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Biomedical subjects

W Krause

Publications and source records attributed to W Krause.

At least 145 records · Page 8Linked to original sources

[Genital skin manifestations in sexually transmissible diseases].

When diseases of the genital skin are treated with topically applied drugs, it must be borne in mind that resorption through the genital skin is facilitated compared with other skin regions, so that toxic reactions can result even with low doses, and that it is not permissible to prescribe antibiotic treatment on the suspicion of ulcers without skillful diagnosis, because a primary syphilis might be overlooked in this way. Important diseases of the genital skin are: Condylomata acuminata. The prevalence has increased in recent years, to the point where genital warts are now one of the commonest sexually transmitted diseases. As they are contagious and involve the risk of malignant transformation, treatment is necessary in every case. Herpes genitalis. The typical blisters occur on the glans penis or the labia minora. At the time of presentation the physician often observes only excoriations and crusts. Herpes genitalis recidivans is particularly problematic, the only effective treatment being long-term acyclovir. Lymphopathia venerea is caused by Chlamydia trachomatis and is rare in central Europe. Treatment with quinolones is effective. Molluca contagiosa is a group of self-limiting viral diseases that occur in children; they are harmless in themselves, but sexual abuse should be considered. Parasitic diseases are caused by Phthirius pubis and Sarcoptes scabiei. The main symptom is severe itching. The diseases can be easily treated with suitable insecticides. Syphilis. The first sign of the disease is chancre, which can be described as a flat, indurated, nontender ulceration.(ABSTRACT TRUNCATED AT 250 WORDS)

Condylomata Acuminata↗

Anti-inflammatory activity of rolipram in a rat ear edema model.

In the present study the anti-inflammatory activity of the phosphodiesterase inhibitor rolipram (ZK 62,711, CAS 61413-54-5) was tested in a rat model where edema was induced in the ears of the animals by the epicutaneous application of croton oil in ethanol (5%, by volume). The administration of 0.015, 0.15 and 1.5 mg rolipram per ear dose-dependently inhibited the formation of edema. Concomitantly, the body temperature of the rats was decreased. 4-14% of rolipram was percutaneously absorbed within a 5-h interval. The absorbed proportion, represented by the area under the plasma level-time curve, correlated with the inhibition of edema formation and with the decrease in body temperature.

Administration, Topical↗

[Comparative parasitological stool studies using the methods of Kato & Miura, Lawless, Heine and BIOSEPAR].

Twenty evidences of parasites were found in 152 stool-samples in comparison of parasitological stool-examinations according to Kato & Miura, Lawless, and Heine with the new diagnostic system BIOSEPAR. Advantages of the system BIOSEPAR: Recording of protozoans and helminths at the same time; not any contacts with samples of examination and reduction of risk of infection. Advantages of the other methods: Saving of material and time; evidence per slide also of smaller numbers of parasite stages; better chance to differentiate the stage of protozoans.

Animals↗

[Andrologic indications for assisted reproduction techniques. When can increased fertilization rates by assisted reproduction be expected?].

Basics: When the cause of a sterile marriage must be assumed to lie with the husband, attempts are often made to resolve the problem by applying the techniques of assisted reproduction, viz insemination and in vitro fertilization (IVF). In such a case, this is the treatment of the wife, who may herself be completely healthy. Major points: In the case of oligoasthenoteratozoospermia (OAT) syndrome, the various techniques available are unable to decisively increase the conception rate. In particular, all IVF working groups are agreed that successes are greatly reduced in the case of inferior sperm quality, as compared with other indications. The "poorer" the original findings, the lower are the fertilization rates. The costs of IVF of about DM 6,000 per cycle mean that, with a success rate of some 8%, the overall cost for each pregnancy is about DM 72,000. This fact tends not to receive sufficient mention in discussions with the married couple. So far, it has not been possible to predict the success rate of an IVF on the basis of an examination of the ejaculate with any degree of accuracy with the aid of the parameters sperm cell density, motility and morphology. Nor do biological tests or an investigation of acrosome function help improve the situation. Even the direct observation of the fertilization of a human ovum, is of questionable value.(ABSTRACT TRUNCATED AT 250 WORDS)

Fertilization in Vitro↗

Clinical and biochemical studies in an American child with sialuria.

