Biomedical subjects
W Krause
Publications and source records attributed to W Krause.
High-performance liquid chromatographic procedure for specificity testing of radioimmunoassays: rolipram.
A high-performance liquid chromatographic (HPLC) procedure for testing the specificity of radioimmunoassays (RIA) was developed using the same method of extraction as in the RIA, followed by fractionation of the extract by HPLC and subsequent measurement of cross-reactions in all the fractions according to the normal RIA procedure. The RIA of rolipram, an antidepressant drug, was checked in plasma samples obtained from pharmacokinetic studies in rats, rabbits, cynomolgus monkeys and humans. The antibody was shown to be specific in the plasma samples from the laboratory animals, but not in human plasma. This was because in human plasma a metabolite occurred with a structure similar to that used for the hapten in the immunization process. This metabolite was not found in the plasma of the animal species investigated. The test procedure described is generally applicable, making the time-consuming development of an alternative method such as gas chromatography-mass spectrometry unnecessary.
The clinical significance of antisperm antibodies in infertile couples.
Sera from 150 women and 162 men with unexplained infertility were examined using a commercial enzyme-linked immunosorbent assay (ELISA) kit for antisperm antibodies. The results were compared to those of the Friberg agglutination test, the post-coital test, the sperm-cervical mucus contact (SCMC) test and the pregnancy rate. We also tested follicular fluids obtained from 38 women who underwent in-vitro fertilization (IVF). These data were compared with those obtained in serum, post-coital test data and with the later development of the oocyte in IVF. Antibodies in follicular fluid were found only in women with antibodies circulating in serum. The correlation coefficient between these was 0.88 (P < 0.001). There was no correlation between antisperm antibodies in serum found with the ELISA test, and with the agglutination test, the post-coital test or the SCMC test. Neither was there any correlation between antibodies in follicular fluid and the post-coital test, the pregnancy rate or successful IVF.
Role of varicocele in male infertility.
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Treatment of idiopathic oligozoospermia with tamoxifen--a randomized controlled study.
There is no conclusive evidence of the usefulness of tamoxifen in the treatment of idiopathic oligozoospermia (OAT-syndrome), as it has been used mostly in uncontrolled studies. We herein report on the controlled treatment of OAT-syndrome with tamoxifen versus placebo following a randomized design. Seventy-six men with sperm counts of 2-20 x 10(6) ml-1, sperm motility of 20-50%, and sperm morphology (abnormal cells) between 50 and 80% were involved in the study. Patients with varicocele, a history of testicular maldescent or genital inflammation were excluded. Thirty-nine patients received tamoxifen (30 mg daily), 37 patients placebo. There was a statistically significant increase in the mean serum testosterone level after treatment in the tamoxifen-treated group (from 4.9 +/- 1.9 to 7.9 +/- 3.6 ng ml-1) in comparison to the placebo group (5.3 +/- 2.0 and 5.6 +/- 2.0 ng ml-1). Serum FSH levels increased slightly in the tamoxifen group (from 6.8 +/- 4.1 to 7.3 +/- 4.8 mU ml-1), but this was not statistically significant in comparison to the placebo group (from 5.9 +/- 3.9 to 5.2 +/- 3.5 mU ml-1). Serum levels of LH did not show any differences between groups. The sperm count increased during treatment from 9.3 +/- 11.7 to 11.4 +/- 13.7 x 10(6) ml-1 in the tamoxifen group and from 9.1 +/- 7.1 to 9.3 +/- 8.8 x 10(6) ml-1 in the placebo group; this difference did not reach statistical significance. The percentage of motile and abnormal sperm was not different between the two treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Semen analysis and fertility prognosis in andrological patients.
