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Umbilical inflammation in the calf represents a regularly occurring disease. The disinfection of the navel immediately after birth is therefore frequently recommended as a prophylactic measure. Within the frame of a literature search this study was to elucidate to what extent this recommendation is supported by scientific data.Within the scope of a literature research, only studies were considered in which the efficacy of navel disinfection was investigated with regard to the prevention of umbilical infections. A clinical database was required.Results A total of merely 6 studies were identified that examined the effect of umbilical disinfection as a prophylactic measure. Of these, only one investigation was able to display the presence of a preventive effect.All of the studies analyzed exhibited limitations in methodology. Based on this, no data is currently available clarifying whether navel disinfection in calves exerts a positive effect on umbilical health.Nabelentzündungen beim Kalb sind eine regelmäßig vorkommende Erkrankung. Zur Prophylaxe wird oftmals eine frühzeitige Desinfektion des Nabels nach der Geburt empfohlen. Inwiefern diese Empfehlung wissenschaftlich belegt ist, sollte im Rahmen einer Literaturrecherche analysiert werden.Im Rahmen einer Literaturrecherche wurden nur Studien beachtet, in denen die Effektivität dieser Maßnahme hinsichtlich der Prävention von Nabelinfektionen untersucht wurde. Eine klinische Datengrundlage musste vorliegen.Insgesamt konnten nur 6 Studien gefunden werden, die den Effekt einer Nabeldesinfektion als prophylaktische Maßnahme untersucht haben. Nur in einer Studie konnte ein präventiver Effekt nachgewiesen werden.Einschränkend muss jedoch festgehalten werden, dass alle Studien methodische Mängel aufwiesen, sodass derzeit keine Daten dazu vorliegen, ob sich eine Nabeldesinfektion beim Kalb positiv auf die Nabelgesundheit auswirkt.

Umbilical cord blood (UCB) contains hematopoietic stem cells with therapeutic potential and unique cellular properties. Due to the limited number of stem cells in the UCB (surrogate marker total nucleated cells, TNC), only one in five donations is suitable for transplantation. The aim of this study was to investigate whether predictive factors exist for a TNC count above the 99th percentile.Retrospective data analysis of the 100 largest donations from 2,299 registered UCB units. Differences between maternal, fetal, and obstetric factors were analyzed and compared with a standardized cohort of 731 registered UCB units.maternal age and BMI in the Top100 cohort were higher compared with the comparative cohort (32 vs. 31 years, p=0.007; 30 kg/m2 vs. 29 kg/m2, p=0.024). There were significantly more P1 (76.0 vs. 62.8%, p=0.013) and women with gestational diabetes (5.00 vs. 1.65%, p=0.044). The gestational week, birth weight, the proportion of vaginal-operative deliveries and secondary caesarean sections were higher in the Top100 cohort (40+4 vs. 40+1 wks, p=0.002), (3700 vs. 3450 g, p0.001), (53.0 vs. 22.7%, p0.001) (10 vs. 6.2%, p=0.014).For a successful transplant, the amount of TNC in the UCB unit is crucial. Vaginal-operative deliveries, secondary caesarean sections, and a birth weight above 3700 g are favorable with regard to stem cell content. In cases with a complicated course of delivery, collection should not be neglected once the mother and child are safely cared for.Nabelschnurblut (NSB) enthält hämatopoetische Stammzellen mit therapeutischem Potenzial und einzigartigen zellulären Eigenschaften. Aufgrund der begrenzten Anzahl an Stammzellen im NSB (Surrogatmarker total nucleated cells, TNC) eignet sich nur jede fünfte Spende für eine Transplantation. Ziel dieser Studie war es, zu untersuchen, ob prädiktive Faktoren für eine TNC-Zahl über der 99. Perzentile existieren.Retrospektive Datenanalyse der 100 größten NSB-Spenden (Top100-Kohorte) aus 2299 registrierten Einheiten. Unterschiede zwischen maternalen, fetalen und geburtshilflichen Faktoren wurden analysiert und mit einer standardisierten Kohorte von 731 NSB-Spenden verglichen.Das mütterliche Alter und der BMI in der Top100-Kohorte waren höher als in der Vergleichskohorte (32 vs. 31 Jahre, p=0,007; 30 kg/m2 vs. 29 kg/m2, p=0,024). Es gab mehr Erstgebärende (76,0 vs. 62,8%, p=0,013) und Gestationsdiabetikerinnen (5,00 vs. 1,65%, p=0,044). Die Schwangerschaftswoche, das Geburtsgewicht, der Anteil vaginal-operativer Geburten und sekundärer Sectiones war in der Top100-Kohorte höher (40+4 vs. 40+1 SSW, p=0,002), (3700 vs. 3450 g, p0,001), (53,0 vs. 22,7%, p0,001) (10 vs. 6,2%, p=0,014).Für eine erfolgreiche Transplantation ist die Höhe der TNC-Zahl entscheidend. Vaginal-operative Entbindungen, sekundäre Sectiones und ein Geburtsgewicht über 3700 g sind günstige Faktoren. Gerade bei Geburten mit einem pathologischen Verlauf sollte nach sicherer Versorgung von Mutter und Kind nicht auf eine Entnahme verzichtet werden.