Sialuria is a rare inborn error of sialic acid (NeuAc) metabolism resulting from failure of CMP-NeuAc to adequately feedback inhibit the rate-limiting enzyme in sialic acid synthesis, UDP N-acetylglucosamine (UDP-GlcNAc) 2-epimerase. We describe the fourth reported sialuria patient, T.W., whose clinical features include developmental delay, coarse facies, and massive urinary excretion of sialic acid. Biochemical studies of T.W. fibroblasts revealed a 200-fold increase in free NeuAc content compared with normal. Bound NeuAc was only slightly elevated. The free NeuAc was predominantly in the cytosol fraction of fibroblasts after differential centrifugation, with only 4% of the free NeuAc content in other (nuclear, granular, and microsomal) cellular compartments. CMP-NeuAc inhibited UDP-GlcNAc 2-epimerase by 80% in normal fibroblasts but inhibited the epimerase of T.W. (sialuria) cells by only 13%. Cytidine feeding of sialuria fibroblasts decreased the intracellular free NeuAc content by 47%; this was accompanied by a fourfold increase in CMP-NeuAc, which may be sufficient to feedback inhibit the mutant epimerase and reduce free NeuAc production. Cytoplasmic pH was determined by the pH sensitive fluorescent indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein, pentaacetoxymethylester (BCECF/AM) using the H+ equilibration method. The intracellular pH of sialuria fibroblasts, 7.18 +/- 0.04, was not found to be significantly different from that of normal cells (7.19 +/- 0.08).

Cells, Cultured↗

Characterization of iopromide liposomes.

RATIONALE AND OBJECTIVES: Iopromide-carrying liposomes were prepared and were characterized pharmaceutically and biologically. METHODS: The liposomes were prepared by the ethanol evaporation method and were characterized by quasi-elastic light scattering (size) and equilibrium dialysis (encapsulation efficiency and stability). Acute and subchronic toxicity was tested in mice and/or rats and cardiovascular tolerance in rabbits. Pharmacokinetic parameters were determined in rats. Computed tomography (CT) imaging efficiency was obtained from rat and rabbit studies. RESULTS: The mean diameter was 0.5 +/- 0.1 micron and the encapsulation efficiency ranged between 30% and 40%. The liposomes were stable in human and rabbit plasma for approximately 24 hours. The LD50 in mouse and rat was approximately 3 g iodine/kg. In a subchronic toxicity study in rats with six doses of 1 g iodine/kg given every three days, no adverse effects were observed. The pharmacokinetics in rats were dose-dependent. Increasing the dose resulted in lower total clearance, and longer terminal half-life. Elimination of iodine was complete and the main route of excretion was via the kidneys. A clinically relevant computed tomography enhancement of the liver was reached after approximately 200 mg iodine/kg in rats and 150 mg iodine/kg in rabbits. CONCLUSIONS: The iopromide-carrying liposomes were well tolerated in animal studies and seemed to be suitable for the imaging of the liver.

Animals↗

Human studies on abecarnil a new beta-carboline anxiolytic: safety, tolerability and preliminary pharmacological profile.

1. Abecarnil (isopropyl-6-benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate), a beta-carboline with high affinity for benzodiazepine receptors, was tested in healthy male subjects; single doses of abecarnil were given in five dosage levels (1 mg, 5 mg, 10 mg, 20 mg, 40 mg) and in a multiple dose study in four dosage levels (15 mg, 30 mg, 60 mg, 90 mg day-1) for 7 days. On two days following multiple dose treatment, placebo was given in single-blind conditions (follow-up). In each dosage level, in both studies drug was given to 10 subjects (7: verum, 3: placebo). 2. Safety and tolerability were evaluated by changes in vital signs, incidence and severity of adverse reactions and biochemical and haematological screening. Drug effects were estimated utilizing a bipolar visual analogue scale (poles: 'sleepy'-'alert') and a psychomotor task, the digit symbol substitution task. The pharmacokinetics of single and multiple doses were also determined in the multiple dose study. 3. Abecarnil was generally well tolerated. In the single dose study the most frequently reported side effects associated with abecarnil at high doses (20 and 40 mg) were dizziness, unsteady gait, and lack of concentration. A decrement in performance on the digit symbol substitution task was also observed in the two high dosage groups 20 mg and 40 mg. Evaluation of visual analogue scale ratings did not reveal a sedative effect even at higher doses. 4. In the multiple dose study the most frequently reported side effects during the treatment period were dizziness, unsteady gait, and lack of concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Biotransformation of the antidepressant D,L-rolipram. II. Metabolite patterns in man, rat, rabbit, rhesus and cynomolgus monkey.

1. The metabolism of D,L-rolipram in man was studied by comparison of h.p.l.c. radiochromatograms of plasma and urine obtained at various times following oral and/or s.c. administration to man, rat, rabbit, and rhesus and cynomolgus monkey. 2. Seven metabolites isolated previously from man, rat, and rhesus monkey urine by preparative h.p.l.c. and identified by mass spectrometry and n.m.r. analysis were used for metabolite identification. 3. In plasma, 3-5 metabolites were found in addition to the unchanged drug. In urine, which was the main excretion route for rolipram metabolites, > 10 metabolites were detected but not the parent compound. 4. Between 40 and 70% of the compounds eliminated renally, were identified by reference to isolated metabolites. 5. Biotransformation proceeded by ether cleavage at the methoxy and pentyloxy groups, and by hydroxylation in positions 2 or 3 of the pentyloxy ring followed by sulphation. 6. In man, not in the other species studied, the 5-position of the pyrrolidone ring was also hydroxylated. This compound cross-reacted with the antibody raised against rolipram which was used formerly for the determination of rolipram in biological fluids.

