[Uterine myomatosis with senile hematometra in a 101-year-old patient]. / Uterus myomatosus mit seniler Hämatometra bei einer 101-jährigen Patientin.

A 101-year-old patient presented with uterine myomatosis and bleeding associated with a large hematometra. An abdominal hysterectomy with adnexectomy was performed following an in-depth consultation with the patient and her daughter. The patient was discharged on the 12(th) postoperative day after a complication-free course. This case report demonstrates not only the current possibilities in the gynecological treatment of very old patients but also the hidden reserves in the gynecological care ot these women.

Cripto-1-induced increase in vimentin expression is associated with enhanced migration of human Caski cervical carcinoma cells.

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.

Expression and function of EGF-related peptides and their receptors in gynecological cancer--from basic science to therapy.

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.

Kinetic studies on rabbit liver glucocorticoid 5alpha-reductase.

The serum concentration of active glucocorticosteroids depends not only on adrenal synthesis but also on enzymatic activation of 11-dehydro-glucocorticoids in the liver by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). In order to define the respective involvement of other regulative enzymes in the metabolism of 11-dehydro-glucocorticoids in the liver, the objective of this study was to evaluate the kinetic behavior of NADPH:delta 4-3-ketosteroid-5alpha-reductase (5alpha-reductase, EC 1.3.99.5). The interrelations to liver 11beta-HSD1 will be discussed. The kinetic properties of 5alpha-reductase of the rabbit liver were measured by a radioenzymatic assay and characterized with respect to protein-, substrate-, cosubstrate-, and pH-dependence. Michaelis-Menten enzyme kinetic parameters (Km and Vmax) were obtained for the formation of 5alpha-reduced 11-dehydrocorticosterone and corticosterone metabolites. We found that both 11-dehydrocorticosterone (Km 4.2 x 10(-6) mol/l, Vmax 2,600 pmol x min(-1) x mg(-1)) and corticosterone (Km 0.5 x 10(-6) mol/l, Vmax 38 pmol x min(-1) x mg(-1)) exhibit a high affinity to 5alpha-reductase. With respect to cosubstrate-, pH-dependence and finasteride inhibition, it is likely that 11-dehydrocorticosterone metabolism is primarily controlled by isoenzyme 5alpha-reductase type 1. This study shows that the deactivation of GCS especially of 11-dehydro-glucocorticoids via 5alpha-reductase is an important metabolic pathway in the liver. The metabolic activation of GCS by 11beta-HSD could possibly lead to an excess of GCS in the hepatocytes. Due to 5alpha-reductase activity this excess can be limited - on the level of CORT as well as of 11-DHC.

Effect of dexamethasone, triiodothyronine and dimethyl-isopropyl-thyronine on lung maturation of the fetal rat lung.

Our purpose was to elucidate why clinical studies have up to now failed to demonstrate a positive effect of TRH combined with glucocorticosteroids on fetal lung maturity. Morphological and biochemical lung maturation were determined by electron microscopy, choline incorporation, and surfactant-protein-A m-RNA synthesis in rat lung organoid cultures after exposure with a series of concentrations of dexamethasone, triiodothyronine, and dimethyl-isopropyl-thyronine. Thyroid hormones improved morphogenesis of lung histotypic structures but had a negative effect on surfactant synthesis whereas glucocorticosteroids had a positive effect on the surfactant synthesis but a negative effect on morphogenesis. The combination of both substances even had the most negative effect on morphogenesis. Since morphogenesis of lung histotypic structures is prerequisite for surfactant synthesis and secretion, we hypothesize that a sequential treatment of thyroid hormones to improve morphogenesis followed by the application of glucocorticosteroids might be an option to improve neonatal lung function.

Cripto-1 induces phosphatidylinositol 3'-kinase-dependent phosphorylation of AKT and glycogen synthase kinase 3beta in human cervical carcinoma cells.

