Biomedical subjects

K O Haustein

Publications and source records attributed to K O Haustein.

At least 55 records · Page 3Linked to original sources

PubMed1988

[Behavior of the aminophenazone breath test in chronic liver diseases].

In 230 patients with histologically ascertained chronic hepathopathies the aminophenazone breathing test in the modification after Haustein and Schenker was carried out. In contrast to a control group consisting of 16 test persons with healthy liver (14CO2 exhalation 1019 +/- 175 DPM/mmol-CO2/70 kg body weight) the hepatic elimination of the [14C]-aminophenazone in chronic liver diseases (626 +/- 203 DPM/mmol CO2/70 kg body weight) was significantly restricted (p less than 0.001). The values of the aminophenazone breathing test showed a dependence on the degree of severity of the liver disease. Hepatoses with partly questionable or slight value of the disease did not differ in their results (841 +/- 230 DPM/mmol CO2/70 kg body weight) from those of persons with healthy liver. Chronic inflammatory liver diseases (668 +/- 185 DPM/mmol CO2/70 kg body weight) occupied an average position (p less than 0.001). The lowest values were to be seen in patients with chronic fibrosing liver diseases, mainly with liver cirrhosis (403 +/- 218 DPM/mmol CO2/70 kg body weight). Compared with the control group the difference was significant (p less than 0.001). Broad regions of overlapping of the individual values of various chronic liver diseases do not allow an unequivocal coordination of regions of the breathing test values to certain morphologically defined chronic hepatopathies. For the determination of size and degree of severity of the damage of liver parenchyma the aminophenazone breathing test, however, may be a valuable help in the framework of a special programme of diagnostics.

Adult↗

PubMed1988

Differences in color discrimination between three cardioactive glycosides.

Color discrimination ability of 100 in-patients suffering from congestive heart failure and treated with digitoxin (D), pengitoxin (P), or digoxin (Dg) was determined with the Farnsworth-Munsell 100 Hue test (FM 100) and compared with the color discrimination of 72 in-patients who were not treated with digitalis glycosides (control group C). Parallel to the performance of the FM 100, the glycoside plasma level was measured by radioimmunoassay. The total error score (TES) of the FM 100 was correlated with the glycoside plasma level and the patient's age. In the C as well as in the D or P groups up to 172 errors and in the Dg group up to 586 errors were observed. With the exception of Dg, no differences were observed between the regression lines indicating an age-dependent increase in TES even under D or P treatment. In contrast to the two glycosides, Dg enhances the TES in therapeutically relevant plasma concentrations. The differences between the glycosides are due to differences in their volume of distribution and their plasma protein binding.

Acetyldigoxins↗

PubMed1988

Studies on the metabolic pattern of propiverine in urine after single administration.

In 11 healthy volunteers the metabolic pattern of propiverine [1; alpha, alpha-diphenyl-n-propoxy-1, 2-acetic acid-4-(1-methyl-piperidinyl)ester] was studied in urine after a single i.v. (5 mg) or oral dose (15 mg). To each dose 30.4 microCi (1.11 MBq) 14C-1 were added. The various urine fractions (0-1, 1-4, 4-8, 8-24 h) were extracted by chloroform and ethyl acetate at different pH-values and TLC was performed. The metabolites were identified by comparison of the RF-values of the radiochromatograms with those of the reference compounds after TLC using various solvent mixtures. Evidence for identity of the metabolites was additionally obtained by ester hydrolysis, ether cleavage or reduction with subsequent TLC after elution of the spots from the plate. The formed products were rechromatographed. 1 undergoes an extensive biotransformation: about 70% of the radioactive substances in urine consisted of 19 different metabolites, while 1 amounted to only 3%. Additionally, 3 acidic metabolites of unknown structure were isolated. Due to the metabolic pattern the following reactions of degradation were found: oxidation of the tertiary nitrogen in the piperidinyl moiety yielding N-oxides (40 to 50% of radioactivity), oxidation of one of the three carbon atoms of the propyl side chain, oxidation of the N-methyl group resulting in N-demethylated products, and ester cleavage. Propiverine N-oxide (20 to 25%) was determined as a major metabolite, whereas demethylated products occurred in minute amounts (1%). There was no evidence for oxidation of both phenyl moieties.

Adult↗

PubMed1988

Pharmacokinetics of pengitoxin and its therapeutic efficacy in congestive heart failure.

