TY - THES A1 - Döring, Christian T1 - Ergebnisse der gynäkologischen Descensuschirurgie unter Verwendung des GYNECARE PROLIFT® prolenemesh am Krankenhaus Agatharied T1 - Results of the gynaecological descensus surgery under application of GYNECARE PROLIFT® prolenemesh at Agatharied Hospital N2 - Ergebnisse der gynäkolgischen Descensuschirurgie unter Verwendung des GYNECARE PROLIFT® prolenemesh am Krankenhaus Agatharied Der Descensus genitalis ist eine der häufigsten gutartigen Erkrankungen der Frau, im Jahr 2010 waren mehr als 316 Millionen Frauen weltweit betroffen. Es besteht ein Lebensrisiko von 11,1% für eine chirurgische Intervention für eine 80jährige Frau. Die Gründe liegen v. a. in der Anzahl vaginaler (operativer) Geburten, Adiopsitas, Z.n. Hysterektomie, Überalterung und chronisch erhöhter intraabdominaler Druck. Die klinische Symptomatik besteht aus den typischen Senkungssymptomen wie Fremdkörper- und Druckgefühl, Ulcerationen mit Blutung, Fluor, Infektionen und Schmerzen. Außerdem kann es zu anorectaler Dysfunktion und Störungen der Blasenspeicher- und entleerungsfunktion kommen. Auch werden häufig Störungen der Sexualfunktion beschrieben. Die anatomiegerechte Beckenbodendefektbehebung mittels Polypropylene-Kunststoffnetzen (GYNECARE PROLIFT® prolenemesh) über den vaginalen Zugang wird zunehmend, neben den klassischen Descensusoperationen, zur Rekonstruktion des weiblichen Beckenbodens verwendet. Anhand der prä- und postoperativen Anamnese und Untersuchung nach dem POP-Q Schema einschließlich intra- und postoperativer Veräufe sowie 4 etablierter Fragebögen (PFDI-20, PFIQ-7, PISQ-12 und PGI-C) zu subjektiven Einschränkungen durch den Descensus erfolgt die Evaluation des Erfolges der Netzimplantation und ein Vergleich mit Ergebnissen anderer Methoden der Descensuschirurgie. Ergebnisse: Netzspezifische Komplikationen wie Exposition in die Scheide, Erosion in Nachbarorgane, Schrumpfung der Netze mit Schmerzen, Auftreten einer De Novo Belastungsinkontinenz oder einer Dyspareunie wurden im vorliegenden Kollektiv deutlich seltener als in der Literatur verzeichnet. Die Netzimplantation war in 81,5% (Stadium 0 oder 1) erfolgreich, es kam in 18,5% zu einem Rezidiv. Je nach Literatur und betroffenem Kompartiment liegen die Rezidivraten nach Mesheinlage zwischen 3,5 und 46% und bei 2 bis 42,5% nach klassischen Descensusoperationen. In allen 4 Fragebögen wurde eine Verbesserung der Lebensqualität, der sexuellen Zufriedenheit und der Speicher- und Entleerungsfunktion von Blase und Darm verzeichnet, jedoch war die Netzimplantation gleichwertig mit den klassischen Senkungsoperationen. N2 - Introduction: Descensus genitalis is one of women’s most frequent benign diseases. In 2010, more than 316 Million women world-wide were affected. There’s an 11.1 % risk for an 80 year-old woman to undergo surgery within her life span. Above all, reasons lie in the number of vaginal births (including surgical intervention), hysterectomy, adipositas, high age and elevated intraabdominal pressure. Typical clinical descensus symptoms include foreign body and pressure sensation, ulceration with bleeding, fluor, infections and pain. Furthermore, anorectal dysfunction, bladder storage and emptying problems. Sexual dysfunctions are also frequently described. Apart from the usual descensus operation for the reconstruction of the female pelvic floor, implementing polypropylene mesh (GYNECARE PROLIFT® prolenemesh) through vaginal access has increasingly become an alternative. Material and methods: Success of the mesh implantation was compared with results of other methods of descensus surgery, using pre- and post-operative medical history, examination based on the POP-Q scale including intra- and post-operative developments as well as on four established questionnaires (PFDI-20, PFIQ-7, PISQ-12 and PGI-C) describing subjective restrictions caused by the descensus. Results/discussion: Mesh-specific complications, such as exposition into the vagina, erosion into adjacent organs, painful shrinking of the mesh, de novo stress incontinence or a dyspareunia were detected much less frequently in the current cohort than described in literature. Mesh implantation was successful in 81.5 % (stage 0 or 1), a recrudescence occurred in 18.5 %. Depending on the respective literature and specific cohort, the rates for recrudescence after mesh implementation lie between 3.5 and 46 %, while they range between 2 and 42.5% after usual descensus surgery. Each of the four questionnaires reported improvement of life quality, of sexual satisfaction as well as better bowel and bladder storage and emptying ability. However, results of mesh implantation showed no significant difference to those of the conventional descensus surgery. KW - Descensus uteri KW - Beckenbodensenkung KW - Descensus vaginalis KW - Prolaps KW - Descensus KW - Mesh KW - Polypropylen-Netz KW - PROLIFT KW - Descensuschirurgie Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111241 ER - TY - JOUR A1 - Soehnlein, Oliver A1 - Drechsler, Maik A1 - Döring, Yvonne A1 - Lievens, Dirk A1 - Hartwig, Helene A1 - Kemmerich, Klaus A1 - Ortega-Gómez, Almudena