Biomedical subjects

K O Haustein

Publications and source records attributed to K O Haustein.

At least 19 recordsLinked to original sources

PubMed1995

Absorption and bioavailability of pentaerithrityl-tetranitrate (PETN, Dilcoran 80).

The effects of 80 mg pentaerithrityl-tetranitrate (PETN) as suspension or formulated as tablets were compared to placebo in a single blind, randomized, crossover study in 18 healthy subjects (study A), and the bioequivalence of two tablet formulations (marketed Dilcoran 80 vs a new formulation) was studied in 24 healthy subjects after administration of single oral doses of 80 mg PETN according to a placebo controlled, randomized, double blind, two-way crossover study design (study B). The perfusion of the right middle finger was measured by rheography (altitude A of the changes of resistance and of the incisure D) before and 24 h post-dose, and blood pressure and heart rate were measured in supine position at the same time. The values of area under curve (AUC) of the ratio A/D were calculated by the trapezoidal rule. In study A the mean A/D-values were reduced from about 2.0 to about 1.3 after intake of PETN (solution or tablet) with a minimum 60 to 90 min postdose (solution) and 2 h postdose (tablet). A significant reduction in this ratio was seen up to 8 (solution) or 12 h (tablet) post dose. Changes in blood pressure were not observed while the heart rate decreased in the subjects of all three groups 1 to 2 h postdose followed by an increase by 6 to 10 beats per min. After subtraction of the AUC values of placebo from the PETN-derived AUC values, mean values of 6.61 (SD 1.52, solution) and 7.25 (SD 1.48, A/D*h, tablet) were calculated (p > 0.1, study A).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Transport of various substances through human enamel and dentine.

The penetration of 14C-labelled alcohols (methanol, ethanol, n-butanol), 14C-labelled carbonic acids (formic, acidic, propionic, valerianic, octanoic, malonic, succinic and lactic acid), 14C-drugs (procain, barbital), and 14C-sugars (saccharose, xylose) into about 800 human deciduous or permanent teeth, both healthy and carious, was investigated. Dental enamel up to the cemento-enamel junction was incubated at a pH-value of 5.0 or 6.8 for 1 or 24 hours. For measurement of radioactivity, the dentine of the root was obtained by trepanation. Between intact and carious permanent teeth only slight differences were observed in case of the diffusion of methanol and ethanol (2% of the incubation medium), while n-butanol penetrated the dentine to an extent of 4.2% at a pH of 5.0. The monocarbonic acids penetrated the enamel of healthy teeth within 24 hours to an extent of 6.6-19.2% of the content of the incubation medium, while the dicarbonic (succinic and malonic) acids reached amounts of 3.6 and 9.2%, and the percentage of lactid acid which penetrated the enamel reached 2.9%, respectively. Under all conditions tested, saccharose penetration was higher in carious than in healthy teeth (3.8 vs 6.5%). The highest uptake was found in experiments with barbital; it was more pronounced in deciduous than permanent teeth (16.2 vs 12.4%). The data could be of interest in the therapy of inflammatory and other processes of the pulp.

Adolescent↗

PubMed1994

Extraordinary efficacy of 16 alpha-gitoxin, an ultra-short acting semi-synthetic digitalis glycoside.

