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Biomedical subjects

W Krause

Publications and source records attributed to W Krause.

At least 235 records · Page 13Linked to original sources
PubMed1986

Pharmacokinetics and pharmacodynamics in man of the dopamine antagonist ergot derivative, bromerguride.

The plasma levels and urinary excretion of the dopamine antagonist, bromerguride, were measured by radioimmunoassay in healthy male volunteers given 50 micrograms i.v. and oral doses of 1 and 2 mg. Plasma prolactin was also measured by radioimmunoassay. Following i.v. injection, the concentration of bromerguride declined biphasically, with half-lives of 7 min and 1.2 h. The total clearance was 32 ml X min-1 X kg-1 and the apparent volume of distribution was 3.61/kg. The bioavailability of oral bromerguride was 29% after 1 mg and 25% after 2 mg. The drug was almost totally metabolized and less than 0.05% of the dose was excreted in urine in 24 h after oral administration. Plasma prolactin levels were increased in a dose-dependent manner for about 8 h. Side-effects were minimal, mainly being tiredness and headache in some of the volunteers.

Administration, Oral↗
PubMed1986

Pharmacokinetics and pharmacodynamics of the prostacyclin analogue iloprost in man.

Plasma levels of the prostacyclin analogue, iloprost, were measured by antibody/GC/MS in healthy male volunteers given 1 and 3 ng/kg per min i.v. for 45 min, and 1 microgram/kg p.o. Following i.v. infusion, the steady-state plasma levels of iloprost were strictly dose-dependent (46 +/- 8 pg/ml and 135 +/- 24 pg/ml). The disposition was biphasic with half-lives of 3-4 min and 0.5 h. After oral administration, absorption of the drug was extremely rapid, the maximum plasma level of 251 +/- 32 pg/ml being achieved after 10 +/- 6 min. The bioavailability was 16 +/- 4%. Platelet aggregation induced by 2 microM ADP was reduced by 53% and 68% at the end of the two different infusions, and by 68% 15 min after p.o. administration. The ex-vivo inhibition of platelet aggregation by iloprost was not affected by preceding drug treatment. The cAMP content of platelets was increased by a factor of 2.5 at the end of the infusions and to a lesser extent 15 min after oral dosing. A slight increase in heart rate occurred during the infusion and within 30 min after oral administration; blood pressure was virtually unaffected. Except for transient side-effects (facial flush and headache) no adverse reactions were observed.

Administration, Oral↗
PubMed1986

Limitation of myocardial unperfused area and necrotic zone 24 hours and 7 days after coronary artery ligation in rats by the stable prostacyclin analogue iloprost.

Protective effects of prostacyclin (PGI2) and Iloprost in experimental cardiac ischemia are reported by several authors. However, the effects of continuous administration on the final outcome of myocardial infarction are not yet known. We investigated the effects of Iloprost on cardiac unperfused area (UA) and necrotic zone (NZ) as assessed by Evans blue perfusion and extraction and nitrobluetetrazolium staining, respectively, using osmotic minipumps for continuous intravenous drug administration. Starting 3-4 hours after left descending coronary artery-ligation (LAD-L) Iloprost was infused at doses of 0.1 microgram and 0.5 microgram X kg-1 X min-1. While the lower dose is below pharmacological effect level, the higher dose in rats slightly lowered blood pressure and effectively inhibited platelet aggregation. LAD-L in control rats resulted in UA and NZ extending to 34.2 and 16.9%, respectively, of total ventricular mass (VM) after 24 hours and 28.3 and 21.3% of VM, respectively, after 7 days. At the dose of 0.1 micrograms X kg-1 X min-1 Iloprost was ineffective in reducing UA 24 hours after LAD-L. However, at 0.5 microgram X kg-1 X min-1 Iloprost with UA and NZ of 16.3 and 8.4% of VM, respectively, after 24 hours and 8.5 and 5.2% of VM, respectively, after 7 days reduced the extension of myocardial infarction by approximately 50% after 24 hours and 70% after 7 days, as compared to controls. As assessed in unperfused ventricular tissue after LAD-L and normal myocardium of sham-operated rats following 24 hours of Iloprost infusion, myocardial tissue concentrations of Iloprost amount to approximately half of the plasma levels irrespective of LAD-L.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Phenylalanine alters the mean power frequency of electroencephalograms and plasma L-dopa in treated patients with phenylketonuria.

