Search

EGF-related peptides and their receptors play an important, but not fully understood role, both, in epithelial physiology and pathophysiology but also in human tumor carcinogenesis and tumor behavior, respectively. Overexpression of EGF-related growth factors from normal epithelium to carcinomas has been demonstrated for several human tissues such as breast, endometrium, cervix and ovary. Additionally, the differential overexpression of EGFR or erb B-2 in various malignancies has already proven to be efficacious in stratifying patients with respect to a poor prognosis. These data suggest that EGF-related growth factors, erb B receptors or signaling proteins that function either upstream or downstream from these receptors may represent novel targets for selective tumor therapy. In the future, conventional chemotherapy regimes will ultimately be wedded to more biologically-oriented therapies. One important target for these novel therapeutic approaches in solid tumors will be the EGF-related growth factors and their receptors.

Purpose: The overall purpose of this exercise is to rigorously determine the relative strenght of the hypothesis that the menstrual cycle timing of operation has an impact on the outcome and to determine whether or not a specific change in the practice of breast surgical oncology can be recommended. Method: In 1989 preliminary results of a retrospective study were published which identified the timing of breast cancer surgery in relation to the menstrual cycle as an independent predictor of disease-free survival. At least dozens of reports have subsequently appeared, some supporting and others refuting the claim. This is a critical review of the outcomes of 8632 women published since 1989 in 31 retrospective studies, relevant to the possibility that the timing of primary breast cancer resection within the menstrual cycle impacts on breast cancer recurrence and/or patient survival. This article contrasts the adequacy of information and data analysis presented in each publication. Therefore we constructed an objective score for evaluating the quality of data. This score consists of the most relevant parameters, necessary to clarify the problem. Results: 14 studies including 3236 patients have reported, that the time of breast cancer resection during the menstrual cycle has an impact on the outcome. 17 retrospective studies with 5396 patients cannot confirm an influence of surgery timing on the prognosis in premenopausal breast cancer patients. A comparison of the quality of data among these studies demonstrates great variability. Arbitrary bisections of the menstrual cycle, the application of vastly different primary and adjuvant treatment strategies, the cumulative distribution (distribution function) of tumour stage of disease at diagnosis, duration of follow-up and the methods and precision of data analysis all differ markedly. Eight high-quality studies have been most completely reported. While two of these find no impact, six (75%) of these studies find that breast cancer outcome is affected by operative timing. The design of two ongoing prospective studies is considered inadequate. Conclusion: Although it is likely that the menstrual cycle phase of operation is relevant to outcome, the nature of the available data does not permit a clear recommendation in respect of the timing of operation. Hence, it is concluded that current retrospective data are insufficient to recommend an immediate change in practice. Prospective studies of this potentially important question are essential. The minimal requirements for adequate prospective study are outlined. Three elements seem to be essential, namely: the accurate triangulation of surgery within the cycle, temporal coordination of multiple surgical procedures if more than one operation is employed, and the investigation of menstrual cycle-coordinated biological functions potentially relevant to breast cancer resection outcome.

Advances in ultrasound technology and sonographer’s experience lead to the description of many rare syndromes and malformations through prenatal diagnosis. Diaphragmatic hernia is a rather common malformation but can be an indicator of different syndromes. We report the prenatal diagnosis of lethal multiple pterygium syndrome type II which has been established in the 34th week of pregnancy. The sonographically detectable symptoms consisted of polyhydramnios, hygroma colli, diaphragmatic hernia, scoliosis, short forearms, hypokinesia of the fetus and pterygia over the large joints. Labour was induced in the 34th week of pregnancy; the neonate died shortly after vaginal delivery as a result of the pulmonary hypoplasia. A multidisciplinary approach in prenatal assessment may help to clarify difficult diagnostic problems and may be of direct benefit for the pregnant patient.

