.8 and 38.9 +/- 9.6 mmol/l/h, respectively.

Cell Separation↗
PubMed1987

Cell membrane handling of sodium in lymphocytes during salt restriction in normotensives.

Lymphocyte sodium content and sodium efflux were studied in 9 healthy normotensive males without history of essential hypertension before, during and after 5 weeks of severe sodium depletion. Sodium depletion caused a significant increase in sodium content and a slight but non-significant decrease in potassium content. Total and ouabain-sensitive sodium efflux rate constants decreased significantly during sodium depletion, while absolute sodium efflux, derived from cellular sodium concentration and the corresponding sodium efflux rate constants, remained unchanged. A significant reduction in arterial mean and diastolic blood pressure, measured by ambulatory as well as by home readings, was observed during salt restriction. Prolonged severe sodium depletion of normotensive subjects leads to changes in lymphocytic sodium homeostasis, probably due to a primary inhibition of the sodium pump and a secondary intralymphocytic sodium accumulation. The mechanism underlying these changes remains unclarified.

Adult↗
PubMed1987

Influence of physical activity on plasma digoxin in hospitalised patients.

The influence of physical activity on the plasma digoxin concentration was investigated in 13 digitalised patients suffering from a variety of cardiac diseases. Plasma digoxin concentration was determined four times during two consecutive days. In the morning, the standing position and one hour of physical activity caused a consistent and significant decrease in the plasma digoxin concentration, the mean reduction being 26.7 percent. In the afternoon, no consistent changes of plasma digoxin concentration were observed during one hour's rest. Consequently, we suggest standardisation of the blood sampling procedure so that no blood collection takes place in the morning until the patient has been performing normal physical activity for at least one hour.

Adult↗
PubMed1986

Use of saliva for monitoring oxcarbazepine therapy in epileptic patients.

The utility of saliva sampling in monitoring oxcarbazepine therapy has been assessed in 17 epileptic outpatients treated with a mean dose 22.7 mg/kg/d for 19-411 days, i.e. at steady-state. Blood was collected before the morning dose measurement of the plasma 10-OH-carbazepine concentration and determination of the protein bound fraction. Immediately after blood sampling resting saliva and saliva produced after a masticatory stimulus were collected. Using equilibrium dialysis and an ultrafiltration technique the protein binding of 10-OH-carbazepine was found to be 40% and 45%, respectively. When the degree of protein binding was expressed as the ratio between the corresponding saliva and plasma concentrations of 10-OH-carbazepine, the concentration in resting saliva indicated that no drug was bound to plasma protein, whereas the use of stimulated saliva suggested a protein-bound fraction of 35%. The concentration in stimulated saliva reflects the free fraction of 10-OH-carbazepine, but regression analysis of paired salivary and plasma values showed that the prediction of plasma concentrations from levels in saliva is uncertain. This, together with the low degree of plasma protein binding, leads to the conclusion that it would be preferable to monitor total plasma concentrations if therapeutic drug monitoring of oxcarbazepine were to prove essential in epileptic patients.

Adult↗
PubMed1986

The significance of the enterohepatic circulation on the metabolism of digoxin in patients with the ability of intestinal conversion of the drug.

A cardiac patient had to be given a very high dosage of digoxin to attain therapeutic plasma level. The increased dosage requirement could partly be explained by reduced bioavailability due to intestinal conversion of digoxin. Consequently, the kinetics of the drug was examined before and after erythromycin treatment. Before treatment the determination of the area under the concentration versus time curve (AUC) following a single dose of digoxin given orally or intravenously demonstrated a substantial reduction in the absolute bioavailability. Erythromycin administration during 20 days caused a dramatic rise in AUC when the single oral dose was repeated, exceeding the two AUC obtained prior to initiation of the antibiotic therapy, and the steady state plasma digoxin level was 2-3-fold increased. The fact that the AUC obtained for a single oral dose of digoxin after erythromycin treatment exceeded that obtained when given intravenously before erythromycin indicated the presence of an enterohepatic circulation of digoxin. This may contribute substantially to the elimination of digoxin in patients with the capability of intestinal conversion of digoxin.

Digoxin↗
PubMed1986

Plasma concentrations of complement split product C3d and immune complexes after procainamide induced production of antinuclear antibodies.

Seventeen patients treated with procainamide for cardiac ventricular arrhythmias were followed for up to 40 weeks. Immunological data as a clue to developing the systemic lupus erythematosus (SLE)-like syndrome was emphasized. Ten patients developed antinuclear antibodies (IgG or IgM), but no increase in the plasma concentration of the complement split product C3d or immune complexes, measured by two different methods, was demonstrated. This finding is in contrast to the high levels of both C3d and immune complexes in SLE. The discrepancy may be caused by a lack of immune complex mediated complement activation by the procainamide induced antibodies, or may be due to a difference in severity of disease. The acetylator phenotype of the patients was determined but due to the low frequency of fast acetylators no comparison of the immunological response of the two phenotypes could be done.

Aged↗