Phenylketonuria is a human model for the study of the effects of phenylalanine on brain function. We found previously a correlation between high blood phenylalanine, prolonged performance times on neuropsychological tests of higher integrative function, and decreased urinary dopamine in 10 patients. In this protocol we examine changes in triplicate of plasma dihydroxyphenylalanine (L-DOPA) and the mean power frequency of the electroencephalogram in eight additional older patients with phenylketonuria using longer intervals in a blinded, cross-over design. Mean power frequency was obtained by Fourier transform of the power spectrum from traditional eight channel electroencephalograms. Plasma L-DOPA was quantitated by radioenzymatic methods. In all patients statistically significant decreases were found in the mean power frequency of the electroencephalogram and in plasma L-DOPA when plasma L-phenylalanine increased. These findings were reversible and correlated in the reverse direction when plasma L-phenylalanine was reduced. Thus changes in the mean power frequency of electroencephalograms and circulating L-DOPA offer sensitive parameters of human brain function in vivo. These findings indicate reversible effects of elevated plasma phenylalanine on electrical function of the brain which may be mediated in part through inhibition of catecholamine synthesis.

Adolescent↗
PubMed1986

[Modification of smooth muscle contractility by Cordemcura].

Cordemcura causes a dose-dependent inhibition of noradrenaline contractions of isolated rabbit aorta as well as of isolated guinea pig ductus deferens. In both organ preparations analogous intensity of effect has been observed. In different intestinal isolated organs Cordemcura also produces a dose-dependent inhibition against different agonists. The Ba2+-induced contraction is inhibited to approximately the same extent as various receptor-induced contractions. Consequently a specific receptor function on smooth muscle has to be excluded with regard to Cordemcura. Furthermore Cordemcura has a bronchodilatory effect. This property could be proved by the protection effect as observed in the inhalative histamine-induced bronchoconstriction in guinea pig.

Aminopyridines↗
PubMed1985

[Physical, physiological, diagnostic and therapeutic aspects of thermography in clinical dermatology].

Clinical application of thermovision in dermatology is a non-contact, sterile, and absolutely harmless method and offers a variety of diagnostic and therapeutical possibilities regarding the detection of irregularities in the temperature distribution of the skin. Thermovision provides us with information about the extent of dermatoses or tumors, metastases, as well as the response to therapy. Another important medical application of thermovision is dynamic testing in dermato-surgery. This technique is fundamental with regard to diagnosis, management planning, differential diagnosis, monitoring of therapeutical effects, and as a very sensitive detector of recurrence. We are going to demonstrate the applications mentioned above on the basis of a few examples.

Aged↗
PubMed1985

[How does ketoconazole affect testosterone metabolism?].

Inhibition of the testosterone synthesis caused by ketoconazole was studied in healthy young men. They received the drug for seven days at a dose of 200 mg daily. Neither the blood level of total plasma testosterone nor that of the free fraction showed any alteration during treatment. 24 hours after treatment, however, the response of plasma testosterone to hCG was diminished. These findings indicate a delayed effect of ketoconazole on the synthesis of testosterone, although its blood levels are decreased to nearly zero. The effects of ketoconazole are due to its binding to enzymatic proteins. Thus the link to other proteins binding androgens might be possible. Our experiments demonstrated that ketoconazole may inhibit the binding of testosterone to antibodies in a RIA system as well that to SHBG.

Adult↗
PubMed1985

[The diagnostic significance of short-time intravenous tests with human chorionic gonadotropin].

The normal response of testosterone synthesis to hCG has a biphasic pattern. After a short peak within four hours, there is a decrease followed by a second peak within 24 to 48 hours. In an endocrine system without other disturbances, the short-term reaction is a good parameter for Leydig cell function. We analyzed the short-term tests of 266 patients. Clinically normal persons (181) showed an increase of testosterone from 8.3 to 10.1 ng/ml after 2 hours. Similar levels were found in patients with varicocele, while men suffering from testicular hypoplasia responded by lower values (6.2 and 7.8 ng/ml). Patients with psychogenic impotence reacted significantly less (9.5 basally and 7.6 ng/ml after 2 h), whereas normal response was observed in patients with impotence due to hypertonus (9.0 to 11.0 ng/ml - n = 7). The comparison of our test results with the outcome of hormonal stimulation of spermatogenesis in oligozoospermia (n = 73) shows that better results are obtained if hCG produces a higher quotient. There have been no side effects of the test observed. In 81 patients, blood was tested at least 4 weeks later for the occurrence of hCG-antibodies; they were not demonstrable in any case. The short-term test is a simple, time-sharing method for testing of Leydig cell function.

