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Biomedical subjects

B Runnebaum

Publications and source records attributed to B Runnebaum.

At least 127 records · Page 7Linked to original sources

Action and formation of inositol bisphosphate and inositol trisphosphate in rat anterior pituitary cells.

Inositol 4,5-bisphosphate and inositol 1,4,5-trisphosphate, administered exogenously at a concentration of 3 x 10(-5) mol/l increased LH release in superfused rat pituitary cells by 950 +/- 267% and 281 +/- 83%, respectively. This stimulatory effect was reversible and dose-dependent. Other inositol phosphates (inositol 1-monophosphate, inositol 1,4,5,6-tetrakisphosphate, inositol 1,3,4,5,6-pentakisphosphate and inositol 1,2,3,4,5,6-hexakisphosphate), tested in vitro, did not significantly influence LH release. In saponin-permeabilized cells, the rate of basal and stimulated LH release was twice that in non-permeabilized cells. Penetration of inositol bisphosphate and inositol trisphosphate into saponin-treated pituitary cells did not increase the secretory potency of these agents compared with their effect on non-permeabilized cells. The new findings document that inositol trisphosphate formation occurs within 5-45 s after GnRH (10(-7) mol/l) administration and seems to be involved in mediating the rapid, first phase of LH release, whereas inositol bisphosphate formation occurs after 3-15 min and is probably related to later phases of LH secretion. Our results suggest that inositol bisphosphate and inositol trisphosphate are important regulators of the release of luteinizing hormone and can exert their effects not only intracellularly, but also extracellularly.

Animals↗

Effects of kallikrein on sperm motility, capillary tube test, and pregnancy rate in an AIH program.

From 1984 to 1986, 172 couples were enrolled in an artificial insemination homologous (AIH) program, because of negative postcoital test, fair PT, positive PT with unexplained infertility, and impotentia coeundi. Patients were randomly assigned to the following procedures: AIH with native semen (N, n = 68), washed sperm (V, n = 50), semen mixed with kallikrein (K, 5 IE/ml semen, n = 45), and timed intercourse. The overall pregnancy rate (PR) was 22% per couple (13% inseminations, 9% spontaneous). PR from insemination (spontaneous) was 13% (8), 13% (13), 23% (0) in PT negative, fair, and positive patients, respectively, and 18% (9), 13% (7), and 11% (9) in AIH groups N, V, and K. Among in vitro studies with K added semen, an improvement of sperm motility was demonstrated in half of the specimens. In the capillary tube test (CTT), with wives' cervical mucus, a deterioration was more frequently seen than an improvement after 2 h, independent of the early effect of K in semen, K induced changes of CTT were less pronounced when donors' cervical mucus was used. The results of the in vitro studies offer an explanation for the low PR in the AIH program with K.

Adult↗

Normal values for a short-time ACTH intravenous and intramuscular stimulation test in women in the reproductive age.

Normal values in endocrine testing are the most important precondition for the recognition of disorders of the endocrine system. To establish a reference range for adrenocorticotropic hormone (ACTH) stimulation tests, an intravenous and intramuscular ACTH stimulation test was conducted in 29 female volunteers without hyperandrogenism. A total of 25 IU of ACTH were administered intravenously or intramuscularly and blood sampling was performed before, 1 h and 2 h after ACTH injection. The test was performed on days 3-5 of the menstrual cycle. The following steroid hormones were assessed in the serum: 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone, dehydroepiandrosterone, testosterone, free testosterone and 5 alpha-dihydrotestosterone. The normal range was defined by the interval between the 5th and 95th percentiles; additionally the 1st, 25th, 50th, 75th and 99th percentiles are reported. A significant increase of serum hormone levels after ACTH administration could be observed for the following hormones: cortisol, 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone and dehydroepiandrosterone. There was no rise after ACTH application for testosterone, 5 alpha-dihydrotestosterone and free testosterone. It could be shown for all hormones that there was no significant difference between the serum levels that were reached after intravenous and intramuscular ACTH injection. Neither could we find a significant difference in the relative increase of the serum hormones when stimulation values were related to basal values. Since in most studies with ACTH stimulation tests, only the serum values 1 h after ACTH application are measured, we investigated whether the measurement of steroid hormones 2 h after ACTH application gave further information. We could demonstrate that for most measured serum hormones the majority of the volunteers had the maximal response 2 h after ACTH application, no matter whether ACTH was injected intramuscularly or intravenously. As a conclusion, we recommend the measurement of the respective hormones not only 1 h but also 2 h after ACTH stimulation. Since there is no increase after ACTH stimulation for total testosterone, free testosterone and 5 alpha-dihydrotestosterone, it is sufficient to assess the basal values of these hormones. Excessive adrenal response is reflected by dehydroepiandrosterone, 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone and cortisol.