Endothelzell-basierte Therapien vermitteln regenerative Effekte hinsichtlich der Revaskularisierung von ischämischen Geweben. Doch ist die Verfügbarkeit von autologen Endothelzellen aufgrund einer krankheitsbedingt reduzierten Frequenz im peripheren Blut oder einer verminderten Integrität der endogenen Endothelzell-Populationen eingeschränkt. Hingegen ist es möglich, allogene endotheliale Vorläuferzellen aus der Nabelschnur in zelltherapeutisch relevanten Mengen zu isolieren. In der vorliegenden Arbeit wurden zunächst die Eigenschaften allogener humaner Nabelschnur (NS)-abgeleiteter sog. Endothelial Colony-Forming Cells (ECFCs) mit denen von venösen NS-abgeleiteten Endothelzellen verglichen. Aufgrund der nachgewiesenen Immunogenität von allogenen ECFCs wurde eine weiterführende Strategie zur Reduktion dieser immunogenen Eigenschaften durch die Koapplikation mit Mesenchymalen Vorläuferzellen (MSCs) verfolgt. Humane ECFCs wurden mit MSCs desselben Spenders kombiniert und in funktionellen in vitro- und in vivo-Assays untersucht. Dadurch konnte nachgewiesen werden, dass IFNγ-stimulierte ECFC/MSC-Kokulturen eine reduzierte Expression von HLA-Molekülen zeigen. Entsprechend induzierten spezifische CD8+ T-Zellen eine reduzierte Lyse der kokultivierten ECFCs und MSCs. Die Kokultur von ECFCs und MSCs mit allogenen Immunzellen führte zu einer nahezu vollständigen Inhibition der T-Zell-Proliferation. Um die reduzierte Immunogenität von ECFC und MSC in vivo zu verifizieren, wurden die Zellen in immundefiziente Mäuse injiziert, welche nachfolgend mit humanen PBMCs rekonstituiert wurden. So konnte nachgewiesen werden, dass die Koapplikation von ECFCs und MSCs nicht nur die Entstehung von stabilen Gefäßnetzwerken begünstigt, sondern zudem in den Transplantaten zu einer verringerten Immunzell-Infiltration führte. Die Koapplikation von ECFCs mit MSCs könnte daher eine klinische Nutzung dieser allogenen Quelle für die therapeutische Unterstützung der Vaskularisierung ermöglichen., Endothelial cell-based therapies promote tissue regeneration and vascularization after ischemic damage. The availability of autologous endothelial progenitor cells is restricted in diseased patients, however therapeutically relevant numbers of allogeneic Endothelial Progenitor Cells can be isolated from an umbilical cord (UC). In the present study, the immunogenic properties of these Endothelial Colony Forming Cells (ECFCs) were first compared to human umbilical vein endothelial cells (HUVECs). Both cytokine-treated endothelial cells induced CD4+ and CD8+ T cell proliferation after coculture with allogeneic immune cells. So far, the potential interactions between ECFCs and Mesenchymal Stem/Progenitor Cells (MSCs) concerning their immunological features is poorly understood, but we hypothesize that MSCs might improve the immune compatibility and vessel building characteristics of ECFCs. Therefore, human UC-derived ECFC and MSC cocultures from the same donor were analyzed using various functional in vitro and in vivo assays. Stimulation of these cocultures with IFNγ caused strongly reduced expression levels of HLA-molecules compared to ECFC monocultures. The decreased molecular density on the cocultured ECFCs resulted in reduced cytotoxic CD8+ T cell-mediated lysis. Further, during IFNγ stimulation, the combination of ECFCs with MSCs prevented initiation of allogeneic T cell proliferation. To verify this concept in vivo, ECFCs and MSCs were co-transplanted in a humanized allograft mouse model in immunodeficient mice in order to effectively induce stable microvessels. These experiments demonstrate that when MSCs are co-applied with ECFCs, they not only support the formation of stable blood vessels, but also lead to fewer HLA-DR+ human vascular structures and fewer infiltrating human leukocytes. The data presented indicate that crosstalk between UC-derived ECFCs and MSCs might lower the risk of allogeneic ECFC rejection.

The emergency caesaran section is a gynecological emergency situation which is potentially life-threatening for mother and child. In the management of these time-critical situations human factors as well as the competence of the crisis resource management team have been shown to be important factors for success. The concept "simulation" has not been validated as a training tool for professional competence of multidisciplinary teams in the delivery suite. The aim of this study was, to assess the competence gain by subjective evaluation of the team members after taking part in an emergency caesarian section training which is integrable into the daily clinic setting.

Congenital syphilis is a rare disease in central Europe. Placental changes may be non-specific but a typical finding is necrotizing funisitis of the umbilical cord. In a case report we describe how the histopathological incidental finding of B lymphocyte-rich, necrotizing funisitis led to the diagnosis of a previously unknown Treponema pallidum infection in parents and their newborn child. The pathological suspicion of congenital syphilis, although rare, has implications for the clinical management (serological evaluation of parents and child as well as the social environment, evaluation of viral coinfection and treatment decision) and is a notifiable disease.