Bei 137 pra- und postmenopausalen Patientinnen mit einem Lokalrezidiv wurde der Krankheitsverlauf in einer retrospektiven Studie uberpruft. Dabei wurde besonders die Abhangigkeit des rezidivfreien Intervalls von tumorbiologischen Parametern des Primartumors untersucht. Es zeigte sich, das in 23% der Falle das Lokalrezidiv Ausdruck der Tumorgeneralisierung mit dem simultanen Auftreten von Fernmetastasen war. Das durchschnittliche rezidivfreie Intervall lag bei 4 Jahren, wobei jedoch mehr als die Halfte der Rezidive in den ersten beiden postoperativen Jahren auftraten. Ein statistisch signifikanter Zusammenhang zum rezidivfreien Intervall lies sich fur folgende Parameter nachweisen: die Grose des Primartumors (p = 0,0003), den Nodalstatus (p = 0,0006) sowie hierbei auch die Anzahl der metastatisch befallenen Lymphknoten (p = 0.0002) und die Hohe des befallenen Lymphknotenlevels (p = 0.00001). Auch der immunhistochemische Ostrogen- und Progesteronrezeptorstatus (p = 0,0005) und die mit dem monoklonalen Antikorper Ki67 ermittelte Wachstumsfraktion (p = 0.0106) korrelierten signifikant mit der Lange des rezidivfreien Intervalls. Die Form der operativen Primartherapie bliebohne Einflus auf das rezidivfreie Uberleben. Die adjuvante The rapie hatte jedoch einen entscheidenden Einflus. Patientinnen nach einer adjuvanten Strahlentherapie entwickelten signifikant spater lokale Rezidive (p = 0,00001). A retrospective study was performed to follow up the course of the disease in 137 female premenopausal and postmenopausal patients in whom local recurrence of carcinoma of the breast had occurred. Particular attention was given to the dependence of the recurrence-free interval on the tumorobiological parameters of the primary tumour. In 23% of the cases the local recurrence was an expression of generalisation of the tumour with simultaneous occurrence of distant metastases. The average recurrence-free interval was four years, but more than half of the recurrences were seen during the first two postoperative years. For the following Parameters we found a statistically significant correlation with the recurrence-free interval: size of the primary tumour (p = 0.0003), the nodal Status (p = 0.0006) and in this connection also the number of the metastatically involved lymphatic nodes (p = 0.0002) and the magnitude of the involved lymphatic node level (p = 0.00001). There was also a significant correlation between the duration of the recurrence-free interval and the immunohistochemical oestrogen and progesterone receptor status (p = 0.0005) and the growth fraction (p = 0.0106) determined with the monoclonal antibody Ki67. However, althoug there was no correlation between recurrence-free survival and the kind of surgical primary therapy that had been employed, adjuvant therapy did exercise a decisive influence: there was significant later incidence of local recurrences (p = 0.00001) subsequent to adjuvant radiotherapy.

The therapeutic approach to ectopic pregnancy (EP) has changed over the last decade. A prerequisite for a differentiated management is an early diagnosis of EP. This can be achieved by transvaginal sonography (TVS). The purpose of this study was to evaluate the accuracy of TVS in the diagnosis of EP. 184 patients with clinically suspected ectopic pregnancy were examined by TVS. In 103 cases suspicion of EP was confirmed, in 81 cases it was ruled out. All cases were evaluated by laparoscopy, D&C, serial HCG determinations or sonographic follow-up in case of an intrauterine pregnancy. Sensitivity of TVS in the diagnosis of EP was 96%, specificity 88%, the positive predictive value was 89%, the negative predictive value was 95%. Four cases with a false negative result at TVS were very early in pregnancy and were subjected to laparoscopy because of persistent high HCG values without demonstration of an intrauterine pregnancy. Five cases of sonographically confirmed ectopic pregnancies were missed by the first laparoscopy. These cases required intervention because of clinical symptoms and had low levels of HCG. TVS has a high diagnostic accuracy in the diagnosis of ectopic pregnancy.

Glucocorticosteroids (GCS) are prerequisite for the induction of surfactant synthesis in the fetal lung. The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) regulates the intracellular concentration of biologically active GCS. In this study we demonstrate the correlation of 11 beta-HSD activity and the GCS-induced surfactant phosphatidylcholine synthesis in organoid cultures of fetal rat lung. In the first series of experiments, [3H]corticosterone (CORT) or [3H]11-dehydrocorticosterone (11-DHC) were added to lung organoid cultures to test 11 beta-HSD activity. We found a low oxidative and a high reductive conversion indicating that in intact cells the equilibrium tends to biologically active GCS. However, in homogenized organoid cultures oxidative outweighed reductive activity. Secondly, the phosphatidylcholine synthesis of organoid cultures was enhanced by preincubation with GCS. CORT, as well as the hormonally inactive 11-DHC, increased the incorporation of [14C]choline into phosphatidylcholine. The effect of the latter was completely inhibited by glycyrrhetinic acid (inhibitor of 11 beta-HSD) indicating that it is caused by a previous conversion of 11-DHC into CORT via 11 beta-HSD. Thirdly, preincubation with GCS also altered 11 beta-HSD activity: dexamethasone or CORT both decreased the oxidative and increased the reductive activity in intact cells, indicating that glucocorticoids increase the rate of their own activation by positive feedback.