Cripto-1 (CR-1), a member of the epidermal growth factor-CFC peptide family, activates the ras/raf/mitogen-activated protein/extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. In the present study, the role of CR-1 in the phosphatidylinositol 3'-kinase (PI3K)/AKT (protein kinase B)/glycogen synthase kinase 3beta (GSK-3beta)-dependent signaling pathway was evaluated in human SiHa cervical carcinoma cells. Our data demonstrate that CR-1 can enhance the tyrosine phosphorylation of the p85 regulatory subunit of PI3K and transiently induce the phosphorylation of AKT in a time- and dose-dependent manner. In addition, CR-1 was found to induce the phosphorylation of GSK-3beta. Phosphorylation of AKT and GSK-3beta by CR-1 can be blocked by LY294002, a specific inhibitor of PI3K, thus leading to apoptosis. Finally, the apoptotic effect of LY294002 can be partially rescued by exogenous CR-1. In summary, our data suggest that human CR-1 may function as a survival factor through a PI3K-dependent signaling pathway involving AKT and GSK-3beta.

Therapy of metastatic breast cancer with humanized antibodies against the HER2 receptor protein.

The HER2 protein, a member of the epidermal growth factor family, is encoded by the protooncogene c-erbB-2. Its overexpression, occurring in approximately one-third of all breast carcinomas, is associated with a poor prognosis. A humanized mouse antibody against HER2 has been developed by genetic engineering. Here an unspecific human IgG was connected to the recognizing mouse IgG fragment. The allergization typical for allogeneic antibodies does not take place in this context. The effectiveness of this antibody has been confirmed by two international prospective phase III trials that tested it alone and combined with chemotherapy. Both modes of application increased the response rates and the time to progression. Side-effects were rare except for a high rate of cardiac dysfunction when the antibody was combined with anthracyclines. The effectiveness and negligible side-effects of the chimeric antibody against HER2 (Herceptin) render it a valuable tool in the treatment of breast cancer.

Acute onset of blindness during labor: report of a case of transient cortical blindness in association with HELLP syndrome.

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.

Effect of epidermal growth factor on enzymes of phospholipid biosynthesis in lung and liver of fetal rat in vivo and in vitro.

Epidermal growth factor (EGF), a mitogenic polypeptide that binds to cell surface receptors, is an important regulator of cell differentiation and fetal lung surfactant synthesis, and may be used as a potential novel therapeutic agent in prematurity. Nevertheless, the distinct role in lung development and its mechanisms of action are not well understood. We investigated in vivo the systemic effect of intrafetally administered EGF (200 ng/g fetal body weight) and maternally administered dexamethasone (DEXA; 0.2 and 2.0mg/kg maternal body weight) on the activity of important enzymes of the phospholipid synthesis in the fetal rat lung and liver: choline kinase (EC 2.7.1.32), cholinephosphate cytidyltransferase (EC 2.7.7.15), choline phosphotransferase (EC 2.7.8.2), lysolecithin acyltransferase (EC 2.3.1.23) and glycerolphosphate phosphatidyltransferase (EC 2.7.8.5). Additionally, in vivo and in vitro effects of DEXA on EGF receptor synthesis, and the effects of EGF on protein content and morphogenesis of the fetal rat lung organoid culture, were evaluated. Whereas DEXA induced the activity of all investigated enzymes of phospholipid synthesis and increased EGF receptor synthesis, EGF has no effects on the enzymes, either in vivo or in vitro. EGF enhanced protein synthesis and morphogenesis in vitro. With respect to our data and the literature, we hypothesize that DEXA and EGF may act on different cellular sides. Whereas glucocorticoids induce surfactant phospholipid synthesis, EGF should be more involved in cell proliferation and morphogenesis.

Hyperemesis in late pregnancy--should we think of cancer? A case report.

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.

Stage I primary malignant mixed müllerian tumor of the fallopian tube. Report of a case with five-year survival after minimal surgery without adjuvant treatment.

