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5 Zusammenfassung

5.2 Englisch

Sudden hearing loss is one of the most common inner-ear diseases. The underlying pathomechanism is still not fully understood and most often it remains idiopathic. One of its discussed causes is the disturbance of cochlear microcirculation that is either the primary cause but also considered to be the final common pathway of other aetiopathological factors.

Fibrinogen affects microcirculation and hyperfibrinogenemia was identified as a risk factor for sudden hearing loss. The present study demonstrated in vivo that acute hyperfibrinogenemia increases hearing threshold. The animal model allows simultaneous measurement of hearing threshold by brainstem evoked response audiometry, and cochlear blood flow by intravital microscopy. Furthermore, by a central venous catheter, blood samples can be taken, and ap-plication of medication is possible. A sudden hearing loss was induced by acute hyperfibrino-genemia. Next, in an experimental therapy trial, drug-induced defibrinogenation by ancrod

44 was demonstrated for treatment of this vascular inner ear impairment. Reduction of patho-logic fibrinogen levels was followed by an increase of cochlear blood flow, accompanied by a recovery of hearing loss. Placebo treatment had no effect on hearing thresholds or parameters of cochlear microcirculation. Ancrod was already marketed in Europe and Canada for indica-tions like peripheral arterial occlusive disease, deep vein thrombosis, and prophylaxis for thromboembolism. It is safe and easy to monitor by routine laboratory tests measuring plasma fibrinogen level. The reduction of plasma fibrinogen might serve as a future treatment option for acute hearing loss.

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Teile dieser Doktorarbeit wurden auf Konferenzen in Form von Pos-tern, Vorträgen und Abstracts vorgestellt.

Originalarbeiten:

Weiss BG, Bertlich M, Bettag SA, Desinger H, Ihler F, Canis M (2017): Drug-induced

defibrinogenation as new treatment approach of acute hearing loss in an animal model for inner ear vascular impairment. Otol Neurotol 38(5):648-654.

Patentanmeldung

Weiss BG, Canis M. Neue Verwendung von Ancrod bei Innenohrerkrankungen. Patentanmel-dung beim Deutschen Patent- und Markenamt am 12.05.2015, Anmeldenummer DE 102015107469.9

Poster / Präsentationen / Abstracts:

Weiss BG, Bertlich M, Bettag SA, Desinger H, Ihler F, Canis M. Medikamentöse Defibrinogenie-rung als neuer Therapieansatz des akuten Hörverlusts in einem vaskulären Schädigungsmodell des Innenohres in vivo. Herbsttagung der Arbeitsgemeinschaft Deutschsprachiger Audiologen, Neurootologen und Otologen (ADANO), Bern 2015

Weiss BG, Bertlich M, Bettag SA, Canis M, Desinger H, Ihler F. Medikamentöse Defibrinogenie-rung zur Therapie des akuten Hörverlusts in einem vaskulären Schädigungsmodell des Inneno-hres in vivo. DGHNO, Berlin 2015

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Danksagung

Mein besonderer Dank gilt meinem Doktorvater Prof. Dr. Martin Canis für die freundliche Vergabe des Themas und die hervorragende Betreuung der Arbeit.

Ebenfalls möchte ich mich bei meinem Betreuer Dr. Bernhard Weiss bedanken. Seine Ideen, Kommentare und Korrekturen waren für mich immer hilfreich, er stand mir stets mit Rat und Tat zur Seite.

Dr. Mattis Bertlich danke ich sehr für die Einarbeitung in die Mikrochirurgie. Er unterstützte mich auch bezüglich des Umgangs mit allen technischen Geräten und half stets bei Proble-men und organisatorischen Herausforderungen.

Weiterhin danke ich Frau Jutta Engelmayer aus dem Institut für klinische Chemie der Univer-sitätsmedizin Göttingen für ihre Hilfe und Beratung.

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Lebenslauf

Am 30.01.1990 wurde ich in Essen als zweites Kind meiner Eltern Christa Bettag, geb. Kiwit, und Prof. Dr. Martin Bettag geboren.

Von 1996 bis 2000 besuchte ich die Schloss-Ardeck-Grundschule in Gau-Algesheim, ab 2000 das Friedrich-Wilhelm-Gymnasium Trier, an welchem ich im März 2009 meine Schulausbil-dung mit dem Abitur beendete.

Von 2009 bis 2010 absolvierte ich als Rettungssanitäter ein Freiwilliges Soziales Jahr bei der Lehrrettungswache der Berufsfeuerwehr Trier.

Zum Sommersemester 2010 begann ich das Studium der Zahnheilkunde an der Georg-Au-gust-Universität Göttingen und beendete es im November 2015 mit dem Abschluss der Zahnärztlichen Prüfung. Meine Approbation als Zahnarzt erhielt ich am 14.12.2015. Bereits während des Studiums begann ich mit den experimentellen Arbeiten zu meiner vorliegenden Dissertation mit dem Thema „Medikamentöse Defibrinogenierung zur Behandlung des akuten Hörverlustes - eine verblindete, Placebo-kontrollierte in vivo-Studie“ in der Arbeits-gruppe von Herrn Prof. Dr. med. Martin Canis.

Im Sommersemester 2016 begann ich das Studium der Humanmedizin an der Georg-August-Universität Göttingen und ich studiere momentan im 8. Fachsemester.