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M Breckwoldt

Publications and source records attributed to M Breckwoldt.

At least 55 records · Page 3Linked to original sources

Human chorionic gonadotropin-dependent expression of vascular endothelial growth factor/vascular permeability factor in human granulosa cells: importance in ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a severe complication arising from controlled ovarian stimulation treatment. This iatrogenic condition is potentially lethal and occurs in 0.3-5% of stimulated ovarian cycles. hCG exacerbates OHSS. The pathophysiology of OHSS is still unknown; therefore, treatment regimens are aimed at ameliorating symptoms. Prominent features of OHSS are an elevated risk of thromboembolism due to enhanced production of von Willebrand factor by endothelial cells and ascites, or pulmonary edema due to increased vascular permeability followed by third space fluid accumulation. Both of these sequelae can be evoked by vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF). High concentrations of VEGF/VPF have been demonstrated in ascitic fluid from patients with OHSS, but the source of VEGF/VPF in these patients remained unidentified. Here we report that the messenger ribonucleic acid expression of VEGF/VPF in human luteinized granulosa cells (GCs) is dose and time dependently enhanced by hCG in vitro. Furthermore, VEGF/VPF proteins are produced by GCs. Our results suggest that the effects of hCG on the development and course of OHSS may be mediated by the production of VEGF/VPF by GCs.

Adult↗

Immunohistochemical localization of thromboxane synthase in human intrauterine tissues.

Uterine tissues are known to be able to synthesize thromboxane A2 (TXA2), but there is little information about the nature of cells actually responsible for its production. In this study human placenta, fetal membranes, umbilical cord and pregnant myometrium were investigated immunohistochemically. The avidin-biotin method for a monoclonal antibody against human thromboxane synthase (Tü 300) was applied on frozen tissue sections. In placenta, fetal membranes and umbilical cord, staining was positive for Hofbauer cells and fibroblasts. Further, in sections of placenta, capillary endothelium showed antigenicity for TX synthase. Leiomyocytes in the umbilical cord vessels contained the enzyme as well. Preparations of pregnant myometrium were shown to express TX synthase in leiomyocytes, endothelial cells and connective tissue cells. Amnion, trophoblast and decidua did not possess antigenicity for this enzyme. Since TXA2 plays an important role for the regulation of vascular tone and aggregation of platelets and may stimulate myometrial contractions during parturition, the abundance of TX synthase in pregnancy-specific tissues confirms previous in vivo and in vitro observations. Further, TXA2 synthesized by Hofbauer cells may be involved in immunological reactions during pregnancy, and the number and level of activation of Hofbauer cells may be closely related to the initiation of labour. Thromboxane production by the endothelium lining the fetal vessels points to its regulatory role for the blood flow in the fetoplacental unit.

Endothelium, Vascular↗

Eicosanoid production by frozen tissue in vitro is markedly changed.

The influence of storing deep frozen human tissue specimens on their eicosanoid production in tissue culture was evaluated. Pieces of placenta and fetal membranes (n = 6) were divided and part processed immediately after obtaining the tissues, part after being kept at -20 degrees C for some days. Eicosanoid production was studied in tissue culture with incubation in oxygenated Hank's balanced salt solution (HBSS) at 37 degrees C for 1 h. Prostaglandin E2 (PGE2), prostacyclin (PGI2), thromboxane A2 (TXA2) and leukotriene B4 (LTB4) production were significantly different in the tissues frozen prior to the incubation. This should be considered when interpreting eicosanoid synthesis in tissue cultures for their significance in vivo.

Cryopreservation↗

Placental progesterone, prostaglandins and mechanisms leading to initiation of parturition in the human.

