Tumorbiology of ovarian cancer remains unclear. However, it is known that ovarian tumors, especially carcinomas, show elevated expression of glucose membrane transporters for facilitated glucose uptake. It can be assumed that increased glucose uptake leads to higher glucose metabolism. The energy resources of fully malignant transformed carcinomas are mainly supplied by aerobic glycolysis, for which several pathways are known. A key role in aerobic glycolysis is described for the transketolase enzymes. Recently, a novel transketolase-like enzyme called transketolase-like 1 (TKTL1) has been described that links aerobic glycolysis to the synthesis of fatty acids via production of acetyl-CoA. In order to investigate the role of TKTL1 for the progression of ovarian carcinomas, we examined paraffin sections of normal ovarian tissues, ovarian borderline tumors, and mucinous or serous papillary ovarian adenocarcinomas with respect to their expression of TKTL1. We identified a significantly elevated expression of TKTL1 in serous papillary ovarian adenocarcinomas, which correlates with poor prognostic parameters in the examined study group. Therefore, it can be assumed that TKTL1 plays a crucial role in ovarian cancer metabolism and that its expression predicts poor prognosis. Further investigations should be performed in order to evaluate whether this new enzyme is important for ovarian cancer tumorbiology and to analyze the potential role of TKTL1 as new target for specific antitumoral therapy.

Die Tartrat-resistente saure Phosphatase (TRAP) gilt als Markerenzym der Knochen-resorbierenden Osteoklasten. Die aktive Isoform 5b wurde bei Tumorpatienten als Indikator für einen durch Knochenmetastasen bedingten verstärkten Knochenabbau beschrieben. Bei Bestimmung von TRAP5b im Serum von Mammakarzinom-Patientinnen mit und ohne ossäre Metastasierung im Rahmen einer Studie fanden wir z.T. deutlich erhöhte Werte bei Patientinnen mit ausschließlich viszeraler Filialisierung in Progression.

Article Normalization of a severely abnormal ductus venosus Doppler flow velocity waveform in the presence of normal arterial flow parameters was published on January 1, 2005 in the journal Journal of Perinatal Medicine (volume 33, issue 1).

It is still not understood how the fetus escapes from being attacked by the maternal immune system. Recent reports based on mouse and in vitro models have suggested that the enzyme indoleamine 2,3-dioxygenase (IDO) is important for materno-fetal tolerance. IDO activity in the human placenta is known to be high and might lead to inhibition of T-cell proliferation, thus preventing fetal tissue from rejection by the maternal immune system. In an attempt to elucidate the precise location of IDO at the feto-maternal junctional zone, we investigated human placental and decidual tissue of first and third trimester of pregnancy using an immunohistochemical approach. In placental tissues, only syncytiotrophoblast and endothelial cells showed moderate expression of IDO. This pattern was observed regardless of whether first or third trimester tissue was investigated. In early and term decidua, cells with the typical morphology of invasive extravillous trophoblast (EVT) were strongly positive for IDO. Blocking immunohistochemical experiments with cytokeratin and IDO antibodies identified invasive EVT as the location of predominant IDO expression. Since EVT are the fetal cells with the closest contact to the maternal immune system, our results suggest that it is EVT which protects the fetus from rejection by downregulating local maternal T-cell responses.

Bei vorzeitiger Wehentätigkeit ist ab der 25. SSW eine Tokolyse mit einem ß-adrenergen Rezeptor-Agonisten die am weitesten verbreitete Vorgehensweise. Bei Langzeitbehandlungen kommt es jedoch zu einem Wirkungsverlust. Über den zugrundeliegenden biochemischen Mechanismus ist wenig bekannt. Die vorliegende Studie untersucht den Effekt von Fenoterol auf die ß-adrenerge Signaltransduktion.

