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Biomedical subjects

B Runnebaum

Publications and source records attributed to B Runnebaum.

At least 37 records · Page 2Linked to original sources
PubMed1998

Antisperm antibodies and microorganisms in genital secretions--a clinically significant relationship?

In asymptomatic infertility patients, no significant relationship was found between the presence of antisperm antibodies (ASA) in serum and in semen samples (IgG and/or IgA ASA), differentiated with the mixed antiglobulin reaction (MAR), and the microbial colonization of ejaculates covering a broad spectrum of microorganisms. Likewise, there was no significant association of ASA with microbial findings in patients' female partners, who also presented without symptoms of genital tract infection and were screened at the same time. Furthermore, ASA in semen (IgG and IgA) were not significantly related to several potential markers of subclinical male sexual gland infection or inflammation (leukocytes, PMN elastase, albumin, C3c) evaluated in aliquots of the same ejaculates used for immunological testing.

Adult↗
PubMed1998

Influence of 5-lipoxygenase on in vitro growth of human mammary carcinoma cell line MCF-7.

The aim of this study was to investigate the direct effect of 5-lipoxygenase (5-LO) on the growth of human mammary cancer cells MCF-7 in vitro. Cell growth was measured according to the level of 3H-thymidine incorporation. 5-LO was shown to inhibit 3H-thymidine incorporation. The inhibitory effect was 19, 42 and 78% when administered at concentrations of 0.1, 0.2 or 0.5 U/ml, respectively. Its effect was time- and dose-dependent and was statistically significant at concentrations of 0.2 and 0.5 U/ml. We have also shown that the specific 5-LO inhibitor MK-886 (1 microM) lifts the inhibitory effect of 5-LO (0.2 U/ml). Moreover, when treated with an activator of 5-lipoxygenase calcium ionophore A23187 (10 microM) MCF-7 cells synthesize LTB4. The results of this study are evidence of the role of 5-lipoxygenase in the regulation of human mammary cancer cells growth in vitro.

Arachidonate 5-Lipoxygenase↗
PubMed1998

Chlorinated hydrocarbons in women with repeated miscarriages.

This study was conducted to investigate a possible etiological role of chlorinated hydrocarbons in the pathogenesis of repeated miscarriages. The blood levels of chlorinated hydrocarbons [CHCs: pentachlorophenol, hexachlorocyclohexane, hexachlorobenzene, the dichlorodiphenyltrichloroethane (DDT) group, polychlorinated biphenyls] were determined in 89 women with repeated miscarriages, who were referred to the University Hospital of Obstetrics and Gynecology of Heidelberg for investigations between 1989 and 1993, and compared to a previously investigated reference population. In more than 20% of the women, at least one of the CHC levels exceeded the reference range. CHC levels did not differ significantly between women with primary or secondary and early or late miscarriages; neither did they differ between women with hormonal or immunological disorders as causes of repeated miscarriages or women with idiopathic repeated miscarriages. No significant associations were detected between CHC levels and further conceptions or the outcome of further pregnancies. As significant associations were found between increasing CHC blood concentrations and immunological and hormonal changes, CHCs may have an impact on the pregnancy course in certain cases.

Abortion, Habitual↗
PubMed1998

Influence of leukotrienes on in vitro growth of human mammary carcinoma cell line MCF-7.

OBJECTIVES: The aim of this work was to study the action of leukotrienes on the growth of human mammary cancer cells MCF-7. STUDY DESIGN: The growth of the cells was measured by incorporation of 3H-thymidine. The action of leukotriene (LT)B4, LTD4, LTC4, LTE4 or arachidonate (AA) was tested in human mammary cancer cells MCF-7 in vitro. RESULTS: LTB4 or LTD4 but not LTC4 or LTE4 reduced significant incorporation of 3H-thymidine in MCF-7 cells up to 52% or 56% respectively, when administered in concentrations 0.1-1000 pM. Agents in concentrations of 0.01 pM or 10000 pM did not effect 3H-thymidine incorporation. We have shown, that MCF-7 cells synthesise LTB4 when treated with calcium ionophor A23187 (10 microM). Leukotriene-antagonist LY171883 (10 microM) lifts inhibitory effects of LTB4 or LTD4. Arachidonic acid (10 microM) inhibits 3H-thymidine incorporation up to 72%. 5-lipoxygenase inhibitor MK-886 (100 nM) lifts the inhibitory effect of arachidonate. CONCLUSIONS: LTB4 or LTD4 inhibits MCF-7 breast cancer cell growth. LT-receptors mediate the growth-inhibitory effect of LTB4 or LTD4.