In a therapeutic study, 120 inpatients suffering from congestive heart failure were treated with a daily maintenance dose of 0.3 mg pengitoxin (penta-acetyl-gitoxin) over several weeks or months. The plasma level and the glycoside concentration in urine were measured by radioimmunoassay. The therapeutic effects were evaluated considering clinical signs and criteria following the functional capacity according to the New York Heart Association (NYHA). In 27 patients both plasma and urine concentration were measured during 2 weeks after the beginning of the pengitoxin therapy. On the 3rd day of the pengitoxin dosage schedule, a mean plasma level of 18.1 ng.ml-1 (SD 5.1 ng.ml-1) was measured. During this day 26.6% of the daily administered glycoside dose was excreted in urine. In 26 of the 120 patients the mean steady state plasma level was between 7.6 and 22.5 ng.ml-1. A maximum of frequency was found in the 17.6 to 22.5 ng-subclass. In 118 patients the mean urinary excretion of 16-acetyl-gitoxin reached 24.7% (SD 11.8%) of the administered dose. The creatinine clearance and the 16-acetyl-gitoxin plasma level did not correlate, while between the renal clearance values of creatinine and the glycoside a correlation was found, however, it was of no significance for dosage schedules in patients with impaired renal function. After treatment, the NYHA classes III and II were reached in 57 patients; in 3 patients suffering from renal diseases, the NYHA class I remained unchanged. In 90 patients the clinical signs improved and in 27 patients the clinical situation remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyldigoxins↗

PubMed1987

The relation of membrane-ATPase activity with congestive heart failure.

By the use of the phosphate method the activity of the (Na+ + K+)-ATPase system (E. C. 3.1.6.1.) of human left ventricle was measured in one tissue sample each obtained from 47 autopsied patients. The subjects between the ages of 20 and 79 years had suffered from congestive heart failure of different functional classes NYHA), from diseases of the heart and circulation, or from tumors. Only 23 of the patients of the entire group took digitalis glycosides. With the exception of one sample (8.58 mumol Pi.mg-1.h-1), the enzyme activity amounted from 0.45 to 4.84 mumol Pi.mg-1. The ATPase activity depends on the age (A), the functional classes of congestive heart failure (CF; CF greater than A), and the time between death and autopsy. Chronic hypoxic alterations decreased the enzyme activity. Digitalization did not influence the post-mortem enzyme activity. Due to the small therapeutic range of digitalis glycosides and a distinctly reduced ATPase activity of the ageing patient, enhanced glycoside maintenance doses will not improve myocardial contractility, but provoke arrhythmias.

Adenosine Triphosphatases↗

PubMed1987

Uptake and liberation of [3H]16-acetyl-gitoxin in the isolated guinea pig atrium.

In isolated, spontaneously beating guinea-pig atria the uptake, liberation and inotropic effect of [3H]16-acetyl-gitoxin were studied. At a concentration of 53.5 nmol/l 16-acetyl-gitoxin caused an increase in contractile force of 21% within 45 min. Within 60 min, 190.7 pmol per g tissue were taken up. The tissue-to-medium radioactivity ratio (T/M ratio) was 4.7. In the wash-out experiments, 40% of the accumulated radioactivity was liberated into the medium within 30 min, while the glycoside-dependent increment of inotropy ceased to continue. The kinetic properties of 16-acetyl-gitoxin were found to resemble more closely those of digitoxin than those of ouabain.

Acetyldigoxins↗

PubMed1987

Dose-dependent shortening of systolic time intervals after intake of pengitoxin.

The systolic time intervals (STI) corrected for changes in the heart rate, electromechanical systole (QS2c) and left ventricular ejection time (LVETc), and the ECG-derived PQ-time and QT-interval were measured in five female and four male healthy subjects. Each volunteer took 0.15, 0.30, 0.45, 0.60, 0.75 or 0.90 mg pengitoxin over six days, with a glycoside-free interval of two or three weeks between two doses. The glycoside plasma level was measured radioimmunologically. Linear correlations were found between the shortening of QS2, LVET, and QT (delta QS2c, delta LVETc, delta QTc) and the plasma level of 16-acetyl-gitoxin. The PQ-time showed a flat dose-dependent increase. The shortening of STI observed after therapeutic and subtoxic doses of pengitoxin was in accordance with that after intake of digitoxin and digoxin in corresponding doses. The efficacy of pengitoxin estimated by shortening of STI justifies the administration of daily maintenance doses between 0.30 and 0.45 mg.