Background: Breast and ovarian tumor cell lines with defined tumor-associated antigens could serve as allogeneic antigen-sources for the biological therapy of cancer. Materials and Methods: Eight breast and 3 ovarian cancer cell lines were stained for the antigens in question by immunohistochemistry. Antigen-expression was graded in 5 steps by light microscopic examination. Results: All cell lines with the exception of PA-1 expressed EMA. Only MCF-7 was CEA-positive. MUC-1 was found in all cell lines apart from MDA-MB and SK-OV3. The highest expression of Her-2/neu was found in ZR-75/1 and SK-OV3. A491D and PA1 cells were CD19-negative, all other lines were positive. Only A491D and BT-20 had p53 accumulation. PR was found in 5 cell lines and ER in 6 cell lines. Conclusion: The cell lines investigated express a different pattern of tumor markers. In consequence, a careful examination should be performed in order to find the "best fitting" cell line to a patient's tumor for a tumor-vaccine.

Zielsetzung: Das Gleichgewicht zwischen aktiver Immunabwehr und Immuntoleranz gegenüber dem allogenen Embryo ist von entscheidender Bedeutung für die normale Frühschwangerschaft. Da dendritische Zellen (DC) an der Ausbildung einer peripheren Immuntoleranz in der Dezidua über eine veränderte Präsentation fetaler Antigene maßgeblich beteiligt sein könnten, führten wir eine detaillierte immunhistochemische und funktionale Analyse der DC-Populationen in der Dezidua der Frühschwangerschaft und nichtschwangerem Endometrium durch.

AIM:To investigate vascular endothelial growth factor (VEGF) serum levels in severe preeclampsia (PE) and HELLP syndrome.PATIENTS AND METHODS:Serum concentrations of VEGF, progesterone, estradiol and estriol were measured in 16 patients with PE and 14 patients with HELLP syndrome and in 30 well-matched normotensive pregnant controls. Determination of VEGF was performed by a commercially available immunoassay (Quantikine(R), R&D Systeme, Wiesbaden), those of sex steroids by a radioimmunoassay (Fa. Biermann, Bad Nauheim).RESULTS:Serum VEGF levels were significantly higher in the study than in the control group (172.0 +/- 98.9 pg/ml versus 41.4 +/- 30.5 pg/ml, U-Test: p < 0.001). In patients with HELLP syndrome mean serum VEGF concentrations were increased when compared with healthy controls but serum levels were significantly lower than in patients with PE (109.2 +/- 68.5 pg/ml versus 219.0 +/- 72.9, U-Test: p < 0.05). We could demonstrate a positive correlation between VEGF and estradiol serum concentrations in the study and control patients (Spearman rang correlation: p < 0.05).CONCLUSIONS:It is concluded that patients suffering from PE or HELLP syndrome have either an increased placental expression of VEGF as a result of hypoxia or show an increased extraplacental production of this growth factor such as in maternal or fetal endothelial cells, macrophages or smooth muscle tissue.

Visual disturbances occur in up to 25 % of the patients with preeclampsia. However, blindness remains a rare phenomenon. A 39 year old primigravida was admitted for observation at 30 weeks gestation with signs of preeclampsia. After 11 days she suffered a complete loss of vision. The blindness reversed completely after cesarean section and antihypertensive treatment. Blindness in preeclamptic patients is mostly caused by hypertensive encephalopathy. We discuss pathophysiological aspects as well as diagnostic approaches and therapeutic options with respect to the available literature.

Objective. Determination of the efficacy and side-effects of the synthetic prostaglandin analog gemeprost for termination of pregnancy in the third trimester.Patients. Retrospective record study of 40 women who had undergone third trimester termination of pregnancy before term by serial administration of gemeprost because of intrauterine fetal death or hopeless fetal prognosis. Patients with multiple pregnancy, a Bishop score > 5, contractions or contraindications to prostaglandins were excluded.Methods. Gemeprost vaginal pessaries (1-mg) were given at 6-hourly intervals until labor intervened. The main parameter studied was the induction-delivery interval, the length of time between administration of the first dose and delivery. Statistical analysis was performed with the chi-square and the Mann-Whitney U-test.Results. The median induction-delivery interval was 14.4 h (range 3-48 h). Delivery occurred within 12 h in 17 women (42.5%), within 24 h in 27 women (67.5%) and within 36 h in 37 women (92.5%). An average of 2.6 doses were given per patient. Multigravidae had a significantly shorter induction-delivery interval than primigravidae (p<0.01). A total of 87.5% women required analgesia. Side-effects were infrequent.Conclusions. The administration of gemeprost vaginal pessaries represents an efficient method with few side-effects for the induction of labor in the third trimester, provided patients are chosen carefully and monitored closely.

