Werner Rath - Academia.edu (original) (raw)

Papers by Werner Rath

Zeitschrift Fur Geburtshilfe Und Neonatologie, Jun 17, 2016

Venose Thromboembolien (VTE) sind weltweit eine der haufigsten mutterlichen Todesursachen. Die st... more Venose Thromboembolien (VTE) sind weltweit eine der haufigsten mutterlichen Todesursachen. Die steigende Zahl an Schwangeren mit Risikofaktoren hat zu einer signifikanten Zunahme der VTE-Inzidenz gefuhrt. Mortalitat und Morbiditat infolge VTE sind potentiell vermeidbar, da mehr als 2/3 dieser Frauen identifizierbare Risikofaktoren aufweisen und von einer adaquaten VTE-Prophylaxe profitieren konnen. Die Eckpfeiler zur Pravention von VTE sind die individuelle und sorgfaltige Erfassung von praexistenten und neu auftretenden/transienten Risikofaktoren in der Schwangerschaft, vor und nach der Geburt sowie eine risikoadaptierte medikamentose Thromboembolie-Prophylaxe. Derzeitige Empfehlungen zur VTE-Prophylaxe basieren nur auf Konsensus-Statements und Expertenmeinungen. Es werden die vor kurzem publizierte AWMF-Leitlinie 003/001 und die Leitlinie Nr. 37a des Royal College of Obstetricians and Gynecologists (RCOG) diskutiert. Die RCOG-Leitlinie empfiehlt eine antenatale Thromboseprophylaxe bei Frauen mit vorangegangener VTE, Hochrisiko-Thrombophilien oder beim Vorliegen von≥4 Risikofaktoren ab Beginn der Schwangerschaft, bei 3 Risikofaktoren ab der 28. SSW. Nach der Geburt sollte bei mittlerem Risiko NMH uber mindestens 10 Tage und bei hohem Risiko uber 6 Wochen gegeben werden. Nach elektiver Sectio wird prophylaktisches NMH uber 10 Tage nur bei zusatzlichen Risikofaktoren empfohlen, das gleiche Vorgehen gilt fur alle Frauen mit sekundarer Sectio. Die Gabe von NMH sollte bei Beginn der Wehen, vaginalen Blutungen, vor geplanter Geburtseinleitung oder mindestens 12 Stunden vor einer elektiven Sectio abgesetzt werden, sie kann 4–6 Stunden nach vaginaler Geburt und 6–12 Stunden nach Sectio fortgesetzt werden, sofern kein erhohtes Blutungsrisiko besteht. Die aktuellen Leitlinien empfehlen eine Korpergewichts-adaptierte Prophylaxe mit NMH.

Clinical Hemorheology and Microcirculation, Oct 28, 2015

Clinical Hemorheology and Microcirculation, Feb 16, 2016

Geburtshilfe Und Frauenheilkunde, Oct 7, 2015

Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obs... more Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Hypertensive pregnancy disorders contribute significantly to perinatal as well as maternal morbidity and mortality worldwide. Also in Germany these diseases are a major course for hospitalization during pregnancy, iatrogenic preterm birth and long-term cardiovascular morbidity. Methods: This S1-guideline is the work of an interdisciplinary group of experts from a range of different professions who were commissioned by DGGG to carry out a systematic literature search of positioning injuries. Members of the participating scientific societies develop a consensus in an informal procedure. Afterwards the directorate of the scientific society approves the consensus. Recommendations: This guideline summarizes the state-of-art for classification, risk stratification, diagnostic, treatment of hypertensive pregnancy disorders. Zusammenfassung ! Ziel: Offizielle Leitlinie, publiziert und koordiniert von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG). Hypertensive Schwangerschaftserkrankungen verursachen weltweit einen hohen Anteil an der neonatalen und mütterlichen Morbidität und Mortalität. Auch in Deutschland tragen sie wesentlich zu Krankenhauseinweisungen während der Schwangerschaft, iatrogener Frühgeburtlichkeit und kardiovaskulärer Langzeitmorbidität bei. Methoden: Mitglieder der beteiligten Fachgesellschaften entwickeln in einem informellen Prozess einen Konsensus. Anschließend bestätigen die Direktorien der Fachgesellschaften diesen Konsensus. Empfehlungen: In der Leitlinie wird der aktuelle Standard für die Benennung, Früherkennung, Diagnostik, Behandlung und Nachsorge hypertensiver Schwangerschaftserkrankungen gegeben. I Guideline Information Guidelines Program of DGGG, OEGGG and SGGG Information on this topic is provided at the end of the guideline.