Chorionic Gonadotropin↗
PubMed1985

The effect of estradiol on the sebaceous gland of the hamster ear and its antagonism by tamoxifen.

To evaluate the antagonism between estradiol and tamoxifen in the sebaceous gland of the hamster ear, animals were topically treated, and the size of the sebaceous glands was measured by histoplanimetry. The systemic effects were described by determining the estradiol and testosterone plasma levels and within the testes, and the size of the seminal vesicles and the contralateral sebaceous gland. The administration of 0.1 micrograms estradiol resulted in a diminution in the size of the treated glands but left all other parameters unchanged, indicating a purely local effect. A higher dose of estradiol (1 microgram) further decreased the size of the treated glands, but this was combined with a systemic effect, i.e. low plasma testosterone, decrease in testis size and a diminution of the contralateral ear gland. Ten micrograms of estradiol maximally suppressed all of the androgen effects without side effects. The administration of tamoxifen alone also decreased the size of the sebaceous glands without side effects, but it did not affect the production or effects of androgens. When administered in combination with estradiol, it antagonized the effects of this hormone completely. We conclude that tamoxifen inhibits the negative effect of estradiol on sebaceous-gland size. It acts predominantly in a systemic manner, because a metabolisation to monohydroxytamoxifen is necessary.

Animals↗
PubMed1985

Development of antibody-mediated extraction followed by GC/MS (antibody/GC/MS) and its application to iloprost determination in plasma.

A new analytical principle has been developed combining the features of both radioimmunoassay and GC/MS. Its application in eicosanoid analysis was tested with the prostacyclin analogue, iloprost. The iloprost antibody, generally employed in RIA measurements, was coupled to Sepharose 4B and used as stationary phase for extraction of the drug. Variations in recovery were corrected by using deuterated iloprost as an internal standard. The samples were derivatized and quantitated by negative-ion chemical ionization-mass spectrometry. Reproducibility was 2.3 % at the 50 pg/ml level and the limit of detection was 5 pg for 1 ml samples. With plasma volumes of up to 20 ml, 0.25 pg/ml could be determined. Antibody/GC/MS proved superior to radioimmunoassay due to its higher specificity and sensitivity and superior to GC/MS with conventional clean-up procedures because of a higher sample capacity.

Epoprostenol↗
PubMed1985

Effects of chloroquine on hepatocytic organelles in rat.

The administration of chloroquine (Resochin) in rats produces significant changes in the hepatocytic organelles, which are described by morphometric and biochemical methods. There is an increase in oxygen uptake by the isolated mitochondria together with an increase in the specific surface of cristae. Volume densities of mitochondria, lysosomes, rough and smooth endoplasmic reticulum and Golgi apparatus increase, while that of glycogen decreases. The affecting mechanisms are discussed.

Animals↗
PubMed1985

[Significance of trial vacuum extraction in the framework of obstetric surgery in vertex presentation].

On the basis of a clinical study of 76 infants born by trial vacuum extraction from the pelvic inlet, 57 infants were examined retrospectively with regard to early and late morbidity after "successful" trial vacuum extraction. In 34 cases surgery was indicated because of fetal distress; in 23 children the operation was performed because of a standstill at the pelvic inlet. The results were compared with a group of infants delivered by vacuum and forceps extraction from the centre of the pelvis (or the pelvic floor) or cesarean section in consequence of fetal distress. The results indicate the high risk for children born by trial vacuum extraction, especially in cases of fetal distress. In addition to statistically significant lower Apgar scores and a statistically significant higher acidosis morbidity (p less than 0.05) as compared to other obstetric operations, there is also a statistically significant greater number of "striking" and "injured" children as opposed to those delivered by vacuum or forceps extraction from the centre of the pelvis (or the pelvic floor) or by cesarean section in consequence of fetal distress. These neurological deviations represent primarily the static-motoric and speech development, and are analogous to late morbidity after births from breech presentation. The findings confirm the clinical impression that trial vacuum extraction-especially in cases of fetal distress at the pelvic inlet-represent an additional risk to the child. In such cases cesarean section is the only alternative method of delivery.