17-alpha-Hydroxypregnenolone↗

[Current approach in the diagnosis and therapy of alopecia in gynecology].

With an increasing frequency patients complaining problems with their hair show up in gynecologic office practices. We observe cases with alopecia androgenetica; both alopecia climacterica and postpartualis, being subgroups of alopecia androgenetica. From symptomatic as well as from pathogenetic point of view two other forms can be subdivided, to be named alopecia diffusa and alopecia areata. At the Department of Obstetrics and Gynecology of the University of Heidelberg an outpatients consulting programme for women with androgenetic symptoms was established some years before. The diagnostic procedures for a possible classification of the alopecia was intensified. The search for underlying internal diseases and/or endocrinopathies will be the first step towards a pathogenetically correct diagnosis, and if there is no plausible explanation reached by that, the investigation will be extended for heavy metal tracing or for the detection of other ecological damaging influences. A local treatment with thymus gland preparations (Thymu-Skin) was examined by following the conditions of a protocol. After treatment with the preparation (Thymu-Skin) 73% of all cases show improvement of the alopecia. The formula seems to be an effective alternative to the hormonal therapy. It is easy to administer and has no side-effects or contraindications. It proved also to be advisable for prophylactic use in combination with chemotherapy.

Administration, Topical↗

[Treatment of endometriosis].

In a randomized study, the effect of gestrinone (2 x 2.5 mg/week) was compared with the effect of danazol (3 x 200 mg/day) in treating 30 patients with laparoscopically proven endometriotic implants for 6 months. Therapy was effective in 80%-90% of cases and pregnancy rates were similar, but the incidence of side effects was different in the groups. In addition, buserelin (900 micrograms/day intranasally) was investigated in a multinational, multicenter trial in 275 patients. In 80%, GnRH agonist treatment induced the disappearance or reduction of endometriotic implants. The main side effects were due to estrogenic suppression. Presently, various methods of hormonal treatment are under investigation, especially to determine recurrency rates of endometriosis and long-term side effects.

Adult↗

[Endocrinology of the climacteric].

The endocrinology of the menopause is determined by the decrease of estrogens. In 250 healthy patients there was an observed decrease of estrone to 35 pg/ml and of estradiol to 10 pg/ml serum between the 49th and 54th year of age. Thereafter no further decline occurred, because the androgen precursors of the estrogens were secreted by the adrenal cortex until advanced age. In a period of 30 years there was a decrease of the androgen levels of only 25%. In 200 patients with severe obesity we found no differences in peripheral steroid concentrations, but the SHBC concentrations were significantly lowered; therefore, the amount of free active estradiol and the effect on the target organ is higher in these patients.

Climacteric↗

[New progestins in oral hormonal contraceptives].

Three new progestins with a high gestagenic potency have been developed as derivatives of the levonorgestrel (in brackets: biological active substance in the human): desogestrel (3-keto-desogestrel), norgestimate (norgestimate), gestodene (gestodene). In combination with low dosages of ethinylestradiol (30-35 micrograms) an excessive steroid overload can be avoided, which is not necessary for contraceptive efficacy and control of the menstrual cycle. As an effect of dose reducing during long-time studies only a mild impact on the lipids and carbohydrates, and blood coagulation could be observed. The clinical side effects are moderate and for most patients acceptable.

Contraceptives, Oral, Hormonal↗

Clinical significance of crossed in vitro sperm-cervical mucus penetration test in infertility investigation.