Acetophenones↗
PubMed1997

Endometrial integrin expression is independent of estrogen or progestin treatment in vitro.

OBJECTIVE: To examine the regulation of endometrial integrin expression by estrogens and progestins in vitro. DESIGN: Immunocytochemical study. SETTING: Academic research unit. PATIENT(S): Twenty-five regularly cycling women without endometrial pathology, of whom seven had endometriosis. INTERVENTION(S): Endometrial cells obtained by aspiration curettage were treated with diethylstilbestrol, promegestone, and antiprogestin. Immunocytochemistry was performed with antibodies directed against integrins alpha 1 beta 1, alpha 2 beta 1, alpha 4 beta 1, alpha 5 beta 1, alpha v beta 3, and beta 3 integrin subunit. MAIN OUTCOME MEASURE(S): Semiquantitative staining score. RESULT(S): Endometrial cells express several integrins in vitro in a consistent and cell specific pattern. Neither differences between treated and untreated cells nor an effect of treatment duration or dosage were observed. Cells from patients with and without endometriosis showed similar patterns. CONCLUSION(S): The cellular distribution of integrin expression was similar to that described in vivo. In contrast, a steroid regulated expression could not be detected in vitro. Rather, a derepression by a factor not included in our model could be responsible for the cyclic appearance of some integrins. In endometriosis, no fundamental difference of integrin expression was detected.

Cells, Cultured↗
PubMed1997

Impact of waist-hip-ratio and body-mass-index on hormonal and metabolic parameters in young, obese women.

BACKGROUND: To investigate the impact of predominantly upper body fat localisation on the hormonal and metabolic profile in obese, infertile women. DESIGN: Prospective observational study of premenopausal women with obesity, infertility and menstrual dysfunction. SETTING: Department of Endocrinology and Reproduction of the University Hospital of Obstetrics and Gynaecology of Heidelberg. SUBJECTS: Eighteen women with android type obesity (waist-hip-ratio = WHR > 0.85, group 1) and 22 women with gynoid type obesity (WHR < or = 0.85, group 2) in a group of 58 premenopausal obese women (median age 28 y) with infertility. Twenty-nine women took part in a weight reducing program lasting 32 +/- 14 (mean +/- s.d.) weeks. MEASUREMENTS: BMI, WHR and blood pressure. Plasma lipids and liver enzymes. Blood glucose, insulin, C-peptide and different steroid and pituitary hormones during oral glucose loading. RESULTS: In the total group of 58 obese women, WHR was directly correlated to plasma triglycerides, AST, ALT and cholesterol/HDL-cholesterol-ratio. WHR correlated inversely with HDL-cholesterol. Insulin resistance was greater with increasing WHR. Systolic blood pressure, glucose, insulin, C-peptide, triglycerides, cholesterol/HDL-cholesterol-ratio, aspartate (AST) and alanine aminotransferase (ALT) were significantly greater in group 1. Group 2 had greater HDL-cholesterol levels. One subject in group 1, five women in group 2 conceived spontaneously after weight reduction. CONCLUSIONS: Determination of the WHR is a simple measurement to identify obese patients who are at a greater risk of developing the metabolic syndrome. WHR is important in preventive medicine, as typical metabolic profiles are already present in young women before clinical manifestation. Women with android obesity seem to be more prone to develop menstrual irregularity and infertility. The hyperinsulinaemia may be the pathway.