The positive inotropic effect of 16 alpha-gitoxin was studied in 52 female and male healthy volunteers between the ages of 21 and 27 years and a body weight between 55 and 76 kg after the single i.v. injection or oral administration in doses between 2.5 and 15 mg. The inotropic effect was evaluated by the use of the systolic time intervals (left ventricular ejection time, LVET, and electromechanic systole, QS2) and by the QT-Interval of the ECG. The glycoside plasma level was measured simultaneously to the pharmacodynamic parameters by a radioimmunoassay, 16 alpha-gitoxin abbreviated dose-dependently the STI (LVET and QS2) for 30 (i.v.) or 15 ms (per os) and the QT interval for 35 ms. A mean plasma concentration of 401 ng/ml was measured 15 minutes after the i.v. injection of 5 mg and a mean plasma level of 402 ng/ml was measured 1 hour after the oral intake of 10 mg 16 alpha-gitoxin as an aqueous-ethanolic solution. The shortening of the STI-values and of the QT-interval correlated with the administered glycoside dose and with the AUC0-6-value. The AUC-values increased linearly with the administered dose. The ratio of the AUC0-6-values after i.v. or oral administration of 7.5 mg 16 alpha-gitoxin amounted to 0.673. Doses of 16 alpha-gitoxin which induce a maximum abbreviation of STI or QT did neither provoke a distinct decrease in heart rate nor cardiac disturbances. Sixteen-alpha-gitoxin develops a positive inotropic effect within a few minutes after i.v. injection and also after oral intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1994

Pharmacokinetics of phenprocoumon.

The pharmacokinetics of phenprocoumon was studied in 24 healthy volunteers between the ages of 23 and 28 years and a mean body weight of 72 kg by intraindividual comparison of the plasma level after i.v. and oral administration of 9 mg phenprocoumon (PPC) or by the evaluation of the total plasma clearance of PPC by simultaneous measurement of the urinary excretion and of the plasma concentration after the administration of 9 mg PPC. The following mean data were obtained after i.v. injection:t1/2 alpha 0.432h, t1/2 beta 128 h, co 0.651 microgram/ml, Vd 14.41,AUCo-omega 121 micrograms x h/ml. After intake of 9 mg PPC the following mean values were measured: tmax 2.25 h, Cmax 1.01 micrograms/ml, tabs 0.553 h, co 0.865 micrograms/ml, t1/2 beta 132 h, AUC0-infinity 164 micrograms x h/ml. By comparison of the PPC plasma level with the corresponding urinary excretion, a total mean PPC clearance of 20.0 (i.v.) and 15.1 (per os) ml/h was calculated within the first 8 h post dose, while the values measured did not differ between 8 and 48 h post dose (14.8 vs 15.3 ml/h). The steep decline in plasma level after i.v. injection of PPC might be caused by an enhanced renal and hepatic elimination of the free drug to a higher degree than after oral intake, while no differences existed between both modes of administration during the phase of elimination. A nearly total absorption of PPC from the tablet formulation is suggested.

Administration, Oral↗

PubMed1993

Drug-prescription in the five new federal lands--a comparison with the prescription of the old federal lands of Germany.

In the present study, the consumption of several drugs on the territories of the former GDR and FRG was compared using 200,000 prescriptions and the defined daily doses (DDD). Furthermore, for the two parts of Germany, the 20 most frequently prescribed drugs were evaluated. Calcium antagonists and the beta-blockers prevailed in East Germany, while cardiac glycosides, vasodilators, reserpin-containing antihypertensives, bronchodilators (beta-adrenoceptor agonists), neuroleptics, tricyclic antidepressants, antacids, H2-receptor blockers, chondroprotectives were used 1.5 to 5 times more frequently in West Germany. Because in East Germany, a shortage of drugs was no longer observed in 1991, several other reasons for the "over-prescription" of drugs for the patients in West Germany must be mentioned.

Drug Prescriptions↗

PubMed1992

The reactivity of peripheral vessels of normo- and hypertensives.