Semen analyses of 529 men who consulted our department due to infertility problems, were related to the time period prior to conception, with factors adversely affecting the fertility of the female partner taken into consideration. The statistical method used was Cox's proportional-hazard model of regression. Untransformed, logarithmically transformed and dichotomized semen analysis variables were included in the calculations. The relationship between the following parameters and the probability of conception was examined: sperm count, sperm motility, progressive sperm motility, morphology and sperm motility remaining 24 h after ejaculation. All variables co-varied with the probability of conception; however, the exact type of relationship could not be determined by regression analyses. Cox's model assumes an exponential relationship. Our data suggest that this assumption is not suitable for fertility investigations. Using conventionally defined limiting values for normal and pathological semen quality, statistical analysis yielded significant differences in fertility between both categories for all of the variables considered; in the stepwise regression analysis, however, it could be shown that progressive motility and morphology alone were sufficient to discriminate between normal and pathological semen quality. The results are interpreted as indicating that, as a result of semen analysis, it is possible to predict the individual probability of conception if the exact shape of the relationship can be determined, which, up to now, has not been accomplished.
Treatment of idiopathic oligozoospermia with tamoxifen--a follow-up report.
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Placental transfer of the anxiolytic beta-carboline abecarnil in rabbit.
The placental transfer of abecarnil (isopropyl 6-(benzyloxy)-4- (methoxymethyl)9H-pyrido(3,4-b)indole-3-carboxylate, ZK 112 119, CAS 11184-1-85-1) was studied in the rabbit after i.v. injection of 0.1 mg/kg and oral dosing of 10 mg/kg using 14C-labeled drug and HPLC with fluorescence detection for measurement of the unchanged drug. Abecarnil easily passed the placental barrier and achieved high concentrations in the fetus. The concentration ratio C(fetus)/C(dam plasma) was 24 +/- 12 for all animals and time points. Metabolites were not able to cross the placental barrier to the same extent as the unchanged drug (ratio 1 +/- 2). The time courses of drug concentration and total radioactivity in the fetus were parallel to the respective time courses in the dams plasma. Accumulation of drug and metabolites upon multiple dosing, therefore, should not differ from that observed in the dam.
[Laparoscopic abdomino-perineal resection of the rectum with high intersection of the inferior mesenteric artery].
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[Measuring mental performance: an old idea and a new approach].
First results are reported from the attempt to make mental performance measurable in terms of elementary thought processes. The formation of order in thought is seen as a unit with which mental performance can be measured. The formation of order is described by complexity-reducing structuring. A measurement process for elementary problem-solving demands based on the symbol-distance effect was also developed. From the comparison with the solution of complex problems, it was shown that those test subjects who attain the best solutions to more complex demands are also those who have the most parsimonious cognitive structures in problem solving. Complexity reduction is measured by the performance of the alpha band in EEG mapping. With the use of a more parsimonious cognitive structure, higher performance is measured in comparison with the use of complexity-intensive cognitive structure.
Intellectual development in 12-year-old children treated for phenylketonuria.
Intelligence and achievement test scores were evaluated for 95 12-year-old children with phenylketonuria who had begun dietary therapy during the neonatal period. Dietary control of blood phenylalanine below 900 mumol/L was maintained beyond age 10 years in 23 children; 72 others had blood phenylalanine persistently above that level at ages ranging from 18 months to 10 years. Test scores at age 12 years were negatively correlated with the age at initiation of diet and with blood phenylalanine levels from ages 4 to 10 years, and positively correlated with parent IQ scores and the age at loss of dietary control. Children who maintained phenylalanine levels below 900 mumol/L beyond age 10 years showed no deficits in test scores, except for arithmetic, the scores of which declined between ages 6 and 12 years in 90% of the children in this study. These data strongly support a recommendation that dietary restriction of phenylalanine should be maintained through adolescence.
The pharmacokinetics and pharmacodynamics of lisuride in healthy volunteers after intravenous, intramuscular, and subcutaneous injection.
The plasma concentration of lisuride and prolactin have been measured in twelve healthy male volunteers after IV, IM or SC injection of 25 micrograms lisuride hydrogen maleate as an aqueous solution. After IV administration the plasma lisuride fell in two phases with half-lives of 14 min and 1.5 h. Total clearance was 13 ml.min-1.kg-1. After IM and SC injection the plasma concentrations peaked at 12 to 15 min and the profiles were similar to that found after IV administration. The systemic availabilities were 90% and 94%, respectively. Prolactin concentrations were reduced by a maximum of 60% relative to the normal circadian rhythm after all three routes of administration. The treatments were well tolerated, the only adverse reactions reported by some of the volunteers being mild, transient dizziness, tiredness, and nausea.