Present knowledge allows the identification of some features of the initiation of human parturition. Progesterone reduces myometrial sensitivity to labour-inducing agents. It suppresses gap junction formation and facilitates beta-adrenergic receptor expression by the myometrium which, in turn, exerts a positive feedback by enhancing beta-adrenergic-induced increases in placental progesterone production. Inhibition of gestagen action does not result in immediate initiation of labor but sensitises myometrial cells to contraction-inducing agents. Estrogens, in contrast, enable the myometrium to prepare for parturition by inducing oxytocin receptors and this seems to be the first step towards parturition. Coordinated myometrial contractions are facilitated by the increased gap junctions due to the estrogen drive. Absence of estrogen will result in failed parturition. The myometrium seems to be sensitised to oxytocin by placental CRF. Myometrial CRF receptors increase their avidity for CRF with ongoing pregnancy. Oxytocin evokes a variety of auto- and paracrine events which culminate in increased free intracellular calcium and the consequent contractions. In this cascade, prostaglandins can be identified as positive feedback agents, as they further enhance estrogen-induced expression of oxytocin receptors. Another second messenger of oxytocin action are the inositol phosphates which can further increase free intracellular calcium concentrations. Finally, endothelin-1, derived from endometrium and decidua, under oxytocin control, may serve as a myometrial contractor following delivery when oxytocin concentrations decline but when a strong myometrial contraction is needed to prevent large blood loss during and after placenta expulsion.

Female↗

[Ovarian hyperstimulation syndrome].

Techniques of assisted fertilization are usually preceded by ovarian stimulation therapies. This implies the risk of development of an ovarian hyperstimulation syndrome (OHS). With this article, clinical relevance, possible pathogenetic mechanisms, diagnosis, therapy and prevention of OHS are discussed. In addition, three patients with severe OHS are presented. Valid parameters for OHS risk assessment are peripheral E2 values as well as number and diameter of follicles. Until now, the mechanisms which lead to severe OHS are unknown, but hCG seems to trigger the development of symptoms, as OHS very rarely occurs without prior hCG application. Symptoms of severe OHS comprise ovarian enlargement, fluid- and electrolyte imbalance, third space fluid accumulation, haemoconcentration and hypercoagulation. Only symptomatic therapy is available. The significance of vascular mediators for the development of OHS is discussed.

Chorionic Gonadotropin↗

[Transvaginal color-coded Doppler ultrasound in ovarian tumors].

In 129 patients with ovarian tumours, a preoperative examination by transvaginal colour Doppler sonography (ATL UM9 HDI) was performed. 45 were malignant and 84 benign. 46 patients were premenopausal and 83 postmenopausal. All tumour vessels were analysed by spectrum analysis. The number of tumour vessels and the lowest resistance index (RImin) and pulsatility index (PImin) of all vessels were evaluated as diagnostic criteria of the neovascularisation. Up to 19 vessels were found in 115 (89%) tumours. In benign lesions, the number of vessels was significantly lower than in malignancies (median 3 versus 9, p < 0.0001). The RImin and PImin values between benign and malignant tumours were also significantly different, independent of the menopausal status. In postmenopausal patients, the median RImin in 42 benign tumours was 0.62 (0.26-1.0) and in 41 malignancies 0.40 (0.22-0.66). The median PImin was 0.98 (0.31-5.84) in benign tumours and 0.53 (0.25-1.22) in malignant tumours. However, due to the overlapping range between benign and malignant tumours, these parameters do not allow an accurate differentiation. With a cut off value for RImin = 0.5 and PImin = 0.7, the sensitivity is 85% or 82.5% respectively. The specificity for RImin and PImin is 77%, and the diagnostic accuracy is 84% and 80% respectively. The correlation coefficient between RImin and PImin is 0.99 in benign and malignant tumours and both indices are adequate. The calculation of the RI is more easily available and should be preferred as a diagnostic parameter.

Adolescent↗

Influence of the developmental stage and the equilibration time on the outcome of ultrarapid cryopreservation of mouse embryos.

Mouse embryos of different developmental stages from 1- to 8-cell inclusive were ultrarapidly frozen in 0.25 ml French straws after various periods of equilibration (1, 3, 5 and 9 min) in freezing-buffer containing 3.5 M dimethylsulphoxide (DMSO), 0.25 M sucrose, and 20% fetal calf serum (FCS) in phosphate buffered saline (PBS). After thawing in a 37 degrees C waterbath and dilution for 5 min in 0.25 M sucrose in PBS/FCS the embryos were cultured in Ham's F10 medium with 10% FCS (37 degrees C, 5% CO2, 95% humidity) for 4-6 days. The rates of expanded and hatching blastocysts were then evaluated and compared to the corresponding rates of non-frozen controls. Thus, for each cleavage stage, the optimal equilibration time was evaluated. It was 1 min for the 1-cell and 8-cell stages (32 and 81% blastocysts, respectively), and 3-5 min for the 2-cell (76 and 73%, respectively) and the 4-cell stage (88 and 87%, respectively). It is concluded that the ultrarapid freezing method described provides satisfactory results for all tested cleavage stages, but not for the 1-cell stage.