Adolescent↗
PubMed1997

The effects of monophasic and triphasic oral contraceptives on ovarian function and endometrial thickness.

OBJECTIVE: To analyze and compare the effects of seven low-dose oral contraceptives (OCs) on ovarian function and endometrial thickness. METHODS: Cross-sectional study of users of one of five monophasic OCs, one of two triphasic OCs and a control group of non-users. Ovarian function, endometrial thickness and serum hormone levels were monitored during days 10-12 and 16-18 of the cycle. RESULTS: Serum estradiol was suppressed in OC users to a greater degree during days 16-18 than during days 10-12, whereas serum progesterone during 16-18 was in the anovulatory range with each preparation. Ovarian activity as measured by follicular size was lowest with desogestrel-containing OCs, whereas greater activity was seen with triphasic levonorgestrel/ethinylestradiol and triphasic norgestimate/ethinylestradiol. Endometrial thickness in OC users was significantly smaller than in controls. CONCLUSIONS: All preparations demonstrated profound suppression of ovarian activity and effectively prevented ovulation. Ovarian suppression with desogestrel/ethinylestradiol 150/20 did not differ from that of other OCs despite its lower ethinylestradiol content. The use of both triphasic OCs, having a relatively low progestogenic activity, was associated with a higher ovarian activity than that of the monophasic OCs.

Adolescent↗
PubMed1997

Chlamydial serology in 1303 asymptomatic subfertile couples.

The clinical significance of antichlamydial antibodies (Chlam Ab) was determined in a total of 1303 subfertile couples consulting for infertility investigation and treatment. Median age of the women was 30 (range 22-44) years and of the men 33 (range 21-53) years. The median duration of infertility was 4 (range 1-21) years. All patients were asymptomatic for genital tract infection. A comprehensive infertility investigation included examination of the endocrine, cervical, and tubal factor, and semen analysis, antisperm antibody (ASA) testing, sperm-mucus interaction testing in vitro using a standardized protocol, and post-coital testing (PCT). Screening for Chlam IgG Ab was performed in serum of both partners, obtained at the same time. Simultaneous microbial cultures in genital secretions of both partners included a broad spectrum of potentially pathogenic bacteria. Elevated titres of Chlam IgG Ab as seromarker for previous infection were found in 20.8% of all women, and in 12.6% of men. Chlam Ab were significantly more frequent in partners of seropositive patients (in 51.8% of women with a Chlam Ab positive partner, compared to 15.8% of the other women). Microbial screening outcome was not significantly related to results of chlamydial serology in both partners. In women, elevated titres of Chlam Ab were significantly associated with a tubal factor, but were not related to reduced quality of the endocervical mucus (CM), including the in-vitro penetrability of the CM (using partners' or donors' spermatozoa). In males, Chlam Ab were not significantly related to the outcome of semen analysis, including screening for ASA (IgG and/or IgA) in semen, and several parameters of sperm functional capacity. After exclusion of couples with tubal disease, subsequent male fertility did not significantly differ in males with or without Chlam Ab. The results suggest that during basic infertility investigation, positive chlamydial serology as an easy screening procedure indicates a higher risk for a tubal infertility factor. However, in asymptomatic patients, Chlam IgG Ab in serum are not associated with a cervical factor or with the male factor, using several determinants for evaluation of semen quality including subsequent fertilizing capacity.

Adult↗
PubMed1997

Soluble urokinase-type plasminogen activator receptor is over-expressed in uterine endometrium from women with endometriosis.

