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Biomedical subjects

L Wildt

Publications and source records attributed to L Wildt.

123 records · Page 7Linked to original sources

Experimental studies on the positive feedback effect of progesterone, 17 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone on the pituitary release of LH and FSH in the human female. The estrogen priming of the progesterone feedback on pituitary gonadotropins in the eugonadal woman.

Administration of progesterone eugonadal women during the midfollicular phase of the menstrual cycle failed to induce a positive feedback effect on the serum concentrations of LH and FSH. The levels of estradiol in serum decreased following the injection of progesterone without a parallel change in LH and FSH concentrations indicating a direct ovarian effect of the exogenous progesterone. In the late follicular phase of the cycle, when preovulatory levels of estradiol were present in serum, or under a ethinyl estradiol treatment progesterone was able to induce an LH discharge indicating the requirement of an estradiol priming of the positive feedback of progesterone in eugonadal women. In order to establish the time required for a sufficient estrogen priming with preovulatory levels of estradiol in serum 3 mg of estradiol-benzoate were administered i.m. 1, 12 and 24 h prior to the administration of 30 mg of microcristalline progesterone in the midfollicular phase of the menstrual cycle, when progesterone alone did not cause an LH surge. Only when estradiol-benzoate was injected 24 h prior to the progesterone administration an LH surge reproducible in time course and magnitude occurred. Administration of estradiol-benzoate alone under these conditions did not cause an LH surge within the elapse of time after the injection when the progesterone induced LH surge occurred. Thus, these experiments demonstrate that a defined estrogen priming is required for the positive feedback effect of progesterone on the gonadotropin release in eugonadal women. Furthermore, progesterone levels in serum of about only 1--2 ng/ml were required for the induction of an LH surge indicating that under physiological conditions progesterone may have an supplementory effect on the primarily estradiol induced LH midcycle peak. 17-hydroxyprogesterone administered during the mid follicular phase of the menstrual cycle and under pretreatment with ethinyl estradiol failed to induce a positive feedback effect on the serum concentrations of LH and FSH, indicating that this steroid does not play a regulatory role on the midcycle LH release in women. 20alpha-dihydroprogesterone administered under the same experimental conditions as 17-hydroxyprogesterone seems to be able to induce an LH surge in serum provided there is an adequate estrogen priming.

20-alpha-Dihydroprogesterone↗

[Disturbed utero-tubal transport in hysterosalpingoscintigraphy as a predictive functional test for IVF therapy].

Hysterosalpingoscintigraphy (HSSG) is a simple method to evaluate the transport function of uterus and fallopian tubes. There is a quick uptake of radionuclides into the uterus and a transport to the side bearing the dominant follicle in 70 % of the patients in the late follicular phase of the cycle. Uptake and transport of the immotile radionuclides imitate the directed sperm transport through the female genital tract at the time of ovulation. 214 of 796 infertility patients with proven patency of fallopian tubes (27 %) showed only an uptake of the particles without a transport towards the fallopian tubes (negative HSSG). In these patients no spontaneous pregnancy occurred and pregnancy rate remained low by the means of timed intercourse or insemination. Indeed, the pregnancy rate (8.4 %) was significantly lower compared with the patients who became pregnant by timed intercourse, insemination or spontaneously and had a positive HSSG before (15 %; p=0.001). However, the pregnancy rate that could only be achieved by methods of ART was significantly higher in the group of patients with negative HSSG (57 % vs. 25 %, p=0.05). Our data suggest that HSSG is a new method to evaluate the integrity of the inner genital tract's transport function, especially in patients suffering from idiopathic infertility. Impaired transport function (negative HSSG) should be considered as an indication for IVF-treatment.

Fallopian Tubes↗

Novel insights into human endometrial paracrinology and embryo-maternal communication by intrauterine microdialysis.