Acetyldigoxins↗

PubMed1987

Elimination of 16-acetyl-gitoxin in patients suffering from impaired liver function.

In ten patients suffering from moderate to severe disturbances of liver function (hepatic cirrhosis, carcinomatous metastases of the liver) the elimination of 16-acetyl-gitoxin from plasma was measured after a single oral dose of 1.2 mg pengitoxin. In 9 of 10 patients the mean half-life amounted to 67.3 h (SD 14.2 h). In one patient with carcinomatous infiltration of the liver and concomitant cirrhosis, the half-life was prolonged to 165.3 h. The results point to an unchanged elimination of 16-acetyl-gitoxin in patients suffering from liver cirrhosis.

Acetyldigoxins↗

PubMed1986

[Value of the 14C-aminophenazone inhalation test: inhibition of the demethylation function of the liver by cimetidine].

On 15 patients with healthy liver and with a peptic ulcer the demethylation capacity of the liver was measured with the 14C-aminophenazone breathing test before the treatment and during the treatment with the H2-antagonist cimetidine (daily dose 1.0 g). As measure of the demethylation capacity the breathed out 14CO2 (DPM/mmol CO2/70 kg body weight) before and 1 hour after intake was chosen. Under influence of cimetidine the mean 14CO2-value of 724.7 DPM (S.D. 127.7) decreased to 404.1 DPM (S. D. 153.1). The enzyme activities (ALAT, ASAT, AP, AAP, GGT, CHE) and the concentrations of serum bilirubin and serum albumin remained unchanged and did not correlate mutually and with the 14CO2-data. The results confirm the independence of the aminophenazone test as technique for the recognition of disturbance of the MFO-system.

Adult↗

PubMed1986

Cardiotoxicity of digitalis.

The principal effect of cardioactive glycosides (CG) is the inhibition of the (Na+ + K+)-ATPase system with subsequent increase in contractility of the myocardium. In subtoxic and toxic concentrations, CG increase O2 consumption due to a transient Ca2+ overload. Furthermore, the activity of several enzymes of the citrate cycle is changed; cAMP transiently rises with reduction of myocardial ATP, and intracellular lactate dehydrogenase and creatine kinase are lost in the coronary fluid. The antagonistic action of beta-receptor blocking agents is caused by their membrane-stabilizing effect. O2-consumption is increased in the non-failing heart, while in the failing one it decreased. The CG-induced arrhythmias are caused (1) by inhibition of the ATPase system of excitable cardiac structures, and (2) by interaction of CG with the autonomic nervous system. Severe intoxications and the rapid disappearance of cardiac symptoms upon administration of Fab fragments suggest that the CG-induced changes on the molecular level (with the exception of those on the ATPase system) are of secondary significance.

Animals↗

PubMed1986

The 14C-aminophenazone breath test in pesticide workers.

In 59 workers between the ages of 22 and 66, who had been exposed to pesticides, and 31 healthy controls between the ages of 22 and 28, the hepatic demethylation capacity was studied using the aminophenazone breath test (ABT). The ABT was carried out in two versions (version A: 111 kBq 14C-aminophenazone per 630 mg, version B: 111 kBq 14C-aminophenazone per 3 mg). The amount of 14CO2 expired per mmol CO2 per 70 kg body weight (b.w.) detected 1 h after 14C-aminophenazone intake was used to determine the demethylation capacity of the liver. The amount of expired 14CO2 depended on the ingested dose (B greater than A). The 14CO2-values measured in 13 controls did not differ from those obtained in 37 subjects who had been exposed to pesticides for 650 h per year on the average [649 vs 726 DPM/mmol X 70 kg b.w. (A)]. The 14CO2-values obtained in 22 subjects exposed to pesticides for 990 h per year on the average (B) were lower than those obtained in 18 healthy controls (736 vs 1024 DPM/mmol CO2 X 70 kg; P less than 0.05). The 14CO2-values of ABT decreased with increasing length of exposure per year (B; r = -0.51, P less than 0.05).

Adult↗

PubMed1986

On the pharmacokinetics of 16-acetyl-gitoxin and its bioavailability from pengitoxin-containing tablet formulations.