To evaluate the clinical significance of in vivo and in vitro testing of sperm ability to penetrate cervical mucus (CM), postcoital testing (PCT) and in vitro sperm-cervical mucus penetration testing were compared in a prospective study. Both in vivo and in vitro tests were standardized and performed after an oral course of estrogen therapy. Crossed in vitro sperm-cervical mucus penetration test, evaluated in 277 couples with CM of patients' wives and additionally with CM and semen of fertile donors, revealed that the male factor contributed to a significantly higher extent to deficient sperm-mucus interaction than the cervical factor. The overall pregnancy rate after 6 months was 23% (64/277). Whereas the outcome of PCT did not significantly predict subsequent fertility (PCT good pregnancy rate 24%/PCT poor 20%), significant differences were found for the sperm-cervical mucus penetration test with CM of patients' wives (pregnancy rate, 30.5% versus 8.5%) and for in vitro testing with donors' CM, but not for the mucus penetration test with donors' spermatozoa. Routine sperm analysis did not prove to be of prognostic value for a subsequent pregnancy. The results suggest that the in vitro sperm-cervical mucus penetration test is a good parameter of sperm function and, in particular, when performed as a cross-matching penetrability test, a valuable adjunct to PCT with regard to fertility prognosis.

Cervix Uteri↗

Prognostic value of in vitro sperm penetration into hormonally standardized human cervical mucus.

To analyze the prognostic value of the sperm cervical mucus penetration test (SCMPT), fresh semen samples of 99 male patients under infertility investigation were exposed to capillary tubes filled with freshly obtained cervical mucus (CM) of the patients' wives (WCM), fertile donors (DCM), and bovine CM (BCM). The quality of the human CM was standardized by oral administration of estrogens. The overall pregnancy rate after 6 months was 17.2% (17/99), and was significantly different in couples with poor and good SCMPT with WCM (1/44, 2.3% versus 16/55, 29%; P less than 0.001) in a prospective study. Human CM was superior to BCM as a penetration medium in providing more information about sperm function. The results suggest that in vitro sperm penetration testing with hormonally standardized CM of female partners adds an important dimension to sperm analysis with regard to fertility prognosis.

Cervix Uteri↗

[Background information on contraception behavior of patients undergoing abortion as an indication of the psychosocial origin of unwanted pregnancies].

269 patients were interviewed in a private abortion clinic in Lindenfels, Hessen, West Germany on aspects of contraception and abortion. The results indicated three crucial points, which influence contraceptive behaviour: social barriers, which affect indirectly the access to and the handling of contraceptives; psychic, mainly unconscious barriers, which counteract contraception; an increasing distrust and rejection of modern medical contraception, especially in highly educated women. These barriers are evident in lack of information, differing in the various social groups; partly irrational and exaggerated fear of side effects, and lack of success of factual information. Furthermore, poor co-operation is evident on the part of the husband or partner together with considerable shortcomings in medical counselling.

Abortion, Induced↗

Circulating antisperm antibodies and fertility prognosis: a prospective study.

In a prospective study performed on 235 couples with long-standing infertility (median 5 years), circulating antisperm antibodies (ASA) were determined with both a standard trayagglutination test (TAT) and a radioimmunoassay (RIA). Serum levels were correlated with results of sperm analysis (SA), postcoital testing (PCT) and in-vitro sperm--cervical mucus penetration testing (SCMPT), performed with cervical mucus and spermatozoa of patients and in parallel with material of fertile donors. A simultaneous microbial screening included Chlamydia trachomatis, mycoplasmas, Herpes simplex virus, gonococci, other potentially pathogenic aerobic and anaerobic bacteria and yeasts. The pregnancy rate 12 months after determination of ASA in the serum samples was 27% (64/235). Between ASA-positive and -negative male and/or female patients (TAT as well as RIA), no significant difference was found for any of the tested variables of SA, PCT, crossed SCMPT and colonization of genital secretions with microorganisms. Patients who later achieved pregnancy and those who did not did not differ with regard to serum antibody status (TAT as well as RIA). The findings suggest that the clinical significance of circulating ASA determined with the currently available methods is low. ASA in serum samples of infertile female and/or male patients do not influence the fertility prognosis.

Agglutination Tests↗

Serum concentration and urinary excretion of the luteinizing hormone-releasing hormone agonist buserelin in patients with endometriosis.