The regulation of human implantation is still unknown. Evidence from mice suggests an essential role for several paracrine mediators but species differences with implantation in the human preclude the extrapolation of these concepts to humans. An intrauterine microdialysis device (IUMD), consisting of microdialysis tubing glued into a balloon catheter on one side and into a polypropylene tube on the other, allows a dynamic and accurate in-vivo measurement of uterine paracrine interactions in humans. Inserted into the uterine cavity in the form of a loop, it can be continuously perfused with saline to reveal a number of relevant cytokines and growth factors in uterine effluents of non-pregnant women in both follicular and luteal phases. These included interleukin (IL)-1alpha, IL-1beta, IL-6, leukaemia inhibitory factor (LIF), macrophage colony-stimulating factor (M-CSF), epidermal growth factor, vascular endothelial growth factor (VEGF), insulin-like growth factor binding protein-1 (IGFBP-1), prolactin, and human chorionic gonadotrophin (HCG). The source of intrauterine HCG is unclear since endometrial mRNA for the HCG beta-subunit is not revealed using reverse transcriptase polymerase chain reaction analysis. Applying urinary HCG locally via the IUMD profoundly alters endometrial secretory parameters. Prolactin, IGFBP-1, and M-CSF are significantly inhibited and VEGF is regulated in a biphasic manner involving early stimulation followed by inhibition of intrauterine levels. Use of the IUMD has thus shown that the urinary HCG preparations routinely used for ovulation induction and luteal support may directly alter endometrial function.

Animals↗

Sperm transport in the human female genital tract and its modulation by oxytocin as assessed by hysterosalpingoscintigraphy, hysterotonography, electrohysterography and Doppler sonography.

The transport function of the uterus and oviducts and its modulation by oxytocin has been examined using hysterosalpingoscintigraphy, recording of intrauterine pressure, electrohysterography and Doppler sonography of the Fallopian tubes. After application to the posterior vaginal fornix, a rapid (within minutes) uptake of the labelled particles into the uterus was observed during the follicular and during the luteal phase of the cycle in all patients. Transport into the oviducts, however, could only be demonstrated during the follicular phase. Transport was directed predominantly into the tube ipsilateral to the ovary bearing the dominant follicle; the contralateral oviduct appeared to be functionally closed. The proportion of patients exhibiting ipsilateral transport did increase concomitant with the increase of the diameter of the dominant follicle. That ipsilateral transport has biological significance is suggested by the observation that the pregnancy rate following spontaneous intercourse or insemination was significantly higher in those women in whom ipsilateral transport could be demonstrated than in those who failed to exhibit lateralization. Oxytocin administration was followed by a dramatic increase in the amount of material transported to the ipsilateral tube, as demonstrated by radionuclide imaging and by Doppler sonography following instillation of ultrasound contrast medium. Continuous recording of intrauterine pressure before and after oxytocin administration did show an increase in basal tonus and amplitude of contractions and a reversal of the pressure gradient from a fundo-cervical to a cervico-fundal direction. These actions of oxytocin were accompanied by an increase in amplitude of potentials recorded by electrohysterography. These data support the view that uterus and Fallopian tubes represent a functional unit that is acting as a peristaltic pump and that the increasing activity of this pump during the follicular phase of the menstrual cycle is reflected by an increased transport into the oviduct ipsilateral to the ovary bearing the dominant follicle. In addition, they strongly suggest a critical role of oxytocin in this process. Failure of this mechanism appears to be a cause of subfertility or infertility, as indicated by the low pregnancy rate following intrauterine insemination or normal intercourse in the presence of patent Fallopian tubes. It may be regarded as a new nosological entity for which we propose the term tubal transport disorder (TTD). Since pregnancy rate of such patients is normal when treated with in-vitro fertilization (IVF), hysterosalpingoscintigraphy seems to be useful for the choice of treatment modalities in patients with patent Fallopian tubes suffering from infertility.

Adult↗

Pregnancy course and complications in patients with systemic lupus erythematosus.

