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Biomedical subjects

K O Haustein

Publications and source records attributed to K O Haustein.

At least 19 recordsLinked to original sources
PubMed1997

Bioequivalence of tolbutamide-containing tablet preparations.

The present crossover study was undertaken to investigate in 22 volunteers (15 males, 7 females, aged 22-28 years) whether the 2 tolbutamide preparations (tolbutamide R.A.N. vs. rastinon Hoechst) are bioequivalent. After administering a single dose of one 1 g tablet of each preparation the plasma tolbutamide concentration was measured by HPLC over a time-period of 48 hours. The mean AUC0-48 values are nearly identical (998.42 vs. 997.73 micrograms x h x ml-1), while the Cmax values (51.1 vs. 58.8 micrograms/ml) and the tmax values (4.55 vs. 3.82 h) show slight differences. The Westlake intervals claimed to prove bioequivalence lies in the 95% confidence interval between the limits 0.972 and 1.046 (AUC), 0.896 and 0.978 (Cmax), and 0.056 and 1.346 (tmax). For example, this is the result of the parametric analysis considering the randomization. In the case of the parameters of the multiplicative model (AUC and Cmax) the probability of correctly concluding bioequivalence (power) between the 2 preparations reaches 2.0. Regarding maintenance therapy it is of minor importance that the maximum plasma tolbutamide concentrations is 0.7 h later observed with the test preparation than with the standard. The results of this study allow the conclusion that the 2 tablet preparations are bioequivalent.

Administration, Oral↗
PubMed1997

State of the art--treatment of peripheral occlusive arterial disease (POAD) with drugs vs. vascular reconstruction or amputation.

Peripheral occlusive arterial disease (POAD) is a disease with a progressive course in about half of the patients affected. The Fontaine stage II and III have been treated not always successfully in the last decades with physical exercise, vasoactive substances (pentoxifyllin, naftidrofuryl, buflomedil) and with alprostadil. Recently methods of vascular surgery such as PTA, stent implantation and bypass operations are introduced in the treatment of Fontaine POAD stages III and IV, but these procedures are not recommended in patients younger than 50 years in order to delay amputation of a limb. The vasoactive substances are seen in a new light, because they improve processes of the microcirculation such as decreasing plasma viscosity, the raised plasma fibrinogen level and increasing the deformability of red blood cells and inhibiting platelet aggregation. According to a number of studies pentoxifylline and naftidrofuryl may delay the progression of arteriosclerosis. Therefore, a new concept of the treatment of POAD must be evaluated (1) resulting in a combination of vascular surgery and intermittent drug therapy with vasoactive agents, (2) leading to a decrease in the risk of amputation frequency and (3) reducing the treatment costs in spite of a higher frequency of the disease and a longer average life expectancy.

Amputation, Surgical↗
PubMed1997

The effects of 2 beta-receptor blocking agents on the microcirculation of healthy subjects and of hypertensive patients.

The effects on parameters of the capillary system of the beta 1-blocker bisoprolol and of the alpha 1/beta-blocker carvedilol were investigated in 12 healthy female and 12 male non-smokers and smokers and in 20 hypertensive patients (state WHO I-II). Besides the antihypertensive and heart rate-reducing effect, carvedilol but not bisoprolol provoked a short-term increase in the capillary red blood cell velocity by 20% and an increase in the oxygen tension (tcpO2) in healthy smokers by 27% (p < 0.05). In hypertensive patients the single intake of carvedilol enhanced the capillary velocity by 16% after the first dose, the effect decreased by 5.4% after the intake for 4 weeks. The simultaneously observed increase in tcpO2 lasted only 30 min post dose, while bisoprolol was without significant effects. Carvedilol did not change the venous capacity after the first dose but increased it by 35% after intake for 4 weeks, while bisoprolol with its slight peripheral resistance-enhancing effect decreased the venous capacity after intake for 2 and 4 weeks. The venous outflow increased 1.5 and 2 h after carvedilol administration, but this was not seen 2 and 4 weeks later. The deformability of red blood cells was not changed by both beta-blockers. The data in volunteers and hypertensives indicate a weak vasodilating effect of carvedilol in contrast to bisoprolol in the arterial and venous capillary bed. These effects must be confirmed by additional studies.