The effect of calcium antagonist nifedipine (N) was studied in the changes of blood pressure, total peripheral resistance, activity of the transport membrane ATPase of erythrocyte ghosts, the plasma level of digitalis-like factor and the plasma renin activity. The studies were performed in 10 healthy volunteers and in 19 hypertensive patients after the intake of a single dose of 20 mg N. The changes were studied in the hypertensives after the intake of the drug in daily doses of 3 times 10 mg over 4 weeks, too. The systolic and diastolic blood pressure and peripheral resistance of the forearm decreased in hypertensives after a single dose of nifedipine as well as after the treatment with 30 mg daily over 4 weeks (170.8/109.5 vs 145.3/98.3 mmHg). As compared with the membrane ATPase activity of normotensives, that of the hypertensives was distinctly depressed (0.403 vs 0.321 mumol P(i).mg-1.h-1; p less than 0.01), while after N treatment, the enzyme activity increased to values of those of the normotensives 0.403 mumol P(i).mg-1.h-1). The mean peripheral resistance was not significantly depressed after the long-term treatment with N (2,085 vs 1,535 dyn.s-1.cm-5), while in several hypertensives (9 of 19) a distinct reduction was measured. Analogous results were found in case of the mean renin activity and the activity of several hypertensives after the N treatment. The N effect on the membrane ATPase system is discussed in connection with the hypothesis of Blaustein [1977] (Na(+)- with consecutive Ca(2+)-overload of the cell) and a possible influence of the drug on the electrolyte transport via membrane.

Adenosine Triphosphatases↗

PubMed1991

[Studies on diagnostic and prognostic validity of aminophenazone breath test in liver cirrhosis].

In 59 patients with liver cirrhosis (23 female, 36 male; aged between 30 and 73 years) the aminophenazone breath-test according to the Haustein-Schenker modification was performed. The results were related to morphological, clinical and haemodynamic criteria. In contrast to a control group, consisting of 8 women and 8 men aged between 23 and 27 years with healthy livers, the aminophenazone elimination proved to be heavily delayed (p less than 0.001). In consideration of the Havanna-classification the 14CO2-elimination was most heavily retarded in patients with portal cirrhosis, but compared with non-portal cirrhosis, the difference was below significance level. A significant dependence on the clinical degree of severity was found. The aminophenazone-elimination was frequently low in portal hypertension and considerably decreased after portocaval shunt with values below 200 DPM/mmol CO2/70 kg body weight. In some cases it could be demonstrated, that the test is not only of diagnostic relevance, but reflects the progression of cirrhosis.

Adult↗

PubMed1991

[Influence of exogenous factors on the behavior of aminophenazone breath test in chronic liver diseases].

230 patients with different chronic liver diseases of various severity were researched because of the influence of nicotine and alcohol on the results of the aminopyrine breath test in the modification of Haustein and Schenker (1985). Smoker with chronic liver diseases had higher 14CO2-results than nonsmoker. The difference was only significant in fatty liver disease in the first stadium (p less than 0,001) and chronic active hepatitis (p less than 0.05). Patients with chronic liver diseases of fewer severity had higher mean values of aminopyrine breath test, if they had chronic alcohol consumption. The difference between these and abstinent patients could secure only in fatty liver disease in the first stadium (p less than 0.001). Patients with severe chronic liver diseases had lower results of aminopyrine breath test, if they drink alcohol regular. These difference was significant in patients with cirrhotic liver disease (p less than 0.05).

Adult↗

PubMed1991

[The diagnostic value of the aminophenazone breath test in chronic liver diseases].

In 230 patients (90 females, 140 males aged between 20 and 73 years, average age 47.8 years) with and without exception histologically and/or laparoscopically ascertained chronic liver diseases (degenerative damages of liver parenchyma in 45, fatty liver stage I in 28, fatty liver stage II in 36, cholangiohepatitis in 4, chronic persisting hepatitis in 31, chronic active hepatitis in 57 and liver cirrhosis in 59 cases) the incorporation of the aminophenazon breathing test in the so-called laboratory chemical liver spectrum was controlled. The restriction of the microsomal biotransformation established by means of the aminophenazon breathing test behaved parallel to the degree of severity of the disease. The aminophenazon breathing test was performed in the modification after Haustein and Schenker (1985). The largest delays in the decomposition were found in the complete cirrhotic transformation of the liver. The unequivocally pathologic result of the aminophenazon breathing test in severe irreversible damages of the liver parenchyma was confirmed by the formation of correlations with parameters of the conventional laboratory spectrum of the liver. Thus the restriction of the performance of the synthesis of the liver for coagulation factors and albumins was parallel to the loss of function of the mixed functional oxidases. In all patients with chronic liver diseases a connection between the value of the thromboplastin time (Quick's test) and result of the breathing test was found. Positive linear correlation between serum albumin and results of the breathing test could also be proved particularly in the group of the severe chronic inflammatory liver diseases. In chronic fibrosing liver diseases there were positive inverse correlations between gamma-globulin concentration in the serum and thymol turbidity test on the one hand as well as the aminophenazon breathing test on the other. There were no correlations between liver enzyme and aminophenazon breathing test. The results of the own investigations incorporate the aminophenazon breathing test as indicator of a severe liver cell damage which at the same time is established by the pathological result of the so-called synthesis parameters of the liver.