PROBLEM: How do major histocompatibility complex (MHC) I positive/negative choriocarcinoma (CC) cells affect the production of tumor necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ), interleukin‐10 (IL‐10), interleukin‐4 (IL‐4), and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) by decidual CD56++ cells (large granular lymphocytes [LGL]), LGL‐depleted decidual cells (WASH) and unseparated decidual cells (DEC) in cocultures? METHOD OF STUDY: Decidual tissue was obtained by legal abortions. CD 56++ LGL were isolated in a magnetic cell separator. Cytokines were measured by ELISA. Differences were analyzed for significance by Wilcoxons test. RESULTS: We found a significant increase of IL‐10 in LGL/JEG‐3 and of TNF‐α in LGL/JAR cocultures compared to noncocultured decidual cells. There was a significant increase of IL‐10 and TNF‐α and a significant decrease of GM‐CSF in WASH and DEC cocultures with both JEG‐3 and JAR. IFN‐γ was only found in 3/11 cases of LGL/JAR cocultures. No IL‐4 was found in any experiment. CONCLUSION: MHC class I positive/negative CC modulate the cytokine production of decidual LGL in different ways.

The frequency of endocrine abnormalities during the follicular phase in non-pregnant women with a history of recurrent abortion was investigated in a case-control study. A total of 42 consecutive women with recurrent spontaneous abortion (three or more consecutive abortions, mean +/- SD: 3.9 +/- 1.1 range 3-8) with no parental chromosome rearrangement or uterine abnormality were studied during the early follicular phase under standardized conditions. Serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, androstenedione, testosterone, dehydroepiandro-stenedione, 17-OH-progesterone, oestradiol, progesterone and thyroid stimulating hormone (TSH) were measured by commercially available radioimmunoassays. Controls were 42 nulligravid females with tubal or male factor infertility without miscarriage. Mean (SD) concentrations of prolactin and androstenedione were 14.2 +/- 6.7 ng/ml versus 10.5 +/- 3.5 ng/ml (95% CI 0.8-6.1) and 2.3 +/- 0.9 ng/ml versus 1.7 +/- 0.6 ng/ml (95% CI 0.2-0.9) in the study and control groups respectively. The other endocrine parameters were comparable in both groups. Obesity [BMI weight (kg)/height (m2) > or = 25] was more prevalent (23 versus 5 women, P = 0.0001) in the study than the control group. Recurrent spontaneous abortion is associated with abnormalities in prolactin and androgen secretion during the follicular phase, suggesting an endocrine aetiology in this disorder. Reduction of body weight and correction of hyperprolactinaemia and of hyperandrogenism may reduce the rate of miscarriage in a subsequent pregnancy in these women.

Background: CA 125 is the most important tumor marker in ovarian cancer. Due to its low specificity and the fact that some ovarian malignancies do not produce considerable amounts of CA 125 a combination with the Cancer Associated Serum Antigen (CASA) may reflect more accurately the clinical situation. Materials and Methods: CA 125 and CASA determination was performed in sera of 78 patients with advanced ovarian cancer pre- and postoperatively, monthly during chemotherapy and during follow-up care. The cut-off values for CASA were 4 U/ml, for CA 125 35 U/ml and 65 U/ml, respectively. Results: In the detection of advanced ovarian cancer a combination of both tumor markers was superior to the use of either CASA or CA 125 alone. In the follow-up situation CA 125 with the 35 U/ml cut-off showed the highest sensitivity. Both markers had similar prognostic relevance when marker levels three months after surgery were used. Conclusion: CA 125 and CASA have similar characteristics in preoperative diagnosis and postoperative follow-up. In clinical situations with inconclusive or negative CA 125 serum values CASA is helpful to improve management of patients with advanced ovarian cancer.

