Doppler sonography of the uterine and the cubital arteries in normal pregnancies, preeclampsia and intrauterine growth restriction: evidence for a systemic vessel involvement

Aims: The decrease in uterine resistance during normal pregnancy is known to be related to invading trophoblast cells which derive from placental tissue. Uterine and peripheral resistance is elevated in preeclampsia. The aim of the present study was to prospectively examine uterine and peripheral resistance in pregnancies complicated by preeclampsia (PE), fetal intrauterine growth restriction (IUGR) and pregnancy induced hypertension (PIH). Methods: Sixty-seven women with normal pregnancies, 17 with PE, 12 with IUGR underwent Doppler sonographic investigation of the uterine and the cubital arteries. The Pulsatility Index (PI) was calculated for each vessel. Statistical analysis was performed and a P-value < 0.05 was considered significant. Results: Patients with preeclampsia and IUGR showed a significant higher resistance at the placental (mean PI 1.267 and 1.063), nonplacental (mean PI 1.631 and 1.124) and cubital artery (mean PI 3,777 and 3.995) compared to the normal pregnancy group (mean PI 0.678; 0.859 and 2.95 respectively). Mean birth weight in the PE group was 1409 g, in the IUGR group 1649 g and 3419 g in the normal pregnancy group. Conclusions: Pregnancies with IUGR are associated with elevated peripheral resistance in the maternal arterial system as seen in pregnancies with preeclampsia. Our findings encourage to further investigate the maternal vascular system in high risk pregnancies

Node-positive breast cancer: Which are the best chemotherapy regimens?

Breast cancer-associated mortality has been significantly reduced since the 1990s, mainly because of early diagnosis and systemic therapeutic interventions. All three therapy components-cytostatic therapy, endocrine therapy and targeted antibody therapy-are at present necessary tools for the curative treatment of primary breast cancer. This article reviews the evidence base for the use of various chemotherapy schedules in patients with primary, node-positive breast cancer, including schedules in combination with targeted HER2/neu therapy

Is induced abortion a risk factor in subsequent pregnancy?

Objective: To determine whether a history of terminations of pregnancy influences subsequent pregnancies in terms of pregnancy risks, prematurity and neonatal biometrics. Patients and methods: Based on the perinatal statistics of eight German federal states, data of 247,593 primiparous women with singleton pregnancies born between 1998 and 2000 were analyzed. The control group consisted of primiparous women without previous induced abortions. Maternal age was adjusted for. Results: There was an overall trend towards an increased rate of preterm delivery at <= 36 weeks' gestation and early preterm delivery at <= 31 weeks' gestation in women who had previous pregnancy terminations. For the cohort of 28-30 years, the observed rates of prematurity in women with one and with >= 2 previous induced abortions were 7.8% and 8.5%, respectively, compared to 6.5% in the control population (P=0.015). Preceding terminations of pregnancy did not alter the rate of small-for-gestational-age newborns. Psychosocial stress and symptoms associated with prematurity such as cervical incompetence and vaginal bleeding before and after 28 weeks of gestation occurred more frequently in women with previous induced abortion compared to the control group (P<0.0001). Conclusion: The rate of preterm births increases with the number of preceding abortions. Similarly, symptoms associated with prematurity are more common. The rate of small-for-gestational-age newborns was not affected by preceding terminations of pregnancy

Effects of Progesterone and Its Antagonist Mifepristone on Progesterone Receptor A Expression in Human Umbilical Vein Endothelial Cells

Effects of female steroid hormones on endothelial cells are gaining increased importance due to several studies on the effects of hormonal treatment on cardiovascular risk. Recent data argue for an improvement of endothelium-derived relaxation and impaired vascular contraction by estradiol, whereas progesterone and testosterone might entail contrary effects. So far, gestagenic influence on endothelial cell physiology is poorly understood. Human umbilical vein endothelial cells (HUVECs) exposed to the female sex hormones estradiol and progesterone show expression of estrogen receptor-beta (ER beta) and progesterone receptor A (PR-A), and are negative for ER alpha and PR-B. The aim of this study was to analyze the expression and stimulation of PR-A and -B in HUVECs after stimulation with progesterone and PR antagonists that are commercially available. PR-B expression or upregulation was abrogated after application of progesterone or antagonists to HUVECs. Expression of PR-A could be significantly upregulated with progesterone and mifepristone. Unexpectedly, stimulation with the progesterone antagonist RU486 (mifepristone) was accomplished by an upregulation of PR-A expression in our study. We conclude that gestagenic effects on HUVECs independent of modulators are mediated via the PR-A. Copyright (C) 2009 S. Karger AG, Base