Journal of Cancer Research and Clinical Oncology, Jun 1, 1994

Amplification of the proto-oncogene c-erbB-2 (HER-2/neu) has been shown to be a prognostic marker... more Amplification of the proto-oncogene c-erbB-2 (HER-2/neu) has been shown to be a prognostic marker in ovarian cancer. In order to obtain further information on the biological role of the c-erbB-2 gene product p185 it is necessary to quantify expression levels. In this study we evaluated an enzyme-linked immunosorbent assay (ELISA) for the extracellular domain of p185 to determine whether a soluble oncoprotein fragment can be detected in the serum of ovarian cancer patients and in the serum of pregnant women. Sera from 199 women (57 previously untreated ovarian cancer patients, 62 pregnant women and 80 healthy controls) were assayed in a sandwich ELISA utilizing two mouse monoclonal antibodies. To study c-erbB-2 overexpression in ovarian cancer tissue samples we have used an immunohistochemical technique involving a monoclonal antibody specifically reactive with the external domain of the protein p185. The mean serum value for the normal controls was 1203 HNU/ml with a standard deviation (SD) of 279 HNU/ml and a range of 595-1947 HNU/ml. We chose a level of 1761 HNU/ml (2 SD above the mean) as a cut-off to distinguish individuals with elevated levels. The ovarian cancer patients' serum values ranged from 526 to 16,332 HNU/ml. Immunohistochemically detectable p185 was noted in 8 of 57 ovarian cancer patients. The oncoprotein fragment levels in the sera from these 8 patients ranged from 878 to 16,332 HNU/ml. Of 8 patients with p185 overexpression in their tumors, 4 had elevated serum levels. In the sera from the 49 cancer patients without overexpression the values were distributed in the range 526-2892 HNU/ml. There was no association between serum oncoprotein fragment levels and tumor stage, histological type or grading. Serum concentrations of the p185 fragment in pregnancy ranged from 612 to 3265 HNU/ml. The highest levels were found in the third trimester. The results of the present study raise the possibility that the soluble c-erbB-2 protein level in serum is an indicator for cell proliferation and therefore deserves further evaluation as a diagnostic tool in ovarian cancer patients and pregnancy.

Journal of Perinatal Medicine, Oct 26, 2017

Aim: Intrauterine growth restriction (IUGR) is an independent risk factor for the development of ... more Aim: Intrauterine growth restriction (IUGR) is an independent risk factor for the development of cardiovascular diseases later in life. The mechanisms whereby slowed intrauterine growth confers vascular risk are not clearly established. In general, a disturbed cholesterol efflux has been linked to atherosclerosis. The capacity of serum to accept cholesterol has been repeatedly evaluated in clinical studies by the use of macrophage-based cholesterol efflux assays and, if disturbed, precedes atherosclerotic diseases years before the clinical diagnosis. We now hypothesized that circulating cholesterol acceptors in IUGR sera specifically interfere with cholesterol transport mechanisms leading to diminished cholesterol efflux. Methods: RAW264.7 cells were used to determine efflux of [ 3 H]-cholesterol in response to [umbilical cord serum (IUGR), n = 20; controls (CTRL), n = 20]. Results: Cholesterol efflux was lower in IUGR as compared to controls [controls: mean 7.7% fractional [ 3 H]cholesterol efflux, standard deviation (SD) = 0.98; IUGR: mean 6.3%, SD = 0.79; P < 0.0001]. Values strongly correlated to HDL (ρ = 0.655, P < 0.0001) and apoE (ρ = 0.510, P = 0.0008), and mildly to apoA1 (ρ = 0.3926, P = 0.0122) concentrations. Conclusions: Reduced cholesterol efflux in IUGR could account for the enhanced risk of developing cardiovascular diseases later in life.