Animals↗

Comparison between prolactin, gonadotrophins and steroid hormones in serum and follicular fluid after stimulation with gonadotrophin-releasing hormone agonists and human menopausal gonadotrophin for an in-vitro fertilization programme.

The inter-relationship between serum and follicular fluid prolactin, oestradiol, progesterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) in two groups of women was investigated. In group 1, 32 women were treated with gonadotrophin-releasing hormone agonist (GnRH-a) in a long term protocol and subsequently stimulated with human menopausal gonadotrophin (HMG). In group 2, 25 women were simultaneously stimulated with GnRH-a in a short protocol with HMG. Follicular fluid was collected from 54 follicles in group 1 and 47 follicles in group 2. Serum was obtained on the day of human chorionic gonadotrophin (HCG) administration. Serum prolactin and oestradiol concentrations were significantly higher (P < 0.025 and P < 0.01, respectively) in group 1 than in group 2. Serum LH (P < 0.005), FSH (P < 0.01) and progesterone (P < 0.025) were significantly lower in group 1 than in group 2. Follicular fluid prolactin was significantly higher (P < 0.005) in group 1. No differences were found in follicular fluid progesterone and oestradiol. Follicular fluid LH was significantly lower (P < 0.05) in group 1. Serum prolactin correlated positively with oestradiol in both groups (P < 0.005 group 1; P < 0.02 group 2). No significant correlation was found between serum prolactin and LH in group 1. We conclude that prolactin secretion is independent from LH secretion. Hyperprolactinaemia, which is observed in women stimulated with GnRH-a and HMG, is positively associated with increased oestradiol.

Adult↗

Twin pregnancies with single fetal death.

OBJECTIVE: Analysis of the fetal outcome of the surviving twin and the cause of fetal death. PATIENTS: Between January 1979 and December 1992, 43 twin pregnancies with single fetal death were observed: in 11 cases (group I) before 16 weeks of gestation, in 11 cases (group II) between 17 and 24 weeks, and in 21 cases (group III) after 24 weeks of gestation. RESULTS: The pregnancies in group I continued without complication. In groups II and III the incidence of preterm delivery was 50%, of cesarean section 59%, of growth retardation of the surviving twin 22% and perinatal mortality was 13%. Twenty-five (78%) of the surviving twins had a normal postnatal development and one (3%) was handicapped. CONCLUSION: Loss of one of the twins in the first trimester does not impair the development of the surviving fetus. In the second trimester however this even is associated with increased risk for the survivor as reflected by a high incidence of growth retardation, premature labor and perinatal mortality.

Female↗

[Doppler ultrasound in high grade multiple pregnancies].

From 1987 until 1992, 16 triplets and 2 quadruplets were studied by pulsed Doppler ultrasound between 17 and 36 weeks of gestation. A resistance index (RI) of the foetal aorta and umbilical artery above the 95th percentile was considered pathological. Elevated RI-values of the umbilical artery as compared to the A. cerebri media were indicative of circulatory centralisation. Intrauterine growth retardation (IUGR) was found in 9 (16%) foetuses, discordant growth occurred in 7 (39%) pregnancies. 41 (73%) of 56 foetuses survived in good health. Four of 7 foetuses with pathological Doppler findings died. The three survivors were markedly retarded. Four of 6 cases of intrauterine endangered foetuses were detected by Doppler sonography. The diagnosis of IUGR or discordant growth was based more frequently on pathological Doppler findings than on biometry and improved upon by combinations of both methods. Doppler sonography proved to be an important complementary method in the monitoring of high-grade multiple pregnancies.

Adolescent↗

[The course of pregnancy in patients with malignancies].