Evaluation of a Novel Anti-Mucin 1 (MUC1) Antibody (PankoMab) as a Potential Diagnostic Tool in Human Ductal Breast Cancer; Comparison with Two Established Antibodies

Aim: PankoMab is a novel antibody that recognizes a tumor-specific epitope of Mucin 1 (MUC1). The aim of this study was the evaluation of PankoMab as a potential diagnostic tool and its comparison with two established antibodies against MUC1 in human ductal breast cancer. Materials and Methods: Breast carcinomas were obtained from 82 patients. MUC1 expression and hormone receptor status were determined by immunohistochemistry of paraffin-embedded material. Results: PankoMab revealed strong correlation to hormone receptor expression. DF3 showed no correlation with grading, lymph node involvement and/or estrogen receptor (ER) expression. In the subgroup of lymph node-positive and ER-negative tumors, we saw a significantly reduced DF3 staining in G3 tumors compared to G2 tumors. VU-4-H5 showed increased staining intensity in correlation with increased grading. In addition, we also identified a significantly higher expression of the VU-4-H5 epitope in lymph node-positive carcinomas compared to carcinomas without lymph node involvement. Conclusion: PankoMab revealed strong correlation to hormone receptor expression in ductal carcinoma of the breast. VU-4-H5 showed increased staining intensity in correlation with increased grading and lymph node involvement. PankoMab and VU-4-H5 staining could be a useful combination in ductal breast cancer prognosis by immunohistochemistry

Risiko in Banken

Ab 2007 ging von den USA eine Bankenkrise aus, die globale Auswirkungen hatte, z.B. den finanziellen (Beinahe-)Zusammenbruch ganzer Staaten wie Griechenland. Die dadurch hervorgerufene Arbeitslosigkeit und Armut führt dazu, dass viele Menschen die Konsequenzen abstrakter Vorgänge der Finanzwelt in ihrem Alltag noch immer sehr konkret spüren. Nicht einmal zehn Jahre nach der Krise sind die Gewinne der Banken größer als jemals zuvor, und sowohl die Verantwortlichen in Politik als auch Wirtschaft versichern, dass verbesserte Verfahren zum Management von Risiken das Entstehen neuer, vergleichbarer Krisen unmöglich gemacht machen. Aber wie konnte diese Krise überhaupt entstehen, wenn doch BankmanagerInnen schon immer das Beherrschen von Risiken als ihre Kernkompetenz angeben? Diese Studie ist das Ergebnis langjähriger teilnehmender Beobachtung in Banken und hat das Ziel, die komplexen Zusammenhänge, die sich hinter dem Begriff Risiko in Banken verbergen, mit ethnologischem Blick zu dekonstruieren. Ausgehend von der Betrachtung der diskursiven Konstruktion des Risikobegriffs geht es um die Beobachtung, wie die in Banken arbeitenden Menschen in ihrem Berufsalltag mit Risiko umgehen. Dabei zeigt sich, dass die mathematischen Formeln des Risikomanagements oft nicht die Beschreibung und Analyse der Finanzmärkte erlauben, denn sie sind rein selbstreferentiell innerhalb einer sozial konstruierten Hyperrealität, so wie sie Baudrillard darstellte, konstruiert. Die soziale Konstruktionen des Risikomanagements erscheinen oft ähnlich zu "magischen" Zukunftstechniken, die die Ethnologie aus anderen Zusammenhängen schon lange kennt, und welche helfen sollen, die Ungewissheit zukünftiger Ereignisse beherrschbar zu machen