The purpose of this retrospective study was to determine the risk factors for the morbidity of the mothers and their fetus in patients with diabetic retinopathy and/or nephropathy with an open family planning. We compared the course of pregnancies, complications as well as the maternal and neonatal morbidity in 76 patients with diabetic retinopathy or nephropathy (White R F) with 85 patients without severe microangiopathy (White C D). We found a correlation between retinopathy progression and hyperglycaemia during the first trimester (p 10 g/d) and unmanageable hypertension or a progression of the retinopathy led to an earlier delivery in 80% of the patients (p < 0.05). A high rate of preterm deliveries (39%) and a frequent occurrence of intrauterine growth retardation's (9%) characterised the fetal outcome. The following examinations for a patient with an open family planning, if diabetes is diagnosed during childhood or the course of the disease is between 10 and 15 years, should be done: Ophthalmological evaluation, control of the renal function, contraceptive advice and an improvement of the metabolic situation. In case of a diabetic nephropathy in combination with hypertonus the patients shoud be warned against pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Only 10% of all gestational diabetic mothers in Germany are diagnosed with the current risk-screening. The elevated perinatal risks in case of an unrecognized or insufficiently treated gestational diabetes remains controversial. The purpose of our study was to determine if the number of recognized cases could be increased by a general screening method, and with intensive medical diagnostics the complication rate reduced. Routine blood glucose samplings during the outpatient care were performed throughout the pregnancy. In case of values over 100 mg/dl a 75 g OGTT was done for an exclusion of gestational diabetes. In case of gestational diabetes the patients were asked to follow a special exercise and diet programme as well as self-blood glucose determinations throughout the day. The amniotic fluid insulin level was of substantial value for the indication of insulin therapy. In 6% of the screened patients a gestational diabetes was diagnosed. There was a significant increase (p < 0.001) of fetal macrosomia and diabetic fetopathy in the group without amniocentesis (n = 22) in comparison to the group with invasive (n = 81). We demand the introduction of a general screening for every pregnant patient. By an intensification of the diagnostic methods as well as by a strictly appropriate therapy it should be possible to reduce the fetal and neonatal complications.

42 pregnancies complicated by severe intrauterine growth retardation (IUGR) were monitored between 1991 and 1992 with the kinetocardiotocogram (K-CTG) comparing them with normal pregnancies of the same gestational age. We evaluated the foetal movements and the heart rate patterns establishing a correlation with pulsed Doppler ultrasound findings. There was a significant reduction of foetal activity in cases of IUGR and pathological Doppler sonography (p < 0.01). The reduction of foetal movements was noticed several days prior to pathological FHR patterns. There was a significant reactivity after vibroacoustical stimulation (VAS) correlating with the Doppler findings. The evaluation of foetal movement patterns in the kinetocardiotocogram proved to be an important complementary method in the monitoring of severe IUGR.

In this study, we have demonstrated for the first time by using U 46619, a stable analogue of thromboxane A2 (TXA2), that TXA2 exerts a cell proliferative effect on HeLa cells which is mediated by specific TXA2 receptors, inasmuch as the cell proliferation could be dose-dependently suppressed by TXA2 receptor antagonist BM 13177. The investigation of the phospholipase C pathway by U 46619 and prostaglandin H2(PGH2) in the presence and absence of BM 13177 in cells with or without pertussis toxin pretreatment, as well as radioligand receptor binding studies, revealed that, in contrast to TXA2 receptors on human platelets, where TXA2 and PGH2 share the same receptor binding sites, HeLa cells possess distinct receptors for TXA2 and PGH2.

We report on a case of unilateral primary fetal hydrothorax leading to nonimmunological fetal hydrops (NIHF). The NIHF was treated successfully by inserting two consecutive intrauterine catheters at 23 weeks gestation. The first catheter was dislocated through the uterine wall to the maternal peritoneal cavity. At 36 weeks gestation, the mother had a spontaneous onset of labor after premature rupture of membranes and a normal vaginal delivery of a healthy infant with good perinatal outcome. Shunting of PFHT has rarely been described up to now. This case report supports observations of previous authors that early shunting of pleural effusions may prevent progression of NIHF as well as postnatal pulmonary hypoplasia. Unexpected perinatal complications of fetus, mother or both should not be neglected.

The modulation of the intracellular glucocorticoidal effect on surfactant synthesis of the fetal lung by the metabolic capacity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) could be an important factor in lung maturation. The kinetic properties of microsomal 11 beta-HSD of the rat lung are characterized with respect to product inhibition, substrate specificity, effect of electrolytes or trace elements, and the dependence of the oxidase reductase (OR) ratio on incubation conditions. With NADP+ product inhibition of the reductase was demonstrated. The most common trace elements and electrolytes exhibited no effect on the activity of 11 beta-HSD. It is shown that the OR ratio was strongly dependent on assay conditions. With optimal assay conditions oxidase activity exceeds reductase activity in adult and fetal rat lung microsomes (OR ratio > 1). Thus, glucocorticoids are mainly metabolized to their inactive forms. The enzyme activity in the adult is about 10 times higher than in the fetal lung. The low enzyme activity in fetal lungs could be the reason why the glucocorticoidal effects on surfactant synthesis are not suppressed despite the predominance of oxidase activity.

One hundred and three intrauterine growth retardation (IUGR) pregnancies were scheduled for pulsed Doppler ultrasound of the common carotid and the umbilical artery, nonstress and contraction stress tests (NST/CST) as well as vibroacoustic stimulation tests (VAST). The last examinations3 days before birth were compared by receiver-operator characteristics: Results of the resistance indices of fetal common carotid/umbilical artery and NST were more predictive of later fetal distress during labour, compared to CST and VAST (p0.001/0.01). Similar results were found for the prediction of low pH and Apgar values, though differences were less pronounced. Our results suggest that stressful examinations should be abolished from mother and fetus in the supervision of IUGR.