Adult↗

PubMed1990

Review: therapeutic concepts of congestive heart failure.

The therapeutic concepts of congestive heart failure (CHF) are based on an increase in myocardial contractility and a decrease in pre- and afterload. Besides the digitalis glycosides, diuretics and vasodilators such as nitrates, hydralazine, ACE-inhibitors, calcium antagonists or prazosine are used. Furthermore, the so-called inodilators such as phosphodiesterase III inhibitors (amrinone, milrinone), dopaminergic and beta-adrenergic receptor agonists were introduced into therapy. The boone and bane of the different classes of drugs were discussed with respect to their hemodynamic and clinical properties.

Adrenergic beta-Agonists↗

PubMed1990

Interaction between nifedipine and cardioactive drugs.

Nifedipine (N) and dehydronifedipine (DHN) plasma levels were measured by gas chromatography in 37 patients before and 2 h after the intake of 20 mg N. They suffered from cardiovascular diseases and were treated with N in daily doses of 30 or 60 mg in combination with nitrates, beta-receptor blocking agents, digitoxin, saluretics and/or vasodilators for several weeks or months. Simultaneously, blood pressure and heart rate were measured. For comparison, six healthy volunteers between the ages of 25 and 46 years took 20 mg N on an empty stomach. Their mean plasma N level amounted to 47.7 (SD: 13.6) ng.ml-1, the DHN level reached a mean value of 46.7 (SD: 22.8) ng.ml-1 2 h after administration. The mean plasma N level of the patients rose from 14.1 to 34.1 ng.ml-1 and that of DHN, from 5.4 to 16.0 ng.ml-1. In 26 of 37 patients the heart rate increased without correlating with the altitude of the N level. The ratio DHN/N was 0.83 (SD 0.24) in the volunteers, while in the patients it amounted to 0.59 (SD 0.30). If the criterion DHN/N plasma level reached values greater than 1.0 the N degradation was enhanced (n = 4), and if it reached values less than 0.2, N degradation was depressed (n = 9). The results did not indicate inhibition of N degradation under long-term treatment with simultaneously administered cardioactive drugs.

Adult↗

PubMed1989

[Therapeutic drug monitoring of digitoxin--results of 3 years' experience].

Between 1986 and 1988 within our therapeutic drug monitoring plasma concentrations were estimated in 1,442 plasma samples by radioimmunoassay. Plasma levels between 0 and 84.2 ng.ml-1 with a mean of 20.8 ng.ml-1 were measured. If the maintenance dose was reduced from 0.1 to 0.07 mg the frequency distribution of the plasma samples was shifted to the left, and the mean value decreased by 5.8 ng.ml-1 (23.5 vs. 17.7 ng.ml-1). The physician's assumptions underdosage?, optimum dosage schedule? or overdosage? were confirmed by the laboratory results in 22.3, 63.6, or 23.0% of the requests, respectively. In 61.2% of all plasma samples were digitoxin concentrations in the range between 10 and 30 ng.ml-1, i.e. in the optimum therapeutic range. Main reasons for the divergent results are non-compliance of the patients and inter-individual differences in the pharmacokinetics of digitoxin. Furthermore, incomplete filling of the forms by the physicians aggravates the assessment of the results. Therefore, a permanent dialogue between clinician and clinical pharmacologist is necessary for an improvement of digitalis therapy.

Adolescent↗

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↗