Extracellular matrix degradation by secreted proteases, e.g. plasmin, is essential for endometrial functions such as blastocyst implantation and menstruation. We investigated whether the expression of plasmin(ogen) activating or inhibiting factors in endometrial cells from women with endometriosis was different from women without the disease. Endometrial biopsies were obtained from 10 patients with and 16 women without endometriosis. Cells were cultured in Dulbecco's modified Eagle's medium (DMEM)/F12 supplemented with diethylstilboestrol (10(-10) M) alone or combined with promegestone (5 x 10(-8) or 5 x 10(-6) M). Urokinase plasminogen activator (uPA), plasminogen activator inhibitor (PAI)-1 and -2, and soluble uPA receptor (suPA-R) concentrations were assayed by enzyme-linked immunosorbent assay (ELISA) in the conditioned media. uPA and PAI-2 concentrations were not influenced by steroid treatment and did not differ between women with and without endometriosis, whereas PAI-1 was significantly up-regulated by promegestone in both groups. In contrast, suPA-R expression was not influenced by steroid treatment but was significantly higher in cells from endometriosis patients. This is the first report on suPA-R secretion in endometrial cells and the results indicate an altered activation of plasmin(ogen) in endometrium from women with endometriosis that could lead to a higher proteolytic potential of retrogradely menstruated endometrial fragments with consecutive development of endometriotic foci.

Cells, Cultured↗
PubMed1997

Inhibitory effect of leukotrienes on luteinizing hormone release.

The aim of this work was to study the effect of high concentrations of leukotrienes on luteinizing hormone (LH) secretion in rat anterior pituitary cells. We also investigated the effect of leukotrienes in parallel with gonadotropin-releasing hormone (GnRH) action. Experiments were on cells gained from trypsinized pituitaries of female rats. Tests were performed by superfusion of the cells attached to cytodex-1 carrier beads. The LH content in samples of perfusate was estimated by radioimmunoassay. This work reports 48% inhibition of basic LH release by action of leukotriene C4 in superfused cells when applied continuously at a concentration of 100 nmol/l. Moreover, we have shown that leukotrienes suppressed GnRH-induced LH secretion in rat pituitary cells when applied in parallel to GnRH (1 nmol/l) as a 4-min pulse at a concentration of 0.1 nmol/l. GnRH-induced LH release was reduced to 66% of its value by leukotriene (LT) B4 (0.1 nmol/l) action; also to 54% by LTC4, 66% by LTD4 and 74% by LTE4 action. In contrast, arachidonic acid (50 pmol/l) and its other 5-lipoxygenase metabolites: 5-hydroperoxyeicosatetraenoic acid (5-HPETE) (50 pmol/l), or 5-hydroxyeicosatetraenoic acid (5-HETE) (50 pmol/l), had no inhibitory effect on GnRH-induced LH release. Arachidonic acid and 5-HETE potentiated GnRH-induced LH release up to 249% and 429%, respectively, when applied in parallel with GnRH (1 nmol/l) as a 4-min pulse at a concentration of 10 pmol/l. In our earlier work we have shown that several leukotrienes are potent stimulants of LH release. The present report documents the finding that the 5-lipoxygenase pathway is also involved in the inhibitory regulation of hormone release in anterior pituitary cells.

Animals↗
PubMed1997

Spacing-out of progestin--efficacy, tolerability and compliance of two regimens for hormonal replacement in the late postmenopause.

Estrogen replacement therapy with sequential progestin at greater than monthly intervals has been frequently used in practice to reduce progestational side-effects and bleeding episodes, but clinical trials are still lacking. Two new regimens were tested. The main objective was to evaluate efficacy, predominantly in urogenital complaints, tolerability, and patient acceptance. Transdermal estradiol (0.05 mg/day) and norethisterone acetate orally (2.5 mg/day) were administered for 12 days every 2 or 3 months (group A, n = 83, group B, n = 89) to patients whose menopause had begun at least 4 years earlier. Study duration was three long cycles in each group within 7-10 months. Efficacy was good [group A/B = 94/92%], as was systemic tolerability [95/97%]; major skin reactions occurred in 7 and 4%, respectively. Patients' acceptance for continuation of spaced-out treatment was 88 and 87%, respectively. Progestin-associated withdrawal bleedings occurred in 66 (61%) of patients; mean duration 4.3 +/- 1.9/4.8 +/- 1.6 days, with no significant changes during therapy; intensity decreased during therapy. Breakthrough bleeding which required sonographic or histological work-up occurred in 8 and 13%, respectively. Despite the low dosage, transdermal estradiol proved to be efficacious in urogenital complaints. The high acceptance and the reduction of the overall progestin dose to avoid side-effects are of particular prognostic importance with regard to the prevention of cardiovascular diseases. Transdermal estradiol combined with 2- or 3-monthly progestin may be a valid regimen in the late post-menopause, but further studies using spacing-out regimens are urgently needed.