A total of 219 women with complicated pregnancies had Doppler assessment of uteroplacental arteries, the umbilical artery, the fetal common carotid artery and the descending thoracic aorta to determine the prognostic value of Doppler examinations to predict the birth of a small-for-gestational-age (SGA) infant with or without fetal distress. Preliminary reproducibility studies showed that the resistance index, pulsatility index and intensity weighted flow velocity had the lowest coefficients of variation. Data on the systolic/diastolic ratio and mean blood flow volume were, therefore, not considered for further evaluation. Measurements were classified according to the time interval of the examination to the delivery of the baby according to the following groupings: 0-14 days, 15-28 days and 29-42 days. For evaluation of the SGA fetus complicated by fetal distress, only measurements within 2 weeks of delivery were analyzed. Significant differences were calculated by considering the area below the receiver operator characteristic (ROC) curves. Only Doppler studies of the uteroplacental arteries (mainly resistance index) were predictive of the later development of the SGA fetus. All fetal parameters showed an increasing improvement in the predictive capacity for an SGA infant, the closer the measurements were made to the time of delivery. This improvement was not observed for uteroplacental vessels. The resistance index of the uteroplacental vessels was significantly higher in SGA pregnancies complicated by fetal distress compared to SGA pregnancies alone. However, ROC analysis revealed that fetal Doppler velocimetry was more strongly related to fetal distress than SGA only. The single best fetal parameter was the mean velocity in the fetal descending thoracic aorta but the velocity ratio of the fetal common carotid artery over the fetal descending thoracic aorta had the highest predictive capacity for the SGA pregnancy complicated by fetal distress.

A rise of DL-methionine in the diet given to DMBA-treated Sprague-Dawley rats had no effect on the induction and growth of mammary adenocarcinoma, but cancer cells were more highly differentiated in the methionine-treated group (grade I and II: 80% and 75% versus 58%).

The coincidence of HELLP syndrome and cortical blindness is an uncommon but very dramatic event, for the patient as well as the obstetrician. This report describes the first case of HELLP-syndrome-associated cortical blindness occuring suddenly in the third stage of labour. There were only modest correlates of cortical blindness in cerebral CT, MRI and angiography findings, but no signs of a posterior leucoencephalopathy syndrome. Mother and baby were discharged from hospital to outpatient care in good health on the 12th day.

A case report is presented on a hepatocellular carcinoma (HCC) during pregnancy, in which a massive increase in alpha-fetoprotein (AFP) was found during a routine screening for neural tube defects in the 17th week of pregnancy. The amniocentesis revealed a normal AFP level in the amniotic fluid. Liver sonography in the 21st week of pregnancy showed a 5-cm tumor, which was interpreted as nodular focal hyperplasia. In the control sonography in the 32nd week of pregnancy, there was growth to 12 cm. The subsequently performed magnetic resonance imaging and fine-needle aspiration led to the diagnosis of a HCC. Delivery was performed in the 34th week of pregnancy by cesarean section, and surgical therapy of the HCC followed.

Cripto-1 (CR-1), a member of the EGF–CFC peptide family, plays an essential role during mesoderm formation in vertebrates as well as in cancer development. Using cDNA gene expression array, Western blot, and indirect immunofluorescence, an increase in vimentin expression was demonstrated in CR-1-transfected human Caski cervical carcinoma cells compared to control vector-transfected cells. In parental Caski cells, recombinant CR-1 induced a dose-dependent increase of vimentin protein expression within 24 h. Since vimentin expression has been demonstrated to correlate with a more aggressive phenotype in human cervical cancer, the migration capacity of CR-1-transfected or CR-1-treated Caski cells was studied in the Boyden chamber assay. Compared to the vector-transfected or untreated Caski cells, CR-1-transfected cells or cells treated with recombinant CR-1 exhibit enhanced migration, both through collagen- and through gelatin-coated membranes. Additionally, CR-1 can function as a chemoattractant for Caski cells. These findings are of biological significance since CR-1 is overexpressed in several types of human carcinomas. The present data demonstrate that CR-1 can increase vimentin expression and modulate migration in human cervical carcinoma cells.

Objective . The aim of this prospective study was to assess erythropoiesis and test for functional iron deficiency in the postpartum period using quantitative red blood cell analysis. Study design . Parameters were determined on admission for delivery and postpartum from 82 obstetric patients at Zurich University Hospital: full blood count, hypochromic and microcytic red cells, reticulocyte count (including subsets), reticulocyte mean corpuscular volume, reticulocyte mean hemoglobin content and reticulocyte mean corpuscular hemoglobin concentration. Results . Microcytic cells increased from 0.9% prepartum to 1.4% on day 42 postpartum; hypochromic cells decreased from 4.3 to 1.9%; reticulocyte mean corpuscular volume decreased from 134 to 125 fl; reticulocyte mean hemoglobin content was unchanged. Conclusion . To our knowledge, this is the first medium scale application of quantitative red blood cell analysis to normal pre- and postpartum women. Our data show no evidence of functional iron deficiency or increased erythropoiesis in the postpartum period.