BACKGROUND The clinical usefulness of tumor markers in the follow-up care of invasive breast cancer is controversial. METHODS In 1228 serum samples of 664 women with history of breast cancer, the diagnostic accuracy and predictive power of CEA and CA 15-3 for the detection of disease relapse was determined prospectively by analyzing the clinical course for at least 6 months after the measurement of the tumor markers in 1994. RESULTS A total of 76 patients relapsed during the period of study. The diagnostic accuracy was 83% for CEA and 88% for CA 15-3. CEA and CA 15-3 had a positive predictive value of 27% and 47% as well as a negative prediction of 91% and 93%, respectively. CONCLUSIONS The low positive predictive value and sensitivity of these tumor markers clearly limit their clinical utility. Therefore, the effectiveness of routine determinations during the follow-up seems questionable.

Objective: To compare maternal and umbilical venous big endothelin (big ET) and endothelin-1 (ET-1) levels of pregnancies complicated by severe preeclampsia (PE) or HELLP-syndrome to those of a well-matched normotensive pregnant control group. Methods: We measured plasma levels of ET-1 and big ET in 16 patients with severe PE and 14 patients with HELLP-syndrome by commercially available RIAs and compared them with those of well-matched normotensive pregnant controls. Additionally, the umbilical venous ET-1 and big ET levels were determined in 10 corresponding newborns. Results: The plasma concentrations of ET-1 and big ET were significantly higher in patients with severe PE and especially in women with HELLP-syndrome when compared with controls. The molar ratios of big ET to ET-1 were significantly lower in the two study groups. The levels of ET-1 and big ET were higher in umbilical venous plasma than in maternal plasma, but there were no significant differences in the umbilical venous concentrations between normotensive and by severe PE or HELLP-syndrome complicated pregnancies. Conclusions: These findings suggest that ET-1 may be considered as a marker of endothelial injury in by severe preeclampsia or HELLP-syndrome complicated pregnancies. The increase of the ET-1 plasma levels may be due, at least in part, to changes in the conversion of big ET to ET-1 by the endothelin-converting enzyme.

s of the 15th Annual Meeting of the ESHRE, Tours, France 1999 stimulation (COH).Initial findings indicate that this shorter treatment regimen versus the agonist regimen utilizes fewer resources and, therefore, reduces the burden on both the patient, health insurance and societal perspective.

A prospective, randomized, double-blind and placebo-controlled study was conducted to assess the effectiveness of i.v. administration of 6% hydroxyethyle starch solution (HES) in preventing moderate and severe ovarian hyperstimulation syndrome (OHSS) in patients in an in-vitro fertilization programme. A total of 101 women who had serum oestradiol concentrations >1500 pg/ml and/or more than 10 follicles on day of human chorionic gonadotrophin (HCG) administration were recruited into two groups: HES group (n = 51) received 1000 ml 6% HES; and the placebo group (n = 50) received 1000 ml of sodium chloride 0.9% solution at the time shortly after embryo transfer. Follow-up examinations 7 +/- 1 and 14 +/- 1 days after embryo transfer included transvaginal ultrasound (diameters of each ovary and maximum cysts, number of cysts, ascites), blood tests (serum oestradiol, progesterone, beta-HCG, C-reactive protein, blood count, plasma proteins, electrolytes, kidney function tests) and evaluation of abdominal pain, nausea, diarrhoea, abdominal swelling and weight gain. Only one moderate OHSS developed in the HES group whereas seven moderate-severe cases were observed in the placebo group (P = 0.031). Furthermore, serum oestradiol concentration, leukocyte count, increase in abdominal circumference and weight gain 14 days after embryo transfer were significantly higher in the placebo group. There were no differences between the two groups in terms of age, oestradiol concentration and number of follicles at time of HCG injection. Administration of 6% HES prevents the development of moderate-severe OHSS in risk patients.