In six volunteers the pharmacokinetics of 16-acetyl-gitoxin (16AG, 0.5 mg) administered intravenously (A1) and as an oral solution (A2) and of pengitoxin (PAG, 0.6 mg) administered intravenously (A3) was evaluated. In six volunteers the bioavailability of 16AG from two PAG tablet formulations (1.2 mg) (B2, B3) was measured by comparison with the absorption after administration of a pengitoxin solution (1.2 mg) (B1). In both studies the test was performed using a crossover design. After a single i.v. injection of equimolar doses, 16AG and PAG showed similar mean kinetic parameters: t1/2 = 51.6 hr (16AG) and 60.8 hr (PAG), CL = 11.7 ml min-1 (16AG) and 12.7 ml min-1 (PAG), CLR = 4.1 ml min-1 (16AG) and 4.2 ml min-1 (PAG). The 16AG was absorbed from solution with a mean half-life of 0.2 hr to an extent of 98.6%. The mean urinary excretion/Ae (0,4)/of 16AG amounted to 24.6% (A1), 20.8% (A2) and 28.1% (A3). On the basis of AUC values, the mean bioavailability of PAG from either tablet formulation amounted to 79.6% (B2) and 89.6% (B3). The pharmacokinetic parameters of 16AG (PAG) are closer to those of digitoxin than those of digoxin. In general, 16AG is characterized as a digitoxin with a digoxin-like elimination half-life.

Acetyldigoxins↗

PubMed1986

On the specificity of the aminophenazone breath test.

In 15 patients suffering from ulcer of the stomach or the duodenum, but without liver disease, the demethylation capacity was studied by the use of 14C-aminophenazone before and under the treatment with the H2-blocker cimetidine in daily doses of 1.0 g. As a measure of demethylation the expired 14CO2 (DPM/mmol CO2/70 kg body weight) was used before and 1 h after intake. Under cimetidine the mean 14CO2-value decreased from 724.7 DPM (SD 127.7 DPM) to 404.1 DPM (SD 153.1 DPM). In 3 patients the cimetidine medication was continued for additional 6 to 8 weeks with a dosage of 0.4 per day. In these subjects a mean of 533.2 DPM was measured. The enzyme activities (ALAT, ASAT, AP, AAP, gamma-GT, ChE) and the albumin and bilirubin concentration in serum measured concomitantly to the ABT did not differ from control values. Thus, the ABT is a useful test to assess changes of the demethylation capacity that can be caused by drugs or xenobiotics without affecting biochemical parameters used for diagnosis of liver diseases. The ABT might be a useful and simple technique to discover environmental disorders due to occupational conditions.

Adult↗

PubMed1985

[Acute beta blocker poisoning].

It is reported of acute beta-blocker intoxications in 34 patients (16 with talinolol, 18 with propranolol ingestion). The mean ingestion dose was for talinolol 2.5 g, for propranolol 1.55 g, the mean time of latency up to the appearance of intoxication symptoms 116 min after intake of talinolol, 79 min after intake of propranolol. The picture of intoxication was characterized in the two substances by the antiadrenergic effects, there was no more a cardioselectivity in the high ingestion doses. In talinolol were in the first place dysrhythmias, hypotension and vomiting and nausea, respectively, in propranolol central-nervous symptoms and hypotension. Substance-specific intoxication symptoms are also possible. In mixed intoxications alcohol accelerated the beginning of the effect, sedatives prolonged the latency. Threatening of life is to be expected in ingestion doses over 2 g. In 6 patients the course was lethal after extreme doses of talinolol - according to the present experiences due to the too late beginning of therapy and/or insufficient intensity of therapy. Distinct intoxication symptoms need extremely high applications of antidotes of beta-stimulants, in their inffectiveness glucagon. Furthermore, treatment with cardiac pacemakers and 24-hour control in an intensive care unit proved necessary.

Adolescent↗

PubMed1985

[Bioavailability of etilefrine from Thomasin and Thomasin sustained-release tablets].