We report a case of feto-feto-fetal-transfusion-syndrome (FFFTS) in a spontaneous monochorionic triamniotic triplet pregnancy primarily diagnosed at 17 weeks of gestation. During the course of pregnancy, sequentially two triplets appeared as donor. Symptoms of a recipient (polyhydramnios, tricuspid valve insufficiency, and ascites) were present in the third triplet. The second of the donor twins died in utero at 25 weeks. At 27 weeks, a cesarean section was performed mainly due to pre-eclampsia. The first donor triplet developed normally, whereas the recipient showed periventricular leucomalacia and neurological impairment.

We report a case of a patient who had highly elevated levels of α-fetoprotein when she was first examined and a positive acetylcholinesterase test result in amniotic fluid. Despite repeated ultrasonographic screening, pathologic findings were not detected and the holoacardius acephalus twin was not identified. After termination of pregnancy the histopathologic findings demonstrated a twin pregnancy with a holoacardius acephalus. (Am J Obstet Gynecol 1997;177:466-8.)

Le diabete de gestation est la complication metabolique la plus frequente pendant la gestation [1]. Il s'agit d'une perturbation du metabolisme glucidique, qui commence et finit avec la gestation. Malgre une production d'insuline normale ou meme elevee, il se trouve une deficience relative d'insuline a cause d'une resistance peripherique a l'insuline. La decompensation du metabolisme se presente le plus souvent dans la deuxieme moitie de la gestation sous la charge grandissante des hormones anti-insulines. La perturbation du metabolisme est demonstrable dans 2-5% des femmes enceintes [8]. Il suffit pour la plupart une stabilisation dietetique, mais 10-15% des patientes avec le diabete de gestation ont aussi besoin d'une insulinotherapie [21]. Les risques d'un diabete de gestation non-reconnu sont extremement sous-estimes. La cause du danger perinatal augmente en cas d'une perturbation du metabolisme non-reconnue ou traitee insuffisamment est le hyperinsulinisme foetal [8, 22]. Le risque infantil prospectif consiste surtout dans l'augmentation signifiante du risque de diabete, parce que l'hyperinsulinisme foetal mene a une lesion intrauterine et a un mauvais conditionnement de l'appareil insulaire foetal [6]. Selon Weiss [21], la stabilisation et le controle du metabolisme glucidique maternel ne permet pas une evaluation exacte de la secretion foetale d'insuline. C'est plutot l'insuline du liquide amniotique en qualite d'un parametre foetal direct qui est decisive pour etablir une insulinotherapie necessaire a cause d'une indication foetale. Une etude prospective randomisee entre 1987 et 1989 a l'Institut Diabetique de Karlsburg a examine si l'analyse de l'insuline du liquide amniotique reduit l'incidence des foetopathies diabetiques. Une comparaison a ete faite entre l'insulinotherapie et le dosage d'insuline base sur les moyennes des profiles du sucre sanguin maternel et l'insulinotherapie base sur une indication foetale (le contenu d'insuline du liquide amniotique). 123 femmes avec un test de glucotolerance oral pathologique de 50 g ont ete randomisees en differents groupes de traitement. L'instruction des patientes a eu lieu avec un conseil dietetique individuel (35 kcal/kg poids ideal) et des directives pour l'auto-controle du sucre sanguin. Pour l'auto-controle, il a ete necessaire de determiner 5 valeurs par jour et 9 valeurs en 24 heures une fois par semaine. Pendant l'hospitalisation, 3 courbes diurnes et nocturnes de sucre sanguin ont ete determinees au moyen de l'electrode GOD chaque fois avec 9 valeurs de sang capillaire complet, suivi par la calculation de la moyenne du sucre sanguin. Une fois toutes les trois semaines, les patientes ont ete sousmises a des controles des courbes de sucre sanguin et a des determinations de HBAI pendant une courte hospitalisation. De plus, pour evaluer la stabilisation du metabolisme dans les deux groupes de traitement, toutes les valeurs de sucre sanguin determinees par l'electrode GOD ont ete mises en 4 sous-groupes selon leur deviation de l'ordre normoglycemique (3,0-7,9 mmol). Les patientes du groupe A avec une determination d'insuline du liquide amniotique dans la 28e jusqu'a 32e semaine de gestation au moyen du radioimmunoessai modifie apres BESCH [3] ont seulement fait une insulinotherapie en plus du regi- mes si on a determine une valeur de 10 μU/ml dans le liquide amniotique. La dose d'insuline a ete augmentee jusqu'a I unite/kg poids corporel. Apres un intervalle de 2 a 4 semaines, une seconde determination d'insuline du liquide amniotique a ete faite pour controler la reaction foetale au traitement commence et, dans le cas echeant, pour augmenter la dose d'insuline. Dans le groupe B, une insulinotherapie etait indiquee si la moyenne