BACKGROUND: Sarcomas of the fallopian tube are rarities in gynecologic oncology, consisting of < 1% of all genital sarcomas. CASE: A 70-year-old woman with a stage I malignant mixed müllerian tumor (MMMT) (International Federation of Gynecology and Obstetrics classification of fallopian tube carcinomas) did not undergo radical surgery or adjuvant treatment because of the patient's refusal of them. The patient underwent only abdominal hysterectomy with bilateral salpingo-oophorectomy. She was discharged feeling well and without abnormal clinical findings. Sixty months after primary surgery there were no signs of recurrence. CONCLUSION: This case suggests the possibility of a good prognosis in early-stage MMMT, especially if there is no deep infiltration of the fallopian tube muscle layer or lymphatic permeation and if the peritoneal cytology is negative. The important feature of this report is the five year disease-free survival after nonradical surgery for prognostically favorable MMMT.

Prenatal diagnosis of a lethal multiple pterygium syndrome type II. Case report.

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.

Inhibition of 11 beta-hydroxysteroid dehydrogenase activity enhances the antiproliferative effect of glucocorticosteroids on MCF-7 and ZR-75-1 breast cancer cells.

This in vitro study on MCF-7 and ZR-75-1 breast cancer cells showed that the antiproliferative action of glucocorticosteroids (GCS) on breast cancer cells is weakened by a high oxidative activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD; EC 1.1.1.146): both endogenic as well as synthetic GCS (dexamethasone, prednisolone) were metabolised to hormonally inactive 11-dehydro metabolites. This enzymatic shield protected the breast cancer cells from the antiproliferative action of GCS. Continuous exposure of breast cancer cells to GCS resulted in enhanced 11 beta-HSD activity. The intracellular GCS concentration was further reduced by this feedback and thus the antiproliferative effect was additionally weakened. These mechanisms of GCS deactivation could be influenced by inhibiting 11 beta-HSD with the liquorice compound glycyrrhetinic acid (GLY). In MCF-7 and ZR-75-1 cultures the antiproliferative effect of GCS was significantly increased by GLY.

Diagnostic dilemma with elevated level of alpha-fetoprotein in an undiagnosed twin pregnancy with a small discordant holoacardius acephalus.

We report a case of a patient who had highly elevated levels of alpha-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.

Interleukin-8 in urine: a new diagnostic parameter for intra-amniotic infection after premature rupture of the membranes.

Interleukin-8 (IL-8), a 72 amino acid peptide secreted by cells of the immune system and of the amnion, chorion and decidua, was measured in women in late pregnancy. IL-8 was detected in the urine of 91 of 104 women with premature rupture of the fetal membranes, with values exceeding 1000 ng/L in cases of severe intra-amniotic infection. Women with urinary tract infections were excluded. The routine measurement of IL-8 in urine, together with C-reactive protein in serum, thus provides a low risk and technically simple approach to the assessment of intra-amniotic infection.

Hypokalaemia in pregnant women treated with the beta 2-mimetic drug fenoterol--a concentration and time dependent effect.

The effect of tocolytic treatment with fenoterol on plasma potassium concentrations was studied in 83 pregnant women on intravenous tocolytic therapy. Plasma concentrations of fenoterol and potassium were measured simultaneously, the time interval between initiation of therapy and taking the blood sample varying from 2 hours to 100 days. In a subset of 13 patients this blood sample was taken after two hours of therapy and pretreatment potassium concentrations were measured also. Pretreatment potassium concentrations were normal in these 13 patients and declined to 2.88 mmol/L (median) fenoterol concentrations being 320 ng/L through 1164 ng/L. Potassium concentrations measured later than 24 hours after initiation of therapy were all in the normal range corresponding fenoterol concentrations varying from 200 ng/L to 2504 ng/L. The multivariate statistical model for the description of all data showed that the duration of treatment was the only variable which explained the data to a significant extent. This might indicate that tolerance to the potassium lowering effect of fenoterol had developed within 24 hours after initiation of therapy. In the subset of 13 patients pretreatment potassium concentrations were found to be more important in explaining potassium concentrations than fenoterol concentrations at two hours. As we did not observe any adverse events in patients with low potassium concentrations and potassium concentrations were normal within 24 hours, we conclude that hypokalaemia due to fenoterol in the treatment of premature labor is not of clinical concern.