Geburtshilfe Und Frauenheilkunde, Jul 20, 2016

Zeitschrift Fur Geburtshilfe Und Neonatologie, Apr 1, 2012

Human Reproduction, Jun 1, 1999

Pregnancy Hypertension, Jul 1, 2012

Tourism [Working Title], 2020

Deep vein thrombosis (DVT) of the lower limbs is a serious condition that can lead to pulmonary e... more Deep vein thrombosis (DVT) of the lower limbs is a serious condition that can lead to pulmonary embolism (PE) in about 15–24% of cases. If it is not diagnosed/treated timely, nearly 15% of these PE are lethal. The relationship between travel and staying in the same position for a long time is well-known since World War II. Generally, it is more frequent in air flights. It is also associated with the economic downturn in airplanes because passengers have limited space and have greater difficulty of moving. It is estimated that approximately 1–6% of long-haul passengers arrive at their destination with a clot in their veins, but most DVT are asymptomatic.

Anaesthesist, Mar 1, 2014

Postpartum hemorrhage (PPH) is one of the main causes of maternal deaths even in industrialized c... more Postpartum hemorrhage (PPH) is one of the main causes of maternal deaths even in industrialized countries. It represents an emergency situation which necessitates a rapid decision and in particular an exact diagnosis and root cause analysis in order to initiate the correct therapeutic measures in an interdisciplinary cooperation. In addition to established guidelines, the benefits of standardized therapy algorithms have been demonstrated. A therapy algorithm for the obstetric emergency of postpartum hemorrhage in the German language is not yet available. The establishment of an international (Germany, Austria and Switzerland D-A-CH) "treatment algorithm for postpartum hemorrhage" was an interdisciplinary project based on the guidelines of the corresponding specialist societies (anesthesia and intensive care medicine and obstetrics) in the three countries as well as comparable international algorithms for therapy of PPH.The obstetrics and anesthesiology personnel must possess sufficient expertise for emergency situations despite lower case numbers. The rarity of occurrence for individual patients and the life-threatening situation necessitate a structured approach according to predetermined treatment algorithms. This can then be carried out according to the established algorithm. Furthermore, this algorithm presents the opportunity to train for emergency situations in an interdisciplinary team.Die postpartale Blutung (PPH) zählt zu den Hauptursachen der Müttersterblichkeit auch in der westlichen Welt. Die PPH stellt eine Notfallsituation dar, die eine rasche Entscheidung und v. a. eine exakte Diagnose und Ursachenanalyse notwendig macht, um die korrekten therapeutischen Maßnahmen in interdisziplinärer Zusammenarbeit rechtzeitig einzuleiten. Neben etablierten Leitlinien ist der Nutzen standardisierter Therapiealgorithmen belegt. Ein Therapiealgorithmus für den geburtshilflichen Notfall „postpartale Hämorrhagie“ fehlte bisher im deutschsprachigen Raum. Die Erstellung des länderübergreifenden (Deutschland, Österreich und Schweiz: D-A-CH) „Handlungsalgorithmus Postpartale Blutung“ erfolgte interdisziplinär, basierend auf den bisherigen Leitlinien der jeweiligen Fachgesellschaften (Anästhesie und Intensivmedizin, Geburtshilfe) der 3 Länder sowie internationalen vergleichbaren Algorithmen zur Therapie der PPH. Das geburtshilfliche und anästhesiologische Personal muss für den Notfall eine ausreichende Expertise trotz geringer Fallzahl besitzen. Die Seltenheit, mit der das Ereignis für die einzelne Patientin auftritt, sowie die vitale Bedrohung in der Situation, erfordern ein strukturiertes Vorgehen nach vorgegebenen Handlungsalgorithmen. Dies kann mit dem nun ausgearbeiteten Algorithmus erfolgen. Darüber hinaus bietet dieser Algorithmus die Möglichkeit, den Notfall im interdisziplinären Team zu trainieren