In 6 healthy volunteers absorption and elimination of etilefrine were studied in cross-over after intake of 20 mg each of a solution (A) and tablet (B) (Thomasin) or after intake of 25 mg as a sustained-release tablet (C; Thomasin retard). Etilefrine and its sulfoconjugate were measured by the GC technique in plasma and urine. From the data obtained the AUC-(plasma) and CUE-values (urine) were calculated. Peak plasma levels of 10 to 25 (A) and 6 to 13 ng . ml-1 were observed 30 min after intake. The concentrations decreased to the lower detection limit (less than 2 ng . ml-1) 2 h after intake. Plasma peak levels of 5 ng . ml-1 were measured 1-2 h after intake of the sustained-release form (C). The etilefrine plasma level decreased more slightly (C) than after intake of the other formulations (A, B). The etilefrine conjugate reached plasma peak concentrations of 600 ng . ml-1 1 h (A, B) or 2 h (C) after intake. A mean bioavailability of 70 and 58 per cent (Thomasin) or of 78 and 108 per cent (Thomasin retard) was calculated by comparison of the corresponding AUC- and CUE-values of the total etilefrine.

Adult↗

PubMed1985

A simple method for routine determination of the metabolic liver capacity: the aminopyrine breath test.

In 16 healthy volunteers and in 39 patients with liver diseases (fatty liver, chronic persistent and chronic active hepatitis, hepatic cirrhosis) a simplified aminopyrine breath test (ABT) was carried out using a "tracer" dose of 3 mg (111 kBq) 14C-aminopyrine. The exhaled 14CO2 measured 1 h after intake amounted to values between 771 and 1337 DPM/mmol CO2/70 kg body weight in healthy controls. The amount of exhaled 14CO2 decreased in the order: fatty liver greater than chronic, active hepatitis greater than active, compensated cirrhosis greater than active, decompensated cirrhosis. Between the values of ABT and various conventional laboratory liver tests (alanine-aminotransferase, alanine-aminopeptidase, aspartate-aminotransferase, gamma-glutamyltransferase, total serum bilirubin) significant correlations were found (r = 0.6019 to 0.7765, n = 55; p less than 0.001). The proposed modification of the breath test is of advantage in that it requires a very low dose of aminopyrine and is easily practicable.

Adult↗

PubMed1984

Therapeutic range of cardiac glycosides.

The narrow therapeutic range of cardiac glycosides continually challenges chemists to synthetize new derivatives with improved therapeutic properties. One of the best investigated semi-synthetic glycosides is 16 alpha-gitoxin. Compared to ouabain and gitoxin, it produces positive inotropic effects on the isolated guinea-pig heart in a wider range of concentrations and causes less pronounced rhythmic disturbances. These results were confirmed by electrophysiological investigations in isolated fibres of the canine myocardium and of the Purkinje system, by investigations in the anaesthetized cat and dog and in healthy volunteers. The effects of various semi-synthetic compounds (e.g. actodigin, ASI-222) are described and possibilities to trigger these effects are discussed. Of some significance seem to be differences in the structure of the (Na+ + K+)-ATPase system of different tissues, e.g. the working muscle and the Purkinje system of the heart, as well as differences due to the formation and dissociation of the glycoside-enzyme complex. The significance of K+, Ca2+ and of several pharmacokinetic parameters (e.g. the volume of distribution) for these reactions are briefly discussed.

Animals↗

PubMed1984

Interaction between phenprocoumon and phytomenadion: a pharmacokinetic investigation in healthy volunteers.

In 23 female and male healthy volunteers the pharmacokinetic behaviour of [3H]phenprocoumon and [3H]phytomenadion was investigated. The time-dependent changes in plasma radioactivity and the amount of urinary excretion were measured. Under simultaneous administration of phytomenadion (PHY) in daily doses of 10 mg, the elimination of phenprocoumon (PPC) was not altered (t0.5 beta 141.4 h, CUE50 20.4% of administered dose) as compared with data of previous investigations, while its anticoagulant effect was inhibited. PHY in doses of 10 mg was absorbed quickly and eliminated with a mean half-life of 60.6 h at a total body clearance (Cltot) of 9.3 ml/min and a renal clearance (Clren) of 1.9 ml/min. Under the co-administration of PPC the vitamin was eliminated with a half-life time of 23.1 h (Cltot 16.7 ml/min) and the amount of excreted radioactivity was enhanced (26.3% of administered dose; Clren 4.5 ml/min) as compared with the data of PHY without co-medication. From the experiments it is concluded that (1) PHY inhibits the action of PPC without influencing its pharmacokinetics, and (2) that PPC distinctly changes the pharmacokinetics of PHY and diminishes its pharmacodynamic action as measured by changes in the prothrombin complex activity.

4-Hydroxycoumarins↗