Afterbirth tissues, which include the umbilical cord, placenta, amnion, and cord blood, are usually discarded. Recent progress in regenerative medicine suggests that we re-evaluate these tissues and assess their therapeutic potential.Firstly the unique properties of afterbirth tissues and their current use in regenerative medicine are summarised. Then we introduce the cooperation of our institutions and our experiences regarding the collection and utilisation of afterbirth tissues.A literature survey suggests that besides the well-known transplantation of hematopoietic stem cells from cord blood, afterbirth tissues were also used as a source of stem cells, progenitor cells, differentiated cells, and blood vessels for tissue engineering purposes. According to our own experience, the two participating OB/GYN departments and the blood donation service were able to organise a sufficient supply of umbilical cords for research purposes. The yield correlated with incentives for the midwives. A total of more than 4,300 cords was collected for experiments designed to create small caliber vessel grafts. The contamination rate was low. Birth mode significantly affected umbilical vein function, whereas ischaemia for up to 40 h did not have any deleterious effects. Umbilical veins were cryopreserved with a moderate loss of function. Fresh umbilical veins were endothelium-denuded and reseeded with endothelial cells harvested from coronary artery disease patients to generate an autologous surface.Afterbirth tissues have unique properties which make them ideally suited for regenerative medicine. These tissues can be procured and utilised in research facilities even in the absence of an in-house birthing centre.

Staphylococcus aureus ist ein ubiquitär vorkommendes Bakterium, dessen Infektionen oft mit schweren endovaskulären Krankheiten assoziiert sind. Die Ursache dafür sind verschiedene Virulenzfaktoren, u.a. das hier bearbeitete Extracellular Adherence Protein (Eap). Eap erfüllt verschiedene Aufgaben: So führt es zu einer Adhärenz der S. aureus-Bakterien untereinander sowie auch der Adhäsion des Bakteriums an eukaryotische Zellen. Außerdem greift es in das Abwehrsystem des Menschen ein, um der humanen Immunantwort zu entgehen. Zudem besitzt es anti-inflammatorisches und anti-angiogenes Potenzial. Verschiedene Plasmaproteine wie Fibrinogen, Fibronektin und Vitronektin und auch ICAM-1 wurden als Bindungspartner für Eap identifiziert. Ob Eap auch an andere Rezeptoren als ICAM-1 binden kann und was nach Bindung an den eukaryotischen Zellen passiert und ob Eap an der Oberfläche der Zellen verbleibt oder in die Endothelzellen und darüber hinaus aufgenommen wird, war Gegenstand dieser Arbeit. Zur Beantwortung dieser Fragen wurden ex vivo-Experimente mit Gefäßen von Nabelschnüren, sowie in vitro-Experimente mit makrovaskulären Endothelzellen (HUVEC) durchgeführt. Zellen und die V. umbilicalis der Nabelschnur wurden unter verschiedenen Bedingungen mit Eap inkubiert und anschließend Immunfluoreszenzbilder mikroskopisch ausgewertet. Durch Permeabilitätsassays wurde der Einfluss von Eap auf die Permeabilität von HUVEC untersucht. Um die Bindung von Eap an eukaryotische Zellen zu bestimmen, wurden Bindungsassays mit biotinyliertem Eap an HUVEC über das ELISA-Prinzip durchgeführt. In der vorliegenden Arbeit konnte gezeigt werden, dass die Aufnahme von Eap in das Zytoplasma von Endothelzellen abhängig von der Eap-Konzentration und der Inkubationszeit ist und nicht nur auf die Endothelzellen beschränkt bleibt, sondern auch in der ECM nachgewiesen wurde. Die Aufnahme von Eap war bei 4 °C und bei gleichzeitiger Inkubation von Eap mit Heparin stark reduziert. Heparansulfate auf den Zelloberflächen hatten einen begrenzten Einfluss auf die Internalisierung von Eap. ICAM-1 war nach Eap-Inkubation in der V. umbilicalis reduziert darstellbar, was die Annahme von ICAM-1 als Bindungspartner von Eap unterstützt. Ebenfalls reduziert, jedoch meist nicht so stark wie ICAM-1 und auch nicht konzentrationsabhängig von Eap oder der Inkubationszeit, war PECAM-1. Dies läßt PECAM-1 als weiteren, aber weniger affinen, „Rezeptor“ für Eap vermuten. Die Permeabilität eines HUVEC-Monolayers wurde jedoch durch Eap nur gering beeinflusst. Eap zeigte eine homogene Verteilung im Zytoplasma ab einer Konzentration von 5 µg/ml Eap und zudem eine perinukleäre Agglomeration. Der Kern blieb allerdings frei von Eap, was darauf hinweist, dass Eap zunächst nicht in den Kern wandert, sich aber dort anlagert. Staphylococcus aureus is a prevalent bacterium; its infections are often associated with severe endovascular diseases because it expresses a variety of virulence factors, including the Extracellular Adherence Protein (Eap). Eap leads not only to the adherence of S. aureus bacteria to each other but also mediates adhesion of the bacteria to eukaryotic cells. It also influences the immune system of its host and has anti-inflammatory and anti-angiogenic potential. Various plasma proteins such as fibrinogen, fibronectin, vitronectin and receptors like ICAM-1 were previously identified as binding partners for Eap. This raises the question whether Eap can bind to receptors other than ICAM-1 and what happens after binding to the eukaryotic cells, whether Eap remains on the surface of cells or is internalized to the endothelial cells and beyond. These questions were examined in ex vivo-experiments with veins of umbilical cords, as well as in in vitro-experiments with macrovascular endothelial cells (HUVEC). HUVEC and V. umbilicalis were incubated with Eap under different conditions and immunofluorescence images were evaluated microscopically. In addition, permeability assays were done to examine the permeability of HUVEC monolayers after incubation with Eap. To investigate the binding of Eap, binding assays of biotinylated Eap to HUVEC were carried out by the ELISA principle. In this work it could be shown that the inclusion of Eap in the cytoplasm of endothelial cells is dependent on the concentration of Eap and time of incubation. The localisation Eap was not limited on the endothelial cells, because Eap could also be detected in the extracellular matrix. The inclusion of Eap was significantly reduced at 4 °C and in the case of simultaneous incubation of Eap with heparin. Heparan sulfates on the cell surface had a limited effect on the internalization of Eap. ICAM-1 was reduced in the V. umbilicalis after incubation of the umbilical cord with Eap. That supports the assumption of ICAM-1 as a binding partner of Eap. PECAM-1 was also reduced, but usually not as strong as ICAM-1, and neither concentration dependent of Eap or of time of incubation. This suggests PECAM-1 as another, but rather nonspecific, ligand for Eap. The permeability of HUVEC monolayers was affected only slightly by Eap, there was only a tendency towards an increasing permeability. In regard to the localization of Eap inside the cell, at a concentration of 5 µg/ml Eap a homogeneous distribution in the cytoplasm could be shown. Although also a perinuclear agglomeration was visible, the core, however, remained free of Eap, suggesting that Eap does not initially moves into the nucleus, but adsorbs at the nucleus.