Preclinical characterization of iopromide-carrying liposomes.
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Evaluation of the acrosome reaction using monoclonal antibodies against different acrosomal antigens--comparison with the triple stain technique.
The acrosome reaction of human sperm was evaluated in vitro with the aid of there monoclonal antibodies TüS-1, TüS-19 and TüS-20, which react with antigens in the anterior part of the acrosome. Data were compared with results obtained using the triple stain technique. Seminal smears were performed prior to, and following incubation for 5 and 24 h in Hams-F10 containing 3% human serum albumin. Using the triple stain technique, 15.2 +/- 7.1% of sperm exhibited acrosome activation after 5 h and 16.8 +/- 8.4% after incubation for 24 h. The corresponding values obtained using antibody TüS-1 were 12.9 +/- 5.8 and 13.2 +/- 2.2%, with TüS-19 10.1 +/- 3.8 and 10.8 +/- 1.4% and with TüS-20, 9.0 +/- 3.4 and 10.4 +/- 2.9%. When the same sperm smears were stained firstly with rose Bengal, and secondly with TüS-1 both methods stained the same cells and the same region of the cells, thus indicating that both methods stain the same substrate. Staining of the acrosome with monoclonal antibodies gives clearer results than the triple stain technique, and could be used in preference in future studies dealing with diagnosis of the acrosome reaction in vitro.
Multiple intragastric treatment versus continuous administration via the diet. Comparative pharmacokinetics of abecarnil in mouse.
1. Abecarnil was administered to female mice at doses of 5, 50 and 150 mg/kg per day for 4 weeks either intragastrically once a day or was offered continuously via the diet. 2. On days 1, 7, 14 and 28 plasma level profiles (0-24 h) were determined in identical groups of animals. Additionally, faecal excretion of abecarnil and distribution in brain, liver and kidney was measured. 3. Drug administration via the diet was characterized by: (a) a circadian rhythm of concentrations with highs at night and lows during the day; (b) a dose-proportional increase in AUC and mean plasma levels; (c) slight accumulation in the plasma after the two higher doses. 4. Intragastric treatment resulted in: (a) clearly distinguishable absorption and disposition phases in the plasma with prominent peaks; (b) slight accumulation at the two higher doses; (c) dose-proportionality for the 50 and 150 mg/kg doses. 5. Drug load after the two routes of administration was different resulting in four times higher peak plasma levels and in double AUC values after intragastric administration than after the diet.
Pharmacokinetics and biotransformation of the anxiolytic abecarnil in healthy volunteers.
1. The pharmacokinetics of abecarnil were studied in eight healthy male volunteers using 14C-abecarnil and an h.p.l.c. method for determination of unchanged drug. 2. Abecarnil was rapidly and nearly completely absorbed after an oral dose of 10 mg; bioavailability was 40%. Plasma levels of the unchanged drug declined with a terminal half-life of 4 h. The total clearance of abecarnil was 11 ml/min per kg. 14C-Abecarnil was excreted rapidly and completely. The main route of elimination was in the faeces. 3. Abecarnil was extensively metabolized resulting in ether cleavage at position 6 with subsequent glucuronidation or sulphation and, to a minor extent, in ester cleavage.
[Hormonal changes in aging from the viewpoint of the andrologist].
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Pharmacokinetics of 3H-terguride in elderly volunteers.
Blood and plasma levels and excretion of labeled compounds and of the unchanged drug were measured after i.v. injection of 54 micrograms and p.o. administration of 540 micrograms of the ergoline derivative, terguride (CAS 37686-84-3), labeled with tritium, in 6 elderly male volunteers. Following i.v. injection plasma levels of terguride declined with a half-life of 0.5 h and those of radiolabeled compounds with half-lives of 0.5 h, 7 h and 19 h. The total clearance was 17 ml/min/kg and the volume of distribution was 0.7 l/kg. After p.o. administration terguride was rapidly and completely absorbed. The bioavailability was around 20%. Elimination of labeled compounds was complete within 7 days and proceeded mainly via the urine. Computer simulation of plasma levels after 4-times-a-day multiple administrations indicated slight accumulation of metabolites (factor 3) and no accumulation of terguride (factor 1).