A1 - Mandl, Manuela A1 - Vijayan, Santosh A1 - Projahn, Delia A1 - Garlichs, Christoph D. A1 - Koenen, Rory R. A1 - Hristov, Mihail A1 - Lutgens, Esther A1 - Zernecke, Alma A1 - Weber, Christian T1 - Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes JF - EMBO Molecular Medicine N2 - We used a novel approach of cytostatically induced leucocyte depletion and subsequent reconstitution with leucocytes deprived of classical \((inflammatory/Gr1^{hi})\) or non-classical \((resident/Gr1^{lo})\) monocytes to dissect their differential role in atheroprogression under high-fat diet (HFD). Apolipoprotein E-deficient \((Apoe^{-/-})\) mice lacking classical but not non-classical monocytes displayed reduced lesion size and macrophage and apoptotic cell content. Conversely, HFD induced a selective expansion of classical monocytes in blood and bone marrow. Increased CXCL1 levels accompanied by higher expression of its receptor CXCR2 on classical monocytes and inhibition of monocytosis by CXCL1-neutralization indicated a preferential role for the CXCL1/CXCR2 axis in mobilizing classical monocytes during hypercholesterolemia. Studies correlating circulating and lesional classical monocytes in gene-deficient \(Apoe^{-/-}\) mice, adoptive transfer of gene-deficient cells and pharmacological modulation during intravital microscopy of the carotid artery revealed a crucial function of CCR1 and CCR5 but not CCR2 or \(CX_3CR1\) in classical monocyte recruitment to atherosclerotic vessels. Collectively, these data establish the impact of classical monocytes on atheroprogression, identify a sequential role of CXCL1 in their mobilization and CCR1/CCR5 in their recruitment. KW - hypercholeterolemia KW - CCR2 KW - atherosclerosis KW - chemokine KW - accumulation KW - subsets KW - inflammatory sites KW - fractalkine KW - marcophages KW - mobilization KW - monocyte KW - recruitment KW - bone-marrow KW - atheriosclerotic lesions KW - hyperlipedemic mice Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122204 SN - 1757-4676 VL - 5 ER - TY - JOUR A1 - Tilstam, Pathricia V. A1 - Gijbels, Marion J. A1 - Habbeddine, Mohamed A1 - Cudejko, Celine A1 - Asare, Yaw A1 - Theelen, Wendy A1 - Zhou, Baixue A1 - Döring, Yvonne A1 - Drechsler, Maik A1 - Pawig, Lukas A1 - Simsekyilmaz, Sakine A1 - Koenen, Rory R. A1 - de Winther, Menno P. J. A1 - Lawrence, Toby A1 - Bernhagen, Jürgen A1 - Zernecke, Alma A1 - Weber, Christian A1 - Noels, Heidi T1 - Bone Marrow-Specific Knock-In of a Non-Activatable Ikkα Kinase Mutant Influences Haematopoiesis but Not Atherosclerosis in Apoe-Deficient Mice JF - PLOS ONE N2 - Background: The Ikkα kinase, a subunit of the NF-kappa B-activating IKK complex, has emerged as an important regulator of inflammatory gene expression. However, the role of Ikkα-mediated phosphorylation in haematopoiesis and atherogenesis remains unexplored. In this study, we investigated the effect of a bone marrow (BM)-specific activation-resistant Ikk alpha mutant knock-in on haematopoiesis and atherosclerosis in mice. Methods and Results: Apolipoprotein E (Apoe)-deficient mice were transplanted with BM carrying an activation-resistant Ikkα gene (Ikkα(AA/AA) Apoe(-/-)) or with Ikkα(+/+) Apoe(-/-) BM as control and were fed a high-cholesterol diet for 8 or 13 weeks. Interestingly, haematopoietic profiling by flow cytometry revealed a significant decrease in B-cells, regulatory T-cells and effector memory T-cells in Ikkα(AA/AA) Apoe(-/-) BM-chimeras, whereas the naive T-cell population was increased. Surprisingly, no differences were observed in the size, stage or cellular composition of atherosclerotic lesions in the aorta and aortic root of Ikkα(AA/AA) Apoe(-/-) vs Ikkα(+/+) Apoe(-/-) BM-transplanted mice, as shown by histological and immunofluorescent stainings. Necrotic core sizes, apoptosis, and intracellular lipid deposits in aortic root lesions were unaltered. In vitro, BM-derived macrophages from Ikkα(AA/AA) Apoe(-/-) vs Ikkα(+/+) Apoe(-/-) mice did not show significant differences in the uptake of oxidized low-density lipoproteins (oxLDL), and, with the exception of Il-12, the secretion of inflammatory proteins in conditions of Tnf-α or oxLDL stimulation was not significantly altered. Furthermore, serum levels of inflammatory proteins as measured with a cytokine bead array were comparable. Conclusion: Our data reveal an important and previously unrecognized role of haematopoietic Ikkα kinase activation in the homeostasis of B-cells and regulatory T-cells. However, transplantation of Ikkα AA mutant BM did not affect atherosclerosis in Apoe(-/-) mice. This suggests that the diverse functions of Ikkα in haematopoietic cells may counterbalance each other or may not be strong enough to influence atherogenesis, and reveals that targeting haematopoietic Ikkα kinase activity alone does not represent a therapeutic approach. KW - NF-KAPPA-B KW - regulatory T cells KW - indoleamine 2,3-dioxygenase KW - dendritic cells KW - gene expression KW - increases atherosclersosis KW - receptor KW - inhibition KW - pathway KW - beta Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117450 VL - 9 IS - 2 ER -