We present the case of an intrapartum umbilical cord rupture in an underwater birth with severe neonatal blood loss.A healthy 25-year-old gravida I with an uneventful pregnancy had an underwater birth. A completed rupture of the umbilical cord was diagnosed immediately after the newborn surfaced from the water and was laid on the mother's chest. The newborn suffered from severe haemorrhage with bradycardia and respiratory distress. It was immediately resuscitated by the neonatologist. Intravenous donation of volume and red blood cell transfusion could stabilise the vital parameters. The newborn was discharged in a state of well-being 6 days postnatally.Cases of umbilical cord rupture are reported in relationship to land and water births. Common causes of a cord rupture include haematoma of the cord vessels, trauma from an operative vaginal delivery, funisitis with localised cord necrosis, velamentous cord insertions, tumours of the umbilical cord and a short umbilical cord. A suspicious foetal heart rate might be absent. In the case of a water birth complications bear serious consequences. Proper team work between obstetricians and neonatologists is essential.Although water birth is restricted to low risk patients, unforeseen complications may occur. Because of the special situation in an underwater birth complications may be diagnosed late and their management will be more difficult. Obstetricians should be aware of this risk.

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Background: Mesenchymal stem cells (MSCs or mesenchymal progenitor cells) have the capability for differentiation into various lineages of mesenchymal tissue. MSCs are widely distributed in a variety of tissues in the adult human body and also present in the fetal environment. However, MSCs are a rare population in these tissues. In this study we evaluated the possibility that MSCs or cells with MSC-like potency are present in the umbilical cord (UC). Methods: Term UCs were collected and stored in sterile saline solution. The UCs (10 cm) were cut into 1 cm length, the vessels were striped manually and the tissue immersed in an enzyme cocktail for 3 h at 37 °C. The isolated umbilical cord mesenchymal stem cells (UCMSCs) were pelleted by low speed centrifugation, suspended and cultured. Results: (1) UCMSCs could be isolated in sufficient quantities and (2) could be cultured easily. (3) These cells demonstrated a fibroblast-like phenotype. (4) They could be expanded in culture and induced to form several different types of cells. (5) In immunochemistry these cells express mesenchymal markers (CD13, CD105) but not haematopoetic lineage markers (CD14 and CD34). Conclusion: Our observation suggested that MSCs are present in human umbilical cord. Instead, it should be considered a valuable resource for the isolation of potent cells for cell-based therapies, especially in general and pediatric surgery.

Foetal growth retardation (IUGR) occurs in approximately 3-10 % of all pregnancies and may result from foetal, maternal or placenta-related conditions. In IUGR, the placental weight is often reduced and the placental capacity, reflected by the organ's weight, is impaired. Uterine malformations have an incidence of 3-4 % and may be the cause of placental abruptions occurring in 0.4-1.3 % of all pregnancies. We report on a patient in the 26 (th) week of pregnancy who was admitted with vaginal bleeding. A uterus bicornis had been found previously. Sonography showed severe foetal growth retardation and a pathological foetal Doppler signal. A haematoma located cranial of the os uteri was sonographically diagnosed, and a partial placental abruption was suspected. Due to a pathological cardiotocography, a primary Caesarean section was performed. Intraoperative evaluation confirmed the presence of a uterus bicornis. In addition, the placenta showed an insertio velamentosa. The growth retarded foetus - 490 g birth weight - was anaemic. Respiratory therapy and surfactant substitution were performed because of a respiratory distress syndrome. At a corrected age of 8 weeks the boy was sent home without neurological sequelae. In the case reported, a malformation of the uterus was the cause of a pathologically altered placenta. The multiple factors responsible for the described severe intrauterine growth retardation were a low placental weight and thus a reduced placental capacity, an impaired foetal circulation caused by the velamentous insertion, as well as a partial placental abruption. In normotensive pregnancies with IUGR, macroscopic and histopathological examinations of the placenta are therefore strongly recommended. Prior to getting pregnant, the therapeutic options should be explained to women with uterine malformations.