Unter einer normoglykamischen Stoffwechseleinstellung wahrend der gesamten Dauer der Schwangerschaft ist es heute moglich geworden, das die meisten Diabetikerinnen gesunde Kinder zur Welt bringen, ohne das sich ihre eigene Prognose verschlechtert. Das gilt aber nicht fur Frauen mit fortgeschrittenem diabetischem Spatsyndrom, da eine irreversible Progredienz der Schadigung moglich ist [1–3]. Ziel der Untersuchung war die Erarbeitung von Risikofaktoren, die die mutterliche und kindliche Morbiditat in hohem Mase beeinflussen und die in die individuelle Beratung bei bestehendem Kinderwunsches einbezogen werden sollten.

Cytokeratin antibodies have been widely used for the identification of trophoblast cells in the placental bed, following their invasion from the developing conceptus. Their identification centres upon the expression of cytokeratin in epithelial cells, from which trophoblast cells are derived. Our recent observations indicate that this strict relationship may be more complex than was thought. Cryostat and paraffin sections of human decidua and myometrium, taken from the placental bed and the uterotomy cut, were examined immunocytochemically for cytokeratins using ten antibody clones selected to identify different cytokeratin proteins and antigenic epitopes. Biopsy specimens were obtained from normal and pathological pregnancies (pre-eclampsia, fetal retardation, amnioninfection, hysterorrhexis, placenta praevia) at the time of caesarean section (26-41 weeks of pregnancy). Antibodies against nine clones, CAM 5.2, MNF 116, AE1/AE3, CK5, KS-B17.2, CY-90, M20, E3, and 34 beta E12 identified, as expected, syncytial giant cells and mononuclear trophoblasts within the placental bed and glandular epithelial cells throughout the uterus. In addition, they stained numerous fusiform cells that were classified by established criteria to represent smooth muscle cells, both within blood vessels and myometrium. No staining differences were observed between normal and pathological disorders. These results indicate that cytokeratin antibodies CAM 5.2, MNF 116 and AE1/AE3, and other antibodies targeting proteins 8 and 18, cross-react with epitopes expressed in cells other than giant trophoblastic cells and mononuclear trophoblasts in the uterus and, thus, caution has to be used when such antibodies are used for the diagnostic characterization of tissues related to the placental bed.

Postterm pregnancies of more than 290 completed gestational days (n = 110) were simultaneously supervised after admission by pulsed Doppler ultrasound of the common carotid and the umbilical arteries, nonstress and contraction stress tests (NST/CST) and vibroacoustic stimulation tests (VAST). The results of these tests were blinded for the clinicians. Further decision making was based mainly on fetal heart rate (FHR) monitoring. The prognostic value of tests performed3 days before birth predicting fetal distress, low Apgar and pH values in the umbilical artery were compared by receiver operator characteristics. Results of the NSTs and fetal Doppler measurements of the ratio of resistance indices of common carotid/umbilical artery were more predictive of later fetal distress than both, VAST and CST (p0.01, p0.05, respectively). There were no significant differences in the prediction of low Apgar values. NST was the only significant test for predicting a low pH in the umbilical artery immediately after birth compared to the other examinations (p0.05). The results suggest that even in prolonged pregnancies VAST and CST might be released from routine supervision.

Neugeborene sind immunologisch unreif. Sie verfugen im Vergleich zum Erwachsenen uber einen geringeren Immunglobulinspiegel, der sich zum grosen Teil aus mutterlichen IgF rekrutiert und vom ersten Lebenstag an vorerst kontinuierlich abfallt (3). Einer der wichtigsten Faktoren der ubertragenen spezifischen, als auch der angeborenen unspezifischen Immunitat des Neugeborenen ist das Komplementsystem. Die Aktivierung des Komplementsystems erfolgt kaskadenartig. Es wird ein klassischer von einem alternativen Aktivierungsweg unterschieden (2).

Die pranatale Behandlung mit Glukokortikoiden zur Prophylaxe des neonatalen Atem- notsyndroms (RDS) kann aufgrund von zahlreichen Studien, die die Wirksamkeit bewiesen haben, als etablierte Behandlungsmethode angesehen werden. Knitza (1), der 1989 an 348 deutschen Kliniken eine Umfrage zum Stand der medikamentosen RDS- Prophylaxe durchfuhrte, konnte zeigen, das 98% der Kliniken eine Prophylaxe routinemasig durchfuhren.