[Notch in the umbilical artery Doppler profile in umbilical cord compression in a twin]. / Der Notch im Nabelarteriendopplerprofil bei Nabelschnurkompression eines Zwillings.

Monoamniotic twins have a mortality rate of up to 50%, mainly due to umbilical cord accidents, e.g. true knots. Because of the rarity of monoamniotic twin gestation, few data are presently available on the optimal management of these gestations. Some authors recommend delivery at 32 weeks of gestation, while others state that the risk of cord accidents declines with advancing gestational age, thus questioning the usefulness of routine delivery at 32 weeks. It is possible nowadays to obtain an impression of the fetal blood supply by Doppler sonography. In our case, Doppler sonographic evaluation showed a notch in the umbilical artery in the twin, who later developed a pathological CTG requiring delivery at 28 weeks of gestation. Both fetuses are liveborn and developed normally. Our case shows that a notch in the umbilical artery could be an indication of umbilical cord compression and that attention should be paid to it in monoamniotic twin gestation.

Feto-feto-fetal triplet transfusion syndrome (FFFTTS).

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.

Prospective study of the atopy preventive effect of maternal avoidance of milk and eggs during pregnancy and lactation.

UNLABELLED: The preventive effect of maternal avoidance of cow's milk and eggs on the development of atopic dermatitis and sensitization to food allergens was studied in a prospective trial with families at high risk for atopy, intervention included encouraging exclusive breast feeding for at least 3 months and delaying the controlled introduction of solid foods. In addition, one group received a maternal diet with the complete avoidance of milk and eggs in the last trimester of pregnancy and during the period of exclusive breast feeding, another group had the same diet starting after delivery, and mothers of the third group had no dietary restrictions. The period prevalences of atopic dermatitis as well as the rates of specific sensitization to eggs and milk at 6 and 12 months were not significantly different between groups. We were unable to demonstrate a significant preventive effect of maternal diet. CONCLUSION: While breast feeding should be promoted for children at risk for atopy, mothers can be encouraged to stay on normal diet during pregnancy and the breast feeding period.

[Insulin-like-growth-factor-binding-protein 1 (IGFBP-1) and fetal fibronectin in diagnosis of premature rupture of fetal membranes]. / Insulin like growth factor binding protein 1 (IGFBP-1) und fetales Fibronectin in der Diagnostik eines vorzeitigen Blasensprunges.

The diagnosis of a premature rupture of membranes presents no problem in the vast majority of cases. However, a reliable diagnosis is clinically not possible in about 10%. Most methods available lack the necessary sensitivity and specificity. Since the clinical consequences of a false diagnosis are considerable (overtreatment for false-positive and risk of infection for false-negative results), it is essential to clinically establish new, minimally invasive methods with higher predictive powers. In the present study we compared: the AMNI Check for detection of insulin-like growth-factor binding protein 1 (IGFBP-1); a membrane immunoassay for detection of fetal fibronectin (fFn); pH indicator paper; and, to verify a rupture of membranes in unclear cases, amniocentesis with installation of indigo carmine. The examination was performed in a group of 75 patients, 35 with and 40 without rupture of the membranes. The best results were obtained for the AMNI Check (sensitivity and negative correctness 100%, specificity and positive correctness 83%). With the same sensitivity and negative correctness, the membrane immunoassay for fFn achieved a specificity of 70% and a positive correctness of 74%. The pH indicator paper had the lowest predictive value (sensitivity 94%, negative correctness 93%, specificity 63%, positive correctness 69%). Both the AMNI Check and the test for detection of fetal fibronectin can be recommended for reliable exclusion of premature rupture of membranes. Amniocentesis should however be performed in uncertain cases with a positive test result. Nevertheless, considerable reduction of this invasive method is possible.