Mesenchymal progenitor cells (MPCs or mesenchymal stem cells, MSC) have the capability for differentiation into various lineages of mesenchymal tissue. MPCs are widely distributed in a variety of tissues in the adult human body and also present in the fetal environment. However, MPCs are a rare population in these tissues. In this study we evaluated the possibility that MPCs or cells with MPC-like potency are present in the umbilical cord (UC).Term UCs were collected and stored in sterile saline solution. The UCs (10 cm) were cut into 1 cm length, the vessels were striped manually and the tissue immersed in an enzyme cocktail for 3 h at 37 degrees C. The isolated umbilical cord mesenchymal progenitor cells (UCMPCs) were pelleted by low speed centrifugation, suspended and cultured.(1) Umbilical cord mesenchymal progenitor cells (UMPCs) could be isolated in sufficient quantities and (2) could be cultured easily. (3) These cells demonstrated a fibroblast-like phenotype. (4) They could be expanded in culture and induced to form several different types of cells. (5) In immunochemistry these cells express mesenchymal markers (CD 13, CD 105) but not haematopoetic lineage markers (CD 14 and CD 34).Our observation suggested that MPCs are present in human umbilical cord. Instead, it should be considered a valuable resource for the isolation of potent cells for cell-based therapies, especially in general and pediatric surgery.

Gesamtdissertation, Diese Dissertation untersucht die frühen Effekte von VEGF auf die Proteine der extrazellulären Matrix (EZM) und auf die vaskuläre Permeabilität an humanen Umbilikalarterien. Es ist bekannt, dass VEGF die Akkumulation von Proteinen der EZM in mesangialen und endothelialen Zellen induziert und zu einer gesteigerten vaskulären Permeabilität führt. So ist eine Vielzahl an Erkrankungen, die mit lokalen und generalisierten Ödemen einhergehen, durch einen erhöhten Serumspiegel von VEGF gekennzeichnet. Die Untersuchungen dieser Arbeit werden mit einem eigens etablierten Perfusionsmodell der humanen Nabelschnur durchgeführt. Die Nabelschnüre von reifen, gesunden Neugeborenen, die via Sectio caesarea entbunden wurden, werden in 3 Untersuchungsgruppen randomisiert: 1\. nicht perfundierte unbehandelte Nabelschnursegmente (0-Probe), 2\. perfundierte unbehandelte Nabelschnursegmente (-VEGF) sowie 3\. perfundierte mit VEGF165 behandelte Nabelschnursegmente (+VEGF). Der Untersuchung, Präparation und intraarteriellen Applikation von VEGF165 (2 ng/ml) oder Kontrollmedium folgt eine Adaptationszeit von 90 Minuten Dauer bei 37 °C. Im Anschluss werden die Nabelschnursegmente für 4 Stunden perfundiert. Arterieller Perfusionsdruck und vaskulärer Fluss werden kontinuierlich gemessen. Die Gefäße werden nach Abschluss des Experiments mittels Hämatoxilin-Eosin-Färbung, Sirius-Rot-Färbung, Polarisationslicht-Mikroskopie, Transmissionselektronenmikroskopie, Immunhistochemie und Western Blot-Analyse untersucht. Das interstitielle Ödem wird durch die Extravasation des Farbstoffes Evans Blau visualisiert und vermessen. Durch die Extravasation von Evans Blau kann nach 4 Stunden Perfusion ein signifikantes interstitielles Ödem in der VEGF165-behandelten Gruppe gefunden werden. Mit Hilfe immunhistochemischer Untersuchungen und Western Blot-Analysen wird nachgewiesen, dass die intraarterielle Applikation von VEGF165 zu einer signifikanten Zunahme der EZM-Proteine Kollagen Typ IV und Laminin im Vergleich zur nicht perfundierten unbehandelten (0-Probe) und zur perfundierten unbehandelten Kontrollgruppe (-VEGF) führt. Darüber hinaus kommt es zu einer signifikanten Induktion von Flt-1, Flk-1 und Osteopontin nach VEGF165-Behandlung, die immunhistochemisch und mittels Western Blot-Analyse nachgewiesen wird. Parallel findet sich ein Anstieg von ß1-Integrin. Die in dieser Dissertationsschrift präsentierten Daten dokumentieren, dass die intraluminale Applikation von VEGF165 zu einem signifikanten Anstieg der Proteine der EZM in der humanen Umbilikalarterie führt. Osteopontin und ß1-Integrin werden ebenfalls von VEGF165 induziert und sind möglicherweise von entscheidender Bedeutung bei vaskulären Remodeling-Prozessen. Die Erhöhung der vaskulären Permeabilität durch die Interaktion von VEGF165 mit seinen Rezeptoren spielt auch im Bereich der Umbilikalarterie eine Rolle. Weitere Untersuchungen müssen an einem in vivo-Modell durchgeführt werden, um die Ergebnisse dieser Dissertation zu validieren. Da die Konditionen der in vivo- Situation sehr ähnlich sind, können mit dem hier etablierten Modell pharmakologische und gefäßbiologische ex vivo-Studien an menschlichen Gefäßen durchgeführt werden. Dadurch können Tierversuche auf dem Gebiet der vaskulären Biologie und Pharmakologie ersetzt werden., VEGF induces extracellular matrix (ECM) accumulation in mesangial and endothelial cells. The precise mechanisms that mediate VEGF-induced ECM expansion remain poorly characterized. Therefore, we established a human perfusion model to investigate the early effects of VEGF on ECM proteins and vascular leakage in human umbilical arteries. In a human vessel perfusion model, we investigated the impact of intraluminal application of VEGF165 (n=10; dose 2 ng/ml) on the umbilical artery. 10 other umbilical cords served as non-treated controls and 10 segments of umbilical cords served as non- perfused, non-treated controls. Arterial pressure and vascular flow were measured online. Vessels were evaluated by Hematoxilin Eosin staining, Sirius red staining, polarization microscopy, electron microscopy, Western blotting and immunohistochemistry. Evans blue extravasation was used to determine a tissue edema. A significant tissue edema was detected after 4 h in VEGF treated arteries. VEGF165 significantly increased laminin and collagen type IV compared to perfused and non-perfused controls. Furthermore, VEGF treatment significantly induced Flt-1, Flk-1 and osteopontin. In parallel, we detected a significant increase in ß1-integrin. Our data clearly document for the first time that intraluminal application of VEGF increases ECM proteins in the umbilical artery. Osteopontin and ß1-integrin induced by VEGF may play an important role in the vascular remodeling process.