Administration, Cutaneous↗
PubMed1997

A study of the influence of a gestodene-containing triphasic oral contraceptive on endometrial morphology.

The objective of the study was to investigate histological changes in the endometrium in 20 volunteers treated with a low-dose, gestodene-containing triphasic oral contraceptive. Endometrial biopsy specimens were taken before, during a 6-month period of oral contraceptive use and in a post-treatment period. These specimens were evaluated using light microscopy, scanning and transmission electron microscopy. In addition, ultrasound examinations of the uterus, endometrial thickness and ovaries were performed. The low-dose, gestodene-containing triphasic oral contraceptive had no adverse effects on the endometrium (e.g. no proliferation, no polyps, no inflammatory processes), was well tolerated and showed a low side-effect profile. The inhibition of endometrial transformation was demonstrated both by endometrial morphology as well as by endometrial thickness, as measured by transvaginal ultrasound examination.

Adolescent↗
PubMed1997

Aneuploidy of human granulosa cells in follicular fluids from in vitro fertilization patients.

OBJECTIVES: To study the proliferative behavior of granulosa cells found in follicular fluids from patients after hormone stimulation in the framework of in vitro fertilization (IVF) with gonadotropins. STUDY DESIGN: The deoxyribonucleic acid ploidy and the proliferation indices of granulosa cells in fresh and unfixed follicles (n = 119) from gonadotropin-stimulated patients (n = 32) were analyzed by flow cytometry. RESULTS: Aneuploid cells were found in a large number of follicles (65/119) as well as patients (25/32). A small number of follicles (8/119) and patients (7/32) contained multiploid cells. There was no correlation between proliferation indices and ploidy. Granulosa cells were the predominant cells in follicular fluids. No malignant cells were found in any case. CONCLUSION: This is the first report concerning the high incidence rate of aneuploidy in ovarian granulosa cells in IVF patients. The clinical relevance of the phenomenon is not clear. There should be further study to determine whether there is any link to a previously discussed possible relation between gonadotropin stimulation in women attempting to become pregnant and the occurrence of ovarian cancer or granulosa cell tumors. Of further interest might be a possible relation between ploidy and proliferation indices of stimulated granulosa cells as well as side effects of gonadotropin therapy and biologic parameters, like maturity, fertilizability of oocytes and rates of pregnancy.

Adult↗
PubMed1997

Effect of central and ovarian endocrine disturbances on the female genital tract--clinical signs and symptoms.

Disorders of the female genital tract caused by endocrine disturbances commonly lead to two presenting complaints: dysfunctional uterine bleeding and infertility. In oestrogen deficiency, sequelae of vaginal atrophy may also be present. The common pathogenic "turntable" of these clinical signs is an impaired ovarian function, for which primary (i.e. intraovarian) and secondary (i.e. resulting from dysfunctions of other endocrine systems) causes are known. Primary ovarian failure can be the result of gonadal dysgenesis or premature menopause. Secondary ovarian dysfunction may be caused by hypothalamic-pituitary dysregulation, hyperprolactinaemia, thyroid disorders, and hyperandrogenaemia, which often also has an intraovarian component. For clinical considerations, several severities of ovarian dysfunction can be distinguished, ranging from corpus luteum insufficiency which is only relevant for the selection of infertility treatment to the complete absence of ovarian steroidogenesis leading to severe long term sequelae of the skeletal, cardiovascular and probably central nervous systems. Diagnosis and differential diagnosis are made by clinical examination, vaginal ultrasound, hormone assays, curettage and laparoscopy. Rarely, additional techniques like magnetic resonance imaging of the pituitary or the adrenals, or sequential catheterization of the inferior vena cava are needed.