We studied the pharmacokinetics of iv and intranasally administered buserelin, a LHRH agonist peptide, in 14 women with endometriosis. Serum and urinary buserelin concentrations were determined by specific RIA (buserelin antiserum AS-639). Intact buserelin and the metabolites in urine were separated by reverse phase high performance liquid chromatography and measured by RIA. The mean serum buserelin concentrations were 101 +/- 33 (+/- SD) ng/mL 20 min and 1.12 +/- 0.12 ng/mL 360 min after its iv injection in 6 women, and the mean elimination half-life between 20 and 360 min was 51 min. In serum, intact buserelin was the main constituent (10 min, 90%; 120 min, 74%; 360 min, 52%), and the major metabolite was the buserelin-(5-9) pentapeptide (10 min, 0.6%; 120 min, 19%; 360 min, 12%). In the urine collected 0-1 h after buserelin administration, intact buserelin was 66% and the 5-9 pentapeptide was 28% of the total excretion. In the urine collected between 6-24 h after buserelin administration, intact buserelin accounted for 67% and the 5-9 pentapeptide for 32% of the total excretion. The urinary buserelin concentration was 1345 +/- 156 micrograms/g creatinine 1 h and 25 +/- 5 micrograms/g creatinine 6-24 h after buserelin administration. Serum LH, FSH, and estradiol concentrations increased acutely up to 10-fold above basal values; the mean peak LH, FSH, and estradiol values occurred at 180-240 min, 240 min, and 24 h, respectively. In therapeutic studies with buserelin nasal spray in 5 women, serum concentrations of 0.9-1.4 ng/mL were found 15 min after a single dose of 300 micrograms, intranasally, and the urinary excretion was 2.52-3.68 micrograms/24 h during daily administration of 3 doses of 300 micrograms at intervals of 8 h. These results confirm that buserelin is slowly inactivated and remains available to pituitary receptors for a prolonged period after its iv or intranasal administration.

Administration, Intranasal↗

[Topical one-time therapy with ketoconazole: a double-blind randomized study in vaginal mycosis].

In a double-blind clinical study 90 women with vaginal candidosis were randomly assigned to treatment with either single-dose ketoconazole (400 mg or 800 mg) or placebo vaginal suppositories. Microscope checks of vaginal fluid and mycological cultures were performed one week and four weeks after the treatment. The four weeks observation period gave no evidence for any significant differences among the three groups regarding symptoms reported as well as clinical picture and microscopy findings. Cure rate after one week, as determined by fungal cultures, was significantly lower in the placebo group (43%) than in the 400 mg (60%) and 800 mg groups (76%; p = 0.031). The mycological cure rate after four weeks did no longer show a significant difference between the groups tested, being 47% in the placebo group and 67% in each of the ketoconazole groups. Treatment of the sexual partner as well as predisposing factors did not influence the therapeutic effect. Due to the low ketoconazole serum concentrations after absorption of single vaginal doses, topical ketoconazole treatment can be applied in pregnancy. It remains to be tested, however, whether repeated vaginal application over three to five days will render higher and longer-lasting cure rates.

Administration, Intravaginal↗

Epidermal growth factor stimulates luteinizing hormone and arachidonic acid release in rat pituitary cells.

Epidermal growth factor (EGF) directly enhanced luteinizing hormone (LH) release from dispersed rat pituitary cells in monolayer cultures as well as in superfusion columns. This 2.3-fold stimulatory effect was dose and time dependent and was also reconfirmed in a superfusion system. Retinal, a protein kinase C inhibitor, counteracted the EGF effect only partially. Further experiments were therefore carried out to investigate alternate EGF mechanisms. Nordihydroguaiaretic acid and chloroquine suppressed the stimulatory effect of EGF in a dose-dependent manner. Moreover, EGF (10(-7) M) stimulated [3H]arachidonate release from pre-labelled rat pituitary cells. This indicates that phospholipase A2 and arachidonic acid may be involved in EGF action on LH release from rat pituicytes.

Animals↗

[Significance of Chlamydia trachomatis for female fertility with special reference to prevalence in the endometrium].

144 patients with longstanding infertility (mean duration of infertility 4.9 years) were screened for endometrial infection with Chlamydia trachomatis by means of endometrial biopsy and McCoy cell-culture. The same day blood was taken for detection of Chlamydia IgG antibodies in serum samples. During a 1 year's period, all new patients of a large infertility clinic without complaints or clinical symptoms of infection of the lower genital tract were consecutively submitted to the study. Elevated titers of IgG antibodies in serum samples (Chlam. AB greater than or equal to 1/256) revealed previous chlamydial infection of 26% of patients, but Chlamydia trachomatis was detected in endometrial biopsies in only 5/144 (3.5%). There was a strong correlation of previous chlamydial infection and reduced tubal patency (p 0.001) and a lower pregnancy rate after 6 months. The results suggested that infections with Chlamydia trachomatis, influenced by demographic and socio-economic aspects, are of minor importance as an actual infection in asymptomatic patients with longstanding infertility. Previous chlamydial infections, however, are of great importance because of their negative influence on tubal function.

Adult↗