The ex-utero intra-partum (EXIT) procedure enables the surgeon to perform invasive procedures in an infant during cesarean section before clamping the umbilical cord. Specific anesthesiological concepts are necessary for ensuring sufficient umbilical perfusion. We report the case of a 33-year-old female undergoing cesarean section in the 36th week of pregnancy because of a large fetal cervical tumor. The EXIT procedure was performed in order to secure the infant's airway during delivery. The anesthesiological management and interdisciplinary tasks are discussed in the literature review.

The identification of appropriate cell types is necessary to establish cell-based therapies in regenerative medicine. These cell types must (1) be available in an appropriate amount, (2) be easy to obtain, (3) be sufficiently expandable in vitro, and (4) fit to or at least be able to differentiate into the required cell type. Since the umbilical cord is available without any intervention and represents a notable amount of tissue, we consider it to be a promising source for isolating cells for cell-based therapies. This study demonstrates that umbilical cord stromal cells (UCSC), the connective tissue cells of the umbilical cord, can be isolated in sufficient quantities and be well expanded. UCSC feature phenotypic plasticity and thus are functionally similar to stem cells. UCSC can be differentiated into cells with osteoblastic properties (expression of alkaline phosphatase, formation of bone nodules). It is concluded that the umbilical cord should no longer be regarded as valueless tissue and be unthinkingly discarded. Instead, it should be considered a valuable resource for the isolation of potent cells for cell-based therapies, especially for treatment of bone defects.

3D power Doppler ultrasonography (3D-PDU) is a new method which allows the spatial presentation of fetal vessels in utero. In the presented study we have examined the feasibility of this technique in prenatal diagnosis. Aim of our pilot study with normal human fetuses was to determine the adjustment of the system presets, the optimal insonation planes and the regions of interest.Seven regions of interest were examined in three different planes. The 3D volume was acquired by a free hand sweep. The feasibility of the method was quantitatively determined for every plane and region. For each of the three planes a total of 25 examinations was planned and the successful rate per region of interest was then assessed for the total of these 75 examinations. In a two year period, a total number of 80 fetuses from 16 to 34 weeks' gestation could be enrolled in the study.Best examinations were achieved in the vessels of the umbilical cord (successful rate 100 %), followed by the placental and abdominal (84 % each), cerebral (80 %), pulmonary (64 %), and renal vessels (51 %). The most difficult conditions for examination and the most unreliable results were found for the fetal heart with a success rate of only 31 % of the cases. Similar to the experience in 2D power Doppler, a plane with blood flow towards the transducer was the best insonation plane.In our study we were able to show that a three dimensional demonstration of fetal vessels is possible with the system used. The feasibility is limited by fetal movements and unfavourable fetal positioning. The possible benefit of the method is to diagnose complex fetal vascular malformations in the future.

The umbilical stalk, vein, arteries, urachal region, liver and urinary bladder in 35 calves with the clinical suspect of umbilical disease were examined ultrasonographically with a 3.5 and 5 MHz convex scanner and a 7.5, 10 and 13 MHz linear scanner (Esaote AU5, Esaote, Florenz). Extra- and intraabdominal umbilical structures could be evaluated well by ultrasonography. An exact description of the extent of the disease and of the involvement of other structures, as the liver or the urinary bladder, was made possible by ultrasonography. Complications during surgery could be reduced and in the case of a poor prognosis the calves were euthanatized to prevent costs for the owner.