Adult↗
PubMed1996

Ectopic growth of endometrium depends on its structural integrity and proteolytic activity in the cynomolgus monkey (Macaca fascicularis) model of endometriosis.

OBJECTIVE: To identify factors influencing the development of endometrial autografts in a monkey model of endometriosis. DESIGN: Prospective, comparative study. SETTING: Animal research unit. SUBJECTS: Thirty regularly cycling cynomolgus monkeys in three groups of 10 each. INTERVENTIONS: Endometrium was minced and spilled into the cul-de-sac in group 1. In group 2, the tissue additionally was digested enzymatically. In group 3, the tissue was incubated with a protease inhibitor. MAIN OUTCOME MEASURES: Staging laparotomies after 3 weeks and 3 months. RESULTS: In groups 1, 2, and 3, moderate or severe disease was seen in eight, two, and four monkeys, respectively, after 3 weeks and in eight, three, and two monkeys, respectively, at 3 months. CONCLUSIONS: An intact structure leads to ectopic implantation of endometrial fragments in most cases. Conversely, enzymatic digestion of endometrial fragments and treatment with proteinase inhibitor impair ectopic growth. Intrinsic endometrial factors that influence extracellular matrix remodeling may play a role in the pathogenesis of human endometriosis.

Animals↗
PubMed1996

Basal and pulsatile secretion of human luteinizing hormone--new methods for the analysis of endocrine secretion processes.

Serum concentrations of hormones show typical time-dependent patterns. The diurnal course of the serum concentrations of the luteinizing hormone (LH) was assessed in 35 healthy females monitoring individual concentrations every ten minutes for 24 hours during the follicular phase of their menstrual cycle. Based on these in vivo data, a mathematical procedure was developed for calculation of the momentary hormone secretion rate of an endocrine gland from the time course of the hormone serum concentrations. By means of this procedure, we were able to define the complete 24 hours secretion pattern of LH, including the fact, that basal and pulsatile secretion could be separated from each other in an objective manner. It is possible to calculate the total amount of LH which is secreted per LH-pulse and the basal LH-secretion rate. Two methods were developed to define the time of the onset of an LH-pulse with a preselected probability. Describing the hormonal secretion pattern with a mathematical model provides the basis for therapeutic application of these methods to program implantable hormone-pumps for the therapy of glandular insufficiency.

Adult↗
PubMed1996

Action of recombinant follicle stimulating hormone in superfused human granulosa cells in vitro.

The aim of this work was to compare the action of recombinant follicle stimulating hormone (rFSH) and urinary FSH (uFSH). Moreover we aimed to compare the secretory efficiency of continuous versus pulsatile stimulation by rFSH in superfused human luteal cells. Progesterone concentration was measured in culture medium by radioimmunoassay. Action of rFSH and uFSH was compared in static cultures of human granulosa cells at doses of 0.001-10 IU/ml. The secretory efficiency of both rFSH and uFSH was found to be similar in a defined range of concentrations (0.001-0.3 IU/ml). At concentrations of 1 and 10 IU/ml, the action of uFSH was significantly more potent than rFSH, up to 139% (P < 0.01) and 133% (P < 0.01) respectively. A concentration of 0.3 IU/ml of rFSH was most potent in static cultures, and evoked progesterone release up to 80 mg/ml. For a stimulation period of up to 4 h, the action of rFSH and uFSH in human granulosa cells was time-dependent and differences between them were not significant. Irregularities were observed at > 4 h stimulation time. In another experiment, in superfused human granulosa cells, we showed that the stimulatory effectiveness of pulsatile rFSH administration (time interval 60 min, application time 10 min) was greater for progesterone release (3973 ng of progesterone/1 IU rFSH) than was continuous administration (848 ng of progesterone/1 IU rFSH). In conclusion, the secretory action of rFSH is similar to that of uFSH for defined times and doses. Moreover, pulsatile rFSH administration is more efficient at stimulating the release of progesterone than continuous administration.

Cells, Cultured↗