There is a low incidence of pregnancy associated with malignancy. We performed a retrospective analysis of patients of 16 to 35 years of age with malignancies, who had given birth to children in Freiburg 1980-1989. 170 patients were included. 118 patients became pregnant before a malignancy was diagnosed. Malignancy was diagnosed during pregnancy in 24 patients, and 28 patients became pregnant after diagnosis of and therapy for neoplasm. The frequency of preterm delivery, growth retardation and performance of Caesarean section was markedly increased only in patients with concurrent pregnancy and malignancy. 59 children were born after their mother had been treated for a malignancy. Treatment was started during pregnancy in 19 cases. 40 children were born to mothers who became pregnant after treatment. Malformations and abnormalities with respect to the development of the children were observed in similar frequency in both groups and occurred more frequently compared to the group of children, who were born before the treatment of the mother. These results were supported by an analysis of 16 siblings. We conclude, that there is a demand for national and international registries for all pregnancies associated with malignancies. Long-time observation of the children born to mothers, who had been treated for malignancy are necessary.

Adolescent↗

[Obstetric complications, incidence and indications of cesarean section in uterus myomatosus].

An increasing percentage of patients with uterine leiomyomas was observed in the Department of Obstetrics, University of Freiburg, on comparing the years 1970-79 (0.25%) and 1980-89 (0.64%). While first trimester bleeding, pain and premature labour, being typical obstetrical complications, were encountered in a comparable frequency, atonic bleeding was observed more often during the nineteen-eighties. Pain and premature labour were often present, if the leiomyomas were large, irrespective of both their number or localization. Atonic bleeding was observed more frequently, if large leiomyomas were present. A correlation between the presence of uterine leiomyomas and placental deficiency, premature birth, and EPH gestosis seems uncertain. The total complication rate among all pregnant patients with uterine leiomyomas was 65% from 1980-89. The Caesarean section rate among patients with uterine leiomyomas increased during the evaluated time span, and reached 51% during the 1980's, as compared to a general frequency of Caesarean sections of 19% during the latter time period; this increase in frequency seems to be rather in keeping with a generally increasing Caesarean section rate as opposed to a changing indication for surgery in patients with myomas. The myomas themselves caused Caesarean sections in 50% of cases, while in the remaining 50% of patients, Caesarean sections were performed for general obstetrical reasons. The probability to be delivered by Caesarean section was especially high amongst patients with multiple myomas or with an isthmic myoma. Our study supports a conservative approach in the case of pregnancy and uterine leiomyomas.

Adult↗

[Effect of pregnancy on the incidence and course of malignant diseases].

Fortunately, coincidence of pregnancy associated with malignant neoplasm is rare. As reported in the literature, incidence is 1.5-10: 10,000 pregnancies. The study presented reports data on the incidence and outcome of 16-35 years old female patients suffering from malignant neoplasms. Patients, who were treated in Freiburg 1980-1989, were considered for evaluation. We analysed the impact of pregnancy on the outcome of these patients by stratifying patients for the time of diagnosis (before, during, or after a pregnancy). 247 patients were included. 118 patients developed a neoplasia after a successful pregnancy. In 24 patients, neoplasia was diagnosed during pregnancy, and 28 patients became pregnant after diagnosis and therapy for a malignancy. Further 77 patients without pregnancy, but in whom neoplasia diagnosed at the age of 16-35 years were included. Cancer of the cervix uteri, breast cancer, ovarian cancer, and malignant lymphomas were the most frequent neoplasias diagnosed in young women. In an analysis stratified for stage of disease, we found no significant difference between 3- and 5-years survival of patients with pregnancies before, during, or after diagnosis and treatment of neoplasia. Due to the inhomogeneity of the subgroups analysed, the question, whether pregnancy has any impact on the outcome of neoplasm could not be conclusively answered. The necessity for the establishment of national and international registries collecting sufficient data about incidence and outcome of patients with pregnancies associated with malignant neoplasms is emphasised.

Adolescent↗

[Improving diagnosis of blood supply of breast tumors by echo-contrast media].

Doppler blood flow measurements allow differentiation of malignant lesions, that are characterised by an abnormal vascularity. The accuracy of this method is limited due to the physiological flow variation in normal breast parenchyma and in tumours. Magnetic resonance imaging in combination with contrast agents can also be used for flow assessment by measurement of the dynamic contrast enhancement. Recently, a new echo contrast agent (Levovist) has been developed, which survives pulmonary transit and increases the Doppler signal intensity after intravenous injection. Fourteen malignancies with low vascularity were selected for the study. Twenty-two seconds after injection of contrast agent, the Doppler signal intensity increased dramatically. This demonstrates, that echo contrast agents might improve the diagnosis of breast lesions in case of non-conclusive Doppler findings.

Blood Flow Velocity↗