The morphology, pathogenesis, complications and differential diagnosis of an intestinal polyp of the umbilical cord are presented. The polyp were detected postnatal on the umbilical cord in an healthy male newborn. The presents of intestinal tissue upon the umbilical cord ist possible about the persistence from remnants of the ductus omphalomesentericus with prolapse and differentiation of the intestinal cells. The ductus omphalomesentericus is a tubular structure, a communication between the developing embryonic gut and the yolk sac, forming during the early embryonic life. Obliteration of the omphalomesenteric duct is usually complete by the 10(th) week of gestation. Various portions of the duct may persist, however, giving rise to polyps, fistulas or cysts of the umbilical cord with potentially dangerous clinical consequences. Other tumors of the umbilical cord are myxoma, angioma and teratoma are differential diagnosis.

The umbilical cord is the "foetal lifeline". Pathological changes of the umbilical cord may strongly threat foetal life. Otherwise there are many morphological abnormalities without any influence on foetal well-being. There is poor knowledge about many special pathologic-anatomical features of the cord.Our aim was to study the incidence and relevance of pathological changes of the umbilical cord, including so-called "cord accidents", in our large autopsy series.Our study is a review of 4267 cases, including 1301 aborted foetuses and 2966 stillborns and lifeborns less than 7 days of age, autopsied from 1971 to 1996 in our department.Of 1301 aborted foetuses, 94 (7.2%) had abnormalities of the umbilical cord. Most of them (about 59%) showed torsion, stricture or "Thin-cord-Syndrome". Other important lesions of the cord in aborted foetuses are omphaloceles and constrictions of the cord secondary to Streeter bands. Most of all changes of the cord found in aborted foetuses were lethal factors. Of 2966 stillborn and lifeborn children, which died before day 7 of life, 456 (15.4%) had abnormal findings in relation to umbilical cord. 228 children showed umbilical cord accidents (i.e. true knots, cord prolapse, cord entanglement). Likewise in 228 children, we found especially changes of cord vessels like singular umbilical artery and others, cord oedema, insertion anomalies and other changes. This findings often represent no lethal factors.Torsion, stricture, and the complex of the thin umbilical cord play the most important role especially in abortion, but is also the most important cause of death of the older foetus in relation to true umbilical cord pathology.

Based on the description of a severe bleeding disorder in a young child a short overview on the genetics, the epidemiology, the pathophysiology, the clinical manifestations and the laboratory diagnosis of factor XIII deficiency is presented. The impressive clinical signs with bleeding starting in the neonatal period (prolonged bleeding from the umbilical cord), followed by severe, life-threatening episodes of intracranial hemorrhages should raise the clinical suspicion of FXIII deficiency. Difficulty of laboratory diagnosis is stressed. The importance of repeating initially negative screening tests and of performing a quantitative FXIII assay in the presence of strong clinical suspicion is strengthened. The diagnosis of factor XIII deficiency is difficult but has important therapeutic consequences: patients with documented severe deficiency should be put on regular substitution with factor XIII concentrates. Appropriately timed periodic infusions of such factor XIII concentrates enable patients to live normal lives, free from catastrophic bleeding episodes.

Modern sonographic technique allows the detection of cord complication as neck cord entanglement. Far more difficult is the detection of a real cord knot. This article describes a theoretical model for detection of a cord knot and proves it in an in-vitro model.

The purpose of this study was to investigate the validity of cardiotocography for the detection of cord complications.A low-risk population of 4196 cases was selected in which cord complications have been recognized in 34.3%. Cases with cord complications and controls were paired by parity, gestational age, maternal age and mode of delivery. 25 pairs were randomly selected. 50 tracings were presented twice to 4 obstetricians in a double-blind manner. As parameters for the determination of the validity of fetal monitoring the reliability, positive (ppv) and negative predictive value (npv), sensitivity and specificity were used. Inter- and intra-observer variability were also examined.Reliability 52%, ppv 52%, npv 52%, sensitivity 46%, specificity 58%. Interobserver variability: All 4 obstetricians agreed in 47 of 100 evaluations. The level of agreement was higher in the controls (63%) than in the cord complication group (56%). The intraobserver variability was 25%.Cardiotocography is not useful for the detection of cord complications. The range of possibilities has not been exploited yet, even for the evaluation of the fetal state.

We report the case of a cavernous hemangioma with a recently developed hematoma of the umbilical cord. Because of a threatening intrauterine asphyxia an operative vaginal delivery was performed followed by pulmonary disturbance of adaptation and anemia with transfusion. Possible complications are discussed both in terms of the case-history and literature.

To evaluate the epidemiology of true knots of the umbilical cord and their impact on pregnancy outcome.22531 singleton deliveries were included in this retrospective study (1976-1994). Newborns with malformations were excluded. The database of the 2nd Department of Obstetrics and Gynaecology, Vienna University Hospital was analyzed.The incidence of true knots was 1.27% (n = 286). Multiparous women are more likely to give birth to a child with a true knot of the umbilical cord than primiparae (1.52% vs. 1.01%, P0.001). Male fetuses are more frequently affected than females (1.49% vs. 1.04%, P = 0.01). Duration of pregnancy, fetal weight, presentation and mode of delivery are not significantly influenced by umbilical knots. Fetal acidosis (pH7.10) was more common in the cohort with true knots as compared with the controls (8.33% vs. 4.03%, P0.01). Apgar score and transfer rate to a neonatal unit were not influenced. Still-births were more common in the cohort with umbilical knots (1.7% vs. 0.6%, P0.05); there was no neonatal death in the cohort with true knots, however.A fetus with a true knot of the umbilical cord is at risk for fetal death. During labour umbilical knots have no adverse effect on pregnancy outcome.