Clinical Hemorheology and Microcirculation, May 5, 2018

INTRODUCTION: Recent studies have shown increased RBC aggregation and no difference in plasma vis... more INTRODUCTION: Recent studies have shown increased RBC aggregation and no difference in plasma viscosity in the presence of markedly lower hematocrit in women at term compared to non-pregnant women. Little is known about the outcome of blood rheological parameters and red blood cell (RBC) deformability particularly in the course of normal pregnancy. METHODS: During a 36 months interval 1.913 blood samples were randomly collected from a total of 945 pregnant women in the course of their pregnancy (n = 1.259) and during puerperium (upto 1 week; n = 654). Next to the blood count, hemorheological parameters including red blood cell (RBC)-aggregation (stasis E0; low shear E1),-deformability (low, moderate and high shear conditions) and plasma viscosity (pv) were assessed. Plasma viscosity (pv) was examined using KSPV 1 Fresenius, RBC aggregation (stasis: E0 and low shear: E1) using MA1-Aggregometer; Myrenne and RBC deformability (def) was determined by Rheodyn SSD Diffractometer, Myrenne, Roetgen, Germany were tested. In some of these women laboratory results prior to pregnancy (n = 145) were available which were compared with those during pregnancy. RESULTS: Mean maternal pv remained unchanged within each trimester and compared to the values before pregnancy and during early puerperium (Range of means: 1.18-1.20 mPa S). In contrast, RBC agg (E0 and E1) was markedly higher in the 2nd (21.8 ± 7.0 and 28.9 ± 9.4; p < 0.001) and 3rd trimester (18.74 ± 8.4 and 28.2 ± 9.4; p < 0.01) compared to the values before pregnancy (16.4 ± 6.4 and 20 ± 7.5) and during 1st trimester (17.49 ± 6.5 and 22.4 ± 7.4). There was a stat. significant temporary reduction in RBC def. under all shear rate conditions during 2nd trimester compared to the values before pregnancy which remained significantly lower during 3rd trimester only under high shear rates. An increase RBC agg was stat. significantly inversely correlated with reduced RBC def being most pronounced under low shear rate conditions. While RBC rigidity was stat. significantly correlated with higher hematocrit values there was only a weak correlation between RBC agg and haematocrit (E0: r =-0.084; p = 0.03; E1: r =-0.06; p = 0.1). Pv was not correlated with haematocrit or RBC def but stat. significantly correlated with RBC agg. CONCLUSION: Blood rheological changes manifest during 1st trimester, and fairly remain unchanged during 2nd trimester until term. Physiologic hemodilution and increasing hypercoagulability is accompanied by high RBC-aggregation and-rigidity during 2nd trimester while plasma viscosity remains nearly unaffected throughout normal pregnancy.