Adrenergic beta-Antagonists↗
PubMed1996

[Homeopathy from the viewpoint of the clinical pharmacologist].

The homeopathy is a therapeutic line developed about 170 years ago which is based on the sciences of the late 18th century. The homeopathy is founded (1) on the vitalism of Aristoteles, (2) on the examination of remedy reactions in healthy subjects as basis of the therapy of patients, (3) on the "simile" rule, that means the treatment of symptoms with remedies which produce similar symptoms of a mild intoxication in healthy subjects, (4) on the principle of potentiation with the opinion that low doses provoke stronger therapeutic effects, (5) on the individual finding of a remedy due to an extensive anamnesis and (6) on the principle of nosodes, that means the use of diluted body secretion due to infectious diseases for therapy. The therapeutic principles of homeopathy are based on insecure hypotheses and on the patient's information of improved behaviour. Thus, homeopathy does not agree with the present natural science.

Homeopathy↗
PubMed1996

Cost-benefit analysis--a prerequisite of a rational pharmacotherapy in cardiovascular diseases. Timely thrombolysis in the acute myocardial infarction.

The worldwide increase in the expenses of the National Health Services compels the legislation of some countries to take economizing regulatory measures. In Germany the existent and planned activities are an essential part of the German Structural Health Act of 1993. In the last years methods have been developed to estimate the cost-benefit relationship of special therapeutic interventions giving the physician an aid to avoid the application of those of low cost-efficiency. The cost-effectiveness and the cost-utility analyses are the recently most usual ones. The timely thrombolysis of the acute myocardial infarction is presented under the viewpoint of the economical drug use in cardiovascular disease. Investigations to evaluate the cost-effectiveness of streptokinase and the newer thrombolytics anistreplase and alteplase are carried out in some European countries and in the USA. Parameters of efficacy are the amelioration of cardiac functions, the shortening of the rehospitalization duration, and the extension of the survival time. The use of a thrombolytic within 4 to 6 hours after the onset of the first signs is recommended and economically justified especially in anterior myocardial infarction and also in patients aged 75 years and above. Streptokinase is designated by a low cost-effectiveness ratio. The successful thrombolysis does not result in a continous deterioration of the quality of life in the patients. In this review no attempt was made to extrapolate the findings to the recent situation because of possible national pecularities with regard to the morbidity of and the therapeutic procedures in the acute myocardial infarction and because of the changes in the cost structure and currency parity which occurred in the meantime.

Acute Disease↗
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↗
PubMed1993

[The blood pressure lowering effect of bisoprolol, a beta 1-selective receptor blocker--a multicenter study in general practice conditions].

The antihypertensive efficacy and compatibility of 5 or 10 mg bisoprolol (Concor) was investigated in patients suffering from essential hypertension (stages I and II according to WHO) in a multicentre, open, non-randomized study. In total, 132 patients were included in the study of 11 outpatient departments. Seventeen patients dropped out because of personal reasons or mistakes of the protocol. If the diastolic blood pressure did not decrease to values < or = 90 mm Hg at the end of the first period of treatment with 5 mg bisoprolol, the dose was doubled to 10 mg within the second period of antihypertensive treatment. At the end of the first period the mean blood pressure decreased from 161.5/104.1 to 141.4/90.8 and after additional 4 weeks to 137.3/87.9 mm Hg. The mean heart rate decreased from 77.5 to 68.8 and 67.7/min, resp. The physicians who treated the patients rated the antihypertensive effect on 80.9% of the patients as good. Undesirable effects of bisoprolol were observed in 20 patients (15.2%). In total, bisoprolol has a good antihypertensive effect. It can be used in most patients as a monotherapeutic drug for treatment of stages I and II of hypertension with daily doses of 5 mg.

Bisoprolol↗
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↗