Animals↗

Laparoscopic abdominoperineal excision of the rectum with high ligation of the inferior mesenteric artery in the management of rectal carcinoma.

Extended lymph node dissection, creation of a safe anastomosis and specimen retrieval pose the greatest problems in laparoscopic colorectal surgery. A safe technique for the performance of extended lymph node dissection with high vessel ligation has been developed on the basis of experimental studies. Abdominoperineal excision of the rectum is ideal for laparoscopic colorectal surgery because this procedure requires no anastomosing, and the specimen is retrieved perianally. From January to August 1992, we performed a laparoscopic excision of the rectum with high ligation of the inferior mesenteric artery in ten patients with low carcinomas. This paper presents clinical and technical data.

Carcinoma↗

Preparation and evaluation of lyophilized iopromide-carrying liposomes for liver tumor detection.

RATIONALE AND OBJECTIVES: The objective of the present investigation was to demonstrate a new method for the production of iopromide-carrying liposomes. We studied biodistribution and elimination behavior, as well as the computed tomography (CT) liver imaging properties. METHODS: Iopromide-containing liposomes were prepared by the ethanol evaporation method and subsequently lyophilized. The resuspended liposomes were tested in rats and rabbits. RESULTS: After resuspension, liposomes with a mean diameter of 467 +/- 66 nm and an encapsulation rate of 41.5 +/- 5.5% were obtained. In rats, a marked accumulation of liposomal iopromide was found in the liver and spleen. In rabbits, complete renal elimination of iopromide within 7 days was demonstrated. At a dose of 150 mg total iodine/kg, a small tumor (< 0.5 cm) could be detected in a VX-2-bearing rabbit. CONCLUSIONS: The ethanol evaporation method proved to be suitable for the reproducible large-scale manufacture of iopromide liposomes with high encapsulation. The resuspended liposomes displayed favorable biodistribution, elimination and imaging characteristics.

Animals↗

[The significance of the "routine spermiogram". A critical analysis].

A spermiogram includes the determination of the sperm count (normal range 20-250 million/ml), the percentage of motile cells (> 50%) and the percentage of abnormal cells (< 60%). Male infertility is the most important indication for a spermiogram. The values for seminal parameters, however, show only a weak correlation with conception rates, even in the case of in vitro fertilization. This may be due to the wide variability of values in an individual man, but it is also likely that the aetiopathogenesis of infertility is not only determined by parameters that can be assessed microscopically, but in addition by functional parameters that have not yet been identified. The assumption that computer-assisted image analysis of motility and morphology (CASA) would improve the predictive power of seminal parameters has not been verified. However, the spermiogram is useful in therapeutic studies of male infertility. When the extent of relevant alterations is assessed the wide intraindividual variability must be borne in mind. Treatment cannot be assumed to have been successful unless the sperm count increases by more than 50% of the initial value. Side effects of drugs affecting spermatogenesis and recovery after cessation of therapy can be demonstrated by repeated spermiograms. Evidence of the effects of environmental factors can also be seen in the spermiogram, but distinct correlations are difficult to determine. Semen analysis continues to be used in the development of male contraceptives, but is no substitute for the measurement of conception rates.

Adolescent↗

Pharmacokinetics of two partial benzodiazepine receptor agonistic beta-carboline derivatives in healthy volunteers.

Plasma levels of the two beta-carboline derivatives, ZK 91,296 (ethyl 5-benzyloxy-4-methoxymethyl-9H-pyrido (3,4-b) indole-3-carboxylate, CAS 83910-34-3) and ZK 95,962 (ethyl 5-isopropoxy-4-methoxymethyl-9H-pyrido (3,4-b) indole-3-carboxylate, CAS 101071-43-6) were measured in a total of 46 healthy male volunteers. The doses ranged from 1 to 40 micrograms/kg injected intravenously and from 40 to 600 mg given orally. Following i.v. injection, plasma levels declined in two phases with half-lives of 2-4 min (both drugs) and 0.5 h (ZK 95,962) or 1 h (ZK 91,296). The total clearance was 40-50 ml/min/kg and the oral bioavailability was estimated to be below 1% for both compounds. The reason was rapid first-pass inactivation, probably in the liver, and the formation of an acid metabolite. The plasma levels of this substance, which were determined after oral administration of ZK 91,296, were linearly correlated with the dose.

Adult↗

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.

Animals↗

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.

Agglutination Tests↗

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)

Adult↗