Zeitschrift Fur Geburtshilfe Und Neonatologie, Oct 1, 2019

Journal of Proteomics, Oct 1, 2016

Intrauterine growth restriction (IUGR) is an important cause of perinatal morbidity and mortality... more Intrauterine growth restriction (IUGR) is an important cause of perinatal morbidity and mortality and contributes substantially to medically indicated preterm birth; preventing fetal death. Molecular profiling of the mothers' peripheral blood was desired to monitor the health conditions of the fetuses. To develop such a minimally invasive assay, we applied a protein affinity fractionation method to peripheral blood serum samples from pregnant women belonging to either the IUGR or to the control group. Proof-of-principle was shown by relative quantitation analysis of mixtures of intact proteoforms using MALDI-ToF mass spectrometry. The two best differentiating proteins and proteoforms, respectively, were apolipoprotein C-II and apolipoprotein C-III 0. Together with three robustly expressed protein proteoforms proapolipoprotein C-II, apolipoprotein C-III 1 , and apolipoprotein C-III 2 , which served as landmarks for relative quantitation analysis, they constituted the maternal IUGR proteome signature. Separation confidence of our IUGR proteoform signature reached a sensitivity of 0.73 and a specificity of 0.87 with an area under curve of 0.86 in receiver operator characteristics. Significance: Identification of IUGR newborns in the case room is required as children are severely diseased and need specialized care during infancy. Yet, at time of birth there is no readily applicable clinical test available. Hence, a molecular profiling assay is highly desired. It needs to be mentioned that current clinical definitions and recommendations for IUGR are unfortunately misleading and are not universally applicable. The most commonly adopted definition is an abdominal circumference (AC) or estimated fetal weight measurement b 10th percentile. Although both, the American College of Obstetricians and Gynecologists (ACOG) and the Royal College of Obstetricians and Gynecologists (RCOG) agree that at this cutoff the risk of perinatal morbidity and mortality increases, this definition does not take into account the individualized growth potential of each fetus. In particular its sole use fails to identify larger fetuses that have not achieved their growth potential and may be at risk of adverse outcomes. Also, this definition, when solely applied, will result in the misdiagnosis of IUGR for some constitutionally small fetuses. It needs to be pointed out that the above mentioned criteria can only be determined during pregnancy in case mothers report from early on during pregnancy. We have developed a test that relies on mass spectrometric analysis of the mother's serum protein composition (IUGR signature) which can be determined just ahead of delivery and at date of delivery, respectively using a minimal invasive blood sampling approach. With this manuscript we describe the use of a mass spectrometric profiling method of 30 peripheral blood samples from pregnant women prior to giving birth of either unsuspicious newborns or IUGR-affected infants. We report for the first time that maternal blood sample analysis via affinity mass spectrometry differentiates IUGR infants from controls with high confidence.

Zeitschrift Fur Geburtshilfe Und Neonatologie, Dec 1, 2020

ZusammenfassungDie Prävalenz hypertensiver Schwangerschaftserkrankungen (HES) beträgt 6–8%. HES g... more ZusammenfassungDie Prävalenz hypertensiver Schwangerschaftserkrankungen (HES) beträgt 6–8%. HES gehören zu den führenden Ursachen mütterlicher Sterbefälle in den Industrieländern. Die Messung des Blutdrucks (RR) ist nach wie vor Eckpfeiler der Diagnose. Die Blutdruckmessung sollte nach standardisierter Vorgehensweise mit automatischen, für die Schwangerschaft validierten Messgeräten erfolgen. Die Blutdruckmessung in der Praxis erlaubt nur eine „punktuelle“ Messung in „artifizieller“ Umgebung und kann eine Weißkittelhypertonie (WCH) nicht erfassen. Nach aktuellen Leitlinien sollte die ambulante 24-Stunden-Blutdruckmessung (ABPM) bei allen Schwangeren mit erhöhten Blutdruckwerten zur Diagnosesicherung und Differenzierung der Hypertonie durchgeführt werden. Die ABPM ist eine geeignete Methode zur frühzeitigen Identifizierung der WCH und der maskierten Hypertonie sowie zur Differenzierung zwischen WCH und chronischer Hypertonie vor der 20. SSW. Fehlender nächtlicher Blutdruckabfall und v. a. Blutdruckspitzen während der Nachtstunden sind mit einem signifikant erhöhten Risiko für Präeklampsie und kardiovaskulärer Morbidität assoziiert. ABPM und häusliche Blutdruckmessung (HBPM) wurden zur Blutdruckkontrolle bei Schwangeren mit Gestationshypertonie, chronischer Hypertonie, milder Präeklampsie und Schwangeren mit Risikofaktoren für eine HES nach der 18. SSW empfohlen. Sie ermöglichen eine exakte Blutdruckeinstellung mit Antihypertensiva. Wichtige Voraussetzungen für die Anwendung beider Methoden ist die Compliance der Patientin. Wie in Studien gezeigt, reduziert die HBPM die Zahl antenataler Arztbesuche und Krankenhausaufnahmen im Vergleich zur Blutdruckmessung in der Praxis ohne erhöhtes Risiko für Mutter und Kind, sie vermindert darüber hinaus die Rate an Geburtseinleitungen und die Diagnose „Präeklampsie“ und trägt zur Vermeidung einer unnötigen antihypertensiven Therapie bei. Die Methode weist eine hohe Akzeptanz bei den Schwangeren auf und ist kosteneffektiv. Die Probleme der ABPM liegen v. a. in ihrer limitierten Verfügbarkeit und der Belästigung der Schwangeren durch Schlafstörungen. Die wesentlichen Nachteile der HBPM sind die Notwendigkeit zur Schulung/Training der Patientin, mögliche Messfehler und dem Fehlen evidenzbasierter Blutdruckgrenzwerte. Derzeit werden Telemonitoring-Plattformen zur ambulanten Überwachung von Schwangeren mit erhöhtem Risiko für HES evaluiert. Die breite Anwendung v. a. der HBPM kann dazu beitragen, die Arbeitsbelastung des geburtshilflichen Personals im Krankenhaus zu reduzieren und Krankenhauskosten einzusparen.