Apgar Score↗
PubMed1985

[Pattern changes in the framework of cesarean sections in 1980/83 as compared to 1974/76 in the University Women's Clinic in Jena].

In a comparative study on Caesarean section problems-based on investigations from 1974/76 and 1980/83-conducted at the Gynaecological and Obstetrical Hospital of Jena University, changes are apparent in the indication for Caesarean section and in maternal morbidity. The evident decrease in statistically uncorrected perinatal mortality as well as in uncorrected intra-and postnatal mortality during this period (difference statistically significant at p less than 0.05) was not due to a further increase in Caesarean sections from 8.23% (period 1974/76) to 9.27% (period 1980/83), but to other factors (improved medical care for pregnant women and improved neonatal check-up). In comparison with uncorrected intra-and postnatal mortality, perinatal Caesarean section lethality even showed a 2,46-fold relative increase. As late morbidity among high-risk children related to the immediate stage of labour is still poorly understood, "extended" indication for Caesarean section is maintained-in spite of high infection morbidity among mothers. General perioperative antibiotic prophylaxis for these women is recommended because of the statistically significant poor situation of secondary Caesarean sections as far as maternal morbidity is concerned.

Apgar Score↗
PubMed1985

Ureaplasmal infections of the male urogenital tract, in particular prostatitis, and semen quality.

Ureaplasma urealyticum is considered an etiologic agent in urogenital tract infections, especially prostatitis. Using the 'four-specimen technique', diagnosis can be based upon significant numbers of these microorganisms. In ejaculate, the critical number seems to be 10(3) cfu/ml of semen to discriminate between real infection and contamination during urethral passage. In our study, 46 of 412 samples (11.2%) exceeded this critical number. Most but not all patients suffering from ureaplasma-associated prostatitis established by the 'four-specimen technique' revealed significantly high ejaculate numbers, whereas all samples from patients with prostatodynia and healthy controls had lower numbers. In these cases, numbers of round cells in semen, i.e. all leukocytes and spermatides, were significantly increased as compared to prostatodynia. A significantly negative correlation was detected between the numbers of ureaplasmas and zinc concentration in semen, and an almost identically negative correlation to the content of fructose, thus indicating secretory dysfunction of the accessory glands in ureaplasmal infections of the prostate.

Adolescent↗
PubMed1985

Biochemical and neuropsychological effects of elevated plasma phenylalanine in patients with treated phenylketonuria. A model for the study of phenylalanine and brain function in man.

Phenylketonuria provides a human model for the study of the effect of phenylalanine on brain function. Although irreversible mental retardation is preventable through newborn diagnosis and dietary phenylalanine restriction, controversy exists regarding the effects of increased concentrations of phenylalanine in older patients. We have studied ten older, treated, phenylketonuric patients using a triple-blind, multiple trials, crossover design. Each patient was tested at the end of each of three 1-wk periods of high or low phenylalanine intakes. Tests included a repeatable battery of neuropsychological tests, analysis of plasma amino acids, and measurement of urine amino acids, phenyl organic acids, dopamine, and serotonin. In all 10 patients plasma phenylalanine rose (900-4,000 microM). In 9 of 10 patients there was an inverse relationship between plasma phenylalanine and urine dopamine excretion. When blood phenylalanine was elevated, these patients had prolonged performance times on neuropsychological tests of higher but not lower integrative function. Urinary serotonin fell during phenylalanine loading in six patients. The concentration of phenylacids in the urine was not proportional to the plasma phenylalanine at concentrations below 1.5 mM. In one patient, neither performance time nor dopamine excretion varied as blood phenylalanine rose or fell. We interpret these data as follows: blood phenylalanine above 1.3 mM impairs performance on neuropsychological tests of higher integrative function, this effect is reversible, and one mechanism may involve impaired biogenic amine synthesis.

Adolescent↗