Der epidermale Wachstumsfaktor (EGF) wurde erstmals 1960 von Cohen beschrieben, wobei er zwei Jahre spater dessen stimulierenden Effekt auf Proliferation und Differenzierung der Epidermis bei Mausen nachweisen konnte [2]. Taylor stellte 1972 die Stimulation der RNA-und Proteinsynthese und Formation der Ribosomen durch EGF fest. EGF stimulierte hier die Proliferation und Keratinisation epidermaler Gewebe in vivo und in vitro [4]. 1979 beobachtete Catterton den Effekt von EGF auf die Lungenreifung fetaler Hasen. EGF induzierte eine beschleunigte Lungenreifung, wobei elektronenmikroskopische Studien einen starken Anstieg der Typ-Ii-Alveolarzellen und der intrazellularen lamellar bodies zeigten [1]. Johnson untersuchte 1989 Ontogenese und Verteilung des EGF-Rezeptors in der fetalen Lunge; der Rezeptor konnte im Epithel der Luftwege am Ende des 1.Trimesters nachgewiesen werden [3].

Zur Bestimmung der fetalen Lungenreife stehen biochemische und biophysikalische Methoden zur Verfugung, die direkt oder indirekt den Phospholipidgehalt des Fruchtwassers messen (1).

Die externe Tokographie ist die nichtinvasive Methode, mit der die Uterusaktivitat in der Schwangerschaft erfast werden kann. Zusatzlich zur Wehenfrequenz und Dauer der einzelnen Wehe bilden sich die Konsistenz der Uteruswand und deren Anderungen in der Wehe einnerseits sowie die Form- und Langenanderung des Uterus wahrend der Wehe anderseits als Basislinie und Kontaktionsamplitude auf dem Tokogramm ab. Wegen der grosen inter- und intraindividuellen Variabilitat der in der klinischen Routine aufgezeichneten Tokogramme wurde dieses Instrument bislang nicht zur quantitativen Messung von Uterusaktivitaten eingesetzt.

Endogene und exogene Glukokortikoide spielen bei der prapartalen Lungenreifeinduktion eine wichtige physiologische und therapeutische Rolle. Die 11 s-Hydroxysteroid Dehydrogenase (11 s-HDS) deaktiviert mit ihrer oxidativen Komponente (Oxidase), b.z.w. aktiviert mit ihrer reduktiven Komponente (Reduktase) Glukokortikoide an der fetalen Lunge und Leber (Vergleichsorgan).

Die antenatale Gabe von Glukokortikoiden zur Pravention des Atemnotsyndroms ist heute ein etabliertes Verfahren. In unserer Klinik applizierten wir 4 x 4 mg Betamethason innerhalb von 48 Stunden, das entspricht je nach Korpergewicht einer Gesamtdosis von 0,2 - 0,3 mg/kg Korpergewicht. Die Effektivitat der Glukokortikoidpraven- tion, so die gangige Auffassung, kann durch hohere Dosierung nicht gesteigert werden. Wir stellen uns die Frage, ob diese klinische Auffassung eine Entsprechung in der pharmakologischen Beeinflussung der Surfactant-Phopholipidbiosynthese hat. Phos- phatidylcholin (PhC) und Phospatidylglycerol (PhG) spielen fur die Wirksamkeit des Surfactant eine zentrale Rolle. Am Tiermodell der fetalen Ratte untersuchten wir darum den Einflus von Dexamethason in vivo auf die Konzentration der beiden Phospho- lipide sowie auf Enzyme der PhC- und PhG-Synthese

Zur Prophylaxe des Atemnotsyndroms wird seit Jahren nach Alternativen und zusatzlichen Therapieformen zur herkommlichen Glukokortikoidtherapie gesucht. Die Wirkung von Aminophyllin auf die biochemischen Mechanismen der fetalen Lungenreife sind bisher nicht hinreichend geklart. Wir benutzten das Tiermodell der fetalen Ratte, um die Wirkung von Aminophyllin auf die Enzyme der Synthese des Surfaktantphos- pholipids Phosphatidylcholin zu untersuchen.

Pulsed Doppler examinations were performed in 143 risk pregnancies. The resistance index (RI) values of the uteroplacental vessels and umbilical artery on the last examination before delivery were correlated to specific patterns of morphological placental findings. The sensitivity and specificity of Doppler blood flow velocity wave forms to predict placental disease as well as the significant relationships were calculated. Impaired uteroplacental perfusion is correlated with: disturbances in growth, such as reduced weight and reduced basal area (p0.005, p0.05); disturbances in villous maturation, such as prematurity or a reduction in intermediate sized villi (p0.05, p0.01), and circulation disorders, such as acute or chronic infarcts (p0.05), villous fibrosis (p0.005) or microfibrin deposits (p0.05). Villous immaturity was not correlated to either pathological utero- or fetoplacental blood flow. Except for acute infarcts, all these findings as well as endangiopathy of truncal arteries are also combined with high RI values in umbilical arteries (p0.005) possibly reflecting the 'down-stream impedance' of the fetoplacental circulation.