A 41-year old woman had a premature rupture of the membranes of the first twin with prolapse of the umbilical cord and the left foot in the 24th gestational week (23 + 4). The treatment consisted of bed rest in the Trendelenburg position, antibiotic prophylaxis and glucocorticoids for lung maturation. After 7 days the first twin was delivered vaginally from breech position. He died 10 hours later due to intraventricular hemorrhage. Tocolysis was administered and the umbilical cord was ligated and cut as high as possible. Seven days later a premature rupture of the membranes of the second twin and a prolapse of the fetal hand occurred. The second twin (birth weight 750 g) was delivered by cesarean section in the 26th gestational week (25 + 4) and survived without neurologic sequelae. Prolongation of pregnancy after a very premature delivery of the first twin of a biamniotic twin pregnancy can improve the neonatal outcome.

Fetal heart rate pathology is seen in up to 40% of complications of the umbilical cord. We report a case in which long lasting bradycardia was associated with fetal grasping of the umbilical cord. Using colour doppler, the reason for the bradycardia could be detected. After vibro-acoustic stimulation the fetus released the grasp of the umbilical cord, following by a normalisation of the fetal heart rate and a spontaneous delivery two hours later. This case report underlines the importance of colour doppler for the diagnosis of fetal heart rate pathology.

Eight children with either panhypopituarism, severe growth hormone deficiency or neurosecretory dysfunction for growth hormone with a common history of umbilical cord encirclement around the neck underwent magnetic resonance imaging of the pituitary gland and the hypothalamus. Panhypopituitarism was associated with small to absent adenohypophysis, narrow or absent stalk and ectopic neurohypophysis whereas patients with partial GHD showed normal anatomical structures. Etiology of the endocrinopathy could be a primary malformation of the pituitary gland, an apoplexy of the gland or disturbation within the hypothalamus. We believe that the latter cause is predominant in umbilical cord encirclement.

Umbilical cord complications are the most common cause of pathologic fetal heart tones during delivery. The inauguration of colour-coded Doppler ultrasound in obstetrics has made the definite diagnosis of umbilical cord encirclement during delivery possible. The prospective study introduced here examines the question of how exactly an encirclement can be seen by Doppler during delivery, its influence on cardiotocographic results, delivery mode, and fetal outcome. 107 patients in labour with cervical dilatation were examined in a prospective study using colour-coded Doppler ultrasound to determine cases of umbilical cord encirclement. In 50 cases, encirclement could be visualised, 48 of which were confirmed post partum. Encirclement could be ruled out in 57 other cases. A sensitivity of 96% and specificity of 100% resulted. No significant differences could be found with regard to mode of delivery and fetal outcome. However, the umbilical cord in cases of encirclement was significantly longer than when no encirclement occurred. Assessment of fetal heart tones demonstrated a significantly higher rate of variable decelerations in the patient group with umbilical cord encirclement compared to that without. In conclusion, our results show that the early diagnosis of umbilical cord encirclement during delivery allows appropriate assessment of fetal heart tone changes,justifying temporising management under continuous monitoring with possible micro-blood analysis.

The incidence of umbilical cord entanglements is about 30-35%. Their role for the fetal outcome and the obstetrical management (in case the entanglement has been detected antenatally) has been assessed differently. In this retrospective study we compared maternal and neonatal parameters of all monozygotic deliveries in 1990 with newborns with twisted fetal umbilical cord around the neck. No higher rate of forceps/VE, cesarean section or umbilical artery acidemia7.10 has been found. An exspectative obstetrical management with good fetal monitoring should be sufficient, because in most cases cord entanglements are harmless.

In a patient with elevated serum alpha-fetoprotein a little haemangioma of the umbilical cord is diagnosed by ultrasound in the 21st week of pregnancy. So far only nine reports exist of prenatal diagnosed haemangiomas of the cord. Severe complications like rupture, cord haematoma, non-immune hydrops fetalis and polyhydramnions as well as a perinatal mortality of 35% have been reported. Therefore, intensive surveillance during pregnancy is mandatory.

The incidence of umbilical cord entanglement is about 20-33%. The present study describes the antepartal detection of nuchal cord using Colour Doppler sonography. In 137 cases, the identification of cord entanglement through a high resolution real-time Colour Doppler equipment (Picker 192/Acuson 128 XP) was achieved with sensitivity of 97%, the positive predictive value was 89%, the negative predictive value 96% and the efficiency 93%. In complicated cases, the pulsed Doppler sonography of the cord vessels provided significant differential diagnostic evaluation (Aa. and V. umbilicales vs. uteroplacental vessels). The use of this new method is especially indicated in situations with uncertain variable decelerations and/or other abnormal findings in the antepartal FHR-registration. The early recognition of a nuchal cord could possibly prevent serious peri-/subpartal complications in many cases. The result of our investigations suggest, that once a cord entanglement has been identified sonographically, the antepartal cardiotocography, sonography, Doppler flow examination and intrapartal foetal monitoring should be more frequently and intensively performed.