Risiko in Banken

Ab 2007 ging von den USA eine Bankenkrise aus, die globale Auswirkungen hatte, z.B. den finanziellen (Beinahe-)Zusammenbruch ganzer Staaten wie Griechenland. Die dadurch hervorgerufene Arbeitslosigkeit und Armut führt dazu, dass viele Menschen die Konsequenzen abstrakter Vorgänge der Finanzwelt in ihrem Alltag noch immer sehr konkret spüren. Nicht einmal zehn Jahre nach der Krise sind die Gewinne der Banken größer als jemals zuvor, und sowohl die Verantwortlichen in Politik als auch Wirtschaft versichern, dass verbesserte Verfahren zum Management von Risiken das Entstehen neuer, vergleichbarer Krisen unmöglich gemacht machen. Aber wie konnte diese Krise überhaupt entstehen, wenn doch BankmanagerInnen schon immer das Beherrschen von Risiken als ihre Kernkompetenz angeben? Diese Studie ist das Ergebnis langjähriger teilnehmender Beobachtung in Banken und hat das Ziel, die komplexen Zusammenhänge, die sich hinter dem Begriff Risiko in Banken verbergen, mit ethnologischem Blick zu dekonstruieren. Ausgehend von der Betrachtung der diskursiven Konstruktion des Risikobegriffs geht es um die Beobachtung, wie die in Banken arbeitenden Menschen in ihrem Berufsalltag mit Risiko umgehen. Dabei zeigt sich, dass die mathematischen Formeln des Risikomanagements oft nicht die Beschreibung und Analyse der Finanzmärkte erlauben, denn sie sind rein selbstreferentiell innerhalb einer sozial konstruierten Hyperrealität, so wie sie Baudrillard darstellte, konstruiert. Die soziale Konstruktionen des Risikomanagements erscheinen oft ähnlich zu "magischen" Zukunftstechniken, die die Ethnologie aus anderen Zusammenhängen schon lange kennt, und welche helfen sollen, die Ungewissheit zukünftiger Ereignisse beherrschbar zu machen

Passive Immunization against Congenital Cytomegalovirus Infection: Current State of Knowledge

Primary infection with the human cytomegalovirus (CMV) occurs in 1-4% of pregnancies. The rates of maternal-fetal CMV transmissions are around 25, 36, 41, and 66%, for infections occurring in the peri-conceptional weeks, first, second, and third trimester of pregnancy, respectively. On the other hand, the severity of fetal organ damage and dysfunction diminishes with increasing gestational age. Congenitally CMV-infected newborns may have neurosensory impairments like mental retardation, cerebral palsy, epilepsy, progressive hearing loss or visual defects, or even may have a fatal outcome. In in-vitro experiments, CMV specific neutralizing IgG antibodies - which are abundant in CMV specific hyperimmune globulin (HIG) products - inhibited the entry of the virus into target cells and hampered viral cell-to-cell spread. This article provides a brief overview on the epidemiology and diagnostic tools in congenital CMV infection. It also concisely summarizes the currently available study results on the safety and effectiveness of HIG treatment. Accordingly, in clinical studies HIG administration to expectant mothers following primary CMV infection (prophylactic use) was shown to lower the risk of maternal-fetal transmission of CMV compared to untreated controls. HIG was also able to ameliorate the disease sequelae in evidently infected fetuses (therapeutic use), as demonstrated by the regression or even resolution of sonographic pathologies including placental inflammation

The mitochondria-independent cytotoxic effect of nelfinavir on leukemia cells can be enhanced by sorafenib-mediated mcl-1 downregulation and mitochondrial membrane destabilization

Background: Nelfinavir is an HIV protease inhibitor that has been used for a long period of time to treat HIVinfected individuals. It has recently emerged that nelfinavir could represent a prospective new anti-cancer drug, prompting us to test the effect of nelfinavir on leukemia cells. Methods: By combining in vitro and ex vivo studies, the effect of nelfinavir on leukemia cells and non-malignant, bone marrow-derived tissue cells was analyzed. Results: At a concentration of 9 mu g/ml, nelfinavir induced death of 90% of HL60, IM9, and Jurkat cells. At the same concentration and treatment conditions, less than 10% of aspirated human bone marrow cells showed nelfinavir-induced cell damage. Nelfinavir-induced death of leukemia cells was accompanied by activation of caspases 3, 7, and 8. Despite caspase activation, the upregulation of the anti-apoptotic bcl-2 family member protein mcl-1 that resulted from nelfinavir treatment stabilized the mitochondrial membrane potential, resulting in primarily mitochondria-independent cell death. Pharmacological downregulation of mcl-1 expression by treatment with sorafenib (2 mu g/ml) significantly enhanced nelfinavir-induced apoptosis even at lower nelfinavir concentrations (5 mu g/ml), but did not have additional detrimental effects on non-malignant bone marrow cells. Conclusions: The ability of nelfinavir to induce apoptosis in leukemia cells as a single agent in a mitochondria-independent manner might suggest it could be used as a second or third line of treatment for leukemia patients for whom standard mitochondria-directed treatment strategies have failed. Combination treatment with nelfinavir and sorafenib might further enhance the efficacy of nelfinavir even on chemo-resistant leukemia cells