Among 165 patients with systemic lupus erythematosus (SLE), we observed 21 pregnancies in 19 patients since 1987. The mean duration of disease at the time of pregnancy was 4.5 +/- 3 years. All but three patients required immunosuppressive treatment before and during pregnancy. The effect of pregnancy on the course of SLE was studied. Severe disease exacerbations were rare and largely confined to patients with renal involvement. Most patients showed elevated titers of dsDNA antibodies during pregnancy but clinical activity of disease was usually mild. Complement C3 decrease appeared to be the most sensitive marker for pregnancy-related complications. The detection of antibodies to phospholipids was frequent during pregnancy in contrast to a low prevalence before and after pregnancy. Their presence could be associated with intrauterine growth retardation. Preterm delivery before the 37th week of pregnancy had to be performed in the majority of patients. None of the patients experienced abortion although three patients had to delivered in the 29th week of pregnancy because of increasing symptoms of pre-eclampsia. Two of these children died and the third child suffered from intracranial hemorrhage in the early postpartum period. Our data demonstrate that successful pregnancy outcome was related to a gestational age of more than 32 weeks, making careful monitoring and appropriate therapeutic management necessary.

Adult↗

Intrauterine treatment of fetal goitrous hypothyroidism controlled by determination of thyroid-stimulating hormone in fetal serum. A case report and review of the literature.

We report a rare case of fetal goitrous hypothyroidism complicated by polyhydramnios and preterm labor in a mother without thyroid gland pathology. The diagnosis was made in the 26th week by ultrasound and cordocentesis [TSH 170 microU/ml, free T(4) 0.2 ng/dl]. The therapeutic regime required repeated fetal blood sampling for determination of thyroid hormones. Five intra-amniotic administrations of 250 microg levothyroxine (LT4) weekly were initiated. Because of the persisting goiter and the elevated level of TSH (128 microU/ml in 32 weeks) in the fetal serum the dosage had to be adjusted to 500 microg LT4 in the next five injections. TSH in fetal serum declined to 49.2 microU/ml in 36 weeks. Normal fetal growth and an uncomplicated course of pregnancy between the 27th and 37th week of gestation were observed. Monitoring of intrauterine therapy by determination of TSH in fetal serum may provide more reliable data than measuring TSH in amniotic fluid. A review of 15 cases of fetal goitrous hypothyroidism in the English literature is presented.

Adult↗

CA 125 production and release by ovarian cancer cells in vitro.

The antigenic determinant CA 125 is a high molecular weight glycoprotein which is elevated in more than 80% of patients with epithelial ovarian cancer. Despite its good performance as a human tumor marker, only little is known about its physiological function. According to recent publications, CA 125 production and release appear to be related to cellular growth. In order to investigate this putative relationship more closely, we analyzed the pattern of CA 125 production and release by ovarian cancer cells during exponential cell growth, during cell cycle arrest by colchicine and during inhibition of cellular protein synthesis by cycloheximide. The results were correlated with the cell cycle distribution. According to our results, the main determinant of CA 125 release into the culture supernatant is the total cell count. Although cell cycle arrest in the G2 + M phase by means of colchicine treatment resulted in the death of most cells, which was reflected by an increased release of CA 125, no differences in the intracellular production rate between colchicine treated and untreated cells were seen. In contrast, treatment of cells with cycloheximide not only resulted in decreasing cell numbers but also in a complete inhibition of CA 125 production by surviving cells.

CA-125 Antigen↗

[Systemic lupus erythematosus and pregnancy].

Our study strengthens the view that successful pregnancy outcome can be achieved in most patients with SLE, although premature delivery and pregnancy-related complications are common. For the differential diagnosis of preeclampsia and lupus flare in pregnancy, levels of anti-DNA antibodies and complement C3 are valuable parameters. In patients with antibodies to phospholipids, no major clinical problems occurred provided that patients were treated with corticosteroids and low-dose aspirin. However, none of our patients with renal involvement of SLE had an uncomplicated pregnancy course.

Adult↗

Rhythmic fluctuations of CEA serum levels in breast cancer patients.

Hourly blood sampling for CEA determination was performed in metastatic breast cancer patients before and during medical treatment. Rhythmic fluctuations of marker concentrations could be detected. These oscillations seemed to be independent of the localisation of metastases and the kind of treatment. No relation between cortisol or prolactin and CEA levels became apparent.

Aminoglutethimide↗