Die heute zur Therapie des Atemnotsyndroms (Surfactantmangelsyndrom) zur Verfugung stehenden pranatal, praventiv wirksamen therapeutischen Ansatze sind in ihrer Wirksamkeit nicht befriedigend und in ihrem Wirkmechanismus nicht ausreichend geklart. Zur Erforschung der pharmokologischen Regelmechanismen der Surfactant-Phospholipid-Biosynthese untersuchten wir die Dexamethasonwirkung auf die Synthese von Dipalmitoyl-Lecithin (DPL). Dazu wurden drei Enzyme, die Cholin-Phosphotransferase (CPT), die Lysolecithin-Acyltransferase (LAT) sowie die Phospholipase A2 (PA2) in der fetalen Rattenlunge und Leber quantifiziert (Abb. 1).

Nach wie vor nimmt das Atemnotsyndrom (RDS) des Neugeborenen eine zentrale Stellung unter den unreifebedingten Erkrankungen des Neugeborenen ein. Im Rahmen der Pravention werden hauptsachlich Analysemethoden verwendet, die den quantitativen oder qualitativen Phospholipidgehalt im Fruchtwasser messen. Verlast man sich bei der Lungenreifebestimmung auf nur eine Methode, treten sehr haufig falsch positive Werte auf, d.h. das Kind entwickelt kein RDS, obwohl der Test Unreife anzeigt.

The neonatal respiratory distress syndrome (RDS), which occurs almost exclusively in premature infants, is a disease caused by a surfactant deficiency. The chances of surviving the disease have markedly improved in the last decade. With the introduction of the L/S ratio, which is now an established method, it has been possible for the first time to predict RDS reliably. Widespread application of this method is limited due to the fact that it is relatively staff- and time-consuming.

Antenatal glucocorticoid administration in order to prevent neonatal respiratory distress syndrome (RDS) has been an established regimen for over 15 years [1]. Use of such therapy is indicated in all cases in which premature delivery is expected or medical reasons require it [2]. Nevertheless, this treatment is only effective to a limited extent and, as before, a considerable number of premature children die of pulmonary complications. Therefore every obstetric unit has to re-evaluate the data in this particular field from time to time.

Eine gezielte Chemotherapie bei malignen Tumoren kann nur durch eine pratherapeutische Chemosensibilitatstestung erreicht werden. Bisher angewandte Methoden wie der HTCA haben sich als Routine verfahren nicht durchgesetzt. Wir haben daher einen fur gynakologische Karzinome modifizierten Dye exclusion-Test aufbauend auf Arbeiten von Weisenthal, entwickelt (Weisenthal et al. 1983). Als Kriterium der Zytostatikawirkung wird das Ausmas einer letalen Wirkung an der gesamten kultivierten Tumorzellpopulation zytomorphologisch erfast.

Gastric cancer is unusual during pregnancy. The diagnosis may be delayed because specific symptoms are similar to typical pregnancy associated complaints. Our therapeutic management with palliative chemotherapy and later gastrectomy differs from other known cases, where surgical resection has been the treatment of choice. Surgery appears to have no influence on the prognosis of gastric cancer patients with hepatic metastases.

Mit dem KCTG wird das antepartale Monitoring von Hochrisikoschwangerschaften verbessert. Eine normale fetale Basisaktivitat und Reaktivitat weisen auf eine kompensatorische Reserve des Feten hin, wahrend eine zunehmende Einschrankung Zeichen einer beginnenden Dekompensation sein kann.

This study was performed to determine the prognostic significance and the biological function of the differentiation associated structure protein keratin 18 (K18) in patients with breast carcinoma. Materials and Methods Paraffin sections from 134 patients with breast carcinoma were examined for the expression of K18 immunohistochemical. The intensity of the expression was compared with clinical follow-up data over 8 years. In addition K18 expression in different human cell lines of breast carcinomas with well defined metastatic behavior were investigated. Results A marked positive staining was observed in 22 (16.4%) women. Mortality rate in the positive group was 4.5% in comparison to 44.6% in the negative group (P Conclusion K18 expression was found to be an independent and significant predictor for disease-free survival whereas the down-regulation of this protein seems to favor early metastatic spread.

In a retrospective study of breast cancer patients, the disease course was examined in 137 pre- and postmenopausal patients with a local recurrence. Here especially the dependency of a recurrence-free interval on biological parameters of the primary tumor was investigated. It was found that in 23% of the cases the local recurrence expressed tumor generalization with the simultaneous occurrence of distant metastases. The average recurrence-free interval was 4 years, whereby more than half of the recurrences took place in the first two postoperative years. A statistically significant relationship to the recurrence-free interval could be demonstrated for the following parameters: Primary tumor size ( P = 0.0003), node status ( P = 0.0006) as well as the number ( P = 0.0002) and level ( P = 0.00001) of metastatically involved lymph nodes. The immunohistochemical estrogen and progesterone receptors ( P = 0.0005) and the growth factor obtained with the monoclonal antibody Ki67 ( P = 0.0005) also significantly correlated with the length of the recurrencefree interval. The type of operative primary therapy did not have an effect on recurrence-free survival. However, adjuvant therapy had a decisive influence—patients developed a local recurrence significantly later after adjuvant radiotherapy ( P = 0.00001).