Journal of The Society for Gynecologic Investigation, Jul 1, 2002

OBJECTIVE: To determine the localization and concentrations of estrogen receptor ox and progester... more OBJECTIVE: To determine the localization and concentrations of estrogen receptor ox and progesterone receptors A and B in the lower uterine segment during term parturition. METHODS: Biopsies were takenfrom 70 patients during nonelective cesarean delivery. The patients were at diferent stages ofcervical dilatation (<2 cm, 2-3.9 cm, 4-6 cm, > 6 cm) and diferent duration oflabor (. 6 hours, > 6-12 hours, > 12 hours). The receptor concentrations were determined with solid phase immunoassays, and their localization was investigated immunohistochemically. RESULTS: Estrogen receptor (X concentration decreased signficantlyfrom 2. 12fmol/mg protein at less than 2 cm dilatation to 1. 08fmol/mg (4-6 cm) but tended to increase at greater than 6 cm. Progesterone receptor A and B concentration was 84. 7fmol/mg at less than 2 cm dilatation, decreased significantly to 36. 6fmol/mg (2-3.9 cm), and increased again withfurther dilation. Concentrations of both receptors did not depend on duration of labor. By immunohistochemistry only progesterone receptor A and B wasfound to be expressed by endothelial and smooth muscle cells of the vessels, stromalfibroblasts, smooth muscle cells in the myometrium, and glandular epithelial cells. Regardless of the extent of cervical dilatation, expression ofprogesterone receptors A and B was marked. CONCLUSION: A decrease in estrogen receptor at and progesterone receptor A and B concentration in the early phase offirst stage labor may play a role in cervical dilation at term.

Molecular human reproduction, Jul 1, 2000

Leptin and its receptor are involved in endocrine and paracrine regulation of metabolism, obesity... more Leptin and its receptor are involved in endocrine and paracrine regulation of metabolism, obesity and reproduction. Here, we describe the detection of the functional long isoform receptor of leptin in human endometrium. The leptin receptor protein was shown to be expressed in glandular and luminal epithelium and is periodically regulated throughout the menstrual cycle, demonstrating main expression in follicular and mid-luteal phase. In contrast, leptin receptor mRNA is detectable by reverse transcription-polymerase chain reaction (RT-PCR) as a constitutive component. Since RT-PCR analyses showed that leptin is not expressed in this tissue, the present study suggests that the human endometrium is a novel target for leptin. Therefore, we investigated 11 subfertile patients who underwent two biopsies in one menstrual cycle. The patients presented with a repetitive endometrial maturation defect, but showed adequate serum hormone concentrations and normal steroid hormone receptor expression and down-regulation in the endometrium. These patients were, however, deficient for expression of the functional leptin receptor. These analyses provide evidence that the lack of the leptin receptor in an ovulatory cycle may contribute to subfertility by a yet undefined 'endometrial factor'.

Clinical and Applied Thrombosis/Hemostasis, 2014